纳米材料在用于癌症诊断的呼出气挥发性有机物检测中的应用

doi:10.13208/j.electrochem.181041

摘要/Abstract

摘要： 细胞新陈代谢的变化会导致挥发性有机化合物（VOCs）类型及含量发生变化，因此可通过分析某些标志性VOCs简立起多种疾病早期诊断的模型. 人体呼出物中特征VOCs的检测作为一种非侵入性、无损的检测手段，近些年在疾病检测领域已成为世界范围内的研究热点. 其中，纳米材料可用于增强传感器性能，并使传感器便携式小型化，推进检测传感器进入临床. 在这篇综述中，作者将种类繁多的传感器中用到的纳米材料归纳总结为金属、金属氧化物、碳基、复合物和MOFs基纳米材料等几类，并讨论了不同类纳米材料在VOCs检测中的优劣势. 本文所建立起的分析方法及讨论有助于进一步了解检测技术的优越性与局限性. 最后，作者对利用VOCs的检测实现癌症早期筛选的研究及发展提出了个人观点.

关键词: 挥发性有机化合物, 纳米材料, 癌症, 生物标志物, 呼出气

Abstract: Volatile organic compounds (VOCs) generated in human body can reflect one’s health state, and numerous diseases are identified by some VOCs biomarkers. More recently, analyses of VOCs biomarkers from exhaled breath have turned into a research frontier worldwide because it offers a noninvasive way for diseases diagnosis. Various kinds of nanomaterials are used to enhance the performance of sensing techniques, and play an essential role in miniaturization detection. In this review, several kinds of nanomaterials (metallic, metal oxide, carbon-based, composites and MOFs-based materials) used in various VOCs detection methods, especially in VOCs sensors are summarized. Learning from the successful utilization of nanomaterials in these methods will help to further understand the superiority and limitation of detection techniques. A personal perspective of the research and development in exhaled breath VOCs detection for cancer diagnosis has been presented.

Key words: volatile organic compounds, nanomaterials, cancer, biomarker, exhaled breath

中图分类号:

O646
O657

白万乔, 乔学志, 王铁. 纳米材料在用于癌症诊断的呼出气挥发性有机物检测中的应用[J]. 电化学（中英文）, 2019, 25(2): 185-201.

BAI Wan-qiao, QIAO Xue-zhi, WANG Tie. Application of Nanomaterials in the Detection of Volatile Organic Compounds in Exhaled Breath for Cancer Diagnosis[J]. Journal of Electrochemistry, 2019, 25(2): 185-201.

导出引用管理器 EndNote|Ris|BibTeX

链接本文: https://electrochem.xmu.edu.cn/CN/10.13208/j.electrochem.181041

https://electrochem.xmu.edu.cn/CN/Y2019/V25/I2/185

参考文献

[1] Oakley-Girvan I, Davis S W. Breath based volatile organic compounds in the detection of breast, lung, and colorectal cancers: A systematic review[J]. Cancer Biomarkers, 2018, 21: 29-39.
[2] Sîngeap A M, Trifan A, Cojocariu C, et al. Colon capsule endoscopy compared to colonoscopy for colorectal neoplasms diagnosis: an initial experience and a brief review of the literature[J]. Revista medico-chirurgicala a Societatii de Medici si Naturalisti din Iasi, 2012, 116(1): 145-149.
[3] Boots A W, Bos L D, van der Schee M P, et al. Exhaled molecular fingerprinting in diagnosis and monitoring: validating volatile promises[J]. Trends in Molecular Medicine, 2015, 21(10): 633-644.
[4] Li M X, Yang D K, Brock G, et al. Breath carbonyl compounds as biomarkers of lung cancer[J]. Lung Cancer, 2015, 90(1): 92-97.
[5] Brandman S, Ko J P. Pulmonary nodule detection, characterization, and management with multidetector computed tomography[J]. Journal of Thoracic Imaging, 2011, 26(2): 90-105.
[6] Handa H, Usuba A, Maddula S, et al. Exhaled breath analysis for lung cancer detection using ion mobility spectrometry[J]. PloS One, 2014, 9(12): e114555.
[7] Sun X H, Shao K, Wang T. Detection of volatile organic compounds (VOCs) from exhaled breath as noninvasive methods for cancer diagnosis[J]. Analytical and Bioanalytical Chemistry, 2016, 408(11): 2759-2780.
[8] Buljubasic F, Buchbauer G. The scent of human diseases: a review on specific volatile organic compounds as diagnostic biomarkers[J]. Flavour and Fragrance Journal, 2015, 30(1): 5-25.
[9] Amann A, de Lacy Costello B, Miekisch W, et al. The human volatilome: volatile organic compounds (VOCs) in exhaled breath, skin emanations, urine, feces and saliva[J]. Journal of Breath Research, 2014, 8(3): 034001.
[10] Fenske J D, Paulson S E. Human breath emissions of VOCs[J]. Journal of the Air & Waste Management Association, 1999, 49(5): 594-598.
[11] Buljubasic F, Buchbauer G. The scent of human diseases: a review on specific volatile organic compounds as diagnostic biomarkers[J]. Flavour and Fragrance Journal, 2015, 30(1): 5-25.
[12] Boots A W, Bos L D, van der Schee M P, et al. Exhaled molecular fingerprinting in diagnosis and monitoring: validating volatile promises[J]. Trends in Molecular Med-
icine, 2015, 21(10): 633-644.
[13] Turner C. Techniques and issues in breath and clinical sample headspace analysis for disease diagnosis[J]. Bioanalysis, 2016, 8(7): 677-690.
[14] Zonta G, Anania G, Fabbri B, et al. Detection of colorectal cancer biomarkers in the presence of interfering gases[J]. Sensors and Actuators B: Chemical, 2015, 218: 289-295.
[15] de Lacy Costello B, Amann A, Al-Kateb H, et al. A review of the volatiles from the healthy human body[J]. Journal of Breath Research, 2014, 8(1): 014001.
[16] Wang Z, Wang C. Is breath acetone a biomarker of diabetes? A historical review on breath acetone measurements[J]. Journal of Breath Research, 2013, 7(3): 037109.
[17] Tangerman A, Meuwese-Arends M T, van Tongeren J H M. A new sensitive assay for measuring volatile sulphur compounds in human breath by Tenax trapping and gas chromatography and its application in liver cirrhosis[J]. Clinica Chimica Acta, 1983, 130(1): 103-110.
[18] Boots A W, Smolinska A, van Berkel J, et al. Identification of microorganisms based on headspace analysis of volatile organic compounds by gas chromatography-mass spectrometry[J]. Journal of Breath Research, 2014, 8(2): 027106.
[19] Mazzatenta A, Pokorski M, Sartucci F, et al. Volatile organic compounds (VOCs) fingerprint of Alzheimer’s disease[J]. Respiratory Physiology & Neurobiology, 2015, 209: 81-84.
[20] Mazzone P J. Analysis of volatile organic compounds in the exhaled breath for the diagnosis of lung cancer[J]. Journal of Thoracic Oncology, 2008, 3(7): 774-780.
[21] Vishinkin R, Haick H. Nanoscale sensor technologies for disease detection via volatolomics[J]. Small, 2015, 11(46): 6142-6164.
[22] Konvalina G, Haick H. Sensors for breath testing: from nanomaterials to comprehensive disease detection[J]. Accounts of Chemical Research, 2013, 47(1): 66-76.
[23] Kulkarni G S, Zhong Z. Detection beyond the Debye screening length in a high-frequency nanoelectronic biosensor[J]. Nano Letters, 2012, 12(2): 719-723.
[24] Garg N, Mohanty A, Lazarus N, et al. Robust gold nanoparticles stabilized by trithiol for application in chemiresistive sensors[J]. Nanotechnology, 2010, 21(40): 405501.
[25] Peng G, Hakim M, Broza Y Y, et al. Detection of lung, breast, colorectal, and prostate cancers from exhaled breath using a single array of nanosensors[J]. British Journal of Cancer, 2010, 103(4): 542-551.
[26] Dovgolevsky E, Konvalina G, Tisch U, et al. Monolayer-capped cubic platinum nanoparticles for sensing nonpolar analytes in highly humid atmospheres[J]. The Journal of Physical Chemistry C, 2010, 114(33): 14042-14049.
[27] Kahn N, Lavie O, Paz M, et al. Dynamic nanoparticlebased flexible sensors: Diagnosis of ovarian carcinoma from exhaled breath[J]. Nano Letters, 2015, 15(10): 7023-7028.
[28] Lentka ?, Kotarski M, Smulko J, et al. Fluctuation-enhanced sensing with organically functionalized gold nanoparticle gas sensors targeting biomedical applications[J]. Talanta, 2016, 160: 9-14.
[29] Zhang Z, Yu W, Wang J, et al. Ultrasensitive surface-enhanced Raman scattering sensor of gaseous aldehydes as biomarkers of lung cancer on dendritic Ag nanocrystals[J]. Analytical Chemistry, 2017, 89(3): 1416-1420.
[30] Yamazoe N. New approaches for improving semiconductor gas sensors[J]. Sensors and Actuators B: Chemical, 1991, 5(1/4): 7-19.
[31] Barsan N, Schweizer-Berberich M, Göpel W. Fundamental and practical aspects in the design of nanoscaled SnO₂ gas sensors: a status report[J]. Fresenius Journal of Analytical Chemistry, 1999, 365(4): 287-304.
[32] Yamazoe N, Kurokawa Y, Seiyama T. Effects of additives on semiconductor gas sensors[J]. Sensors and Actuators, 1983, 4: 283-289.
[33] Korotcenkov G, Brinzari V, Boris Y, et al. Influence of surface Pd doping on gas sensing characteristics of SnO₂ thin films deposited by spray pirolysis[J]. Thin Solid Films, 2003, 436(1): 119-126.
[34] Korotcenkov G. Gas response control through structural and chemical modification of metal oxide films: state of the art and approaches[J]. Sensors and Actuators B: Chemical, 2005, 107(1): 209-232.
[35] Shin J, Choi S J, Lee I, et al. Thin-wall assembled SnO₂ fibers functionalized by catalytic Pt nanoparticles and their superior exhaled-breath-sensing properties for the diagnosis of diabetes[J]. Advanced Functional Materials, 2013, 23(19): 2357-2367.
[36] Righettoni M, Tricoli A, Gass S, et al. Breath acetone monitoring by portable Si: WO₃ gas sensors[J]. Analytica Chimica Acta, 2012, 738: 69-75.
[37] Katwal G, Paulose M, Rusakova I A, et al. Rapid growth of zinc oxide nanotube-nanowire hybrid architectures and their use in breast cancer-related volatile organics detection[J]. Nano Letters, 2016, 16(5): 3014-3021.
[38] Phillips M, Cataneo R N, Ditkoff B A, et al. Prediction of breast cancer using volatile biomarkers in the breath[J]. Breast Cancer Research and Treatment, 2006, 99(1): 19-21.
[39] Tomer V K, Duhan S. Ordered mesoporous Ag-doped TiO₂/SnO₂ nanocomposite based highly sensitive and selective VOC sensors[J]. Journal of Materials Chemistry A, 2016, 4(3): 1033-1043.
[40] Zhang R, Zhou T T, Zhang T. Functionalization of hybrid 1D SnO₂-ZnO nanofibers for formaldehyde detection[J]. Advanced Materials Interfaces, 2018, 5(20): 1800967.
[41] Wang C X, Yin L W, Zhang L Y, et al. Metal oxide gas sensors: sensitivity and influencing factors[J]. Sensors, 2010, 10(3): 2088-2106.
[42] Jalal A, Alam F, RoyChoudhury S, et al. Prospects and challenges of volatile organic compound (VOC) sensors in human healthcare[J]. ACS Sensors, 2018, 3(7): 1246-1263.
[43] Ellis J E, Star A. Carbon nanotube based gas sensors toward breath analysis[J]. ChemPlusChem, 2016, 81(12): 1248-1265.
[44] Zilberman Y, Tisch U, Shuster G, et al. Carbon nanotube/hexa-peri-hexabenzocoronene bilayers for discrimination between nonpolar volatile organic compounds of cancer and humid atmospheres[J]. Advanced Materials, 2010, 22(38): 4317-4320.
[45] Wang F, Swager T M. Diverse chemiresistors based upon covalently modified multiwalled carbon nanotubes[J]. Journal of the American Chemical Society, 2011, 133(29): 11181-11193.
[46] Van Quang V, Hung V N, Phan V N, et al. Graphene-coated quartz crystal microbalance for detection of volatile organic compounds at room temperature[J]. Thin Solid Films, 2014, 568: 6-12.
[47] Zhang G J, Guo X X, Wang S L, et al. New graphene fiber coating for volatile organic compounds analysis[J]. Journal of Chromatography B, 2014, 969: 128-131.
[48] Chatterjee S, Castro M, Feller J F. Tailoring selectivity of sprayed carbon nanotube sensors (CNT) towards volatile organic compounds (VOC) with surfactants[J]. Sensors and Actuators B: Chemical, 2015, 220: 840-849.
[49] Nag S, Sachan A, Castro M, et al. Spray layer-by-layer assembly of POSS functionalized CNT quantum chemo-resistive sensors with tuneable selectivity and ppm resolution to VOC biomarkers[J]. Sensors and Actuators B: Chemical, 2016, 222: 362-373.
[50] Zhang X Y, Gao B, Creamer A E, et al. Adsorption of VOCs onto engineered carbon materials: A review[J].Journal of Hazardous Materials, 2017, 338: 102-123.
[51] Huang L Z, Wang Z, Zhu X F, et al. Electrical gas sensors based on structured organic ultra-thin films and nanocrystals on solid state substrates[J]. Nanoscale Horizons, 2016, 1(5): 383-393.
[52] Peng H L, Li W J, Ning F J, et al. Amphiphilic chitosan derivatives-based liposomes: synthesis, development, and properties as a carrier for sustained release of salidroside[J]. Journal of Agricultural and Food Chemistry, 2014, 62(3): 626-633.
[53] Qin Y M, Shi J J, Gong X G, et al. A luminescent inorganic/organic composite ultrathin film based on a 2D Cascade FRET process and its potential VOC selective sensing properties[J]. Advanced Functional Materials, 2016, 26(37): 6752-6759.
[54] Gao R, Yan D. Ordered assembly of hybrid room-temperature phosphorescence thin films showing polarized emission and the sensing of VOCs[J]. Chemical Communications, 2017, 53(39): 5408-5411.
[55] Dolai S, Bhunia S K, Beglaryan S S, et al. Colorimetric polydiacetylene-aerogel detector for volatile organic compounds (VOCs)[J]. ACS Applied Materials & Interfaces, 2017, 9(3): 2891-2898.
[56] Broza Y Y, Haick H. Nanomaterial-based sensors for detection of disease by volatile organic compounds[J]. Nanomedicine, 2013, 8(5): 785-806.
[57] Peng G, Tisch U, Haick H. Detection of nonpolar molecules by means of carrier scattering in random networks of carbon nanotubes: toward diagnosis of diseases via breath samples[J]. Nano Letters, 2009, 9(4): 1362-1368.
[58] Peng G, Tisch U, Adams O, et al. Diagnosing lung cancer in exhaled breath using gold nanoparticles[J]. Nature Nanotechnology, 2009, 4(10): 669.
[59] Zilberman Y, Ionescu R, Feng X, et al. Nanoarray of polycyclic aromatic hydrocarbons and carbon nanotubes for accurate and predictive detection in real-world environmental humidity[J]. ACS Nano, 2011, 5(8): 6743-6753.
[60] Nag S, Duarte L, Bertrand E, et al. Ultrasensitive QRS made by supramolecular assembly of functionalized cyclodextrins and graphene for the detection of lung cancer VOC biomarkers[J]. Journal of Materials Chemistry B, 2014, 2(38): 6571-6579.
[61] Chen L, Huang L, Lin Y J, et al. Fully gravure-printed WO₃/Pt-decorated rGO nanosheets composite film for detection of acetone[J]. Sensors and Actuators B: Chemical, 2018, 255: 1482-1490.
[62] Li Y, Li J H, Xu H. Graphene/polyaniline electrodeposited needle trap device for the determination of volatile organic compounds in human exhaled breath vapor and A549 cell[J]. RSC Advances, 2017, 7(20): 11959-11968.
[63] Daneshkhah A, Shrestha S, Agarwal M, et al. Poly (vinylidene fluoride-hexafluoropropylene) composite sensors for volatile organic compounds detection in breath[J]. Sensors and Actuators B: Chemical, 2015, 221: 635-643.
[64] Liu L, Zhang D M, Zhang Q, et al. Smartphone-based sensing system using ZnO and graphene modified electrodes for VOCs detection[J]. Biosensors and Bioelectronics, 2017, 93: 94-101.
[65] Zhang M, Feng G X, Song Z G, et al. Two-dimensional metal-organic framework with wide channels and responsive turn-on fluorescence for the chemical sensing of volatile organic compounds[J]. Journal of the American Chemical Society, 2014, 136(20): 7241-7244.
[66] Dong M J, Zhao M, Ou S, et al. A luminescent dye@MOF platform: emission fingerprint relationships of volatile organic molecules[J]. Angewandte Chemie International Edition, 2014, 53(6): 1575-1579.
[67] Nugent P, Belmabkhout Y, Burd S D, et al. Porous materials with optimal adsorption thermodynamics and kinetics for CO₂ separation[J]. Nature, 2013, 495(7439): 80-84.
[68] Deng H, Doonan C J, Furukawa H, et al. Multiple functional groups of varying ratios in metal-organic frameworks[J]. Science, 2010, 327(5967): 846-850.
[69] Férey G, Serre C, Devic T, et al. Why hybrid porous solids capture greenhouse gases?[J]. Chemical Society Reviews, 2011, 40(2): 550-562.
[70] Wu H H, Gong Q H, Olson D H, et al. Commensurate adsorption of hydrocarbons and alcohols in microporous metal organic frameworks[J]. Chemical Reviews, 2012, 112(2): 836-868.
[71] Luan Q（栾琼）, Xue C F（薛春峰）, Zhu H Y（祝红叶）, et al. Electrochemical synthesis of porous polyaniline electrodes using HKUST-1 as a template and their electrochemical supercapacitor property[J]. Journal of Electrochemistry(电化学), 2017, 23(1): 13-20
[72] Li Y F（李亚峰）, Sun Q Q（孙晴晴）, Wei M D（魏明灯）. Application of metal-organic frameworks in dye-sensitised solar cells[J]. Journal of Electrochemistry（电化学）, 2016, 22(4): 332-339
[73] Cui Y J, Yue Y F, Qian G D, et al. Luminescent functional metal-organic frameworks[J]. Chemical Reviews, 2011, 112(2): 1126-1162.
[74] Kreno L E, Leong K, Farha O K, et al. Metal-organic framework materials as chemical sensors[J]. Chemical Reviews, 2011, 112(2): 1105-1125.
[75] Khoshaman A H, Bahreyni B. Application of metal organic framework crystals for sensing of volatile organic gases[J]. Sensors and Actuators B: Chemical, 2012, 162(1): 114-119.
[76] Homayoonnia S, Zeinali S. Design and fabrication of capacitive nanosensor based on MOF nanoparticles as sensing layer for VOCs detection[J]. Sensors and Actuators B: Chemical, 2016, 237: 776-786.
[77] Ghanbarian M, Zeinali S, Mostafavi A. A novel MIL-53 (Cr-Fe)/Ag/CNT nanocomposite based resistive sensor for sensing of volatile organic compounds[J]. Sensors and Actuators B: Chemical, 2018, 267: 381-391.
[78] Qiao X Z, Su B S, Liu C, et al. Selective surface enhanced Raman scattering for quantitative detection of lung cancer biomarkers in superparticle@ MOF structure[J]. Advanced Materials, 2018, 30(5): 1702275.
[79] Lee H K, Lee Y H, Morabito J V, et al. Driving CO₂ to a quasi-condensed phase at the interface between a nanoparticle surface and a metal-organic framework at 1 bar and 298 K[J]. Journal of the American Chemical Society, 2017, 139(33): 11513-11518.
[80] Qiao X Z, Xue Z J, Liu L, et al. Superficial layer-enhanced raman scattering (SLERS) for depth detection of non-contact molecules[J]. Advanced Materials, 2019, 31(4): 1804275.