Clogging-free continuous operation with whole blood in a radial pillar device (RAPID)

Pillar-based passive microfluidic devices combine the advantages of simple designs, small device footprint, and high selectivity for size-based separation of blood cells. Most of these device designs have been validated with dilute blood samples. Handling whole blood in pillar-based devices is extremely challenging due to clogging. The high proportion of cells (particularly red blood cells) in blood, the varying sizes and stiffness of the different blood cells, and the tendency of the cells to aggregate lead to clogging of the pillars within a short period. We recently reported a radial pillar device (RAPID) design for continuous and high throughput separation of multi-sized rigid polystyrene particles in a single experiment. In the current manuscript, we have given detailed guidelines to modify the design of RAPID for any application with deformable objects (e.g. cells). We have adapted RAPID to work with whole blood without any pre-processing steps. We were successful in operating the device with whole blood for almost 6 h, which is difficult to achieve with most pillar-based devices. The availability of multiple parallel paths for the cells and the provision for a self-generating cross flow in the device design were the main reasons behind the minimal clogging in our device. We also observed that a vibrator motor attached to the inlet tubing occasionally disturbed the cell clumps. As an illustration of the improved device design, we demonstrated up to similar to 60-fold enrichment of platelets.