(200b) Evaluation of Microfluidic Device Designs for a Potassium Release Toxicity Assay

With the integration of mixing systems, microfluidic devices offer potential applications in the fields of reactor design and assay development ^[1]. This project investigates key design parameters of commonly-used mixing systems to optimize a microfluidic device for use with the potassium release toxicity assay.

The potassium release toxicity assay offers a measure of drug toxicity by exposing red blood cells (RBCs) to various concentrations of drug solution; as RBCs are exposed to more toxic environments, levels of potassium released from the cells increase towards a maximum value ^[2]. Drug toxicity is quantified by the drug concentration corresponding to half-maximum potassium release.

Insufficient mixing of RBCs and drug solution can artificially reduce the drug toxicity determined by this assay. Additionally, inconsistent mixing between trials can cause random fluctuations in assessed drug toxicity. Incorporating the mixing step of the potassium release toxicity assay into a microfluidic device can ensure that assessment of drug toxicity is conducted consistently, even with low fluid volumes.

During the study, CFD simulations in COMSOL Multiphysics are being used to simulate flow of RBCs and drug solutions through various device designs. Among the design parameters being tested are the lengths, widths, and shapes of channels and baffles integrated into the device. Following simulation, fluid velocities, compositions, and pressure drops will be collected and assessed to quantify the mixing efficiency accompanying each design. The combination of design parameters corresponding to the greatest mixing efficiency will be recommended for microfluidic device manufacturing and use in the potassium release toxicity assay.

[1] Losey, M.; Jackman, R.; Firebaugh, S.; Schmidt, M.; Jensen, K. Journal of Microelectromechanical Systems 2002, 11 (6), 709–717.

[2] Jensen, G. M.; Skenes, C. R.; Bunch, T. H.; Weissman, C. A.; Amirghahari, N.; Satorius, A.; Moynihan, K. L.; Eley, C. G. S. Drug Delivery 1999, 6 (2), 81–88.