NCMIR pursues a coordinated, three-pronged approach to achieving its goals of imaging biological systems on a grand scale, focusing core technology development in three areas:
- biological specimen development for intermediate voltage electron microscopes (IVEMs) and correlated microscopies
- instrumentation, including IVEM, camera development, and instrument automation
- advanced software infrastructure applications and database development
Biological Specimen Development for IVEM
NCMIR activities in biological specimen development advance technologies to increase the ability to retrieve higher-fidelity information from biological specimens with standard as well as more advanced microscopies.¬† Effort is focused on the development and enhancement of new probes for multi-resolution, 4D correlated light and electron microscopic observations.¬† Working in close collaboration with the laboratory of Roger Tsien, NCMIR probe development aims to improve the versatility, detection sensitivity, and spatial resolution of general methods to image the dynamic location and function of nearly any desired protein(s) inside cells, both under normal conditions and during disease processes.¬† Extending this effort, NCMIR is advancing the development of new labeling technologies and specimen processing to produce material for observation when using wide-field, multi-color, and multi-resolution imaging instruments.¬† NCMIR also develops and refines methods for creating specimens for EM with unique geometries more suitable for 3D and ultra-wide field imaging.
Imaging Instrument Development
NCMIR instrument development activities advance and combine the use of intermediate voltage electron microscopy with electron microscopic tomography, electron energy loss spectroscopy, energy filtering, and ultra-wide field serial sectioning microscopy.¬† With the increasing emphasis on multi-scale integration in biological systems, NCMIR has expanded its activities in correlated microscopy, integrating new advances in serial block-face scanning electron microscopy, super-resolution light microscopy (PALM) as well as refining multi-photon light and ultra high-voltage electron microscopic techniques.¬† As a leader in the development of technologies for high performance digital imaging for EM, NCMIR continues to build on the success of its ultra large-field lens-coupled CCD camera technologies and direct detection device detectors, refining the automation and hardening the application of these state-of-the-art systems across its suite of advanced EM platforms. ¬†As each resource instrument is improved to deliver unique and important new capabilities, they are tightly coupled to NCMIR‚Äôs software and hardware cyber-infrastructure for high performance data management, archival, computation and analysis.
Advanced Software Infrastructure Applications and Database Development
NCMIR software development activities accelerate, refine, and increase the efficiency of processing data and metadata as well as improve the ability to mine that data as is necessary to enhance the research accomplishments of resource collaborators and the extended biomedical research community we support.¬† To increase data processing throughput and fidelity, NCMIR advances computational technologies for reconstruction, visualization, segmentation and analysis, including high-throughput methods for processing massive ultra-scale data. To structure, organize, archive, and mine data and resultant knowledge at each stage in its lifecycle, NCMIR is leading the development of an overarching informatics framework that combines databases and knowledge bases.