IDBR: Field-Based Tomographic Microscopy Instruments

Massachusetts Institute Of Technology, Cambridge MA

Investigators

Abstract

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.