Proton exchange membrane electrolyzers (PEMs) are an integral technology for driving the transition to a renewable energy economy. For water splitting and the production of green hydrogen, PEMs are the industry standard due to their relatively high efficiency and flexible operating conditions. Water splitting PEMs operate under acidic conditions, and typically rely on Pt catalysts at the cathode where protons are reduced to H2 via the hydrogen evolution reaction (HER), and IrOx catalysts at the anode, where water is oxidized to O2 via the oxygen evolution reaction (OER). State-of-the-art PEM electrolyzers for CO2 utilization also rely on IrOx OER catalysts, which exhibit reasonable activity but excellent stability in the acidic conditions of PEM electrolyzers. Yet, the cost of iridium as a raw material has increased dramatically in the past few years (from ~$1,000 per oz to ~$4,000 per oz), while total global production is limited primarily to South Africa and has remained constant around eight tons per year (approximately one ton per year is available for PEM electrolyzers). Regardless of iridiums price, which appears poised to continue increasing with electrolyzer deployment, the total quantity of iridium mined each year is significantly short of what is required to meet projected PEM electolyzer demands throughout the next decade and beyond. Specifically, one ton of raw iridium would be enough to supply catalysts for 2 GW of electrolyzers (assuming 2 mg cm2 loading), while annual water electrolyzer projections average ~10 GW in 2025 and ~30 GW in 2030, with deployments accelerating. Even with improved loading efficiency, an OER catalyst replacement for IrOx will be necessary to approach modest projections for electrolyzer deployment. If electrolysis is to achieve reasonable scale, a new anode catalyst must be discovered to replace IrOx. Through our proprietary Megalibrary platform, Stoicheia, Inc. is poised to rapidly accelerate the discovery of a PEM anode catalyst that replaces IrOx as the industry standard. The Megalibrary platform enables the rapid synthesis and characterization of hundreds of thousands of unique materials in a single experiment. Using parallelized tip-defined nanoparticle synthesis, we prepare 2 cm x 2 cm chips containing well-defined polyelemental nanoparticles (in the design space consisting of IrCuCoNiAuAgPdPtSnInFe and their oxides, with an ever-expanding materials palette) with controlled chemical gradients across the substrate. Accordingly, Stoicheia can positionally encode monodisperse nanoparticles with arbitrary component ratios and known chemical gradients across a substrate. Coupled with high-throughput electrochemical screening, this synthetic technique enables the generation of massive structure-function datasets, leading to the rapid identification of highly active and selective electrocatalysts for OER. Specifically, we propose two methods of high-throughput electrochemical characterization of catalyst candidates: 1) optical screening of O2 formation over catalyst materials exposed to relevant OER reaction conditions within micro-scale reactors, and 2) scanning droplet cell electrochemistry, in which a miniaturized 3-electrode cell is contained in a small droplet (0.1-0.5 mm in diameter) of constantly flowing electrolyte over catalyst materials. Optical screening will be enabled by microfluidic devices, wherein electrolyte can be physically isolated within ~50 µm catalyst-containing reaction chambers. Upon application of a potential, O2 formation will be monitored by fluorescent probes and quantified via optical microscopy. This method enables the generation of tens of thousands of high-quality data points in minutes. Taken together, our high-throughput synthesis and screening of combinatorial material libraries will enable the discovery of low-Ir electrocatalysts for OER, which is critical to the deployment of water and CO2 electrolyzers at scale.