The Defense Advanced Research Projects Agency (DARPA), through its Microsystems Technology Office (MTO), has issued a new Program Announcement (DARPA-PA-25-06) for its PROtein SEquencing (PROSE) initiative. This bold program seeks to overcome longstanding challenges in protein sequencing by investing in novel microsystems and signal processing architectures.
PROSE responds to a pressing Department of Defense (DoD) need: the capability to detect and identify novel and engineered protein-based biothreats, which often evade traditional genomic identification methods. With the rising accessibility of AI-enabled protein design tools, the threat landscape is rapidly evolving, and DARPA aims to close this detection gap with high-throughput, high-accuracy sequencing technologies.
Solicitation Overview and Program Goals
The PROSE initiative is a 36-month effort focused on developing microsystems that can read long protein sequences, ≥300 units in length, with ≥99% accuracy and throughput of ≥10¹⁰ letters/day. This ambitious program requires a co-development approach involving advanced read element design, microsystem fabrication, and algorithmic innovation to decode the immense chemical complexity of proteins.
The program is divided into two phases:
- Phase 1 (15 months): Focuses on novel read element development and de-risking microsystem fabrication.
- Phase 2 (21 months): Concentrates on integrating and validating complete microsystem architectures capable of meeting throughput and accuracy targets.
Proposers are expected to address two core technical challenges:
- Development of molecular reader elements that can discriminate across a broad and evolving protein alphabet.
- Design and fabrication of microsystem architectures capable of translating these molecular interactions into accurate sequence data.
Key Dates and Deadlines
DARPA has established the following timeline for the PROSE solicitation:
- Abstracts Due: July 24, 2025, 1:00 PM ET
- Final Proposal Submission: On August 28, 2025, 4:00 PM ET
- Via the DARPA submission portal
- Notification of Intent to Propose: August 14, 2025, 4:00 PM ET
- Questions Due: August 14, 2025, 1:00 PM ET
Funding and Award Information
DARPA anticipates making multiple awards under this solicitation using Other Transactions (OTs) for Research under 10 U.S.C. § 4021. While no specific funding ceiling is listed, the awards are expected to cover the entire 36-month period, including both technical phases. There is potential for follow-on awards under 10 U.S.C. § 4023 for performers who demonstrate successful transition-ready technology.
Awardees will retain ownership of intellectual property and are expected to deliver hardware/software packages sufficient for independent government evaluation. Commercialization strategies will be assessed as part of proposal evaluation and are mandatory deliverables at two key milestones: Month 9 and Month 30.
Advancing Human Health and National Security
PROSE has the potential to revolutionize proteomics by enabling scalable, de novo protein sequencing at a level never before achieved. The ability to rapidly characterize proteins, including those with post-translational modifications and novel amino acid structures, will dramatically enhance our ability to identify unknown biothreats, support warfighter health, and enable real-time decision-making in complex field environments. Beyond defense, this foundational capability has significant implications for personalized medicine, infectious disease surveillance, and synthetic biology.
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