Fast track proposals will be accepted. Direct-to-Phase II proposals will not be accepted. Number of anticipated awards: 3-5 Budget (total costs, per award): Phase I: up to $400,000 for up to 9 months; Phase II: up to $2,000,000 for up to 2 years PROPOSALS THAT EXCEED THE BUDGET OR PROJECT DURATION LISTED ABOVE MAY NOT BE FUNDED. Summary Advances in microscopy have improved the ability to resolve, describe, and quantify subcellular anatomic structures, organization, and dynamics. Concurrently, single-cell molecular ‘omics technologies have revolutionized our understanding of intracellular processes and intercellular communication. Our understanding of basic cancer mechanisms is informed by multiple orthogonal perspectives, including employment of technologies such as high-resolution microscopy and multiscale ‘omics. However, experimental or computational methods that facilitate true integration of advanced high-resolution cellular and subcellular microscopy and multi-scale molecular ‘omics technologies are not readily available to the broader research community. Technologies that offer such integration will facilitate multidimensional and spatially preserved mapping of the tumor ecosystem, leading to a broader understanding of tumor heterogeneity, and the role of cell-cell and/or cell-matrix interactions in response to cancer therapy, and will provide data for building predictive computational models of cancer initiation, progression, metastasis, and response to treatment. Recommendations of the Cancer Moonshot Blue Ribbon Panel call for enabling technologies that combine approaches from disparate fields, such as imaging at the cellular to subcellular scales with single cell “-omics” approaches. It is anticipated that the innovation in the small business sector can provide instrumentation and enabling technologies to serve the basic cancer biology research needs, in particular, technologies that directly link cellular phenotypes measured through high-resolution cellular and sub-cellular imaging in combination with multi-scale ‘omics measurements. Project Goals The main objective of this contract topic is to support the broader goal of developing an infrastructure to accelerate the microscopy-omics community and enable transformative research in cancer cell biology, diagnostics, or monitoring strategies. The short-term goal of this contract topic will be to stimulate innovation that integrates cellular imaging modalities with technologies that provide single cell -omic level data (e.g. proteomic, transcriptomic, etc.) that are relevant to cellular processes and are disabled or exploited in cancer. Projects supported by this contract topic should enable multidimensional interrogation of cancer cell biology in a manner that combines the spatial-temporal strengths of imaging modalities with complementary orthogonal measurements achieved through -omics and physicochemical approaches. This solicitation seeks to encourage the development of new imaging platforms, probes, or a unique combination of platforms with image-based approaches that leverage a multidimensional perspective of cancer cell biology. It is anticipated that that projects may include the development of new algorithms or software that facilitates image analysis or multimodal data analysis to render an understanding of cancer cell biology from a multidimensional perspective; however, proposals that are solely software based will not be responsive. The focus of this topic is on non-sequencing based -omic technologies. Proposals to integrate single cell sequencing technologies with imaging should respond to the contract solicitation for the “Spatial Sequencing Technologies with Single Cell Resolution for Cancer Research”. Phase I Activities and Deliverables Phase I activities should generate data to confirm the feasibility and potential of the technology(ies) to combine microscopy at the subcellular scale with orthogonal cell “-omics” and physicochemical measurement approaches. Activities and deliverables include: • Define the cancer biology application the device(s) or combined device-computational approaches addresses. • Generate proof-of-concept data in a generally accepted cancer cell model system that demonstrates the ability to sense, interrogate, detect or resolve and map spatial cellular anatomy and/or dynamics using microscopy or other imaging modalities with nano- to micro-scale resolution. • Demonstrate feasibility of combining the imaging modality(ies) in Phase I Deliverable #2 with orthogonal assessments at the molecular scale (such as genomic, proteomic, metabolomic, or epigenomic analyses), physicochemical scale (such as redox, pH, force/stiffness), and/or functional scale (such as proliferation, transformation, motility, invasion, resistance, or cell death) to generate multidimensional data. • Offerors should specify quantitative technical and commercially-relevant milestones that can be used to evaluate the success of the tool or technology being developed. Offerors should also provide appropriate justification relevant to both the development and commercialization of these technologies. • Quantitative milestones may be relative metrics (e.g. compared to benchmarks, alternative assays) or absolute metrics (e.g. minimum level of detection). Phase II Activities and Deliverables Phase II activities should support the commercialization of the proposed technology and include the following activities: • Demonstrate reliability, robustness and usability in basic and/or clinical cancer research. • Demonstrate system performance and functionality against commercially relevant quantitative milestones. • Offerors should specify quantitative technical and commercially-relevant milestones that can be used to evaluate the success of the tool or technology being developed. Offerors should also provide appropriate justification relevant to both the development and commercialization of these technologies. • Quantitative milestones may be relative metrics (e.g. compared to benchmarks, alternative assays) or absolute metrics (e.g. minimum level of detection). • Demonstrate utility with benchmark experiments obtained across a range of generally accepted cancer cell model systems. • Show feasibility to be scaled up at a price point that is compatible with market success and widespread adoption by the basic research community.