Impedance spectroscopy with field-effect transistor arrays for the analysis of anti-cancer drug action on individual cells.
In this study, impedance spectroscopy measurements of silicon-based open-gate field-effect transistor (FET) devices were utilized to study the adhesion status of cancer cells at a single cell level. We developed a trans-impedance amplifier circuit for the FETs with a higher bandwidth compared to a previously described system. The new system was characterized with a fast lock-in amplifier, which enabled measuring of impedance spectra up to 50 MHz. We studied cellular activities, including cell adhesion and anti-cancer drug induced apoptosis of human embryonic kidney (HEK293) and human lung adenocarcinoma epithelial (H441) cells. A well-known chemotherapeutic drug, topotecan hydrochloride, was used to investigate the effect of this drug to tumor cells cultured on the FET devices. The presence of the drug resulted in a 20% change in the amplitude of the impedance spectra at 200 kHz as a result of the induced apoptosis process. Real-time impedance measurements were performed inside an incubator at a constant frequency. The experimental results can be interpreted with an equivalent electronic circuit to resolve the influence of the system parameters. The developed method could be applied for the analysis of the specificity and efficacy of novel anti-cancer drugs in cancer therapy research on a single cell level in parallelized measurements.
University of Applied Sciences Kaiserslautern, Informatics and Microsystem Technology, Amerikastr. 1, 66482 Zweibruecken, Germany.
A
A
Susloparova
D
D
Koppenhöfer
X T
XT
Vu
M
M
Weil
S
S
Ingebrandt
D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D015374:Biosensing Techniques / Q000295:instrumentation*; D045744:Cell Line, Tumor; D002469:Cell Separation / Q000295:instrumentation; D002470:Cell Survival / Q000187:drug effects; D058266:Dielectric Spectroscopy / Q000295:instrumentation*; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation*; D004867:Equipment Design; D019544:Equipment Failure Analysis; D005434:Flow Cytometry / Q000295:instrumentation; D006801:Humans; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000503:physiopathology*; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D019772:Topotecan / Q000627:therapeutic use*; D014173:Transistors, Electronic; D016896:Treatment Outcome
D000970:Antineoplastic Agents; D019772:Topotecan