Cellular and molecular bioseparations using coherently patterned micro/nano devices

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This NSF award by the Chemical and Biological Separations program supports work by Professor Brian Kirby at Cornell University to use the nonlinear electrokinetic effects of coherent micro- and nanopatterned ridges on particle and macromolecule transport to create new techniques for rapidly separating components of either (a) cellular suspensions or (b) solutions containing amyloid fibrils. Coherently micro- and nanopatterned surfaces provide exciting opportunities for scientific and technological breakthoughs owing to both the rich interplay of multiple physical processes and increased experimental flexibility achieved through electric field-mediated control of cellular and molecular transport.While dielectrophoretic forces have been used to trap and manipulate particles and, in selected cases, to manipulate macromolecules, their implementation in rapid, continuous-flow techniques has been minimal, and its exquisite sensitivity to dielectric properties has not been implemented to create inexpensive and specific separation screens for cell membrane lipid mutation and molecular agglomeration. The proposed work combines a novel micro/nanodevice design with detailed dielectric, ion transport, and fluid transport modeling. Electrokinetic actuation of cells and molecules will be combined with geometric manipulation of electric fields to allow for continuous-flow separation dependent primarily on induced or existing electrical dipoles. A critical and novel component of the design focuses on the use of coherently patterned perturbations in a microchannel surface to create a secondary dielectrophoretic force field that superposes with the linear electromigratory force field. By using DC-offset AC fields, the relative magnitudes of linear and nonlinear electromigratory phenomena can be tuned to optimize the separation. The proposed work bridges the gap between existing batch-processing DEP sorting techniques and the needed continuous-flow separation screens.The long-term goal of this work is to develop a design methodology by which devices can be fabricated for continuous-flow separations of cells and molecules. The overall objective of the proposed research is to use geometric manipulation of electrical dipoles to develop rapid, continuous-flow separations for cells and proteins. The proposal will focus on two distinct but related hypotheses: 1) coherently-patterned microdevices will allow for continuous-flow separation of mutated cells owing to coulomb interaction between a spatially-varying electric field and induced particle electrical dipoles; and 2) coherently-patterned nanodevices will allow for continuous-flow separation of proteins (particularly those in fibrillated states) due to coulomb interaction between spatially-varying electric fields and native protein electrical dipoles.By implementing design via a model-based engineering formalism for describing particle transport in ridged micro- and nanochannels, the proposed work will enable surface patterning design that generates unique nanoparticle and macromolecule sorting capabilities. Asynchronous instructional materials related to the ethics of nanotechnology and the modeling of nanoscale transport will be developed to integrate ethics, coursework, and research.