Computational and Experimental Investigation of Microfluidics into Biophysical Interaction.

다국어 초록 (Multilingual Abstract)

Microfluidic techniques have been widely adopted in biomedical research due to the precise control of fluids, small volume requirement, low cost and etc, and have boosted the development of biomolecular interaction analysis, point-of-care diagnostics, and biosensors.Protein-protein interaction plays a key role in biological, biomedical and pharmaceutical research. The technical development of biosensors, new drugs and vaccines, and disease diagnostics heavily rely on the characterization of protein-protein interaction kinetics. The current gold standard assays for measuring protein-protein interaction are surface plasmon resonance (SPR), and bio-layer interferometry (BLI). These commercial devices are accurate but expensive, however.Here, I have developed new microfluidic techniques and models in protein-protein interaction kinetics measurement, rotational diffusion coefficient modeling, electrochemical impedance spectroscopy-based biosensors, and two-phase porous media flow models. Firstly, I applied particle diffusometry (PD) in the streptavidin-biotin binding kinetics measurement, utilizing a Y-junction microchannel. Secondly, to reduce solution volumes used in an analysis experiment, I designed a low-volume chip and coupled it with PD to measure the binding kinetics of human immunodeficiency virus p24 antibody-antigen interactions. Thirdly, considering the Brownian motion of the non-symmetric particles, I developed a new model to efficiently compute particles' rotational diffusion coefficients. Fourthly, to make economic biosensors to detect multiple biomarkers, I created a new chip, enabling hundreds of tests in a single droplet (∼ 50 μL) on one chip. Finally, to understand the liquid flow in porous media, such as nitrocellulose in lateral flow assays, I built a new two-phase porous media flow model based on the Navier-Stokes equation and compared it with experiments. These techniques and models underwent rigorous experimental and computational validation, demonstrating their effectiveness and performance.