Development of impedance based biosensor arrays

Electrical sensing systems for cellular detection provide high throughput and capability of continuous and non-destructive detection, which are valuable for drug testing and genomic studies but cannot be attained by traditional microscopic observation.;In this thesis, planar impedance sensor arrays were developed for monitoring cell growth and cell responses to drugs. Simulation models and lumped circuit models were used for studying the impedance changes with cells present. Validation experiments of impedance sensing were performed on relatively large electrodes (∼0.01 mm2∼0.5mm2). Impedance spectra over a wide frequency range were measured and the impedance changes with cells were characterized using the peak magnitude of the impedance change and the position of the peak. Impedance increases resulting from cell attachment, spreading and proliferation at intermediate frequencies (30 kHz∼100 kHz) by a large factor (1∼3) were observed.;The impedance sensor was successfully used to distinguish cell lines differing in the number of the cell-substrate contacts and the manner of growth. The peak magnitude and the evolution of the impedance change over the growth course have different signatures for normal 3T3 fibroblasts and carcinoma HCT-116 cells. Impedance changes corresponding to a drug H-7 effect on the 3T3 fibroblast cells adhesion were observed. The relationship between the impedance decrease at low frequencies and the cellular metabolic activity was also studied.;An active matrix-addressed array of cell-size electrodes was proposed for single cell detection. Active matrix sensor arrays were developed using two technologies: thin film transistor display technology and CMOS technology. Gated impedance measurement of the active matrix arrays were both simulated and experimentally measured. The CMOS chip with remetallized sensing electrodes and appropriate passivation has a promising future. These sensor arrays have the potential for applications in pharmaceutical screening and environmental monitoring.