The implementation of bioassays in pin-constrained digital microfluidic biochips may involve pin-actuation conflicts if the concurrently-implemented fluidic operations are not carefully synchronized. We propose a two-phase optimization method to identify and synchronize the fluidic operations that can be executed in parallel. The goal is to implement these fluidic operations without pin-actuation conflict, and minimize the duration of implementing the outcome sequence after synchronization. We also extend the synchronization method with the addition of a small number of control pins, in order to further minimize the completion time while avoiding pin-actuation conflicts. The effectiveness of the proposed synchronization method is demonstrated for a representative 3-plex assay performed on a commercial pin-constrained biochip and for multiplexed in-vitro diagnostics performed on an experimental pin-constrained biochip.

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 ¿digital¿ microfluidics 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.

Proteins crystallization is a commonly used technique for protein analysis and subsequent drug design. It predicts the three-dimensional arrangement of the constituent amino acids, which in turn indicates the specific biological function of a protein. Protein crystallization experiments are typically carried out manually on multi-well plates in the laboratory. These experiments are slow, expensive, and error-prone. 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 to achieve high-throughput and defect-tolerant well loading.

Thermal management is critical for integrated circuit (IC) design. With each new IC technology generation, feature sizes decrease, while operating speeds and package densities increase. These factors contribute to elevated die temperatures detrimental to circuit performance and reliability. Furthermore, hot spots due to spatially nonuniform heat flux in ICs can cause physical stress that further reduces reliability. While a number of chip cooling techniques have been proposed in the literature, most are still unable to address the varying thermal profiles of an IC and their capability to remove a large amount of heat is undermined by their lack of reconfigurability of flows. We present an alternative cooling technique based on a recently invented ";digital microfluidic"; platform. This novel digital fluid handling platform uses a phenomenon known as electrowetting, and allows for a vast array of discrete droplets of liquid, ranging from microliters to nanoliters, and potentially picoliters, to be independently moved along a substrate. While this technology was originally developed for a biological and chemical lab-on-a-chip, we show how it can be adapted to be used as a fully reconfigurable, adaptive cooling platform.

As microfluidics-based biochips become more complex, manufacturing yield will have significant influence on production volume and product cost. We propose an interstitial redundancy approach to enhance the yield of biochips that are based on droplet-based microfluidics. In this design method, spare cells are placed in the interstitial sites within the microfluidic array, and they replace neighboring faulty cells via local reconfiguration. The proposed design method is evaluated using a set of concurrent real-life bioassays.

Decreasing feature sizes and increasing package densities are making thermal issues extremely important in IC design. Uneven thermal maps and hot spots in ICs cause physical stress and performance degradation. Many MEMS and microfluidics-based solutions were proposed in the past. We present a cooling method based on high-speed electrowetting manipulation of discrete sub-microliter droplets under voltage control with volume flow rates in excess of 10 mL/min. We also propose a flow-rate feedback control where the hot areas get increased supply of droplets without the need for external sensors and electrothermocapillary control where hot areas attract droplets due to thermocapillarity and are returned to their reservoirs by electrowetting resulting in a self-contained and a self-regulated system.