Synthesis of Cyberphysical Digital-Microfluidic Biochips for Real-Time Quantitative Analysis

Abstract

Considerable effort has recently been directed toward the implementation of molecular bioassays on digital-microfluidic biochips (DMFBs). However, today’s solutions suffer from the drawback that multiple sample pathways are not supported and on-chip reconfigurable devices are not efficiently exploited. As a result, impractical manual intervention is needed to process protocols for gene-expression analysis. To overcome this problem, we first describe our benchtop experimental studies to understand gene-expression analysis and its relationship to the biochip design specification. We then introduce an integrated framework for quantitative gene-expression analysis using DMFBs. The proposed framework includes: 1) a spatial-reconfiguration technique that incorporates resource-sharing specifications into the synthesis flow; 2) an interactive firmware that collects and analyzes sensor data based on quantitative polymerase chain reaction; and 3) a real-time resource-allocation scheme that responds promptly to decisions about the protocol flow received from the firmware layer. This framework is combined with cyberphysical integration to develop the first design-automation framework for quantitative gene expression. Simulation results show that our adaptive framework efficiently utilizes on-chip resources to reduce time-to-result without sacrificing the chip’s lifetime.