Biological Cell Preparation and On-Chip Particle Sorting Systems at High Flow Rate

Abstract

Cell analysis is critical for biology research and clinical applications. Therefore, thequality and speed of a cell preparation process have a considerable impact on the credibility of the analysis. This process begins with harvesting cells from the biological samples, such as tissues, blood, body fluid, etc. Then multiple processes might be performed, including labeling with dye or antibody, cell sorting based on a variety of the properties of the target cells, fixation for microscopy, washing to remove the excessive chemical and unbound labels, and more. In the conventional approach, each process typically requires multiple steps, including pipetting, mixing, centrifugation, and re-suspension of a pellet after centrifugation. Microfabricated devices with functional structures capable of automated and inte- grated cell processing have great potential for achieving a high recovery efficiency, high purity and quality, and high consistency of cell sample preparation in various areas of biomedical and clinical applications. This thesis will first discuss a hybrid microfluidic cell incubation and washing systems, which includes a chip with a microfluidic cross- flow filter with a pre-focusing structure and a conventional liquid handling systems. Combining the adventures of microfluidic and conventional fluid handling devices, we achieve high performance with unlimited incubation time. Then we discuss a method of scaling the deterministic lateral displacement (DLD) device into a single column of obstacles. As a result, the throughput per device area increased by an order compared to conventional DLD devices by minimizing the device area. Finally, we discuss using the two-dimensional “unit cell” method to facilitate the design of our DLD device with a single column of obstacles which has a smaller critical diameter. We also discussed the three-dimensional “unit cell” method, which overcame the problem, the decline in particle separation efficiency and resolution with increased device depth, which the two-dimensional methods suffer to further increase the throughput in a given device area