Date of Graduation

12-2019

Document Type

Thesis

Degree Name

Master of Science in Microelectronics-Photonics (MS)

Degree Level

Graduate

Department

Microelectronics-Photonics

Advisor

Julie Stenken

Committee Member

Rick Wise

Second Committee Member

Robert Coridan

Third Committee Member

D. Keith Roper

Keywords

COMSOL, Membrane Separations, Microdialysis, Microfluidics

Abstract

Microdialysis (µD) sampling is a diffusion-limited sampling method that has been widely used in different biomedical fields for greater than 35 years. Device calibration for in vivo studies is difficult for current non-steady state analytes of interest correlated with both inflammatory response and microbial signaling molecules (QS); which exist in low ng/mL to pg/mL with molecular weights over a wide range of 170 Da to 70 kDa. The primary performance metric, relative recovery (RR), relating the collected sample to the extracellular space concentration varies from 10% to 60% per analyte even under controlled bench-top conditions. Innovations in microdialysis device design have not deviated or improved upon the commercially-available cylindrical geometry for over 35 years. COMSOL Multiphysics finite element method (FEM) software was used to iteratively model and refine microfluidic-based (µF) µD device designs with the primary focus on optimizing channel geometry for improved RR. The primary focus was to improve fluid to membrane perimeter (P) to fluid cross-sectional area (A) and alter the concentration boundary layer (CBL) using passive µF mixing; which are not possible to fabricate using cylindrical geometries. The current µF µD design uses a simple asymmetric linear-looped (LL) geometry optimized with a P/A of 20 vs. 16.4 for a commercial CMA 20 µD probe with an equal 10 mm length. The simulated LL µF µD achieves a 16.1% relative increase in RR vs. experimental data at a 1.0 µL/min inlet flow rate using a 10 kDa FITC-labeled dextran as the analyte. Mixing was implemented and simulated using a modified herringbone geometry (HBM) and compared to an equivalent linear channel (LC). The HBM is shown to shift the CBL and increase diffusive flux at the membrane-fluid interface resulting in a 16.9 ± 0.7% relative increase in RR for 7 flow rates ranging from 0.125 to 2.0 µL/min vs. the LC. The combination of these changes is shown to increase RR above what is currently commercially available.

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