Efficient Regulation of Synthetic Biocircuits Using Droplet-Aliquot Operations on MEDA Biochips

Abstract

Microfluidic platforms have recently emerged as an invaluable component for studying synthetic biology as they are capable of emulating complex molecular networks of biological pathways (biocircuits) on a chip. A special type of biochemical assays, known as biocircuit-regulatory scanning (BRS) assays, is employed to regulate gene expression, enabling comprehensive exploration of related biocircuit parameters. Prior work has provided high-level design methodologies for implementing BRS; however, most of these methods are abstract and cannot be used in practice as they overlook the dynamics of interactions between the samples and the biochip. In this article, we address this limitation by providing a comprehensive framework that implements BRS assays. The proposed framework, named BioScan, includes: 1) a statistical method that selects suitable volumetric ratios of biochemicals used to execute a BRS assay; 2) a high-level synthesis method that generates the specifications of the target BRS assay; 3) a translation technique enabling implementation of BRS on a microelectrode-dot array (MEDA) biochip; and 4) a Dirichlet-regressor that constructs the parameter space of the associated biocircuit. Simulation results show that the proposed framework can efficiently perform parameter-space exploration (PSE) while significantly reducing completion time and reagent cost.