Design, Optimization and Test Methods for Robust Digital Microfluidic Biochips

Abstract

<p>Microfluidic biochips are now being used for biochemical applications such as high-throughput DNA sequencing, point-of-care clinical diagnostics, and immunoassays. In particular, digital microfluidic biochips (DMFBs) are especially promising. They manipulate liquid as discrete droplets of nanoliter or picoliter volumes based on the principle of electrowetting-on-dielectric under voltage-based electrode actuation. DMFBs have been commercially adopted for sample preparation and clinical diagnostics. Techniques have also been developed for high-level synthesis, module placement, and droplet routing.</p><p>However, reliability is a major concern in the use of DMFBs for laboratory protocols. In addition to manufacturing defects and imperfections, faults can also arise during a bioassay. For example, excessive or prolonged actuation voltage may lead to electrode breakdown and charge trapping, and DNA fouling may lead to the malfunction of electrodes. Faults may eventually result in errors in droplet operations. If an unexpected error appears during an experiment, the outcome of the experiment will be incorrect. The repetition of an experiment leads to wastage of valuable reagents and time.</p><p>Therefore, it is necessary to ensure the correctness of the hardware and bioassay execution on the biochip. In this thesis, we focus on three types of reliability: biochip testing, error/fault recovery, and fault-tolerant synthesis. First, when a biochip is fabricated, defects might occur in parts of the biochip. Therefore, our objective is to develop biochip testing methods to detect and locate faults. Second, to faults that appear during droplet operation or in the hardware, we develop error-recovery procedures and redundancy solutions. Finally, we develop fault-tolerant synthesis techniques so that even if faults occur during droplet operations (e.g., unbalance splitting), the bioassay can proceed unimpeded. The proposed solutions are applied to two new types of biochip platforms, namely micro-electrode-dot-array (MEDA) and digital acoustofluidics.</p>