Skip to main content
SpringerLink
Log in

Biological application of microelectrode arrays in drug discovery and basic research

  • Review
  • Published:
Analytical and Bioanalytical Chemistry Aims and scope Submit manuscript

Abstract

Electrical activity of electrogenic cells in neuronal and cardiac tissue can be recorded by means of microelectrode arrays (MEAs) that offer the unique possibility for non-invasive extracellular recording from as many as 60 sites simultaneously. Since its introduction 30 years ago, the technology and the related culture methods for electrophysiological cell and tissue assays have been continually improved and have found their way into many academic and industrial laboratories. Currently, this technology is attracting increased interest owing to the industrial need to screen selected compounds against ion channel targets in their native environment at organic, cellular, and sub-cellular level.

As the MEA technology can be applied to any electrogenic tissue (i.e., central and peripheral neurons, heart cells, and muscle cells), the MEA biosensor is an ideal in vitro system to monitor both acute and chronic effects of drugs and toxins and to perform functional studies under physiological or induced pathophysiological conditions that mimic in vivo damages. By recording the electrical response of various locations on a tissue, a spatial map of drug effects at different sites can be generated, providing important clues about a drug's specificity.

In this survey, examples of MEA biosensor applications are described that have been developed for drug screening and discovery and safety pharmacology in the field of cardiac and neural research. Additionally, biophysical basics of recording and concepts for analysis of extracellular electrical signals are presented.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1A,B.
Fig. 2A–D.
Fig. 3A–C.
Fig. 4A–D.
Fig. 5A–E.
Fig. 6A–C.
Fig. 7.
Fig. 8.
Fig. 9A,B.

Similar content being viewed by others

Abbreviations

AP:

action potential

DG:

dentate gyrus

EC:

entorhinal cortex

ECG:

electrocardiogram

ERG:

electroretinogram

LFP:

local field potentials

MEA:

microelectrode array

PSTH:

peri-stimulus–time histogram

SNR:

signal-to-noise ratio

References

  1. Lehmann-Horn F, Jurkat-Rott K (1999) Physiol Rev 79:1317–1372

    PubMed  Google Scholar 

  2. Owen D, Silverthorne A (2002) Drug Discovery World 3:48–61

    Google Scholar 

  3. Stett A, Burckhardt C, Weber U, van Stiphout P, Knott T (2003) Recept Channels 9:59–66

    CAS  PubMed  Google Scholar 

  4. Willumsen NJ, Bech M, Olesen S-P, Jensen BS, Korsgaard MPG, Christophersen P (2003) Recept Channels 9:3–12

    CAS  PubMed  Google Scholar 

  5. Thomas CA, Springer PA, Loeb GE, Berwald-Netter Y, Okun LM (1972) Exp Cell Res 74:61–66

    PubMed  Google Scholar 

  6. Potter SM (2001) Prog Brain Res 130:49–62

    CAS  PubMed  Google Scholar 

  7. http://www.brainworks.uni-freiburg.de/group/egert/egert_links.html. Cited 8 April 2003

  8. Bucher V, Schubert M, Kern D, Nisch W (2001) Microelectron Eng 57–58:705–712

    Google Scholar 

  9. Janders M, Egert U, Stelzle M, Nisch W (1996) Proc 18th Ann Int Conf IEEE Eng Med Biol Soc, p 364

  10. Bucher V, Graf M, Stelzle M, Nisch W (1999) Biosens Bioelectron 14:639–649

    Article  CAS  Google Scholar 

  11. Nisch W, Böck J, Haemmerle H, Mohr A (1994) Biosens Bioelectron 9:737–741

    Article  CAS  PubMed  Google Scholar 

  12. Haemmerle H, Egert U, Mohr A, Nisch W (1994) Biosens Bioelectron 9:691–696

    Article  CAS  PubMed  Google Scholar 

  13. Bucher V, Brunner B, Leibrock C, Schubert M, Nisch W (2001) Biosens Bioelectron 16:205–10

    Article  CAS  PubMed  Google Scholar 

  14. Egert U, Schlosshauer B, Fennrich S, Nisch W, Fejtl M, Knott T, Haemmerle H (1998) Brain Res Protoc 2:229–242

    CAS  Google Scholar 

  15. Hofmann F, Leibrock C, Volkmer H, Haemmerle H (2000) Restor Neurol Neurosci 16:54

    Google Scholar 

  16. Knott T (2001) Osnabrück. Der Andere Verlag

  17. Leibrock C, Hofmann F, Haemmerle H (2001) Soc Neurosci Abstr 982.2

  18. Stett A, Barth W, Weiss S, Haemmerle H, Zrenner E (2000) Vis Res 40:1785–1795

    Article  CAS  PubMed  Google Scholar 

  19. Hofmann F, Fejtl M, Egert U, Haemmerle H (1999) Proceedings of the 27th Göttingen neurobiology conference. Thieme, Stuttgart 2:537:

  20. Egert U, Haemmerle H (2002) In: Baselt JP, Gerlach G (eds) Sensoren im Fokus neuer Anwendungen. w.e.b. Universitätsverlag, Dresden, pp 51–54

  21. Egert U, Knott T, Schwarz C, Nawrot M, Brandt A, Rotter S, Diesmann M (2002) J Neurosci Methods 117:33–42

    Article  CAS  PubMed  Google Scholar 

  22. Halbach MD, Egert U, Hescheler J, Banach K (2002) Biophys J 82:457

    Google Scholar 

  23. Halbach MD, Egert U, Hescheler J, Banach K (2003) Cell Physiol Biochem

  24. Droge MH, Gross GW, Hightower MH, Czisny LE (1986) J Neurosci 6:1583–92

    CAS  PubMed  Google Scholar 

  25. Meister M, Pine J, Baylor DA (1994) J Neurosci Methods 51:95–106

    CAS  PubMed  Google Scholar 

  26. Gramowski A, Schiffmann D, Gross GW (2000) Neurotoxicology 21:331–42

    CAS  PubMed  Google Scholar 

  27. Gholmieh G, Soussou W, Courellis S, Marmarelis V, Berger T, Baudry M (2001) Biosens Bioelectron 16:491–501

    Article  CAS  PubMed  Google Scholar 

  28. Streit J, Tscherter A, Heuschkel MO, Renaud P (2001) Eur J Neurosci 14:191–202

    Article  CAS  PubMed  Google Scholar 

  29. Besl B, Fromherz P (2002) Eur J Neurosci 15:999–1005

    PubMed  Google Scholar 

  30. Shimono K, Baudry M, Panchenko V, Taketani M (2002) J Neurosci Methods 120:193–202

    Article  CAS  PubMed  Google Scholar 

  31. Banach K, Halbach M, Hu P, Hescheler J, Egert U (2003) Am J Physiol

  32. http://webvision.med.utah.edu/. Cited 8 April 2003

  33. Ronn LC, Olsen M, Ostergaard S, Kiselyov V, Berezin V, Mortensen MT, Lerche MH, Jensen PH, Soroka V, Saffell JL, Doherty P, Poulsen FM, Bock E, Holm A, Saffells JL (1999) Nat Biotechnol 17:1000–1005

    Article  CAS  PubMed  Google Scholar 

  34. Johnston D, Wu SM-S (1995) In: Foundations of cellular neurophysiology. MIT Press, Cambridge, Massachusetts, pp 423–440

  35. Egert U, Heck D, Aertsen A (2002) Exp Brain Res 142:268–274

    Article  PubMed  Google Scholar 

  36. Lind R, Connolly P, Wilkinson CDW, Thomson RD (1991) Sens Actuators B 3:23–30

    Article  Google Scholar 

  37. Fromherz P (2002) Eur Biophys J 31:228–231

    Article  PubMed  Google Scholar 

  38. Buitenweg JR, Rutten WLC, Marani E (2003) IEEE Trans Biomed Eng 50

  39. Buitenweg JR, Rutten WL, Marani E (2002) IEEE Trans Biomed Eng 49:1580–90

    Article  PubMed  Google Scholar 

  40. Fromherz P (2003) In: Waser R (ed) Nanoelectronics and information technology. Wiley-VCH, Berlin, pp 781–810

  41. Nicolelis MAL (1999) In: Nicolelis MAL (ed) Methods for neural ensemble recordings. CRC Press, Boca Raton

  42. Kleber AG, Fast VG, Kucera J, Rohr S (1996) Zeitschrift für Kardiologie 85:25–33

    Google Scholar 

  43. Banach K, Egert U, Juergen H (2001) Biophys J 80:2909

    Google Scholar 

  44. Banach K, Hescheler E, Egert U (2002) Biophys J 82:474

    PubMed  Google Scholar 

  45. Jost B, Aertsen A, Egert U (2002) FENS Abstr 1:A012.11

    Google Scholar 

  46. Gross GW, Harsch A, Rhoades BK, Göpel W (1997) Biosens Bioelectron 12:373–393

    CAS  PubMed  Google Scholar 

  47. Krupa DJ, Nicolelis MA (2000) Prog Brain Res 128:161–172

    CAS  PubMed  Google Scholar 

  48. Laubach M, Wessberg J, Nicolelis MA (2000) Nature 405:567–571

    Article  CAS  PubMed  Google Scholar 

  49. Aertsen AMHJ, Gerstein GL (1985) Brain Res 340:341–354

    Article  CAS  PubMed  Google Scholar 

  50. Gerstein G, Aertsen A, Bloom M, Espinosa E, Evanczuk S, Turner M (1985) In: Haken H (ed) Complex systems—operational approaches. Springer, Berlin Heidelberg New York, pp 58–70

  51. Abeles M, Gerstein GL (1988) J Neurophysiol 60:909–925

    CAS  PubMed  Google Scholar 

  52. Kirkland KL, Sillito AM, Jones HE, West DC, Gerstein GL (2000) J Neurophysiol 84:1863–1868

    CAS  PubMed  Google Scholar 

  53. Kisley MA, Gerstein GL (2001) Eur J Neurosci 13:1993–2003

    Article  CAS  PubMed  Google Scholar 

  54. Welsh JP, Schwarz C (1999) In: Nicolelis MAL (ed) Methods for neural ensemble recordings. CRC Press, Boca Raton, pp 79–100

  55. Nicolelis MA, Katz D, Krupa DJ (1998) Rev Neurosci 9:213–224

    Google Scholar 

  56. Gundlfinger A, Metzger F, Aertsen A, Egert U (2002) FENS Abstr 1:A104.5

    Google Scholar 

  57. Gerstein GL (2000) J Neurosci Methods 100:41–51

    Article  CAS  PubMed  Google Scholar 

  58. Eckhorn R (1986) J Neurosci 29:165–166

    Google Scholar 

  59. Eckhorn R, Stett A, Schanze T, Gekeler F, Schwahn H, Zrenner E, Wilms M, Eger M, Hesse L (2001) Ophthalmologe 98:369–375

    Article  CAS  PubMed  Google Scholar 

  60. Frien A, Eckhorn R (2000) Eur J Neurosci 12:1466–1478

    CAS  PubMed  Google Scholar 

  61. Roth SH, Bland BH, MacIver BM (1983) Prog Neuro-Psychoph 7:821–825

    Google Scholar 

  62. Deadwyler SA, West JR, Cotman CW, Lynch GS (1975) J Neurophysiol 38:167–184

    CAS  PubMed  Google Scholar 

  63. Abe H, Ogata N (1981) Jap J Pharmacol 31:661–675

    CAS  Google Scholar 

  64. Abraham WC, Manis PB, Hunter BE, Zornetzer SF, Walker DW (1982) Brain Res 237:91–105

    Article  CAS  PubMed  Google Scholar 

  65. Granger R, Whitson J, Larson J, Lynch G (1994) Proc Natl Acad Sci USA 91:10104–10108

    CAS  PubMed  Google Scholar 

  66. Avoli M, Psarropoulou C, Tancredi V, Fueta Y (1993) J Neurophysiol 70:1018–1029

    CAS  PubMed  Google Scholar 

  67. Kolta A, Ambros-Ingerson J, Lynch G (1996) Brain Res 737:133–145

    Article  CAS  PubMed  Google Scholar 

  68. Borroni A, Chen FM, LeCursi N, Grover LM, Teyler TJ (1991) J Neurosci Methods 36:177–184

    Article  CAS  PubMed  Google Scholar 

  69. Robert F, Correges P, Duport S, Stoppini L (1997) Curr Sep 16:3–10

    CAS  Google Scholar 

  70. Straub B, Meyer E, Fromherz P (2001) Nat Biotechnol 19:121–4

    Article  CAS  PubMed  Google Scholar 

  71. http://www.infineon.com/news/press/302_041e.htm. Cited 8 April 2003

Download references

Acknowledgement

We thank Doris Gasse, Alexander Gatto, Thoralf Herrmann, Cornelia Leibrock, and Andreas Schuker for diligent and valuable tissue culture work and data collecting. This work was supported by the BMBF (FKZ 0310964, 0310965, V2336/2433), and the Land Baden–Württemberg with grants to A. Aertsen and U. Egert.

Author information

Authors and Affiliations

  1. NMI Naturwissenschaftliches und Medizinisches Institut an der Universität Tübingen, Markwiesenstr. 55, 72770, Reutlingen, Germany

    Alfred Stett, Elke Guenther, Frank Hofmann, Wilfried Nisch & Hugo Haemmerle

  2. Neurobiology and Biophysics, Institute for Biology III, Albert-Ludwigs University Freiburg, Schänzlestrasse 1, 79104, Freiburg, Germany

    Ulrich Egert

  3. Multi Channel Systems MCS GmbH, Markwiesenstr. 55, 72770, Reutlingen, Germany

    Thomas Meyer

Authors
  1. Alfred Stett
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ulrich Egert
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Elke Guenther
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Frank Hofmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Thomas Meyer
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Wilfried Nisch
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Hugo Haemmerle
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hugo Haemmerle.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Stett, A., Egert, U., Guenther, E. et al. Biological application of microelectrode arrays in drug discovery and basic research. Anal Bioanal Chem 377, 486–495 (2003). https://doi.org/10.1007/s00216-003-2149-x

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00216-003-2149-x

Keywords

Search

Navigation