Skip to main content

Multiplexing neurochemical detection with carbon fiber multielectrode arrays using fast-scan cyclic voltammetry

Analytical and Bioanalytical Chemistry volume 413, pages 6715–6726 (2021)Cite this article

Abstract

Carbon fiber microelectrodes (CFMEs) have been extensively used to measure neurotransmitters with fast-scan cyclic voltammetry (FSCV) due to their ability to adsorb cationic monoamine neurotransmitters. Although FSCV, in tandem with CFMEs, provides high temporal and spatial resolution, only single-channel potentiostats and electrodes have been primarily utilized. More recently, the need and use of carbon fiber multielectrode arrays has risen to target multiple brain regions. Previous studies have shown the ability to detect dopamine using multielectrode arrays; however, they are not readily available to the scientific community. In this work, we interfaced a carbon fiber multielectrode array (MEA or multielectrode array), to a commercially available four-channel potentiostat for multiplexing neurochemical measurements. The MEA’s relative performance was compared to single CFMEs where dopamine detection was found to be adsorption controlled to the electrode’s surface. Multiple waveforms were applied to each fiber of the multielectrode array simultaneously to detect different analytes on each electrode of the array. A proof of concept ex vivo experiment showed that the multielectrode array could record redox activity in different areas within the mouse caudate putamen and detect dopamine in a 3-mm2 area. To our knowledge, this is the first use of the multielectrode array paired with a commercially available multichannel potentiostat for multi-waveform application and neurotransmitter co-detection. This novel array may aid in future studies to better understand complex brain heterogeneity, the dynamic neurochemical environment, and how disease states or drugs affect separate brain areas concurrently.

Graphical abstract

This is a preview of subscription content, access via your institution.

Access options

Buy single article

Instant access to the full article PDF.

USD 39.95

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Data availability

All materials noted in this manuscript include the name and company from where they were purchased to aid in replication.

References

  1. Armstrong-James M, Millar J. Carbon fibre microelectrodes. J Neurosci Methods. 1979;1(3):279–87.

    Article  CAS  PubMed  Google Scholar 

  2. Zestos AG. Carbon nanoelectrodes for the electrochemical detection of neurotransmitters [Internet]. Vol. 2018, International Journal of Electrochemistry. Hindawi; 2018 [cited 2021 Feb 9]. p. e3679627. Available from: https://www.hindawi.com/journals/ijelc/2018/3679627/

  3. Huffman ML, Venton JB. Carbon-fiber microelectrodes for in vivo applications. Analyst. 2009;134(1):18–24.

    Article  CAS  PubMed  Google Scholar 

  4. Rafi H, Zestos AG. Review—recent advances in FSCV detection of neurochemicals via waveform and carbon microelectrode modification. J Electrochem Soc. 2021 May;168(5):057520.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Howell JO, Wightman RM. Ultrafast voltammetry and voltammetry in highly resistive solutions with microvoltammetric electrodes. Anal Chem. 1984;56(3):524–9.

    Article  CAS  Google Scholar 

  6. Asrat TM, Cho W, Liu FA, Shapiro SM, Bracht JR, Zestos AG. Direct detection of DNA and RNA on carbon fiber microelectrodes using fast-scan cyclic voltammetry. ACS Omega. 2021;6(10):6571–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Calhoun SE, Meunier CJ, Lee CA, McCarty GS, Sombers LA. Characterization of a multiple-scan-rate voltammetric waveform for real-time detection of met-enkephalin. ACS Chem Neurosci. 2019;10(4):2022–32.

    Article  CAS  PubMed  Google Scholar 

  8. Mendoza A, Asrat T, Liu F, Wonnenberg P, Zestos AG. Carbon nanotube yarn microelectrodes promote high temporal measurements of serotonin using fast scan cyclic voltammetry. Sensors. 2020;20(4):1173.

    Article  CAS  PubMed Central  Google Scholar 

  9. Clark JJ, Sandberg SG, Wanat MJ, Gan JO, Horne EA, Hart AS, et al. Chronic microsensors for longitudinal, subsecond dopamine detection in behaving animals. Nat Methods. 2010;7(2):126–9.

    Article  CAS  PubMed  Google Scholar 

  10. Kuhr WG, Wightman RM. Real-time measurement of dopamine release in rat brain. Brain Res. 1986;381(1):168–71.

    Article  CAS  PubMed  Google Scholar 

  11. Berridge KC. The debate over dopamine’s role in reward: the case for incentive salience. Psychopharmacology. 2007;191(3):391–431.

    Article  CAS  PubMed  Google Scholar 

  12. González-Flores D, Belén V, Garrido M, Gonzalez-Gomez D, Lozano M, Ayuso M, et al. Ingestion of Japanese plums (Prunus salicina Lindl. cv. Crimson Globe) increases the urinary 6 sulfatoxymelatonin and total antioxidant capacity levels in young, middle-aged and elderly humans: nutritional and functional characterization of their content. J Food Nutr Res. 2011;50:229–36.

    Google Scholar 

  13. Young SN. How to increase serotonin in the human brain without drugs. J Psychiatry Neurosci. 2007;32(6):394–9.

    PubMed  PubMed Central  Google Scholar 

  14. Yeager JD, Phillips DJ, Rector DM, Bahr DF. Characterization of flexible ECoG electrode arrays for chronic recording in awake rats. J Neurosci Methods. 2008;173(2):279–85.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Zestos AG, Venton BJ. Communication—carbon nanotube fiber microelectrodes for high temporal measurements of dopamine. J Electrochem Soc. 2018;165(12):G3071–G3073.

  16. Raju D, Mendoza A, Wonnenberg P, Mohanaraj S, Sarbanes M, Truong C, Zestos AG. Polymer modified carbon fiber-microelectrodes and waveform modifications enhance neurotransmitter metabolite detection. Anal Methods. 2019;11(12):1620–1630.

  17. Wonnenberg PM, Cho W, Liu F, Asrat T, Zestos AG. Polymer modified carbon fiber microelectrodes for precision neurotransmitter metabolite measurements. J Electrochem Soc. 2020;167(16):167507.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Wonnenberg PM, Zestos AG. Polymer-modified carbon fiber microelectrodes for neurochemical detection of dopamine and metabolites. ECS Trans. 2020;97(7):901–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Cho W, Liu F, Hendrix A, McCray B, Asrat T, Connaughton V, et al. Timed electrodeposition of PEDOT:Nafion onto carbon fiber-microelectrodes enhances dopamine detection in zebrafish retina. J Electrochem Soc. 2020;167(11):115501.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Yang C, Jacobs CB, Nguyen MD, Ganesana M, Zestos AG, Ivanov IN, et al. Carbon nanotubes grown on metal microelectrodes for the detection of dopamine. Anal Chem. 2016;88(1):645–52.

    Article  CAS  PubMed  Google Scholar 

  21. Zestos AG, Yang C, Jacobs BC, Hensley D, Jill Venton B. Carbon nanospikes grown on metal wires as microelectrode sensors for dopamine. Analyst. 2015;140(21):7283–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Wei H, Li L, Jin J, Wu F, Yu P, Ma F, et al. Galvanic redox potentiometry based microelectrode array for synchronous ascorbate and single-unit recordings in rat brain. Anal Chem. 2020;92(14):10177–82.

    Article  CAS  PubMed  Google Scholar 

  23. Alba NA, Du ZJ, Catt KA, Kozai TDY, Cui XT. In vivo electrochemical analysis of a PEDOT/MWCNT neural electrode coating. Biosensors. 2015;5(4):618–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Schwerdt HN, Kim M, Amemori S, Homma D, Yoshida T, Shimazu H, et al. Subcellular probes for neurochemical recording from multiple brain sites. Lab Chip. 2017;17(6):1104–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Demuru S, Nela L, Marchack N, Holmes SJ, Farmer DB, Tulevski GS, et al. Scalable nanostructured carbon electrode arrays for enhanced dopamine detection. ACS Sens. 2018;3(4):799–805.

    Article  CAS  PubMed  Google Scholar 

  26. Schwerdt HN, Kim M, Karasan E, Amemori S, Homma D, Shimazu H, et al. Subcellular electrode arrays for multisite recording of dopamine in vivo. In: 2017 IEEE 30th International Conference on Micro Electro Mechanical Systems (MEMS). 2017. p. 549–52.

  27. Patel PR, Popov P, Caldwell CM, Welle EJ, Egert D, Pettibone JR, et al. High density carbon fiber arrays for chronic electrophysiology, fast scan cyclic voltammetry, and correlative anatomy. J Neural Eng. 2020;17(5):056029.

    Article  PubMed  Google Scholar 

  28. Schwerdt HN, Shimazu H, Amemori K, Amemori S, Tierney PL, Gibson DJ, et al. Long-term dopamine neurochemical monitoring in primates. Proc Natl Acad Sci. 2017;114(50):13260.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Schwerdt HN, Gibson DJ, Amemori K, Stanwicks LL, Yoshida T, Cima MJ, et al. Chronic multi-modal monitoring of neural activity in rodents and primates. In: Integrated sensors for biological and neural sensing [Internet]. International Society for Optics and Photonics; 2021 [cited 2021 Jun 11]. p. 1166308. Available from: https://www.spiedigitallibrary.org/conference-proceedings-of-spie/11663/1166308/Chronic-multi-modal-monitoring-of-neural-activity-in-rodents-and/10.1117/12.2583029.short

  30. Marsh MP, Koehne JE, Andrews RJ, Meyyappan M, Bennet KE, Lee KH. Carbon nanofiber multiplexed array and wireless instantaneous neurotransmitter concentration sensor for simultaneous detection of dissolved oxygen and dopamine. Biomed Eng Lett. 2012;2(4):271–7.

    Article  PubMed  Google Scholar 

  31. Zachek MK, Park J, Takmakov P, Mark Wightman R, McCarty SG. Microfabricated FSCV-compatible microelectrode array for real-time monitoring of heterogeneous dopamine release. Analyst. 2010;135(7):1556–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Richie JM, Patel PR, Welle EJ, Dong T, Chen L, Shih AJ, et al. Benchtop carbon fiber microelectrode array fabrication toolkit bioRxiv 2021 Mar 22;2021.03.22.436422.

  33. Spijker S. Dissection of rodent brain regions. In: Li KW, editor. Neuroproteomics [Internet]. Totowa, NJ: Humana Press; 2011 [cited 2021 Apr 6]. p. 13–26. (Neuromethods). Available from: https://doi.org/10.1007/978-1-61779-111-6_2.

  34. Lein ES, Hawrylycz MJ, Ao N, Ayres M, Bensinger A, Bernard A, et al. Genome-wide atlas of gene expression in the adult mouse brain. Nature. 2007;445(7124):168–76.

    Article  CAS  PubMed  Google Scholar 

  35. Paxinos G, Franklin KBJ. Paxinos and Franklin’s the mouse brain in stereotaxic coordinates. 4th ed. Amsterdam: Academic Press; 2012. 360 p

  36. Papouin T, Haydon PG. Obtaining acute brain slices. Bio-Protoc [Internet]. 2018 Jan 20 [cited 2020 Dec 23];8(2). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5856250/

  37. Butcher JT, Goodwill AG, Frisbee JC. The ex vivo isolated skeletal microvessel preparation for investigation of vascular reactivity. J Vis Exp JoVE [Internet]. 2012 Apr 28 [cited 2021 May 5];(62). Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3466634/

  38. Dorris DM, Hauser CA, Minnehan CE, Meitzen J. An aerator for brain slice experiments in individual cell culture plate wells. J Neurosci Methods. 2014;238:1–10.

    Article  PubMed  Google Scholar 

  39. Araujo CBL, Bendhack LM. High concentrations of KCl release noradrenaline from noradrenergic neurons in the rat anococcygeus muscle. Braz J Med Biol Res. 2003;36(1):97–104.

    Article  CAS  PubMed  Google Scholar 

  40. Venton BJ, Cao Q. Fundamentals of fast-scan cyclic voltammetry for dopamine detection. Analyst. 2020;145(4):1158–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Bard AJ, Faulkner LR. Electrochemical methods: fundamentals and applications. 2nd ed. New York: Wiley; 2000. 864 p

  42. Sanford AL, Morton SW, Whitehouse KL, Oara HM, Lugo-Morales LZ, Roberts JG, et al. Voltammetric detection of hydrogen peroxide at carbon fiber microelectrodes. Anal Chem. 2010;82(12):5205–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Giniatullin A, Petrov A, Giniatullin R. Action of hydrogen peroxide on synaptic transmission at the mouse neuromuscular junction. Neuroscience. 2019;399:135–45.

    Article  CAS  PubMed  Google Scholar 

  44. Jackson BP, Dietz SM, Wightman RM. Fast-scan cyclic voltammetry of 5-hydroxytryptamine. Anal Chem. 1995;67(6):1115–20.

    Article  CAS  PubMed  Google Scholar 

  45. Dunham KE, Venton BJ. Improving serotonin fast-scan cyclic voltammetry detection: new waveforms to reduce electrode fouling. Analyst. 2020;145(22):7437–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Cryan MT, Ross AE. Scalene waveform for codetection of guanosine and adenosine using fast-scan cyclic voltammetry. Anal Chem. 2019;91(9):5987–93.

    Article  CAS  PubMed  Google Scholar 

  47. Cryan MT, Ross AE. Subsecond detection of guanosine using fast-scan cyclic voltammetry. Analyst. 2018;144(1):249–57.

    Article  PubMed  Google Scholar 

  48. Takmakov P, Zachek MK, Keithley RB, Walsh PL, Donley C, McCarty GS, et al. Carbon microelectrodes with a renewable surface. Anal Chem. 2010;82(5):2020–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Dunham KE, Venton BJ. Improving serotonin fast-scan cyclic voltammetry detection: new waveforms to reduce electrode fouling. Analyst [Internet]. 2020 Sep 11 [cited 2020 Oct 8]; Available from: https://pubs.rsc.org/en/content/articlelanding/2020/an/d0an01406k

  50. Nguyen MD, Venton BJ. Fast-scan cyclic voltammetry for the characterization of rapid adenosine release. Comput Struct Biotechnol J. 2015;13:47–54.

    Article  CAS  PubMed  Google Scholar 

  51. Shon Y-M, Chang S-Y, Tye SJ, Kimble CJ, Bennet KE, Blaha CD, et al. Comonitoring of adenosine and dopamine using the wireless instantaneous neurotransmitter concentration system: proof of principle. J Neurosurg. 2010;112(3):539–48.

    Article  PubMed  PubMed Central  Google Scholar 

  52. Nicolai EN, Trevathan JK, Ross EK, Lujan JL, Blaha CD, Bennet KE, et al. Detection of norepinephrine in whole blood via fast scan cyclic voltammetry. IEEE Int Symp Med Meas Appl Proc IEEE Int Symp Med Meas Appl. 2017;2017:111–6.

    Google Scholar 

  53. Zhang Y, Liang Y, Randesi M, Yuferov V, Zhao C, Kreek MJ. Chronic oxycodone self-administration altered reward-related genes in the ventral and dorsal striatum of C57BL/6J mice: an RNA-seq analysis. Neuroscience. 2018;393:333–49.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors would like to acknowledge the NSF 1707316 grant along with Dr. Paras Patel and Julianna Richie from the Department of Biomedical Engineering at the University of Michigan for the technical assistance and with providing electrode materials.

Code availability

Not applicable.

Funding

The authors would like to acknowledge the following funding sources: American University Faculty Research Support Grant (AGZ), Faculty Mellon Grant, NASA DC Space Grant, NIH 1R41NS113702–01 (AGZ), SACP Pittcon Starter Grant, NSF I-Corps #1936173 (AGZ), NSF MRI # 1625977 (scanning electron microscopy), and American University Fall 2020 Graduate Student Research Grant (HR).

Author information

Authors and Affiliations

  1. Center for Neuroscience and Behavior, American University, Washington, DC, 20016, USA

    Harmain Rafi & Alexander G. Zestos

  2. Department of Neuroscience, American University, Washington, DC, 20016, USA

    Harmain Rafi

  3. Department of Chemistry, American University, Washington, DC, 20016, USA

    Alexander G. Zestos

Authors
  1. Harmain Rafi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alexander G. Zestos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Alexander G. Zestos.

Ethics declarations

Ethics approval

All ex vivo animal experiments were conducted in accordance with IACUC guidelines, protocol #20–04.

Consent to participate

Not applicable

Consent for publication

Consent from all authors was obtained prior to submission.

Conflict of interest

The authors declare no competing interests.

Additional information

Published in the topical collection Electrochemistry for Neurochemical Analysis with guest editors Ashley E. Ross and Alexander G. Zestos.

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

ESM 1

(PDF 1052 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Rafi, H., Zestos, A.G. Multiplexing neurochemical detection with carbon fiber multielectrode arrays using fast-scan cyclic voltammetry. Anal Bioanal Chem 413, 6715–6726 (2021). https://doi.org/10.1007/s00216-021-03526-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-021-03526-x

Keywords

  • FSCV
  • Neurotransmitters
  • Microelectrodes
  • Carbon fiber