Modeling and Validation of Mass Transport Dynamics in a Microfluidic Vascular Model

Wong, Jeremy F. 1 ;  Young, Edmond W.K. 1, 2 ;  Simmons, Craig A. 1, 2

1. Institute of Biomaterials and Biomedical Engineering, University of Toronto; 2. Department of Mechanical and Industrial Engineering, University of Toronto

Microfluidic models of the vascular system have been used to provide novel insight into the effects of hemodynamic shear stress on vascular cell behaviour. The dynamic fluidic environment within vascular culture models, however, poses significant challenges to integration of on-chip quantitative assays as such assays are often sensitive to flow with severe sample dilution occurring at elevated levels of flow-induced shear stress. In this work, we developed and experimentally validated a computational model of the fluid dynamics and mass transport in a microfluidic vascular cell culture model with on-chip secreted protein biosensing that enables application of physiological levels of shear stress to cultured cells.

The microfluidic culture model is a bilayer device in which cell and biosensor compartments are separated by a porous membrane, isolating the biosensor from the elevated flow rates in the cell compartment while still allowing analyte transport between compartments. A bilayer microfluidic culture model with integrated electrodes was successfully designed and fabricated. Computational modeling of transport dynamics in the microfluidic device indicated that increases in transmembrane pressure, ?PT, result in significant non-linear reductions in mass transport times. Based on measured physical cell compartment dimensions, applying post-capillary venous and aortic shear stresses of 0-6 dyn/cm2 in the device results in a corresponding ?PT range of 0-180 Pa. Within this range, mass transport times for a cell-free porous membrane were simulated at different ?PTs values and also obtained experimentally by electrochemically monitoring the concentration of an electroactive species over time in the biosensor compartment at the same ?PT values. There was a close agreement between the model and experimental values, validating the predictive capabilities of the analyte transport dynamics model.

A computational model of analyte transport dynamics within a bilayer microfluidic vascular model with on-chip sensing was developed using finite element methods and experimentally validated using the electrochemical measurement of an electroactive species over time. The computational model will therefore be used to optimize analyte transport conditions and maximize biosensor performance.