Critical Illness Immunological Reprogramming and Control Point Learning Engine (CIRCLE) Program is a grant from the Advanced Research Projects Agency for Health (ARPA-H) that funds the development of AI-powered digital twin capabilities to transform critical care medicine.

The program aims to create tools that track and modulate the immune system in real time, enabling clinicians in intensive care units to intervene more precisely when inflammatory responses threaten organ failure. With a total program budget of over $100 million across multiple awards, CIRCLE seeks to advance immune system diagnostics, computational modeling, and next-generation immunotherapies for critically ill patients.

The application deadline is March 30, 2026. Eligible applicants include academic institutions, non-profit organizations, and corporate entities with expertise in clinical critical care, computational modeling, and immune system interventions.

Critical Illness Immunological Reprogramming and Control Point Learning Engine What if we could harness the immune system using AI for faster and better critical care? 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 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. 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. 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. Solution Summary Due: March 30, 2026, 1:00PM ET A solution summary is required to submit a proposal.

Proposal Due: 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. Review Solicitation Details 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. Review FAQs and Ask A Question This is an optional event for the proposer community to learn more about this opportunity, ask questions, and make connections.

Event date: March 11, 2026 | 9am - 5pm ET 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. Register for Proposers’ Day 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.

"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. ” ARPA-H launches program to revolutionize critical care and help prevent life-threatening events