Single Cell Characterization Using Microfluidic Dielectric Spectroscopy (MDS)

A. Beskok
Southern Methodist University,
United States

Keywords: single cell analysis, dielectric spectroscopy

Summary:

Dielectric properties of biological cells can reveal information on cells’ health, function, and stage. We recently developed a MDS device that measures the dielectric properties of biological cells in response to variations in cell environment or drug uptake. DS is a label free and noninvasive measurement technique. The current device captures cells in individual microwells using positive dielectrophoresis (p-DEP) and pressure driven flow, and then makes frequency dependent electrical impedance measurements as a function of time under varying inflow conditions. Cell release is achieved using pressure driven flow and negative dielectrophoresis (n-DEP). After their release, the cells can be harvested at the device exit for further studies. This technology enables real-time measurements of cytoplasmic resistance and cell membrane capacitance. The chip allows measurement of cell response to changing buffer conductivity, pH, osmolality, and drug uptake. Transparent chip also enables simultaneous fluorescence measurements. Overall, this is a quantitative biology tool which can be used for ion-channel studies (while using ion channel blockers), drug discovery or personalized medicine. Even well-known cancer cell lines have different strains that may or may not respond to known drug therapies. Upon treatment, cancer may become undetectable until the surviving strains take over. This problem of minimum residual disease can be addressed if one can test large number of cells (~10,000) and distinguish their response to various drugs. One can also use heterogeneous mix of cells obtained from a tumor site or cells harvested after a liquid biopsy procedure and characterize them based on their size and dielectric properties, and selectively harvest them for further studies. This device can be very impactful, if it would enable label free information on cell viability. Nonviable cells can be sent to the waste while other drug mixtures be tested on the viable cells, etc. The proposed device can achieve on-chip cell electroporation so that one can measure the dielectric response of cells as a function of time. It is important to note that being able to vary the cell environment, one can introduce drugs, virus, DNA, nano-particles or macro-molecules to the electroporated cells using this device in a controllable fashion. The talk will outline the device concept along with the preliminary results. Also our group's progress in addressing basic technological issues, such as minimization of the electrode polarization effects, pertinent for micro electrodes in high conductivity physiological buffers, will be explained.