Ramachandra Dasari - US grants

The Chemistry Division through its Chemical Instrumentation Program, its Experimental Physical Chemistry Program, and its Inorganic/Bioinorganic/Organometallic Chemistry Program supports a research project involving a large number of MIT scientists working within the George R. Harrison Spectroscopy Laboratory on the development and application of modern laser spectroscopic techniques to a wide range of fundamental problems. Led by Professors Feld and Steinfeld and Dr. Dasari, this endeavor has achieved efficient collaborative use of expensive optical facilities, while becoming a model for effective training of large numbers of students in state-of-the-art optical techniques. Multiple-resonance and nonlinear laser techniques are being used to study the spectroscopy of highly excited electronic and vibrational levels (including the regime of quantum chaos) and to follow the evolution of phase, velocity, and quantum states in collisional processes. Raman and resonance Raman techniques are being used to study diverse systems, ranging from technetium pharmaceuticals to enzymes. Pump-probe studies of the conversion of light to chemical energy are being investigated with nanosecond to femtosecond techniques. New work is being initiated to investigate photochemical processes at surfaces, interfaces, or in bulk materials and to develop spectroscopic instrumentation for deployment at hydrothermal vents on the ocean floor.

This award funded by the Chemistry Division renews support for the Laser Research Facility (LRF) at the Harrison Spectroscopy Laboratory at MIT directed by Professor Michael S. Feld. The LRF is a shared research facility in which physical scientists in chemistry, physics, biology and engineering pursue a broad range of problems using lasers and state-of-the-art spectroscopic techniques. The research is focussed in five areas: multidimensional infrared spectroscopy, high sensitivity spectroscopy for combustion and environmental science, spectroscopy of nanomaterials, proton-coupled electron transfer, and biological spectroscopy.

The Laser Research Facility features training for undergraduate, graduate, and postdoctoral students as well as outreach through dissemination of scientific results, topical seminars, and links with local schools. The Laser Research Facility, as a shared facility with state-of-the-art equipment and personnel skilled in its use, enables new research opportunities to be seized upon and carried out quickly, economically, and effectively. It leads to new collaborations and research programs that would not exist in the absence of the facility, sometimes resulting in significant discoveries that are unanticipated.

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Training, education and dissemination of information are important components of the Center. As part of its mission, seminars and lectures are held on topics related to lasers and spectroscopy in medicine. The LBRC cosponsors the semiannual Lester Wolfe Workshop in Biomedicine, a one-day workshop on a relevant topic in biomedicine and brings together researchers in multidisciplinary areas from academic institutions, hospitals and industry to have in depth discussions on the subject. Topics chosen during this period were "Probing blood disorders with light" and "Optogenetics - probing the brain with light." At the conclusion of the Workshop, opportunities are available for audience to participate in discussion with the speakers. The Spectroscopy Laboratory also sponsors the Modern Optics and Spectroscopy seminar series, a long running seminar series, where topics of interest to biomedicine are also presented. As another component, special training on Center facilities are provided to collaborators and other users of the Center.

lasers; education; biomedical resource;

lasers; education; biomedical resource;

lasers; education; biomedical resource;

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Laboratory disseminates information to the public though a semi-annual newsletter and website. The newsletter entitled "The Spectrograph" describes research activities of the Laser Biomedical Research Center (LBRC) and is published periodically with distribution to about 1000 researchers across the country. "The Spectrograph" features research reports, special activities, seminar/workshop details and publications from the Center.

A grant has been awarded to Drs. Feld and Badizadegan at the Massachusetts Institute of Technology to develop next generation phase microscopy instruments for biological research. The phase contrast microscope and related techniques have been a cornerstone of nearly every biology laboratory for more than half a century. The popularity of these methods lies in their unique ability to visualize live cells and their internal structures without any specific preparation or chemical modification. In spite of their enormous value to biological research, however, current phase microscopy techniques provide only qualitative information about cell structures. In addition, current phase microscopy techniques reduce the three-dimensional structure of the cell to two-dimensional images, thus reducing the value of these techniques in studies in which identifying the precise location of subcellular structures is of value.

Research supported by this grant will enable the MIT group to design and fabricate novel instrumentation that will overcome limitations of the current phase microscopy methods, thus significantly broadening the value and scope of phase microscopy in biological research. Most cells and tissue are as transparent as glass, and therefore not clearly visible without chemical alteration such as staining with exogenous dyes. The standard intensity-based phase microscopy methods, which measure the absorption or reflection of light, have therefore difficulty in visualizing live cells in detail. The group will utilize so-called "field-based" approach to analyze variations in the speed of light (or refractive index) which result from variations in the structural components of the cell. This approach enables them to visualize and measure transparent cellular materials with extreme sensitivity. Combined with a novel imaging method that is similar to X-ray computed tomography (CT scan) used by physicians to image the human body, the MIT group will produce 3-dimensional, quantitative images of live cells in real time by quantifying variations in the speed of light at every location inside the cells. In addition, the group proposes to utilize a high-throughput method that will enable extracting quantitative information from a large number of cells in a short period of time. Collectively, these advanced instruments will enable biologists to visualize, measure and monitor the structure of live cells in ways that have not been possible before.

Quantitative characterization of cellular structures in their native state (without chemical or physical alterations) is the ultimate goal in biological microscopy. The instrumentation that will be constructed as a result of this grant award will advance biomedical phase microscopy into the next generation by enabling quantitative, 3-dimensional, real-time, and high-throughput imaging. The biological and biomedical applications of these novel methods are numerous and diverse. In addition, this research is conducted within an interdisciplinary academic environment with scientists, engineers and physicians who are uniquely qualified to guide and oversee successful translation of these novel instruments in biology.

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DESCRIPTION (provided by applicant): Established in 1985, the MIT Laser Biomedical Research Center (LBRC) has continued to consolidate and expand through sustained NIH funding. Under the proposed program, the research and development will progress through core, collaborative and outside projects, the training and education will be carried out at the undergraduate, graduate and postgraduate level, while the information dissemination will be maintained through our laboratory's publication -The Spectrograph- and various other communications. Experimental techniques that merge optical spectroscopy, imaging, scattering, and interferometry will be applied to study the biophysics and biochemistry of healthy and diseased biological structures from the subcellular to the entire-organ scale. Probe-based spectral diagnosis instruments based on near-infrared Raman scattering, intrinsic fluorescence, diffuse reflectance, and single light scattering will provide complementary data on human disease and the possibility of combining these techniques into a single, versatile instrument will be explored. This multimodal investigation will be applied for diagnostics in various organs, including cervix, oral cavity, Barrett's esophagus, artery, breast, skin, as well as for transcutaneous measurements of blood constituents. Spectroscopic imaging will advance in the direction of wide-area tissue characterization and tomography. Elastic light scattering studies will contribute to our understanding of tissue organization at the sub-micron scale. New technology on quantitative interferometric microscopy will be exploited for measuring cellular structures at the nanometer level. Rapid cell motions associated with neuronal action potentials and membrane fluctuations will be quantified at the sub-millisecond scale. The future LBRC research effort will channel on existing areas, as well as on new and extremely exciting core projects. Several additional, promising collaborative projects will be established. Modern facilities will be made available and new core research staff and outside collaborators will join the center.