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Here, we describe workflows to address the scale, speed and reproducibility of common in vitro protein testing methods, enabling at least an order of magnitude increase in throughput while reducing wetlab time. Semi-Automated Protein Production (SAPP) is a rapid, modular, scalable and cost-effective protocol, enabling up to milligram-scale protein production and standardized characterization \u2013 including yield, dispersity, and oligomeric state \u2013 of hundreds of designs per day, at the cost-equivalent of a few DNA oligos per construct. End-to-end protocol execution takes 48\u2009hours, with ~6\u2009hours spent benchside using standard laboratory equipment. We showcase the platform by rapidly screening redesigned fluorescent proteins, as well as identifying de novo binders that potently neutralize respiratory syncytial virus. We also developed a barcoding and demultiplexing protocol (DMX) to further reduce gene synthesis cost 5-fold by leveraging oligo pools as input DNA for the generation of thousands of sequence-verified arrayed clones. These protocols which combine\u00a0optimized molecular biology, automated analysis, and optional open-source robotics should be\u00a0widely adoptable, accelerating protein design.<\/jats:p>","DOI":"10.1038\/s41467-026-76740-9","type":"journal-article","created":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T11:05:07Z","timestamp":1787223907000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Accelerating protein design by scaling experimental characterization"],"prefix":"10.1038","volume":"17","author":[{"given":"Jason","family":"Qian","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lukas F.","family":"Milles","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2501-7875","authenticated-orcid":false,"given":"Basile I. 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