DARPA-SN-25-92.pdf

DARPA-SN-25-92

Special Notice Request for Information:

Sequence Defined Polymer Synthesis with Molecular Machines for Microsystems Applications

DARPA-SN-25-92

July 25, 2025

Defense Advanced Research Projects Agency Microsystems Technology Office 675 North Randolph Street Arlington, VA 22203-2114

Request for Information (RFI) Special Notice DARPA-SN-25-92

Sequence Defined Polymer Synthesis with Molecular Machines for Microsystems Applications Defense Advanced Research Projects Agency (DARPA)

Microsystems Technology Office (MTO)

Posting Date: July 25, 2025 Responses Due: September 22, 2025, at 5:00 p.m. Eastern Time (ET) Technical POC: Dr. John M. Hoffman, MTO Program Manager E-mail: DARPA-SN-25-92@darpa.mil

RFI DESCRIPTION:

The Defense Advanced Research Projects Agency (DARPA) Microsystems Technology Office (MTO) seeks information on potential approaches, platforms, and systems for the templated synthesis of sequence-defined polymers using novel synthetic methods and/or molecular machines. DARPA is interested in disruptive ideas and concepts significantly beyond current practice. Approaches resulting in incremental improvement and mere description of existing capabilities or prior work without a clear vision for advancing the field are not of interest.

The goals of this Request for Information (RFI) include, but are not limited to:

Molecular machines, templated synthesis, and/or biologically-inspired approaches for the production of sequence-defined macromolecules that would enable asymmetric technologies for DoD applications

Organic, inorganic, and/or hybrid polymers relevant to the development of novel catalysts, optical materials, textiles, microsystems manufacturing, or other DoD applications

Desired characteristics of synthetic systems, molecular machines, and polymer performance along with associated metrics

Analytical testing approaches for performance characterization and system/polymer validation and verification.

Responses to this RFI may be used to inform future program development.

BACKGROUND:

The precise synthesis of sequence-defined polymers holds the potential to revolutionize a wide variety of fields by enabling unprecedented control over physical properties at the molecular scale. In nature, the templated synthesis of perfectly sequence-defined polymers enables essential functions such as information storage in the form of DNA and chemical catalysis in the form of protein-based enzymes.

Within the cell, the template-directed synthesis of biological polymers is accomplished via molecular machines such as DNA polymerase and ribosomes. These machines have evolved unique performance characteristics such as exquisite substrate recognition, very fast reaction kinetics, low error rates, and high processivity. However, these machines are limited in the breadth of chemistries they can realize.

Despite decades of research, synthetic chemistry methods still lag behind the efficiency and versatility of biological systems, and struggle with throughput, polymer length, and the error rate. Conversely, the repurposing of natural molecular machines for the synthesis of chemically diverse sequence defined polymers outside of the cell has largely failed for several reasons. These include lack of robustness, limited mailto:DARPA-SN-25-92@darpa.mil chemical bond forming potential (i.e. peptide and phosphodiester bonds), solvent incompatibility, scalability and cost.

DARPA seeks to understand potential novel methods, approaches and platforms capable of marrying the exquisite selectivity, processivity, and throughput of molecular machines with the chemical diversity, scalability, and robustness of synthetic chemistry methods to produce novel, high-value sequence defined polymers.

REQUESTED INFORMATION:

DARPA seeks innovative insights to address the technical challenge areas described below. Responses are welcome from all capable sources including, but not limited to, private or public companies, individuals, universities, university-affiliated research centers, not-for-profit research institutions, and U.S.

Government-sponsored labs. Responses can address any or all of the following areas:

1. What are the current limitations in engineering processive, sequence-defined polymer-generating molecular machines? Of interest are methodologies to developing machines either found in nature or designed de novo. This includes novel design algorithms, directed-evolution approaches, and high-throughput screening approaches.

2. What are the current limitations in purely synthetic techniques? Of interest are methodologies in iterative step growth, iterative exponential growth, template-assisted synthesis, and precise macromonomer approaches.

3. What microsystems applications are uniquely enabled by sequence defined polymers and what role does the polymer play? Of interest are approaches to fabricating novel device architectures and novel materials with physical properties that cannot be realized any other way.

SUBMISSION INSTRUCTIONS:

Responses to this RFI should be submitted no later than 5:00 p.m. ET on September 22, 2025.

Unclassified responses to this RFI should be submitted to DARPA-SN-25-92@darpa.mil. NO CLASSIFIED INFORMATION SHOULD BE SENT TO DARPA-SN-25-92@darpa.mil.

Classified responses should be coordinated with DARPA prior to submission. Respondents wishing to provide a classified response should send an e-mail to DARPA-SN-25-92@darpa.mil with the subject line “Classified Coordination Requested”. Respondents should allow at least three (3) business days for processing requests. NO CLASSIFIED INFORMATION SHOULD BE SENT TO DARPA-SN-25-92@darpa.mil.

To the maximum extent possible, respondents should submit non-proprietary information. If proprietary information is submitted, it must be appropriately and specifically marked. It is the respondent’s responsibility to clearly define to the Government what is considered proprietary data. Any proprietary information should be clearly labeled as “Proprietary.” DARPA will disclose submission contents only for the purpose of review by DARPA staff, other Government agencies, or DARPA Support Contractors/SETAs.

NOTE: DARPA intends to conduct individual discussions with respondents as necessary to gain a full understanding of the technical and partnership models submitted. DARPA will contact respondents individually via e-mail.

mailto:DARPA-SN-25-92@darpa.mil mailto:DARPA-SN-25-92@darpa.mil

FORMAT INSTRUCTIONS:

Responses to the RFI should be concise. Respondents should submit a single integrated response addressing the areas described above. DARPA will only review responses submitted as an unprotected Microsoft Word/PowerPoint document or PDF file. Each response is limited to no more than 8 pages using 11-point font and 1-inch margins on 8.5-inch by 11-inch page size. Effective responses that can be provided in fewer than 8 pages are encouraged. Any submitted material in excess of these limits will not be reviewed.

Responses should adhere to the following formatting instructions:

1. Cover page (1 page)

a. Title

b. Organization(s)

c. Respondent’s technical and administrative points of contact (names, addresses, phone and fax numbers, and email addresses)

2. Technical challenge areas (2 pages maximum per technical challenge area)

a. A discussion of the capabilities/challenges addressed (from your perspective)

b. Theoretical and/or simulation discussion

c. Development strategy, especially versus requested metrics

d. Identify current data (if any)

e. Estimated time to availability and risk assessment (technical and other)

3. References (1 page)

a. All references to previously published work should be contained within this space.

4. OPTIONAL: Summary slides (1 summary slide and 1 technical description slide per technical challenge area)

a. Responses are requested to include slides that summarizes the main idea and development strategy. The purpose of these slides is to visually and succinctly indicate the new insights, main objectives, underlying technical mechanisms, fundamental assumptions and limitations, key innovations, expected impact, and/or other unique aspects of the response.

DARPACONNECT:

Entities who have not worked with DARPA before are encouraged to learn more about DARPAConnect, an initiative established to facilitate collaboration between DARPA and potential performers. The DARPAConnect team offers customized support, resources, and guidance on how to prepare your ideas for high-impact conversations with DARPA program managers. Please visit DARPAConnect.us to access a digital hub of online resources, including a curriculum for self-paced learning, personalized support, and in-person and virtual events. In addition to the self-paced online materials, the DARPAConnect team is able to schedule one-on-one conversations to discuss your specific ideas, questions, and paths to DARPA.

You can use the contact form at DARPAConnect.us or email the DARPAConnect team directly at darpaconnect@darpa.mil to request assistance.

ADMINISTRATIVE:

This announcement contains all information required to submit a response. No additional forms, kits, or other materials are needed. All administrative and technical questions should be directed to DARPA-SN- 25-92@darpa.mil. Please refer to the Special Notice number (DARPA-SN-25-92) in all correspondence.

https://www.darpaconnect.us/ mailto:darpaconnect@darpa.mil

This RFI is issued solely for information and program planning purposes and does not constitute a formal solicitation for proposals or proposal abstracts; any so sent will be disregarded. In accordance with FAR 15.201(e), responses to this notice are not offers and cannot be accepted by the Government to form a binding contract. Submission of a response is strictly voluntary and is not required to propose to subsequent Announcements (if any) or Solicitations (if any) on this topic. DARPA will not provide reimbursement for costs incurred in responding to this RFI. Respondents are advised that DARPA is under no obligation to acknowledge receipt of the information received or provide feedback to respondents with respect to any information submitted under this RFI.