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An Equilibrium Method for Continuous-Flow Cell Sorting Using Dielectrophoresis
journal contribution
posted on 2008-05-01, 00:00 authored by M. D. Vahey, J. VoldmanSeparations represent a fundamental unit operation in
biology and biotechnology. Commensurate with their
importance is the diversity of methods that have been
developed for performing them. One important class of
separations are equilibrium gradient methods, wherein
a medium with some type of spatial nonuniformity is
combined with a force field to focus particles to equilibrium positions related to those particles' intrinsic properties. A second class of techniques that is nonequilibrium
exploits labels to sort particles based upon their extrinsic
properties. While equilibrium techniques such as iso-electric focusing (IEF) have become instrumental within
analytical chemistry and proteomics, cell separations
predominantly rely upon the second, label-based class of
techniques, exemplified by fluorescence-activated cell
sorting (FACS) and magnetic-activated cell sorting (MACS).
To extend the equilibrium techniques available for separating cells, we demonstrate the first implementation of a
new microfluidic equilibrium separation method, which
we call isodielectric separation (IDS), for sorting cells
based upon electrically distinguishable phenotypes. IDS
is analogous to isoelectric focusing, except instead of
separating amphoteric molecules in a pH gradient using
electrophoresis, we separate cells and particles in an
electrical conductivity gradient using dielectrophoresis.
IDS leverages many of the advantages of microfluidics and
equilibrium gradient separation methods to create a
device that is continuous-flow, capable of parallel separations of multiple (>2) subpopulations from a heterogeneous background, and label-free. We demonstrate the
separation of polystyrene beads based upon surface
conductance as well as sorting nonviable from viable cells
of the budding yeast Saccharomyces cerevisiae.