Microfluidic continuous-flow manipulation of particles and cells inside ferrofluids
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Current technologies for cell enrichment such as fluorescence-activated cell sorting are often labor-intensive and require labeling step to identify cells of interests. Microfluidic sorting techniques based on intrinsic physical properties of cells were exploited for their advantages of portability and low cost. We developed a novel label-free method for continuous sorting of microparticles and cells based on their size difference. The associated devices are inexpensive and simple, only requiring a micro-channel and hand-held permanent magnets. Non-magnetic microparticles and commercial ferrofluids were first used to demonstrate the feasibility of the technology, including particles focusing and sorting. It was then optimized for bacteria and yeast cell separation with increased reproducibility, reduced screening time, and improved screening throughput and accuracy. The ultimate application of the proposed technology relies on the synthesis of biocompatible ferrofluids that meet the stringent requirements of the mammalian cell manipulation. Therefore, a polyethylene glycol (PEG) copolymer stabilized ferrofluid was developed to facilitate the mammlian cell manipulation and enrichment. We characterized the ferrofluids and confirmed the inert influence on the mammalian cells properties, such as the viability of HeLa cells and mouse red blood cells. Then we demonstrated the separation of these two cell types with high efficiency and throughput. Label free cell manipulation inside biocompatible magnetic medium promised new applications in dealing with other types of cells. Furthermore, we combined positive and negative magnetophoresis to separate particles of different magnetic properties in both commercial and custom-made ferrofluids. Its success extends the capability of the ferrohydrodynamic platform for future development.