1. Beijing National Laboratory for Molecular Science, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, the Chinese Academy of Sciences, Beijing 100190, China
2. College of Chemistry, Beijing Normal University, Beijing 100875, China
3. University of Chinese Academy of Sciences, Beijing 100049, China
Brain, as the source of neural activities such as perceptions and emotions, consists of the dynamic and complex networks of neurons that implement brain functions through electrical and chemical interactions. Therefore, analyzing and monitoring neurochemicals in living brain can greatly contribute to uncovering the molecular mechanism in both physiological and pathological processes, and to taking a further step in developing precise medical diagnosis and treatment against brain diseases. Through collaborations across disciplines, a handful of analytical tools have been proven to be befitting in neurochemical measurement, spanning the level of vesicles, cells, and living brains. Among these, electrochemical methods endowed with high sensitivity and spatiotemporal resolution provide a promising way to precisely describe the dynamics of target neurochemicals during various neural activities. In this review, we expand the discussion on strategies to address two key issues of in vivo electrochemical sensing, namely, selectivity and biocompatibility, taking our latest studies as typical examples. We systematically elaborate for the first time the rationale behind engineering electrode/brain interface, as well as the unique advantages of potentiometric sensing methods. In particular, we highlight our recent progress on employing the as-prepared in vivo electrochemical sensors to unravel the molecular mechanism of ascorbate in physiological and pathological processes, aiming to draw a blueprint for the future development of in vivo electrochemical sensing of brain neurochemicals.
Keywords：in vivo electrochemical sensing;
brain chemistry;
selectivity;
biocompatibility
The human brain confers on us the capacities of thinking, feeling, learning and acting, which essentially emerges from the electrical and chemical interactions among tens of billions of neurons that compose the brain circuits. Through worldwide collaborations across disciplines, studies have been conducted to gain comprehensive understanding of the relationship between structural maps and functional maps, spanning the levels of vesicles, cells, circuits, and even higher levels[1,2,3,4]. Despite of these breakthroughs, it is still a long-term goal to obtain selective, quantitative, and real-time information on the kinetics of chemicals in living animal brain, providing promising ways to uncover molecular mechanism in both physiological and pathological processes. To date, a handful of analytical tools have been developed for measurement of targeted neurochemicals, which broadly fall into two categories, namely, noninvasive ones and invasive ones[5,6,7]. Noninvasive methods (e.g., functional magnetic resonance imaging and fluorescent assays) are capable of providing cross-scale pattern of neural activities while keeping the intact brain circuits injury-free[8,9,10,11,12]. On the other hand, invasive methods (e.g., in vivo electrochemistry) endowed with superior spatiotemporal resolution are capable of providing precise and dynamic pattern of specific targets during various neural activities[13,14,15,16,17,18]. This review aims to briefly outline our studies in tissue-implantable electrochemical sensing technologies in terms of molecular selectivity, biocompatibility, and potential applications in brain sciences. We will summarize for the first time the rationale behind engineering interfacial electron transfer and the development of potentiometric systems to control over the electrochemical selectivity and the biocompatibility of the in vivo sensors, with a specific highlight on employing these sensors for revealing molecular mechanism in physiological and pathological processes.
2 Developing Highly Selective In Vivo Sensors
Central nervous system (CNS) as sort of biological systems is highly dynamic and chemically complex, posing grand challenges for selective measurement of desired species. Ideally, analytes with electrochemical activity can be electrochemically transformed at electrode surface and generate a current or voltage change as readout for selective detection and quantification. However, the coexistence of structurally and electrochemically similar species such as their precursors and metabolites often present the big interference for highly selective measurement.
The emerging of fast scan cyclic voltammetry (FSCV) represents a great step forward to in vivo monitoring of the fast kinetics of neurochemicals sensitively, selectively and quantitively[19,20,21]. In specific, the electrochemical kinetics at carbon fiber electrode (CFE) among different neurochemicals becomes distinguishable at ultrahigh potential sweeping speed, resulting in distinct redox peak potentials for qualitative measurements. Over years of development and improvement, FSCV has greatly facilitated the understanding of rapid release of neurotransmitters in some pathological and physiological processes. Notably, these rapid release processes often bring with concurrent change of other neurochemicals (e.g., local pH). Therefore, with imperative need of eliminating mutual interferences and acquiring accurate measurements, strict requirements have been put forward on concurrent multicomponent analysis. Confronted with this challenge, the ongoing improvements in computational methods provide immense opportunities[22,23,24,25]. Recently, we proposed a deep learning-based voltammetric (DLV) platform for in vivo analysis of multiple neurochemicals by using vapor grown carbon fiber microelectrodes (VGCFEs). Dopamine (DA), ascorbate (AA) and ions were selected as a typical neurotransmitter, an important neuromodulator, and main component of extracellular fluid in CNS, respectively[26]. This method enables us to record the interplaying concentration changes in living rat brain during spreading depression (SD), which indicates a bright perspective not only in molecular mechanism discovery, but also in medical diagnosis and treatment.
In addition to voltammetry, potential-controlled amperometry as another important branch of in vivo electrochemical methods is well suited for continuous sensing of neurochemicals. Specifically, amperometry measures the concentration-dependent current transient over time at a constant potential, which quantitatively measures the rapid dynamics of target analytes. To achieve selective sensing, dedicated efforts have been devoted into constructing electrode/brain interfaces to exclusively permit specific electrochemical reactions[27, 28]. One common strategy is to immobilize recognition elements onto electrode surface, exemplified by biomacromolecules such as enzymes and aptamers. Besides, electrocatalysts modified onto the electrode could also achieve selective sensing by either accelerating the adsorption/desorption process or altering electron transfer kinetics and pathways of specific neurochemicals. More recently, ion transport-based sensors also provide another complementary strategy for selective sensing, greatly expanding the scope of detectable neurochemicals to encompass not only electroactive but also electroinactive ones. We herein highlight our latest progress on tuning electrochemical behavior of targeted neurochemicals, with a focus on unraveling the rationale behind engineering electrode/brain interface.
2.1 Biological Recognition Elements
Natural enzymes featured with high specificity and quick response are befitting recognition elements for in vivo biosensing[29]. Oxidases and dehydrogenases are the most widely utilized natural enzymes in design and construction of sensing interfaces[30,31,32,33,34,35,36,37]. After years of exploring and practicing, we gradually established the oxidase/dehydrogenase-based online electrochemical systems (OECSs) that realize in vivo bio-sensing of important neurochemicals (e.g., glucose, lactate, hypoxanthine), which have been comprehensively reviewed previously[38,39,40,41,42]. However, interferences coming from oxygen or cofactors hinder these oxidase/dehydrogenase-based biosensors from in vivo neurochemical biosensing.
Confronted with these challenges, we believe that exploring new types of enzymes can push the boundaries of interference-free in vivo biosensing. Recently, we introduced ferredoxin-dependent glutamate synthase (Fd-GltS) as a new candidate to catalyze both glutamate synthesis and glutamate oxidation through different mediated electron transfer pathways (Figure 1(A))[43]. Specifically, Fd-GltS can catalyze bio-electrosynthesis of glutamate from glutamine and 2-oxog-lutarate when using methyl viologen as the mediator. While using mediators with high redox potential, oxygen-independent bio-electrooxidation of glutamate was realized in the presence of Fd-GltS. With the redox center close to its surface, Fd-Glts holds great potential in the design of glutamate-based in vivo biosensor through direct electron transfer between the enzyme and electrode.
Figure 1
(A) Schematic illustration of mediated electron transfer pathways catalyzed by Fd-Glts[43]. Reproduced with permission of Ref. 43, copyright 2018 American Chemical Society. (B) Schematic illustration of aptCFE and typical current response of in vivo DA dynamics upon electrical stimulation[46]. Reproduced with permission of Ref. 46, copyright 2020 WILEY-VCH. (color on line)
Besides both natural and artificial enzymes, aptamers also provide a powerful tool for developing high selective in vivo electrochemical biosensors[44]. Aptamers are short, synthetic single-stranded nucleic acids that possess recognition ability of specific target molecules with high affinity. Generally, aptamers undergo conformational changes upon binding with analyte molecules, resulting in an altered electron transfer pathway between electrodes and redox moieties modified on aptamers. Our early attempt of developing aptamer-based biosensor provides a dual recognition unit strategy for selective ATP sensing in vivo, by incorporating polyimidazolium-brush (PimB) and aptamers together to realize selective recognition of both triphosphate moieties and A nucleobase simultaneously[45]. Following that, we made more efforts on developing interfacial functionalization strategies and extending application of aptamer-based in vivo sensor. More recently, we demonstrated that the aptamer-modified CFE (aptCFE) shows a high selectivity for in vivo sensing of DA in living rat brain (Figure 1(B)). This study opens up a versatile strategy in the design of electrode/brain interface for exploring brain chemistry[46].
2.2 Interface Design Guided by Formal Po-tential Sequence
In addition to biological entities that are endowed with high specificity, electrocatalysis with functional materials also provide promising opportunities for in vivo sensing[47,48,49]. Then, the question was asked: how could we identify the materials that can selectively recognize target analytes among numerous coexisting neurochemicals? In this case, we implemented the idea of guiding the interface design based on the formal potential (E0') of the neurochemicals. In general, for the molecules with low E0', such as ascorbic acid (AA), we demonstrate that by constructing the electrode surface with catalysts that can sufficiently accelerate the electrochemical processes, the “optimal selectivity” would be realized. AA, mostly known as the name of vitamin C, gains intense interests in brain research as it has been revealed recently to act more than simply a “micronutrient” in the CNS[50, 51]. Accumulating evidence suggests a close association between AA and neurochemical processes involved in both cognitively intact and impaired brain, which was almost unrecognized due to the lack of in vivo and qualitative assessment of this chemically unstable molecule in living systems[52, 53]. The availability of selective and reliable sensing approach essentially offers great opportunities for in vivo sensing of AA in both fundamental and clinical researches.
We found that the confinement of carbon nanotubes (CNTs) onto electrode surface remarkably accelerates the electrochemical oxidation of AA, enabling the oxidation to occur almost without an overpotential[54,55,56,57]. The excellent electrochemical activity of CNTs made it possible for us to selectively monitor AA without interference from other co-exiting species in biological systems. Further mechanistic study revealed that both chemical and electronic properties of CNTs are dominant factors for providing the sensing selectivity toward AA[56].
We further extended our studies on designing electrochemical sensors for molecules with high E0'. We reasoned that electrocatalysts that are highly reactive for analytes, while show minimal reactivity to the interfering species, could fulfill the selectivity requirement. In this case, single-atom catalysts (SACs), featuring maximum atom utilization and chemically tunable coordination environment, are appealing candidates for rationally designing electrocatalyst with tailor-made selectivity and catalytic activity[58, 59]. Taken oxygen, a highly important biomolecule with high E0', as a typical target, we demonstrated that through tailoring catalytic metal atom-adsorbates (including both O2 and H2O2) interactions, single-atom electrocatalysts can realize selective catalytic activity toward O2 reduction without interference from H2O2. Specifically, we found that with designed Co-N4/C catalyst, H2O2 shows very weak adsorption on Co centers, enabling the priority of direct four-electron reduction of O2 on the electrode[60]. The excellent sele-ctivity toward O2 reduction endows the Co-N4/C-based sensor with a high selectivity for O2 sensing without interference from H2O2, offering a novel avenue to selective O2 sensing in living animals (Figure 2(A)). Subsequent studies using different SACs further outline a more general role of tailoring catalytic metal atom-adsorbates interaction in achieving high selectivity, especially in (bio)sensing of physiological important chemicals with high E0' values, such as nitric oxide[61] (Figure 2(B)) and glucose[62] (Figure 2(C)).
Figure 2
(A) (a-b) HAADF-STEM image (a) and EXAFS fitting curve (b) of Co-N4/C. (c) Relative current ratio of H2O2 to O2 recorded by three catalysts shown in the figure, and (d) in vivo O2 fluctuation recorded by Co-N4/C-based sensor[60]. Reproduced with permission of Ref. 60, copyright 2020 American Chemical Society. (B) (a-b) Schematic illustration of fabrication process (a) and stretching process (b) of Ni SAC/N-C-based sensor. (c) Real-time monitoring of NO release[61]. Reproduced with permission of Ref. 61, copyright 2020 Springer Nature. (C) (a) Schematic illustration of online electrochemical system (OECS) with a SAC-based electrochemical sensor for continuous glucose monitoring, and (b) typical amperometric response of OECS toward microdialysate in vivo sampled from rat brain[62]. Reproduced with permission of Ref. 62, copyright 2019 Springer. (color on line)
In addition to the attempts to modulate interfacial electron transfer property of the neurochemicals with single atom catalysts, we recently tried to modulate the electron transfer pathway of different neurochemicals. Graphdiyne (GDY), featuring unique chemical and electronic properties, is an appealing target for this line of research[63]. For example, this two-dimensional carbon allotrope shows a low reduction potential and highly conjugated electronic structure. We reasoned that these would make GDY an efficient reducing agent and stabilizer for synthesizing nanoparticles on the surface, therefore, generating new type of catalyst with tunable catalytic activity[64]. Using Pd as an example, we demonstrated that GDY enables electroless deposition of ultrafine Pd clusters on its surface, yielding an excellent composite catalyst with superior selectivity and activity toward the reduction of 4-nitrophenol (Figure 3(A)). Giving a variety of metals are available, the electroless deposition approach provides a versatile platform for designing of electrocatalysts with tailorable selectivity, paving new avenues to modulating electron transfer for diverse selectivity needs in in vivo sensing applications. Furthermore, we have established a liquid phase exfoliation method with lithium hexafluorosilicate (Li2SiF6) for GDY, which is envisaged useful to understand the intrinsic property of GDY[65] (Figure 3(B)). The mec-hanism behind this efficient exfoliation probably attributed to the strong non-covalent interactions between SiF62- and GDY, and the easy diffusion of the cation (Li+ and K+) into the interlayers, thus synergistically weaken the attractive forces between GDY interlayers. With this method, damage-free single-, and few-layered GDY flakes can be obtained under ambient and mild conditions. Moreover, the exfoliated GDY flakes in the form of solvent suspension allow an immediate utilization for spin-coating or any other solution processing to address crucial prospects for sensor construction. Besides GDY, its oxidized form named graphdiyne oxide (GDYO) that possesses not only acetylenic bonds but also various forms of oxygen-containing functional groups on its surface also exhibits attractive properties for in vivo sensing. The exploration of the structure-activity relationship of GDYO greatly improves our understanding of the mechanism behind modulating the interfacial electron transfer, contributing to the development of a highly selective GDYO-based humidity sensor for potential human health and disease monitoring[66] (Figure 3(C)).
Figure 3
(A) Schematic illustration of Pd/GDY formation via electroless deposition[64]. Reproduced with permission of Ref. 64, copyright 2015 American Chemical Society. (B) TEM image (a), HRTEM image (b), STEM image (c), FFT pattern (d) and AFM images (e-f) of exfoliated GDY[65]. Reproduced with permission of Ref. 65, copyright 2019 WILEY-VCH. (C) (a) Schematic illustration of bonding model between water molecules and carbon nanomaterials (i.e., GO and GDYO). (b) Normalized current responses of GDYO-based sensor towards different human respiratory patterns[66]. Reproduced with permission of Ref. 66, copyright 2018 WILEY-VCH. (D) (a) Construction of the mediated biosensor interface and (b) typical amperometric responses to glucose and other neurochemicals[67]. Reproduced with permission of Ref. 67, copyright 2020 American Chemical Society. (color on line)
Based on these studies, we demonstrated that the electron transfer pathway can be further regulated by interfacing GDY and redox molecules[67] (e.g., methylene green, MG). While the semiconducting GDY films decelerate the oxidation of AA, the intercalated MG molecules that relay electrons by fast self-exchange can accelerate the oxidation of dihydronicotinamide adenine dinucleotide (NADH), making it possible to construct a selective bioelectrocatalytic interface. As a typical example, NAD+-dependent glucose dehydro-genase (GDH) is immobilized onto the MG-intercalated GDY nanosheets. The resulted GDH-MG/GDY-based biosensor shows great selectivity of glucose, free from the interference from coexisting neurochemicals including AA, DA and serotonin (5-HT) (Figure 3(D)). This study provides a universal strategy for tuning electrochemical properties of semiconducting or insulating materials, greatly broadening the studies on in vivo sensing sciences.
2.3 Ion Transport-Based In Vivo Sensor
In the complex environment of living brains, the electroactive neurochemicals are only the minority. For the other neurochemicals, their sluggish electrochemical reaction kinetics poses grand challenges on in vivo sensing by direct electrolysis. To circumvent this issue, ion transport-based sensing method opens a new paradigm in design of in vivo neurochemical sensors[68]. For example, ion current rectification (ICR), an ion transport behavior featured with unequal current intensities at the negative/positive potential with the same magnitude, reflects specific interaction between analytes and recognition elements modified on the inner-surface of nanopipettes. However, nanopi-pettes are inapplicable to be directly implanted into the living brain, mainly due to their fragileness and nanometer size. To address this issue, we prepared polyimidazolium-brush (PimB)-modified micropipe-ttes and successfully extended ICR from nanoscale to microscale in symmetric electrolyte solution[69, 70]. For deep understanding of the experimental observations, we proposed a three-layer model consisting of a charged layer (CL), a double layer (DL) and a bulk layer (BL) (Figure 4(A)). Validated by both numeric simulation and experimental results, it is demonstrated that influencing factors including the length of PimB, the concentration of electrolyte and the radius of micropipette collectively account for the observed microscale ion current rectification (MICR). With sufficient mechanical robustness and a designable inner surface, this MICR-based sensor unlocks the potential for ion transport-based in vivo neurochemical sensing. By coupling ATP aptamer and MICR-based sensors, we were able to determine the basal level of ATP in brain cortex[71].
Figure 4
(A) (a) Typical current-voltage responses acquired by using bare micropipette (black curve) and PimB-modified micro-pipette (red curve). (b) Schematic illustration of proposed three-layer model[69]. Reproduced with permission of Ref. 69, copyright 2017 American Chemical Society. (B) Schematic illustrations of (a) experimental setup of in vivo pH sensing by using PvimB-modified micropipette and (b) transient ion transport behaviors and generated ion currents under high-frequency pulse potential[72]. Reproduced with permission of Ref. 72, copyright 2021 Royal Society of Chemistry. (color on line)
We envisioned that MICR-based sensing methods may be capable of monitoring the dynamics of electrochemically inactive neurochemicals in the living brains. To improve the spatiotemporal resolution of MICR-based sensors, we developed the first transient ion transport-based microsensor by applying high-fre-quency square-wave pulse potential[72]. In general, the rapid association/dissociation of specific analytes on the modification alters surface charge density of the inner surface of the micropipette, resulting in variation of ion current output with temporal resolution at milliseconds level. Taking pH as a model target, we prepared poly(N-vinylimidazole)-brush (PvimB)-mod-ified micropipette sensors, which exhibited high temporal resolution, sensitivity, selectivity, repeatability and stability (Figure 4(B)). The as-prepared microsen-sor was then implanted into the living rat brain, successfully monitoring pH variation during acid-base disturbance upon CO2 inhalation. We proposed that this study established a versatile sensing platform based on transient ion transport behavior, opening up a new avenue for in vivo monitoring of transient process of neurochemical dynamics through rationale interface design.
3 Developing Highly Biocompatible In Vivo Sensors
The voltammetric and amperometric sensors enable selective and sensitive analyses of biomolecules in living systems, showing great potential in unraveling the physio-pathological role of neurochemicals in brain. However, as these sensors are based on electrolytic-cell mechanism, an external voltage is always required to drive the oxidation/reduction of the analyte. This inevitably generates a current flow in the electrolytic cell, and potentially changes the activity of cells that is sensitive to electrical stimulus, such as neurons in the CNS. For example, it was observed that low-voltage-activated currents decrease the firing frequency of neurons[73].
To tackle the biocompatibility issue, potentiometric methods offer a possible solution that determines analyte concentrate by potential difference according to the Nernst equation. Under equilibrium conditions, the preferred transport of target analytes across the selective membrane introduces a mensurable electromotive force (EMF) between an indicating electrode and a reference electrode, as the readout of relative concentration of analytes. Based on this principle, potentiometric sensors with different ion selective membranes, termed as ion-selective electrode (ISE), make a powerful tool for ion analysis[74]. To explore the application of ISEs in in vivo ion sensing, we coupled H+-selective membrane with CFEs (CF-H+ISEs)[75]. This as-prepared potentiometric sensor showed not only high selectivity and reversibility but also strong antifouling property against proteins, therefore allowing us to investigate pH changes in living rat brains during quick acid-base disturbances. We thereafter utilized carbon materials as transducing layers to establish a more stable sensing interface, realizing extended applications in monitoring the dynamics of extracellular K+[76] and Ca2+[77]in vivo.
However, there are only limited choices of permselective membranes, posing a significant challenge to potentiometric sensing methods to be well-suited for sensing the majority of neurochemicals. More recently, we proposed a galvanic cell-based sensing mechanism that realizes the sensing of neurochemicals under nearly zero current flow. Generally, a GRP-based sensing system consists of two separated compartments (Figure 5(A)). In different compartments, reductants and oxidants undergo electro-redox rection at an anode (i.e., the indicating electrode) and a cathode (i.e., the reference electrode), respectively. For spontaneous redox reactions, the established potential difference measured by a voltmeter with high internal resistance could provide information of target redox pairs. In practice, the potential readout is determined by the concentration and electrode kinetics of analytes, presence of coexisting redox species, and other factors. Therefore, the designs of cathodes and anodes are essential for making a self-driven galvanic cell[78]. We first demonstrated that laccase can undergo an efficient direct electron transfer (DET) and show efficient electrochemical catalysis on carbon nanotube(CNT)-modified electrodes. This initiates the employment of laccase based direct electron transfer systems at the cathode of biofuel cells. Moreover, with controlling the orientation of the laccase at CNT electrodes using ethanol-assisted immobilization, a dramatic enhancement of the catalytic activity was observed as revealed by 600% increase of oxygen reduction current (Figure 5(B))[79]. As oxygen can be reduced at the highest potential where the thermodynamics allowed, laccase electrode provides the foundation for the establishment of ideal galvanic redox potentiometric (GRP) cathode. Based on these results, we developed the first GRP sensor with laccase/CNT and CNT electrode as a cathode and an anode, respectively. The as-designed two-electrode GRP sensor shows high sensitivity and selectivity to AA, enabling the reliable measurement of the basal level of cortical AA in living rat brain with excellent biocompatibility (Figure 5(C))[80].
Figure 5
(A) Schematic illustration of GRP sensor[80]. (B) Schematic illustration of orientation and cyclic voltammograms of untreated and ethanol-treated laccase on SWCNT/GCE[79]. Reproduced with permission of Ref. 79, copyright 2017 American Chemical Society. (C) (a) Schematic illustration of GRP sensor for in vivo sensing of AA. (b) Calibration curves of the GRP sensor before and after BSA absorption. (c) Real-time recording of cortical AA level during global cerebral ischemia (red arrow) and reperfusion (blue arrow)[80]. Reproduced with permission of Ref. 80, copyright 2018 American Chemical Society. (D) (a) Schematic illustration of the single-carbon-fiber-powered microsensor and in vivo sensing of AA with the microsensor. (b) Change in open circuit voltage (OCV) after adding AA and interferents. (c) In vivo synchronous OCV measurement with the microsensor and electrophysiological recording by the MEA[81]. Reproduced with permission of Ref. 81, copyright 2020 WILEY-VCH. (color on line)
Encouraged by these studies, we took a further step to develop a single-carbon-fiber-powered GRP microsensor for neurochemical monitoring[81]. Specifically, we combined the bipolar electrochemistry and GRP to fabricate a single-electrode powered GRP sensor. We selected AA as the model neurochemical and modified the anodic pole with multi-walled carbon nanotubes (MWNTs), on which the onset potential of AA oxidation is -0.10 V vs. Ag/AgCl. The micropipette was backfilled with 3 mol·L-1 KCl solution containing K3Fe(CN)6/K4Fe(CN)6 with higher reduction potential (i.e., +0.30 V) to accomplish the spont-aneous reaction. The as-designed bipolar GRP sensor exhibits high selectivity and sensitivity to AA, and most importantly, shows undetectable effects on transient or lasting, excitatory or inhibitory activity of neurons as closely investigated with electrophysiological recording (Figure 5(D)). The excellent neuronal compatibility of the GRP sensor diminishes the potential crosstalk between multimodal recording systems, paving an effective way to study the correlation between chemical and electrical signaling of neurons in brain research.
4 In Vivo Neurochemical Sensing: from Basic Research to Application
Our bodies and the systems that comprise them are very complex, rendering results obtained from in vitro studies must be considered carefully. It is also clear that neurochemicals in physiological and pathological processes are largely different in terms of their quantitative, spatial and temporal information. Therefore, in vivo analysis can provide critical information for understanding the intrinsic molecular mechanism of brain function, as well as the cause of neurodegenerative disorders.
We have demonstrated above that our micro-sized electrochemical sensors, featured with implantable to specific region, high selectivity of target neurochemicals and high biocompatibility of nervous system, hold great promise for in vivo sensing of neurochemicals in living animals. Indeed, with these sensors, we have successfully monitored the dynamic changes of a great variety of neurochemicals including AA[55, 56], dopamine[46], oxygen[60], ATP[44, 71], glucose[30, 31, 33], lactic acid[36], catecholamine[82], K+[76], Ca2+[77] and Mg2+[83] in living brain of animals with high temporal and spatial resolution.
Taken in vivo sensing of AA as an example here to demonstrate how we started from molecule detection to revealing molecular mechanism. With the brain-im-plantable ascorbate sensor (CFEAA1.0 and CFEAA2.0), we reported the first observation on the release of ascorbate in response to spreading depression[84] (Figure 6(A)) and cytotoxic edema[85] (Figure 6(B)), both frequently happened during brain injury. Further mechanistic studies with inhibitors revealed that the AA release may undergo through volume sensitive organic anion channels. Interestingly, by combining electroanalytical chemistry with single-cell amperometry, we also found that AA may also be released by vesicular-mediated exocytosis[86].
Figure 6
(A) (a) Current signals recorded with CFEAA1.0 under different bias voltages and (b) in vivo sensing of AA in the rat cortex during SD process[84]. Reproduced with permission of Ref. 84, copyright 2019 WILEY-VCH. (B) Schematic illustration and typical current responses of in vivo AA release in rat brain by using CFEAA2.0[85]. Reproduced with permission of Ref. 85, copyright 2020 American Chemical Society. (color on line)
More excitingly, with the controlled fabrication, our in vivo sensors show great potential for commercialization, and many of our in vivo sensing system have been widely adopted by doctors in dozens of hospitals, and validated their effectiveness with clinically relevant animal models. We together observed the dynamic changes of AA[87,88,89,90,91], DA[92], norepinephrine[93], glutamic acid[94,95,96], Mg2+[97] and other biomolecules in tinnitus, vertigo, olfactory dysfunction, spinal cord injury, and many other disease related animal models, providing rich information to reveal the molecular mechanism of related diseases. Taken together, our in vivo sensors can reliably monitor the neurochemicals in the complicated central nervous system, providing essential means for understanding brain function and disease.
5 Summary and Outlooks
To gain insight into essential features of the brain, it is of great importance to provide series of sensing science and technology that fill a vital need for understanding the chemistry nature behind physiological and pathological processes. We have been working in this field for about 20 years, devoting to constructing new principles of electrochemistry in designing platforms for dynamic analysis and sensing in vivo with high selectivity and biocompatibility. To fulfill the selectivity requirement, we construct the sensing interface by modulating electrochemical reaction kinetics, for example, via tailoring catalytic active site-analyte interactions and via building an electron transfer way specifically for the target analytes. To tackle the biocompatibility issue of electrolytic cell-based methods, we develop the first galvanic redox potentiometric sensor that provides not only excellent sensing performance but also superior neuronal compatibility. Along with these progresses, we have realized the spatiotemporal resolution analysis and sensing of neurochemicals with high selectivity, which greatly promotes the understanding of brain chemistry.
Nevertheless, we must note that these in vivo sensors still face many challenges. One urgent need is to minimize the sensors design and improve its biocompatibility to overcome the body’s natural rejection response[98]. Another important aspect is to realize high-throughput and multimodal analysis, where artificial intelligence, physiological techniques, and wireless technology can be combined to resolving multiple biological parameters, and allowing remote monitoring and assessments in real-time. In addition, electrochemical systems can be further improved to be multifunctional, incorporating sensors and then applying a drug or intervention based on the sensor data obtained for precise medicine. Taken together, with the development of chemistry, materials science, micro-processing technology, information engineering and other related technologies, the establishment of highly selective, highly sensitive, high spatial and temporal resolution sensors for in vivo analysis of multi-species will become the focus of research in this field. The in vivo sensing system will greatly contribute to the deep understanding of brain function, and promote the development of accurate diagnosis and assist in treatment decision.
Acknowledgements
This work was supported by the National Key Research and Development Program (No. 2018YFE0200800), the National Natural Science Foundation of China (Nos. 21790390, 21790391 and 22134002), the National Basic Research Program of China (Nos. 2018YFA0703501 and 2016YFA0200104), the Strategic Priority Research Program of Chinese Academy of Sciences (XDB30000000), and Chinese Academy of Sciences (QYZDJ-SSWSLH030).
Sun FM, Zeng JZ, JingM, Zhou JH, Feng JS, Owen SF, Luo YC, Li FN, WangH, YamaguchiT, Yong ZH, Gao YJ, Peng WL, Wang LZ, Zhang SY, Du JL, Lin DY, XuM, Kreitzer AC, Cui GH, Li YL.
A genetically encoded fluorescent sensor enables rapid and specific detection of dopamine in flies, fish, and mice
The extracellular space (ECS) of the brain has an extremely complex spatial organization, which has defied conventional light microscopy. Consequently, despite a marked interest in the physiological roles of brain ECS, its structure and dynamics remain largely inaccessible for experimenters. We combined 3D-STED microscopy and fluorescent labeling of the extracellular fluid to develop super-resolution shadow imaging (SUSHI) of brain ECS in living organotypic brain slices. SUSHI enables quantitative analysis of ECS structure and reveals dynamics on multiple scales in response to a variety of physiological stimuli. Because SUSHI produces sharp negative images of all cellular structures, it also enables unbiased imaging of unlabeled brain cells with respect to their anatomical context. Moreover, the extracellular labeling strategy greatly alleviates problems of photobleaching and phototoxicity associated with traditional imaging approaches. As a straightforward variant of STED microscopy, SUSHI provides unprecedented access to the structure and dynamics of live brain ECS and neuropil.
VilletteV, ChavarhaM, Dimov IK, BradleyJ, PradhanL, MathieuB, Evans SW, ChamberlandS, Shi DQ, Yang RZ, Kim BB, AyonA, JalilA, St-PierreF, Schnitzer MJ, Bi GQ, TothK, DingJ, DieudonneS, Lin MZ.
Ultrafast two-photon imaging of a high-gain voltage indicator in awake behaving mice
Communication between cells by release of specific chemical messengers via exocytosis plays crucial roles in biological process. Electrochemical detection based on ultramicroelectrodes (UMEs) has become one of the most powerful techniques in real-time monitoring of an extremely small number of released molecules during very short time scales, owing to its intrinsic advantages such as fast response, excellent sensitivity, and high spatiotemporal resolution. Great successes have been achieved in the use of UME methods to obtain quantitative and kinetic information about released chemical messengers and to reveal the molecular mechanism in vesicular exocytosis. In this paper, we review recent developments in monitoring exocytosis by use of UMEs-electrochemical-based techniques including electrochemical detection using micrometer and nanometer-sized sensors, scanning electrochemical microscopy (SECM), and UMEs implemented in lab-on-a-chip (LOC) microsystems. These advances are of great significance in obtaining a better understanding of vesicular exocytosis and chemical communications between cells, and will facilitate developments in many fields, including analytical chemistry, biological science, and medicine. Furthermore, future developments in electrochemical probing of exocytosis are also proposed.
Fast-scan cyclic voltammetry (FSCV) has been used for over 20 years to study rapid neurotransmission in awake and behaving animals. These experiments were first carried out with carbon-fiber microelectrodes (CFMs) encased in borosilicate glass, which can be inserted into the brain through micromanipulators and guide cannulas. More recently, chronically implantable CFMs constructed with small diameter fused-silica have been introduced. These electrodes can be affixed in the brain with minimal tissue response, which permits longitudinal measurements of neurotransmission in single recording locations during behavior. Both electrode designs have been used to make novel discoveries in the fields of neurobiology, behavioral neuroscience, and psychopharmacology. The purpose of this Review is to address important considerations for the use of FSCV to study neurotransmitters in awake and behaving animals, with a focus on measurements of striatal dopamine. Common issues concerning experimental design, data collection, and calibration are addressed. When necessary, differences between the two methodologies (acute vs chronic recordings) are discussed. The topics raised in this Review are particularly important as the field moves beyond dopamine toward new neurochemicals and brain regions.
Roberts JG, Sombers LA.
Fast-scan cyclic voltammetry: chemical sensing in the brain and beyond
Fast-scan cyclic voltammetry (FSCV) at carbon-fiber microelectrodes (CFMEs) is a versatile electrochemical technique to probe neurochemical dynamics in vivo. Progress in FSCV methodology continues to address analytical challenges arising from biological needs to measure low concentrations of neurotransmitters at specific sites. This review summarizes recent advances in FSCV method development in three areas: (1) waveform optimization, (2) electrode development, and (3) data analysis. First, FSCV waveform parameters such as holding potential, switching potential, and scan rate have been optimized to monitor new neurochemicals. The new waveform shapes introduce better selectivity toward specific molecules such as serotonin, histamine, hydrogen peroxide, octopamine, adenosine, guanosine, and neuropeptides. Second, CFMEs have been modified with nanomaterials such as carbon nanotubes or replaced with conducting polymers to enhance sensitivity, selectivity, and antifouling properties. Different geometries can be obtained by 3D-printing, manufacturing arrays, or fabricating carbon nanopipettes. Third, data analysis is important to sort through the thousands of CVs obtained. Recent developments in data analysis include preprocessing by digital filtering, principal components analysis for distinguishing analytes, and developing automated algorithms to detect peaks. Future challenges include multisite measurements, machine learning, and integration with other techniques. Advances in FSCV will accelerate research in neurochemistry to answer new biological questions about dynamics of signaling in the brain.
HeienM, Khan AS, Ariansen JL, Cheer JF, PhillipsP E M, WassumK M, WightmanR M.
Real-time measurement of dopamine fluctuations after cocaine in brain of behaving rats
[J]. Proc. Natl. Acad. Sci. U.S.A., 2005, 102(29):10023-10028.
A facile electrochemical method for simultaneous and on-line measurements of glucose and lactate in brain microdialysate with prussian blue as the electrocatalyst for reduction of hydrogen peroxide
Physiologically relevant online electrochemical method for continuous and simultaneous monitoring of striatum glucose and lactate following global cerebral ischemia/reperfusion
Zhuang XM, Wang DL, Lin YQ, Yang LF, YuP, JiangW, Mao LQ.
Strong interaction between imidazolium-based polycationic polymer and ferricyanide: toward redox potential regulation for selective in vivo electrochemical measurements
Hybridization of bioelectrochemically functional infinite coordination polymer nanoparticles with carbon nanotubes for highly sensitive and selective in vivo electrochemical monitoring
Online ele-ctrochemical systems for continuous neurochemical measurements with low-potential mediator-based electroche-mical biosensors as selective detectors
The microelectrode is referred to the scale (at least one dimension) is not more than 25 μm, and the size is smaller than the diffusion layer thickness. Microelectrode has unique nature due to their small size. Increasing interests have been drawn in microelectrode fabrication and application since microelectrode possesses special features such as high current density, rapid response, immunity to ohmic drop, high signal to noise ratio. Microelectrode plays an important role in electrochemical technology for its unique properties, and there are many applications in the field of life analysis, such as the single cell detection and in vivo analysis. The preparation of microelectrode is the key to the application of microelectrode electrochemical development. According to the excellent performance of microelectrode, many technologies are involved in the preparation of microelectrode, such as electrochemical etching, electro-deposition method, self-assembly technology, electroless plating technology.Meanwhile, the preparation methods provide the possibility for rapid preparation of microelectrodes. According to different characteristics of the conventional electrodes, microelectrode research progress in recent years are reviewed, including the unique characteristics of microelectrode, classification and preparation methods of microelectrodes, applications in the field of life analysis, the challenge for the microelectrode and development direction.<br>Contents<br>1 Introduction<br>2 Unique characteristics of microelectrode<br>2.1 High current density<br>2.2 Immunity to ohmic drop<br>2.3 High signal to noise ratio<br>2.4 Fast mass transfer speed<br>2.5 Simple device<br>2.6 Drawbacks<br>3 Classification and preparation methods of microelectrodes<br>3.1 Carbon ultra-microelectrode<br>3.2 Carbon nanotube microelectrode<br>3.3 Carbon fiber microelectrode<br>3.4 Platinum microelectrode<br>3.5 Gold microelectrode<br>4 The in vivo/single cell applications of microelectrodes<br>4.1 In vivo detection<br>4.2 Single cell detection<br>5 Conclusion
Hu KK, Liu YL, OleinickA, Mirkin MV, Huang WH, AmatoreC.
Nanoelectrodes for intracellular measurements of reactive oxygen and nitrogen species in single living cells
Haloperidol, a widely used antipsychotic drug, was tested for its ability to block the behavioral response to amphetamine and to elicit catalepsy in rats treated with saline or ascorbic acid (1000 milligrams per kilogram of body weight). By itself, ascorbic acid failed to exert significant behavioral effects, but it enhanced the antiamphetamine and cataleptogenic effects of haloperidol (0.1 or 0.5 milligrams per kilogram). These results, combined with a growing body of biochemical evidence, suggest that ascorbic acid plays an important role in modulating the behavioral effects of haloperidol and related antipsychotic drugs.
Rice ME.
Ascorbate regulation and its neuroprotective role in the brain
Ascorbic acid (vitamin C) occurs physiologically as the ascorbate anion: a water-soluble antioxidant that is found throughout the body. However, despite the high, homeostatically regulated levels of brain ascorbate, its specific functions in the CNS are only beginning to be elucidated. Certainly, it acts as part of the intracellular antioxidant network, and as such is normally neuroprotective. There is also evidence that it acts as a neuromodulator. A possibly unique role it might have is as an antioxidant in the brain extracellular microenvironment, where its concentration is modulated by glutamate-ascorbate heteroexchange at glutamate uptake sites. Ongoing studies of ascorbate and glutamate transporters should lead to rapid progress in understanding ascorbate regulation and function.
Zhang MN, LiuK, Gong KP, SuL, ChenY, Mao LQ.
Continuous on-line monitoring of extracellular ascorbate depletion in the rat striatum induced by global ischemia with carbon nanotube-modified glassy carbon electrode integrated into a thin-layer radial flow cell
Using as-synthesized vertically aligned carbon nanotube-sheathed carbon fibers (VACNT-CFs) as microelectrodes without any postsynthesis functionalization, we have developed in this study a new method for in vivo monitoring of ascorbate with high selectivity and reproducibility. The VACNT-CFs are formed via pyrolysis of iron phthalocyanine (FePc) on the carbon fiber support. After electrochemical pretreatment in 1.0 M NaOH solution, the pristine VACNT-CF microelectrodes exhibit typical microelectrode behavior with fast electron transfer kinetics for electrochemical oxidation of ascorbate and are useful for selective ascorbate monitoring even with other electroactive species (e.g., dopamine, uric acid, and 5-hydroxytryptamine) coexisting in rat brain. Pristine VACNT-CFs are further demonstrated to be a reliable and stable microelectrode for in vivo recording of the dynamic increase of ascorbate evoked by intracerebral infusion of glutamate. Use of a pristine VACNT-CF microelectrode can effectively avoid any manual electrode modification and is free from person-to-person and/or electrode-to-electrode deviations intrinsically associated with conventional CF electrode fabrication, which often involves electrode surface modification with randomly distributed CNTs or other pretreatments, and hence allows easy fabrication of highly selective, reproducible, and stable microelectrodes even by nonelectrochemists. Thus, this study offers a new and reliable platform for in vivo monitoring of neurochemicals (e.g., ascorbate) to largely facilitate future studies on the neurochemical processes involved in various physiological events.
Xiao TF, Jiang YN, Ji WL, Mao LQ.
Controllable and reproducible sheath of carbon fibers with single-walled carbon nanotubes through electrophoretic deposition for in vivo electrochemical measurements
Nitric oxide (NO) has been implicated in a variety of physiological and pathological processes. Monitoring cellular levels of NO requires a sensor to feature adequate sensitivity, transient recording ability and biocompatibility. Herein we report a single-atom catalysts (SACs)-based electrochemical sensor for the detection of NO in live cellular environment. The system employs nickel single atoms anchored on N-doped hollow carbon spheres (Ni SACs/N-C) that act as an excellent catalyst for electrochemical oxidation of NO. Notably, Ni SACs/N-C shows superior electrocatalytic performance to the commonly used Ni based nanomaterials, attributing from the greatly reduced Gibbs free energy that are required for Ni SACs/N-C in activating NO oxidation. Moreover, Ni SACs-based flexible and stretchable sensor shows high biocompatibility and low nanomolar sensitivity, enabling the real-time monitoring of NO release from cells upon drug and stretch stimulation. Our results demonstrate a promising means of using SACs for electrochemical sensing applications.
Hou HF, Mao JJ, Han YH, WuF, Zhang MN, Wang DS, Mao LQ, Li YD.
Single-atom electrocatalysis: a new approach to in vivo electrochemical biosensing
High antifouling property of ion-selective membrane: toward in vivo monitoring of pH change in live brain of rats with membrane-coated carbon fiber electrodes
In vivo monitoring of extracellular calcium ion (Ca2+) is of great importance due to its significant contributions in different (patho)physiological processes. In this study, we develop a potentiometric method with solid-state ion-selective electrodes (ISEs) for in vivo monitoring of the dynamics of the extracellular Ca2+ by using hollow carbon nanospheres (HCNs) as a transducing layer and solid contact to efficiently promote the ion-to-electron transduction between an ionophore-doped solvated polymeric membrane and a conducting substrate. We find that the use of HCNs essentially improves the stability of the signal response and minimizes the potential drift of the as-prepared ISEs. With three-shelled HCNs (3s-HCNs) as the transducing layer, we fabricate a solid-state Ca2+-selective microelectrode by forming a Ca2+-selective membrane with calcium ionophore II as the recognition unit, 2-nitrophenyl octyl ether as the plasticizer, sodium tetrakis[3,5-bis(trifluoromethyl)phenyl] borate as the ion exchanger, and polyvinyl chloride polymeric as the matrix onto the 3s-HCN-modified carbon fiber electrodes. The as-prepared electrode shows a high stability and a near Nernst response of 28 mV/decade toward Ca2+ over a concentration range from 10(-5) to 0.05 M as well as a good selectivity against species endogenously existing in the central nervous system. With these properties, the electrode is used for real-time recording of the dynamics of extracellular Ca2+ during spreading depression induced by electrical stimulation, in which the extracellular Ca2+ in rat cortex is found to decrease by 50.0 +/- 7.5% (n = 5) during spreading depression. This study essentially offers a new platform to develop solid-state ISEs, which is particularly useful for in vivo measurements of metal ions and pH in live rat brain.
WuF, YuP, MaoL.
Self-powered electrochemical systems as neurochemical sensors: toward self-triggered in vivo analysis of brain chemistry
Selective amperometric recording of endogenous ascorbate secretion from a single rat adrenal chromaffin cell with pretreated carbon fiber microelectrodes
Quantitative description of ascorbate secretion at a single-cell level is of great importance in physiological studies; however, most studies on the ascorbate secretion have so far been performed through analyzing cell extracts with high performance liquid chromatography, which lacks time resolution and analytical performance on a single-cell level. This study demonstrates a single-cell amperometry with carbon fiber microelectrodes (CFEs) to selectively monitor amperometric vesicular secretion of endogenous ascorbate from a single rat adrenal chromaffin cell. The CFEs are electrochemically pretreated in a weakly basic solution (pH 9.5), and such pretreatment essentially enables the oxidation of ascorbate to occur at a relatively low potential (i.e., 0.0 V vs Ag/AgCl), and further a high selectivity for ascorbate measurement over endogenously existing electroactive species such as epinephrine, norepinephrine, and dopamine. The selectivity is ensured by much larger amperometric response at the pretreated CFEs toward ascorbate over those toward other endogenously existing electroactive species added into the solution or ejected to the electrode with a micropuffer pipet, and by the totally suppressed current response by adding ascorbate oxidase into the cell lysate. With the pretreated CFE-based single-cell amperometry developed here, exocytosis of endogenous ascorbate of rat adrenal chromaffin cells is directly observed and ensured with the calcium ion-dependent high K-induced secretion of endogenous ascorbate from the cells. Moreover, the quantitative information on the exocytosis of endogenous ascorbate is provided.
ZhangN, Liu JX, Ma FR, Yu LS, Lin YQ, LiuK, Mao LQ.
Change of extracellular ascorbic acid in the brain cortex following ice water vestibular stimulation: an on-line electrochemical detection coupled with in vivo microdialysis sampling for guinea pigs
Zhang YH, Li LJ, LiT, XinY, Liu JX, Ma FR, Mao LQ.
In vivo measurement of the dynamics of norepinephrine in an olfactory bulb following ischemia-induced olfactory dysfunction and its responses to dexamethasone treatment
In vivo ele-ctrochemical recording of continuous change of magnesium in medial vestibular nucleus following vertigo induced by ice water vestibular stimulation
Real-time measurement of transmitter release from single synaptic vesicles
1
1995
... The human brain confers on us the capacities of thinking, feeling, learning and acting, which essentially emerges from the electrical and chemical interactions among tens of billions of neurons that compose the brain circuits. Through worldwide collaborations across disciplines, studies have been conducted to gain comprehensive understanding of the relationship between structural maps and functional maps, spanning the levels of vesicles, cells, circuits, and even higher levels[1,2,3,4]. Despite of these breakthroughs, it is still a long-term goal to obtain selective, quantitative, and real-time information on the kinetics of chemicals in living animal brain, providing promising ways to uncover molecular mechanism in both physiological and pathological processes. To date, a handful of analytical tools have been developed for measurement of targeted neurochemicals, which broadly fall into two categories, namely, noninvasive ones and invasive ones[5,6,7]. Noninvasive methods (e.g., functional magnetic resonance imaging and fluorescent assays) are capable of providing cross-scale pattern of neural activities while keeping the intact brain circuits injury-free[8,9,10,11,12]. On the other hand, invasive methods (e.g., in vivo electrochemistry) endowed with superior spatiotemporal resolution are capable of providing precise and dynamic pattern of specific targets during various neural activities[13,14,15,16,17,18]. This review aims to briefly outline our studies in tissue-implantable electrochemical sensing technologies in terms of molecular selectivity, biocompatibility, and potential applications in brain sciences. We will summarize for the first time the rationale behind engineering interfacial electron transfer and the development of potentiometric systems to control over the electrochemical selectivity and the biocompatibility of the in vivo sensors, with a specific highlight on employing these sensors for revealing molecular mechanism in physiological and pathological processes. ...
Cortical column and whole-brain imaging with molecular contrast and nanoscale resolution
1
2019
... The human brain confers on us the capacities of thinking, feeling, learning and acting, which essentially emerges from the electrical and chemical interactions among tens of billions of neurons that compose the brain circuits. Through worldwide collaborations across disciplines, studies have been conducted to gain comprehensive understanding of the relationship between structural maps and functional maps, spanning the levels of vesicles, cells, circuits, and even higher levels[1,2,3,4]. Despite of these breakthroughs, it is still a long-term goal to obtain selective, quantitative, and real-time information on the kinetics of chemicals in living animal brain, providing promising ways to uncover molecular mechanism in both physiological and pathological processes. To date, a handful of analytical tools have been developed for measurement of targeted neurochemicals, which broadly fall into two categories, namely, noninvasive ones and invasive ones[5,6,7]. Noninvasive methods (e.g., functional magnetic resonance imaging and fluorescent assays) are capable of providing cross-scale pattern of neural activities while keeping the intact brain circuits injury-free[8,9,10,11,12]. On the other hand, invasive methods (e.g., in vivo electrochemistry) endowed with superior spatiotemporal resolution are capable of providing precise and dynamic pattern of specific targets during various neural activities[13,14,15,16,17,18]. This review aims to briefly outline our studies in tissue-implantable electrochemical sensing technologies in terms of molecular selectivity, biocompatibility, and potential applications in brain sciences. We will summarize for the first time the rationale behind engineering interfacial electron transfer and the development of potentiometric systems to control over the electrochemical selectivity and the biocompatibility of the in vivo sensors, with a specific highlight on employing these sensors for revealing molecular mechanism in physiological and pathological processes. ...
Dissociable dopamine dynamics for learning and motivation
1
2019
... The human brain confers on us the capacities of thinking, feeling, learning and acting, which essentially emerges from the electrical and chemical interactions among tens of billions of neurons that compose the brain circuits. Through worldwide collaborations across disciplines, studies have been conducted to gain comprehensive understanding of the relationship between structural maps and functional maps, spanning the levels of vesicles, cells, circuits, and even higher levels[1,2,3,4]. Despite of these breakthroughs, it is still a long-term goal to obtain selective, quantitative, and real-time information on the kinetics of chemicals in living animal brain, providing promising ways to uncover molecular mechanism in both physiological and pathological processes. To date, a handful of analytical tools have been developed for measurement of targeted neurochemicals, which broadly fall into two categories, namely, noninvasive ones and invasive ones[5,6,7]. Noninvasive methods (e.g., functional magnetic resonance imaging and fluorescent assays) are capable of providing cross-scale pattern of neural activities while keeping the intact brain circuits injury-free[8,9,10,11,12]. On the other hand, invasive methods (e.g., in vivo electrochemistry) endowed with superior spatiotemporal resolution are capable of providing precise and dynamic pattern of specific targets during various neural activities[13,14,15,16,17,18]. This review aims to briefly outline our studies in tissue-implantable electrochemical sensing technologies in terms of molecular selectivity, biocompatibility, and potential applications in brain sciences. We will summarize for the first time the rationale behind engineering interfacial electron transfer and the development of potentiometric systems to control over the electrochemical selectivity and the biocompatibility of the in vivo sensors, with a specific highlight on employing these sensors for revealing molecular mechanism in physiological and pathological processes. ...
Microglia monitor and protect neuronal function through specialized somatic purinergic junctions
1
2020
... The human brain confers on us the capacities of thinking, feeling, learning and acting, which essentially emerges from the electrical and chemical interactions among tens of billions of neurons that compose the brain circuits. Through worldwide collaborations across disciplines, studies have been conducted to gain comprehensive understanding of the relationship between structural maps and functional maps, spanning the levels of vesicles, cells, circuits, and even higher levels[1,2,3,4]. Despite of these breakthroughs, it is still a long-term goal to obtain selective, quantitative, and real-time information on the kinetics of chemicals in living animal brain, providing promising ways to uncover molecular mechanism in both physiological and pathological processes. To date, a handful of analytical tools have been developed for measurement of targeted neurochemicals, which broadly fall into two categories, namely, noninvasive ones and invasive ones[5,6,7]. Noninvasive methods (e.g., functional magnetic resonance imaging and fluorescent assays) are capable of providing cross-scale pattern of neural activities while keeping the intact brain circuits injury-free[8,9,10,11,12]. On the other hand, invasive methods (e.g., in vivo electrochemistry) endowed with superior spatiotemporal resolution are capable of providing precise and dynamic pattern of specific targets during various neural activities[13,14,15,16,17,18]. This review aims to briefly outline our studies in tissue-implantable electrochemical sensing technologies in terms of molecular selectivity, biocompatibility, and potential applications in brain sciences. We will summarize for the first time the rationale behind engineering interfacial electron transfer and the development of potentiometric systems to control over the electrochemical selectivity and the biocompatibility of the in vivo sensors, with a specific highlight on employing these sensors for revealing molecular mechanism in physiological and pathological processes. ...
Measuring synaptic vesicles using cellular electrochemistry and nanoscale molecular imaging
1
2017
... The human brain confers on us the capacities of thinking, feeling, learning and acting, which essentially emerges from the electrical and chemical interactions among tens of billions of neurons that compose the brain circuits. Through worldwide collaborations across disciplines, studies have been conducted to gain comprehensive understanding of the relationship between structural maps and functional maps, spanning the levels of vesicles, cells, circuits, and even higher levels[1,2,3,4]. Despite of these breakthroughs, it is still a long-term goal to obtain selective, quantitative, and real-time information on the kinetics of chemicals in living animal brain, providing promising ways to uncover molecular mechanism in both physiological and pathological processes. To date, a handful of analytical tools have been developed for measurement of targeted neurochemicals, which broadly fall into two categories, namely, noninvasive ones and invasive ones[5,6,7]. Noninvasive methods (e.g., functional magnetic resonance imaging and fluorescent assays) are capable of providing cross-scale pattern of neural activities while keeping the intact brain circuits injury-free[8,9,10,11,12]. On the other hand, invasive methods (e.g., in vivo electrochemistry) endowed with superior spatiotemporal resolution are capable of providing precise and dynamic pattern of specific targets during various neural activities[13,14,15,16,17,18]. This review aims to briefly outline our studies in tissue-implantable electrochemical sensing technologies in terms of molecular selectivity, biocompatibility, and potential applications in brain sciences. We will summarize for the first time the rationale behind engineering interfacial electron transfer and the development of potentiometric systems to control over the electrochemical selectivity and the biocompatibility of the in vivo sensors, with a specific highlight on employing these sensors for revealing molecular mechanism in physiological and pathological processes. ...
Analytical and quantitative in vivo monitoring of brain neurochemistry by electrochemical and imaging approaches
1
2018
... The human brain confers on us the capacities of thinking, feeling, learning and acting, which essentially emerges from the electrical and chemical interactions among tens of billions of neurons that compose the brain circuits. Through worldwide collaborations across disciplines, studies have been conducted to gain comprehensive understanding of the relationship between structural maps and functional maps, spanning the levels of vesicles, cells, circuits, and even higher levels[1,2,3,4]. Despite of these breakthroughs, it is still a long-term goal to obtain selective, quantitative, and real-time information on the kinetics of chemicals in living animal brain, providing promising ways to uncover molecular mechanism in both physiological and pathological processes. To date, a handful of analytical tools have been developed for measurement of targeted neurochemicals, which broadly fall into two categories, namely, noninvasive ones and invasive ones[5,6,7]. Noninvasive methods (e.g., functional magnetic resonance imaging and fluorescent assays) are capable of providing cross-scale pattern of neural activities while keeping the intact brain circuits injury-free[8,9,10,11,12]. On the other hand, invasive methods (e.g., in vivo electrochemistry) endowed with superior spatiotemporal resolution are capable of providing precise and dynamic pattern of specific targets during various neural activities[13,14,15,16,17,18]. This review aims to briefly outline our studies in tissue-implantable electrochemical sensing technologies in terms of molecular selectivity, biocompatibility, and potential applications in brain sciences. We will summarize for the first time the rationale behind engineering interfacial electron transfer and the development of potentiometric systems to control over the electrochemical selectivity and the biocompatibility of the in vivo sensors, with a specific highlight on employing these sensors for revealing molecular mechanism in physiological and pathological processes. ...
Recent advances in development of devices and probes for sensing and imaging in the brain
1
2021
... The human brain confers on us the capacities of thinking, feeling, learning and acting, which essentially emerges from the electrical and chemical interactions among tens of billions of neurons that compose the brain circuits. Through worldwide collaborations across disciplines, studies have been conducted to gain comprehensive understanding of the relationship between structural maps and functional maps, spanning the levels of vesicles, cells, circuits, and even higher levels[1,2,3,4]. Despite of these breakthroughs, it is still a long-term goal to obtain selective, quantitative, and real-time information on the kinetics of chemicals in living animal brain, providing promising ways to uncover molecular mechanism in both physiological and pathological processes. To date, a handful of analytical tools have been developed for measurement of targeted neurochemicals, which broadly fall into two categories, namely, noninvasive ones and invasive ones[5,6,7]. Noninvasive methods (e.g., functional magnetic resonance imaging and fluorescent assays) are capable of providing cross-scale pattern of neural activities while keeping the intact brain circuits injury-free[8,9,10,11,12]. On the other hand, invasive methods (e.g., in vivo electrochemistry) endowed with superior spatiotemporal resolution are capable of providing precise and dynamic pattern of specific targets during various neural activities[13,14,15,16,17,18]. This review aims to briefly outline our studies in tissue-implantable electrochemical sensing technologies in terms of molecular selectivity, biocompatibility, and potential applications in brain sciences. We will summarize for the first time the rationale behind engineering interfacial electron transfer and the development of potentiometric systems to control over the electrochemical selectivity and the biocompatibility of the in vivo sensors, with a specific highlight on employing these sensors for revealing molecular mechanism in physiological and pathological processes. ...
Functional surface engineering of C-dots for fluorescent biosensing and in vivo bioimaging
1
2014
... The human brain confers on us the capacities of thinking, feeling, learning and acting, which essentially emerges from the electrical and chemical interactions among tens of billions of neurons that compose the brain circuits. Through worldwide collaborations across disciplines, studies have been conducted to gain comprehensive understanding of the relationship between structural maps and functional maps, spanning the levels of vesicles, cells, circuits, and even higher levels[1,2,3,4]. Despite of these breakthroughs, it is still a long-term goal to obtain selective, quantitative, and real-time information on the kinetics of chemicals in living animal brain, providing promising ways to uncover molecular mechanism in both physiological and pathological processes. To date, a handful of analytical tools have been developed for measurement of targeted neurochemicals, which broadly fall into two categories, namely, noninvasive ones and invasive ones[5,6,7]. Noninvasive methods (e.g., functional magnetic resonance imaging and fluorescent assays) are capable of providing cross-scale pattern of neural activities while keeping the intact brain circuits injury-free[8,9,10,11,12]. On the other hand, invasive methods (e.g., in vivo electrochemistry) endowed with superior spatiotemporal resolution are capable of providing precise and dynamic pattern of specific targets during various neural activities[13,14,15,16,17,18]. This review aims to briefly outline our studies in tissue-implantable electrochemical sensing technologies in terms of molecular selectivity, biocompatibility, and potential applications in brain sciences. We will summarize for the first time the rationale behind engineering interfacial electron transfer and the development of potentiometric systems to control over the electrochemical selectivity and the biocompatibility of the in vivo sensors, with a specific highlight on employing these sensors for revealing molecular mechanism in physiological and pathological processes. ...
Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors
1
2018
... The human brain confers on us the capacities of thinking, feeling, learning and acting, which essentially emerges from the electrical and chemical interactions among tens of billions of neurons that compose the brain circuits. Through worldwide collaborations across disciplines, studies have been conducted to gain comprehensive understanding of the relationship between structural maps and functional maps, spanning the levels of vesicles, cells, circuits, and even higher levels[1,2,3,4]. Despite of these breakthroughs, it is still a long-term goal to obtain selective, quantitative, and real-time information on the kinetics of chemicals in living animal brain, providing promising ways to uncover molecular mechanism in both physiological and pathological processes. To date, a handful of analytical tools have been developed for measurement of targeted neurochemicals, which broadly fall into two categories, namely, noninvasive ones and invasive ones[5,6,7]. Noninvasive methods (e.g., functional magnetic resonance imaging and fluorescent assays) are capable of providing cross-scale pattern of neural activities while keeping the intact brain circuits injury-free[8,9,10,11,12]. On the other hand, invasive methods (e.g., in vivo electrochemistry) endowed with superior spatiotemporal resolution are capable of providing precise and dynamic pattern of specific targets during various neural activities[13,14,15,16,17,18]. This review aims to briefly outline our studies in tissue-implantable electrochemical sensing technologies in terms of molecular selectivity, biocompatibility, and potential applications in brain sciences. We will summarize for the first time the rationale behind engineering interfacial electron transfer and the development of potentiometric systems to control over the electrochemical selectivity and the biocompatibility of the in vivo sensors, with a specific highlight on employing these sensors for revealing molecular mechanism in physiological and pathological processes. ...
A genetically encoded fluorescent sensor enables rapid and specific detection of dopamine in flies, fish, and mice
1
2018
... The human brain confers on us the capacities of thinking, feeling, learning and acting, which essentially emerges from the electrical and chemical interactions among tens of billions of neurons that compose the brain circuits. Through worldwide collaborations across disciplines, studies have been conducted to gain comprehensive understanding of the relationship between structural maps and functional maps, spanning the levels of vesicles, cells, circuits, and even higher levels[1,2,3,4]. Despite of these breakthroughs, it is still a long-term goal to obtain selective, quantitative, and real-time information on the kinetics of chemicals in living animal brain, providing promising ways to uncover molecular mechanism in both physiological and pathological processes. To date, a handful of analytical tools have been developed for measurement of targeted neurochemicals, which broadly fall into two categories, namely, noninvasive ones and invasive ones[5,6,7]. Noninvasive methods (e.g., functional magnetic resonance imaging and fluorescent assays) are capable of providing cross-scale pattern of neural activities while keeping the intact brain circuits injury-free[8,9,10,11,12]. On the other hand, invasive methods (e.g., in vivo electrochemistry) endowed with superior spatiotemporal resolution are capable of providing precise and dynamic pattern of specific targets during various neural activities[13,14,15,16,17,18]. This review aims to briefly outline our studies in tissue-implantable electrochemical sensing technologies in terms of molecular selectivity, biocompatibility, and potential applications in brain sciences. We will summarize for the first time the rationale behind engineering interfacial electron transfer and the development of potentiometric systems to control over the electrochemical selectivity and the biocompatibility of the in vivo sensors, with a specific highlight on employing these sensors for revealing molecular mechanism in physiological and pathological processes. ...
Super-resolution imaging of the extracellular space in living brain tissue
1
2018
... The human brain confers on us the capacities of thinking, feeling, learning and acting, which essentially emerges from the electrical and chemical interactions among tens of billions of neurons that compose the brain circuits. Through worldwide collaborations across disciplines, studies have been conducted to gain comprehensive understanding of the relationship between structural maps and functional maps, spanning the levels of vesicles, cells, circuits, and even higher levels[1,2,3,4]. Despite of these breakthroughs, it is still a long-term goal to obtain selective, quantitative, and real-time information on the kinetics of chemicals in living animal brain, providing promising ways to uncover molecular mechanism in both physiological and pathological processes. To date, a handful of analytical tools have been developed for measurement of targeted neurochemicals, which broadly fall into two categories, namely, noninvasive ones and invasive ones[5,6,7]. Noninvasive methods (e.g., functional magnetic resonance imaging and fluorescent assays) are capable of providing cross-scale pattern of neural activities while keeping the intact brain circuits injury-free[8,9,10,11,12]. On the other hand, invasive methods (e.g., in vivo electrochemistry) endowed with superior spatiotemporal resolution are capable of providing precise and dynamic pattern of specific targets during various neural activities[13,14,15,16,17,18]. This review aims to briefly outline our studies in tissue-implantable electrochemical sensing technologies in terms of molecular selectivity, biocompatibility, and potential applications in brain sciences. We will summarize for the first time the rationale behind engineering interfacial electron transfer and the development of potentiometric systems to control over the electrochemical selectivity and the biocompatibility of the in vivo sensors, with a specific highlight on employing these sensors for revealing molecular mechanism in physiological and pathological processes. ...
Ultrafast two-photon imaging of a high-gain voltage indicator in awake behaving mice
1
2019
... The human brain confers on us the capacities of thinking, feeling, learning and acting, which essentially emerges from the electrical and chemical interactions among tens of billions of neurons that compose the brain circuits. Through worldwide collaborations across disciplines, studies have been conducted to gain comprehensive understanding of the relationship between structural maps and functional maps, spanning the levels of vesicles, cells, circuits, and even higher levels[1,2,3,4]. Despite of these breakthroughs, it is still a long-term goal to obtain selective, quantitative, and real-time information on the kinetics of chemicals in living animal brain, providing promising ways to uncover molecular mechanism in both physiological and pathological processes. To date, a handful of analytical tools have been developed for measurement of targeted neurochemicals, which broadly fall into two categories, namely, noninvasive ones and invasive ones[5,6,7]. Noninvasive methods (e.g., functional magnetic resonance imaging and fluorescent assays) are capable of providing cross-scale pattern of neural activities while keeping the intact brain circuits injury-free[8,9,10,11,12]. On the other hand, invasive methods (e.g., in vivo electrochemistry) endowed with superior spatiotemporal resolution are capable of providing precise and dynamic pattern of specific targets during various neural activities[13,14,15,16,17,18]. This review aims to briefly outline our studies in tissue-implantable electrochemical sensing technologies in terms of molecular selectivity, biocompatibility, and potential applications in brain sciences. We will summarize for the first time the rationale behind engineering interfacial electron transfer and the development of potentiometric systems to control over the electrochemical selectivity and the biocompatibility of the in vivo sensors, with a specific highlight on employing these sensors for revealing molecular mechanism in physiological and pathological processes. ...
Monitoring rapid chemical communication in the brain
1
2008
... The human brain confers on us the capacities of thinking, feeling, learning and acting, which essentially emerges from the electrical and chemical interactions among tens of billions of neurons that compose the brain circuits. Through worldwide collaborations across disciplines, studies have been conducted to gain comprehensive understanding of the relationship between structural maps and functional maps, spanning the levels of vesicles, cells, circuits, and even higher levels[1,2,3,4]. Despite of these breakthroughs, it is still a long-term goal to obtain selective, quantitative, and real-time information on the kinetics of chemicals in living animal brain, providing promising ways to uncover molecular mechanism in both physiological and pathological processes. To date, a handful of analytical tools have been developed for measurement of targeted neurochemicals, which broadly fall into two categories, namely, noninvasive ones and invasive ones[5,6,7]. Noninvasive methods (e.g., functional magnetic resonance imaging and fluorescent assays) are capable of providing cross-scale pattern of neural activities while keeping the intact brain circuits injury-free[8,9,10,11,12]. On the other hand, invasive methods (e.g., in vivo electrochemistry) endowed with superior spatiotemporal resolution are capable of providing precise and dynamic pattern of specific targets during various neural activities[13,14,15,16,17,18]. This review aims to briefly outline our studies in tissue-implantable electrochemical sensing technologies in terms of molecular selectivity, biocompatibility, and potential applications in brain sciences. We will summarize for the first time the rationale behind engineering interfacial electron transfer and the development of potentiometric systems to control over the electrochemical selectivity and the biocompatibility of the in vivo sensors, with a specific highlight on employing these sensors for revealing molecular mechanism in physiological and pathological processes. ...
In-vivo electrochemistry: What can we learn about living systems?
1
2008
... The human brain confers on us the capacities of thinking, feeling, learning and acting, which essentially emerges from the electrical and chemical interactions among tens of billions of neurons that compose the brain circuits. Through worldwide collaborations across disciplines, studies have been conducted to gain comprehensive understanding of the relationship between structural maps and functional maps, spanning the levels of vesicles, cells, circuits, and even higher levels[1,2,3,4]. Despite of these breakthroughs, it is still a long-term goal to obtain selective, quantitative, and real-time information on the kinetics of chemicals in living animal brain, providing promising ways to uncover molecular mechanism in both physiological and pathological processes. To date, a handful of analytical tools have been developed for measurement of targeted neurochemicals, which broadly fall into two categories, namely, noninvasive ones and invasive ones[5,6,7]. Noninvasive methods (e.g., functional magnetic resonance imaging and fluorescent assays) are capable of providing cross-scale pattern of neural activities while keeping the intact brain circuits injury-free[8,9,10,11,12]. On the other hand, invasive methods (e.g., in vivo electrochemistry) endowed with superior spatiotemporal resolution are capable of providing precise and dynamic pattern of specific targets during various neural activities[13,14,15,16,17,18]. This review aims to briefly outline our studies in tissue-implantable electrochemical sensing technologies in terms of molecular selectivity, biocompatibility, and potential applications in brain sciences. We will summarize for the first time the rationale behind engineering interfacial electron transfer and the development of potentiometric systems to control over the electrochemical selectivity and the biocompatibility of the in vivo sensors, with a specific highlight on employing these sensors for revealing molecular mechanism in physiological and pathological processes. ...
Monitoring of vesicular exocytosis from single cells using micrometer and nanometer-sized electrochemical sensors
1
2009
... The human brain confers on us the capacities of thinking, feeling, learning and acting, which essentially emerges from the electrical and chemical interactions among tens of billions of neurons that compose the brain circuits. Through worldwide collaborations across disciplines, studies have been conducted to gain comprehensive understanding of the relationship between structural maps and functional maps, spanning the levels of vesicles, cells, circuits, and even higher levels[1,2,3,4]. Despite of these breakthroughs, it is still a long-term goal to obtain selective, quantitative, and real-time information on the kinetics of chemicals in living animal brain, providing promising ways to uncover molecular mechanism in both physiological and pathological processes. To date, a handful of analytical tools have been developed for measurement of targeted neurochemicals, which broadly fall into two categories, namely, noninvasive ones and invasive ones[5,6,7]. Noninvasive methods (e.g., functional magnetic resonance imaging and fluorescent assays) are capable of providing cross-scale pattern of neural activities while keeping the intact brain circuits injury-free[8,9,10,11,12]. On the other hand, invasive methods (e.g., in vivo electrochemistry) endowed with superior spatiotemporal resolution are capable of providing precise and dynamic pattern of specific targets during various neural activities[13,14,15,16,17,18]. This review aims to briefly outline our studies in tissue-implantable electrochemical sensing technologies in terms of molecular selectivity, biocompatibility, and potential applications in brain sciences. We will summarize for the first time the rationale behind engineering interfacial electron transfer and the development of potentiometric systems to control over the electrochemical selectivity and the biocompatibility of the in vivo sensors, with a specific highlight on employing these sensors for revealing molecular mechanism in physiological and pathological processes. ...
Electrochemical analysis of neurotransmitters
1
2015
... The human brain confers on us the capacities of thinking, feeling, learning and acting, which essentially emerges from the electrical and chemical interactions among tens of billions of neurons that compose the brain circuits. Through worldwide collaborations across disciplines, studies have been conducted to gain comprehensive understanding of the relationship between structural maps and functional maps, spanning the levels of vesicles, cells, circuits, and even higher levels[1,2,3,4]. Despite of these breakthroughs, it is still a long-term goal to obtain selective, quantitative, and real-time information on the kinetics of chemicals in living animal brain, providing promising ways to uncover molecular mechanism in both physiological and pathological processes. To date, a handful of analytical tools have been developed for measurement of targeted neurochemicals, which broadly fall into two categories, namely, noninvasive ones and invasive ones[5,6,7]. Noninvasive methods (e.g., functional magnetic resonance imaging and fluorescent assays) are capable of providing cross-scale pattern of neural activities while keeping the intact brain circuits injury-free[8,9,10,11,12]. On the other hand, invasive methods (e.g., in vivo electrochemistry) endowed with superior spatiotemporal resolution are capable of providing precise and dynamic pattern of specific targets during various neural activities[13,14,15,16,17,18]. This review aims to briefly outline our studies in tissue-implantable electrochemical sensing technologies in terms of molecular selectivity, biocompatibility, and potential applications in brain sciences. We will summarize for the first time the rationale behind engineering interfacial electron transfer and the development of potentiometric systems to control over the electrochemical selectivity and the biocompatibility of the in vivo sensors, with a specific highlight on employing these sensors for revealing molecular mechanism in physiological and pathological processes. ...
Progress of in vivo electrochemical analysis of brain neurochemistry
1
2019
... The human brain confers on us the capacities of thinking, feeling, learning and acting, which essentially emerges from the electrical and chemical interactions among tens of billions of neurons that compose the brain circuits. Through worldwide collaborations across disciplines, studies have been conducted to gain comprehensive understanding of the relationship between structural maps and functional maps, spanning the levels of vesicles, cells, circuits, and even higher levels[1,2,3,4]. Despite of these breakthroughs, it is still a long-term goal to obtain selective, quantitative, and real-time information on the kinetics of chemicals in living animal brain, providing promising ways to uncover molecular mechanism in both physiological and pathological processes. To date, a handful of analytical tools have been developed for measurement of targeted neurochemicals, which broadly fall into two categories, namely, noninvasive ones and invasive ones[5,6,7]. Noninvasive methods (e.g., functional magnetic resonance imaging and fluorescent assays) are capable of providing cross-scale pattern of neural activities while keeping the intact brain circuits injury-free[8,9,10,11,12]. On the other hand, invasive methods (e.g., in vivo electrochemistry) endowed with superior spatiotemporal resolution are capable of providing precise and dynamic pattern of specific targets during various neural activities[13,14,15,16,17,18]. This review aims to briefly outline our studies in tissue-implantable electrochemical sensing technologies in terms of molecular selectivity, biocompatibility, and potential applications in brain sciences. We will summarize for the first time the rationale behind engineering interfacial electron transfer and the development of potentiometric systems to control over the electrochemical selectivity and the biocompatibility of the in vivo sensors, with a specific highlight on employing these sensors for revealing molecular mechanism in physiological and pathological processes. ...
Materials for flexible bioelectronic systems as chronic neural interfaces
1
2020
... The human brain confers on us the capacities of thinking, feeling, learning and acting, which essentially emerges from the electrical and chemical interactions among tens of billions of neurons that compose the brain circuits. Through worldwide collaborations across disciplines, studies have been conducted to gain comprehensive understanding of the relationship between structural maps and functional maps, spanning the levels of vesicles, cells, circuits, and even higher levels[1,2,3,4]. Despite of these breakthroughs, it is still a long-term goal to obtain selective, quantitative, and real-time information on the kinetics of chemicals in living animal brain, providing promising ways to uncover molecular mechanism in both physiological and pathological processes. To date, a handful of analytical tools have been developed for measurement of targeted neurochemicals, which broadly fall into two categories, namely, noninvasive ones and invasive ones[5,6,7]. Noninvasive methods (e.g., functional magnetic resonance imaging and fluorescent assays) are capable of providing cross-scale pattern of neural activities while keeping the intact brain circuits injury-free[8,9,10,11,12]. On the other hand, invasive methods (e.g., in vivo electrochemistry) endowed with superior spatiotemporal resolution are capable of providing precise and dynamic pattern of specific targets during various neural activities[13,14,15,16,17,18]. This review aims to briefly outline our studies in tissue-implantable electrochemical sensing technologies in terms of molecular selectivity, biocompatibility, and potential applications in brain sciences. We will summarize for the first time the rationale behind engineering interfacial electron transfer and the development of potentiometric systems to control over the electrochemical selectivity and the biocompatibility of the in vivo sensors, with a specific highlight on employing these sensors for revealing molecular mechanism in physiological and pathological processes. ...
Hitchhiker’s guide to voltammetry: acute and chronic electrodes for in vivo fast-scan cyclic voltammetry
1
2017
... The emerging of fast scan cyclic voltammetry (FSCV) represents a great step forward to in vivo monitoring of the fast kinetics of neurochemicals sensitively, selectively and quantitively[19,20,21]. In specific, the electrochemical kinetics at carbon fiber electrode (CFE) among different neurochemicals becomes distinguishable at ultrahigh potential sweeping speed, resulting in distinct redox peak potentials for qualitative measurements. Over years of development and improvement, FSCV has greatly facilitated the understanding of rapid release of neurotransmitters in some pathological and physiological processes. Notably, these rapid release processes often bring with concurrent change of other neurochemicals (e.g., local pH). Therefore, with imperative need of eliminating mutual interferences and acquiring accurate measurements, strict requirements have been put forward on concurrent multicomponent analysis. Confronted with this challenge, the ongoing improvements in computational methods provide immense opportunities[22,23,24,25]. Recently, we proposed a deep learning-based voltammetric (DLV) platform for in vivo analysis of multiple neurochemicals by using vapor grown carbon fiber microelectrodes (VGCFEs). Dopamine (DA), ascorbate (AA) and ions were selected as a typical neurotransmitter, an important neuromodulator, and main component of extracellular fluid in CNS, respectively[26]. This method enables us to record the interplaying concentration changes in living rat brain during spreading depression (SD), which indicates a bright perspective not only in molecular mechanism discovery, but also in medical diagnosis and treatment. ...
Fast-scan cyclic voltammetry: chemical sensing in the brain and beyond
1
2018
... The emerging of fast scan cyclic voltammetry (FSCV) represents a great step forward to in vivo monitoring of the fast kinetics of neurochemicals sensitively, selectively and quantitively[19,20,21]. In specific, the electrochemical kinetics at carbon fiber electrode (CFE) among different neurochemicals becomes distinguishable at ultrahigh potential sweeping speed, resulting in distinct redox peak potentials for qualitative measurements. Over years of development and improvement, FSCV has greatly facilitated the understanding of rapid release of neurotransmitters in some pathological and physiological processes. Notably, these rapid release processes often bring with concurrent change of other neurochemicals (e.g., local pH). Therefore, with imperative need of eliminating mutual interferences and acquiring accurate measurements, strict requirements have been put forward on concurrent multicomponent analysis. Confronted with this challenge, the ongoing improvements in computational methods provide immense opportunities[22,23,24,25]. Recently, we proposed a deep learning-based voltammetric (DLV) platform for in vivo analysis of multiple neurochemicals by using vapor grown carbon fiber microelectrodes (VGCFEs). Dopamine (DA), ascorbate (AA) and ions were selected as a typical neurotransmitter, an important neuromodulator, and main component of extracellular fluid in CNS, respectively[26]. This method enables us to record the interplaying concentration changes in living rat brain during spreading depression (SD), which indicates a bright perspective not only in molecular mechanism discovery, but also in medical diagnosis and treatment. ...
Recent advances in fast-scan cyclic voltammetry
1
2020
... The emerging of fast scan cyclic voltammetry (FSCV) represents a great step forward to in vivo monitoring of the fast kinetics of neurochemicals sensitively, selectively and quantitively[19,20,21]. In specific, the electrochemical kinetics at carbon fiber electrode (CFE) among different neurochemicals becomes distinguishable at ultrahigh potential sweeping speed, resulting in distinct redox peak potentials for qualitative measurements. Over years of development and improvement, FSCV has greatly facilitated the understanding of rapid release of neurotransmitters in some pathological and physiological processes. Notably, these rapid release processes often bring with concurrent change of other neurochemicals (e.g., local pH). Therefore, with imperative need of eliminating mutual interferences and acquiring accurate measurements, strict requirements have been put forward on concurrent multicomponent analysis. Confronted with this challenge, the ongoing improvements in computational methods provide immense opportunities[22,23,24,25]. Recently, we proposed a deep learning-based voltammetric (DLV) platform for in vivo analysis of multiple neurochemicals by using vapor grown carbon fiber microelectrodes (VGCFEs). Dopamine (DA), ascorbate (AA) and ions were selected as a typical neurotransmitter, an important neuromodulator, and main component of extracellular fluid in CNS, respectively[26]. This method enables us to record the interplaying concentration changes in living rat brain during spreading depression (SD), which indicates a bright perspective not only in molecular mechanism discovery, but also in medical diagnosis and treatment. ...
Real-time measurement of dopamine fluctuations after cocaine in brain of behaving rats
1
2005
... The emerging of fast scan cyclic voltammetry (FSCV) represents a great step forward to in vivo monitoring of the fast kinetics of neurochemicals sensitively, selectively and quantitively[19,20,21]. In specific, the electrochemical kinetics at carbon fiber electrode (CFE) among different neurochemicals becomes distinguishable at ultrahigh potential sweeping speed, resulting in distinct redox peak potentials for qualitative measurements. Over years of development and improvement, FSCV has greatly facilitated the understanding of rapid release of neurotransmitters in some pathological and physiological processes. Notably, these rapid release processes often bring with concurrent change of other neurochemicals (e.g., local pH). Therefore, with imperative need of eliminating mutual interferences and acquiring accurate measurements, strict requirements have been put forward on concurrent multicomponent analysis. Confronted with this challenge, the ongoing improvements in computational methods provide immense opportunities[22,23,24,25]. Recently, we proposed a deep learning-based voltammetric (DLV) platform for in vivo analysis of multiple neurochemicals by using vapor grown carbon fiber microelectrodes (VGCFEs). Dopamine (DA), ascorbate (AA) and ions were selected as a typical neurotransmitter, an important neuromodulator, and main component of extracellular fluid in CNS, respectively[26]. This method enables us to record the interplaying concentration changes in living rat brain during spreading depression (SD), which indicates a bright perspective not only in molecular mechanism discovery, but also in medical diagnosis and treatment. ...
Automated stoichiometry analysis of single-molecule fluorescence imaging traces via deep learning
1
2019
... The emerging of fast scan cyclic voltammetry (FSCV) represents a great step forward to in vivo monitoring of the fast kinetics of neurochemicals sensitively, selectively and quantitively[19,20,21]. In specific, the electrochemical kinetics at carbon fiber electrode (CFE) among different neurochemicals becomes distinguishable at ultrahigh potential sweeping speed, resulting in distinct redox peak potentials for qualitative measurements. Over years of development and improvement, FSCV has greatly facilitated the understanding of rapid release of neurotransmitters in some pathological and physiological processes. Notably, these rapid release processes often bring with concurrent change of other neurochemicals (e.g., local pH). Therefore, with imperative need of eliminating mutual interferences and acquiring accurate measurements, strict requirements have been put forward on concurrent multicomponent analysis. Confronted with this challenge, the ongoing improvements in computational methods provide immense opportunities[22,23,24,25]. Recently, we proposed a deep learning-based voltammetric (DLV) platform for in vivo analysis of multiple neurochemicals by using vapor grown carbon fiber microelectrodes (VGCFEs). Dopamine (DA), ascorbate (AA) and ions were selected as a typical neurotransmitter, an important neuromodulator, and main component of extracellular fluid in CNS, respectively[26]. This method enables us to record the interplaying concentration changes in living rat brain during spreading depression (SD), which indicates a bright perspective not only in molecular mechanism discovery, but also in medical diagnosis and treatment. ...
U-Net: deep learning for cell counting, detection, and morphometry
1
2019
... The emerging of fast scan cyclic voltammetry (FSCV) represents a great step forward to in vivo monitoring of the fast kinetics of neurochemicals sensitively, selectively and quantitively[19,20,21]. In specific, the electrochemical kinetics at carbon fiber electrode (CFE) among different neurochemicals becomes distinguishable at ultrahigh potential sweeping speed, resulting in distinct redox peak potentials for qualitative measurements. Over years of development and improvement, FSCV has greatly facilitated the understanding of rapid release of neurotransmitters in some pathological and physiological processes. Notably, these rapid release processes often bring with concurrent change of other neurochemicals (e.g., local pH). Therefore, with imperative need of eliminating mutual interferences and acquiring accurate measurements, strict requirements have been put forward on concurrent multicomponent analysis. Confronted with this challenge, the ongoing improvements in computational methods provide immense opportunities[22,23,24,25]. Recently, we proposed a deep learning-based voltammetric (DLV) platform for in vivo analysis of multiple neurochemicals by using vapor grown carbon fiber microelectrodes (VGCFEs). Dopamine (DA), ascorbate (AA) and ions were selected as a typical neurotransmitter, an important neuromodulator, and main component of extracellular fluid in CNS, respectively[26]. This method enables us to record the interplaying concentration changes in living rat brain during spreading depression (SD), which indicates a bright perspective not only in molecular mechanism discovery, but also in medical diagnosis and treatment. ...
Deep learning enables cross-modality super-resolution in fluorescence microscopy
1
2019
... The emerging of fast scan cyclic voltammetry (FSCV) represents a great step forward to in vivo monitoring of the fast kinetics of neurochemicals sensitively, selectively and quantitively[19,20,21]. In specific, the electrochemical kinetics at carbon fiber electrode (CFE) among different neurochemicals becomes distinguishable at ultrahigh potential sweeping speed, resulting in distinct redox peak potentials for qualitative measurements. Over years of development and improvement, FSCV has greatly facilitated the understanding of rapid release of neurotransmitters in some pathological and physiological processes. Notably, these rapid release processes often bring with concurrent change of other neurochemicals (e.g., local pH). Therefore, with imperative need of eliminating mutual interferences and acquiring accurate measurements, strict requirements have been put forward on concurrent multicomponent analysis. Confronted with this challenge, the ongoing improvements in computational methods provide immense opportunities[22,23,24,25]. Recently, we proposed a deep learning-based voltammetric (DLV) platform for in vivo analysis of multiple neurochemicals by using vapor grown carbon fiber microelectrodes (VGCFEs). Dopamine (DA), ascorbate (AA) and ions were selected as a typical neurotransmitter, an important neuromodulator, and main component of extracellular fluid in CNS, respectively[26]. This method enables us to record the interplaying concentration changes in living rat brain during spreading depression (SD), which indicates a bright perspective not only in molecular mechanism discovery, but also in medical diagnosis and treatment. ...
Deep learning for voltammetric sensing in a living animal brain
1
2021
... The emerging of fast scan cyclic voltammetry (FSCV) represents a great step forward to in vivo monitoring of the fast kinetics of neurochemicals sensitively, selectively and quantitively[19,20,21]. In specific, the electrochemical kinetics at carbon fiber electrode (CFE) among different neurochemicals becomes distinguishable at ultrahigh potential sweeping speed, resulting in distinct redox peak potentials for qualitative measurements. Over years of development and improvement, FSCV has greatly facilitated the understanding of rapid release of neurotransmitters in some pathological and physiological processes. Notably, these rapid release processes often bring with concurrent change of other neurochemicals (e.g., local pH). Therefore, with imperative need of eliminating mutual interferences and acquiring accurate measurements, strict requirements have been put forward on concurrent multicomponent analysis. Confronted with this challenge, the ongoing improvements in computational methods provide immense opportunities[22,23,24,25]. Recently, we proposed a deep learning-based voltammetric (DLV) platform for in vivo analysis of multiple neurochemicals by using vapor grown carbon fiber microelectrodes (VGCFEs). Dopamine (DA), ascorbate (AA) and ions were selected as a typical neurotransmitter, an important neuromodulator, and main component of extracellular fluid in CNS, respectively[26]. This method enables us to record the interplaying concentration changes in living rat brain during spreading depression (SD), which indicates a bright perspective not only in molecular mechanism discovery, but also in medical diagnosis and treatment. ...
Rational design of surface/interface chemistry for quantitative in vivo monitoring of brain chemistry
1
2012
... In addition to voltammetry, potential-controlled amperometry as another important branch of in vivo electrochemical methods is well suited for continuous sensing of neurochemicals. Specifically, amperometry measures the concentration-dependent current transient over time at a constant potential, which quantitatively measures the rapid dynamics of target analytes. To achieve selective sensing, dedicated efforts have been devoted into constructing electrode/brain interfaces to exclusively permit specific electrochemical reactions[27, 28]. One common strategy is to immobilize recognition elements onto electrode surface, exemplified by biomacromolecules such as enzymes and aptamers. Besides, electrocatalysts modified onto the electrode could also achieve selective sensing by either accelerating the adsorption/desorption process or altering electron transfer kinetics and pathways of specific neurochemicals. More recently, ion transport-based sensors also provide another complementary strategy for selective sensing, greatly expanding the scope of detectable neurochemicals to encompass not only electroactive but also electroinactive ones. We herein highlight our latest progress on tuning electrochemical behavior of targeted neurochemicals, with a focus on unraveling the rationale behind engineering electrode/brain interface. ...
Bioelectrochemistry for in vivo analysis: Interface engineering toward implantable electrochemical biosensors
1
2017
... In addition to voltammetry, potential-controlled amperometry as another important branch of in vivo electrochemical methods is well suited for continuous sensing of neurochemicals. Specifically, amperometry measures the concentration-dependent current transient over time at a constant potential, which quantitatively measures the rapid dynamics of target analytes. To achieve selective sensing, dedicated efforts have been devoted into constructing electrode/brain interfaces to exclusively permit specific electrochemical reactions[27, 28]. One common strategy is to immobilize recognition elements onto electrode surface, exemplified by biomacromolecules such as enzymes and aptamers. Besides, electrocatalysts modified onto the electrode could also achieve selective sensing by either accelerating the adsorption/desorption process or altering electron transfer kinetics and pathways of specific neurochemicals. More recently, ion transport-based sensors also provide another complementary strategy for selective sensing, greatly expanding the scope of detectable neurochemicals to encompass not only electroactive but also electroinactive ones. We herein highlight our latest progress on tuning electrochemical behavior of targeted neurochemicals, with a focus on unraveling the rationale behind engineering electrode/brain interface. ...
Designing recognition molecules and tailoring functional surfaces for in vivo monitoring of small molecules in the brain
1
2018
... Natural enzymes featured with high specificity and quick response are befitting recognition elements for in vivo biosensing[29]. Oxidases and dehydrogenases are the most widely utilized natural enzymes in design and construction of sensing interfaces[30,31,32,33,34,35,36,37]. After years of exploring and practicing, we gradually established the oxidase/dehydrogenase-based online electrochemical systems (OECSs) that realize in vivo bio-sensing of important neurochemicals (e.g., glucose, lactate, hypoxanthine), which have been comprehensively reviewed previously[38,39,40,41,42]. However, interferences coming from oxygen or cofactors hinder these oxidase/dehydrogenase-based biosensors from in vivo neurochemical biosensing. ...
A facile electrochemical method for simultaneous and on-line measurements of glucose and lactate in brain microdialysate with prussian blue as the electrocatalyst for reduction of hydrogen peroxide
2
2007
... Natural enzymes featured with high specificity and quick response are befitting recognition elements for in vivo biosensing[29]. Oxidases and dehydrogenases are the most widely utilized natural enzymes in design and construction of sensing interfaces[30,31,32,33,34,35,36,37]. After years of exploring and practicing, we gradually established the oxidase/dehydrogenase-based online electrochemical systems (OECSs) that realize in vivo bio-sensing of important neurochemicals (e.g., glucose, lactate, hypoxanthine), which have been comprehensively reviewed previously[38,39,40,41,42]. However, interferences coming from oxygen or cofactors hinder these oxidase/dehydrogenase-based biosensors from in vivo neurochemical biosensing. ...
... We have demonstrated above that our micro-sized electrochemical sensors, featured with implantable to specific region, high selectivity of target neurochemicals and high biocompatibility of nervous system, hold great promise for in vivo sensing of neurochemicals in living animals. Indeed, with these sensors, we have successfully monitored the dynamic changes of a great variety of neurochemicals including AA[55, 56], dopamine[46], oxygen[60], ATP[44, 71], glucose[30, 31, 33], lactic acid[36], catecholamine[82], K+[76], Ca2+[77] and Mg2+[83] in living brain of animals with high temporal and spatial resolution. ...
Physiologically relevant online electrochemical method for continuous and simultaneous monitoring of striatum glucose and lactate following global cerebral ischemia/reperfusion
2
2009
... Natural enzymes featured with high specificity and quick response are befitting recognition elements for in vivo biosensing[29]. Oxidases and dehydrogenases are the most widely utilized natural enzymes in design and construction of sensing interfaces[30,31,32,33,34,35,36,37]. After years of exploring and practicing, we gradually established the oxidase/dehydrogenase-based online electrochemical systems (OECSs) that realize in vivo bio-sensing of important neurochemicals (e.g., glucose, lactate, hypoxanthine), which have been comprehensively reviewed previously[38,39,40,41,42]. However, interferences coming from oxygen or cofactors hinder these oxidase/dehydrogenase-based biosensors from in vivo neurochemical biosensing. ...
... We have demonstrated above that our micro-sized electrochemical sensors, featured with implantable to specific region, high selectivity of target neurochemicals and high biocompatibility of nervous system, hold great promise for in vivo sensing of neurochemicals in living animals. Indeed, with these sensors, we have successfully monitored the dynamic changes of a great variety of neurochemicals including AA[55, 56], dopamine[46], oxygen[60], ATP[44, 71], glucose[30, 31, 33], lactic acid[36], catecholamine[82], K+[76], Ca2+[77] and Mg2+[83] in living brain of animals with high temporal and spatial resolution. ...
Bioelectrochemically active infinite coordination polymer nanoparticles: one-pot synjournal and biosensing property
1
2011
... Natural enzymes featured with high specificity and quick response are befitting recognition elements for in vivo biosensing[29]. Oxidases and dehydrogenases are the most widely utilized natural enzymes in design and construction of sensing interfaces[30,31,32,33,34,35,36,37]. After years of exploring and practicing, we gradually established the oxidase/dehydrogenase-based online electrochemical systems (OECSs) that realize in vivo bio-sensing of important neurochemicals (e.g., glucose, lactate, hypoxanthine), which have been comprehensively reviewed previously[38,39,40,41,42]. However, interferences coming from oxygen or cofactors hinder these oxidase/dehydrogenase-based biosensors from in vivo neurochemical biosensing. ...
Strong interaction between imidazolium-based polycationic polymer and ferricyanide: toward redox potential regulation for selective in vivo electrochemical measurements
2
2012
... Natural enzymes featured with high specificity and quick response are befitting recognition elements for in vivo biosensing[29]. Oxidases and dehydrogenases are the most widely utilized natural enzymes in design and construction of sensing interfaces[30,31,32,33,34,35,36,37]. After years of exploring and practicing, we gradually established the oxidase/dehydrogenase-based online electrochemical systems (OECSs) that realize in vivo bio-sensing of important neurochemicals (e.g., glucose, lactate, hypoxanthine), which have been comprehensively reviewed previously[38,39,40,41,42]. However, interferences coming from oxygen or cofactors hinder these oxidase/dehydrogenase-based biosensors from in vivo neurochemical biosensing. ...
... We have demonstrated above that our micro-sized electrochemical sensors, featured with implantable to specific region, high selectivity of target neurochemicals and high biocompatibility of nervous system, hold great promise for in vivo sensing of neurochemicals in living animals. Indeed, with these sensors, we have successfully monitored the dynamic changes of a great variety of neurochemicals including AA[55, 56], dopamine[46], oxygen[60], ATP[44, 71], glucose[30, 31, 33], lactic acid[36], catecholamine[82], K+[76], Ca2+[77] and Mg2+[83] in living brain of animals with high temporal and spatial resolution. ...
Hybridization of bioelectrochemically functional infinite coordination polymer nanoparticles with carbon nanotubes for highly sensitive and selective in vivo electrochemical monitoring
1
2013
... Natural enzymes featured with high specificity and quick response are befitting recognition elements for in vivo biosensing[29]. Oxidases and dehydrogenases are the most widely utilized natural enzymes in design and construction of sensing interfaces[30,31,32,33,34,35,36,37]. After years of exploring and practicing, we gradually established the oxidase/dehydrogenase-based online electrochemical systems (OECSs) that realize in vivo bio-sensing of important neurochemicals (e.g., glucose, lactate, hypoxanthine), which have been comprehensively reviewed previously[38,39,40,41,42]. However, interferences coming from oxygen or cofactors hinder these oxidase/dehydrogenase-based biosensors from in vivo neurochemical biosensing. ...
Zeolitic imidazolate framework-based electrochemical biosensor for in vivo electrochemical measurements
1
2013
... Natural enzymes featured with high specificity and quick response are befitting recognition elements for in vivo biosensing[29]. Oxidases and dehydrogenases are the most widely utilized natural enzymes in design and construction of sensing interfaces[30,31,32,33,34,35,36,37]. After years of exploring and practicing, we gradually established the oxidase/dehydrogenase-based online electrochemical systems (OECSs) that realize in vivo bio-sensing of important neurochemicals (e.g., glucose, lactate, hypoxanthine), which have been comprehensively reviewed previously[38,39,40,41,42]. However, interferences coming from oxygen or cofactors hinder these oxidase/dehydrogenase-based biosensors from in vivo neurochemical biosensing. ...
Continuous and simultaneous electrochemical measurements of glucose, lactate, and ascorbate in rat brain following brain ischemia
2
2014
... Natural enzymes featured with high specificity and quick response are befitting recognition elements for in vivo biosensing[29]. Oxidases and dehydrogenases are the most widely utilized natural enzymes in design and construction of sensing interfaces[30,31,32,33,34,35,36,37]. After years of exploring and practicing, we gradually established the oxidase/dehydrogenase-based online electrochemical systems (OECSs) that realize in vivo bio-sensing of important neurochemicals (e.g., glucose, lactate, hypoxanthine), which have been comprehensively reviewed previously[38,39,40,41,42]. However, interferences coming from oxygen or cofactors hinder these oxidase/dehydrogenase-based biosensors from in vivo neurochemical biosensing. ...
... We have demonstrated above that our micro-sized electrochemical sensors, featured with implantable to specific region, high selectivity of target neurochemicals and high biocompatibility of nervous system, hold great promise for in vivo sensing of neurochemicals in living animals. Indeed, with these sensors, we have successfully monitored the dynamic changes of a great variety of neurochemicals including AA[55, 56], dopamine[46], oxygen[60], ATP[44, 71], glucose[30, 31, 33], lactic acid[36], catecholamine[82], K+[76], Ca2+[77] and Mg2+[83] in living brain of animals with high temporal and spatial resolution. ...
Online ele-ctrochemical systems for continuous neurochemical measurements with low-potential mediator-based electroche-mical biosensors as selective detectors
1
2015
... Natural enzymes featured with high specificity and quick response are befitting recognition elements for in vivo biosensing[29]. Oxidases and dehydrogenases are the most widely utilized natural enzymes in design and construction of sensing interfaces[30,31,32,33,34,35,36,37]. After years of exploring and practicing, we gradually established the oxidase/dehydrogenase-based online electrochemical systems (OECSs) that realize in vivo bio-sensing of important neurochemicals (e.g., glucose, lactate, hypoxanthine), which have been comprehensively reviewed previously[38,39,40,41,42]. However, interferences coming from oxygen or cofactors hinder these oxidase/dehydrogenase-based biosensors from in vivo neurochemical biosensing. ...
Recent advances in analytical metho-dology for in vivo electrochemistry in mammals
1
2016
... Natural enzymes featured with high specificity and quick response are befitting recognition elements for in vivo biosensing[29]. Oxidases and dehydrogenases are the most widely utilized natural enzymes in design and construction of sensing interfaces[30,31,32,33,34,35,36,37]. After years of exploring and practicing, we gradually established the oxidase/dehydrogenase-based online electrochemical systems (OECSs) that realize in vivo bio-sensing of important neurochemicals (e.g., glucose, lactate, hypoxanthine), which have been comprehensively reviewed previously[38,39,40,41,42]. However, interferences coming from oxygen or cofactors hinder these oxidase/dehydrogenase-based biosensors from in vivo neurochemical biosensing. ...
In vivo analysis with electrochemical sensors and biosensors
1
2017
... Natural enzymes featured with high specificity and quick response are befitting recognition elements for in vivo biosensing[29]. Oxidases and dehydrogenases are the most widely utilized natural enzymes in design and construction of sensing interfaces[30,31,32,33,34,35,36,37]. After years of exploring and practicing, we gradually established the oxidase/dehydrogenase-based online electrochemical systems (OECSs) that realize in vivo bio-sensing of important neurochemicals (e.g., glucose, lactate, hypoxanthine), which have been comprehensively reviewed previously[38,39,40,41,42]. However, interferences coming from oxygen or cofactors hinder these oxidase/dehydrogenase-based biosensors from in vivo neurochemical biosensing. ...
Advances in electrochemical biosensors for in vivo analysis
1
2019
... Natural enzymes featured with high specificity and quick response are befitting recognition elements for in vivo biosensing[29]. Oxidases and dehydrogenases are the most widely utilized natural enzymes in design and construction of sensing interfaces[30,31,32,33,34,35,36,37]. After years of exploring and practicing, we gradually established the oxidase/dehydrogenase-based online electrochemical systems (OECSs) that realize in vivo bio-sensing of important neurochemicals (e.g., glucose, lactate, hypoxanthine), which have been comprehensively reviewed previously[38,39,40,41,42]. However, interferences coming from oxygen or cofactors hinder these oxidase/dehydrogenase-based biosensors from in vivo neurochemical biosensing. ...
In vivo electrochemical sensors for neurochemicals: recent update
1
2019
... Natural enzymes featured with high specificity and quick response are befitting recognition elements for in vivo biosensing[29]. Oxidases and dehydrogenases are the most widely utilized natural enzymes in design and construction of sensing interfaces[30,31,32,33,34,35,36,37]. After years of exploring and practicing, we gradually established the oxidase/dehydrogenase-based online electrochemical systems (OECSs) that realize in vivo bio-sensing of important neurochemicals (e.g., glucose, lactate, hypoxanthine), which have been comprehensively reviewed previously[38,39,40,41,42]. However, interferences coming from oxygen or cofactors hinder these oxidase/dehydrogenase-based biosensors from in vivo neurochemical biosensing. ...
Enzymatic electrochemical biosensors for in situ neurochemical measurement
1
2020
... Natural enzymes featured with high specificity and quick response are befitting recognition elements for in vivo biosensing[29]. Oxidases and dehydrogenases are the most widely utilized natural enzymes in design and construction of sensing interfaces[30,31,32,33,34,35,36,37]. After years of exploring and practicing, we gradually established the oxidase/dehydrogenase-based online electrochemical systems (OECSs) that realize in vivo bio-sensing of important neurochemicals (e.g., glucose, lactate, hypoxanthine), which have been comprehensively reviewed previously[38,39,40,41,42]. However, interferences coming from oxygen or cofactors hinder these oxidase/dehydrogenase-based biosensors from in vivo neurochemical biosensing. ...
Exploring ferredoxin-dependent glutamate synthase as an enzymatic bioelectrocatalyst
2
2018
... Confronted with these challenges, we believe that exploring new types of enzymes can push the boundaries of interference-free in vivo biosensing. Recently, we introduced ferredoxin-dependent glutamate synthase (Fd-GltS) as a new candidate to catalyze both glutamate synthesis and glutamate oxidation through different mediated electron transfer pathways (Figure 1(A))[43]. Specifically, Fd-GltS can catalyze bio-electrosynthesis of glutamate from glutamine and 2-oxog-lutarate when using methyl viologen as the mediator. While using mediators with high redox potential, oxygen-independent bio-electrooxidation of glutamate was realized in the presence of Fd-GltS. With the redox center close to its surface, Fd-Glts holds great potential in the design of glutamate-based in vivo biosensor through direct electron transfer between the enzyme and electrode. ...
... [43]. Reproduced with permission of Ref. 43, copyright 2018 American Chemical Society. (B) Schematic illustration of aptCFE and typical current response of in vivo DA dynamics upon electrical stimulation[46]. Reproduced with permission of Ref. 46, copyright 2020 WILEY-VCH. (color on line)
Besides both natural and artificial enzymes, aptamers also provide a powerful tool for developing high selective in vivo electrochemical biosensors[44]. Aptamers are short, synthetic single-stranded nucleic acids that possess recognition ability of specific target molecules with high affinity. Generally, aptamers undergo conformational changes upon binding with analyte molecules, resulting in an altered electron transfer pathway between electrodes and redox moieties modified on aptamers. Our early attempt of developing aptamer-based biosensor provides a dual recognition unit strategy for selective ATP sensing in vivo, by incorporating polyimidazolium-brush (PimB) and aptamers together to realize selective recognition of both triphosphate moieties and A nucleobase simultaneously[45]. Following that, we made more efforts on developing interfacial functionalization strategies and extending application of aptamer-based in vivo sensor. More recently, we demonstrated that the aptamer-modified CFE (aptCFE) shows a high selectivity for in vivo sensing of DA in living rat brain (Figure 1(B)). This study opens up a versatile strategy in the design of electrode/brain interface for exploring brain chemistry[46]. ...
Analysis of aptamer discovery and technology
2
2017
... Besides both natural and artificial enzymes, aptamers also provide a powerful tool for developing high selective in vivo electrochemical biosensors[44]. Aptamers are short, synthetic single-stranded nucleic acids that possess recognition ability of specific target molecules with high affinity. Generally, aptamers undergo conformational changes upon binding with analyte molecules, resulting in an altered electron transfer pathway between electrodes and redox moieties modified on aptamers. Our early attempt of developing aptamer-based biosensor provides a dual recognition unit strategy for selective ATP sensing in vivo, by incorporating polyimidazolium-brush (PimB) and aptamers together to realize selective recognition of both triphosphate moieties and A nucleobase simultaneously[45]. Following that, we made more efforts on developing interfacial functionalization strategies and extending application of aptamer-based in vivo sensor. More recently, we demonstrated that the aptamer-modified CFE (aptCFE) shows a high selectivity for in vivo sensing of DA in living rat brain (Figure 1(B)). This study opens up a versatile strategy in the design of electrode/brain interface for exploring brain chemistry[46]. ...
... We have demonstrated above that our micro-sized electrochemical sensors, featured with implantable to specific region, high selectivity of target neurochemicals and high biocompatibility of nervous system, hold great promise for in vivo sensing of neurochemicals in living animals. Indeed, with these sensors, we have successfully monitored the dynamic changes of a great variety of neurochemicals including AA[55, 56], dopamine[46], oxygen[60], ATP[44, 71], glucose[30, 31, 33], lactic acid[36], catecholamine[82], K+[76], Ca2+[77] and Mg2+[83] in living brain of animals with high temporal and spatial resolution. ...
Dual recognition unit strategy improves the specificity of the Adenosine Triphosphate (ATP) aptamer biosensor for cerebral ATP assay
1
2015
... Besides both natural and artificial enzymes, aptamers also provide a powerful tool for developing high selective in vivo electrochemical biosensors[44]. Aptamers are short, synthetic single-stranded nucleic acids that possess recognition ability of specific target molecules with high affinity. Generally, aptamers undergo conformational changes upon binding with analyte molecules, resulting in an altered electron transfer pathway between electrodes and redox moieties modified on aptamers. Our early attempt of developing aptamer-based biosensor provides a dual recognition unit strategy for selective ATP sensing in vivo, by incorporating polyimidazolium-brush (PimB) and aptamers together to realize selective recognition of both triphosphate moieties and A nucleobase simultaneously[45]. Following that, we made more efforts on developing interfacial functionalization strategies and extending application of aptamer-based in vivo sensor. More recently, we demonstrated that the aptamer-modified CFE (aptCFE) shows a high selectivity for in vivo sensing of DA in living rat brain (Figure 1(B)). This study opens up a versatile strategy in the design of electrode/brain interface for exploring brain chemistry[46]. ...
A generalizable and noncovalent strategy for interfacing aptamers with a microelectrode for the selective sensing of neurotransmitters in vivo
3
2020
... Confronted with these challenges, we believe that exploring new types of enzymes can push the boundaries of interference-free in vivo biosensing. Recently, we introduced ferredoxin-dependent glutamate synthase (Fd-GltS) as a new candidate to catalyze both glutamate synthesis and glutamate oxidation through different mediated electron transfer pathways (Figure 1(A))[43]. Specifically, Fd-GltS can catalyze bio-electrosynthesis of glutamate from glutamine and 2-oxog-lutarate when using methyl viologen as the mediator. While using mediators with high redox potential, oxygen-independent bio-electrooxidation of glutamate was realized in the presence of Fd-GltS. With the redox center close to its surface, Fd-Glts holds great potential in the design of glutamate-based in vivo biosensor through direct electron transfer between the enzyme and electrode.
(A) Schematic illustration of mediated electron transfer pathways catalyzed by Fd-Glts<sup>[<xref ref-type="bibr" rid="b43">43</xref>]</sup>. Reproduced with permission of Ref. 43, copyright 2018 American Chemical Society. (B) Schematic illustration of aptCFE and typical current response of <i>in vivo</i> DA dynamics upon electrical stimulation<sup>[<xref ref-type="bibr" rid="b46">46</xref>]</sup>. Reproduced with permission of Ref. 46, copyright 2020 WILEY-VCH. (color on line)
Besides both natural and artificial enzymes, aptamers also provide a powerful tool for developing high selective in vivo electrochemical biosensors[44]. Aptamers are short, synthetic single-stranded nucleic acids that possess recognition ability of specific target molecules with high affinity. Generally, aptamers undergo conformational changes upon binding with analyte molecules, resulting in an altered electron transfer pathway between electrodes and redox moieties modified on aptamers. Our early attempt of developing aptamer-based biosensor provides a dual recognition unit strategy for selective ATP sensing in vivo, by incorporating polyimidazolium-brush (PimB) and aptamers together to realize selective recognition of both triphosphate moieties and A nucleobase simultaneously[45]. Following that, we made more efforts on developing interfacial functionalization strategies and extending application of aptamer-based in vivo sensor. More recently, we demonstrated that the aptamer-modified CFE (aptCFE) shows a high selectivity for in vivo sensing of DA in living rat brain (Figure 1(B)). This study opens up a versatile strategy in the design of electrode/brain interface for exploring brain chemistry[46]. ...
... Besides both natural and artificial enzymes, aptamers also provide a powerful tool for developing high selective in vivo electrochemical biosensors[44]. Aptamers are short, synthetic single-stranded nucleic acids that possess recognition ability of specific target molecules with high affinity. Generally, aptamers undergo conformational changes upon binding with analyte molecules, resulting in an altered electron transfer pathway between electrodes and redox moieties modified on aptamers. Our early attempt of developing aptamer-based biosensor provides a dual recognition unit strategy for selective ATP sensing in vivo, by incorporating polyimidazolium-brush (PimB) and aptamers together to realize selective recognition of both triphosphate moieties and A nucleobase simultaneously[45]. Following that, we made more efforts on developing interfacial functionalization strategies and extending application of aptamer-based in vivo sensor. More recently, we demonstrated that the aptamer-modified CFE (aptCFE) shows a high selectivity for in vivo sensing of DA in living rat brain (Figure 1(B)). This study opens up a versatile strategy in the design of electrode/brain interface for exploring brain chemistry[46]. ...
... We have demonstrated above that our micro-sized electrochemical sensors, featured with implantable to specific region, high selectivity of target neurochemicals and high biocompatibility of nervous system, hold great promise for in vivo sensing of neurochemicals in living animals. Indeed, with these sensors, we have successfully monitored the dynamic changes of a great variety of neurochemicals including AA[55, 56], dopamine[46], oxygen[60], ATP[44, 71], glucose[30, 31, 33], lactic acid[36], catecholamine[82], K+[76], Ca2+[77] and Mg2+[83] in living brain of animals with high temporal and spatial resolution. ...
Preparation, surface modification and in vivo/single cell electroanalytical application of microelectrode
1
2017
... In addition to biological entities that are endowed with high specificity, electrocatalysis with functional materials also provide promising opportunities for in vivo sensing[47,48,49]. Then, the question was asked: how could we identify the materials that can selectively recognize target analytes among numerous coexisting neurochemicals? In this case, we implemented the idea of guiding the interface design based on the formal potential (E0') of the neurochemicals. In general, for the molecules with low E0', such as ascorbic acid (AA), we demonstrate that by constructing the electrode surface with catalysts that can sufficiently accelerate the electrochemical processes, the “optimal selectivity” would be realized. AA, mostly known as the name of vitamin C, gains intense interests in brain research as it has been revealed recently to act more than simply a “micronutrient” in the CNS[50, 51]. Accumulating evidence suggests a close association between AA and neurochemical processes involved in both cognitively intact and impaired brain, which was almost unrecognized due to the lack of in vivo and qualitative assessment of this chemically unstable molecule in living systems[52, 53]. The availability of selective and reliable sensing approach essentially offers great opportunities for in vivo sensing of AA in both fundamental and clinical researches. ...
Nanoelectrodes for intracellular measurements of reactive oxygen and nitrogen species in single living cells
1
2020
... In addition to biological entities that are endowed with high specificity, electrocatalysis with functional materials also provide promising opportunities for in vivo sensing[47,48,49]. Then, the question was asked: how could we identify the materials that can selectively recognize target analytes among numerous coexisting neurochemicals? In this case, we implemented the idea of guiding the interface design based on the formal potential (E0') of the neurochemicals. In general, for the molecules with low E0', such as ascorbic acid (AA), we demonstrate that by constructing the electrode surface with catalysts that can sufficiently accelerate the electrochemical processes, the “optimal selectivity” would be realized. AA, mostly known as the name of vitamin C, gains intense interests in brain research as it has been revealed recently to act more than simply a “micronutrient” in the CNS[50, 51]. Accumulating evidence suggests a close association between AA and neurochemical processes involved in both cognitively intact and impaired brain, which was almost unrecognized due to the lack of in vivo and qualitative assessment of this chemically unstable molecule in living systems[52, 53]. The availability of selective and reliable sensing approach essentially offers great opportunities for in vivo sensing of AA in both fundamental and clinical researches. ...
In vivo detection of hydrogen sulfide in brain and cell
1
2021
... In addition to biological entities that are endowed with high specificity, electrocatalysis with functional materials also provide promising opportunities for in vivo sensing[47,48,49]. Then, the question was asked: how could we identify the materials that can selectively recognize target analytes among numerous coexisting neurochemicals? In this case, we implemented the idea of guiding the interface design based on the formal potential (E0') of the neurochemicals. In general, for the molecules with low E0', such as ascorbic acid (AA), we demonstrate that by constructing the electrode surface with catalysts that can sufficiently accelerate the electrochemical processes, the “optimal selectivity” would be realized. AA, mostly known as the name of vitamin C, gains intense interests in brain research as it has been revealed recently to act more than simply a “micronutrient” in the CNS[50, 51]. Accumulating evidence suggests a close association between AA and neurochemical processes involved in both cognitively intact and impaired brain, which was almost unrecognized due to the lack of in vivo and qualitative assessment of this chemically unstable molecule in living systems[52, 53]. The availability of selective and reliable sensing approach essentially offers great opportunities for in vivo sensing of AA in both fundamental and clinical researches. ...
Recent advances on in vivo analysis of ascorbic acid in brain functions
1
2018
... In addition to biological entities that are endowed with high specificity, electrocatalysis with functional materials also provide promising opportunities for in vivo sensing[47,48,49]. Then, the question was asked: how could we identify the materials that can selectively recognize target analytes among numerous coexisting neurochemicals? In this case, we implemented the idea of guiding the interface design based on the formal potential (E0') of the neurochemicals. In general, for the molecules with low E0', such as ascorbic acid (AA), we demonstrate that by constructing the electrode surface with catalysts that can sufficiently accelerate the electrochemical processes, the “optimal selectivity” would be realized. AA, mostly known as the name of vitamin C, gains intense interests in brain research as it has been revealed recently to act more than simply a “micronutrient” in the CNS[50, 51]. Accumulating evidence suggests a close association between AA and neurochemical processes involved in both cognitively intact and impaired brain, which was almost unrecognized due to the lack of in vivo and qualitative assessment of this chemically unstable molecule in living systems[52, 53]. The availability of selective and reliable sensing approach essentially offers great opportunities for in vivo sensing of AA in both fundamental and clinical researches. ...
Recent advances on in vivo electrochemical analysis of Vitamin C in rat brain
1
2019
... In addition to biological entities that are endowed with high specificity, electrocatalysis with functional materials also provide promising opportunities for in vivo sensing[47,48,49]. Then, the question was asked: how could we identify the materials that can selectively recognize target analytes among numerous coexisting neurochemicals? In this case, we implemented the idea of guiding the interface design based on the formal potential (E0') of the neurochemicals. In general, for the molecules with low E0', such as ascorbic acid (AA), we demonstrate that by constructing the electrode surface with catalysts that can sufficiently accelerate the electrochemical processes, the “optimal selectivity” would be realized. AA, mostly known as the name of vitamin C, gains intense interests in brain research as it has been revealed recently to act more than simply a “micronutrient” in the CNS[50, 51]. Accumulating evidence suggests a close association between AA and neurochemical processes involved in both cognitively intact and impaired brain, which was almost unrecognized due to the lack of in vivo and qualitative assessment of this chemically unstable molecule in living systems[52, 53]. The availability of selective and reliable sensing approach essentially offers great opportunities for in vivo sensing of AA in both fundamental and clinical researches. ...
Ascorbic-acid and the behavioral-response to haloperidol -implications for the action of antipsychotic-drugs
1
1985
... In addition to biological entities that are endowed with high specificity, electrocatalysis with functional materials also provide promising opportunities for in vivo sensing[47,48,49]. Then, the question was asked: how could we identify the materials that can selectively recognize target analytes among numerous coexisting neurochemicals? In this case, we implemented the idea of guiding the interface design based on the formal potential (E0') of the neurochemicals. In general, for the molecules with low E0', such as ascorbic acid (AA), we demonstrate that by constructing the electrode surface with catalysts that can sufficiently accelerate the electrochemical processes, the “optimal selectivity” would be realized. AA, mostly known as the name of vitamin C, gains intense interests in brain research as it has been revealed recently to act more than simply a “micronutrient” in the CNS[50, 51]. Accumulating evidence suggests a close association between AA and neurochemical processes involved in both cognitively intact and impaired brain, which was almost unrecognized due to the lack of in vivo and qualitative assessment of this chemically unstable molecule in living systems[52, 53]. The availability of selective and reliable sensing approach essentially offers great opportunities for in vivo sensing of AA in both fundamental and clinical researches. ...
Ascorbate regulation and its neuroprotective role in the brain
1
2000
... In addition to biological entities that are endowed with high specificity, electrocatalysis with functional materials also provide promising opportunities for in vivo sensing[47,48,49]. Then, the question was asked: how could we identify the materials that can selectively recognize target analytes among numerous coexisting neurochemicals? In this case, we implemented the idea of guiding the interface design based on the formal potential (E0') of the neurochemicals. In general, for the molecules with low E0', such as ascorbic acid (AA), we demonstrate that by constructing the electrode surface with catalysts that can sufficiently accelerate the electrochemical processes, the “optimal selectivity” would be realized. AA, mostly known as the name of vitamin C, gains intense interests in brain research as it has been revealed recently to act more than simply a “micronutrient” in the CNS[50, 51]. Accumulating evidence suggests a close association between AA and neurochemical processes involved in both cognitively intact and impaired brain, which was almost unrecognized due to the lack of in vivo and qualitative assessment of this chemically unstable molecule in living systems[52, 53]. The availability of selective and reliable sensing approach essentially offers great opportunities for in vivo sensing of AA in both fundamental and clinical researches. ...
Continuous on-line monitoring of extracellular ascorbate depletion in the rat striatum induced by global ischemia with carbon nanotube-modified glassy carbon electrode integrated into a thin-layer radial flow cell
1
2005
... We found that the confinement of carbon nanotubes (CNTs) onto electrode surface remarkably accelerates the electrochemical oxidation of AA, enabling the oxidation to occur almost without an overpotential[54,55,56,57]. The excellent electrochemical activity of CNTs made it possible for us to selectively monitor AA without interference from other co-exiting species in biological systems. Further mechanistic study revealed that both chemical and electronic properties of CNTs are dominant factors for providing the sensing selectivity toward AA[56]. ...
Carbon nanotube-modified carbon fiber microelectrodes for in vivo voltammetric measurement of ascorbic acid in rat brain
2
2007
... We found that the confinement of carbon nanotubes (CNTs) onto electrode surface remarkably accelerates the electrochemical oxidation of AA, enabling the oxidation to occur almost without an overpotential[54,55,56,57]. The excellent electrochemical activity of CNTs made it possible for us to selectively monitor AA without interference from other co-exiting species in biological systems. Further mechanistic study revealed that both chemical and electronic properties of CNTs are dominant factors for providing the sensing selectivity toward AA[56]. ...
... We have demonstrated above that our micro-sized electrochemical sensors, featured with implantable to specific region, high selectivity of target neurochemicals and high biocompatibility of nervous system, hold great promise for in vivo sensing of neurochemicals in living animals. Indeed, with these sensors, we have successfully monitored the dynamic changes of a great variety of neurochemicals including AA[55, 56], dopamine[46], oxygen[60], ATP[44, 71], glucose[30, 31, 33], lactic acid[36], catecholamine[82], K+[76], Ca2+[77] and Mg2+[83] in living brain of animals with high temporal and spatial resolution. ...
Vertically aligned carbon nanotube-sheathed carbon fibers as pristine microelectrodes for selective monitoring of ascorbate in vivo
3
2014
... We found that the confinement of carbon nanotubes (CNTs) onto electrode surface remarkably accelerates the electrochemical oxidation of AA, enabling the oxidation to occur almost without an overpotential[54,55,56,57]. The excellent electrochemical activity of CNTs made it possible for us to selectively monitor AA without interference from other co-exiting species in biological systems. Further mechanistic study revealed that both chemical and electronic properties of CNTs are dominant factors for providing the sensing selectivity toward AA[56]. ...
... [56]. ...
... We have demonstrated above that our micro-sized electrochemical sensors, featured with implantable to specific region, high selectivity of target neurochemicals and high biocompatibility of nervous system, hold great promise for in vivo sensing of neurochemicals in living animals. Indeed, with these sensors, we have successfully monitored the dynamic changes of a great variety of neurochemicals including AA[55, 56], dopamine[46], oxygen[60], ATP[44, 71], glucose[30, 31, 33], lactic acid[36], catecholamine[82], K+[76], Ca2+[77] and Mg2+[83] in living brain of animals with high temporal and spatial resolution. ...
Controllable and reproducible sheath of carbon fibers with single-walled carbon nanotubes through electrophoretic deposition for in vivo electrochemical measurements
1
2018
... We found that the confinement of carbon nanotubes (CNTs) onto electrode surface remarkably accelerates the electrochemical oxidation of AA, enabling the oxidation to occur almost without an overpotential[54,55,56,57]. The excellent electrochemical activity of CNTs made it possible for us to selectively monitor AA without interference from other co-exiting species in biological systems. Further mechanistic study revealed that both chemical and electronic properties of CNTs are dominant factors for providing the sensing selectivity toward AA[56]. ...
Bridging homogeneous and heterogeneous catalysis by heterogeneous single-metal-site catalysts
1
2018
... We further extended our studies on designing electrochemical sensors for molecules with high E0'. We reasoned that electrocatalysts that are highly reactive for analytes, while show minimal reactivity to the interfering species, could fulfill the selectivity requirement. In this case, single-atom catalysts (SACs), featuring maximum atom utilization and chemically tunable coordination environment, are appealing candidates for rationally designing electrocatalyst with tailor-made selectivity and catalytic activity[58, 59]. Taken oxygen, a highly important biomolecule with high E0', as a typical target, we demonstrated that through tailoring catalytic metal atom-adsorbates (including both O2 and H2O2) interactions, single-atom electrocatalysts can realize selective catalytic activity toward O2 reduction without interference from H2O2. Specifically, we found that with designed Co-N4/C catalyst, H2O2 shows very weak adsorption on Co centers, enabling the priority of direct four-electron reduction of O2 on the electrode[60]. The excellent sele-ctivity toward O2 reduction endows the Co-N4/C-based sensor with a high selectivity for O2 sensing without interference from H2O2, offering a novel avenue to selective O2 sensing in living animals (Figure 2(A)). Subsequent studies using different SACs further outline a more general role of tailoring catalytic metal atom-adsorbates interaction in achieving high selectivity, especially in (bio)sensing of physiological important chemicals with high E0' values, such as nitric oxide[61] (Figure 2(B)) and glucose[62] (Figure 2(C)). ...
Heterogeneous single-atom catalysis
1
2018
... We further extended our studies on designing electrochemical sensors for molecules with high E0'. We reasoned that electrocatalysts that are highly reactive for analytes, while show minimal reactivity to the interfering species, could fulfill the selectivity requirement. In this case, single-atom catalysts (SACs), featuring maximum atom utilization and chemically tunable coordination environment, are appealing candidates for rationally designing electrocatalyst with tailor-made selectivity and catalytic activity[58, 59]. Taken oxygen, a highly important biomolecule with high E0', as a typical target, we demonstrated that through tailoring catalytic metal atom-adsorbates (including both O2 and H2O2) interactions, single-atom electrocatalysts can realize selective catalytic activity toward O2 reduction without interference from H2O2. Specifically, we found that with designed Co-N4/C catalyst, H2O2 shows very weak adsorption on Co centers, enabling the priority of direct four-electron reduction of O2 on the electrode[60]. The excellent sele-ctivity toward O2 reduction endows the Co-N4/C-based sensor with a high selectivity for O2 sensing without interference from H2O2, offering a novel avenue to selective O2 sensing in living animals (Figure 2(A)). Subsequent studies using different SACs further outline a more general role of tailoring catalytic metal atom-adsorbates interaction in achieving high selectivity, especially in (bio)sensing of physiological important chemicals with high E0' values, such as nitric oxide[61] (Figure 2(B)) and glucose[62] (Figure 2(C)). ...
Single-atom Co-N4 Electrocatalyst enabling four-electron oxygen reduction with enhanced hydrogen peroxide tolerance for selective sensing
3
2020
... We further extended our studies on designing electrochemical sensors for molecules with high E0'. We reasoned that electrocatalysts that are highly reactive for analytes, while show minimal reactivity to the interfering species, could fulfill the selectivity requirement. In this case, single-atom catalysts (SACs), featuring maximum atom utilization and chemically tunable coordination environment, are appealing candidates for rationally designing electrocatalyst with tailor-made selectivity and catalytic activity[58, 59]. Taken oxygen, a highly important biomolecule with high E0', as a typical target, we demonstrated that through tailoring catalytic metal atom-adsorbates (including both O2 and H2O2) interactions, single-atom electrocatalysts can realize selective catalytic activity toward O2 reduction without interference from H2O2. Specifically, we found that with designed Co-N4/C catalyst, H2O2 shows very weak adsorption on Co centers, enabling the priority of direct four-electron reduction of O2 on the electrode[60]. The excellent sele-ctivity toward O2 reduction endows the Co-N4/C-based sensor with a high selectivity for O2 sensing without interference from H2O2, offering a novel avenue to selective O2 sensing in living animals (Figure 2(A)). Subsequent studies using different SACs further outline a more general role of tailoring catalytic metal atom-adsorbates interaction in achieving high selectivity, especially in (bio)sensing of physiological important chemicals with high E0' values, such as nitric oxide[61] (Figure 2(B)) and glucose[62] (Figure 2(C)). ...
... [60]. Reproduced with permission of Ref. 60, copyright 2020 American Chemical Society. (B) (a-b) Schematic illustration of fabrication process (a) and stretching process (b) of Ni SAC/N-C-based sensor. (c) Real-time monitoring of NO release[61]. Reproduced with permission of Ref. 61, copyright 2020 Springer Nature. (C) (a) Schematic illustration of online electrochemical system (OECS) with a SAC-based electrochemical sensor for continuous glucose monitoring, and (b) typical amperometric response of OECS toward microdialysate in vivo sampled from rat brain[62]. Reproduced with permission of Ref. 62, copyright 2019 Springer. (color on line)
In addition to the attempts to modulate interfacial electron transfer property of the neurochemicals with single atom catalysts, we recently tried to modulate the electron transfer pathway of different neurochemicals. Graphdiyne (GDY), featuring unique chemical and electronic properties, is an appealing target for this line of research[63]. For example, this two-dimensional carbon allotrope shows a low reduction potential and highly conjugated electronic structure. We reasoned that these would make GDY an efficient reducing agent and stabilizer for synthesizing nanoparticles on the surface, therefore, generating new type of catalyst with tunable catalytic activity[64]. Using Pd as an example, we demonstrated that GDY enables electroless deposition of ultrafine Pd clusters on its surface, yielding an excellent composite catalyst with superior selectivity and activity toward the reduction of 4-nitrophenol (Figure 3(A)). Giving a variety of metals are available, the electroless deposition approach provides a versatile platform for designing of electrocatalysts with tailorable selectivity, paving new avenues to modulating electron transfer for diverse selectivity needs in in vivo sensing applications. Furthermore, we have established a liquid phase exfoliation method with lithium hexafluorosilicate (Li2SiF6) for GDY, which is envisaged useful to understand the intrinsic property of GDY[65] (Figure 3(B)). The mec-hanism behind this efficient exfoliation probably attributed to the strong non-covalent interactions between SiF62- and GDY, and the easy diffusion of the cation (Li+ and K+) into the interlayers, thus synergistically weaken the attractive forces between GDY interlayers. With this method, damage-free single-, and few-layered GDY flakes can be obtained under ambient and mild conditions. Moreover, the exfoliated GDY flakes in the form of solvent suspension allow an immediate utilization for spin-coating or any other solution processing to address crucial prospects for sensor construction. Besides GDY, its oxidized form named graphdiyne oxide (GDYO) that possesses not only acetylenic bonds but also various forms of oxygen-containing functional groups on its surface also exhibits attractive properties for in vivo sensing. The exploration of the structure-activity relationship of GDYO greatly improves our understanding of the mechanism behind modulating the interfacial electron transfer, contributing to the development of a highly selective GDYO-based humidity sensor for potential human health and disease monitoring[66] (Figure 3(C)). ...
... We have demonstrated above that our micro-sized electrochemical sensors, featured with implantable to specific region, high selectivity of target neurochemicals and high biocompatibility of nervous system, hold great promise for in vivo sensing of neurochemicals in living animals. Indeed, with these sensors, we have successfully monitored the dynamic changes of a great variety of neurochemicals including AA[55, 56], dopamine[46], oxygen[60], ATP[44, 71], glucose[30, 31, 33], lactic acid[36], catecholamine[82], K+[76], Ca2+[77] and Mg2+[83] in living brain of animals with high temporal and spatial resolution. ...
Single-atom Ni-N4 provides a robust cellular NO sensor
2
2020
... We further extended our studies on designing electrochemical sensors for molecules with high E0'. We reasoned that electrocatalysts that are highly reactive for analytes, while show minimal reactivity to the interfering species, could fulfill the selectivity requirement. In this case, single-atom catalysts (SACs), featuring maximum atom utilization and chemically tunable coordination environment, are appealing candidates for rationally designing electrocatalyst with tailor-made selectivity and catalytic activity[58, 59]. Taken oxygen, a highly important biomolecule with high E0', as a typical target, we demonstrated that through tailoring catalytic metal atom-adsorbates (including both O2 and H2O2) interactions, single-atom electrocatalysts can realize selective catalytic activity toward O2 reduction without interference from H2O2. Specifically, we found that with designed Co-N4/C catalyst, H2O2 shows very weak adsorption on Co centers, enabling the priority of direct four-electron reduction of O2 on the electrode[60]. The excellent sele-ctivity toward O2 reduction endows the Co-N4/C-based sensor with a high selectivity for O2 sensing without interference from H2O2, offering a novel avenue to selective O2 sensing in living animals (Figure 2(A)). Subsequent studies using different SACs further outline a more general role of tailoring catalytic metal atom-adsorbates interaction in achieving high selectivity, especially in (bio)sensing of physiological important chemicals with high E0' values, such as nitric oxide[61] (Figure 2(B)) and glucose[62] (Figure 2(C)). ...
... [61]. Reproduced with permission of Ref. 61, copyright 2020 Springer Nature. (C) (a) Schematic illustration of online electrochemical system (OECS) with a SAC-based electrochemical sensor for continuous glucose monitoring, and (b) typical amperometric response of OECS toward microdialysate in vivo sampled from rat brain[62]. Reproduced with permission of Ref. 62, copyright 2019 Springer. (color on line)
In addition to the attempts to modulate interfacial electron transfer property of the neurochemicals with single atom catalysts, we recently tried to modulate the electron transfer pathway of different neurochemicals. Graphdiyne (GDY), featuring unique chemical and electronic properties, is an appealing target for this line of research[63]. For example, this two-dimensional carbon allotrope shows a low reduction potential and highly conjugated electronic structure. We reasoned that these would make GDY an efficient reducing agent and stabilizer for synthesizing nanoparticles on the surface, therefore, generating new type of catalyst with tunable catalytic activity[64]. Using Pd as an example, we demonstrated that GDY enables electroless deposition of ultrafine Pd clusters on its surface, yielding an excellent composite catalyst with superior selectivity and activity toward the reduction of 4-nitrophenol (Figure 3(A)). Giving a variety of metals are available, the electroless deposition approach provides a versatile platform for designing of electrocatalysts with tailorable selectivity, paving new avenues to modulating electron transfer for diverse selectivity needs in in vivo sensing applications. Furthermore, we have established a liquid phase exfoliation method with lithium hexafluorosilicate (Li2SiF6) for GDY, which is envisaged useful to understand the intrinsic property of GDY[65] (Figure 3(B)). The mec-hanism behind this efficient exfoliation probably attributed to the strong non-covalent interactions between SiF62- and GDY, and the easy diffusion of the cation (Li+ and K+) into the interlayers, thus synergistically weaken the attractive forces between GDY interlayers. With this method, damage-free single-, and few-layered GDY flakes can be obtained under ambient and mild conditions. Moreover, the exfoliated GDY flakes in the form of solvent suspension allow an immediate utilization for spin-coating or any other solution processing to address crucial prospects for sensor construction. Besides GDY, its oxidized form named graphdiyne oxide (GDYO) that possesses not only acetylenic bonds but also various forms of oxygen-containing functional groups on its surface also exhibits attractive properties for in vivo sensing. The exploration of the structure-activity relationship of GDYO greatly improves our understanding of the mechanism behind modulating the interfacial electron transfer, contributing to the development of a highly selective GDYO-based humidity sensor for potential human health and disease monitoring[66] (Figure 3(C)). ...
Single-atom electrocatalysis: a new approach to in vivo electrochemical biosensing
2
2019
... We further extended our studies on designing electrochemical sensors for molecules with high E0'. We reasoned that electrocatalysts that are highly reactive for analytes, while show minimal reactivity to the interfering species, could fulfill the selectivity requirement. In this case, single-atom catalysts (SACs), featuring maximum atom utilization and chemically tunable coordination environment, are appealing candidates for rationally designing electrocatalyst with tailor-made selectivity and catalytic activity[58, 59]. Taken oxygen, a highly important biomolecule with high E0', as a typical target, we demonstrated that through tailoring catalytic metal atom-adsorbates (including both O2 and H2O2) interactions, single-atom electrocatalysts can realize selective catalytic activity toward O2 reduction without interference from H2O2. Specifically, we found that with designed Co-N4/C catalyst, H2O2 shows very weak adsorption on Co centers, enabling the priority of direct four-electron reduction of O2 on the electrode[60]. The excellent sele-ctivity toward O2 reduction endows the Co-N4/C-based sensor with a high selectivity for O2 sensing without interference from H2O2, offering a novel avenue to selective O2 sensing in living animals (Figure 2(A)). Subsequent studies using different SACs further outline a more general role of tailoring catalytic metal atom-adsorbates interaction in achieving high selectivity, especially in (bio)sensing of physiological important chemicals with high E0' values, such as nitric oxide[61] (Figure 2(B)) and glucose[62] (Figure 2(C)). ...
... [62]. Reproduced with permission of Ref. 62, copyright 2019 Springer. (color on line)
In addition to the attempts to modulate interfacial electron transfer property of the neurochemicals with single atom catalysts, we recently tried to modulate the electron transfer pathway of different neurochemicals. Graphdiyne (GDY), featuring unique chemical and electronic properties, is an appealing target for this line of research[63]. For example, this two-dimensional carbon allotrope shows a low reduction potential and highly conjugated electronic structure. We reasoned that these would make GDY an efficient reducing agent and stabilizer for synthesizing nanoparticles on the surface, therefore, generating new type of catalyst with tunable catalytic activity[64]. Using Pd as an example, we demonstrated that GDY enables electroless deposition of ultrafine Pd clusters on its surface, yielding an excellent composite catalyst with superior selectivity and activity toward the reduction of 4-nitrophenol (Figure 3(A)). Giving a variety of metals are available, the electroless deposition approach provides a versatile platform for designing of electrocatalysts with tailorable selectivity, paving new avenues to modulating electron transfer for diverse selectivity needs in in vivo sensing applications. Furthermore, we have established a liquid phase exfoliation method with lithium hexafluorosilicate (Li2SiF6) for GDY, which is envisaged useful to understand the intrinsic property of GDY[65] (Figure 3(B)). The mec-hanism behind this efficient exfoliation probably attributed to the strong non-covalent interactions between SiF62- and GDY, and the easy diffusion of the cation (Li+ and K+) into the interlayers, thus synergistically weaken the attractive forces between GDY interlayers. With this method, damage-free single-, and few-layered GDY flakes can be obtained under ambient and mild conditions. Moreover, the exfoliated GDY flakes in the form of solvent suspension allow an immediate utilization for spin-coating or any other solution processing to address crucial prospects for sensor construction. Besides GDY, its oxidized form named graphdiyne oxide (GDYO) that possesses not only acetylenic bonds but also various forms of oxygen-containing functional groups on its surface also exhibits attractive properties for in vivo sensing. The exploration of the structure-activity relationship of GDYO greatly improves our understanding of the mechanism behind modulating the interfacial electron transfer, contributing to the development of a highly selective GDYO-based humidity sensor for potential human health and disease monitoring[66] (Figure 3(C)). ...
Graphdiyne as electrode material: tuning electronic state and surface chemistry for improved electrode reactivity
1
2017
... In addition to the attempts to modulate interfacial electron transfer property of the neurochemicals with single atom catalysts, we recently tried to modulate the electron transfer pathway of different neurochemicals. Graphdiyne (GDY), featuring unique chemical and electronic properties, is an appealing target for this line of research[63]. For example, this two-dimensional carbon allotrope shows a low reduction potential and highly conjugated electronic structure. We reasoned that these would make GDY an efficient reducing agent and stabilizer for synthesizing nanoparticles on the surface, therefore, generating new type of catalyst with tunable catalytic activity[64]. Using Pd as an example, we demonstrated that GDY enables electroless deposition of ultrafine Pd clusters on its surface, yielding an excellent composite catalyst with superior selectivity and activity toward the reduction of 4-nitrophenol (Figure 3(A)). Giving a variety of metals are available, the electroless deposition approach provides a versatile platform for designing of electrocatalysts with tailorable selectivity, paving new avenues to modulating electron transfer for diverse selectivity needs in in vivo sensing applications. Furthermore, we have established a liquid phase exfoliation method with lithium hexafluorosilicate (Li2SiF6) for GDY, which is envisaged useful to understand the intrinsic property of GDY[65] (Figure 3(B)). The mec-hanism behind this efficient exfoliation probably attributed to the strong non-covalent interactions between SiF62- and GDY, and the easy diffusion of the cation (Li+ and K+) into the interlayers, thus synergistically weaken the attractive forces between GDY interlayers. With this method, damage-free single-, and few-layered GDY flakes can be obtained under ambient and mild conditions. Moreover, the exfoliated GDY flakes in the form of solvent suspension allow an immediate utilization for spin-coating or any other solution processing to address crucial prospects for sensor construction. Besides GDY, its oxidized form named graphdiyne oxide (GDYO) that possesses not only acetylenic bonds but also various forms of oxygen-containing functional groups on its surface also exhibits attractive properties for in vivo sensing. The exploration of the structure-activity relationship of GDYO greatly improves our understanding of the mechanism behind modulating the interfacial electron transfer, contributing to the development of a highly selective GDYO-based humidity sensor for potential human health and disease monitoring[66] (Figure 3(C)). ...
Graphdiyne oxides as excellent substrate for electroless deposition of Pd clusters with high catalytic activity
2
2015
... In addition to the attempts to modulate interfacial electron transfer property of the neurochemicals with single atom catalysts, we recently tried to modulate the electron transfer pathway of different neurochemicals. Graphdiyne (GDY), featuring unique chemical and electronic properties, is an appealing target for this line of research[63]. For example, this two-dimensional carbon allotrope shows a low reduction potential and highly conjugated electronic structure. We reasoned that these would make GDY an efficient reducing agent and stabilizer for synthesizing nanoparticles on the surface, therefore, generating new type of catalyst with tunable catalytic activity[64]. Using Pd as an example, we demonstrated that GDY enables electroless deposition of ultrafine Pd clusters on its surface, yielding an excellent composite catalyst with superior selectivity and activity toward the reduction of 4-nitrophenol (Figure 3(A)). Giving a variety of metals are available, the electroless deposition approach provides a versatile platform for designing of electrocatalysts with tailorable selectivity, paving new avenues to modulating electron transfer for diverse selectivity needs in in vivo sensing applications. Furthermore, we have established a liquid phase exfoliation method with lithium hexafluorosilicate (Li2SiF6) for GDY, which is envisaged useful to understand the intrinsic property of GDY[65] (Figure 3(B)). The mec-hanism behind this efficient exfoliation probably attributed to the strong non-covalent interactions between SiF62- and GDY, and the easy diffusion of the cation (Li+ and K+) into the interlayers, thus synergistically weaken the attractive forces between GDY interlayers. With this method, damage-free single-, and few-layered GDY flakes can be obtained under ambient and mild conditions. Moreover, the exfoliated GDY flakes in the form of solvent suspension allow an immediate utilization for spin-coating or any other solution processing to address crucial prospects for sensor construction. Besides GDY, its oxidized form named graphdiyne oxide (GDYO) that possesses not only acetylenic bonds but also various forms of oxygen-containing functional groups on its surface also exhibits attractive properties for in vivo sensing. The exploration of the structure-activity relationship of GDYO greatly improves our understanding of the mechanism behind modulating the interfacial electron transfer, contributing to the development of a highly selective GDYO-based humidity sensor for potential human health and disease monitoring[66] (Figure 3(C)). ...
... [64]. Reproduced with permission of Ref. 64, copyright 2015 American Chemical Society. (B) TEM image (a), HRTEM image (b), STEM image (c), FFT pattern (d) and AFM images (e-f) of exfoliated GDY[65]. Reproduced with permission of Ref. 65, copyright 2019 WILEY-VCH. (C) (a) Schematic illustration of bonding model between water molecules and carbon nanomaterials (i.e., GO and GDYO). (b) Normalized current responses of GDYO-based sensor towards different human respiratory patterns[66]. Reproduced with permission of Ref. 66, copyright 2018 WILEY-VCH. (D) (a) Construction of the mediated biosensor interface and (b) typical amperometric responses to glucose and other neurochemicals[67]. Reproduced with permission of Ref. 67, copyright 2020 American Chemical Society. (color on line)
Based on these studies, we demonstrated that the electron transfer pathway can be further regulated by interfacing GDY and redox molecules[67] (e.g., methylene green, MG). While the semiconducting GDY films decelerate the oxidation of AA, the intercalated MG molecules that relay electrons by fast self-exchange can accelerate the oxidation of dihydronicotinamide adenine dinucleotide (NADH), making it possible to construct a selective bioelectrocatalytic interface. As a typical example, NAD+-dependent glucose dehydro-genase (GDH) is immobilized onto the MG-intercalated GDY nanosheets. The resulted GDH-MG/GDY-based biosensor shows great selectivity of glucose, free from the interference from coexisting neurochemicals including AA, DA and serotonin (5-HT) (Figure 3(D)). This study provides a universal strategy for tuning electrochemical properties of semiconducting or insulating materials, greatly broadening the studies on in vivo sensing sciences. ...
High-yield and damage-free exfoliation of layered Graphdiyne in aqueous phase
2
2019
... In addition to the attempts to modulate interfacial electron transfer property of the neurochemicals with single atom catalysts, we recently tried to modulate the electron transfer pathway of different neurochemicals. Graphdiyne (GDY), featuring unique chemical and electronic properties, is an appealing target for this line of research[63]. For example, this two-dimensional carbon allotrope shows a low reduction potential and highly conjugated electronic structure. We reasoned that these would make GDY an efficient reducing agent and stabilizer for synthesizing nanoparticles on the surface, therefore, generating new type of catalyst with tunable catalytic activity[64]. Using Pd as an example, we demonstrated that GDY enables electroless deposition of ultrafine Pd clusters on its surface, yielding an excellent composite catalyst with superior selectivity and activity toward the reduction of 4-nitrophenol (Figure 3(A)). Giving a variety of metals are available, the electroless deposition approach provides a versatile platform for designing of electrocatalysts with tailorable selectivity, paving new avenues to modulating electron transfer for diverse selectivity needs in in vivo sensing applications. Furthermore, we have established a liquid phase exfoliation method with lithium hexafluorosilicate (Li2SiF6) for GDY, which is envisaged useful to understand the intrinsic property of GDY[65] (Figure 3(B)). The mec-hanism behind this efficient exfoliation probably attributed to the strong non-covalent interactions between SiF62- and GDY, and the easy diffusion of the cation (Li+ and K+) into the interlayers, thus synergistically weaken the attractive forces between GDY interlayers. With this method, damage-free single-, and few-layered GDY flakes can be obtained under ambient and mild conditions. Moreover, the exfoliated GDY flakes in the form of solvent suspension allow an immediate utilization for spin-coating or any other solution processing to address crucial prospects for sensor construction. Besides GDY, its oxidized form named graphdiyne oxide (GDYO) that possesses not only acetylenic bonds but also various forms of oxygen-containing functional groups on its surface also exhibits attractive properties for in vivo sensing. The exploration of the structure-activity relationship of GDYO greatly improves our understanding of the mechanism behind modulating the interfacial electron transfer, contributing to the development of a highly selective GDYO-based humidity sensor for potential human health and disease monitoring[66] (Figure 3(C)). ...
... [65]. Reproduced with permission of Ref. 65, copyright 2019 WILEY-VCH. (C) (a) Schematic illustration of bonding model between water molecules and carbon nanomaterials (i.e., GO and GDYO). (b) Normalized current responses of GDYO-based sensor towards different human respiratory patterns[66]. Reproduced with permission of Ref. 66, copyright 2018 WILEY-VCH. (D) (a) Construction of the mediated biosensor interface and (b) typical amperometric responses to glucose and other neurochemicals[67]. Reproduced with permission of Ref. 67, copyright 2020 American Chemical Society. (color on line)
Based on these studies, we demonstrated that the electron transfer pathway can be further regulated by interfacing GDY and redox molecules[67] (e.g., methylene green, MG). While the semiconducting GDY films decelerate the oxidation of AA, the intercalated MG molecules that relay electrons by fast self-exchange can accelerate the oxidation of dihydronicotinamide adenine dinucleotide (NADH), making it possible to construct a selective bioelectrocatalytic interface. As a typical example, NAD+-dependent glucose dehydro-genase (GDH) is immobilized onto the MG-intercalated GDY nanosheets. The resulted GDH-MG/GDY-based biosensor shows great selectivity of glucose, free from the interference from coexisting neurochemicals including AA, DA and serotonin (5-HT) (Figure 3(D)). This study provides a universal strategy for tuning electrochemical properties of semiconducting or insulating materials, greatly broadening the studies on in vivo sensing sciences. ...
Carbon atom hybridization matters: ultrafast humidity response of Graphdiyne oxides
2
2018
... In addition to the attempts to modulate interfacial electron transfer property of the neurochemicals with single atom catalysts, we recently tried to modulate the electron transfer pathway of different neurochemicals. Graphdiyne (GDY), featuring unique chemical and electronic properties, is an appealing target for this line of research[63]. For example, this two-dimensional carbon allotrope shows a low reduction potential and highly conjugated electronic structure. We reasoned that these would make GDY an efficient reducing agent and stabilizer for synthesizing nanoparticles on the surface, therefore, generating new type of catalyst with tunable catalytic activity[64]. Using Pd as an example, we demonstrated that GDY enables electroless deposition of ultrafine Pd clusters on its surface, yielding an excellent composite catalyst with superior selectivity and activity toward the reduction of 4-nitrophenol (Figure 3(A)). Giving a variety of metals are available, the electroless deposition approach provides a versatile platform for designing of electrocatalysts with tailorable selectivity, paving new avenues to modulating electron transfer for diverse selectivity needs in in vivo sensing applications. Furthermore, we have established a liquid phase exfoliation method with lithium hexafluorosilicate (Li2SiF6) for GDY, which is envisaged useful to understand the intrinsic property of GDY[65] (Figure 3(B)). The mec-hanism behind this efficient exfoliation probably attributed to the strong non-covalent interactions between SiF62- and GDY, and the easy diffusion of the cation (Li+ and K+) into the interlayers, thus synergistically weaken the attractive forces between GDY interlayers. With this method, damage-free single-, and few-layered GDY flakes can be obtained under ambient and mild conditions. Moreover, the exfoliated GDY flakes in the form of solvent suspension allow an immediate utilization for spin-coating or any other solution processing to address crucial prospects for sensor construction. Besides GDY, its oxidized form named graphdiyne oxide (GDYO) that possesses not only acetylenic bonds but also various forms of oxygen-containing functional groups on its surface also exhibits attractive properties for in vivo sensing. The exploration of the structure-activity relationship of GDYO greatly improves our understanding of the mechanism behind modulating the interfacial electron transfer, contributing to the development of a highly selective GDYO-based humidity sensor for potential human health and disease monitoring[66] (Figure 3(C)). ...
... [66]. Reproduced with permission of Ref. 66, copyright 2018 WILEY-VCH. (D) (a) Construction of the mediated biosensor interface and (b) typical amperometric responses to glucose and other neurochemicals[67]. Reproduced with permission of Ref. 67, copyright 2020 American Chemical Society. (color on line)
Based on these studies, we demonstrated that the electron transfer pathway can be further regulated by interfacing GDY and redox molecules[67] (e.g., methylene green, MG). While the semiconducting GDY films decelerate the oxidation of AA, the intercalated MG molecules that relay electrons by fast self-exchange can accelerate the oxidation of dihydronicotinamide adenine dinucleotide (NADH), making it possible to construct a selective bioelectrocatalytic interface. As a typical example, NAD+-dependent glucose dehydro-genase (GDH) is immobilized onto the MG-intercalated GDY nanosheets. The resulted GDH-MG/GDY-based biosensor shows great selectivity of glucose, free from the interference from coexisting neurochemicals including AA, DA and serotonin (5-HT) (Figure 3(D)). This study provides a universal strategy for tuning electrochemical properties of semiconducting or insulating materials, greatly broadening the studies on in vivo sensing sciences. ...
Electron hopping by interfacing semiconducting Graphdiyne nanosheets and redox molecules for selective electrocatalysis
2
2020
... In addition to the attempts to modulate interfacial electron transfer property of the neurochemicals with single atom catalysts, we recently tried to modulate the electron transfer pathway of different neurochemicals. Graphdiyne (GDY), featuring unique chemical and electronic properties, is an appealing target for this line of research[63]. For example, this two-dimensional carbon allotrope shows a low reduction potential and highly conjugated electronic structure. We reasoned that these would make GDY an efficient reducing agent and stabilizer for synthesizing nanoparticles on the surface, therefore, generating new type of catalyst with tunable catalytic activity[64]. Using Pd as an example, we demonstrated that GDY enables electroless deposition of ultrafine Pd clusters on its surface, yielding an excellent composite catalyst with superior selectivity and activity toward the reduction of 4-nitrophenol (Figure 3(A)). Giving a variety of metals are available, the electroless deposition approach provides a versatile platform for designing of electrocatalysts with tailorable selectivity, paving new avenues to modulating electron transfer for diverse selectivity needs in in vivo sensing applications. Furthermore, we have established a liquid phase exfoliation method with lithium hexafluorosilicate (Li2SiF6) for GDY, which is envisaged useful to understand the intrinsic property of GDY[65] (Figure 3(B)). The mec-hanism behind this efficient exfoliation probably attributed to the strong non-covalent interactions between SiF62- and GDY, and the easy diffusion of the cation (Li+ and K+) into the interlayers, thus synergistically weaken the attractive forces between GDY interlayers. With this method, damage-free single-, and few-layered GDY flakes can be obtained under ambient and mild conditions. Moreover, the exfoliated GDY flakes in the form of solvent suspension allow an immediate utilization for spin-coating or any other solution processing to address crucial prospects for sensor construction. Besides GDY, its oxidized form named graphdiyne oxide (GDYO) that possesses not only acetylenic bonds but also various forms of oxygen-containing functional groups on its surface also exhibits attractive properties for in vivo sensing. The exploration of the structure-activity relationship of GDYO greatly improves our understanding of the mechanism behind modulating the interfacial electron transfer, contributing to the development of a highly selective GDYO-based humidity sensor for potential human health and disease monitoring[66] (Figure 3(C)).
(A) Schematic illustration of Pd/GDY formation via electroless deposition<sup>[<xref ref-type="bibr" rid="b64">64</xref>]</sup>. Reproduced with permission of Ref. 64, copyright 2015 American Chemical Society. (B) TEM image (a), HRTEM image (b), STEM image (c), FFT pattern (d) and AFM images (e-f) of exfoliated GDY<sup>[<xref ref-type="bibr" rid="b65">65</xref>]</sup>. Reproduced with permission of Ref. 65, copyright 2019 WILEY-VCH. (C) (a) Schematic illustration of bonding model between water molecules and carbon nanomaterials (i.e., GO and GDYO). (b) Normalized current responses of GDYO-based sensor towards different human respiratory patterns<sup>[<xref ref-type="bibr" rid="b66">66</xref>]</sup>. Reproduced with permission of Ref. 66, copyright 2018 WILEY-VCH. (D) (a) Construction of the mediated biosensor interface and (b) typical amperometric responses to glucose and other neurochemicals<sup>[<xref ref-type="bibr" rid="b67">67</xref>]</sup>. Reproduced with permission of Ref. 67, copyright 2020 American Chemical Society. (color on line)
Based on these studies, we demonstrated that the electron transfer pathway can be further regulated by interfacing GDY and redox molecules[67] (e.g., methylene green, MG). While the semiconducting GDY films decelerate the oxidation of AA, the intercalated MG molecules that relay electrons by fast self-exchange can accelerate the oxidation of dihydronicotinamide adenine dinucleotide (NADH), making it possible to construct a selective bioelectrocatalytic interface. As a typical example, NAD+-dependent glucose dehydro-genase (GDH) is immobilized onto the MG-intercalated GDY nanosheets. The resulted GDH-MG/GDY-based biosensor shows great selectivity of glucose, free from the interference from coexisting neurochemicals including AA, DA and serotonin (5-HT) (Figure 3(D)). This study provides a universal strategy for tuning electrochemical properties of semiconducting or insulating materials, greatly broadening the studies on in vivo sensing sciences. ...
... Based on these studies, we demonstrated that the electron transfer pathway can be further regulated by interfacing GDY and redox molecules[67] (e.g., methylene green, MG). While the semiconducting GDY films decelerate the oxidation of AA, the intercalated MG molecules that relay electrons by fast self-exchange can accelerate the oxidation of dihydronicotinamide adenine dinucleotide (NADH), making it possible to construct a selective bioelectrocatalytic interface. As a typical example, NAD+-dependent glucose dehydro-genase (GDH) is immobilized onto the MG-intercalated GDY nanosheets. The resulted GDH-MG/GDY-based biosensor shows great selectivity of glucose, free from the interference from coexisting neurochemicals including AA, DA and serotonin (5-HT) (Figure 3(D)). This study provides a universal strategy for tuning electrochemical properties of semiconducting or insulating materials, greatly broadening the studies on in vivo sensing sciences. ...
Tuning interionic interaction for highly selective in vivo analysis
1
2015
... In the complex environment of living brains, the electroactive neurochemicals are only the minority. For the other neurochemicals, their sluggish electrochemical reaction kinetics poses grand challenges on in vivo sensing by direct electrolysis. To circumvent this issue, ion transport-based sensing method opens a new paradigm in design of in vivo neurochemical sensors[68]. For example, ion current rectification (ICR), an ion transport behavior featured with unequal current intensities at the negative/positive potential with the same magnitude, reflects specific interaction between analytes and recognition elements modified on the inner-surface of nanopipettes. However, nanopi-pettes are inapplicable to be directly implanted into the living brain, mainly due to their fragileness and nanometer size. To address this issue, we prepared polyimidazolium-brush (PimB)-modified micropipe-ttes and successfully extended ICR from nanoscale to microscale in symmetric electrolyte solution[69, 70]. For deep understanding of the experimental observations, we proposed a three-layer model consisting of a charged layer (CL), a double layer (DL) and a bulk layer (BL) (Figure 4(A)). Validated by both numeric simulation and experimental results, it is demonstrated that influencing factors including the length of PimB, the concentration of electrolyte and the radius of micropipette collectively account for the observed microscale ion current rectification (MICR). With sufficient mechanical robustness and a designable inner surface, this MICR-based sensor unlocks the potential for ion transport-based in vivo neurochemical sensing. By coupling ATP aptamer and MICR-based sensors, we were able to determine the basal level of ATP in brain cortex[71]. ...
Micrometer-Scale ion current rectification at Polyelectrolyte brush-modified micropipets
2
2017
... In the complex environment of living brains, the electroactive neurochemicals are only the minority. For the other neurochemicals, their sluggish electrochemical reaction kinetics poses grand challenges on in vivo sensing by direct electrolysis. To circumvent this issue, ion transport-based sensing method opens a new paradigm in design of in vivo neurochemical sensors[68]. For example, ion current rectification (ICR), an ion transport behavior featured with unequal current intensities at the negative/positive potential with the same magnitude, reflects specific interaction between analytes and recognition elements modified on the inner-surface of nanopipettes. However, nanopi-pettes are inapplicable to be directly implanted into the living brain, mainly due to their fragileness and nanometer size. To address this issue, we prepared polyimidazolium-brush (PimB)-modified micropipe-ttes and successfully extended ICR from nanoscale to microscale in symmetric electrolyte solution[69, 70]. For deep understanding of the experimental observations, we proposed a three-layer model consisting of a charged layer (CL), a double layer (DL) and a bulk layer (BL) (Figure 4(A)). Validated by both numeric simulation and experimental results, it is demonstrated that influencing factors including the length of PimB, the concentration of electrolyte and the radius of micropipette collectively account for the observed microscale ion current rectification (MICR). With sufficient mechanical robustness and a designable inner surface, this MICR-based sensor unlocks the potential for ion transport-based in vivo neurochemical sensing. By coupling ATP aptamer and MICR-based sensors, we were able to determine the basal level of ATP in brain cortex[71]. ...
... [69]. Reproduced with permission of Ref. 69, copyright 2017 American Chemical Society. (B) Schematic illustrations of (a) experimental setup of in vivo pH sensing by using PvimB-modified micropipette and (b) transient ion transport behaviors and generated ion currents under high-frequency pulse potential[72]. Reproduced with permission of Ref. 72, copyright 2021 Royal Society of Chemistry. (color on line)
We envisioned that MICR-based sensing methods may be capable of monitoring the dynamics of electrochemically inactive neurochemicals in the living brains. To improve the spatiotemporal resolution of MICR-based sensors, we developed the first transient ion transport-based microsensor by applying high-fre-quency square-wave pulse potential[72]. In general, the rapid association/dissociation of specific analytes on the modification alters surface charge density of the inner surface of the micropipette, resulting in variation of ion current output with temporal resolution at milliseconds level. Taking pH as a model target, we prepared poly(N-vinylimidazole)-brush (PvimB)-mod-ified micropipette sensors, which exhibited high temporal resolution, sensitivity, selectivity, repeatability and stability (Figure 4(B)). The as-prepared microsen-sor was then implanted into the living rat brain, successfully monitoring pH variation during acid-base disturbance upon CO2 inhalation. We proposed that this study established a versatile sensing platform based on transient ion transport behavior, opening up a new avenue for in vivo monitoring of transient process of neurochemical dynamics through rationale interface design. ...
Chao-tropic monovalent anion-induced rectification inversion at nanopipettes modified by polyimidazolium brushes
1
2018
... In the complex environment of living brains, the electroactive neurochemicals are only the minority. For the other neurochemicals, their sluggish electrochemical reaction kinetics poses grand challenges on in vivo sensing by direct electrolysis. To circumvent this issue, ion transport-based sensing method opens a new paradigm in design of in vivo neurochemical sensors[68]. For example, ion current rectification (ICR), an ion transport behavior featured with unequal current intensities at the negative/positive potential with the same magnitude, reflects specific interaction between analytes and recognition elements modified on the inner-surface of nanopipettes. However, nanopi-pettes are inapplicable to be directly implanted into the living brain, mainly due to their fragileness and nanometer size. To address this issue, we prepared polyimidazolium-brush (PimB)-modified micropipe-ttes and successfully extended ICR from nanoscale to microscale in symmetric electrolyte solution[69, 70]. For deep understanding of the experimental observations, we proposed a three-layer model consisting of a charged layer (CL), a double layer (DL) and a bulk layer (BL) (Figure 4(A)). Validated by both numeric simulation and experimental results, it is demonstrated that influencing factors including the length of PimB, the concentration of electrolyte and the radius of micropipette collectively account for the observed microscale ion current rectification (MICR). With sufficient mechanical robustness and a designable inner surface, this MICR-based sensor unlocks the potential for ion transport-based in vivo neurochemical sensing. By coupling ATP aptamer and MICR-based sensors, we were able to determine the basal level of ATP in brain cortex[71]. ...
Highly selective cerebral ATP assay based on micrometer scale ion current rectification at Polyimidazolium-modified micropipettes
2
2017
... In the complex environment of living brains, the electroactive neurochemicals are only the minority. For the other neurochemicals, their sluggish electrochemical reaction kinetics poses grand challenges on in vivo sensing by direct electrolysis. To circumvent this issue, ion transport-based sensing method opens a new paradigm in design of in vivo neurochemical sensors[68]. For example, ion current rectification (ICR), an ion transport behavior featured with unequal current intensities at the negative/positive potential with the same magnitude, reflects specific interaction between analytes and recognition elements modified on the inner-surface of nanopipettes. However, nanopi-pettes are inapplicable to be directly implanted into the living brain, mainly due to their fragileness and nanometer size. To address this issue, we prepared polyimidazolium-brush (PimB)-modified micropipe-ttes and successfully extended ICR from nanoscale to microscale in symmetric electrolyte solution[69, 70]. For deep understanding of the experimental observations, we proposed a three-layer model consisting of a charged layer (CL), a double layer (DL) and a bulk layer (BL) (Figure 4(A)). Validated by both numeric simulation and experimental results, it is demonstrated that influencing factors including the length of PimB, the concentration of electrolyte and the radius of micropipette collectively account for the observed microscale ion current rectification (MICR). With sufficient mechanical robustness and a designable inner surface, this MICR-based sensor unlocks the potential for ion transport-based in vivo neurochemical sensing. By coupling ATP aptamer and MICR-based sensors, we were able to determine the basal level of ATP in brain cortex[71]. ...
... We have demonstrated above that our micro-sized electrochemical sensors, featured with implantable to specific region, high selectivity of target neurochemicals and high biocompatibility of nervous system, hold great promise for in vivo sensing of neurochemicals in living animals. Indeed, with these sensors, we have successfully monitored the dynamic changes of a great variety of neurochemicals including AA[55, 56], dopamine[46], oxygen[60], ATP[44, 71], glucose[30, 31, 33], lactic acid[36], catecholamine[82], K+[76], Ca2+[77] and Mg2+[83] in living brain of animals with high temporal and spatial resolution. ...
Micrometer-scale transient ion transport for real-time pH assay in living rat brains
2
2021
... In the complex environment of living brains, the electroactive neurochemicals are only the minority. For the other neurochemicals, their sluggish electrochemical reaction kinetics poses grand challenges on in vivo sensing by direct electrolysis. To circumvent this issue, ion transport-based sensing method opens a new paradigm in design of in vivo neurochemical sensors[68]. For example, ion current rectification (ICR), an ion transport behavior featured with unequal current intensities at the negative/positive potential with the same magnitude, reflects specific interaction between analytes and recognition elements modified on the inner-surface of nanopipettes. However, nanopi-pettes are inapplicable to be directly implanted into the living brain, mainly due to their fragileness and nanometer size. To address this issue, we prepared polyimidazolium-brush (PimB)-modified micropipe-ttes and successfully extended ICR from nanoscale to microscale in symmetric electrolyte solution[69, 70]. For deep understanding of the experimental observations, we proposed a three-layer model consisting of a charged layer (CL), a double layer (DL) and a bulk layer (BL) (Figure 4(A)). Validated by both numeric simulation and experimental results, it is demonstrated that influencing factors including the length of PimB, the concentration of electrolyte and the radius of micropipette collectively account for the observed microscale ion current rectification (MICR). With sufficient mechanical robustness and a designable inner surface, this MICR-based sensor unlocks the potential for ion transport-based in vivo neurochemical sensing. By coupling ATP aptamer and MICR-based sensors, we were able to determine the basal level of ATP in brain cortex[71].
(A) (a) Typical current-voltage responses acquired by using bare micropipette (black curve) and PimB-modified micro-pipette (red curve). (b) Schematic illustration of proposed three-layer model<sup>[<xref ref-type="bibr" rid="b69">69</xref>]</sup>. Reproduced with permission of Ref. 69, copyright 2017 American Chemical Society. (B) Schematic illustrations of (a) experimental setup of <i>in vivo</i> pH sensing by using PvimB-modified micropipette and (b) transient ion transport behaviors and generated ion currents under high-frequency pulse potential<sup>[<xref ref-type="bibr" rid="b72">72</xref>]</sup>. Reproduced with permission of Ref. 72, copyright 2021 Royal Society of Chemistry. (color on line)
We envisioned that MICR-based sensing methods may be capable of monitoring the dynamics of electrochemically inactive neurochemicals in the living brains. To improve the spatiotemporal resolution of MICR-based sensors, we developed the first transient ion transport-based microsensor by applying high-fre-quency square-wave pulse potential[72]. In general, the rapid association/dissociation of specific analytes on the modification alters surface charge density of the inner surface of the micropipette, resulting in variation of ion current output with temporal resolution at milliseconds level. Taking pH as a model target, we prepared poly(N-vinylimidazole)-brush (PvimB)-mod-ified micropipette sensors, which exhibited high temporal resolution, sensitivity, selectivity, repeatability and stability (Figure 4(B)). The as-prepared microsen-sor was then implanted into the living rat brain, successfully monitoring pH variation during acid-base disturbance upon CO2 inhalation. We proposed that this study established a versatile sensing platform based on transient ion transport behavior, opening up a new avenue for in vivo monitoring of transient process of neurochemical dynamics through rationale interface design. ...
... We envisioned that MICR-based sensing methods may be capable of monitoring the dynamics of electrochemically inactive neurochemicals in the living brains. To improve the spatiotemporal resolution of MICR-based sensors, we developed the first transient ion transport-based microsensor by applying high-fre-quency square-wave pulse potential[72]. In general, the rapid association/dissociation of specific analytes on the modification alters surface charge density of the inner surface of the micropipette, resulting in variation of ion current output with temporal resolution at milliseconds level. Taking pH as a model target, we prepared poly(N-vinylimidazole)-brush (PvimB)-mod-ified micropipette sensors, which exhibited high temporal resolution, sensitivity, selectivity, repeatability and stability (Figure 4(B)). The as-prepared microsen-sor was then implanted into the living rat brain, successfully monitoring pH variation during acid-base disturbance upon CO2 inhalation. We proposed that this study established a versatile sensing platform based on transient ion transport behavior, opening up a new avenue for in vivo monitoring of transient process of neurochemical dynamics through rationale interface design. ...
Chronoamperometry in vivo - Does it interfere with spontaneous neuronal-activity in the brain
1
1983
... The voltammetric and amperometric sensors enable selective and sensitive analyses of biomolecules in living systems, showing great potential in unraveling the physio-pathological role of neurochemicals in brain. However, as these sensors are based on electrolytic-cell mechanism, an external voltage is always required to drive the oxidation/reduction of the analyte. This inevitably generates a current flow in the electrolytic cell, and potentially changes the activity of cells that is sensitive to electrical stimulus, such as neurons in the CNS. For example, it was observed that low-voltage-activated currents decrease the firing frequency of neurons[73]. ...
Recent advances of ion-selective electrode for in vivo analysis in brain neurochemistry
1
2019
... To tackle the biocompatibility issue, potentiometric methods offer a possible solution that determines analyte concentrate by potential difference according to the Nernst equation. Under equilibrium conditions, the preferred transport of target analytes across the selective membrane introduces a mensurable electromotive force (EMF) between an indicating electrode and a reference electrode, as the readout of relative concentration of analytes. Based on this principle, potentiometric sensors with different ion selective membranes, termed as ion-selective electrode (ISE), make a powerful tool for ion analysis[74]. To explore the application of ISEs in in vivo ion sensing, we coupled H+-selective membrane with CFEs (CF-H+ISEs)[75]. This as-prepared potentiometric sensor showed not only high selectivity and reversibility but also strong antifouling property against proteins, therefore allowing us to investigate pH changes in living rat brains during quick acid-base disturbances. We thereafter utilized carbon materials as transducing layers to establish a more stable sensing interface, realizing extended applications in monitoring the dynamics of extracellular K+[76] and Ca2+[77]in vivo. ...
High antifouling property of ion-selective membrane: toward in vivo monitoring of pH change in live brain of rats with membrane-coated carbon fiber electrodes
1
2016
... To tackle the biocompatibility issue, potentiometric methods offer a possible solution that determines analyte concentrate by potential difference according to the Nernst equation. Under equilibrium conditions, the preferred transport of target analytes across the selective membrane introduces a mensurable electromotive force (EMF) between an indicating electrode and a reference electrode, as the readout of relative concentration of analytes. Based on this principle, potentiometric sensors with different ion selective membranes, termed as ion-selective electrode (ISE), make a powerful tool for ion analysis[74]. To explore the application of ISEs in in vivo ion sensing, we coupled H+-selective membrane with CFEs (CF-H+ISEs)[75]. This as-prepared potentiometric sensor showed not only high selectivity and reversibility but also strong antifouling property against proteins, therefore allowing us to investigate pH changes in living rat brains during quick acid-base disturbances. We thereafter utilized carbon materials as transducing layers to establish a more stable sensing interface, realizing extended applications in monitoring the dynamics of extracellular K+[76] and Ca2+[77]in vivo. ...
Graphdiyne oxide enhances the stability of solid contact-based ionselective electrodes for excellent in vivo analysis
2
2019
... To tackle the biocompatibility issue, potentiometric methods offer a possible solution that determines analyte concentrate by potential difference according to the Nernst equation. Under equilibrium conditions, the preferred transport of target analytes across the selective membrane introduces a mensurable electromotive force (EMF) between an indicating electrode and a reference electrode, as the readout of relative concentration of analytes. Based on this principle, potentiometric sensors with different ion selective membranes, termed as ion-selective electrode (ISE), make a powerful tool for ion analysis[74]. To explore the application of ISEs in in vivo ion sensing, we coupled H+-selective membrane with CFEs (CF-H+ISEs)[75]. This as-prepared potentiometric sensor showed not only high selectivity and reversibility but also strong antifouling property against proteins, therefore allowing us to investigate pH changes in living rat brains during quick acid-base disturbances. We thereafter utilized carbon materials as transducing layers to establish a more stable sensing interface, realizing extended applications in monitoring the dynamics of extracellular K+[76] and Ca2+[77]in vivo. ...
... We have demonstrated above that our micro-sized electrochemical sensors, featured with implantable to specific region, high selectivity of target neurochemicals and high biocompatibility of nervous system, hold great promise for in vivo sensing of neurochemicals in living animals. Indeed, with these sensors, we have successfully monitored the dynamic changes of a great variety of neurochemicals including AA[55, 56], dopamine[46], oxygen[60], ATP[44, 71], glucose[30, 31, 33], lactic acid[36], catecholamine[82], K+[76], Ca2+[77] and Mg2+[83] in living brain of animals with high temporal and spatial resolution. ...
In vivo measurement of calcium ion with solid-state ion-selective electrode by using shelled hollow carbon nanospheres as a transducing layer
2
2019
... To tackle the biocompatibility issue, potentiometric methods offer a possible solution that determines analyte concentrate by potential difference according to the Nernst equation. Under equilibrium conditions, the preferred transport of target analytes across the selective membrane introduces a mensurable electromotive force (EMF) between an indicating electrode and a reference electrode, as the readout of relative concentration of analytes. Based on this principle, potentiometric sensors with different ion selective membranes, termed as ion-selective electrode (ISE), make a powerful tool for ion analysis[74]. To explore the application of ISEs in in vivo ion sensing, we coupled H+-selective membrane with CFEs (CF-H+ISEs)[75]. This as-prepared potentiometric sensor showed not only high selectivity and reversibility but also strong antifouling property against proteins, therefore allowing us to investigate pH changes in living rat brains during quick acid-base disturbances. We thereafter utilized carbon materials as transducing layers to establish a more stable sensing interface, realizing extended applications in monitoring the dynamics of extracellular K+[76] and Ca2+[77]in vivo. ...
... We have demonstrated above that our micro-sized electrochemical sensors, featured with implantable to specific region, high selectivity of target neurochemicals and high biocompatibility of nervous system, hold great promise for in vivo sensing of neurochemicals in living animals. Indeed, with these sensors, we have successfully monitored the dynamic changes of a great variety of neurochemicals including AA[55, 56], dopamine[46], oxygen[60], ATP[44, 71], glucose[30, 31, 33], lactic acid[36], catecholamine[82], K+[76], Ca2+[77] and Mg2+[83] in living brain of animals with high temporal and spatial resolution. ...
Self-powered electrochemical systems as neurochemical sensors: toward self-triggered in vivo analysis of brain chemistry
1
2017
... However, there are only limited choices of permselective membranes, posing a significant challenge to potentiometric sensing methods to be well-suited for sensing the majority of neurochemicals. More recently, we proposed a galvanic cell-based sensing mechanism that realizes the sensing of neurochemicals under nearly zero current flow. Generally, a GRP-based sensing system consists of two separated compartments (Figure 5(A)). In different compartments, reductants and oxidants undergo electro-redox rection at an anode (i.e., the indicating electrode) and a cathode (i.e., the reference electrode), respectively. For spontaneous redox reactions, the established potential difference measured by a voltmeter with high internal resistance could provide information of target redox pairs. In practice, the potential readout is determined by the concentration and electrode kinetics of analytes, presence of coexisting redox species, and other factors. Therefore, the designs of cathodes and anodes are essential for making a self-driven galvanic cell[78]. We first demonstrated that laccase can undergo an efficient direct electron transfer (DET) and show efficient electrochemical catalysis on carbon nanotube(CNT)-modified electrodes. This initiates the employment of laccase based direct electron transfer systems at the cathode of biofuel cells. Moreover, with controlling the orientation of the laccase at CNT electrodes using ethanol-assisted immobilization, a dramatic enhancement of the catalytic activity was observed as revealed by 600% increase of oxygen reduction current (Figure 5(B))[79]. As oxygen can be reduced at the highest potential where the thermodynamics allowed, laccase electrode provides the foundation for the establishment of ideal galvanic redox potentiometric (GRP) cathode. Based on these results, we developed the first GRP sensor with laccase/CNT and CNT electrode as a cathode and an anode, respectively. The as-designed two-electrode GRP sensor shows high sensitivity and selectivity to AA, enabling the reliable measurement of the basal level of cortical AA in living rat brain with excellent biocompatibility (Figure 5(C))[80]. ...
Role of organic solvents in immobilizing fungus laccase on single-walled carbon nanotubes for improved current response in direct bioelectrocatalysis
2
2017
... However, there are only limited choices of permselective membranes, posing a significant challenge to potentiometric sensing methods to be well-suited for sensing the majority of neurochemicals. More recently, we proposed a galvanic cell-based sensing mechanism that realizes the sensing of neurochemicals under nearly zero current flow. Generally, a GRP-based sensing system consists of two separated compartments (Figure 5(A)). In different compartments, reductants and oxidants undergo electro-redox rection at an anode (i.e., the indicating electrode) and a cathode (i.e., the reference electrode), respectively. For spontaneous redox reactions, the established potential difference measured by a voltmeter with high internal resistance could provide information of target redox pairs. In practice, the potential readout is determined by the concentration and electrode kinetics of analytes, presence of coexisting redox species, and other factors. Therefore, the designs of cathodes and anodes are essential for making a self-driven galvanic cell[78]. We first demonstrated that laccase can undergo an efficient direct electron transfer (DET) and show efficient electrochemical catalysis on carbon nanotube(CNT)-modified electrodes. This initiates the employment of laccase based direct electron transfer systems at the cathode of biofuel cells. Moreover, with controlling the orientation of the laccase at CNT electrodes using ethanol-assisted immobilization, a dramatic enhancement of the catalytic activity was observed as revealed by 600% increase of oxygen reduction current (Figure 5(B))[79]. As oxygen can be reduced at the highest potential where the thermodynamics allowed, laccase electrode provides the foundation for the establishment of ideal galvanic redox potentiometric (GRP) cathode. Based on these results, we developed the first GRP sensor with laccase/CNT and CNT electrode as a cathode and an anode, respectively. The as-designed two-electrode GRP sensor shows high sensitivity and selectivity to AA, enabling the reliable measurement of the basal level of cortical AA in living rat brain with excellent biocompatibility (Figure 5(C))[80]. ...
... [79]. Reproduced with permission of Ref. 79, copyright 2017 American Chemical Society. (C) (a) Schematic illustration of GRP sensor for in vivo sensing of AA. (b) Calibration curves of the GRP sensor before and after BSA absorption. (c) Real-time recording of cortical AA level during global cerebral ischemia (red arrow) and reperfusion (blue arrow)[80]. Reproduced with permission of Ref. 80, copyright 2018 American Chemical Society. (D) (a) Schematic illustration of the single-carbon-fiber-powered microsensor and in vivo sensing of AA with the microsensor. (b) Change in open circuit voltage (OCV) after adding AA and interferents. (c) In vivo synchronous OCV measurement with the microsensor and electrophysiological recording by the MEA[81]. Reproduced with permission of Ref. 81, copyright 2020 WILEY-VCH. (color on line)
Encouraged by these studies, we took a further step to develop a single-carbon-fiber-powered GRP microsensor for neurochemical monitoring[81]. Specifically, we combined the bipolar electrochemistry and GRP to fabricate a single-electrode powered GRP sensor. We selected AA as the model neurochemical and modified the anodic pole with multi-walled carbon nanotubes (MWNTs), on which the onset potential of AA oxidation is -0.10 V vs. Ag/AgCl. The micropipette was backfilled with 3 mol·L-1 KCl solution containing K3Fe(CN)6/K4Fe(CN)6 with higher reduction potential (i.e., +0.30 V) to accomplish the spont-aneous reaction. The as-designed bipolar GRP sensor exhibits high selectivity and sensitivity to AA, and most importantly, shows undetectable effects on transient or lasting, excitatory or inhibitory activity of neurons as closely investigated with electrophysiological recording (Figure 5(D)). The excellent neuronal compatibility of the GRP sensor diminishes the potential crosstalk between multimodal recording systems, paving an effective way to study the correlation between chemical and electrical signaling of neurons in brain research. ...
Galvanic redox potentiometry for self-driven in vivo measurement of neurochemical dynamics at open-circuit potential
3
2018
... However, there are only limited choices of permselective membranes, posing a significant challenge to potentiometric sensing methods to be well-suited for sensing the majority of neurochemicals. More recently, we proposed a galvanic cell-based sensing mechanism that realizes the sensing of neurochemicals under nearly zero current flow. Generally, a GRP-based sensing system consists of two separated compartments (Figure 5(A)). In different compartments, reductants and oxidants undergo electro-redox rection at an anode (i.e., the indicating electrode) and a cathode (i.e., the reference electrode), respectively. For spontaneous redox reactions, the established potential difference measured by a voltmeter with high internal resistance could provide information of target redox pairs. In practice, the potential readout is determined by the concentration and electrode kinetics of analytes, presence of coexisting redox species, and other factors. Therefore, the designs of cathodes and anodes are essential for making a self-driven galvanic cell[78]. We first demonstrated that laccase can undergo an efficient direct electron transfer (DET) and show efficient electrochemical catalysis on carbon nanotube(CNT)-modified electrodes. This initiates the employment of laccase based direct electron transfer systems at the cathode of biofuel cells. Moreover, with controlling the orientation of the laccase at CNT electrodes using ethanol-assisted immobilization, a dramatic enhancement of the catalytic activity was observed as revealed by 600% increase of oxygen reduction current (Figure 5(B))[79]. As oxygen can be reduced at the highest potential where the thermodynamics allowed, laccase electrode provides the foundation for the establishment of ideal galvanic redox potentiometric (GRP) cathode. Based on these results, we developed the first GRP sensor with laccase/CNT and CNT electrode as a cathode and an anode, respectively. The as-designed two-electrode GRP sensor shows high sensitivity and selectivity to AA, enabling the reliable measurement of the basal level of cortical AA in living rat brain with excellent biocompatibility (Figure 5(C))[80]. ...
... [80]. (B) Schematic illustration of orientation and cyclic voltammograms of untreated and ethanol-treated laccase on SWCNT/GCE[79]. Reproduced with permission of Ref. 79, copyright 2017 American Chemical Society. (C) (a) Schematic illustration of GRP sensor for in vivo sensing of AA. (b) Calibration curves of the GRP sensor before and after BSA absorption. (c) Real-time recording of cortical AA level during global cerebral ischemia (red arrow) and reperfusion (blue arrow)[80]. Reproduced with permission of Ref. 80, copyright 2018 American Chemical Society. (D) (a) Schematic illustration of the single-carbon-fiber-powered microsensor and in vivo sensing of AA with the microsensor. (b) Change in open circuit voltage (OCV) after adding AA and interferents. (c) In vivo synchronous OCV measurement with the microsensor and electrophysiological recording by the MEA[81]. Reproduced with permission of Ref. 81, copyright 2020 WILEY-VCH. (color on line)
Encouraged by these studies, we took a further step to develop a single-carbon-fiber-powered GRP microsensor for neurochemical monitoring[81]. Specifically, we combined the bipolar electrochemistry and GRP to fabricate a single-electrode powered GRP sensor. We selected AA as the model neurochemical and modified the anodic pole with multi-walled carbon nanotubes (MWNTs), on which the onset potential of AA oxidation is -0.10 V vs. Ag/AgCl. The micropipette was backfilled with 3 mol·L-1 KCl solution containing K3Fe(CN)6/K4Fe(CN)6 with higher reduction potential (i.e., +0.30 V) to accomplish the spont-aneous reaction. The as-designed bipolar GRP sensor exhibits high selectivity and sensitivity to AA, and most importantly, shows undetectable effects on transient or lasting, excitatory or inhibitory activity of neurons as closely investigated with electrophysiological recording (Figure 5(D)). The excellent neuronal compatibility of the GRP sensor diminishes the potential crosstalk between multimodal recording systems, paving an effective way to study the correlation between chemical and electrical signaling of neurons in brain research. ...
... [80]. Reproduced with permission of Ref. 80, copyright 2018 American Chemical Society. (D) (a) Schematic illustration of the single-carbon-fiber-powered microsensor and in vivo sensing of AA with the microsensor. (b) Change in open circuit voltage (OCV) after adding AA and interferents. (c) In vivo synchronous OCV measurement with the microsensor and electrophysiological recording by the MEA[81]. Reproduced with permission of Ref. 81, copyright 2020 WILEY-VCH. (color on line)
Encouraged by these studies, we took a further step to develop a single-carbon-fiber-powered GRP microsensor for neurochemical monitoring[81]. Specifically, we combined the bipolar electrochemistry and GRP to fabricate a single-electrode powered GRP sensor. We selected AA as the model neurochemical and modified the anodic pole with multi-walled carbon nanotubes (MWNTs), on which the onset potential of AA oxidation is -0.10 V vs. Ag/AgCl. The micropipette was backfilled with 3 mol·L-1 KCl solution containing K3Fe(CN)6/K4Fe(CN)6 with higher reduction potential (i.e., +0.30 V) to accomplish the spont-aneous reaction. The as-designed bipolar GRP sensor exhibits high selectivity and sensitivity to AA, and most importantly, shows undetectable effects on transient or lasting, excitatory or inhibitory activity of neurons as closely investigated with electrophysiological recording (Figure 5(D)). The excellent neuronal compatibility of the GRP sensor diminishes the potential crosstalk between multimodal recording systems, paving an effective way to study the correlation between chemical and electrical signaling of neurons in brain research. ...
Single-carbon-fiber-powered microsensor for in vivo neurochemical sensing with high neuronal compatibility
2
2020
... However, there are only limited choices of permselective membranes, posing a significant challenge to potentiometric sensing methods to be well-suited for sensing the majority of neurochemicals. More recently, we proposed a galvanic cell-based sensing mechanism that realizes the sensing of neurochemicals under nearly zero current flow. Generally, a GRP-based sensing system consists of two separated compartments (Figure 5(A)). In different compartments, reductants and oxidants undergo electro-redox rection at an anode (i.e., the indicating electrode) and a cathode (i.e., the reference electrode), respectively. For spontaneous redox reactions, the established potential difference measured by a voltmeter with high internal resistance could provide information of target redox pairs. In practice, the potential readout is determined by the concentration and electrode kinetics of analytes, presence of coexisting redox species, and other factors. Therefore, the designs of cathodes and anodes are essential for making a self-driven galvanic cell[78]. We first demonstrated that laccase can undergo an efficient direct electron transfer (DET) and show efficient electrochemical catalysis on carbon nanotube(CNT)-modified electrodes. This initiates the employment of laccase based direct electron transfer systems at the cathode of biofuel cells. Moreover, with controlling the orientation of the laccase at CNT electrodes using ethanol-assisted immobilization, a dramatic enhancement of the catalytic activity was observed as revealed by 600% increase of oxygen reduction current (Figure 5(B))[79]. As oxygen can be reduced at the highest potential where the thermodynamics allowed, laccase electrode provides the foundation for the establishment of ideal galvanic redox potentiometric (GRP) cathode. Based on these results, we developed the first GRP sensor with laccase/CNT and CNT electrode as a cathode and an anode, respectively. The as-designed two-electrode GRP sensor shows high sensitivity and selectivity to AA, enabling the reliable measurement of the basal level of cortical AA in living rat brain with excellent biocompatibility (Figure 5(C))[80].
(A) Schematic illustration of GRP sensor<sup>[<xref ref-type="bibr" rid="b80">80</xref>]</sup>. (B) Schematic illustration of orientation and cyclic voltammograms of untreated and ethanol-treated laccase on SWCNT/GCE<sup>[<xref ref-type="bibr" rid="b79">79</xref>]</sup>. Reproduced with permission of Ref. 79, copyright 2017 American Chemical Society. (C) (a) Schematic illustration of GRP sensor for <i>in vivo</i> sensing of AA. (b) Calibration curves of the GRP sensor before and after BSA absorption. (c) Real-time recording of cortical AA level during global cerebral ischemia (red arrow) and reperfusion (blue arrow)<sup>[<xref ref-type="bibr" rid="b80">80</xref>]</sup>. Reproduced with permission of Ref. 80, copyright 2018 American Chemical Society. (D) (a) Schematic illustration of the single-carbon-fiber-powered microsensor and <i>in vivo</i> sensing of AA with the microsensor. (b) Change in open circuit voltage (OCV) after adding AA and interferents. (c) <i>In vivo</i> synchronous OCV measurement with the microsensor and electrophysiological recording by the MEA<sup>[<xref ref-type="bibr" rid="b81">81</xref>]</sup>. Reproduced with permission of Ref. 81, copyright 2020 WILEY-VCH. (color on line)
Encouraged by these studies, we took a further step to develop a single-carbon-fiber-powered GRP microsensor for neurochemical monitoring[81]. Specifically, we combined the bipolar electrochemistry and GRP to fabricate a single-electrode powered GRP sensor. We selected AA as the model neurochemical and modified the anodic pole with multi-walled carbon nanotubes (MWNTs), on which the onset potential of AA oxidation is -0.10 V vs. Ag/AgCl. The micropipette was backfilled with 3 mol·L-1 KCl solution containing K3Fe(CN)6/K4Fe(CN)6 with higher reduction potential (i.e., +0.30 V) to accomplish the spont-aneous reaction. The as-designed bipolar GRP sensor exhibits high selectivity and sensitivity to AA, and most importantly, shows undetectable effects on transient or lasting, excitatory or inhibitory activity of neurons as closely investigated with electrophysiological recording (Figure 5(D)). The excellent neuronal compatibility of the GRP sensor diminishes the potential crosstalk between multimodal recording systems, paving an effective way to study the correlation between chemical and electrical signaling of neurons in brain research. ...
... Encouraged by these studies, we took a further step to develop a single-carbon-fiber-powered GRP microsensor for neurochemical monitoring[81]. Specifically, we combined the bipolar electrochemistry and GRP to fabricate a single-electrode powered GRP sensor. We selected AA as the model neurochemical and modified the anodic pole with multi-walled carbon nanotubes (MWNTs), on which the onset potential of AA oxidation is -0.10 V vs. Ag/AgCl. The micropipette was backfilled with 3 mol·L-1 KCl solution containing K3Fe(CN)6/K4Fe(CN)6 with higher reduction potential (i.e., +0.30 V) to accomplish the spont-aneous reaction. The as-designed bipolar GRP sensor exhibits high selectivity and sensitivity to AA, and most importantly, shows undetectable effects on transient or lasting, excitatory or inhibitory activity of neurons as closely investigated with electrophysiological recording (Figure 5(D)). The excellent neuronal compatibility of the GRP sensor diminishes the potential crosstalk between multimodal recording systems, paving an effective way to study the correlation between chemical and electrical signaling of neurons in brain research. ...
Unveiling the role of DJ-1 protein in vesicular storage and release of catechola-mine with nano/micro-tip electrodes
1
2020
... We have demonstrated above that our micro-sized electrochemical sensors, featured with implantable to specific region, high selectivity of target neurochemicals and high biocompatibility of nervous system, hold great promise for in vivo sensing of neurochemicals in living animals. Indeed, with these sensors, we have successfully monitored the dynamic changes of a great variety of neurochemicals including AA[55, 56], dopamine[46], oxygen[60], ATP[44, 71], glucose[30, 31, 33], lactic acid[36], catecholamine[82], K+[76], Ca2+[77] and Mg2+[83] in living brain of animals with high temporal and spatial resolution. ...
Online electrochemical measurements of Ca2+ and Mg2+ in rat brain based on divalent cation enhancement toward electrocatalytic NADH oxidation
1
2010
... We have demonstrated above that our micro-sized electrochemical sensors, featured with implantable to specific region, high selectivity of target neurochemicals and high biocompatibility of nervous system, hold great promise for in vivo sensing of neurochemicals in living animals. Indeed, with these sensors, we have successfully monitored the dynamic changes of a great variety of neurochemicals including AA[55, 56], dopamine[46], oxygen[60], ATP[44, 71], glucose[30, 31, 33], lactic acid[36], catecholamine[82], K+[76], Ca2+[77] and Mg2+[83] in living brain of animals with high temporal and spatial resolution. ...
Electrochemical monitoring of propagative fluctuation of ascorbate in the live rat brain during spreading depolarization
2
2019
... Taken in vivo sensing of AA as an example here to demonstrate how we started from molecule detection to revealing molecular mechanism. With the brain-im-plantable ascorbate sensor (CFEAA1.0 and CFEAA2.0), we reported the first observation on the release of ascorbate in response to spreading depression[84] (Figure 6(A)) and cytotoxic edema[85] (Figure 6(B)), both frequently happened during brain injury. Further mechanistic studies with inhibitors revealed that the AA release may undergo through volume sensitive organic anion channels. Interestingly, by combining electroanalytical chemistry with single-cell amperometry, we also found that AA may also be released by vesicular-mediated exocytosis[86]. ...
... [84]. Reproduced with permission of Ref. 84, copyright 2019 WILEY-VCH. (B) Schematic illustration and typical current responses of in vivo AA release in rat brain by using CFEAA2.0[85]. Reproduced with permission of Ref. 85, copyright 2020 American Chemical Society. (color on line)
More excitingly, with the controlled fabrication, our in vivo sensors show great potential for commercialization, and many of our in vivo sensing system have been widely adopted by doctors in dozens of hospitals, and validated their effectiveness with clinically relevant animal models. We together observed the dynamic changes of AA[87,88,89,90,91], DA[92], norepinephrine[93], glutamic acid[94,95,96], Mg2+[97] and other biomolecules in tinnitus, vertigo, olfactory dysfunction, spinal cord injury, and many other disease related animal models, providing rich information to reveal the molecular mechanism of related diseases. Taken together, our in vivo sensors can reliably monitor the neurochemicals in the complicated central nervous system, providing essential means for understanding brain function and disease. ...
Electrochemically probing dynamics of ascorbate during cytotoxic edema in living rat brain
2
2020
... Taken in vivo sensing of AA as an example here to demonstrate how we started from molecule detection to revealing molecular mechanism. With the brain-im-plantable ascorbate sensor (CFEAA1.0 and CFEAA2.0), we reported the first observation on the release of ascorbate in response to spreading depression[84] (Figure 6(A)) and cytotoxic edema[85] (Figure 6(B)), both frequently happened during brain injury. Further mechanistic studies with inhibitors revealed that the AA release may undergo through volume sensitive organic anion channels. Interestingly, by combining electroanalytical chemistry with single-cell amperometry, we also found that AA may also be released by vesicular-mediated exocytosis[86]. ...
... [85]. Reproduced with permission of Ref. 85, copyright 2020 American Chemical Society. (color on line)
More excitingly, with the controlled fabrication, our in vivo sensors show great potential for commercialization, and many of our in vivo sensing system have been widely adopted by doctors in dozens of hospitals, and validated their effectiveness with clinically relevant animal models. We together observed the dynamic changes of AA[87,88,89,90,91], DA[92], norepinephrine[93], glutamic acid[94,95,96], Mg2+[97] and other biomolecules in tinnitus, vertigo, olfactory dysfunction, spinal cord injury, and many other disease related animal models, providing rich information to reveal the molecular mechanism of related diseases. Taken together, our in vivo sensors can reliably monitor the neurochemicals in the complicated central nervous system, providing essential means for understanding brain function and disease. ...
Selective amperometric recording of endogenous ascorbate secretion from a single rat adrenal chromaffin cell with pretreated carbon fiber microelectrodes
1
2017
... Taken in vivo sensing of AA as an example here to demonstrate how we started from molecule detection to revealing molecular mechanism. With the brain-im-plantable ascorbate sensor (CFEAA1.0 and CFEAA2.0), we reported the first observation on the release of ascorbate in response to spreading depression[84] (Figure 6(A)) and cytotoxic edema[85] (Figure 6(B)), both frequently happened during brain injury. Further mechanistic studies with inhibitors revealed that the AA release may undergo through volume sensitive organic anion channels. Interestingly, by combining electroanalytical chemistry with single-cell amperometry, we also found that AA may also be released by vesicular-mediated exocytosis[86]. ...
Change of extracellular ascorbic acid in the brain cortex following ice water vestibular stimulation: an on-line electrochemical detection coupled with in vivo microdialysis sampling for guinea pigs
1
2008
... More excitingly, with the controlled fabrication, our in vivo sensors show great potential for commercialization, and many of our in vivo sensing system have been widely adopted by doctors in dozens of hospitals, and validated their effectiveness with clinically relevant animal models. We together observed the dynamic changes of AA[87,88,89,90,91], DA[92], norepinephrine[93], glutamic acid[94,95,96], Mg2+[97] and other biomolecules in tinnitus, vertigo, olfactory dysfunction, spinal cord injury, and many other disease related animal models, providing rich information to reveal the molecular mechanism of related diseases. Taken together, our in vivo sensors can reliably monitor the neurochemicals in the complicated central nervous system, providing essential means for understanding brain function and disease. ...
In vivo electrochemical monitoring of the change of cochlear perilymph ascorbate during salicylate-induced tinnitus
1
2012
... More excitingly, with the controlled fabrication, our in vivo sensors show great potential for commercialization, and many of our in vivo sensing system have been widely adopted by doctors in dozens of hospitals, and validated their effectiveness with clinically relevant animal models. We together observed the dynamic changes of AA[87,88,89,90,91], DA[92], norepinephrine[93], glutamic acid[94,95,96], Mg2+[97] and other biomolecules in tinnitus, vertigo, olfactory dysfunction, spinal cord injury, and many other disease related animal models, providing rich information to reveal the molecular mechanism of related diseases. Taken together, our in vivo sensors can reliably monitor the neurochemicals in the complicated central nervous system, providing essential means for understanding brain function and disease. ...
Continuously monitoring of concentration of extracellular ascorbic acid in spinal cord injury model
1
2017
... More excitingly, with the controlled fabrication, our in vivo sensors show great potential for commercialization, and many of our in vivo sensing system have been widely adopted by doctors in dozens of hospitals, and validated their effectiveness with clinically relevant animal models. We together observed the dynamic changes of AA[87,88,89,90,91], DA[92], norepinephrine[93], glutamic acid[94,95,96], Mg2+[97] and other biomolecules in tinnitus, vertigo, olfactory dysfunction, spinal cord injury, and many other disease related animal models, providing rich information to reveal the molecular mechanism of related diseases. Taken together, our in vivo sensors can reliably monitor the neurochemicals in the complicated central nervous system, providing essential means for understanding brain function and disease. ...
In vivo recording of ascorbate and neural excitability in medial vestibular nucleus and hippocampus following ice water vestibular stimulation in rats
1
2018
... More excitingly, with the controlled fabrication, our in vivo sensors show great potential for commercialization, and many of our in vivo sensing system have been widely adopted by doctors in dozens of hospitals, and validated their effectiveness with clinically relevant animal models. We together observed the dynamic changes of AA[87,88,89,90,91], DA[92], norepinephrine[93], glutamic acid[94,95,96], Mg2+[97] and other biomolecules in tinnitus, vertigo, olfactory dysfunction, spinal cord injury, and many other disease related animal models, providing rich information to reveal the molecular mechanism of related diseases. Taken together, our in vivo sensors can reliably monitor the neurochemicals in the complicated central nervous system, providing essential means for understanding brain function and disease. ...
Persistent oppression and simple decompression both exacerbate spinal cord ascorbate levels
1
2020
... More excitingly, with the controlled fabrication, our in vivo sensors show great potential for commercialization, and many of our in vivo sensing system have been widely adopted by doctors in dozens of hospitals, and validated their effectiveness with clinically relevant animal models. We together observed the dynamic changes of AA[87,88,89,90,91], DA[92], norepinephrine[93], glutamic acid[94,95,96], Mg2+[97] and other biomolecules in tinnitus, vertigo, olfactory dysfunction, spinal cord injury, and many other disease related animal models, providing rich information to reveal the molecular mechanism of related diseases. Taken together, our in vivo sensors can reliably monitor the neurochemicals in the complicated central nervous system, providing essential means for understanding brain function and disease. ...
Role of the caudate-putamen nucleus in sensory gating in induced tinnitus in rats
1
2021
... More excitingly, with the controlled fabrication, our in vivo sensors show great potential for commercialization, and many of our in vivo sensing system have been widely adopted by doctors in dozens of hospitals, and validated their effectiveness with clinically relevant animal models. We together observed the dynamic changes of AA[87,88,89,90,91], DA[92], norepinephrine[93], glutamic acid[94,95,96], Mg2+[97] and other biomolecules in tinnitus, vertigo, olfactory dysfunction, spinal cord injury, and many other disease related animal models, providing rich information to reveal the molecular mechanism of related diseases. Taken together, our in vivo sensors can reliably monitor the neurochemicals in the complicated central nervous system, providing essential means for understanding brain function and disease. ...
In vivo measurement of the dynamics of norepinephrine in an olfactory bulb following ischemia-induced olfactory dysfunction and its responses to dexamethasone treatment
1
2018
... More excitingly, with the controlled fabrication, our in vivo sensors show great potential for commercialization, and many of our in vivo sensing system have been widely adopted by doctors in dozens of hospitals, and validated their effectiveness with clinically relevant animal models. We together observed the dynamic changes of AA[87,88,89,90,91], DA[92], norepinephrine[93], glutamic acid[94,95,96], Mg2+[97] and other biomolecules in tinnitus, vertigo, olfactory dysfunction, spinal cord injury, and many other disease related animal models, providing rich information to reveal the molecular mechanism of related diseases. Taken together, our in vivo sensors can reliably monitor the neurochemicals in the complicated central nervous system, providing essential means for understanding brain function and disease. ...
Paraflocculus plays a role in salicylate-induced tinnitus
1
2017
... More excitingly, with the controlled fabrication, our in vivo sensors show great potential for commercialization, and many of our in vivo sensing system have been widely adopted by doctors in dozens of hospitals, and validated their effectiveness with clinically relevant animal models. We together observed the dynamic changes of AA[87,88,89,90,91], DA[92], norepinephrine[93], glutamic acid[94,95,96], Mg2+[97] and other biomolecules in tinnitus, vertigo, olfactory dysfunction, spinal cord injury, and many other disease related animal models, providing rich information to reveal the molecular mechanism of related diseases. Taken together, our in vivo sensors can reliably monitor the neurochemicals in the complicated central nervous system, providing essential means for understanding brain function and disease. ...
Neuroprotective effects of MK-801 on auditory cortex in salicylate-induced tinnitus: Involvement of neural activity, glutamate and ascorbate
1
2019
... More excitingly, with the controlled fabrication, our in vivo sensors show great potential for commercialization, and many of our in vivo sensing system have been widely adopted by doctors in dozens of hospitals, and validated their effectiveness with clinically relevant animal models. We together observed the dynamic changes of AA[87,88,89,90,91], DA[92], norepinephrine[93], glutamic acid[94,95,96], Mg2+[97] and other biomolecules in tinnitus, vertigo, olfactory dysfunction, spinal cord injury, and many other disease related animal models, providing rich information to reveal the molecular mechanism of related diseases. Taken together, our in vivo sensors can reliably monitor the neurochemicals in the complicated central nervous system, providing essential means for understanding brain function and disease. ...
Participation of the anterior cingulate cortex in sodium salicylate-induced tinnitus
1
2021
... More excitingly, with the controlled fabrication, our in vivo sensors show great potential for commercialization, and many of our in vivo sensing system have been widely adopted by doctors in dozens of hospitals, and validated their effectiveness with clinically relevant animal models. We together observed the dynamic changes of AA[87,88,89,90,91], DA[92], norepinephrine[93], glutamic acid[94,95,96], Mg2+[97] and other biomolecules in tinnitus, vertigo, olfactory dysfunction, spinal cord injury, and many other disease related animal models, providing rich information to reveal the molecular mechanism of related diseases. Taken together, our in vivo sensors can reliably monitor the neurochemicals in the complicated central nervous system, providing essential means for understanding brain function and disease. ...
In vivo ele-ctrochemical recording of continuous change of magnesium in medial vestibular nucleus following vertigo induced by ice water vestibular stimulation
1
2013
... More excitingly, with the controlled fabrication, our in vivo sensors show great potential for commercialization, and many of our in vivo sensing system have been widely adopted by doctors in dozens of hospitals, and validated their effectiveness with clinically relevant animal models. We together observed the dynamic changes of AA[87,88,89,90,91], DA[92], norepinephrine[93], glutamic acid[94,95,96], Mg2+[97] and other biomolecules in tinnitus, vertigo, olfactory dysfunction, spinal cord injury, and many other disease related animal models, providing rich information to reveal the molecular mechanism of related diseases. Taken together, our in vivo sensors can reliably monitor the neurochemicals in the complicated central nervous system, providing essential means for understanding brain function and disease. ...
Recent advances on antifouling of microelectrode for in vivo electrochemistry
1
2019
... Nevertheless, we must note that these in vivo sensors still face many challenges. One urgent need is to minimize the sensors design and improve its biocompatibility to overcome the body’s natural rejection response[98]. Another important aspect is to realize high-throughput and multimodal analysis, where artificial intelligence, physiological techniques, and wireless technology can be combined to resolving multiple biological parameters, and allowing remote monitoring and assessments in real-time. In addition, electrochemical systems can be further improved to be multifunctional, incorporating sensors and then applying a drug or intervention based on the sensor data obtained for precise medicine. Taken together, with the development of chemistry, materials science, micro-processing technology, information engineering and other related technologies, the establishment of highly selective, highly sensitive, high spatial and temporal resolution sensors for in vivo analysis of multi-species will become the focus of research in this field. The in vivo sensing system will greatly contribute to the deep understanding of brain function, and promote the development of accurate diagnosis and assist in treatment decision. ...
