Fabrication method of multi-depth circular microchannels for investigating arterial thrombosis-on-a-chip

The circular cross-section of the microchannel plays an important role in recapitulating the physiological relevance of an in-vitro model of blood vessels. In this study, we demonstrate a simple process for turning the single depth of a rectangular microchannel of the mold into a multi-depth circular polydimethylsiloxane (PDMS) microchannel of the replica. The method uses inflated air pressure to deform a partially cured PDMS with simple bench-top equipment. We can produce a wide range of circular microchannels with diameters from 100 μm to 500 μm. Based on the self-aligning and bonding principles of partially cured PDMS, this technique can eliminate oxygen plasma bonding and tedious alignment processes. The bonding strength based on the partially cured PDMS can obtain 375 kPa, which is comparable with oxygen plasma bonding. The fabrication parameters, such as the partial curing time of PDMS and the applied pressure, are controlled well to obtain various channel geometries from elliptical to circular cross-sections. We applied the fabrication scheme to reconstruct the geometry of the thrombosis blood vessel in a microfluidic device. Four different geometries of stenosis vessels were successfully produced for investigating the influence of the occlusion shape on thrombus formation. The platelet deposition along the post-stenosis channels was quantitatively observed under time-lapse fluorescence microscopy. Our results indicate that the accumulation of platelets for downstream stenosis is slower and more stable for a concentric stenosis lesion than for an eccentric stenosis lesion. This thrombosis device can be used in real-time clotting analysis models and for antithrombotic drug testing.