Abstract The advance of biotechnology is dependent on approaches for rapidly iterating through genetically engineered enzymes and pathways. While computational and gene synthesis techniques have seen considerable innovation in the last few decades, screening variants for desired activities has lagged behind, with few notable advances. Indeed, microwell plates, a nearly 60-year-old technology, remain the dominant tool. The objective of Fluid Discovery is to transform this field by introducing a novel screening paradigm based on precision nanoliter fluid handling; this groundbreaking approach will increase the scale of screens that can be performed by 100x while driving down costs. In addition to a fundamentally new hardware architecture for scalable screening, our approach implements label-free mass spectrometry and computational techniques to enable discovery of unanticipated enzyme activities and enhancements. Fluid Discovery is founded by the inventor of the key technologies and, thus, is in a prime position to advance this space and become a commercial success. This grant will fuel the development of the first alpha prototype that can be run by early access customers, to illustrate the utility of the technology, its appropriateness for industrial research and development, and its maturity for the market; all of which will be necessary to raise private funding for commercial scale up. Our team includes experts in pharmaceutical development (Dr. Prince), commercialization (Dr. Sunkara), and science and technology (Dr. Abate). This team has a demonstrated track record of commercial success, having built companies with current value >$1 billion. Fluid Discovery’s technology will allow engineering campaigns infeasible with today’s technology at a price point accessible to biotech startups and academic research labs, and with transformative efficiencies attractive to Big Pharma.

Narrative The objective of this grant is to fuel the development of an innovative nanoliter screening technology. This platform will increase, by orders of magnitude, the scale of screens that can be performed to enable efficient directed evolution of novel biocatalysts.