High Throughput Centrifuge Microfluidic Device for Simultaneous Particle Separation and Solution Exchange

Microfluidic centrifuge devices have gained increasing attention for point-of-need (PoN) sample preparation processes, e.g., in separation or solution exchange of various microparticles, bacteria, and mammalian cells. Yet, those devices capable of simultaneous solution exchange and particle separation are low in throughput (can operate at up to 2 mL/min), hindering their applicability to real-world settings. This thesis introduces a multilayer microfluidic device designed for high-throughput solution exchange and efficient microparticle separation, addressing the need for processing large sample volumes at elevated flow rates. The device integrates Dean flow recirculation and selective inertial focusing of microparticles within 24 curved microchannels assembled in a compact three-layer configuration via in-plane and out-of-plane parallelization. Exploring substrate materials (glass or PDMS) and operational flow rates, we studied solution exchange and particle migration using singleplex and duplex samples across devices with varying curve numbers (2-curve, 8-curve, and 24-curve). Transitioning from glass to PDMS enhanced solution exchange efficiency in curved channels. Processing 5 µm and 10 µm microparticles at flow rates up to 16.8 mL/min (33.6 mL/min total in the multilayer device) achieved a solution exchange efficiency of 96.7%. In singleplex suspensions, 10 µm and 5 µm particles selectively migrated to different outlets of the device, demonstrating separation efficiencies of 99.7% and 90.3%, respectively. With duplex samples, sample purity was measured to be 93.4% and 98.6% for 10 µm and 5 µm particles collected from different outlets, respectively. Application of our device in biological assays was shown by performing duplex experiments where 10 µm particles were isolated from Salmonella bacterial suspension with purity of 97.8%. This parallelization enabled desirable combinations of high throughput, low-cost, and scalability, without compromising efficiency and purity, advancing the technology towards sample preparation.