High resolution monitoring of chemotherapeutic agent potency in cancer cells using a CMOS capacitance biosensor

Biosens Bioelectron. 2019 Oct 1;142:111501. doi: 10.1016/j.bios.2019.111501. Epub 2019 Jul 13.

Abstract

Monitoring cell viability and proliferation in real-time provides a more comprehensive picture of the changes cells undergo during their lifecycle than can be achieved using traditional end-point assays. Particularly for drug screening applications, high-temporal resolution cell viability data could inform decisions on drug application protocols that might lead to better treatment outcomes. We describe a CMOS biosensor that monitors cell viability through high-resolution capacitance measurements of cell adhesion quality. The system consists of a 3 × 3 mm2 chip with an array of 16 sensors, on-chip digitization, and serial data output that can be interfaced with inexpensive off-the-shelf components. An imaging system was developed to provide ground-truth data of cell coverage concurrently with data recordings. Results showed the sensor's ability to detect single-cell binding events, track cell morphology changes, and monitor cell motility. A chemotherapeutic assay was conducted to examine dose-dependent cytotoxic effects on drug-resistant and drug-sensitive cancer cell lines. Concentrations higher than 5 μM elicited cytotoxic effects on both cell lines, while a dose of 1 μM allowed discrimination of the two cell types. The system demonstrates the use of real-time capacitance measurements as a proof-of-concept tool that has potential to hasten the drug development process.

Keywords: CMOS capacitance biosensor; Cancer cell cytotoxicity; Drug screening; Lab-on-chip.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Biosensing Techniques / instrumentation*
  • Cell Death / drug effects
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Drug Screening Assays, Antitumor / instrumentation*
  • Electric Capacitance
  • Equipment Design
  • Female
  • Humans
  • Lab-On-A-Chip Devices*
  • Ovarian Neoplasms / drug therapy

Substances

  • Antineoplastic Agents
  • Cisplatin