Technology, Research and Development (TR&D)

NCMIR technology, research and development (TR&D) efforts are organized around four major core activities:

TR&D Project 1: Development and Enhancement of New Probes, Labeling Technologies, and Methods for Correlative, Multiscale Light, X-ray, and Electron Microscopy

The overall objective of this core TR&D effort is to develop next-generation molecular-genetic and chemical-labeling approaches to advance the application of high-resolution, correlated, multiscale and multimodal microscopy to biomedical research. With these expanding methods, we aim to improve our ability to determine the locations of specific proteins in situ, a critical capability for projects where localization of molecular constituents in cell and tissue contexts will provide important new understanding.

TR&D Project 2: Development of Hybrid Specimen-preparation Methods for Multiscale – Multimodal Imaging

The main objective of this TR&D core is to introduce new methods of specimen preparation that will rapidly broaden the application of new molecular probe technologies developed at NCMIR during the current award period, particularly in the context of multiscale, multimodal imaging. While the efforts in Core 1 focus on labeling strategies with various probes, the thrust of Core 2 is to further the refinement of specimen-preparation protocols and materials to provide more suitable samples for examination when investigators use correlated microscopy in their research projects. The proposed new methods are being designed to facilitate work on specific projects that now require the traversal of scales, which is becoming an increasing requirement of biomedical research projects that aim to advance understanding of molecular mechanisms underlying normal and abnormal cell and tissue biology. Our objectives are to create specimens suitable for wide-field, multi-color, and multi-resolution imaging using combinations of light microscopy (LM), X-ray microscopy (XRM), scanning EM (SEM), transmission EM (TEM), and scanning transmission EM (STEM) instruments.

TR&D Project 3: Instrumentation Development for Multiscale, Multimodal Imaging

The overall objective of this Core TR&D effort is to provide biomedical scientists with new capabilities to obtain wider-field, higher-resolution data, including molecular localizations with multiple imaging modalities, by developing, implementing, and refining the analytical capabilities of imaging instruments, such as NCMIR’s advanced high-throughput Intermediate-high Voltage TEM and SEM platforms. The proposed work is motivated by the needs of current Driving Biomedical Projects (DBPs) and other user projects whose ongoing activities push us to refine and extend our imaging-platform capabilities to track new molecular labels or fiduciary markers to facilitate examination of the same specimen across multiple modalities. Our goals are to image wider, see deeper, increase contrast and differentiate complex structures, and observe complex phenomena at higher resolution on faster timescales.

TR&D Project 4: Advanced Applications and Information Technology Development – New Technologies for Data Refinement, Integration, and Analysis

The activities of TR&D Core 4 involve development of software tools and infrastructure to refine, integrate, quantify, interpret, and add value to the increasingly complex multiscale image data derived through use of Resource technologies. Like our other TR&D activities, Core 4 leverages work supported by other grants to NCMIR Co-Is and collaborators as well as open-source and commercial-off-the-shelf (COTS) software tools where most appropriate.  The overarching goal of Core 4 is to better enable work with large multidimensional and multimodal data by developing methods and software tools that extend beyond what is presently available.