Abstract

One goal of synthetic biology is to design and build genetic circuits in living cells for a range of applications. Our incomplete knowledge of the effects of metabolic load and biological “crosstalk” on the host cell make it difficult to construct multilevel genetic logic circuits in a single cell, limiting the scalability of engineered biological systems. Microfluidic technologies provide reliable and scalable construction of synthetic biological systems by allowing compartmentalization of cells encoding simple genetic circuits and the spatiotemporal control of communication among these cells. This control is achieved via valves on the microfluidics chip which restrict fluid flow when activated. We describe a Computer Aided Design (CAD) framework called “Fluigi” for optimizing the layout of genetic circuits on a microfluidic chip, generating the control sequence of the associated signaling fluid valves, and simulating the behavior of the configured biological circuits. We demonstrate the capabilities of Fluigi on a set of Boolean algebraic benchmark circuits found in both synthetic biology and electrical engineering and a set of assay-based benchmark circuits. The integration of microfluidics and synthetic biology has the capability to increase the scale of engineered biological systems for applications in DNA assembly, biosensors, and screening assays for novel orthogonal genetic parts.

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