A Framework for Automated Correctness Checking of Biochemical Protocol Realizations on Digital Microfluidic Biochips

Abstract: Recent advances in digital microfluidic (DMF) technologies offer a promising platform for a wide variety of biochemical applications, such as DNA analysis, automated drug discovery, and toxicity monitoring. For on-chip implementation of complex bioassays, automated synthesis tools have been developed to meet the design challenges. Currently, the synthesis tools pass through a number of complex design steps to realize a given biochemical protocol on a target DMF architecture. Thus, design errors can arise during the synthesis steps. Before deploying a DMF biochip on a safety critical system, it is necessary to ensure that the desired biochemical protocol has been correctly implemented, i.e., the synthesized output (actuation sequences for the biochip) is free from any design or realization errors. We propose a symbolic constraint-based analysis framework for checking the correctness of a synthesized biochemical protocol with respect to the original design specification. The verification scheme based on this framework can detect several post-synthesis fluidic violations and realization errors in 2D-array based or pin-constrained biochips as well as in cyberphysical systems. It further generates diagnostic feedback for error localization. We present experimental results on the polymerase chain reaction (PCR) and in-vitro multiplexed bioassays to demonstrate the proposed verification approach.