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Electrochemical biosensors based on nucleic acid aptamers

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Abstract

During recent decades, nucleic acid aptamers have emerged as powerful biological recognition elements for electrochemical affinity biosensors. These bioreceptors emulate or improve on antibody-based biosensors because of their excellent characteristics as bioreceptors, including limitless selection capacity for a large variety of analytes, easy and cost-effective production, high stability and reproducibility, simple chemical modification, stable and oriented immobilization on electrode surfaces, enhanced target affinity and selectivity, and possibility to design them in target-sensitive 3D folded structures. This review provides an overview of the state of the art of electrochemical aptasensor technology, focusing on novel aptamer-based electroanalytical assay configurations and providing examples to illustrate the different possibilities. Future prospects for this technology are also discussed.

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References

  1. Yáñez Sedeño P, Villalonga R, Pingarrón JM. Electroanalytical methods based on hybrid nanomaterials. In: Meyer RA, editor. Encyclopedia of analytical chemistry: applications, theory and instrumentation. Wiley; 2015. p. 1-18.

  2. Ronkainen NJ, Halsall HB, Heineman WR. Electrochemical biosensors. Chem. Soc. Rev. 2010;39:1747–63.

    CAS  PubMed  Google Scholar 

  3. da Silva ETSG, Souto DEP, Barragan JTC, de F Giarola J, de Moraes ACM, Kubota LT. Electrochemical biosensors in point of care devices: recent advances and future trends. ChemElectroChem. 2017;4:778–94.

    Google Scholar 

  4. WiseGuy Reports (2017) Global electrochemical biosensors market trends & forecast 2017 To 2022. Report No. WGR2375992 (https://www.wiseguyreports.com/reports/2375992-global-electrochemical-biosensors-market-trends-forecast-2017-to-2022

  5. Kirsch J, Siltanen C, Zhou Q, Revzin A, Simonian A. Biosensor technology: recent advances in threat agent detection and medicine. Chem. Soc. Rev. 2013;42:8733–68.

    CAS  PubMed  Google Scholar 

  6. Song Y, Luo Y, Zhu C, Li H, Du D, Lin Y. Recent advances in electrochemical biosensors based on graphene two-dimensional nanomaterials. Biosens. Bioelectron. 2016;76:195–212.

    CAS  PubMed  Google Scholar 

  7. Wang L, Xiong Q, Xiao F, Duan H. 2D nanomaterials based electrochemical biosensors for cancer diagnosis. Biosens. Bioelectron. 2017;89:136–51.

    CAS  PubMed  Google Scholar 

  8. Wang Z, Dai Z. Carbon nanomaterial-based electrochemical biosensors: an overview. Nanoscale. 2015;7:6420–31.

    CAS  PubMed  Google Scholar 

  9. Song S, Wang L, Li J, Fan C, Zhao J. Aptamer-based biosensors. Trends. Anal. Chem. 2008;27:108–17.

    CAS  Google Scholar 

  10. Plaxco KW, Soh HT. Switch-based biosensors: a new approach towards real-time, in vivo molecular detection. Trends. Biotechnol. 2011;29:1–5.

    CAS  PubMed  Google Scholar 

  11. Kaur H, Bruno JG, Kumar A, Sharma TK. Aptamers in the therapeutics and diagnostics pipelines. Theranostics. 2018;8:4016.

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Razmi N, Baradaran B, Hejazi M, Hasanzadeh M, Mosafer J, Mokhtarzadeh A, et al. Recent advances on aptamer-based biosensors to detection of platelet-derived growth factor. Biosens. Bioelectron. 2018;113:58–71.

    CAS  PubMed  Google Scholar 

  13. Ellington AD, Szostak JW. In vitro selection of RNA molecules that bind specific ligands. Nature. 1990;346:818.

    CAS  PubMed  Google Scholar 

  14. Tuerk C, Gold L. Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science. 1990;249:505–10.

    CAS  PubMed  Google Scholar 

  15. Colas P, Cohen B, Jessen T, Grishina I, McCoy J, Brent R. Genetic selection of peptide aptamers that recognize and inhibit cyclin-dependent kinase 2. Nature. 1996;380:548.

    CAS  PubMed  Google Scholar 

  16. Darmostuk M, Rimpelova S, Gbelcova H, Ruml T. Current approaches in SELEX: An update to aptamer selection technology. Biotechnol. Adv. 2015;33:1141–61.

    CAS  PubMed  Google Scholar 

  17. Wu YX, Kwon YJ. Aptamers: The “evolution” of SELEX. Methods. 2016;106:21–8.

    CAS  PubMed  Google Scholar 

  18. Bayat P, Nosrati R, Alibolandi M, Rafatpanah H, Abnous K, Khedri M, et al. SELEX methods on the road to protein targeting with nucleic acid aptamers. Biochimie. 2018;154:132–55.

    CAS  PubMed  Google Scholar 

  19. Dunn MR, Jimenez RM, Chaput JC. Analysis of aptamer discovery and technology. Nat. Rev. Chem. 2017;1:0076.

    CAS  Google Scholar 

  20. Cai S, Yan J, Xiong H, Liu Y, Peng D, Liu Z. Investigations on the interface of nucleic acid aptamers and binding targets. Analyst. 2018;143:5317–38.

    CAS  PubMed  Google Scholar 

  21. Mayer G. The chemical biology of aptamers. Angew. Chem. 2009;48:2672–89.

    CAS  Google Scholar 

  22. Iliuk AB, Hu L, Tao WA. Aptamer in bioanalytical applications. Anal. Chem. 2011;83:4440–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Vermeer AW, Norde W. The thermal stability of immunoglobulin: unfolding and aggregation of a multi-domain protein. Biophys. J. 2000;78:394–404.

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Nutiu R, Li Y. Structure-switching signaling aptamers. J. Am. Chem. Soc. 2003;125:4771–8.

    CAS  PubMed  Google Scholar 

  25. Xiao Y, Lai RY, Plaxco KW. Preparation of electrode-immobilized, redox-modified oligonucleotides for electrochemical DNA and aptamer-based sensing. Nat. Protoc. 2007;2:2875–80.

    CAS  PubMed  Google Scholar 

  26. Cheng AK, Sen D, Yu HZ. Design and testing of aptamer-based electrochemical biosensors for proteins and small molecules. Bioelectrochemistry. 2009;77:1–12.

    CAS  PubMed  Google Scholar 

  27. Schoukroun-Barnes LR, Macazo FC, Gutierrez B, Lottermoser J, Liu J, White RJ. Reagentless, structure-switching, electrochemical aptamer-based sensors. Annu. Rev. Anal. Chem. 2016;9:163–81.

    CAS  Google Scholar 

  28. Vallée-Bélisle A, Plaxco KW. Structure-switching biosensors: inspired by nature. Curr. Opin. Struct. Biol. 2010;20:518–26.

    PubMed  PubMed Central  Google Scholar 

  29. Mao Y, Luo C, Ouyang Q. Studies of temperature-dependent electronic transduction on DNA hairpin loop sensor. Nucleic Acids Res. 2003;31:108.

    Google Scholar 

  30. Hianik T, Ostatná V, Sonlajtnerova M, Grman I. Influence of ionic strength, pH and aptamer configuration for binding affinity to thrombin. Bioelectrochemistry. 2007;70:127–33.

    CAS  PubMed  Google Scholar 

  31. Pilehvar S, Jambrec D, Gebala M, Schuhmann W, De Wael K. Intercalation of proflavine in ssDNA aptamers: effect on binding of the specific target chloramphenicol. Electroanalysis. 2015;27:1836–41.

    CAS  Google Scholar 

  32. Kékedy-Nagy L, Shipovskov S, Ferapontova EE. Effect of a dual charge on the DNA-conjugated redox probe on DNA sensing by short hairpin beacons tethered to gold electrodes. Anal. Chem. 2016;88:7984–90.

    PubMed  Google Scholar 

  33. Sachan A, Ilgu M, Kempema A, Kraus GA, Nilsen-Hamilton M. Specificity and ligand affinities of the cocaine aptamer: impact of structural features and physiological NaCl. Anal. Chem. 2016;88:7715–23.

    CAS  PubMed  Google Scholar 

  34. Chen Y, Pui TS, Kongsuphol P, Tang KC, Arya SK. Aptamer-based array electrodes for quantitative interferon-γ detection. Biosen. Bioelectron. 2014;53:257–62.

    CAS  Google Scholar 

  35. Yu ZG, Lai RY. A reagentless and reusable electrochemical aptamer-based sensor for rapid detection of ampicillin in complex samples. Talanta. 2018;176:619–24.

    CAS  PubMed  Google Scholar 

  36. Das R, Dhiman A, Mishra SK, Haldar S, Sharma N, Bansal A, et al. Structural switching electrochemical DNA aptasensor for the rapid diagnosis of tuberculous meningitis. Int. J. Nanomed. 2019;14:2103.

    CAS  Google Scholar 

  37. Liu Y, Matharu Z, Rahimian A, Revzin A. Detecting multiple cell-secreted cytokines from the same aptamer-functionalized electrode. Biosens. Bioelectron. 2015;64:43–50.

    CAS  PubMed  Google Scholar 

  38. Jia J, Feng J, Chen HG, Luo HQ, Li NB. A simple electrochemical method for the detection of ATP using target-induced conformational change of dual-hairpin DNA structure. Sens. Actuators B. 2016;222:1090–5.

    CAS  Google Scholar 

  39. Pividori MI, Merkoci A, Alegret S. Electrochemical genosensor design: immobilisation of oligonucleotides onto transducer surfaces and detection methods. Biosens. Bioelectron. 2000;15:291–303.

    CAS  PubMed  Google Scholar 

  40. Tabrizi MA, Shamsipur M, Saber R, Sarkar S, Besharati M. An electrochemical aptamer-based assay for femtomolar determination of insulin using a screen printed electrode modified with mesoporous carbon and 1,3,6,8-pyrenetetrasulfonate. Microchim. Acta. 2018;85:59.

    Google Scholar 

  41. Yu Z, Luan Y, Li H, Wang W, Wang X, Zhang Q. A disposable electrochemical aptasensor using single-stranded DNA-methylene blue complex as signal-amplification platform for sensitive sensing of bisphenol A. Sens. Actuators B. 2019;284:73–80.

    CAS  Google Scholar 

  42. Roushani M, Shahdost-fard F. Covalent attachment of aptamer onto nanocomposite as a high performance electrochemical sensing platform: fabrication of an ultra-sensitive ibuprofen electrochemical aptasensor. Mater. Sci. Eng. 2016;68:128–35.

    CAS  Google Scholar 

  43. Wei M, Zhang W. The determination of ochratoxin A based on the electrochemical aptasensor by carbon aerogels and methylene blue assisted signal amplification. Chem. Cent. J. 2018;12:45.

    CAS  PubMed  PubMed Central  Google Scholar 

  44. Raouafi A, Sánchez A, Raouafi N, Villalonga R. Electrochemical aptamer-based bioplatform for ultrasensitive detection of prostate specific antigen. Sens. Actuators B. 2019;297:126762.

    CAS  Google Scholar 

  45. Karimipour M, Heydari-Bafrooei E, Sanjari M, Johansson MB, Molaei M. A glassy carbon electrode modified with TiO2(200)-rGO hybrid nanosheets for aptamer based impedimetric determination of the prostate specific antigen. Microchim. Acta. 2019;186:33.

    Google Scholar 

  46. Arya SK, Zhurauski P, Jolly P, Batistuti MR, Mulato M, Estrela P. Capacitive aptasensor based on interdigitated electrode for breast cancer detection in undiluted human serum. Biosens. Bioelectron. 2018;102:106–12.

    CAS  PubMed  Google Scholar 

  47. Grabowska I, Sharma N, Vasilescu A, Iancu M, Badea G, Boukherroub R, et al. Electrochemical aptamer-based biosensors for the detection of cardiac biomarkers. ACS Omega. 2018;3:12010–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Fenzl C, Nayak P, Hirsch T, Wolfbeis OS, Alshareef HN, Baeumner AJ. Laser-scribed graphene electrodes for aptamer-based biosensing. ACS Sens. 2017;2:616–20.

    CAS  PubMed  Google Scholar 

  49. Singh NK, Thungon PD, Estrela P, Goswami P. Development of an aptamer-based field effect transistor biosensor for quantitative detection of Plasmodium falciparum glutamate dehydrogenase in serum samples. Biosens. Bioelectron. 2019;123:30–5.

    CAS  PubMed  Google Scholar 

  50. Argoubi W, Sánchez A, Parrado C, Raouafi N, Villalonga R. Label-free electrochemical aptasensing platform based on mesoporous silica thin film for the detection of prostate specific antigen. Sens. Actuators B. 2018;255:309–15.

    CAS  Google Scholar 

  51. Jolly P, Tamboli V, Harniman RL, Estrela P, Allender CJ, Bowen JL. Aptamer-MIP hybrid receptor for highly sensitive electrochemical detection of prostate specific antigen. Biosens. Bioelectron. 2016;75:188–95.

    CAS  PubMed  Google Scholar 

  52. Wang YH, Xia H, Huang KJ, Wu X, Ma YY, Deng R, et al. Ultrasensitive determination of thrombin by using an electrode modified with WSe2 and gold nanoparticles, aptamer-thrombin-aptamer sandwiching, redox cycling, and signal enhancement by alkaline phosphatase. Microchim. Acta. 2018;185:502.

    Google Scholar 

  53. Kim SH, Nam O, Jin E, Gu MB. A new coccolith modified electrode-based biosensor using a cognate pair of aptamers with sandwich-type binding. Biosens. Bioelectron. 2019;123:160–6.

    CAS  PubMed  Google Scholar 

  54. Seo HB, Gu MB. Aptamer-based sandwich-type biosensors. J. Biol. Eng. 2017;11:11.

    PubMed  PubMed Central  Google Scholar 

  55. Shui B, Tao D, Cheng J, Mei Y, Jaffrezic-Renault N, Guo Z. A novel electrochemical aptamer-antibody sandwich assay for the detection of tau-381 in human serum. Analyst. 2018;143:3549–54.

    CAS  PubMed  Google Scholar 

  56. Lee S, Hayati S, Kim S, Lee HJ. Determination of protein tyrosine kinase-7 concentration using electrocatalytic reaction and an aptamer-antibody sandwich assay platform. Catal. Today. 2019. https://doi.org/10.1016/j.cattod.2019.05.029.

  57. Chung S, Moon JM, Choi J, Hwang H, Shim YB. Magnetic force assisted electrochemical sensor for the detection of thrombin with aptamer-antibody sandwich formation. Biosens. Bioelectron. 2018;117:480–6.

    CAS  PubMed  Google Scholar 

  58. Wang QL, Cui HF, Song X, Fan SF, Chen LL, Li MM, et al. A label-free and lectin-based sandwich aptasensor for detection of carcinoembryonic antigen. Sens. Actuators B. 2018;260:48–54.

    CAS  Google Scholar 

  59. Paniagua G, Villalonga A, Eguílaz M, Vegas B, Parrado C, Rivas G, et al. Amperometric aptasensor for carcinoembryonic antigen based on the use of bifunctionalized Janus nanoparticles as biorecognition-signaling element. Anal. Chim. Acta. 2019;1061:84–91.

    CAS  PubMed  Google Scholar 

  60. Jiang B, Li F, Yang C, Xie J, Xiang Y, Yuan R. Target-induced catalytic hairpin assembly formation of functional Y-junction DNA structures for label-free and sensitive electrochemical detection of human serum proteins. Sens. Actuators B. 2017;244:61–6.

    CAS  Google Scholar 

  61. Shi K, Dou B, Yang J, Yuan R, Xiang Y. Target-triggered catalytic hairpin assembly and TdT-catalyzed DNA polymerization for amplified electronic detection of thrombin in human serums. Biosens. Bioelectron. 2017;87:495–500.

    CAS  PubMed  Google Scholar 

  62. Zhang R, Gu Y, Wang Z, Li Y, Fan Q, Jia Y. Aptamer cell sensor based on porous graphene oxide decorated ion-selective-electrode: double sensing platform for cell and ion. Biosens. Bioelectron. 2018;117:303–11.

    CAS  PubMed  Google Scholar 

  63. Aktas GB, Skouridou V, Masip L. Sandwich-type aptasensor employing modified aptamers and enzyme-DNA binding protein conjugates. Anal.Bioanal. Chem. 2019; 411:3581.

    CAS  PubMed  Google Scholar 

  64. Chen X, Wang Y, Zhang Y, Chen Z, Liu Y, Li Z, et al. Sensitive electrochemical aptamer biosensor for dynamic cell surface N-glycan evaluation featuring multivalent recognition and signal amplification on a dendrimer–graphene electrode interface. Anal. Chem. 2014;86:4278–86.

    CAS  PubMed  Google Scholar 

  65. Shangguan D, Li Y, Tang Z, Cao ZC, Chen HW, Mallikaratchy P, et al. Aptamers evolved from live cells as effective molecular probes for cancer study. Proc. Natl. Acad. Sci. U. S. A. 2006;103:11838–43.

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Kiernan JA. Localization of α-D-glucosyl and α-D-mannosyl groups of mucosubstances with concanavalin A and horseradish peroxidase. Histochemistry. 1975;44:39–45.

    CAS  PubMed  Google Scholar 

  67. Abbaspour A, Norouz-Sarvestani F, Noori A, Soltani N. Aptamer-conjugated silver nanoparticles for electrochemical dual-aptamer-based sandwich detection of Staphylococcus aureus. Biosens. Bioelectron. 2015;68:149–55.

    CAS  PubMed  Google Scholar 

  68. Brosel-Oliu S, Ferreira R, Uria N, Abramova N, Gargallo R, Muñoz-Pascual FX, et al. Novel impedimetric aptasensor for label-free detection of Escherichia coli O157: H7. Sens. Actuators B. 2018;255:2988–95.

    CAS  Google Scholar 

  69. Li Z, Yin J, Gao C, Sheng L, Meng A. A glassy carbon electrode modified with graphene oxide, poly (3, 4-ethylenedioxythiophene), an antifouling peptide and an aptamer for ultrasensitive detection of adenosine triphosphate. Microchim. Acta. 2019;186:90.

    Google Scholar 

  70. Eissa S, Siaj M, Zourob M. Aptamer-based competitive electrochemical biosensor for brevetoxin-2. Biosens. Bioelectron. 2015;69:148–54.

    CAS  PubMed  Google Scholar 

  71. Kazane I, Gorgy K, Gondran C, Spinelli N, Zazoua A, Defrancq E, et al. Highly sensitive bisphenol-A electrochemical aptasensor based on poly(pyrrole-nitrilotriacetic acid)-aptamer film. Anal. Chem. 2016;88:7268–73.

    CAS  PubMed  Google Scholar 

  72. Wu M, Kempaiah R, Huang PJJ, Maheshwari V, Liu J. Adsorption and desorption of DNA on graphene oxide studied by fluorescently labeled oligonucleotides. Langmuir. 2011;27:2731–8.

    CAS  PubMed  Google Scholar 

  73. Liu B, Sun Z, Zhang X, Liu J. Mechanisms of DNA sensing on graphene oxide. Anal. Chem. 2013;85:7987–93.

    CAS  PubMed  Google Scholar 

  74. Park JS, Goo NI, Kim DE. Mechanism of DNA adsorption and desorption on graphene oxide. Langmuir. 2014;30:12587–95.

    CAS  PubMed  Google Scholar 

  75. Ahour F, Ahsani MK. An electrochemical label-free and sensitive thrombin aptasensor based on graphene oxide modified pencil graphite electrode. Biosens. Bioelectron. 2016;86:764–9.

    CAS  PubMed  Google Scholar 

  76. Eissa S, Zourob M. In vitro selection of DNA aptamers targeting β-lactoglobulin and their integration in graphene-based biosensor for the detection of milk allergen. Biosens. Bioelectron. 2017;91:169–74.

    CAS  PubMed  Google Scholar 

  77. Yu SH, Lee CS, Kim TH. Electrochemical detection of ultratrace lead ion through attaching and detaching DNA aptamer from electrochemically reduced graphene oxide electrode. Nanomaterials. 2019;9:817.

    PubMed Central  Google Scholar 

  78. Aceta Y, Del Valle M. Graphene electrode platform for impedimetric aptasensing. Electrochim. Acta. 2017;229:458–66.

    CAS  Google Scholar 

  79. Jain P, Das S, Chakma B, Goswami P. Aptamer-graphene oxide for highly sensitive dual electrochemical detection of Plasmodium lactate dehydrogenase. Anal. Biochem. 2016;514:32–7.

    CAS  PubMed  Google Scholar 

  80. Stephanopoulos N, Freeman R. DNA-based materials as self-assembling scaffolds for interfacing with cells. In: Azevedo HS, da Silva RMP, editors. Self-assembling biomaterials. Elsevier; 2018, p. 157-175.

  81. Taghdisi SM, Danesh NM, Ramezani M, Emrani AS, Abnous K. A novel electrochemical aptasensor based on Y-shape structure of dual-aptamer-complementary strand conjugate for ultrasensitive detection of myoglobin. Biosens. Bioelectron. 2016;80:532–7.

    CAS  PubMed  Google Scholar 

  82. Wang D, Xiao X, Xu S, Liu Y, Li Y. Electrochemical aptamer-based nanosensor fabricated on single Au nanowire electrodes for adenosine triphosphate assay. Biosens. Bioelectron. 2018;99:431–7.

    CAS  PubMed  Google Scholar 

  83. Qing Y, Li X, Chen S, Zhou X, Luo M, Xu X, et al. Differential pulse voltammetric ochratoxin A assay based on the use of an aptamer and hybridization chain reaction. Microchim. Acta. 2017;184:863–70.

    CAS  Google Scholar 

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Acknowledgment

Financial support from the Spanish Ministry of Economy and Competitiveness (projects CTQ2014-58989-P, CTQ2015-71936-REDT, and CTQ2017-87954-P) is gratefully acknowledged.

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  1. Nanosensors and Nanomachines Group, Department of Analytical Chemistry, Faculty of Chemistry, Complutense University of Madrid, 28040, Madrid, Spain

    Anabel Villalonga, Ana María Pérez-Calabuig & Reynaldo Villalonga

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  1. Anabel Villalonga
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Villalonga, A., Pérez-Calabuig, A.M. & Villalonga, R. Electrochemical biosensors based on nucleic acid aptamers. Anal Bioanal Chem 412, 55–72 (2020). https://doi.org/10.1007/s00216-019-02226-x

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