Models and ultra-sensitive apparatus for electronic single cell analysis

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Cells are dynamic electronic materials that change electronic state in response to environmental pressures. There have been many demonstrations that cells exhibit dielectric changes that coincide with important physiological changes such as the differentiation of stem cells, the development of multi drug resistance (MDR) in cancer cells, and programmed cell death (apoptosis). Single cell measurements of the dielectric response can identify dielectric sub-populations and temporal changes to these sub-populations that are not possible with common bulk probes. The proposed research program will derive quantitative models of the relationship between electronic and physiological changes in cells and also to produce instrumentation with superior ability to detect these dielectric changes in single cells. The work will focus on the use of dielectrophoresis (DEP) in a flow system that bring cells from a reservoir to the analysis region, making the analysis of a large number of cells practical in a reasonable time frame. In collaboration with G. Bridges I have developed a flow based single cell DEP analysis instrument. It can detect apoptosis by sensing the modified polarization that results from a drop in intracellular potassium, concentrations. Using a microwave interferometer in a differential detection approach, this DEP cytometer detected apoptosis in Chinese Hamster Ovary (CHO) cells.