Selection of mammalian cells based on their cell-cycle phase using dielectrophoresis

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Abstract
An effective, noninvasive means of selecting cells based on their phase within the cell cycle is an important capability for biological research. Current methods of producing synchronous cell populations, however, tend to disrupt the natural physiology of the cell or suffer from low synchronization yields. In this work, we report a microfluidic device that utilizes the dielectrophoresis phenomenon to synchronize cells by exploiting the relationship between the cell's volume and its phase in the cell cycle. The dielectrophoresis activated cell synchronizer (DACSync) device accepts an asynchronous mixture of cells at the inlet, fractionates the cell populations according to the cell-cycle phase (G(1)/S and G(2)/M), and elutes them through different outlets. The device is gentle and efficient; it utilizes electric fields that are 1-2 orders of magnitude below those used in electroporation and enriches asynchronous tumor cells in the G(1) phase to 96% in one round of sorting, in a continuous flow manner at a throughput of 2 x 10(5) cells per hour per microchannel. This work illustrates the feasibility of using laminar flow and electrokinetic forces for the efficient, noninvasive separation of living cells.