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Non-PDMS Biocompatible Alternatives for Organs-on-Chips

Description:

018 Non-PDMS Biocompatible Alternatives for Organs-on-Chips

Fast-Track proposals will not be accepted.

Number of anticipated awards: 1-2

Budget (total costs, per award): Phase I: $225,000 for 9 months; Phase II: $1,500,000 for 2 years

PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED.

Phase II information is provided only for informational purposes to assist Phase I offerors with their long-term strategic planning.

Summary:

The development of organs-on-chips, also known as microphysiological systems (MPS), has provided tools that can be used to investigate the effects of drugs, compounds and therapeutics on human tissues in vitro, providing information on safety and efficacy of promising compounds. They are also used to model a wide variety of disease states and investigate pathophysiology and disease mechanisms in novel ways. Organs-on-chips are often fabricated in part or wholly from polydimethylsiloxane (PDMS), an oxygen-permeable, optically-clear, non-flammable, non-toxic silicon-based organic polymer. However, PDMS absorbs or binds compounds or proteins under certain conditions, leading to loss of drugs or compounds that are introduced into the system. This is undesirable in the context of organs-on-chips as it reduces the ability

to accurately assess protein binding or calculate dosage ranges and responses of small molecules. Additionally, it can lead to cross-contamination of surrounding areas or tissues, reducing the reliability and predictivity of these systems for producing human-relevant drug responses.

Currently, researchers employ a variety of techniques to account for these shortcomings but these are expensive, time-consuming or not feasible to recreate due to the need for specialized equipment. Previously, NCATS has awarded supplemental funding for researchers funded under the Tissue Chips for Drug Screening program to address this issue, leading to development of some surface coating techniques and mathematical modeling to account for various adsorption properties of PDMS. An alternative material is desired for fabrication of organ chips for studies involving small molecule drugs/compounds and therapeutics. Replacement of PDMS will enable a broader range of experiments to be performed on tissue chip platforms and increase the utility of these systems to a wider community.

Topic Goals:

This topic aims to address a pressing need in the field of microphysiological systems (MPS), or organs-on-chips, to develop and produce a biocompatible alternative material that can be used in place of PDMS, which is a silicon-based material currently widely used in the fabrication of organ-on-chip platforms.

This goal will be achieved through the following:

(1) Fabrication of a biocompatible, non-toxic material that could feasibly provide an alternative to PDMS;

(2) Fabrication of a material that mimics the MPS-appropriate properties of PDMS such as gas permeability, optical clarity, non-toxicity, easy fabrication or availability, and predictable molecular binding;

(3) Demonstration of appropriate material properties and a lack of undesirable properties such as drug/compound absorption, channel cross-contamination, or high variability in binding of different compounds.

Phase I Activities and Expected Deliverables:

Development and production of an alternative material to PDMS that displays at least three of the following nine properties: o Optical clarity – proven ability of material to allow penetration of light at wavelengths of ~400-700nm.

o Gas permeability of oxygen and carbon dioxide.

o Non-toxic and biocompatible to a wide variety of iPSC-derived cells and tissues (5-10 cell/tissue types tested).

o Widely available/accessible, either whole or by material components.

o Proven reliable and reproducible manufacturing properties.

o Easily manipulated without the need for extensive specialist equipment (above what PDMS requires).

o Proven ability for manufacture of microfluidic components e.g. channels, ports, etc.

o Proven lack of microfluidic channel cross-contamination at distances of <20μm for a variety of substances e.g. cell culture media, drugs, compounds, small molecules etc.

o Reliable and predictable (variability <5%) molecular binding properties e.g. Log P, surface binding of plasma proteins etc.

o Non-reactive with other standard materials used in MPS production e.g. glass, PDMS, poly(methyl methacrylate) (PMMA) etc.

 

• Provide NCATS Program staff with all data and resources resulting from Phase I Activities and Deliverables.

 

Phase II Activities and Expected Deliverables:

Development of an alternative material to PDMS that displays an additional 4-6 of the following nine properties: o Optical clarity – proven ability of material to allow penetration of light at wavelengths of ~400-700nm.

o Gas permeability of oxygen and carbon dioxide.

o Non-toxic and biocompatible to a wide variety of iPSC-derived cells and tissues (5-10 cell/tissue types tested).

o Widely available/accessible, either whole or by material components.

o Proven reliable and reproducible manufacturing properties.

o Easily manipulated without the need for extensive specialist equipment (above what PDMS requires).

o Proven ability for manufacture of microfluidic components e.g. channels, ports, etc.

 

o Proven lack of microfluidic channel cross-contamination at distances of <20μm for a variety of substances e.g. cell culture media, drugs, compounds, small molecules etc.

o Reliable and predictable (variability <5%) molecular binding properties e.g. Log P, surface binding of plasma proteins etc.

o Non-reactive with other standard materials used in MPS production e.g. glass, PDMS, PMMA etc.

• Proven success in culturing at least 5 types of viable, mature and functional iPSC-derived cell types and/or tissues; o Viability as shown by standard tissue-appropriate markers of cell health and survival e.g. lack of apoptotic markers;

o Maturity as shown by presence of standard tissue-appropriate markers of mature phenotype or lack of dedifferentiation markers;

o Functionality as shown by presence of standard tissue-appropriate markers of cell functionality e.g. albumin secretion in hepatocytes; contractility in cardiomyocytes etc.

 

• Employment of Quality Assurance manufacture standards to ensure the validity of analytical and quantitative measurements.

• Proven success in fabrication and employment of the alternative material in a microfluidic setting.

• Proven success in replacement of PDMS in a microphysiological systems setting e.g. adaptation of existing MPS platforms with PDMS components replaced by the alternative material.

• Provide NCATS Program staff with all data and resources resulting from Phase II Activities and Deliverables.

• In the first year of the Phase II contract, provide the Program and contract officers with (a) letter(s) of commercial interest.

• In the second year of the Phase II contract, provide the Program and contract officers with (a) letter(s) of commercial commitment.

• Present Phase II findings and demonstrate final deliverables to the NCATS Program staff via webinar.

 

NATIONAL CANCER INSTITUTE (NCI)

The NCI is the Federal Government’s principal agency established to conduct and support cancer research, training, health information dissemination, and other related programs. As the effector of the National Cancer Program, the NCI supports a comprehensive approach to the problems of cancer through intensive investigation in the cause, diagnosis, prevention, early detection, and treatment of cancer, as well as the rehabilitation and continuing care of cancer patients and families of cancer patients. To speed the translation of research results into widespread application, the National Cancer Act of 1971 authorized a cancer control program to demonstrate and communicate to both the medical community and the general public the latest advances in cancer prevention and management. The NCI SBIR program acts as NCI’s catalyst of innovation for developing and commercializing novel technologies and products to research, prevent, diagnose, and treat cancer.

It is strongly suggested that potential offerors do not exceed the total costs (direct costs, facilities and administrative (F&A)/indirect costs, and fee) listed under each topic area.

Unless the Fast-Track option is specifically allowed as stated within the topic areas below, applicants are requested to submit only Phase I proposals in response to this solicitation.

NCI Phase IIB Bridge Award

The National Cancer Institute would like to provide notice of a recent funding opportunity entitled the SBIR Phase IIB Bridge Award. This notice is for informational purposes only and is not a call for Phase IIB Bridge Award proposals. This informational notice does not commit the government to making such awards to contract awardees.

Successful transition of SBIR research and technology development into the commercial marketplace is difficult, and SBIR Phase II awardees often encounter significant challenges in navigating the regulatory approval process, raising capital, licensure and production, as they try to advance their projects towards commercialization.

The NCI views the SBIR program as a long-term effort; to help address these difficult issues, the NCI has developed the SBIR Phase IIB Bridge Award under the grants mechanism. The previously-offered Phase IIB Bridge Award was designed to provide additional funding of up to $4M for a period of up to three additional years to facilitate the transition of SBIR Phase II projects to the commercialization stage. The specific requirements for the previously offered Phase IIB Bridge Award can be reviewed in the full RFA announcement: https://grants.nih.gov/grants/guide/rfa-files/RFA-CA-18-011.html.

In FY2011, the NCI expanded the Phase IIB Bridge Award program to allow previous SBIR Phase II contract awardees to compete for SBIR Phase IIB Bridge Award grants. Provided it is available in the future, the Phase IIB Bridge Award program will be open to contractors that are successfully awarded a Phase II contract (or have an exercised Phase II option under a Fast-Track contract). NIH SBIR Phase II contractors who satisfy the above requirements may be able to apply for a Phase IIB Bridge Award under a future Phase IIB Bridge Award grant funding opportunity announcement (FOA), if they meet the eligibility requirements detailed therein. Selection decisions for a Phase IIB Bridge Award will be based both on scientific/technical merit as well as business/commercialization potential.

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