Design of cyberphysical digital microfluidic biochips under completion-time uncertainties in fluidic operations

Abstract

Cyberphysical digital microfluidics enables the integration of fluid-handling operations, reaction-outcome detection, and software-based control in a biochip. However, synthesis algorithms and biochip design methods proposed in the literature are oblivious to completion-time uncertainties in fluidic operations, and they do not meet the requirements of cyberphysical integration in digital microfluidics. We present an operation-interdependency-aware synthesis method that uses frequency scaling and is responsive to uncertainties that are inherent in the completion times of fluidic operations such as mixing and thermal cycling. Using this design approach, we can carry out dynamic on-line decision making for the execution of fluidic operations in response to detector feedback. We use three common laboratorial protocols to demonstrate that, compared to uncertainty-oblivious biochip design, the proposed dynamic decision making approach is more effective in satisfying realistic physical constraints. As a result, it decreases the likelihood of erroneous reaction outcomes, and it leads to reduced time-to-results, less repetition of reaction steps, and less wastage of precious samples and reagents.