CIRCLE
Critical Illness Immunological Reprogramming and Control Point Learning Engine
What if we can harness the immune system using AI for faster and better critical care?
The Problem
- More than 7 million Americans are treated in the intensive care units (ICU) of hospitals each year. Many are critically ill with infections, severe injuries, complications of chronic disease, and other factors that elicit a response from the body’s immune system. The body’s immune response is pivotal in fighting disease; however, when immune and inflammatory responses go into overdrive, these normally beneficial mechanisms can lead to worse health outcomes, such as organ failure and death.
- Currently, clinicians lack the tools to accurately track the body’s rapidly changing immune response and therefore cannot intervene precisely or quickly enough to reduce inflammation before it damages organs.
- Today's critical care systems often miss opportunities to detect and treat these harmful changes in the immune system because inflammatory and immune responses are notoriously complex and because options to influence the immune system during critical illness are limited.
The Solution
- The Critical Illness Immunological Reprogramming and Control Point Learning Engine (CIRCLE) aims to develop new digital twin capabilities to treat critical illness using the latest in AI and diagnostics. This innovation will determine immune system control points that can enable better use of existing immunotherapies as well as next-generation interventions for critical care.
- CIRCLE seeks to unlock the ability to track and modulate the body’s immune response on a massive scale, giving clinicians AI-based tools for better diagnosis and care of critically ill patients.
Only ARPA-H can...
- Harness the power of American innovation to provide clinicians in the ICU with robust, data-driven tools to save more lives and improve the quality of life after critical illness.
- Leverage sophisticated immune system data collection combined with computational technologies to deliver actionable insights and to drive new therapies for life-saving critical care.
- Empower the best technical experts to unravel the complexity of the immune system and develop innovative strategies for critical care that could eventually also be used to treat a host of chronic inflammatory conditions beyond critical illness.
- Catalyze early integration of commercialization and clinical translation efforts to accelerate the transition of these innovations to intensivists and their critically ill patients.
Solicitation
What ARPA-H needs to solve this problem
CIRCLE seeks teams with expertise in clinical care of critically ill patients, pre-clinical models of critical illness, data platforms, computational modeling, and relevant intervention modalities. Teams may include academic institutions, non-profit organizations, corporate entities, or a combination of highly skilled performers across sectors. The program has three technical areas to be addressed by integrated teams: creating and compiling datasets that characterize the progression and resolution of critical illness in real time; developing patient-specific computational models of their immune systems—called "digital twins"—that can provide reliable and actionable insights into the trajectory of their condition; and testing approaches to leverage these data and insights to modulate the immune system and provide sophisticated, individualized treatment. These efforts are expected to be combined with a robust commercialization plan to ensure rapid translation of CIRCLE’s output to benefit the American public.
Notice ID: ARPA-H-SOL-26-139
ARPA-H invites interested parties to review the solicitation, which is posted and maintained on SAM.gov. The solicitation outlines the opportunity and its requirements, key dates and deadlines, submission documents and templates, evaluation criteria for submissions, and information on how to apply.
Key Dates:
Solution Summary Due: Monday, March 30, 2026, 1:00PM ET
A solution summary is required to submit a proposal.
Proposal Due: Thursday, May 28, 2026, 1:00PM ET
After submission of a solution summary, proposers will either be encouraged or discouraged from submission of a full proposal. It is strongly recommended that only proposers who are encouraged to submit a full proposal do so.
Reminder: Dates are estimates and subject to change. Please reference the solicitation for the most up-to-date information.
Ready to apply? To submit a Solution Summary or Full Proposal, sign-in to the ARPA-H Solutions Portal.
Frequently Asked Questions
Review responses to common questions about this funding opportunity asked by others in the proposer community.
You can also ask a question.
Proposers’ Day
This is an optional event for the proposer community to learn more about this opportunity, ask questions, and make connections. This event is not intended for patients, patient advocates, the media, or general interest audiences.
Event date: March 11, 2026
Event location: Hybrid in Arlington, VA
Reminder, dates are subject to change. For the most up-to-date information about this event, reference the Special Notice (ARPA-H-SN-26-149) on SAM.gov.
Teaming
ARPA-H anticipates that teaming will be necessary to achieve the goals of CIRCLE. Prospective proposers are encouraged to form teams with varied technical expertise to submit a research proposal.
To facilitate this process, we have created a teaming page where prospective proposers can share their profiles and learn more about other interested parties.
Program Manager
"Our body’s immune system is one of the most powerful defenses against disease, but because it is extremely fast-moving, complex, and imperfect, it can paradoxically lead to critical illness, especially in individuals with chronic disease. CIRCLE seeks to unlock the ability to track and modulate the body’s immune response like never before and, in doing so, give clinicians the tools to prevent critical illness from claiming millions of lives.”
