PROtein SEquencing (PROSE) Program Announcement

The Defense Advanced Research Projects Agency (DARPA), through its Microsystems Technology Office (MTO), has announced the PROtein SEquencing (PROSE) Program under Program Announcement DARPA-PA-25-06. This initiative is aimed at addressing the Department of Defense’s (DoD) critical need for rapid identification and sequencing of unknown protein-based biothreats. Current detection technologies fall short in identifying threats that lack genetic material or feature unreadable post-translational modifications. By developing a high-throughput sequencing technology capable of reading these complex proteins, the PROSE program intends to enhance DoD capabilities in threat detection, warfighter health, intelligence gathering, and operational decision-making. PROSE is a 36-month research program structured in two phases: a 15-month Phase 1 focused on the development of novel protein read elements, and a 21-month Phase 2 dedicated to integrating high-accuracy microsystem architectures. Participants will develop innovative devices and systems capable of sequencing protein molecules at high accuracy (≥ 99%) and high throughput (≥ 10^10 letters/day), even as the chemical complexity of amino acid sequences continues to expand through synthetic biology. The program specifically excludes methods reliant on reference sequences and approaches that lack scalability or fail to develop a microsystem. Eligible proposers must demonstrate a plan to co-develop advanced read elements, novel microsystem designs, and robust algorithms for letter calling. Participants are expected to deliver integrated systems that can read protein sequences of at least 300 units with a capability to recognize at least 100 letters by the end of Phase 2. Throughout the project, performers will collaborate with an Independent Verification and Validation (IV&V) team, which will support the evaluation of technologies using a library of control proteins. Design reviews, hardware and software deliverables, commercialization strategies, and five major capability demonstrations are core milestones in the program. Proposals are evaluated on three primary criteria: scientific and technical merit, relevance to the DARPA mission, and budget and cost realism. The program encourages submissions from a wide range of U.S. and non-U.S. sources, including small businesses, minority institutions, and universities, although UARCs, FFRDCs, and government labs are restricted from proposing as performers. IP rights developed under this program remain with the performers, with the government receiving a non-exclusive license for government use. The abstract submission deadline is July 24, 2025, at 1:00 PM ET. Full proposals are due by August 28, 2025, at 4:00 PM ET. Notification of intent to propose must be submitted by August 14, 2025, at 4:00 PM ET, and the Q&A period also closes on that date at 1:00 PM ET. Proposals must comply with Controlled Unclassified Information (CUI) handling requirements as specified in the PROSE CUI Guide. The anticipated award instrument is an Other Transaction for Research under 10 U.S.C. § 4021, with multiple awards expected. All proposal-related questions must be directed to PROSE@darpa.mil.

Include prior results or modeling/simulation to support technical claims. Articulate a complete commercialization plan. Clearly define major technical risks and mitigation strategies.