Broadband impedance analysis of individual cells yields a wealth of information about cell size, viability, morphology and interior structure. Cell dielectric properties including membrane conductivity, cytoplasmic conductivity, and membrane capacitance can be derived from multi-frequency impedance data and used to differentiate and enumerate cell populations in a mixed sample. Additionally, impedance analysis can be used to deduce cell differentiation, the onset of apoptosis, or cellular changes due to toxicant exposure. We have built a proof-of-principle particle analysis system that measures the impedance characteristics of individual cells at multiple frequencies as they pass through a sensor incorporated into a microfluidic flow channel. The goal of the effort described in this proposal is to improve our current particle impedance analyzer to yield a high-throughput, multipurpose unit for cell analysis. Specifically, a scalable impedance measurement circuit based on relatively low cost discrete components will be developed to allow for particle impedance spectroscopy at three frequencies. A more facile fabrication method for the impedance sensor channel will be developed to yield a credit-card sized, potentially disposable microfluidic device. The sensor channel cartridge and impedance sensing electronics will be integrated and the resulting prototype device used to characterize the dielectric properties of cultured cells and blood cell subpopulations. The long-term goal of this project is to realize an inexpensive, commercializable, hand-held multi-frequency particle impedance sensor that can be used for many cell analysis applications, including tissue culture, drug discovery, point-of-care diagnostics, and other scientific and industrial needs.
