This Notice of Funding Opportunity (NOFO) solicits grant applications proposing exploratory research projects focused on further development and validation of emerging technologies that improve the quality of the samples used for cancer research or clinical care. This includes new capabilities to address issues related to pre-analytical degradation of targeted analytes during the collection, processing, handling, and/or storage of cancer-relevant biospecimens. This NOFO solicits R33 applications where major feasibility gaps for the technology or methodology have been overcome, as demonstrated with supportive preliminary data, but still requires further development and rigorous validation to encourage adoption by the research community. The overall goal is to support the development of highly innovative technologies capable of maximizing or otherwise interrogating the quality and utility of biological samples used for downstream analyses. This NOFO will support the development of tools, devices, instrumentation, and associated methods to preserve or protect sample integrity, or establish verification criteria for quality assessment/quality control and handling under diverse conditions. These technologies are expected to accelerate and/or enhance research in cancer biology, early detection and screening, clinical diagnosis, treatment, epidemiology, or address issues associated with cancer health disparities, by reducing pre-analytical variations that affect biospecimen sample quality.