SBIR-STTR Award

This project will develop a new microscopy instrument that is, in essence, a miniaturized fluoroscope. Living samples are placed onto a grainless fluorescent-screen, and illuminated with a laser-plasma soft x-ray source. Observation of the resultant luminescent shadow-image is accomplished using optical microscopy. The device can produce images containing three-dimensional information at a resolution that is routinely 200 nm or below. The extremely brief exposure duration of several nanoseconds results in very sharp images, even in the presence of significant specimen motility. Such capabilities will be invaluable for investigators in medical research, cell biology, microbiology, and other life sciences. Preliminary results have demonstrated the technique using a relatively large apparatus. This project will develop a much more compact device that fits directly onto a standard microscope stage, without interfering with the microscope's other imaging capabilities. Either optical microscopy, or soft x-ray microfluoroscopy can be performed in rapid succession without altering the sample environment. Phase I research will determine the practicality of the instrument by constructing a simple prototype device, and producing initial images of dry and wet samples. Phase II will develop a more advanced research tool that will be appropriately designed for subsequent commercialization

This project will develop a new microscopy instrument that is, in essence, a miniaturized fluoroscope. Samples are placed in direct contact with a grainless fluorescent-screen and illuminated with soft x-rays radiated by an extremely hot laser-produced plasma. The resulting luminescent shadowgraph is observed using optical microscopy. The device can produce images showing the three dimensional structure of unstained living cells at a resolution near 100 nm. An extremely brief exposure duration of several nanoseconds results in very sharp images, even in the presence of significant specimen motility. The instrument should find widespread application in many biomedical research areas. Phase I research demonstrated the feasibility of construction such an instrument using a design that was sufficiently compact for mounting directly onto the sample stage of a commercial optical microscope. This allowed the observation of both dry and hydrated test objects using either optical microscopy or soft x-ray microfluoroscopy. Phase II research will develop an advanced version of the instrument that will take full advantage of the unique imaging characteristics of the technique. The instrument will be appropriately designed for subsequent commercialization. Testing will include evaluating the instruments effectiveness in a real research investigation. PROPOSED COMMERCIAL APPLICATIONS: The ultimate goal of this project is to produce an accessory instrument that can be used with virtually any standard optical microscope. Due to the ubiquitous nature of optical microscopy, the commercial potential of this work is very substantial. The instrument's imaging capabilities are not achievable with any existing product. In addition to basic research applications in the life sciences, this technology may find significant usage in clinical medicine.

Thesaurus Terms:
X ray, biomedical equipment development, fluoroscopy, microscopy, miniature biomedical equipment charge coupled device camera, fluoroscopic image intensifier, laser, optics, radiofluorescent probe, synchrotron bioengineering /biomedical engineering, bioimaging /biomedical imaging