PROJECT SUMMARY: The Scripps Research Molecular Screening Center (SRMSC) is requesting funds for the purchase of a MaxCyte ExPERT STx® Scalable Transfection instrument to replace an older unit which has reached end-of-life service. The MaxCyte is an electroporation instrument capable of producing highly efficient transfections of plasmid DNA, siRNA, RNAi and more, while maintaining high cell viability. Electroporation uses electrical pulses to create temporary pores in cell membranes through which substances can pass into cells to create either transient or stable transfections of all cell types. Although lipid and PEI reagent-based transfections are adequate for small batch production as used in bench-top research, their use for large batch transfections becomes cost prohibitive especially for high throughput screening (HTS) needs or extensive research projects that require the consistency of a large single batch transfection to sustain longer term research needs. The current MaxCyte STX instrument was acquired in 2006 in support of NIH's MPLCN program, but after ~15-years of usage, the OEM vendor has decided to discontinue support (December 31, 2021) and will no longer sell, lease, repair, upgrade or provide maintenance to this end-of-life instrument. While there are several manufacturers of electroporation instruments, the MaxCyte STX is uniquely suited to the magnitude of the SRMSC operations and is designed for a niche that requires the agility to perform micro- to macro- scale transfections in support of our AUT users and HTS needs. Not surprisingly, many comprehensive HTS screening centers (both Pharma & academic) employ electroporation transfection systems. High Throughput Screening (HTS) in transient cell-based expression systems has become an indispensable tool for probe development and drug discovery and the Scripps Research Molecular Screening Center (SRMSC) has been in the forefront in serving NIH investigators at Scripps and other academic institutes. Since establishing operations in 2005, we have screened over 370 targets to generate more than 100 million data points for our collaborators at Scripps and at other institutions. Over 136 scientific papers and numerous presentations demonstrate our ability to produce excellent research-driven data. Our screening results have led to the development of over 77 bioactive molecular probes against novel drug targets including some that have successfully advanced as INDs for clinical trial testing and eventually NDA/FDA drugs (e.g., ZEPOSIA® (a.k.a. ozanimod). The MaxCyte STX will allow SRMSC to fulfill its current HTS screening obligations and continue to serve the NIH community at large with its comprehensive HTS drug discovery capabilities.