Electrochemical aptamer-based sensors

Abstract

The valuable properties of aptamers, such as specificity, sensitivity, stability, cost-effectiveness and design flexibility, have favoured their use as biorecognition elements in biosensor development. These synthetic affinity probes can be developed for almost any target molecule, covering a wide range of applications in fields such as clinical diagnosis and therapy, environmental monitoring and food control. The combination of aptamers with high-performance electrochemical transducers, with their inherent high sensitivities, fast response times and simple equipment, has already provided several electrochemical aptamer-based sensors. Moreover, the small size and versatility of aptamers allow efficient immobilisations in high-density monolayers, an important feature towards miniaturisation and integration of compact electrochemical devices. This review describes the state-of-the-art of electrochemical aptamer-based sensors, entering into the details of the different strategies and types of electrochemical transduction and also considering their advantages when applied to the analysis of complex matrices.

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References

  1. 1.

    Bakker E, Qin Y (2006) Electrochemical sensors. Anal Chem 78:3965–3983

    Article  CAS  Google Scholar 

  2. 2.

    Campàs M (2002) DNA sensors: a review. Anal Lett 35:1875–1894

    Article  CAS  Google Scholar 

  3. 3.

    Junhui Z, Hong C, Ruifu Y (1997) DNA based biosensors. Biotech Adv 15:43–58

    Article  Google Scholar 

  4. 4.

    Kleinjung F, Klussmann S, Erdmann VA, Scheller FW, Fürste JP, Bier FF (1998) High-affinity RNA as a recognition element in a biosensor. Anal Chem 70:328–331

    Article  CAS  Google Scholar 

  5. 5.

    Potyrailo RA, Conrad RC, Ellington AD, Hieftje GM (1998) Adapting selected nucleic acid ligands (aptamers) to biosensors. Anal Chem 70:3419–3425

    Article  CAS  Google Scholar 

  6. 6.

    Luzi E, Minunni M, Tombelli S, Mascini M (2003) New trends in affinity sensing: aptamers for ligand binding. TrAC 22:810–818

    CAS  Google Scholar 

  7. 7.

    Ellington AD, Szostak JW (1990) In vitro selection of RNA molecules that bind specific ligands. Nature 346:818–822

    Article  CAS  Google Scholar 

  8. 8.

    Tuerk C, Gold L (1990) Systematic evolution of ligands by exponential enrichment: RNA ligands to bacteriophage T4 DNA polymerase. Science 249:505–510

    Article  CAS  Google Scholar 

  9. 9.

    Stoltenburg R, Reinemann C, Strehlitz B (2007) SELEX—a (r)evolutionary method to generate high-affinity nucleic acid ligands. Biomol Eng 24:381–403

    Article  CAS  Google Scholar 

  10. 10.

    Göringer HU, Homann M, Lorger M (2003) In vitro selection of high-affinity nucleic acid ligands to parasite target molecules. Int J Parasitol 33:1309–1317

    Article  CAS  Google Scholar 

  11. 11.

    James W (2000) Aptamers. In: Meyers RA (ed) Encyclopedia of analytical chemistry. Wiley, Chichester, pp 4848–4871

    Google Scholar 

  12. 12.

    Palecek E, Fojta M (1994) Differential pulse voltammetric determination of RNA at the picomole level in the presence of DNA and nucleic acid component. Anal Chem 66:1566–1571

    Article  CAS  Google Scholar 

  13. 13.

    Wang J (1999) Electroanalysis and biosensors. Anal Chem 71:328–332

    Article  Google Scholar 

  14. 14.

    Wang J (2000) Survey and summary: from DNA biosensors to gene chips. Nucleic Acids Res 28:3011–3016

    Article  CAS  Google Scholar 

  15. 15.

    Mairal T, Oezalp VC, Sanchez PL, Mir M, Katakis I, O’Sullivan CK (2008) Aptamers: molecular tools for analytical applications. Anal Bioanal Chem 390:989–1007

    Article  CAS  Google Scholar 

  16. 16.

    Ikebukuro K, Kiyohara C, Sode K (2005) Novel electrochemical sensor system for protein using the aptamers in sandwich manner. Biosens Bioelectron 20:2168–2172

    Article  CAS  Google Scholar 

  17. 17.

    Tyagi S, Kramer FR (1996) Molecular beacons: probes that fluoresce upon hybridization. Nat Biotechnol 14:303–308

    Article  CAS  Google Scholar 

  18. 18.

    Yamamoto R, Kumar PKR (2000) Molecular beacon aptamer fluoresces in the presence of Tat protein of HIV-1. Genes Cells 5:389–396

    Article  CAS  Google Scholar 

  19. 19.

    Ikebukuro K, Kiyohara C, Sode K (2004) Electrochemical detection of protein using a double aptamer sandwich. Anal Lett 37:2901–2909

    Article  CAS  Google Scholar 

  20. 20.

    Mir M, Vreeke M, Katakis I (2006) Different strategies to develop an electrochemical thrombin aptasensor. Electrochem Commun 8:505–511

    Article  CAS  Google Scholar 

  21. 21.

    Feng K, Kang Y, Zhao J-J, Liu Y-L, Jiang J-H, Shen G-L, Yu R-Q (2008) Electrochemical immunosensor with aptamer-based enzymatic amplification. Anal Biochem 378:38–42

    Article  CAS  Google Scholar 

  22. 22.

    Centi S, Bonel SL, Tombelli S, Palchetti I, Mascini M (2009) Detection of C reactive protein (CRP) in serum by an electrochemical aptamer-based sandwich assay. Electroanalysis 21:1309–1315

    Article  CAS  Google Scholar 

  23. 23.

    Centi S, Tombelli S, Minunni M, Mascini M (2007) Aptamer-based detection of plasma proteins by an electrochemical assay coupled to magnetic beads. Anal Chem 79:1466–1473

    Article  CAS  Google Scholar 

  24. 24.

    Polsky R, Gill R, Kaganovsky L, Willner I (2006) Nucleic acid-functionalized Pt nanoparticles: catalytic labels for the amplified electrochemical detection of biomolecules. Anal Chem 78:2268–2271

    Article  CAS  Google Scholar 

  25. 25.

    Numnuam A, Chumbimuni-Torres KY, Xiang Y, Bash R, Thavarungkul P, Kanatharana P, Pretsch E, Wang J, Bakker E (2008) Aptamer-based potentiometric measurements of proteins using ion-selective microelectrodes. Anal Chem 80:707–712

    Article  CAS  Google Scholar 

  26. 26.

    Sharon E, Freeman R, Tel-Vered R, Willner I (2009) Impedimetric or ion-sensitive field-effect transistor (ISFET) aptasensors based on the self-assembly of Au nanoparticle-functionalized supramolecular aptamer nanostructures. Electroanalysis 21:1291–1296

    Article  CAS  Google Scholar 

  27. 27.

    Wang J, Meng W, Zheng X, Liu S, Li G (2009) Combination of aptamer with gold nanoparticles for electrochemical signal amplification: application to sensitive detection of platelet-derived growth factor. Biosens Bioelectron 24:1598–1602

    Article  CAS  Google Scholar 

  28. 28.

    Ding C, Ge Y, Lin J-M (2010) Aptamer based electrochemical assay for the determination of thrombin using the amplification of the nanoparticles. Biosens Bioelectron 25:1290–1294

    Article  CAS  Google Scholar 

  29. 29.

    Zhang Y-L, Pang P-F, Jiang J-H, Shen G-L, Yu R-Q (2009) Electrochemical aptasensor based on proximity-dependent surface hybridization assay for protein detection. Electroanalysis 21:1327–1333

    Article  CAS  Google Scholar 

  30. 30.

    He P, Shen L, Cao Y, Li D (2007) Ultrasensitive electrochemical detection of proteins by amplification of aptamer–nanoparticle bio bar codes. Anal Chem 79:8024–8029

    Article  CAS  Google Scholar 

  31. 31.

    Papamichael KI, Kreuzer MP, Guilbault GG (2007) Viability of allergy (IgE) detection using an alternative aptamer receptor and electrochemical means. Sensor Actuat B-Chem 121:178–186

    Article  CAS  Google Scholar 

  32. 32.

    Hansen JA, Wang J, Kawde A-N, Xiang Y, Gothelf KV, Collins G (2006) Quantum-dot/aptamer-based ultrasensitive multi-analyte electrochemical biosensor. J Am Chem Soc 128:2228–2229

    Article  CAS  Google Scholar 

  33. 33.

    Wu Z-S, Guo M-M, Zhang S-B, Chen C-R, Jiang J-H, Shen G-L, Yu R-Q (2007) Reusable electrochemical sensing platform for highly sensitive detection of small molecules based on structure-switching signalling aptamers. Anal Chem 79:2933–2939

    Article  CAS  Google Scholar 

  34. 34.

    Lu Y, Zhu N, Yu P, Mao L (2008) Aptamer-based electrochemical sensors that are not based on the target binding-induced conformational change of aptamers. Analyst 133:1256–1260

    Article  CAS  Google Scholar 

  35. 35.

    Fukasawa M, Yoshida W, Yamazaki H, Sode K, Ikebukuro K (2009) An aptamer-based bound/free separation system for protein detection. Electroanalysis 21:1297–1302

    Article  CAS  Google Scholar 

  36. 36.

    Xiao Y, Lubin AA, Heeger AJ, Plaxco KW (2005) Label-free electronic detection of thrombin in blood serum by using an aptamer-based sensor. Angew Chem Int Ed 44:5456–5459

    Article  CAS  Google Scholar 

  37. 37.

    White RJ, Phares N, Lubin AA, Xiao Y, Plaxco KW (2008) Optimization of electrochemical aptamer-based sensors via optimization of probe packing density and surface chemistry. Langmuir 24:10513–10518

    Article  CAS  Google Scholar 

  38. 38.

    Xiao Y, Piorek BD, Plaxco KW, Heeger AJ (2005) A reagentless signal-on architecture for electronic, aptamer-based sensors via target-induced strand displacement. J Am Chem Soc 127:17990–17991

    Article  CAS  Google Scholar 

  39. 39.

    Zuo X, Song S, Zhang J, Pan D, Wang L, Fan C (2007) A target-responsive electrochemical aptamer switch (TREAS) for reagentless detection of nanomolar ATP. J Am Chem Soc 129:1042–1043

    Article  CAS  Google Scholar 

  40. 40.

    Lai RY, Plaxco KW, Heeger AJ (2007) Aptamer-based electrochemical detection of picomolar platelet-derived growth factor directly in blood serum. Anal Chem 79:229–233

    Article  CAS  Google Scholar 

  41. 41.

    Radi AE, Acero Sánchez JL, Baldrich E, O’Sullivan CK (2006) Reagentless, reusable, ultrasensitive electrochemical molecular beacon aptasensor. J Am Chem Soc 128:117–124

    Article  CAS  Google Scholar 

  42. 42.

    Acero Sánchez JL, Baldrich E, Radi AEG, Dondapati S, Lozano SP, Katakis I, O’Sullivan CK (2006) Electronic “off-on” molecular switch for rapid detection of thrombin. Electroanalysis 18:1957–1962

    Article  CAS  Google Scholar 

  43. 43.

    Baker BR, Lai RY, Wood MS, Doctor EH, Heeger AJ, Plaxco KW (2006) An electronic, aptamer-based small-molecule sensor for the rapid, label-free detection of cocaine in adulterated samples and biological fluids. J Am Chem Soc 128:3138–3139

    Article  CAS  Google Scholar 

  44. 44.

    Ferapontova EE, Olsen EM, Gothelf KV (2008) An RNA aptamer-based electrochemical biosensor for detection of theophylline in serum. J Am Chem Soc 130:4256–4258

    Article  CAS  Google Scholar 

  45. 45.

    Rankin CJ, Fuller EN, Hamor KH, Gabarra SA, Shields TP (2006) A simple fluorescent biosensor for theophylline based on its RNA aptamer. Nucleosides Nucleotides Nucleic Acids 25:1407–1424

    Article  CAS  Google Scholar 

  46. 46.

    Ferapontova EE, Gothelf KV (2009) Optimization of the electrochemical RNA-aptamer based biosensor for theophylline by using a methylene blue redox label. Electroanalysis 21:1261–1266

    Article  CAS  Google Scholar 

  47. 47.

    Lu Y, Li X, Zhang L, Yu P, Su L, Mao L (2008) Aptamer-based electrochemical sensors with aptamer-complementary DNA oligonucleotides as probe. Anal Chem 80:1883–1890

    Article  CAS  Google Scholar 

  48. 48.

    Cheng AKH, Sen D, Yu H-Z (2009) Design and testing of aptamer-based electrochemical biosensors for proteins and small molecules. Bielectrochemistry 77:1–12

    Article  CAS  Google Scholar 

  49. 49.

    Kim YS, Jung HS, Matsuura T, Lee HY, Kawai T, Gu MB (2007) Electrochemical detection of 17β-estradiol using DNA aptamer immobilized gold electrode chip. Biosens Bioelectron 22:2525–2531

    Article  CAS  Google Scholar 

  50. 50.

    Cheng AKH, Ge BX, Yu HZ (2007) Aptamer-based biosensors for label-free voltammetric detection of lysozyme. Anal Chem 79:5158–5164

    Article  CAS  Google Scholar 

  51. 51.

    Le Floch F, Ho HA, Leclerc M (2006) Label-free electrochemical detection of protein based on a ferrocene-bearing cationic polythiopene and aptamer. Anal Chem 78:4727–4731

    Article  CAS  Google Scholar 

  52. 52.

    Evtugyn GA, Porfireva AV, Hianik T, Cheburova MS, Budnikov HC (2009) Potentiometric DNA sensor based on electropolymerized phenothiazines for protein detection. Electroanalysis 21:1300–1308

    Article  CAS  Google Scholar 

  53. 53.

    Dua Y, Chena C, Li B, Zhoua M, Wanga E, Dong S (2010) Layer-by-layer electrochemical biosensor with aptamer-appended active polyelectrolyte multilayer for sensitive protein determination. Biosens Bioelectron 25:1902–1907

    Article  CAS  Google Scholar 

  54. 54.

    Tuite E, Norden B (1994) Sequence-specific interaction of methylene blue with polynucleotides and DNA: a spectroscopic study. J Am Chem Soc 116:7548–7556

    Article  CAS  Google Scholar 

  55. 55.

    Kelley SO, Boon EM, Barton JK, Jackson NM, Hill MG (1999) Single-base mismatch detection based on charge transduction through DNA. Nucleic Acids Res 27:4830–4837

    Article  CAS  Google Scholar 

  56. 56.

    Erdem A, Kerman K, Meric B, Akarca US, Ozsoz M (2000) Novel hybridization indicator methylene blue for the electrochemical detection of short DNA sequences related to the hepatitis B virus. Anal Chim Acta 422:139–149

    Article  CAS  Google Scholar 

  57. 57.

    Rohs R, Sklenar H, Lavery R, Röder B (2000) Methylene blue binding to DNA with alternating GC base sequence: a modeling study. J Am Chem Soc 122:2860–2866

    Article  CAS  Google Scholar 

  58. 58.

    Hianik T, Ostatna V, Zajacova Z, Stoikova E, Evtugyn G (2005) Detection of aptamer–protein interactions using QCM and electrochemical indicator methods. Bioorg Med Chem Lett 15:291–295

    Article  CAS  Google Scholar 

  59. 59.

    Kang Y, Feng K-J, Chen J-W, Jiang J-H, Shen G-L, Yu R-Q (2008) Electrochemical detection of thrombin by sandwich approach using antibody and aptamer. Bioelectrochemistry 73:76–81

    Article  CAS  Google Scholar 

  60. 60.

    Kawde A-N, Rodriguez MC, Lee TMH, Wang J (2005) Label-free bioelectronic detection of aptamer–protein interactions. Electrochem Commun 7:537–540

    Article  CAS  Google Scholar 

  61. 61.

    Erdem A, Karadeniz H, Mayer G, Famulok M, Caliskan A (2009) Electrochemical sensing of aptamer–protein interactions using a magnetic particle assay and single-use sensor technology. Electroanalysis 21:1278–1284

    Article  CAS  Google Scholar 

  62. 62.

    So H-M, Won K, Kim YH, Kim B-K, Ryu BH, Na PS, Kim H, Lee J-O (2005) Single-walled carbon nanotube biosensors using aptamers as molecular recognition elements. J Am Chem Soc 127:11906–11907

    Article  CAS  Google Scholar 

  63. 63.

    Maehashi K, Katsura T, Kerman K, Takamura Y, Matsumoto K, Tamiya E (2007) Label-free protein biosensor based on aptamer-modified carbon nanotube field-effect transistors. Anal Chem 79:782–787

    Article  CAS  Google Scholar 

  64. 64.

    Maehashi K, Matsumoto K, Takamura Y, Tamiya E (2009) Aptamer-based label-free immunosensors using carbon nanotube field-effect transistors. Electroanalysis 21:1285–1290

    Article  CAS  Google Scholar 

  65. 65.

    Lee H-S, Kim KS, Kim C-J, Hahn SK, Jo M-H (2009) Electrical detection of VEGFs for cancer diagnoses using anti-vascular endothelial growth factor aptamer-modified Si nanowire FETs. Biosens Bioelectron 24:1801–1805

    Article  CAS  Google Scholar 

  66. 66.

    Xu D, Xu D, Yu X, Liu Z, He W, Ma Z (2005) Label-free electrochemical detection for aptamer-based array electrodes. Anal Chem 77:5107–5113

    Article  CAS  Google Scholar 

  67. 67.

    Rodriguez MC, Kawde A-N, Wang J (2005) Aptamer biosensor for label-free impedance spectroscopy detection of proteins based on recognition-induced switching of the surface charge. Chem Commun 34:4267–4269

    Article  CAS  Google Scholar 

  68. 68.

    Pan C, Guo M, Nie Z, Xiao X, Yao S (2009) Aptamer-based electrochemical sensor for label-free recognition and detection of cancer cells. Electroanalysis 21:1321–1326

    Article  CAS  Google Scholar 

  69. 69.

    Radi A-E, Acero Sánchez JL, Baldrich E, O'Sullivan CK (2005) Reusable impedimetric aptasensor. Anal Chem 77:6320–6323

    Article  CAS  Google Scholar 

  70. 70.

    Evtugyn G, Porfireva A, Ivanov A, Konovalova O, Hianik T (2009) Molecularly imprinted polymerized methylene green as a platform for electrochemical sensing of aptamer–thrombin interactions. Electroanalysis 21:1272–1277

    Article  CAS  Google Scholar 

  71. 71.

    Cai H, Lee TM-H, Hsing I-M (2006) Label-free protein recognition using an aptamer-based impedance measurement assay. Sensor Actuat B-Chem 114:433–437

    Article  CAS  Google Scholar 

  72. 72.

    Lee JA, Hwang S, Kwak J, Park SII, Lee SS, Lee K-C (2008) An electrochemical impedance biosensor with aptamer-modified pyrolyzed carbon electrode for label-free protein detection. Sensor Actuat B-Chem 129:372–379

    Article  CAS  Google Scholar 

  73. 73.

    Hianik T, Porfireva A, Grman I, Evtugyn G (2008) Aptabodies—new type of artificial receptors for detection proteins. Prot Pept Lett 15:799–805

    Article  CAS  Google Scholar 

  74. 74.

    Hianik T, Porfireva A, Grman I, Evtugyn G (2009) EQCM biosensors based on DNA aptamers and antibodies for rapid detection of prions. Prot Pept Lett 16:363–367

    Article  CAS  Google Scholar 

  75. 75.

    Xu Y, Yang L, Ye X, He P, Fang Y (2006) An aptamer-based protein biosensor by detecting the amplified impedance signal. Electroanalysis 18:1449–1456

    Article  CAS  Google Scholar 

  76. 76.

    Zayats M, Huang Y, Gill R, Ma C, Willner I (2006) Label-free and reagentless aptamer-based sensors for small molecules. J Am Chem Soc 128:13666–13667

    Article  CAS  Google Scholar 

  77. 77.

    Shen L, Chen Z, Li Y, Jing P, Xie S, He S, He P, Shao Y (2007) A chronocoulometric aptamer sensor for adenosine monophosphate. Chem Commun 2169–2171

  78. 78.

    Li B, Du Y, Wei H, Dong S (2007) Reusable, label-free electrochemical aptasensor for sensitive detection of small molecules. Chem Commun 3780–3782

  79. 79.

    Bang GS, Cho S, Kim B-G (2005) A novel electrochemical detection method for aptamer biosensors. Biosens Bioelectron 21:863–870

    Article  CAS  Google Scholar 

  80. 80.

    Xiao Y, Uzawa T, White RJ, DeMartini D, Plaxco KW (2009) On the signaling of electrochemical aptamer-based sensors: collision- and folding-based mechanisms. Electroanalysis 21:1267–1271

    Article  CAS  Google Scholar 

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Acknowledgements

Dr. Prieto-Simón is grateful to the Ministerio de Ciencia e Innovación for a Juan de la Cierva fellowship supporting her research at the IBEC. Dr. Campàs acknowledges financial support from the Ministerio de Ciencia e Innovación and the Fondo Social Europeo through the Ramón y Cajal programme as well as the Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria through the FEDER-RTA2008-00084-00-00 project.

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Correspondence to Beatriz Prieto-Simón.

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Prieto-Simón, B., Campàs, M. & Marty, JL. Electrochemical aptamer-based sensors. Bioanal Rev 1, 141–157 (2010). https://doi.org/10.1007/s12566-010-0010-1

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Keywords

  • Aptamer
  • Biosensor
  • Electrochemical detection
  • Aptabeacon
  • Redox label