Cellular and molecular bioseparations using coherently patterned micro/nano devices

这项由美国国家科学基金会化学和生物分离项目颁发的奖项支持了康奈尔大学布莱恩·柯比教授的工作，他利用相干微和纳米模式脊对粒子和大分子运输的非线性电动力学效应，创造了快速分离(a)细胞悬浊液或(b)含有淀粉样原纤维的溶液成分的新技术。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增加的实验灵活性，相干微和纳米图案表面为科学和技术突破提供了令人兴奋的机会。虽然介电力已被用于捕获和操纵颗粒，并在选定的情况下，用于操纵大分子，但它们在快速连续流动技术中的应用一直很小，并且其对介电特性的精致敏感性尚未实现，无法为细胞膜脂质突变和分子团聚创造廉价和特定的分离筛选。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、离子输运和流体输运建模。细胞和分子的电动驱动将与电场的几何操纵相结合，以允许主要依赖于感应或现有电偶极子的连续流动分离。该设计的一个关键和新颖的组成部分侧重于在微通道表面使用相干图案扰动来创建与线性电迁移力场叠加的二次介电泳力场。利用直流偏置的交流电场，可以调节线性和非线性电迁移现象的相对大小，从而优化分离效果。提出的工作弥合了现有的批处理DEP分选技术和所需的连续流分离屏幕之间的差距。这项工作的长期目标是开发一种设计方法，通过该方法可以制造用于细胞和分子连续流动分离的设备。提出的研究的总体目标是使用电偶极子的几何操作来开发细胞和蛋白质的快速连续流分离。该提案将侧重于两个不同但相关的假设：1)由于空间变化电场和诱导粒子电偶极子之间的库仑相互作用，相干图案微器件将允许突变细胞的连续流动分离；2)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，相干图案纳米器件将允许蛋白质（特别是那些在纤颤状态下的蛋白质）的连续流动分离。通过基于模型的工程形式化设计来描述脊状微纳米通道中的粒子传输，所提出的工作将使表面图案化设计能够产生独特的纳米粒子和大分子分选能力。将开发与纳米技术伦理和纳米尺度传输建模相关的异步教学材料，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.