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Automated Cell-free Protein Synthesis for Distributed Biomanufacturing

da Silva, S. J. R.; Simchi, M.; Matthews, Q.; Bayat, P.; Vigar, J. R. J.; Singh, S.; Iwe, I. A.; Santos, B. N. R.; Duplat, D.; Benitez Bolivar, P.; Bozovicar, K.; Fobel, R.; Tinafar, A.; Cicek, S.; Guo, Y.; Masum, F.; Cranmer, L. A.; Norouzi, M.; Mendes, R. P. G.; Leon, C.; C. Machado, L.; Wu, W.; Talebi, S.; Klenov, A.; Rayhan, A.; Magalhaes, J. J. F.; Narvaez, C. F.; Charania, M.; Paiva, M. H. S.; Wallau, G. d. L.; Mazzulli, T.; Sinton, D.; Bernal, A.; Gonzalez, C.; Pena, L.; Pardee, K.

2025-10-17 public and global health
10.1101/2025.10.15.25338083 medRxiv
Show abstract

Recombinant proteins are fundamental to modern medicine, enabling research, diagnostics, and drug discovery, yet their access is often restricted by centralized manufacturing and cold-chain distribution. Decentralized, on-site biomanufacturing can enable research, provide resilience, and advance personalized medicine. Here, we introduce MANGO (MANufacturing on the GO), a purpose-built, open-source device designed for automated, benchtop cell-free protein synthesis and purification. Computer-controlled synthesis and purification are mediated through biomedical-grade pumps, valves, and a microchannel manifold, enabling rapid protein production directly at the point-of-use. To demonstrate MANGOs utility, we produced and validated a diverse range of proteins, including nanobodies against SARS-CoV-2 and TNF, cloning enzymes, and diagnostic enzymes, with performance equivalent to their commercial counterparts. We further deployed MANGO in Brazil and Colombia to support patient trials for SARS-CoV-2 and dengue virus diagnostics. These results establish MANGO as a low-cost, portable platform that can democratize access to bioreagents in both high- and low-resource settings and, ultimately, expand participation in the bioeconomy.

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