Skip to main content
Log in

Interdigitated impedance sensors for analysis of biological cells in microfluidic biochips

Mikrofluidische Lab-on-a-Chip-Systeme zur Analyse biologischer Zellen mittels integrierter planarer Impedanzsensoren

  • Originalarbeit
  • Published:
e & i Elektrotechnik und Informationstechnik Aims and scope Submit manuscript

Zusammenfassung

Ein neuartiges miniaturisiertes Analysesystem zur quantitativen Zellanalyse, auf Basis dielektrischer Mikrosensoren und Mikrofluidik, wird in dieser Arbeit vorgestellt. Das realisierte Lab-on-a-Chip beinhaltet in Kammern eingebettete, passivierte interdigitale Elektrodensysteme. Die Einführung einer Multilagen-Passivierung ermöglicht, im Gegensatz zu herkömmlichen Bioimpedanz-Systemen, die Isolation und somit die räumliche Trennung der dielektrischen Mikrosensoren von der Flüssigkeitsumgebung in den Analysekammern. Anhand von unterschiedlichen, in vitro cultivated cells. The overall performance of the system is demonstrated on various bacterial and yeast strains. Due to the high sensitivity of the contact-less dielectric microsensors it is possible to directly identify microbial strains, based on morphological differences and biological composition in the absence of any indicators or labels. Additionally, dielectric changes occurring in sub-cellular structures such as membranes can be directly monitored over a wide frequency range. As a result, microfluidic biochips are developed to continuously monitor cell morphology changes in a non-invasive manner over long periods of time.

Summary

In the presented work we describe the novel combination of contact-less dielectric microsensors and microfluidics for quantitative cell analysis. The lab-on-a-chip system consists of microfluidic channels and chambers together with integrated and passivated interdigitated electrode structures. In contrast to existing bioimpedance methods implemented for cell analysis, the dielectric microsensors are completely insulated and physically removed from the liquid sensing environment using defined multi-passivation layer of distinct size and composition. Consequently, these structures act as contact-less microsensors for the characterization of in vitro kultivierten, Bakterien und Hefezellen wird das Lab-on-a-Chip charakterisiert. Es zeigt sich, dass mikrobiologische Substanzen aufgrund morphologischer Unterschiede bzw. ihrer biologischen Zusammensetzung ohne Verwendung von Markern oder Indikatoren identifiziert werden können. Dielektrische Variationen in subzellularen Strukturen, wie beispielsweise der Membranen, sind über einen weiten Messfrequenzbereich beobachtbar. Der präsentierte mikrofluidische Biochip wurde speziell für die kontinuierliche und nicht-invasive Beobachtung der Zellmorphologie über lange Zeiträume entwickelt.

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.

Institutional subscriptions

References

  • Arndt, S., Seebach, J., Psathaki, K., Galla, H. J., Wegener, J. (2004): Bioelectrical impedance assay to monitor changes in cell shape during apoptosis. Biosens. Bioelectron., 19 (6): 583–594

    Article  Google Scholar 

  • Asami, K. (2002): Characterization of biological cells by dielectric spectroscopy. J. Non-Crystal. Solids., 305 (1–3): 268–277

    Article  Google Scholar 

  • Auroux, P. A., Iossifidis, D., Reyes, D. R., Manz, A. (2002): Micro total analysis systems. 2. Analytical standard operations and applications. Anal. Chem., 74 (12): 2637–2652

    Article  Google Scholar 

  • Bard, A. J., Faulkner, L. R. (2001): Electrochemical methods. 2 ed. New York: John Wiley & Sons

    Google Scholar 

  • Breslauer, D. N., Lee, P. J., Lee, L. P. (2006): Microfluidics-based systems biology. Molecul. Biosys., 2 (2): 97–112

    Article  Google Scholar 

  • Ciambrone, G. J., Liu, V. F., Lin, D. C., McGuinness, R. P., Leung, G. K., Pitchford, S. (2004): Cellular dielectric spectroscopy: a powerful new approach to label-free cellular analysis. J. Biomolecul. Screen., 9 (6): 467–480

    Article  Google Scholar 

  • Coates, A. R. M. (2003): Dormancy and low-growth states in microbial disease. Cambridge University Press, Cambridge

    Google Scholar 

  • Ehret, R., Baumann, W., Brischwein, M., Schwinde, A., Wolf, B. (1998): On-line control of cellular adhesion with impedance measurements using interdigitated electrode structures. Med. Biol. Eng. Comput., 36 (3): 365–370

    Article  Google Scholar 

  • Gerwen, P. V., Laureyn, W., Laureys, W., Huyberechts, G. M., De Beeck, O., Baert, K., Suls, J., Sansen, W., Jacobs, P., Hermans, L., Mertens, R. (1998): Nanoscaled interdigitated electrode arrays for biochemical sensors. Sens. Act. B, 49: 73

    Article  Google Scholar 

  • Giaever, I., Keese, C. R. (1984): Monitoring fibroblast behavior in tissue culture with an applied electric field. Proc. Nat. Acad. Sci. USA, 81: 3761–3764

    Article  Google Scholar 

  • Gomez, R., Bashir, R., Bhunia, A. K. (2002): Microscale electronic detection of bacterial metabolism. Sens. Act. B-Chem., 86 (2–3): 198–208

    Article  Google Scholar 

  • Harrison, D. J., Manz, A., Fan, Z. H., Ludi, H., Widmer, H. M. (1992): Capillary electrophoresis and sample injection systems integrated on a planar Glass Chip. Anal. Chem., 64 (17): 1926–1932

    Article  Google Scholar 

  • Igreja, R., Dias, C. J. (2004): Analytical evaluation of the interdigital electrodes capacitance for a multi-layered structure. Sens. Act. A-Physical, 112 (2–3): 291–301

    Article  Google Scholar 

  • Ionescu-Zanetti, C., Shaw, R. M., Seo, J. G., Jan, Y. N., Jan, L. Y., Lee, L. P. (2005): Mammalian electrophysiology on a microfluidic platform. Proc. Nat. Acad. Sci. USA, 102 (26): 9112–9117

    Article  Google Scholar 

  • Mamishev, A. V., Sundara-Rajan, K., Yang, F., Du, Y. Q., Zahn, M. (2004): Interdigital sensors and transducers. Proc. IEEE., 92 (5): 808–845

    Article  Google Scholar 

  • Markx, G. H., Davey, C. L. (1999): The dielectric properties of biological cells at radiofrequencies: applications in biotechnology, Enzy. Microbiol. Technol., 25 (3–5): 161–171

    Article  Google Scholar 

  • Polevaya, Y., Ermolina, I., Schlesinger, M., Ginzburg, B. Z., Feldman, Y. (1999): Time domain dielectric spectroscopy study of human cells-II. Normal and malignant white blood cells. Biochimica Et Biophysica Acta-Biomembranes, 1419 (2): 257–271

    Article  Google Scholar 

  • Prodan, C., Mayo, F., Claycomb, J. R., Miller, J. H., Benedik, M. J. (2004): Low-frequency, low-field dielectric spectroscopy of living cell suspensions, J. Appl. Phys., 95 (7): 3754–3756

    Article  Google Scholar 

  • Richter, L., Stepper, C., Mak, A., Reinthaler, A., Heer, R., Kast, M., Brueckl, H., Ertl, P. (2007): Development of a microfluidic biochip for online monitoring of fungal biofilm dynamics. Lab Chip, 7: 1723–1731

    Article  Google Scholar 

  • Storz, G., Hengge-Aronis, R. (2000): Bacterial Stress Responses. Washington D.C.: ASM Press

    Google Scholar 

  • Suehiro, J., Hamada, R., Noutomi, D., Shutou, M., Hara, M. (2003): Selective detection of viable bacteria using dielectrophoretic impedance measurement method. J. Electrostat., 57 (2): 157–168

    Article  Google Scholar 

  • Takashima, S. (1989): Electrical properties of biopolymers and membranes. Bristol: Adam Hilger

    Google Scholar 

  • Vilkner, T., Janasek, D., Manz, A. (2004): Micro total analysis systems. Recent developments. Anal. Chem., 76 (12): 3373–3385

    Google Scholar 

  • Whitesides, G. M. (2003): The 'right' size in nanobiotechnology. Nat. Biotechn., 21 (10): 1161–1165

    Article  Google Scholar 

  • Yardley, Y. E., Kell, D. B., Barrett, J., Davey, C. L. (2000): On-line, real-time measurements of cellular biomass using dielectric spectroscopy. In: Biotechnology and Genetic Engineering Reviews, Vol. 17. Andover: Intercept Ltd Scientific, Technical & Medical Publishers: pp. 3–35

    Google Scholar 

  • Yeon, J. H., Park, J. K. (2005): Cytotoxicity test based on electrochemical impedance measurement of HepG2 cultured in microfabricated cell chip. Anal. Biochem., 341 (2): 308–315

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ertl, P., Heer, R. Interdigitated impedance sensors for analysis of biological cells in microfluidic biochips. Elektrotech. Inftech. 126, 47–50 (2009). https://doi.org/10.1007/s00502-009-0607-7

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00502-009-0607-7

Schlüsselwörter

Keywords

Navigation