High-density impedance-sensing array on complementary metal-oxide-semiconductor circuitry assisted by negative dielectrophoresis for single-cell-resolution measurement

Abstract

A microarray biosensor that measures the electrical impedance of cell suspensions is presented. Single-cell–resolution measurement was facilitated by physically positioning individual cells on sensing electrodes by dielectrophoresis, obviating chemical or biological surface modification. The high-density (104 × 104) electrode array was incorporated with a complementary metal-oxide-semiconductor (CMOS) integrated chip (IC) to support impedance spectroscopy at frequencies ranging from 100 kHz to 1 MHz, achieving a rapid and cost-effective platform with a small form factor. Experiments with microbeads (10, 15, and 20 μm in diameter) and a live breast cancer cell line (MCF-7) have demonstrated that the developed prototype quantifies loaded microbeads or cells rapidly (<1 min), with a mapping accuracy over 95%, showing good agreement with optical observation. In addition, a new impedance model of a cancer cell suspended in buffer media was constructed to interpret the measurement results, and the simulation results obtained with the model showed good agreement with the experimental results.