Manipulation of Cell and Particle Trajectory in Microfluidic Devices

Microfluidics, the manipulation of fluid samples on the order of nanoliters and picoliters, is rapidly emerging as an important field of research. The ability to miniaturize existing scientific and medical tools, while also enabling entirely new ones, positions microfluidic technology at the forefront of a revolution in chemical and biological analysis. There remain, however, many hurdles to overcome before mainstream adoption of these devices is realized. One area of intense study is the control of cell motion within microfluidic channels. To perform sorting, purification, and analysis of single cells or rare populations, precise and consistent ways of directing cells through the microfluidic maze must be perfected. The aims of this study focused on developing novel and improved methods of controlling the motion of cells within microfluidic devices, while simultaneously probing their physical and chemical properties. To this end we developed protein-patterned smart surfaces capable of inducing changes in cell motion through interaction with membrane-bound ligands. By linking chemical properties to physical behavior, protein expression could then be visually identified without the need for traditional fluorescent staining. Tracking and understanding motion on cytotactic surfaces guided our development of new software tools for analyzing this motion. To enhance these cell-surface interactions, we then explored methods to adjust and measure the proximity of cells to the channel walls using electrokinetic forces and 3D printed microstructures. Combining our work with patterned substrates and 3-dimensional microfabrication, we created micro-robots capable of rapid and precise movements via magnetic actuation. The micro-robots were shown to be effective tools for mixing laminar flows, capturing or transporting individual cells, and selectively isolating cells on the basis of size. In the course of development of these microfluidic tools we gained valuable new insights into the differences and limitations of planar vs. 3D lithography, especially for fabrication of magnetic micro-machines. This work as a whole enables new mechanisms of control within microfluidics, improving our ability to detect, sort, and analyze cells in both a high throughput and high resolution manner