On-Chip Preparation of Biological Cells Using Microfluidic Arrays

Abstract

The analysis of biological cells plays an important role in disease detection and treatment. The credibility of analysis results depends on the quality of prepared cells. The preparation usually starts from extracting the target cells from biological samples, such as tissue, body fluid, and blood. Then multiple preparation processes could be performed: staining with dye, extracellular labeling with monoclonal antibodies, permeabilization for intracellular labeling, fixation for optical observation, lysis for DNA sequencing, and washing to remove unbound labels and unreacted chemicals. Each preparation process often requires several manual steps which may include pipetting, manual shaking, centrifugation, and re-suspension of a pellet after centrifugation.

For more uniformly prepared cell samples, automated and integrated processing and preparation of cells is preferred. Microfabricated arrays of functional structures driven by continuous flow have shown great potentials in achieving high recovery efficiency, purity and quality of prepared cell sample with good practicality in a broad range of cell preparation applications. In this thesis, we will first discuss a methodology for on-chip chemical processing of biological cells using deterministic lateral displacement (DLD) arrays by directing the target cells through sequential regions of treatment chemical and washing streams. With separator walls and long serpentine channels properly designed, the performance can be greatly improved. We then discuss a trap structure array to capture, process, and wash the target cells. Unlike DLD arrays, target cells are immobilized by the trap structures and then processed by sequentially loading treatment chemical, washing, and releasing streams, other than being directed through multiple fixed functional regions. Finally, we discuss concentrating genomic-length DNA using DLD arrays. The experimental and theoretical study is the first step towards high-speed and high-throughput sorting of genomic-length DNA for sequencing applications.