BRAIN Initiative: Next-Generation Devices for Recording and Modulation in the Human Central Nervous System (UG3/UH3 Clinical Trial Optional) | RFA NS 25 021

Opportunity Information: Apply for RFA NS 25 021

The National Institutes of Health is offering a BRAIN Initiative funding opportunity focused on moving next-generation devices for recording from and modulating activity in the human central nervous system closer to real clinical use. The core aim is translational: taking promising neurotechnology concepts and pushing them through the practical development steps needed to become therapeutic or diagnostic devices for neurological or neuromuscular disorders. This includes not only engineering progress, but also the regulatory, safety, and early clinical work that is often the bottleneck between a research prototype and a device that can actually be evaluated in people.

This opportunity uses the UG3/UH3 phased cooperative agreement structure and is labeled “Clinical Trial Optional,” meaning applicants may propose a project that includes a small clinical study, but the announcement is designed to support that pathway when it is justified. In the UG3 phase, teams are generally expected to complete key, well-defined milestone work that reduces risk and proves readiness to move into humans, such as building and implementing a clinical prototype, completing non-clinical safety and efficacy testing, and conducting design verification and validation activities. A major goal can be to prepare for and obtain an Investigational Device Exemption (IDE) for a Significant Risk study, which is the FDA pathway typically required when an invasive or higher-risk device is being studied in human participants. If UG3 milestones are met, the project can transition to the UH3 phase, which supports the subsequent small clinical study intended to answer questions that cannot realistically be resolved through additional bench testing or animal studies. The program explicitly emphasizes that the clinical work should be driven by novelty or intended use cases where human data are necessary to finalize device function, feasibility, or design decisions.

A defining feature of this funding announcement is that it is milestone-driven and uses a cooperative agreement mechanism. In practice, that means NIH program staff are not passive funders; they are expected to take an active role in shaping the final project plan before an award is made and in monitoring progress after funding begins. Applicants should expect a negotiated set of clear, quantitative milestones and decision points, and continued funding is typically tied to meeting those milestones. This structure is meant to keep projects tightly focused on the translational deliverables needed for regulatory readiness and early human evaluation, rather than open-ended exploratory research.

Eligibility is broad across U.S.-based organizations and spans public and private institutions of higher education, nonprofits (with or without 501(c)(3) status), for-profit organizations (other than small businesses), small businesses, and multiple levels of government (state, county, city/township, special districts), along with independent school districts and public housing authorities/Indian housing authorities. The announcement also calls out additional eligible applicant types such as Historically Black Colleges and Universities, Hispanic-serving institutions, Tribally Controlled Colleges and Universities, Alaska Native and Native Hawaiian Serving Institutions, and Asian American Native American Pacific Islander Serving Institutions, as well as faith-based or community-based organizations, eligible federal agencies, regional organizations, and U.S. territories or possessions. At the same time, the FOA draws clear boundaries around foreign participation: non-U.S. (foreign) organizations are not eligible to apply, and non-domestic components of U.S. organizations are not eligible to apply. However, “foreign components” as defined by NIH policy are allowed, which typically means a U.S. applicant can include certain discrete project elements performed outside the U.S. if they meet NIH requirements and are well-justified.

Administrative details provided in the source include the funding opportunity title “BRAIN Initiative: Next-Generation Devices for Recording and Modulation in the Human Central Nervous System (UG3/UH3 Clinical Trial Optional),” funding opportunity number RFA-NS-25-021, and the sponsoring agency as NIH. The mechanism is a cooperative agreement, and the opportunity sits within NIH health-related assistance listings (CFDA numbers provided include 93.173, 93.213, 93.242, 93.273, 93.279, 93.286, 93.853, 93.865, 93.866, and 93.867). The original closing date listed is 2026-09-28, and the opportunity was created on 2024-11-05. The award ceiling and expected number of awards are not specified in the provided data, which usually means applicants need to consult the full FOA text for budget guidance, project period expectations, and any institute-specific caps or constraints.

Overall, the opportunity is designed for teams that are ready to do the hard translational work: turning advanced human CNS recording or modulation technologies into clinically plausible devices, generating the required non-clinical evidence, completing verification and validation, navigating IDE preparation for significant risk studies when applicable, and then running a small, targeted clinical study to obtain the specific human data needed to lock down device design or function.

• The National Institutes of Health in the education, health, income security and social services sector is offering a public funding opportunity titled "BRAIN Initiative: Next-Generation Devices for Recording and Modulation in the Human Central Nervous System (UG3/UH3 Clinical Trial Optional)" and is now available to receive applicants.
• Interested and eligible applicants and submit their applications by referencing the CFDA number(s): 93.173, 93.213, 93.242, 93.273, 93.279, 93.286, 93.853, 93.865, 93.866, 93.867.
• This funding opportunity was created on 2024-11-05.
• Applicants must submit their applications by 2026-09-28. (Agency may still review applications by suitable applicants for the remaining/unused allocated funding in 2026.)
• Eligible applicants include: State governments, County governments, City or township governments, Special district governments, Independent school districts, Public and State controlled institutions of higher education, Native American tribal governments (Federally recognized), Public housing authorities/Indian housing authorities, Native American tribal organizations (other than Federally recognized tribal governments), Nonprofits having a 501 (c) (3) status with the IRS, other than institutions of higher education, Nonprofits that do not have a 501 (c) (3) status with the IRS, other than institutions of higher education, Private institutions of higher education, For-profit organizations other than small businesses, Small businesses, Others.

Apply for RFA NS 25 021

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