An automated and programmable microfluidic platform for combinatorial gene assembly and biosynthesis applications

HJ Science & Technology (HJS & T) and the Joint BioEnergy Institute (JBEI) propose to develop an automated, software-controlled, programmable, low-cost, and compact platform capable of running rapid and complex bioengineering processes and optimization of new biomanufacturing systems. Our approach combines the microfluidic automation technology of HJS & T with the novel synthetic biology technologies of combinatorial gene library generation, host transfection, and gene product screening at JBEI. Compared with conventional approaches, the integrated microfluidic technology has these advantages: 1) on-chip automation, eliminating the need for bulky and expensive sample handling robots, 2) small volume, reducing reagent consumption, and 3) multifunctional integration on a microchip level. In Phase I, we will establish the feasibility of the microfluidic automation technology by performing 1) construction of a combinatorial library of Green Fluorescent Protein and Red Fluorescent Protein gene expression cassettes, and 2) subsequent transformation into yeast cells/chromosomal integration and screening of expression products, on the same microfluidic chip in a fully automated format. In Phase II, we will realize a fully automated and programmable platform for the biological design-build-test cycle that encompasses 4 basic steps: 1) software DNA design; 2) DNA synthesis and assembly; 3) transfection/chromosomal integration and product screening; and 4) real-time feedback and control.