Development of novel microfluidic cell sorters using dielectrophoresis and magnetophoresis
Microfluidics offers an attractive platform to separate biological components out of a complex mixture at high purity, which is indispensable in biotechnology. This dissertation describes three novel microfluidic techniques which achieve separation by exploiting dielectrophoresis and magnetophoresis. It describes unique approaches in utilizing microfluidic technology for advanced applications in cellular and molecular separations, and demonstrates novel and useful functionalities are difficult to implement using conventional, macro-microscale methods.
First, I 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 (G1/S and G2/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 G1 phase to 96% in one round of sorting, in a continuous flow manner at a throughput of 2×105 cells per hour per microchannel.
Second, I describe a microfluidic platform to sort out multiple cell types simultaneously with high purity and recovery. I describe a novel approach to specifically label multiple cell types with unique synthetic dielectrophoretic tags that modulate the complex permittivities of the labeled cells, allowing them to be sorted with high purity using the multitarget dielectrophoresis activated cell sorter (MT-DACS) chip. Here I describe the underlying physics and design of the MT-DACS microfluidic device and demonstrate ∼1000-fold enrichment of multiple bacterial target cell types in a single-pass separation.
Finally, I further expand our multi-target cell sorter scheme and report the development of integrated Dielectrophoretic-Magnetic Activated Cell Sorter (iDMACS), which is, to the best of our knowledge, the first platform to integrate two different force fields in a single microfluidic device for highly efficient multi-target separation. I describe the underlying physics and design of the iDMACS and demonstrate ∼900-fold enrichment of multiple bacterial target cell types with over 95% purity after a single round of separation.
0544: Electrical engineering
0548: Mechanical engineering