Current cell separation technologies are limited to sorting and analyzing heterogenous cell populations basedon differences in cell size or cell density or by leveraging the expression of specific immunological targets orreceptor-ligand interactions. Other cytophysical characteristics such as deformability, electrical charge, andelectrical polarizability are correlated with important biological differences between subpopulations of cells andwould serve as valuable biomarkers for these populations; however, currently available instruments lack thecapability to separate cells based on these cytophysical/cytoelectrical parameters. Aincobio is developing"ElectroFlow", the first electrokinetic flow cytometer, to address this gap. ElectroFlow combines dielectrophoresis(DEP), an electrical-field-induced force that is well-established as a method to separate and characterizeparticles, with field-flow-fractionation (FFF) to separate cells based on differences in membrane polarization andother cytoelectric phenotypes. ElectroFlow will allow for different force combinations to be programmed fordifferent cell types or different aspects of cells, achieving specialized differentiation of cellular features (size,shape, density, membrane composition and morphology, surface markers, surface charge, and cytosolcomposition). The Aincobio team has built a prototype ElectroFlow instrument and demonstrated proof-of-concept with both eukaryotic and prokaryotic cells at ~5,000 cells/min. To enable scaling to accommodate largenumbers of cells, Aincobio has applied multi-physics simulations to redesign the device construction and DEPelectronics to allow for a 10x scale-up in number of cells per run. In this Phase I SBIR, Aincobio will leveragethis simulation data to 1) build and bench-test prototype microelectrode array circuit boards and signal amplifierelectronics, and 2) improve thermal management and validate prototype by measuring separation efficiency ofmixtures of activated and resting T-cells as a function of voltage and ionic strength. Successful completion of thePhase I aims will establish proof-of-concept for a commercially viable instrument that can analyze ï¾ 106 cells ina 20-minute run and sort by cytoelectric/cytophysical features. Commercialization of ElectroFlow will provide anaccessible means for all researchers to study and harness differences in cytoelectric properties, opening entirelynew avenues of biological research and biomedical application.
Public Health Relevance Statement: PROJECT NARRATIVE
Cell separation technologies are limited to exploiting differences in cell size, density, specific immunological
targets, or receptor-ligand interactions. Aincobio is developing ElectroFlow, the first electrokinetic cytometer that
can separate sub-populations of cells based on biologically relevant physical and electrical properties without
the need for a label. ElectroFlow will allow the researcher to exploit a wide array of additional cellular features to
obtain more specialized differentiation of cellular populations for study and analyses and will enable research
into understanding how differences in electric properties of cells map to biological functions.
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