A Universal Platform for Ultrahigh-Throughput Biocatalyst Evolution With micro-Mass Spectrometry - Abstract The advancement of biotechnology relies on the ability to rapidly screen and optimize genetically engineered enzymes and pathways. While significant innovations have occurred in computational methods and gene synthesis, screening technologies have stagnated, with traditional microwell plates—developed nearly 60 years ago—still dominating the field. Fluid Discovery aims to disrupt this space with a novel screening platform based on precision nanoliter fluid handling, enabling screens at 100 times the scale of current methods while significantly reducing costs. This transformative approach combines scalable hardware, label-free mass spectrometry, and advanced computational techniques to uncover unanticipated enzyme activities and improvements. Founded by the inventor of these key technologies, Fluid Discovery is uniquely positioned to drive innovation and commercial success. This grant will support the development of commercial prototype for early access customers, demonstrating the technology's utility, industrial relevance, and market readiness—key milestones for securing private funding for commercial scale-up. The team comprises experts in pharmaceutical development (Dr. Prince), complex instrumentation development and commercialization (Dr. Kiani), and micro mass spectrometry (Dr. Abate). Together, they bring a proven track record of building successful companies valued at over $1 billion. Fluid Discovery’s platform will make high-throughput engineering campaigns practical and affordable for biotech startups and academic labs, while offering efficiencies that appeal to Big Pharma, transforming the landscape of enzyme and pathway optimization.