Defect-Tolerant Design and Optimization of a Digital Microfluidic Biochip for Protein Crystallization

Protein crystallization is a commonly used technique for protein analysis and subsequent drug design. It predicts the 3-D arrangement of the constituent amino acids, which in turn indicates the specific biological function of a protein. Protein crystallization experiments are typically carried out in well-plates in the laboratory. As a result, these experiments are slow, expensive, and error-prone due to the need for repeated human intervention. Recently, droplet-based digitalmicrofluidics have been used for executing protein assays on a chip. Protein samples in the form of nanoliter-volume droplets are manipulated using the principle of electrowetting-on-dielectric. We present the design of a multi-well-plate microfluidic biochip for protein crystallization; this biochip can transfer protein samples, prepare candidate solutions, and carry out crystallization automatically. To reduce the manufacturing cost of such devices, we present an efficient algorithm to generate a pin-assignment plan for the proposed design. The resulting biochip enables control of a large number of on-chip electrodes using only a small number of pins. Based on the pin-constrained chip design, we present an efficient shuttle-passenger-like droplet manipulation method and test procedure to achieve high-throughput and defect-tolerant well loading.