Abstract
Impedance spectroscopy (IS) is a powerful technique for analysis of the complex electrical impedance of a large variety of biological systems, because it is sensitive both to surface phenomena and to changes of bulk properties. A simple and convenient method of analysis of cell properties by IS is described. An interdigitated electrodes configuration was used for the measurements; human epithelial cells were grown on the device to investigate the complex dielectric response as a function of frequency, in order to test the suitability of the device for use as a label-free biosensor. To test the ability of the device to detect channels in the cell membrane, the effect of drugs known to affect membrane integrity was also investigated. The frequency response of the admittance (i.e. the reciprocal of the impedance) can be well fitted by a model based on very simple assumptions about the cells coating the device surface and the current flow; from the calculations, membrane-specific capacitance and information about cell adhesion can be inferred. These preliminary efforts have shown that our configuration could lead to a label-free non-invasive technique for biosensing and cellular behavior monitoring which might prove useful in investigation of the basic properties of cells and the effect of drugs by estimation of some fundamental properties and modification of the electrical characteristics of the device.
Similar content being viewed by others
References
Arndt S, Seebach J, Psathaki K, Galla HJ, Wegener J (2004) Biolectrical impedance assay to monitor changes in cell shape during apoptosis. Biosens Bioelectron 19:583–594
Asami K (2002) Characterization of heterogeneous systems by dielectric spectroscopy. Prog Polym Sci 27:1617–1659
Asami K (2006) Dielectric dispersion in biological cells of complex geometry simulated by the three-dimensional finite difference method. J Phys D Appl Phys 39:492–499
Asami K, Takahashi Y, Takashima S (1990) Frequency domain analysis of membrane capacitance of cultured cells (HeLa and myeloma) using the micropipette technique. Biophys J 58:143–148
Bot C, Prodan C (2009) Probing the membrane potential of living cells by dielectric spectroscopy. Eur Biophys J 38:1049–1059
Ceriotti L, Ponti J, Broggi F, Kob A, Drechsler S, Thedinga E, Colpo P, Sabbioni E, Ehret R, Rossi F (2007a) Real-time assessment of cytotoxicity by impedance measurement on a 96-well plate. Sens Actuators B 123:769–778
Ceriotti L, Ponti J, Colpo P, Sabbioni E, Rossi F (2007b) Assessment of cytotoxicity by impedance spectroscopy. Biosens Bioelectron 22:3057–3063
Cho S, Thielecke H (2008) Electrical characterization of human mesenchymal stem cell growth on microelectrode. Microelectron Eng 85:1272–1274
Cortina M, Esplandiu MJ, Alegret S, del Valle M (2006) Urea impedimetric biosensor based on polymer degradation onto interdigitated electrodes. Sens Actuators B 118:84–89
Dickert FL, Hayden O, Lieberzeit PA, Haderspoeck C, Bindeus R, Palfinger C, Wirl B (2003) Nano-and micro-structuring of sensor materials—from molecule to cell detection. Synth Met 138:65–69
Ehret R, Baumann W, Brischwein M, Schwinde A, Stegbauer K, Wolf B (1997) Monitoring of cellular behaviour by impedance measurements on interdigitated electrode structures. Biosens Bioelectron 12:29–41
Giaever I, Keese CR (1991) Micro motion of mammalian cells measured electrically. Proc Natl Acad Sci USA 88:7896–7900
Grosse C, Schwan HP (1992) Cellular membrane potentials induced by alternating fields. Biophys J 63:1632–1642
Hleli S, Martelet C, Abdelghani A, Burais N, Jaffrezic-Renault N (2006) Atrazine analysis using an impedimetric immunosensor based on mixed biotinylated self-assembled monolayer. Sens Actuators B 113:711–717
Kafka J, Pänke O, Abendroth B, Lisdat F (2008) A label-free DNA sensor based on impedance spectroscopy. Electrochim. Acta 53:7467–7474
Katz E, Willner I (2003) Probing biomolecular interactions at conductive and semiconductive surfaces by impedance spectroscopy: routes to impedimetric immunosensors, DNA-sensors, and enzyme biosensors. Electroanalysis 15:913–947
Lehmann M, Baumann W, Brischwein M, Ehret R, Kraus M, Schwinde A, Bitzenhofer M, Freund I, Wolf B (2000) Non-invasive measurement of cell membrane associated proton gradients by ion-sensitive field effect transistor arrays for micro physiological and bioelectronical applications. Biosens Bioelectron 15:117–124
Lehmann M, Baumann W, Brischwein M, Gahle HJ, Freund I, Ehret R, Drechsler S, Palzer H, Kleintges M, Sieben U, Wolf B (2001) Simultaneous measurement of cellular respiration and acidification with a single CMOS ISFET. Biosens Bioelectron 16:195–203
Lisdat F, Schäfer D (2008) The use of electrochemical impedance spectroscopy for biosensing. Anal Bioanal Chem 391:1555–1567
Maalouf R, Fournier-Wirth C, Coste J, Chebib H, Saikali Y, Vittori O, Errachid A, Cloarec JP, Martelet C, Jaffrezic-Renault N (2007) Label-free detection of bacteria by electrochemical impedance spectroscopy: comparison to surface plasmon resonance. Anal Chem 79:4879–4886
Malleo D, Nevill JT, Lee LP, Morgan H (2009) Continous differential impedance spectroscopy of single cells. Microfluid Nanofluidics 9:191–198
McAdams ET, Lackermeier A, McLaughlin JA, Macken D (1995) The linear and non-linear electrical properties of the electrode-electrolyte interface. Biosens Bioelectron 10:67–74
Mihai CM, Mehedintu M, Gheorghiu E (1996) The derivation of cellular properties from dielectric spectroscopy data. Bioelectrochem Bioenerg 40:187–192
Morgan H, Sun T, Holmes D, Gawad S, Green NG (2007) Single cell dielectric spectroscopy. J Phys D Appl Phys 40:61–70
Pan J (2007) Direct and rapid monitoring the biochemical reaction of interleukin-6 in human using a flow-injection capacitive immunosensor in clinical immunoassay. Sens. Actuators B 125:517–525
Park JW, Jung HS, Lee HY, Kawai T (2005) Electrical recognition of label-free oligonucleotides upon streptavidin-modified electrode surfaces. Biotechnol Bioprocess Eng 10:505–509
Poghossian A, Ingebrandt S, Offenhausser A, Schoning MJ (2009) Field-effect devices for detecting cellular signals. Semin Cell Dev Biol 20:41–48
Prodan E, Prodan C, Miller JH Jr (2008) The dielectric response of spherical live cells in suspension: an analytic solution. Biophys J 95:4174–4182
Rümenapp C, Remm M, Wolf B, Gleich B (2009) Improved method for impedance measurements of mammalian cells. Biosens Bioelectron 24:2915–2919
Strasak L, Dvorak J, Hason S, Vetterl V (2002) Electrochemical impedance spectroscopy of polynucleotide adsorption. Bioelectrochemistry 56:37–41
Wang R, Zhang T, Bao QY, Rawson DM (2006) Study on fish embryo responses to the treatment of cryoprotective chemicals using impedance spectroscopy. Eur Biophys J 35:224–230
Wang R, Guan M, Rawson DM, Zhang T (2007) Ultrasound enhanced methanol penetration of zebrafish (Danio rerio) embryos measured by permittivity changes using impedance spectroscopy. Eur Biophys J 37:1039–1044
Yang LJ, Li YB (2006) Detection of viable salmonella using microelectrode-based capacitance measurement coupled with immunomagnetic separation. J Microbiol Methods 64:9–16
Zhang MIN, Repo T, Willison JHM, Sutinen S (1995) Electrical impedance analysis in plant tissues: on the biological meaning of Cole–Cole α in Scots pine needles. Eur Biophys J 24:99–106
Acknowledgments
This work was partially supported by a grant from the Department of Health Sciences, University of Molise. Financial support from the regional projects MEDIREN “Innovative methods and devices for the detection of electrophysiology parameters from neuronal cells and tissues” is gratefully acknowledged.
Author information
Authors and Affiliations
Corresponding author
Additional information
An erratum to this article can be found at http://dx.doi.org/10.1007/s00249-012-0788-6.
Rights and permissions
About this article
Cite this article
Di Capua, R., Barra, M., Santoro, F. et al. Towards the realization of label-free biosensors through impedance spectroscopy integrated with IDES technology. Eur Biophys J 41, 249–256 (2012). https://doi.org/10.1007/s00249-011-0782-4
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00249-011-0782-4