Geometric design of microfluidic chambers: platelet adhesion versus accumulation

Arterial, platelet-rich thrombosis depends on shear rates and integrin binding to either a collagen surface or to the growing thrombus, which are mechanistically different. In general, small microfluidic test sections may favor platelet-surface adhesion without testing for the primary mode of intra-arterial thrombosis, i.e. platelet-platelet bonding and accumulation. In the present report, the ratio of platelet-platelet to platelet-surface interactions, R, and the percentage of platelet-platelet interactions, P, are estimated using an analytical approach for circular and rectangular test sections. Results show that the test section geometry strongly affects both R and P, with test section height in low-aspect ratio channels or diameter greater than 90 μm dominated by platelet-platelet interactions (R >10). Increasing rectangular test section aspect ratio decreases the required height. R increases linearly while P approaches 100 % asymptotically with increasing channel dimension. Analysis of platelet shape shows that the assumption of spherical platelets has a small effect on R compared to discoid platelets adhering flat against test section wall. However, an increase in average platelet volume resulted in a large decrease in R. Nonetheless, Monte Carlo simulations of a typical distribution of human platelet sizes show intrasubject variation in platelet size has only a 10 % net effect on R. Finally, experiments of thrombus formation show that platelet-surface lag times and platelet-platelet accumulation are similar for rectangular microfluidic test sections and round test sections when R >10. The findings show that the size of a microfluidic test section should be carefully considered in studies of cell-cell accumulation versus cell-surface adhesion.