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Peptide-Based Electrochemical Biosensors and Their Applications in Disease Detection

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Abstract

Biosensors based on small molecule peptides have developed rapidly in the detection of disease markers with the characteristics of high sensitivity, rapid analysis speed and easy miniaturization. The properties of the sensor, such as the sensitivity and detection range, are closely related to the material and structure of the electrodes. The electrodes mainly used in peptide-based biosensors are gold electrodes, glassy carbon electrodes (GCE), indium tin oxide (ITO) conductive glass electrodes and screen-printed electrodes. In addition, to improve the biomolecule loading rate, antifouling performance, electrical conductivity of the biosensor, a variety of nanomaterials and organic molecules are used to construct the biosensor for disease detection. This review summarizes the properties of several commonly used electrodes for peptide-based electrochemical biosensors, and introduces some modified materials of the electrode and their effects on sensor performance. In the future, the peptide-based biosensors will be widely used in clinical detection and other related fields.

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Fig. 1
Fig. 2

Copyright 2022 Elsevier. b The biosensor for TnI detection. Reprinted with permission Ref. [33] Copyright 2019 Elsevier

Fig. 3

Copyright 2021 American Chemical Society. b Electrochemical aptamer sensor for sensitive detection of PSA. Reprinted with permission Ref. [24] Copyright 2019 Elsevier. c Antifouling biosensor with designed peptide for APN and HepG2 cells detection. Reprinted with permission from Ref. [45] Copyright 2020 American Chemical Society

Fig. 4

Copyright 2019 American Chemical Society. b The biosensor for early apoptotic cells detection. Reprinted with permission from Ref. [53] Copyright 2018 American Chemical Society

Fig. 5

Copyright 2021 Elsevier. b Biosensor for the detection of CEA and PSA. Reprinted with permission from Ref. [67] Copyright 2018 American Chemical Society

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References

  1. Jiang Z, Yuan B, Qiu N, Wang Y, Sun L, Wei Z, Li Y, Zheng J, Jin Y, Li Y, Du S, Li J, Wu A. Manganese-zeolitic imidazolate frameworks-90 with high blood circulation stability for MRI-guided tumor therapy. Nano-micro Lett. 2019;11(1):61.

    Article  CAS  Google Scholar 

  2. Zhang Q, Zhang X, Ma Q. Recent advances in visual electrochemiluminescence analysis. J Anal Test. 2020;4(2):92–106.

    Article  Google Scholar 

  3. Xu Y, Tuo W, Yang L, Sun Y, Li C, Chen X, Yang W, Yang G, Stang PJ, Sun Y. Design of a metallacycle-based supramolecular photosensitizer for in vivo image-guided photodynamic inactivation of bacteria. Angew Chem Int Ed. 2022;61(5): e202110048.

    Article  CAS  Google Scholar 

  4. Zhang Y, Zhang X, Yang H, Yu L, Xu Y, Sharma A, Yin P, Li X, Kim JS, Sun Y. Advanced biotechnology-assisted precise sonodynamic therapy. Chem Soc Rev. 2021;50(20):11227–48.

    Article  CAS  PubMed  Google Scholar 

  5. Li Y, Tu L, Ma X, Chen H, Fan Y, Zhou Q, Sun Y. Engineering a smart nanofluidic sensor for high-performance peroxynitrite sensing through a spirocyclic ring open/close reaction strategy. ACS Sens. 2021;6(3):808–14.

    Article  CAS  PubMed  Google Scholar 

  6. Qin J, Cho M, Lee Y. Ultrasensitive detection of amyloid-β using cellular prion protein on the highly conductive Au nanoparticles–poly(3,4-ethylene dioxythiophene)–poly(thiophene-3-acetic acid) composite electrode. Anal Chem. 2019;91(17):11259–65.

    Article  CAS  PubMed  Google Scholar 

  7. Fereja TH, Du F, Wang C, Snizhko D, Guan Y, Xu G. Electrochemiluminescence imaging techniques for analysis and visualizing. J Anal Test. 2020;4(2):76–91.

    Article  Google Scholar 

  8. Qin J, Cho M, Lee Y. Ferrocene-encapsulated Zn zeolitic imidazole framework (ZIF-8) for optical and electrochemical sensing of amyloid-β oligomers and for the early diagnosis of alzheimer’s disease. ACS Appl Mater Interfaces. 2019;11(12):11743–8.

    Article  CAS  PubMed  Google Scholar 

  9. Park J, Park JS, Huang CH, Jo A, Cook K, Wang R, Lin HY, Van Deun J, Li H, Min J, Wang L, Yoon G, Carter BS, Balaj L, Choi GS, Castro CM, Weissleder R, Lee H. An integrated magneto-electrochemical device for the rapid profiling of tumour extracellular vesicles from blood plasma. Nat Biomed Eng. 2021;5(7):678–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Zhang R, Huang J, Chen K, Boussouar I, Chen X, Fan Y, Sun Y, Li H. Highly efficient ionic gating of solid-state nanosensors by the reversible interaction between pillar[6]arene-AuNPs and azobenzene. Anal Chem. 2021;93(6):3280–6.

    Article  CAS  PubMed  Google Scholar 

  11. Kou BB, Zhang L, Xie H, Wang D, Yuan YL, Chai YQ, Yuan R. DNA enzyme-decorated DNA nanoladders as enhancer for peptide cleavage-based electrochemical biosensor. ACS Appl Mater Interfaces. 2016;8(35):22869–74.

    Article  CAS  PubMed  Google Scholar 

  12. Kou BB, Chai YQ, Yuan YL, Yuan R. PtNPs as scaffolds to regulate interenzyme distance for construction of efficient enzyme cascade amplification for ultrasensitive electrochemical detection of MMP-2. Anal Chem. 2017;89(17):9383–7.

    Article  CAS  PubMed  Google Scholar 

  13. Chen H, Crum M, Chavan D, Vu B, Kourentzi K, Willson RC. Nanoparticle-based proximity ligation assay for ultrasensitive, quantitative detection of protein biomarkers. ACS Appl Mater Interfaces. 2018;10(38):31845–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Thapa K, Liu W, Wang R. Nucleic acid-based electrochemical biosensor: Recent advances in probe immobilization and signal amplification strategies. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2021;14(1): e1765.

    PubMed  Google Scholar 

  15. Yu KX, Qiao ZJ, Song WL, Bi S. DNA nanotechnology for multimodal synergistic theranostics. J Anal Test. 2021;5(2):112–29.

    Article  Google Scholar 

  16. Wang M, Li L, Zhang L, Zhao J, Jiang Z, Wang W. Peptide-derived biosensors and their applications in tumor immunology-related detection. Anal Chem. 2022;94(1):431–41.

    Article  CAS  PubMed  Google Scholar 

  17. Karimzadeh A, Hasanzadeh M, Shadjou N, Guardia Mdl. Peptide based biosensors. TrAC Trend Anal Chem. 2018;107:1–20.

  18. Li H, Huang H, Feng JJ, Luo X, Fang KM, Wang ZG, Wang AJ. A polypeptide-mediated synthesis of green fluorescent gold nanoclusters for Fe3+ sensing and bioimaging. J Colloid Interface Sci. 2017;506:386–92.

    Article  CAS  PubMed  Google Scholar 

  19. Dong ZM, Cheng L, Zhang P, Zhao GC. Label-free analytical performances of a peptide-based QCM biosensor for trypsin. Analyst. 2020;145(9):3329–38.

    Article  CAS  PubMed  Google Scholar 

  20. Hu J, Zhang ZH, Zhu Z, Chen J, Hu X, Chen H. Specific intracellular binding peptide as sPD-L1 antibody mimic: Robust binding capacity and intracellular region specific modulation upon applied to sensing research. Biosens Bioelectron. 2021;185: 113269.

    Article  CAS  PubMed  Google Scholar 

  21. Sun Z, Wu S, Peng Y, Wang M, Jalalah M, Al-Assiri MS, Harraz FA, Yang J, Li G. Sensor array for rapid pathogens identification fabricated with peptide-conjugated 2D metal-organic framework nanosheets. Chem Eng J. 2021;405: 126707.

    Article  CAS  Google Scholar 

  22. Yuan K, Mei Q, Guo X, Xu Y, Yang D, Sanchez BJ, Sheng B, Liu C, Hu Z, Yu G, Ma H, Gao H, Haisch C, Niessner R, Jiang Z, Jiang Z, Zhou H. Antimicrobial peptide based magnetic recognition elements and Au@Ag-GO SERS tags with stable internal standards: a three in one biosensor for isolation, discrimination and killing of multiple bacteria in whole blood. Chem Sci. 2018;9(47):8781–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Yaman YT, Vural OA, Bolat G, Abaci S. One-pot synthesized gold nanoparticle-peptide nanotube modified disposable sensor for impedimetric recognition of miRNA 410. Sens Actuators B. 2020;320: 128343.

    Article  CAS  Google Scholar 

  24. Li ZJ, Yin JF, Gao CH, Qiu GH, Meng AA, Li QD. The construction of electrochemical aptasensor based on coral-like polyaniline and Au nano-particles for the sensitive detection of prostate specific antigen. Sens Actuators B. 2019;295:93–100.

    Article  CAS  Google Scholar 

  25. Liu S, Jia Y, Dong H, Yu X, Zhang DP, Ren X, Li Y, Wei Q. Intramolecular photoelectrochemical system using tyrosine-modified antibody-targeted peptide as electron donor for detection of biomarkers. Anal Chem. 2020;92(16):10935–9.

    Article  CAS  PubMed  Google Scholar 

  26. Liu N, Song J, Lu Y, Davis JJ, Gao F, Luo X. Electrochemical aptasensor for ultralow fouling cancer cell quantification in complex biological media based on designed branched peptides. Anal Chem. 2019;91(13):8334–40.

    Article  CAS  PubMed  Google Scholar 

  27. Puiu M, Idili A, Moscone D, Ricci F, Bala C. A modular electrochemical peptide-based sensor for antibody detection. Chem Commun. 2014;50(64):8962–5.

    Article  CAS  Google Scholar 

  28. Huang GB, Guo ZY, Ye TX, Zhang C, Zhou YM, Yao QH, Chen X. Colorimetric determination of chloridion in domestic water based on the wavelength shift of CsPbBr3 perovskite nanocrystals via halide exchange. J Anal Test. 2021;5(1):3–10.

    Article  Google Scholar 

  29. Huang Y, Zhang B, Yuan L, Liu L. A signal amplification strategy based on peptide self-assembly for the identification of amyloid-β oligomer. Sens Actuators B. 2021;335: 129697.

    Article  CAS  Google Scholar 

  30. Cho H, Lee CS, Kim TH. Label-free assay of protein kinase a activity and inhibition using a peptide-based electrochemical sensor. Biomedicines. 2021;9(4):423.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Meng F, Sun H, Huang Y, Tang Y, Chen Q, Miao P. Peptide cleavage-based electrochemical biosensor coupling graphene oxide and silver nanoparticles. Anal Chim Acta. 2019;1047:45–51.

    Article  CAS  PubMed  Google Scholar 

  32. Nisiewicz MK, Kowalczyk A, Gajda A, Kasprzak A, Bamburowicz-Klimkowska M, Grudzinski IP, Nowicka AM. Enzymatic cleavage of specific dipeptide conjugated with ferrocene as a flexible ultra-sensitive and fast voltammetric assay of matrix metalloproteinase-9 considered a prognostic cancer biomarker in plasma samples. Biosens Bioelectron. 2022;195: 113653.

    Article  CAS  PubMed  Google Scholar 

  33. Negahdary M, Heli H. An electrochemical troponin I peptisensor using a triangular icicle-like gold nanostructure. Biochem Eng J. 2019;151: 107326.

    Article  CAS  Google Scholar 

  34. Hu X, Zhang N, Shen L, Yu L, Huang LY, Wang AJ, Shan D, Yuan PX, Feng JJ. The enhanced photoelectrochemical platform constructed by N-doped ZnO nanopolyhedrons and porphyrin for ultrasensitive detection of brain natriuretic peptide. Anal Chim Acta. 2021;1183: 338870.

    Article  CAS  PubMed  Google Scholar 

  35. Wang B, Jing R, Qi H, Gao Q, Zhang C. Label-free electrochemical impedance peptide-based biosensor for the detection of cardiac troponin I incorporating gold nanoparticles modified carbon electrode. J Electroanal Chem. 2016;781:212–7.

    Article  CAS  Google Scholar 

  36. Xu Y, Wang X, Ding C, Luo X. Ratiometric antifouling electrochemical biosensors based on multifunctional peptides and MXene loaded with Au nanoparticles and methylene blue. ACS Appl Mater Interfaces. 2021;13(17):20388–96.

    Article  CAS  PubMed  Google Scholar 

  37. Yang L, Gao Y, Fang K, Sun H, Sun J, Liu H, Feng W, Jiang L. Photocatalytically renewable peptide-based electrochemical impedance method for sensing lipopolysaccharide. Microchim Acta. 2020;187(6):349.

    Article  CAS  Google Scholar 

  38. Tang Z, Wang L, Ma Z. Triple sensitivity amplification for ultrasensitive electrochemical detection of prostate specific antigen. Biosens Bioelectron. 2017;92:577–82.

    Article  CAS  PubMed  Google Scholar 

  39. Dimcheva N. Nanostructures of noble metals as functional materials in biosensors. Curr Opin Electrochem. 2020;19:35–41.

    Article  CAS  Google Scholar 

  40. Chen Y, Zhang S, Hong Z, Lin Y, Dai H. A mimotope peptide-based dual-signal readout competitive enzyme-linked immunoassay for non-toxic detection of zearalenone. J Mater Chem B. 2019;7(44):6972–80.

    Article  CAS  PubMed  Google Scholar 

  41. Xi X, Wen M, Song S, Zhu J, Wen W, Zhang X, Wang S. A H2O2-free electrochemical peptide biosensor based on Au@Pt bimetallic nanorods for highly sensitive sensing of matrix metalloproteinase 2. Chem Commun. 2020;56(45):6039–42.

    Article  CAS  Google Scholar 

  42. Hao Q, Xu Q, Niu S, Ding C, Luo X. Anti-fouling magnetic beads combined with signal amplification strategies for ultra-sensitive and selective electrochemiluminescence detection of micrornas in complex biological media. Anal Chem. 2021;93(30):10679–87.

    Article  CAS  PubMed  Google Scholar 

  43. Liu N, Fan X, Hou H, Gao F, Luo X. Electrochemical sensing interfaces based on hierarchically architectured zwitterionic peptides for ultralow fouling detection of alpha fetoprotein in serum. Anal Chim Acta. 2021;1146:17–23.

    Article  CAS  PubMed  Google Scholar 

  44. Chen M, Han R, Wang W, Li Y, Luo X. Antifouling aptasensor based on self-assembled loop-closed peptides with enhanced stability for CA125 assay in complex biofluids. Anal Chem. 2021;93(40):13555–63.

    Article  CAS  PubMed  Google Scholar 

  45. Song Z, Chen M, Ding C, Luo X. Designed three-in-one peptides with anchoring, antifouling, and recognizing capabilities for highly sensitive and low-fouling electrochemical sensing in complex biological media. Anal Chem. 2020;92(8):5795–802.

    Article  CAS  PubMed  Google Scholar 

  46. El-Said WA, Choi JW. High selective spectroelectrochemical biosensor for HCV-RNA detection based on a specific peptide nucleic acid. Spectrochim Acta A. 2019;217:288–93.

    Article  CAS  Google Scholar 

  47. Wu FF, Zhou Y, Zhang H, Yuan R, Chai YQ. Electrochemiluminescence peptide-based biosensor with hetero-nanostructures as coreaction accelerator for the ultrasensitive determination of tryptase. Anal Chem. 2018;90(3):2263–70.

    Article  CAS  PubMed  Google Scholar 

  48. Zhang Q, Chen Z, Shi Z, Li Y, An Z, Li X, Shan J, Lu Y, Liu Q. Smartphone-based photoelectrochemical biosensing system with graphitic carbon nitride/gold nanoparticles modified electrodes for matrix metalloproteinase-2 detection. Biosens Bioelectron. 2021;193: 113572.

    Article  CAS  PubMed  Google Scholar 

  49. Wang Y, Li X, Waterhouse GIN, Zhou Y, Yin H, Ai S. Photoelectrochemical biosensor for protein kinase A detection based on carbon microspheres, peptide functionalized Au-ZIF-8 and TiO2/g-C3N4. Talanta. 2019;196:197–203.

    Article  CAS  PubMed  Google Scholar 

  50. Ding C, Wang X, Luo X. Dual-mode electrochemical assay of prostate-specific antigen based on antifouling peptides functionalized with electrochemical probes and internal references. Anal Chem. 2019;91(24):15846–52.

    Article  CAS  PubMed  Google Scholar 

  51. Yang R, Yan X, Li Y, Zhang X, Chen J. Nitrogen-doped porous carbon-ZnO nanopolyhedra derived from ZIF-8: new materials for photoelectrochemical biosensors. ACS Appl Mater Interfaces. 2017;9(49):42482–91.

    Article  CAS  PubMed  Google Scholar 

  52. Yang R, Li Y, Zou K, Meng L, Zhang X, Chen J. A label-free and blocker-free photoelectrochemical strategy for highly sensitive caspase-3 assay. Chem Commun. 2018;54(38):4830–3.

    Article  CAS  Google Scholar 

  53. Wu R, Fan GC, Jiang LP, Zhu JJ. Peptide-based photoelectrochemical cytosensor using a hollow-TiO2/EG/ZnIn2S4 cosensitized structure for ultrasensitive detection of early apoptotic cells and drug evaluation. ACS Appl Mater Interfaces. 2018;10(5):4429–38.

    Article  CAS  PubMed  Google Scholar 

  54. Barros Azeredo NF, Ferreira Santos MS, Sempionatto JR, Wang J, Angnes L. Screen-printed technologies combined with flow analysis techniques: moving from benchtop to everywhere. Anal Chem. 2022;94(1):250–68.

    Article  CAS  PubMed  Google Scholar 

  55. Lee H, Lee YS, Reginald SS, Baek S, Lee EM, Choi IG, Chang IS. Biosensing and electrochemical properties of flavin adenine dinucleotide (FAD)-dependent glucose dehydrogenase (GDH) fused to a gold binding peptide. Biosens Bioelectron. 2020;165: 112427.

    Article  CAS  PubMed  Google Scholar 

  56. Eissa S, Zourob M. A dual electrochemical/colorimetric magnetic nanoparticle/peptide-based platform for the detection of staphylococcus aureus. Analyst. 2020;145(13):4606–14.

    Article  PubMed  Google Scholar 

  57. Lee MH, Thomas JL, Liao CL, Jurcevic S, Crnogorac-Jurcevic T, Lin HY. Polymers imprinted with three REG1B peptides for electrochemical determination of regenerating protein 1B, a urinary biomarker for pancreatic ductal adenocarcinoma. Microchim Acta. 2017;184(6):1773–80.

    Article  CAS  Google Scholar 

  58. Baek SH, Kim MW, Park CY, Choi CS, Kailasa SK, Park JP, Park TJ. Development of a rapid and sensitive electrochemical biosensor for detection of human norovirus via novel specific binding peptides. Biosens Bioelectron. 2019;123:223–9.

    Article  CAS  PubMed  Google Scholar 

  59. Chang PH, Weng CC, Li BR, Li YK. An antifouling peptide-based biosensor for determination of streptococcus pneumonia markers in human serum. Biosens Bioelectron. 2020;151: 111969.

    Article  CAS  PubMed  Google Scholar 

  60. Selvam SP, Chinnadayyala SR, Cho S. Electrochemical nanobiosensor for early detection of rheumatoid arthritis biomarker: anti-cyclic citrullinated peptide antibodies based on polyaniline (PANI)/MoS2-modified screen-printed electrode with PANI-Au nanomatrix-based signal amplification. Sens Actuators B. 2021;333: 129570.

    Article  CAS  Google Scholar 

  61. Hou Y, Lv CC, Guo YL, Ma XH, Liu W, Jin Y, Li BX, Yang M, Yao SY. Recent advances and applications in paper-based devices for point-of-care testing. J Anal Test. 2022;1–27.

  62. Li L, Zhang Y, Ge S, Zhang L, Cui K, Zhao P, Yan M, Yu J. Triggerable H2O2-cleavable switch of paper-based biochips endows precision of chemometer/ratiometric electrochemical quantification of analyte in high-efficiency point-of-care testing. Anal Chem. 2019;91(15):10273–81.

    Article  CAS  PubMed  Google Scholar 

  63. Kong Q, Cui K, Zhang L, Wang Y, Sun J, Ge S, Zhang Y, Yu J. “On-off-on” photoelectrochemical/visual lab-on-paper sensing via signal amplification of CdS quantum dots@leaf-shape ZnO and quenching of Au-modified prism-anchored octahedral CeO2 nanoparticles. Anal Chem. 2018;90(19):11297–304.

    Article  CAS  PubMed  Google Scholar 

  64. Hu M, Yang H, Li Z, Zhang L, Zhu P, Yan M, Yu J. Signal-switchable lab-on-paper photoelectrochemical aptasensing system integrated triple-helix molecular switch with charge separation and recombination regime of type-II CdTe@CdSe core-shell quantum dots. Biosens Bioelectron. 2020;147: 111786.

    Article  CAS  PubMed  Google Scholar 

  65. Wang H, Jian Y, Kong Q, Liu H, Lan F, Liang L, Ge S, Yu J. Ultrasensitive electrochemical paper-based biosensor for microRNA via strand displacement reaction and metal-organic frameworks. Sens Actuators B. 2018;257:561–9.

    Article  CAS  Google Scholar 

  66. Zheng X, Li L, Zhang L, Xie L, Song X, Yu J. Multiple self-cleaning paper-based electrochemical ratiometric biosensor based on the inner reference probe and exonuclease III-assisted signal amplification strategy. Biosens Bioelectron. 2020;147: 111769.

    Article  CAS  PubMed  Google Scholar 

  67. Zheng X, Li L, Cui K, Zhang Y, Zhang L, Ge S, Yu J. Ultrasensitive enzyme-free biosensor by coupling cyclodextrin functionalized Au nanoparticles and high-performance Au-paper electrode. ACS Appl Mater Interfaces. 2018;10(4):3333–40.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors are grateful for financial support from National Natural Science Foundation of China (22074006), Beijing Natural Science Foundation (2222029), National Key R&D Program of China (2018YFE0205400) and Beijing Institute of Technology Research Fund Program for Young Scholars. We thank Analysis & Testing Center, Beijing Institute of Technology for their kind help.

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Correspondence to Jie Cao or Wei-Zhi Wang.

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Zhao, JG., Cao, J. & Wang, WZ. Peptide-Based Electrochemical Biosensors and Their Applications in Disease Detection. J. Anal. Test. 6, 193–203 (2022). https://doi.org/10.1007/s41664-022-00226-y

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