This Funding Opportunity Announcement (FOA) solicits grant applications to further develop enabling technologies and transformative platforms to catalyze next-generation predictive, diagnostic and therapeutic products to address heart, lung, blood, and sleep (HLBS)-related disorders and diseases. This FOA solicits R33 applications where major feasibility gaps for the enabling technology or transformative platform have already been overcome, as demonstrated with supportive preliminary data, but still requires further development and rigorous validation to encourage downstream demonstration, utilization and adoption. Well-suited applications must offer the potential to accelerate and/or transform the areas of early detection and screening, model development, clinical diagnosis, treatment, control, prevention or epidemiology, while addressing issues associated with HLBS-related diseases and disorders. Projects proposing application of existing technologies where the novelty resides in the biological or clinical target/question being pursued are not appropriate for this solicitation and will not be reviewed. This FOA is part of a suite of NHLBI Catalyze program to advance projects to the point where they can meet the entry criteria for the NHLBI Catalyze Product Definition or Preclinical FOAs.