Cellular and molecular bioseparations using coherently patterned micro/nano devices

化学和生物分离计划的NSF奖项支持康奈尔大学的Brian Kirby教授的工作，该工作利用相干微米和纳米图案化脊对颗粒和大分子运输的非线性电动效应，以创建快速分离（a）细胞悬浮液或（B）含有淀粉样蛋白纤维的溶液组分的新技术。 由于多种物理过程的丰富相互作用和通过电场介导的细胞和分子运输控制实现的增加的实验灵活性，相干的微米和纳米图案化表面为科学和技术突破提供了令人兴奋的机会。虽然介电泳力已被用于捕获和操纵粒子，并且在选定的情况下，操纵大分子，连续流技术已经被最小化，并且其对介电性质的精确灵敏度尚未被实现以产生用于细胞膜脂质突变和分子聚集的廉价和特异性分离筛选。 所提出的工作结合了一种新的微/纳米器件设计与详细的介电，离子传输和流体传输建模。 细胞和分子的电动致动将与电场的几何操纵相结合，以允许主要依赖于诱导的或现有的电偶极子的连续流分离。 该设计的一个关键和新颖的组成部分集中在使用相干图案化微通道表面的扰动，以创建一个次级介电泳力场与线性电迁移力场叠加。 通过使用DC偏移AC场，可以调谐线性和非线性电迁移现象的相对幅度以优化分离。 建议的工作桥梁之间的差距差距现有的批量处理DEP分选技术和所需的连续流分离screen.The长期的目标，这项工作是开发一种设计方法，通过该设备可以制造连续流分离的细胞和分子。 拟议的研究的总体目标是使用电偶极子的几何操作，以开发快速，连续流分离细胞和蛋白质。 该提案将集中在两个不同但相关的假设：1）相干图案化的微器件将允许由于空间变化的电场和诱导的粒子电偶极子之间的库仑相互作用而连续流动分离突变细胞;和2）相干图案化的纳米器件将允许蛋白质的连续流动分离由于空间变化的电场和天然蛋白质电偶极子之间的库仑相互作用，蛋白质（特别是那些处于原纤化状态的蛋白质）的电偶极被破坏。基于工程形式主义，用于描述颗粒在脊状微米和纳米通道中的传输，所提出的工作将使表面图案化设计能够产生独特的纳米颗粒和大分子分选能力。 与纳米技术伦理和纳米尺度运输建模相关的异步教学材料将被开发，以整合伦理，课程和研究。

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.