Title:  High Throughput Multi-modal Microfluidic System for Isolation of Blood Cells

Committee: 

Dr. Sulchek, Advisor

Dr. Sarioglu, Co-Advisor

Dr. Brand, Chair

Dr. Alexeev

Abstract: The objective of the proposed research is to design, fabricate and test a continuous high throughput lab on a chip, multi modal microfluidic platform for whole blood sorting. The proposed device utilizes size and adhesion as label-free biomarkers. The separation device consists of a microchannel with periodically arranged diagonal ridges. In the first part of the study, we explore the impact of hydrodynamics caused by the diagonal ridges on microparticle flow and how it can be optimized for size based sorting. We find that the diagonal ridges create helical flow fields that impact similar particles of different z-positions differently. Our preliminary studies show that by incorporating z-axis focusing of the sample inlet so as to position all particles to a uniform z-position, we can make consistent the particle exposure to transverse flow fields for more accurate size-dependent sorting. In this work, a 3D tracking algorithm is developed to analyze 2D images for fast and accurate extraction of three dimensional trajectories of particles that are used to understand the device working mechanism. In the second part of this work, we study the impact of specific molecular attachment to the diagonal ridges on cell trajectories and thus for adhesion based sorting. The unique aspect of this sorting design is the impact of the gap size on cell trajectories and cell kinetics, in which a sufficiently small gap size can lightly squeeze the cells while flowing under the ridged part of the channel to increase the surface area for interaction between the ligand on cell surface and coated receptor molecule but large enough so that biomechanical markers, stiffness and viscoelasticity, do not dominate the cell separation mechanism. This way we can flow the cells at high flow rate to achieve high throughput, while maintaining sensitivity to adhesiveness.