Skip to main content
Log in

Recent Advances of Nanoelectrodes for Single-Cell Electroanalysis: From Extracellular, Intercellular to Intracellular

  • Review
  • Published:
Journal of Analysis and Testing Aims and scope Submit manuscript

Abstract

Detection at single-cell level plays a critical role in revealing cell behavior in different organisms. Nanoelectrodes with high temporal–spatial resolution can precisely and dynamically monitor the physiological and pathological processes of various single cells. The field of using nanoelectrodes in single-cell electroanalysis is blooming in recent years. In this review, we mainly summarize the recent advances of nanoelectrodes for single-cell electroanalysis from extracellular, intercellular to intracellular levels in the past decade. First, we introduce the main types of nanoelectrodes based on their geometry and characteristics for single-cell electroanalysis. Then, the representative works of using nanoelectrodes to investigate cellular signaling biomolecules and to understand various cellular processes from the extracellular, intercellular, and intracellular levels are introduced. Finally, the challenges and future prospects of nanoelectrodes for single-cell electroanalysis are proposed. This review gives a comprehensive summary of nanoelectrodes for single-cell electroanalysis in the prospects of monitoring cell physiological topography, understanding communication mechanism and revealing physiological functions, which can provide new insights into cell-based pharmacological screening and fundamental studies of disease development mechanisms.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Lin TE, Rapino S, Girault HH, Lesch A. Electrochemical imaging of cells and tissues. Chem Sci. 2018;9(20):4546–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Polcari D, Dauphin-Ducharme P, Mauzeroll J. Scanning electrochemical microscopy: a comprehensive review of experimental parameters from 1989 to 2015. Chem Rev. 2016;116(22):13234–78.

    Article  CAS  PubMed  Google Scholar 

  3. Zhang J, Zhou J, Pan R, Jiang D, Burgess JD, Chen H-Y. New frontiers and challenges for single-cell electrochemical analysis. ACS Sens. 2018;3(2):242–50.

    Article  CAS  PubMed  Google Scholar 

  4. Zhang J, Zhu T, Lang J, Fu W, Li F. Recent advances of scanning electrochemical microscopy and scanning ion conductance microscopy for single-cell analysis. Curr Opin Electrochem. 2020;22:178–85.

    Article  CAS  Google Scholar 

  5. Valenti G, Scarabino S, Goudeau B, Lesch A, Jovic M, Villani E, Sentic M, Rapino S, Arbault S, Paolucci F, Sojic N. Single cell electrochemiluminescence imaging: from the proof-of-concept to disposable device-based analysis. J Am Chem Soc. 2017;139(46):16830–7.

    Article  CAS  PubMed  Google Scholar 

  6. Cox JT, Zhang B. Nanoelectrodes: recent advances and new directions. Annu Rev Anal Chem. 2012;5(1):253–72.

    Article  CAS  Google Scholar 

  7. Murray RW. Nanoelectrochemistry: metal nanoparticles, nanoelectrodes, and nanopores. Chem Rev. 2008;108(7):2688–720.

    Article  CAS  PubMed  Google Scholar 

  8. Oja SM, Wood M, Zhang B. Nanoscale electrochemistry. Anal Chem. 2013;85(2):473–86.

    Article  CAS  PubMed  Google Scholar 

  9. Lyon AR, MacLeod KT, Zhang Y, Garcia E, Kanda GK, Lab MJ, Korchev YE, Harding SE, Gorelik J. Loss of T-tubules and other changes to surface topography in ventricular myocytes from failing human and rat heart. Proc Natl Acad Sci USA. 2009;106(16):6854–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Ren L, Pour MD, Majdi S, Li X, Malmberg P, Ewing AG. Zinc regulates chemical-transmitter storage in nanometer vesicles and exocytosis dynamics as measured by amperometry. Angew Chem Int Ed. 2017;56(18):4970–5.

    Article  CAS  Google Scholar 

  11. Zhang XW, Qiu QF, Jiang H, Zhang FL, Liu YL, Amatore C, Huang WH. Real-time intracellular measurements of ROS and RNS in living cells with single core-shell nanowire electrodes. Angew Chem Int Ed. 2017;56(42):12997–3000.

    Article  CAS  Google Scholar 

  12. Zhang XW, Oleinick A, Jiang H, Liao QL, Qiu QF, Svir I, Liu YL, Amatore C, Huang W-H. Electrochemical monitoring of ROS/RNS homeostasis within individual phagolysosomes inside single macrophages. Angew Chem Int Ed. 2019;58(23):7753–6.

    Article  CAS  Google Scholar 

  13. Ali SMU, Asif MH, Fulati A, Nur O, Willander M, Brännmark C, Strålfors P, Englund UH, Elinder F, Danielsson B. Intracellular K determination with a potentiometric microelectrode based on ZnO nanowires. IEEE Trans Nanotechnol. 2011;10(4):913–9.

    Article  Google Scholar 

  14. Welle Theresa M, Alanis K, Colombo ML, Sweedler JV, Shen M. A high spatiotemporal study of somatic exocytosis with scanning electrochemical microscopy and nanoITIES electrodes. Chem Sci. 2018;9(22):4937–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Asif MH, Ali SMU, Nur O, Willander M, Brännmark C, Strålfors P, Englund UH, Elinder F, Danielsson B. Functionalised ZnO-nanorod-based selective electrochemical sensor for intracellular glucose. Biosens Bioelectron. 2010;25(10):2205–11.

    Article  CAS  PubMed  Google Scholar 

  16. Erofeev A, Gorelkin P, Garanina A, Alova A, Efremova M, Vorobyeva N, Edwards C, Korchev Y, Majouga A. Novel method for rapid toxicity screening of magnetic nanoparticles. Sci Rep UK. 2018;8(1):7462.

    Article  CAS  Google Scholar 

  17. Vaneev AN, Gorelkin PV, Garanina AS, Lopatukhina HV, Vodopyanov SS, Alova AV, Ryabaya OO, Akasov RA, Zhang Y, Novak P, Salikhov SV, Abakumov MA, Takahashi Y, Edwards CRW, Klyachko NL, Majouga AG, Korchev YE, Erofeev AS. In vitro and in vivo electrochemical measurement of reactive oxygen species after treatment with anticancer drugs. Anal Chem. 2020;92(12):8010–4.

    Article  CAS  PubMed  Google Scholar 

  18. Song J, Xu CH, Huang SZ, Lei W, Ruan YF, Lu HJ, Zhao W, Xu JJ, Chen HY. Ultrasmall nanopipette: toward continuous monitoring of redox metabolism at subcellular level. Angew Chem Int Ed. 2018;57(40):13226–30.

    Article  CAS  Google Scholar 

  19. Marquitan M, Clausmeyer J, Actis P, Córdoba AL, Korchev Y, Mark MD, Herlitze S, Schuhmann W. Intracellular hydrogen peroxide detection with functionalised nanoelectrodes. Chem Electro Chem. 2016;3(12):2125–9.

    CAS  Google Scholar 

  20. Lu SM, Peng YY, Ying YL, Long YT. Electrochemical sensing at a confined space. Anal Chem. 2020;92(8):5621–44.

    Article  CAS  PubMed  Google Scholar 

  21. Li Z, Xu K, Wei F. Recent development of samples’ surface properties using scanning ion conductance microscopy. Micro Nano Lett. 2019;14(7):744–8.

    Article  CAS  Google Scholar 

  22. Li X, Majdi S, Dunevall J, Fathali H, Ewing AG. Quantitative Measurement of Transmitters in Individual Vesicles in the Cytoplasm of Single Cells with Nanotip Electrodes. Angew Chem Int Ed. 2015;54(41):11978–82.

    Article  CAS  Google Scholar 

  23. Pan R, Xu M, Jiang D, Burgess JD, Chen H-Y. Nanokit for single-cell electrochemical analyses. Proc Natl Acad Sci USA. 2016;113:11436.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Zheng J, Li X, Wang K, Song J, Qi H. Electrochemical nanoaptasensor for continuous monitoring of ATP fluctuation at subcellular level. Anal Chem. 2020;92(16):10940–5.

    Article  CAS  PubMed  Google Scholar 

  25. Li Y, Hu K, Yu Y, Rotenberg SA, Amatore C, Mirkin MV. Direct electrochemical measurements of reactive oxygen and nitrogen species in nontransformed and metastatic human breast cells. J Am Chem Soc. 2017;139(37):13055–62.

    Article  CAS  PubMed  Google Scholar 

  26. Abbott J, Ye T, Ham D, Park H. Optimizing nanoelectrode arrays for scalable intracellular electrophysiology. Acc Chem Res. 2018;51(3):600–8.

    Article  CAS  PubMed  Google Scholar 

  27. Abbott J, Ye T, Qin L, Jorgolli M, Gertner RS, Ham D, Park H. CMOS nanoelectrode array for all-electrical intracellular electrophysiological imaging. Nat Nanotechnol. 2017;12(5):460–6.

    Article  CAS  PubMed  Google Scholar 

  28. Kim J, Renault C, Nioradze N, Arroyo-Currás N, Leonard KC, Bard AJ. Nanometer scale scanning electrochemical microscopy instrumentation. Anal Chem. 2016;88(20):10284–9.

    Article  CAS  PubMed  Google Scholar 

  29. Liu Y-Z, Li M-N, Zhang F, Zhu A-W, and Shi G-Y. Development of Au disk nanoelectrode down to 3 nm in radius for detection of dopamine release from a single cell. Anal Chem. 2015;87(11:5531–8.

    Article  CAS  Google Scholar 

  30. Ying YL, Hu YX, Gao R, Yu RJ, Gu Z, Lee LP, Long YT. Asymmetric nanopore electrode-based amplification for electron transfer imaging in live cells. J Am Chem Soc. 2018;140(16):5385–92.

    Article  CAS  PubMed  Google Scholar 

  31. Fessenden M. Metabolomics: small molecules, single cells. Nature. 2016;540(7631):153–5.

    Article  CAS  PubMed  Google Scholar 

  32. Takahashi Y, Miyamoto T, Shiku H, Asano R, Yasukawa T, Kumagai I, Matsue T. Electrochemical detection of epidermal growth factor receptors on a single living cell surface by scanning electrochemical microscopy. Anal Chem. 2009;81(7):2785–90.

    Article  CAS  PubMed  Google Scholar 

  33. Wang K, Zhou L, Li J, Liu W, Wei Y, Guo Z, Fan C, Hu J, Li B, Wang L. Label-free and three-dimensional visualization reveals the dynamics of plasma membrane-derived extracellular vesicles. Nano Lett. 2020;20(9):6313–9.

    Article  CAS  PubMed  Google Scholar 

  34. Sanchez-Alonso JL, Loucks A, Schobesberger S, van Cromvoirt AM, Poulet C, Chowdhury RA, Trayanova N, Gorelik J. Nanoscale regulation of L-type calcium channels differentiates between ischemic and dilated cardiomyopathies. eBio Med. 2020;57:e102845.

    Google Scholar 

  35. Shiwarski DJ, Tashman JW, Tsamis A, Bliley JM, Blundon MA, Aranda-Michel E, Jallerat Q, Szymanski JM, McCartney BM, Feinberg AW. Fibronectin-based nanomechanical biosensors to map 3D surface strains in live cells and tissue. Nat Commun. 2020;11(1):5883.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Miragoli M, Moshkov A, Novak P, Shevchuk A, Nikolaev VO, El-Hamamsy I, Potter CM, Wright P, Kadir SH, Lyon AR, Mitchell JA, Chester AH, Klenerman D, Lab MJ, Korchev YE, Harding SE, Gorelik J. Scanning ion conductance microscopy: a convergent high-resolution technology for multi-parametric analysis of living cardiovascular cells. J R Soc Interface. 2011;8(60):913–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Johnson N, Li C, Ostanin V, Bruckbauer A, Korchev Y, Klenerman D. Improved scanning ion conductance microscopy (SICM) for live cell imaging. Biophys J. 2007;323a–323a.

  38. Zhu C, Huang K, Siepser NP, Baker LA. Scanning ion conductance microscopy. Chem Rev. 2021;121(19):11726–68.

    Article  CAS  PubMed  Google Scholar 

  39. Gorelik J, Yang LQ, Zhang Y, Lab M, Korchev Y, Harding SE. A novel Z-groove index characterizing myocardial surface structure. Cardiovasc Res. 2006;72(3):422–9.

    Article  CAS  PubMed  Google Scholar 

  40. Park SH, Kim A, An J, Cho HS, Kang TM. Nanoscale imaging of rat atrial myocytes by scanning ion conductance microscopy reveals heterogeneity of T-tubule openings and ultrastructure of the cell membrane. Korean J Physiol Pharmacol. 2020;24(6):529–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Page A, Perry D, Unwin PR. Multifunctional scanning ion conductance microscopy. Proc R Soc A. 2017;473(2200):20160889.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Chen CC, Zhou Y, Baker LA. Scanning ion conductance microscopy. Annu Rev Anal Chem. 2012;5(1):207–28.

    Article  CAS  Google Scholar 

  43. Wong SuS, Chieng A, Parres-Gold J, Chang M, Wang Y. Real-time determination of aggregated alpha-synuclein induced membrane disruption at neuroblastoma cells using scanning ion conductance microscopy. Faraday Discuss. 2018;210:131–43.

    Article  Google Scholar 

  44. Parres-Gold J, Chieng A, Wong SuS, Wang Y. Real-time characterization of cell membrane disruption by alpha-synuclein oligomers in live SH-SY5Y neuroblastoma cells. ACS Chem Neurosci. 2020;11(17):2528–34.

    Article  CAS  PubMed  Google Scholar 

  45. Wu L, Liu T, Gu Y. Microvillar dynamic in renal tubular epithelial cells mediated by insulin/PLCgamma signal pathway. Biochem Biophys Res Commun. 2021;534:1020–5.

    Article  CAS  PubMed  Google Scholar 

  46. Schultz F, Swiatlowska P, Alvarez-Laviada A, Sanchez-Alonso JL, Song Q, de Vries AAF, Pijnappels DA, Ongstad E, Braga VMM, Entcheva E, Gourdie RG, Miragoli M, Gorelik J. Cardiomyocyte-myofibroblast contact dynamism is modulated by connexin-43. FASEB J. 2019;33(9):10453–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Seifert J, Rheinlaender J, Lang F, Gawaz M, Schaffer TE. Thrombin-induced cytoskeleton dynamics in spread human platelets observed with fast scanning ion conductance microscopy. Sci Rep. 2017;7(1):4810.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Takahashi Y, Shevchuk AI, Novak P, Babakinejad B, Macpherson J, Unwin PR, Shiku H, Gorelik J, Klenerman D, Korchev YE, Matsue T. Topographical and electrochemical nanoscale imaging of living cells using voltage-switching mode scanning electrochemical microscopy. Proc Natl Acad Sci USA. 2012;109(29):11540–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Page A, Kang M, Armitstead A, Perry D, Unwin PR. Quantitative visualization of molecular delivery and uptake at living cells with self-referencing scanning ion conductance microscopy-scanning electrochemical microscopy. Anal Chem. 2017;89(5):3021–8.

    Article  CAS  PubMed  Google Scholar 

  50. Takahashi Y, Shevchuk AI, Novak P, Zhang Y, Ebejer N, Macpherson JV, Unwin PR, Pollard AJ, Roy D, Clifford CA, Shiku H, Matsue T, Klenerman D, Korchev YE. Multifunctional nanoprobes for nanoscale chemical imaging and localized chemical delivery at surfaces and interfaces. Angew Chem Int Ed. 2011;50(41):9638–42.

    Article  CAS  Google Scholar 

  51. Wnf A, Jin HB, Syl A, Dan YA, Hnl A, Gcy A, Qiang FC, Yps A. Detection of secretion of exosomes from individual cell in real-time by multifunctional nanoelectrode-nanopore nanopipettes. Chin J Anal Chem. 2020;48(6):e20061–8.

    Article  Google Scholar 

  52. Yang XK, Zhang FL, Wu WT, Tang Y, Yan J, Liu YL, Amatore C, Huang WH. Quantitative nano-amperometric measurement of intravesicular glutamate content and its sub-quantal release by living neurons. Angew Chem Int Ed. 2021;60(29):15803–8.

    Article  CAS  Google Scholar 

  53. Li YT, Zhang SH, Wang L, Xiao RR, Liu W, Zhang XW, Zhou Z, Amatore C, Huang WH. Nanoelectrode for amperometric monitoring of individual vesicular exocytosis inside single synapses. Angew Chem Int Ed. 2014;53(46):12456–60.

    CAS  Google Scholar 

  54. Li YT, Zhang SH, Wang XY, Zhang XW, Oleinick AI, Svir I, Amatore C, Huang WH. Real-time monitoring of discrete synaptic release events and excitatory potentials within self-reconstructed neuromuscular junctions. Angew Chem Int Ed. 2015;54(32):9313–8.

    Article  CAS  Google Scholar 

  55. Shen M, Qu Z, DesLaurier J, Welle TM, Sweedler JV, Chen R. Single synaptic observation of cholinergic neurotransmission on living neurons: concentration and dynamics. J Am Chem Soc. 2018;140(25):7764–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Marinesco S. Micro- and nano-electrodes for neurotransmitter monitoring. Curr Opin Electrochem. 2021;29:100746.

    Article  CAS  Google Scholar 

  57. Tang Y, Yang XK, Zhang XW, Wu WT, Zhang FL, Jiang H, Liu YL, Amatore C, Huang WH. Harpagide, a natural product, promotes synaptic vesicle release as measured by nanoelectrode amperometry. Chem Sci. 2020;11(3):778–85.

    Article  CAS  Google Scholar 

  58. Zhang X, Hatamie A, Ewing AG. Nanoelectrochemical analysis inside a single living cell. Curr Opin Electrochem. 2020;22:94–101.

    Article  CAS  Google Scholar 

  59. Yu RJ, Ying YL, Gao R, Long YT. Confined nanopipette sensing: from single molecules, single nanoparticles, to single cells. Angew Chem Int Ed. 2019;58(1):3706–14.

    Article  CAS  Google Scholar 

  60. Kwon N, Kim D, Swamy KMK, Yoon J. Metal-coordinated fluorescent and luminescent probes for reactive oxygen species (ROS) and reactive nitrogen species (RNS). Coord Chem Rev. 2021;427: 213581.

    Article  CAS  Google Scholar 

  61. Yang B, Chen Y, Shi J. Reactive oxygen species (ROS)-based nanomedicine. Chem Rev. 2019;119(8):4881–985.

    Article  CAS  PubMed  Google Scholar 

  62. Sies H, Jones DP. Reactive oxygen species (ROS) as pleiotropic physiological signalling agents. Nat Rev Mol Cell Biol. 2020;21(7):363–83.

    Article  CAS  PubMed  Google Scholar 

  63. Chen X, Wang F, Hyun JY, Wei T, Qiang J, Ren X, Shin I, Yoon J. Recent progress in the development of fluorescent, luminescent and colorimetric probes for detection of reactive oxygen and nitrogen species. Chem Soc Rev. 2016;45(10):2976–3016.

    Article  CAS  PubMed  Google Scholar 

  64. Wang Y, Noël JM, Velmurugan J, Nogala W, Mirkin MV, Lu C, Guille Collignon M, Lemaître F, Amatore C. Nanoelectrodes for determination of reactive oxygen and nitrogen species inside murine macrophages. Proc Natl Acad Sci USA. 2012;109(29):11534.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Pan R, Hu K, Jia R, Rotenberg SA, Jiang D, Mirkin MV. Resistive-pulse sensing inside single living cells. J Am Chem Soc. 2020;142(12):5778–84.

    Article  CAS  PubMed  Google Scholar 

  66. Wu WT, Jiang H, Qi YT, Fan WT, Yan J, Liu YL, Huang WH. Large-scale synthesis of functionalized nanowires to construct nanoelectrodes for intracellular sensing. Angew Chem Int Ed. 2021;60(35):19337–43.

    Article  CAS  Google Scholar 

  67. Jiang H, Zhang XW, Liao QL, Wu WT, Liu YL, Huang WH. Electrochemical monitoring of paclitaxel-induced ROS release from mitochondria inside single cells. Small. 2019;15(48):1901787.

    Article  CAS  Google Scholar 

  68. Wang Y, Feng H, Zhang H, Chen Y, Huang W, Zhang J, Jiang X, Wang M, Jiang H, Wang X. Nanoelectrochemical biosensors for monitoring ROS in cancer cells. Analyst. 2020;145(4):1294–301.

    Article  CAS  PubMed  Google Scholar 

  69. Wang Y, Jin R, Sojic N, Jiang D, Chen HY. Intracellular wireless analysis of single cells by bipolar electrochemiluminescence confined in a nanopipette. Angew Chem Int Ed. 2020;59(26):10416–20.

    Article  CAS  Google Scholar 

  70. Wang N, Wang D, Pan R, Wang D, Jiang D, Chen H-Y. Self-referenced nanopipette for electrochemical analysis of hydrogen peroxide in the nucleus of a single living cell. Anal Chem. 2021;93(31):10744–9.

    Article  CAS  PubMed  Google Scholar 

  71. Crunkhorn S. Disrupting energy metabolism. Nat Rev Drug Discov. 2018;17(10):708–708.

    PubMed  Google Scholar 

  72. Luengo A, Li Z, Gui DY, Sullivan LB, Zagorulya M, Do BT, Ferreira R, Naamati A, Ali A, Lewis CA, Thomas CJ, Spranger S, Matheson NJ, Vander Heiden MG. Increased demand for NAD+ relative to ATP drives aerobic glycolysis. Mol Cell. 2021;81(4):691–707.

    Article  CAS  PubMed  Google Scholar 

  73. Fei J, Wu K, Wang F, Hu S. Glucose nanosensors based on redox polymer/glucose oxidase modified carbon fiber nanoelectrodes. Talanta. 2005;65(4):918–24.

    Article  CAS  PubMed  Google Scholar 

  74. Nascimento RAS, Özel RE, Mak WH, Mulato M, Singaram B, Pourmand N. Single cell “glucose nanosensor” verifies elevated glucose levels in individual cancer cells. Nano Lett. 2016;16(2):1194–200.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  75. Liao QL, Jiang H, Zhang XW, Qiu QF, Tang Y, Yang XK, Liu YL, Huang WH. A single nanowire sensor for intracellular glucose detection. Nanoscale. 2019;11(22):10702–8.

    Article  CAS  PubMed  Google Scholar 

  76. Pan R, Xu M, Burgess JD, Jiang D, Chen HY. Direct electrochemical observation of glucosidase activity in isolated single lysosomes from a living cell. Proc Natl Acad Sci USA. 2018;115(16):4087–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Kueng A, Kranz C, Mizaikoff B. Imaging of ATP membrane transport with dual micro-disk electrodes and scanning electrochemical microscopy. Biosens Bioelectron. 2005;21(2):346–53.

    Article  CAS  PubMed  Google Scholar 

  78. Ruan YF, Wang HY, Shi XM, Xu YT, Yu XD, Zhao WW, Chen HY, Xu JJ. Target-triggered assembly in a nanopipette for electrochemical single-cell analysis. Anal Chem. 2021;93(2):1200–8.

    Article  CAS  PubMed  Google Scholar 

  79. Maynard AG, Kanarek N. NADH ties one-carbon metabolism to cellular respiration. Cell Metab. 2020;31(4):660–2.

    Article  CAS  PubMed  Google Scholar 

  80. Singh P, Pandey SK, Singh J, Srivastava S, Sachan S, Singh SK. Biomedical perspective of electrochemical nanobiosensor. Nano Micro Lett. 2016;8(3):193–203.

    Article  CAS  Google Scholar 

  81. Jiang H, Qi YT, Wu WT, Wen MY, Liu YL, Huang WH. Intracellular monitoring of NADH release from mitochondria using a single functionalized nanowire electrode. Chem Sci. 2020;11(33):8771–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Liu Y, Du J, Wang M, Zhang J, Liu C, Li X. Recent progress in quantitatively monitoring vesicular neurotransmitter release and storage with micro/nanoelectrodes. Front Chem. 2021;8:2296–646.

    Google Scholar 

  83. Li BR, Hsieh YJ, Chen YX, Chung YT, Pan CY, Chen YT. An Ultrasensitive nanowire-transistor biosensor for detecting dopamine release from living PC12 Cells under hypoxic stimulation. J Am Chem Soc. 2013;135(43):16034–7.

    Article  CAS  PubMed  Google Scholar 

  84. Aref M, Ranjbari E, Romiani A, Ewing AG. Intracellular injection of phospholipids directly alters exocytosis and the fraction of chemical release in chromaffin cells as measured by nano-electrochemistry. Chem Sci. 2020;11(43):11869–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Gu C, Ewing AG. Simultaneous detection of vesicular content and exocytotic release with two electrodes in and at a single cell. Chem Sci. 2021;12(21):7393–400.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Yue Q, Li X, Wu F, Ji W, Zhang Y, Yu P, Zhang M, Ma W, Wang M, Mao L. Unveiling the role of DJ-1 protein in vesicular storage and release of catecholamine with nano/micro-tip electrodes. Angew Chem Int Ed. 2020;59(27):11061–5.

    Article  CAS  Google Scholar 

  87. Shekarabi M, Zhang J, Khanna AR, Ellison DH, Delpire E, Kahle KT. WNK kinase signaling in ion homeostasis and human disease. Cell Metab. 2017;25(2):285–99.

    Article  CAS  PubMed  Google Scholar 

  88. Clausmeyer J, Schuhmann W. Nanoelectrodes: applications in electrocatalysis, single-cell analysis and high-resolution electrochemical imaging. TrAC Trends Anal Chem. 2016;79:46–59.

    Article  CAS  Google Scholar 

  89. Özel RE, Lohith A, Mak WH, Pourmand N. Single-cell intracellular nano-pH probes. Rsc Adv. 2015;5:52436–43.

    Article  PubMed  CAS  Google Scholar 

  90. Xu H, Yang D, Jiang D, Chen HY. Phosphate assay kit in one cell for electrochemical detection of intracellular phosphate ions at single cells. Front Chem. 2019;7(360):2296–646.

    Google Scholar 

  91. Ferapontova EE. DNA electrochemistry and electrochemical sensors for nucleic acids. Annu Rev Anal Chem. 2018;11(1):197–218.

    Article  CAS  Google Scholar 

  92. Wu Y, Arroyo-Currás N. Advances in nucleic acid architectures for electrochemical sensing. Curr Opin Electrochem. 2021;27: 100695.

    Article  CAS  Google Scholar 

  93. Liu N, Jiang Y, Zhou Y, Xia F, Guo W, Jiang L. Two-way nanopore sensing of sequence-specific oligonucleotides and small-molecule targets in complex matrices using integrated DNA supersandwich structures. Angew Chem Int Ed. 2013;52(7):2007–11.

    Article  CAS  Google Scholar 

  94. Zhang S, Sun T, Wang E, Wang J. Investigation of self-assembled protein dimers through an artificial ion channel for DNA sensing. Chin Sci Bull. 2014;59(35):4946–52.

    Article  CAS  Google Scholar 

  95. Wang HY, Ruan YF, Zhu LB, Shi XM, Zhao WW, Chen HY, Xu JJ. An integrated electrochemical nanodevice for intracellular RNA collection and detection in single living cell. Angew Chem Int Ed. 2020;60(24):13244–50.

    Article  CAS  Google Scholar 

  96. Zhang S, Cheng J, Shi W, Li KB, Han DM, Xu JJ. Fabrication of a biomimetic nanochannel logic platform and its applications in the intelligent detection of miRNA related to liver cancer. Anal Chem. 2020;92(8):5952–9.

    Article  CAS  PubMed  Google Scholar 

  97. Xiao PP, Wan QQ, Liao T, Tu JY, Zhang GJ, Sun ZY. Peptide nucleic acid-functionalized nanochannel biosensor for the highly sensitive detection of tumor exosomal microRNA. Anal Chem. 2021;93(31):10966–73.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

This work was financially supported from the National Natural Science Foundation of China (22174106), the Natural Science Foundation of Shannxi Province, China (2020JC-06) and the Fundamental Research Funds for the Central Universities (PY3A081, xjh012019044).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Fei Li.

Ethics declarations

Conflict of interest

The authors declare no competing financial interest.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Liu, YL., Zhao, YX., Li, YB. et al. Recent Advances of Nanoelectrodes for Single-Cell Electroanalysis: From Extracellular, Intercellular to Intracellular. J. Anal. Test. 6, 178–192 (2022). https://doi.org/10.1007/s41664-022-00223-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s41664-022-00223-1

Keywords

Navigation