Quantitative Thrombogenesis Analysis in an In-vitro Microfluidic Chip Using Image Analysis and CFD

A thrombus is a blood coagulated by external stimuli. Excessive thrombi are dangerous because they have some potential to block blood vessels. The formation of a thrombus is closely related to the wall shear rate (WSR), and studies on this relationship have been investigated worldwide. In this paper, the thrombus formation process as a function of WSR was observed and analyzed using an in-vitro microfluidic chip. In order to locally realize a high WSR, a stenosis section in which the diameter of the channel becomes narrow was designed. The channel with the stenosis section was fabricated with a microfluidic chip made of transparent polydimethylsiloxane (PDMS) material through the thermal expansion method. A blood experiment was conducted to flow whole blood into a microfluidic chip constantly. It was recorded in real-time through a portable microscope. Through the image analysis method presented in this paper, the thrombus formation process was visualized without using fluorescent material, and the thrombus area was quantitatively calculated. In this process, it was observed that the thrombus was formed over three stages: lag time (adhesion of thrombus to the wall), aggregation (thrombus growth), and occlusion (blockage of a channel by the thrombus). In addition, computational fluid dynamics was performed to predict the location of thrombus formation. The volume fraction of plasma was simulated using a two-phase model, assuming that blood is a mixture of red blood cells and plasma. After the stenosis, it was confirmed that the volume fraction of plasma increased as it approached the channel wall.