Hybrid microfluidic herringbone mixer for tangential flow filtration

• Main Author: Goh, Kelly Jia Yi
• Other Authors: Hou Han Wei
• Format: Final Year Project
• Language: English
• Published: Nanyang Technological University 2024
• Subjects: Engineering; Herringbone mixer; Tangential flow filtration
• Online Access: https://hdl.handle.net/10356/177521
• Institution: Nanyang Technological University

Extracellular vesicles (EVs) serve as crucial mediators of intercellular communication, carrying disease-specific cargo such as proteins and nucleic acids, making them promising biomarkers for various diseases in clinical diagnostics. However, the complexity of current EV isolation methods poses challenges for clinical adoption, highlighting the need for more efficient solutions. A key challenge is the presence of the plasma proteins which require additional methods in order to deplete them from EVs prior to EV analysis. For effective EV filtration, tangential flow filtration (TFF), a method of isolation that passes fluids across a membrane is employed. Micromixers are devices that use mechanical components to induce mixing. Mixing of fluids in laminar flow within microchannels is limited due to diffusive mixing , which compromises filtration efficiency and accuracy of downstream analysis. In this thesis, we present the integration of a staggered herringbone micromixer (SHM) into a microfluidic TFF (µTFF) device. Fabricated using polydimethylsiloxane (PDMS) through soft lithography and plasma bonding, the device incorporates a membrane layer (50 nm pore size) between top and bottom microchannels. Key parameters tested include width-to-spacing ratio, angle, flow rate, stagger ratio, and concavity, with the angle of the SHM identified as the most influential factor affecting mixing efficiency. The hybrid SHM-µTFF device demonstrated protein removal rates of 82.83% as compared to the original µTFF device of 79.05% and doubled EV recovery concentration from 17.3% to 35.7%, underscoring the role of improved mixing efficiency in enhancing filtration outcomes. These findings emphasizes the potential of optimised SHM integration in improving EV isolation for point-of-care (POC) testing applications.