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Miniaturization and Automation of Tissue Chip Systems (MATChS) (U43/U44 Clinical Trial Not Allowed)

Description:

This Notice of Funding Opportunity (NOFO) invites eligible United States small business concerns (SBCs) to submit Small Business Innovation Research (SBIR) Phase I, Phase II, Fast-Track and Direct to Phase II grant applications. The funding opportunity will utilize a U43/U44 cooperative agreement to support small business concerns (SBCs) to propose applications to create bench top, portable, automated, self-contained systems that maintain 3D tissue constructs (e.g., precise thermal control, fluid pumping and sampling) and provide biologically relevant outputs of tissue health and function. The companion Small Business Technology Transfer (STTR) NOFO allows for submission of Phase I and Phase II, and Fast-Track grant applications. NCATS has consistently shown leadership in the development of tissue chip technology, in the demonstration of its utility in drug development for safety, efficacy and precision medicine, and in the dissemination of the technology (https://ncats.nih.gov/tissuechip/about). FDA Modernization Act 2.0 declared that the FDA no longer requires animal tests before drug trials in humans, which stimulated increased interest in in vitro New Approach Methods (NAMs) that are more predictive of human response in the safety and efficacy assessment of leading therapeutics. Tissue/organs on chips systems are considered as one of the NAMs. However, the widespread dissemination of tissue chip technology is hindered by the relatively large and complex instrumentation system needed to support the function of the chips, low throughput and specialized expertise needed to operate the systems. The instrumentation typically requires a multidisciplinary team of biomedical engineers and microfluidics experts to assure smooth operations, and biologists to acquire and analyze the data. This underscores the need for improvements in design towards systems capable of real-time, repeated measurements, with ease of manufacturability, and broader user-friendliness. Through partnerships between NCATS, NASA and the Center for Advancement of Science in Space, the Tissue Chips in Space program has enabled advances in the study of microgravity-associated age?related conditions and has made key technological improvements in the tissue chips instrumentation systems towards automation and miniaturization required for space flight. Previously, NASA has partnered with NIH, BARDA and FDA to develop extended longevity tissue chips (cell culture life up to 6 months) with a focus on the development of systems requiring minimal human intervention. Working with spaceflight payload implementation partners, NCATS-supported tissue chip investigators have developed compact, robust, and reliable platforms which integrate basic support systems (incubation, refrigeration, thermal control, fluid reservoirs, microfluidic pumping systems etc.) as well as technologies to monitor cell health and function (pH, gas concentrations, repeated fluid sampling, microscopy, electrophysiology etc.). This Miniaturization and Automation of Tissue Chip Systems (MATCHs) NOFO seeks to engineer tissue chip platforms towards a smaller footprint and the simplification of systems for ease of use that will result in ease of use and broader accessibility of tissue chips in drug discovery and biomedical research. Objectives This NOFO seeks to fund technology development research efforts in instrumentation innovation and approaches for automation and miniaturization of MPS. The technology development proposed should have the potential to significantly propel the field of MPS forward and have the potential to have a large impact on the future analysis of safety and efficacy assessment of therapeutics. A main objective for this funding opportunity would be to create a bench top, portable, easy-to-use, automated MPS with integrated in-line sensors, flow generator with system control and data processing software to provide rapid and reproducible high-throughput analysis. The project could integrate manual methods into an automated system to develop a standalone module. Improved tissue chips instrumentation systems should demonstrate automation capabilities in maintaining culture without external intervention and can be monitored remotely through real-time biosensing and readout capabilities, including telemetry operations. Automation may include automation of tissue preculture and loading, system operation, perfusion systems with or without pumps, automation of cell culture conditions, monitoring and sensing, include in-line sensors, e.g., pressure, pH and oxygen sensors. This self-contained system should maintain 3D tissue constructs (via precise thermal control, fluid pumping and sampling) for extended periods of time and provide biologically relevant outputs of tissue health and function (e.g., by means of fluid sampling, electrode incorporation, microscopy, biosensors). If automated chip exchange is proposed, the system should have proper optical, mechanical, and electrical couplings. The fabrication procedure must be cost effective, mass producible, and robust. The application may include development of a software for instrument control, data acquisition and real-time detection, fast data processing and analysis for high throughput measurements. Performance metrics of an integrated system for a multi-day protocol should be developed once standard protocols are established and instrument performance is assessed. Once optimal assay parameters are identified, and optimized chips created and integrated for use in the fully automated system with alignment features ensuring proper connection of the fluidic path to the chip, the performance of the system should be characterized and validated. An automated system may be validated by demonstrating compatibility with developed chips and organ-on a chip model and by pre-market end-user testing. The NOFO deliberately does not specify cost, quality, scale, sensitivity, dynamic range, throughput, or other key metrics since achievable endpoints are likely to substantially differ from one technology to another. However, the applicant must propose quantitative metrics so progress can be evaluated and present convincing rationale that the proposed technology has the potential to scale long-term and to achieve a throughput compatible with widespread adoption by the biomedical and clinical research community. It is expected that applicants will develop and detail scientific and practical definitions of optimal throughput, cost, accuracy, sensitivity, dynamic range, and scale. The long-term goal is to achieve technological advances that enable generation of data at sufficient scale, speed, cost and accuracy to use routinely in safety and efficacy assessment of therapeutics. MATChS is expected to accelerate commercialization and catalyze the widespread use of tissue chips through automation and miniaturization of the instrumentation systems and will lead to the general utility of tissue chips in drug development and regulatory decision-making, as well as in biomedical research in general as a major research tool. The SBIR U43/U44 cooperative agreement mechanism is milestone-driven and involves significant input from NIH program staff regarding project and milestone planning, monitoring of research progress, and go/no-go decision-making. Applicants are encouraged to contact staff at NCATS per Agency Contacts below to ensure that their study design and objectives are in line with the goals of the NOFO. Award recipients will be expected to work with NCATS staff post-award. Examples of responsive activities and corresponding SBIR Phase assignment includes but is not limited to the following technological developments. SBIR Phase I (U43) Development of components of the system Development of real-time biosensing Development of automated readout capabilities Telemetry operations Automation of tissue preculture and loading Automation of system operation Development of perfusion systems Development of automation to maintain 3D tissue SBIR Phase II (U44) Integration of the system Development of a stand-alone instrument prototype Militarization of the system Development of software for instrument control and data processing software Standard protocols Assessment of instrument performance System characterization and validation Pre-market end-user testing U44 Phase I/II Transition Applicants can submit separate Phase 1 (U43) or Phase II (U44) applications. However, if Phase I and Phase II are submitted together in one application (U44 Fast-Track), then an administrative review will be conducted by NCATS Program staff to decide whether a project will be considered for transition from Phase I to Phase II. Phase II eligible projects must successfully accomplish milestones of Phase 1 as defined in Milestones Plan. Funding for the Phase II application will be contingent upon (1) assessment of the Phase I progress report and determination that the Phase I goals and milestones were achieved; (2) an update (as necessary) of the Commercialization Plan; (3) determination of the project's potential for meeting the mission of the awarding component and for commercial success; (4) review and approval of other documents necessary for continuation; and (5) availability of funds. The continuation application package is due 2 months prior to the anticipated start date of Phase II.
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