基于适体的石英晶体微天平传感器的研究进展
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摘要
适体(Aptamer)是通过指数富集配体系统进化技术(Systematic evolution of ligands by exponential enrichment,SELEX)从人工合成的随机单链寡核苷酸文库里筛选出来的短链寡核苷酸序列,具有分子量小、结构简单、易进行修饰、靶标范围广泛,并且与靶标分子之间具有高特异性和高亲和力等特点。相应地,适体的这些独特的性质可用于制备各种不同的传感器,根据各种传感器的不同原理,本文着重概述了常用于检测适体与靶标之间亲和力的电化学生物传感器、光学生物传感器和压电晶体传感器。这3种方法的检测都具有检测时间短和检测限低的优势。其中压电晶体传感器又称石英晶体微天平(Quartz crystal microbalance,QCM),除了在SELEX技术中可应用于表征候选适体的靶向能力外,还可用于构建高灵敏度和高特异性的适体石英晶体传感器。简要介绍了基于适体的石英晶体微天平传感器基本原理,对近年来QCM在表征和检测适体与其靶标,包括小分子、离子、蛋白质、细胞、细菌和病毒等物质相互作用的研究现状进行综述,总结分析了QCM技术的优缺点。旨在为适体的筛选以及适体在基础研究、临床诊断和疾病治疗中的进一步应用提供参考。
Aptamers are short-chain oligonucleotides sequence selected from synthetic random single-stranded oligonucleotide libraries via a technology of Systematic Evolution of Ligands by Exponential Enrichment(SELEX). They have the advantages of low molecular weight,simple structure,easily modified,and wide-ranging target,as well as high specificity and affinity with target molecules. Correspondingly,these characteristics of aptamers may be applied for preparing a variety of sensors. Accordingly to the different principles of various aptamersbased sensors to detect their targets,here we focus on electrochemical,optical,and piezoelectric crystal sensors that are commonly usedfor detecting the affinity between aptamers and target. These three methods all have the advantages of short detection time and low detectionlimit. Piezoelectric crystal sensor is also called quartz crystal microbalance(QCM). In addition to characterization of candidate aptamersduring SELEX process,aptamers-based quartz crystal sensors can be built up with QCM to detect their targets with high sensitivity and highspecificity. Thus,the basic principle of aptamer-based quartz crystal microbalance sensor is briefly introduced. Further,the recently publishedreports of QCM on the characterization and detection of interactions between aptamers and their targets,including the small molecules,ions,proteins,cells,bacteria,and viruses,are reviewed. Moreover,the advantages and disadvantages of QCM technology are summarized andanalyzed. This review is aimed at providing a reference for the screening of aptamers and their further application in basic research,clinical diagnosis and disease treatment.
Aptamers are short-chain oligonucleotides sequence selected from synthetic random single-stranded oligonucleotide libraries via a technology of Systematic Evolution of Ligands by Exponential Enrichment(SELEX). They have the advantages of low molecular weight,simple structure,easily modified,and wide-ranging target,as well as high specificity and affinity with target molecules. Correspondingly,these characteristics of aptamers may be applied for preparing a variety of sensors. Accordingly to the different principles of various aptamersbased sensors to detect their targets,here we focus on electrochemical,optical,and piezoelectric crystal sensors that are commonly usedfor detecting the affinity between aptamers and target. These three methods all have the advantages of short detection time and low detectionlimit. Piezoelectric crystal sensor is also called quartz crystal microbalance(QCM). In addition to characterization of candidate aptamersduring SELEX process,aptamers-based quartz crystal sensors can be built up with QCM to detect their targets with high sensitivity and highspecificity. Thus,the basic principle of aptamer-based quartz crystal microbalance sensor is briefly introduced. Further,the recently publishedreports of QCM on the characterization and detection of interactions between aptamers and their targets,including the small molecules,ions,proteins,cells,bacteria,and viruses,are reviewed. Moreover,the advantages and disadvantages of QCM technology are summarized andanalyzed. This review is aimed at providing a reference for the screening of aptamers and their further application in basic research,clinical diagnosis and disease treatment.
引文
[1]Hermann T, Patel DJ. Adaptive recognition by nucleic acidaptamers[J]. Science, 2000, 287(5454):820-825.
[2]Huang R, Xi Z, He N. Applications of aptamers for chemistryanalysis, medicine and food security[J]. Science China Chemistry,2015, 58(7):1122-1130.
[3]Song K, Lee S, Ban C. Aptamers and their biological applications[J]. Sensors, 2012, 12(12):612-631.
[4]Jing M, Bowser MT. Methods for measuring aptamer-proteinequilibria:a review[J]. Anal Chim Acta, 2011, 686(1-2):9-18.
[5]Cheng CI, Chang Y, Chu Y. Biomolecular interactions and tools fortheir recognition:focus on the quartz crystal microbalance and itsdiverse surface chemistries and applications[J]. Chem Soc Rev,2012, 41(5):1947-1971.
[6]Zhao M, Fan G, Chen J, et al. Highly sensitive and selectivephotoelectrochemical biosensor for Hg2+detectionbasedondualsignal amplification by exciton energy transfer coupled withsensitization effect[J]. Anal Chem, 2015, 24:12340-12347.
[7]Politi J, Rea I, NiciF,etal. Nanogravimetricandopticalcharacterizations of thrombin interaction with a self-assembledthiolated aptamer[J]. Journal of Sensors, 2016, 2016:1-8.
[8]Shan W, Pan Y, Fang H, et al. An aptamer-based quartz crystalmicrobalance biosensor for sensitive and selective detection ofleukemia cells using silver-enhanced gold nanoparticle label[J].Talanta, 2014, 126:130-135.
[9]Ozalp VC, Bayramoglu G, Erdem Z, et al. Pathogen detection incomplex samples by quartz crystal microbalance sensor coupled toaptamer functionalized core-shell type magnetic separation[J].Anal Chim Acta, 2015, 853:533-540.
[10]Xu L, Wang R, Kelso LC, et al. A target-responsive and sizedependent hydrogel aptasensor embedded with QD fluorescentreporters for rapid detection of avian influenza virus H5N1[J].Sensors and Actuators B:Chemical, 2016, 234:98-108.
[11]MacKay S, Wishart D, Xing JZ, et al. Developing trends in aptamerbased biosensor devices and their applications[J]. IEEE TransBiomed Circuits Syst, 2014, 8(1):4-14.
[12]Hansen JA, Wang J, Kawde A, et al. Quantum-dot/aptamer-basedultrasensitive multi-analyte electrochemical biosensor[J]. J AmChem Soc, 2006, 128(7):2228-2229.
[13]Lu Y, Zhu N, Yu P, Mao L. Aptamer-based electrochemical sensorsthat are not based on the target binding-induced conformationalchange of aptamers[J]. Analyst, 2008, 133(9):1256-1260.
[14]Kang Y, Feng KJ, Chen JW, et al. Electrochemical detection ofthrombin by sandwich approach using antibody and aptamer[J].Bioelectrochemistry, 2008, 73(1):76-81.
[15]Arroyo-Currás N, Scida K, Ploense KL, et al. High surface areaelectrodes generated via electrochemical roughening improve thesignaling of electrochemical aptamer-based biosensors[J]. AnalChem, 2017, 89(22):12185-12191.
[16]Abi A, Mohammadpour Z, Zuo X, et al. Nucleic acid-basedelectrochemical nanobiosensors[J]. Biosens Bioelectron, 2018,102:479-489.
[17]Ikebukuro K, Kiyohara C, Sode K. Novel electrochemical sensorsystem for protein using the aptamers in sandwich manner[J].Biosens Bioelectron, 2005, 20(10):2168-2172.
[18]肖丽娟,孙娟,柴雅琴.基于壳聚糖/碳纳米管/石墨烯/铁氰化镍纳米复合材料构建的电化学适体传感器用于凝血酶的检测[J].化学传感器, 2014(3):53-57.
[19]Lv Y, Zhang Z, Chen F. Chemiluminescence microfluidic systemsensor on a chip for determination of glucose in human serum withimmobilized reagents[J]. Talanta, 2003, 59(3):571-576.
[20]Marquette CA, Blum LJ. Regenerable immunobiosensor for thechemiluminescent flow injection analysis of the herbicide 2, 4-D[J]. Talanta, 2000, 51(2):395-401.
[21]Zhao L, Li B, Zhang Z, et al. Chemiluminescent flow-through sensorfor automated dissolution testing of analgin tablets using manganesedioxide as oxidate[J]. Sensors and Actuators, 2004, 97(2/3):266-271.
[22]严喜鸾,陈馨,肖义陂,等.基于适体生物传感器的碱性磷酸酯酶化学发光检测腺苷[J].分析测试学报, 2017(4):565-569.
[23]Lee M, Walt DR. A fiber-optic microarray biosensor using aptamersas receptors[J]. Anal Biochem, 2000, 282(1):142-146.
[24]Plomer M, Guilbault GG, Hock B. Development of a piezoelectricimmunosensor for the detection of enterobacteria[J]. EnzymeMicrob Technol, 1992, 14(3):230-235.
[25]Sun H, Zhang YY, Si SH, et al. Piezoelectric quartz crystal(PQC)with photochemically deposited nano-sized Ag particlesfor determining cyanide at trace levels in water[J]. Sensors andActuators B:Chemical, 2005, 108(1-2):925-932.
[26]Bunroddith K, Viseshakul N, Chansiri K, et al. QCM-based rapiddetection of PCR amplification products of Ehrlichia canis[J].Anal Chim Acta, 2018, 1001:106-111.
[27]Abadian PN, Buch P, Goluch ED, et al. Real-time monitoring ofurinary encrustation using a quartz crystal microbalance[J].Anal Chem, 2018. doi:10. 1021/acs. analchem.
[28]Song S, Wang L, Li J, et al. Aptamer-based biosensors[J]. TrACTrends in Anal Chem, 2008, 27(2):108-117.
[29]Sauerbrey G. The use of quartz oscillators for weighing layers andfor micro-weighing[J]. Z Physik, 1959, 155-206.
[30]Groff K, Brown J, Clippinger AJ. Modern affinity reagents:Recombinant antibodies and aptamers[J]. BiotechnologyAdvances, 2015, 33(8):1787-1798.
[31]Osypova A, Thakar D, Dejeu J, et al. Sensor based on aptamerfolding to detect low-molecular weight analytes[J]. Anal Chem,2015, 87(15):7566-7574.
[32]?zalp VC. Acoustic quantification of ATP using a quartz crystalmicrobalance with dissipation[J]. Analyst, 2011, 136(23):5046-5050.
[33]Dong ZM, Zhao GC. A theophylline quartz crystal microbalancebiosensor based on recognition of RNA aptamer and amplificationof signal[J]. Analyst, 2013, 138(8):2456-2462.
[34]Yao C, Qi Y, Zhao Y, et al. Aptamer-based piezoelectric quartzcrystal microbalance biosensor array for the quantification ofIgE[J]. Biosens Bioelectron, 2009, 24(8):2499-2503.
[35]Chen Q, Tang W, Wang D, et al. Amplified QCM-D biosensor forprotein based on aptamer-functionalized gold nanoparticles[J].Biosens Bioelectron, 2010, 26(2):575-579.
[36]Sun W, Song W, Guo X, et al. Ultrasensitive detection of nucleicacids and proteins using quartz crystal microbalance and surfaceplasmon resonance sensors based on target-triggering multiplesignal amplification strategy[J]. Anal Chim Acta, 2017, 978:42-47.
[37]Wu C, Du L, Zou L, et al. A biomimetic bitter receptor-basedbiosensor with high efficiency immobilization and purification usingself-assembled aptamers[J]. Analyst, 2013, 20:5989-5994.
[38]Du L, Wu C, Peng H, et al. Piezoelectric olfactory receptorbiosensor prepared by aptamer-assisted immobilization[J].Sensors and Actuators B:Chemical, 2013, 187:481-487.
[39]Pan Y, Guo M, Nie Z, et al. Selective collection and detectionof leukemia cells on a magnet-quartz crystal microbalancesystem using aptamer-conjugated magnetic beads[J]. BiosensBioelectron, 2010, 25(7):1609-1614.
[40]Wang L, Wang R, Chen F, et al. QCM-based aptamer selectionand detection of Salmonella typhimurium[J]. Food Chem, 2017,221:776-782.
[41]Yu X, Chen F, Wang R, et al. Whole-bacterium SELEX of DNAaptamers for rapid detection of E. coli O157:H7 using a QCMsensor[J]. J Biotechnol, 2018, 266:39-49.
[42]Brockman L, Wang R, Lum J, et al. QCM Aptasensor for rapid andspecific detection of avian influenza virus[J]. Open Journal ofApplied Biosensor, 2013, 02(04):97-103.
[43]冯阳阳,李杜娟,叶尊忠,等.纳米颗粒在石英晶体微天平生物传感器中的应用与研究进展[J].中国生物医学工程学报,2011(02):299-307.
[44]Dong Z, Zhao G. Quartz crystal microbalance aptasensor forsensitive detection of mercury(ii)based on signal amplificationwith gold nanoparticles[J]. Sensors, 2012, 6:7080-7094.
[45]Chen Q, Wu X, Wang D, et al. Oligonucleotide-functionalized goldnanoparticles-enhanced QCM-D sensor for mercury(II)ions withhigh sensitivity and tunable dynamic range[J]. The Analyst,2011, 136(12):2572.
[46]Sheng Z, Han J, Zhang J, et al. Method for detection of Hg2+basedon the specific thymine-Hg2+-thymineinteractionintheDNAhybridization on the surface of quartz crystal microbalance[J].Colloids and Surfaces B:Biointerfaces, 2011, 87(2):289-292.
[47]Zheng B, Cheng S, Liu W, et al. Small organic molecules detectionbased on aptamer-modified gold nanoparticles-enhanced quartzcrystal microbalance with dissipation biosensor[J]. AnalBiochem, 2013, 438(2):144-149.
[48]SongW,ZhuZ,MaoY,etal.Asensitivequartzcrystalmicrobalance assay of adenosine triphosphate via DNAzymeactivatedandaptamer-basedtarget-triggeringcircularamplification[J]. Biosens Bioelectron, 2014, 53:288-294.
[49]Hianik T, OstatnáV, Sonlajtnerova M, et al. Influence of ionicstrength, pH and aptamer configuration for binding affinity tothrombin[J]. Bioelectrochemistry, 2007, 70(1):127-133.
[50]Nübel C, Appel B, Hospach I, et al. Challenges and opportunitiesin the development of aptamers for TNFα[J]. Appl BiochemBiotechnol, 2016, 179(3):398-414.
[51]He P, Liu L, Qiao W, et al. Ultrasensitive detection of thrombinusing surface plasmon resonance and quartz crystal microbalancesensors by aptamer-based rolling circle amplification andnanoparticle signal enhancement[J]. Chem Commun(Camb),2014, 50(12):1481-1484.
[52]Wang R, Li Y. Hydrogel based QCM aptasensor for detection ofavian influenzavirus[J]. Biosens Bioelectron, 2013, 42:148-155.
[53]Xu L, Wang R, Kelso LC, et al. A target-responsive and sizedependent hydrogel aptasensor embedded with QD fluorescentreporters for rapid detection of avian influenza virus H5N1[J].Sensors and Actuators B:Chemical, 2016, 234:98-108.
[54]苏雪,何逸婷,林俊生.适体和蛋白质解离常数检测方法比较分析[J].传感器与微系统, 2016(11):47-50.
[2]Huang R, Xi Z, He N. Applications of aptamers for chemistryanalysis, medicine and food security[J]. Science China Chemistry,2015, 58(7):1122-1130.
[3]Song K, Lee S, Ban C. Aptamers and their biological applications[J]. Sensors, 2012, 12(12):612-631.
[4]Jing M, Bowser MT. Methods for measuring aptamer-proteinequilibria:a review[J]. Anal Chim Acta, 2011, 686(1-2):9-18.
[5]Cheng CI, Chang Y, Chu Y. Biomolecular interactions and tools fortheir recognition:focus on the quartz crystal microbalance and itsdiverse surface chemistries and applications[J]. Chem Soc Rev,2012, 41(5):1947-1971.
[6]Zhao M, Fan G, Chen J, et al. Highly sensitive and selectivephotoelectrochemical biosensor for Hg2+detectionbasedondualsignal amplification by exciton energy transfer coupled withsensitization effect[J]. Anal Chem, 2015, 24:12340-12347.
[7]Politi J, Rea I, NiciF,etal. Nanogravimetricandopticalcharacterizations of thrombin interaction with a self-assembledthiolated aptamer[J]. Journal of Sensors, 2016, 2016:1-8.
[8]Shan W, Pan Y, Fang H, et al. An aptamer-based quartz crystalmicrobalance biosensor for sensitive and selective detection ofleukemia cells using silver-enhanced gold nanoparticle label[J].Talanta, 2014, 126:130-135.
[9]Ozalp VC, Bayramoglu G, Erdem Z, et al. Pathogen detection incomplex samples by quartz crystal microbalance sensor coupled toaptamer functionalized core-shell type magnetic separation[J].Anal Chim Acta, 2015, 853:533-540.
[10]Xu L, Wang R, Kelso LC, et al. A target-responsive and sizedependent hydrogel aptasensor embedded with QD fluorescentreporters for rapid detection of avian influenza virus H5N1[J].Sensors and Actuators B:Chemical, 2016, 234:98-108.
[11]MacKay S, Wishart D, Xing JZ, et al. Developing trends in aptamerbased biosensor devices and their applications[J]. IEEE TransBiomed Circuits Syst, 2014, 8(1):4-14.
[12]Hansen JA, Wang J, Kawde A, et al. Quantum-dot/aptamer-basedultrasensitive multi-analyte electrochemical biosensor[J]. J AmChem Soc, 2006, 128(7):2228-2229.
[13]Lu Y, Zhu N, Yu P, Mao L. Aptamer-based electrochemical sensorsthat are not based on the target binding-induced conformationalchange of aptamers[J]. Analyst, 2008, 133(9):1256-1260.
[14]Kang Y, Feng KJ, Chen JW, et al. Electrochemical detection ofthrombin by sandwich approach using antibody and aptamer[J].Bioelectrochemistry, 2008, 73(1):76-81.
[15]Arroyo-Currás N, Scida K, Ploense KL, et al. High surface areaelectrodes generated via electrochemical roughening improve thesignaling of electrochemical aptamer-based biosensors[J]. AnalChem, 2017, 89(22):12185-12191.
[16]Abi A, Mohammadpour Z, Zuo X, et al. Nucleic acid-basedelectrochemical nanobiosensors[J]. Biosens Bioelectron, 2018,102:479-489.
[17]Ikebukuro K, Kiyohara C, Sode K. Novel electrochemical sensorsystem for protein using the aptamers in sandwich manner[J].Biosens Bioelectron, 2005, 20(10):2168-2172.
[18]肖丽娟,孙娟,柴雅琴.基于壳聚糖/碳纳米管/石墨烯/铁氰化镍纳米复合材料构建的电化学适体传感器用于凝血酶的检测[J].化学传感器, 2014(3):53-57.
[19]Lv Y, Zhang Z, Chen F. Chemiluminescence microfluidic systemsensor on a chip for determination of glucose in human serum withimmobilized reagents[J]. Talanta, 2003, 59(3):571-576.
[20]Marquette CA, Blum LJ. Regenerable immunobiosensor for thechemiluminescent flow injection analysis of the herbicide 2, 4-D[J]. Talanta, 2000, 51(2):395-401.
[21]Zhao L, Li B, Zhang Z, et al. Chemiluminescent flow-through sensorfor automated dissolution testing of analgin tablets using manganesedioxide as oxidate[J]. Sensors and Actuators, 2004, 97(2/3):266-271.
[22]严喜鸾,陈馨,肖义陂,等.基于适体生物传感器的碱性磷酸酯酶化学发光检测腺苷[J].分析测试学报, 2017(4):565-569.
[23]Lee M, Walt DR. A fiber-optic microarray biosensor using aptamersas receptors[J]. Anal Biochem, 2000, 282(1):142-146.
[24]Plomer M, Guilbault GG, Hock B. Development of a piezoelectricimmunosensor for the detection of enterobacteria[J]. EnzymeMicrob Technol, 1992, 14(3):230-235.
[25]Sun H, Zhang YY, Si SH, et al. Piezoelectric quartz crystal(PQC)with photochemically deposited nano-sized Ag particlesfor determining cyanide at trace levels in water[J]. Sensors andActuators B:Chemical, 2005, 108(1-2):925-932.
[26]Bunroddith K, Viseshakul N, Chansiri K, et al. QCM-based rapiddetection of PCR amplification products of Ehrlichia canis[J].Anal Chim Acta, 2018, 1001:106-111.
[27]Abadian PN, Buch P, Goluch ED, et al. Real-time monitoring ofurinary encrustation using a quartz crystal microbalance[J].Anal Chem, 2018. doi:10. 1021/acs. analchem.
[28]Song S, Wang L, Li J, et al. Aptamer-based biosensors[J]. TrACTrends in Anal Chem, 2008, 27(2):108-117.
[29]Sauerbrey G. The use of quartz oscillators for weighing layers andfor micro-weighing[J]. Z Physik, 1959, 155-206.
[30]Groff K, Brown J, Clippinger AJ. Modern affinity reagents:Recombinant antibodies and aptamers[J]. BiotechnologyAdvances, 2015, 33(8):1787-1798.
[31]Osypova A, Thakar D, Dejeu J, et al. Sensor based on aptamerfolding to detect low-molecular weight analytes[J]. Anal Chem,2015, 87(15):7566-7574.
[32]?zalp VC. Acoustic quantification of ATP using a quartz crystalmicrobalance with dissipation[J]. Analyst, 2011, 136(23):5046-5050.
[33]Dong ZM, Zhao GC. A theophylline quartz crystal microbalancebiosensor based on recognition of RNA aptamer and amplificationof signal[J]. Analyst, 2013, 138(8):2456-2462.
[34]Yao C, Qi Y, Zhao Y, et al. Aptamer-based piezoelectric quartzcrystal microbalance biosensor array for the quantification ofIgE[J]. Biosens Bioelectron, 2009, 24(8):2499-2503.
[35]Chen Q, Tang W, Wang D, et al. Amplified QCM-D biosensor forprotein based on aptamer-functionalized gold nanoparticles[J].Biosens Bioelectron, 2010, 26(2):575-579.
[36]Sun W, Song W, Guo X, et al. Ultrasensitive detection of nucleicacids and proteins using quartz crystal microbalance and surfaceplasmon resonance sensors based on target-triggering multiplesignal amplification strategy[J]. Anal Chim Acta, 2017, 978:42-47.
[37]Wu C, Du L, Zou L, et al. A biomimetic bitter receptor-basedbiosensor with high efficiency immobilization and purification usingself-assembled aptamers[J]. Analyst, 2013, 20:5989-5994.
[38]Du L, Wu C, Peng H, et al. Piezoelectric olfactory receptorbiosensor prepared by aptamer-assisted immobilization[J].Sensors and Actuators B:Chemical, 2013, 187:481-487.
[39]Pan Y, Guo M, Nie Z, et al. Selective collection and detectionof leukemia cells on a magnet-quartz crystal microbalancesystem using aptamer-conjugated magnetic beads[J]. BiosensBioelectron, 2010, 25(7):1609-1614.
[40]Wang L, Wang R, Chen F, et al. QCM-based aptamer selectionand detection of Salmonella typhimurium[J]. Food Chem, 2017,221:776-782.
[41]Yu X, Chen F, Wang R, et al. Whole-bacterium SELEX of DNAaptamers for rapid detection of E. coli O157:H7 using a QCMsensor[J]. J Biotechnol, 2018, 266:39-49.
[42]Brockman L, Wang R, Lum J, et al. QCM Aptasensor for rapid andspecific detection of avian influenza virus[J]. Open Journal ofApplied Biosensor, 2013, 02(04):97-103.
[43]冯阳阳,李杜娟,叶尊忠,等.纳米颗粒在石英晶体微天平生物传感器中的应用与研究进展[J].中国生物医学工程学报,2011(02):299-307.
[44]Dong Z, Zhao G. Quartz crystal microbalance aptasensor forsensitive detection of mercury(ii)based on signal amplificationwith gold nanoparticles[J]. Sensors, 2012, 6:7080-7094.
[45]Chen Q, Wu X, Wang D, et al. Oligonucleotide-functionalized goldnanoparticles-enhanced QCM-D sensor for mercury(II)ions withhigh sensitivity and tunable dynamic range[J]. The Analyst,2011, 136(12):2572.
[46]Sheng Z, Han J, Zhang J, et al. Method for detection of Hg2+basedon the specific thymine-Hg2+-thymineinteractionintheDNAhybridization on the surface of quartz crystal microbalance[J].Colloids and Surfaces B:Biointerfaces, 2011, 87(2):289-292.
[47]Zheng B, Cheng S, Liu W, et al. Small organic molecules detectionbased on aptamer-modified gold nanoparticles-enhanced quartzcrystal microbalance with dissipation biosensor[J]. AnalBiochem, 2013, 438(2):144-149.
[48]SongW,ZhuZ,MaoY,etal.Asensitivequartzcrystalmicrobalance assay of adenosine triphosphate via DNAzymeactivatedandaptamer-basedtarget-triggeringcircularamplification[J]. Biosens Bioelectron, 2014, 53:288-294.
[49]Hianik T, OstatnáV, Sonlajtnerova M, et al. Influence of ionicstrength, pH and aptamer configuration for binding affinity tothrombin[J]. Bioelectrochemistry, 2007, 70(1):127-133.
[50]Nübel C, Appel B, Hospach I, et al. Challenges and opportunitiesin the development of aptamers for TNFα[J]. Appl BiochemBiotechnol, 2016, 179(3):398-414.
[51]He P, Liu L, Qiao W, et al. Ultrasensitive detection of thrombinusing surface plasmon resonance and quartz crystal microbalancesensors by aptamer-based rolling circle amplification andnanoparticle signal enhancement[J]. Chem Commun(Camb),2014, 50(12):1481-1484.
[52]Wang R, Li Y. Hydrogel based QCM aptasensor for detection ofavian influenzavirus[J]. Biosens Bioelectron, 2013, 42:148-155.
[53]Xu L, Wang R, Kelso LC, et al. A target-responsive and sizedependent hydrogel aptasensor embedded with QD fluorescentreporters for rapid detection of avian influenza virus H5N1[J].Sensors and Actuators B:Chemical, 2016, 234:98-108.
[54]苏雪,何逸婷,林俊生.适体和蛋白质解离常数检测方法比较分析[J].传感器与微系统, 2016(11):47-50.