Newsletters: 2006, Issue 2

PSI's World Class Applied Research Laboratories

Physical Sciences Inc. has a well-earned reputation for innovation, advanced technologies, and development of commercial products. In this newsletter, we highlight the world class basic and applied research underway in our laboratories. The examples we have selected illustrate the application of optical instrumentation, a core strength of the company, to cell biology, opthalmology, and chemical detection.

Key characteristics of each of these projects are collaborations with other internationally recognized scientists and clinicians, publication of scientific data in archival journals, and development of new technologies for use in the broader research community. On a larger time scale, new diagnostic or therapeutic products may evolve from these studies. While this is a key financial metric for corporate success, the scientific contributions of our staff are of equal importance.

Confocal Imaging of Osteoblast Cell Cultures

Anthony Ferrante, lead scientist, along with Anton Chestukhin, Chad Bigelow, and Danthu Vu are developing an innovative osteoblast cell culture model and associated confocal imaging system aimed at understanding changes at the cellular level that lead to the skeletal changes occurring during long-term space travel. The knowledge gained will enable rapid development of effective countermeasures for microgravity-induced bone loss. In addition, the genetic constructs and the confocal imaging system may also provide enhanced capabilities for understanding the cellular mechanisms of cardiovascular changes found in astronauts. This same cell culture model may have additional applications in the search for novel agents to prevent or reverse osteoporosis.

Fluorescence images of cells that express a signal protein that is fused to a green fluorescent protein (GFP) were collected using a GFP filter. A region from the image is expanded (right) to show the fluorescence patterns in greater detail.

PSI has constructed three genetic fusions between cell structural and signaling proteins and three different reef coral fluorescent proteins (RCFPs). Construction of an osteoblast model cell line that expresses two of these, a signalling protein that is fused to a green fluorescent protein and a structured protein fused to a red fluorescent protein is complete and a cell line that also expresses a third fluorescent fusion protein is under development. A green fluorescence image of the completed cell line is shown above. As anticipated, the green fluorescent signalling protein is concentrated in the cell membranes. The red structural protein is predominantly confined to the cytoskeleton.

Biomedical Adaptive Optics

Led by Dan Hammer, the biomedical optics group (Dan Ferguson, Nick Iftimia, Chad Bigelow, and Teoman Ustun) has recently applied adaptive optics (AO) imaging of the eye. AO is used to correct ocular aberrations and deliver diffraction-limited spots to the retinal layers in the back of the eye for improved imaging and therapeutic beam presentation.

Retinal image from PSI's AOSLO and AO-SDOCT systems with and without adaptive optics. The cone mosaic is clearly visible in the AOSLO image (upper left) and the AO-SDOCT image shows improvement in brightness and resolution in the upper retinal layers (lower left)

Funded by the NIH and the U.S. Air Force, this research involves the design and construction of complex multi- component imaging systems, and builds upon PSI's previous development of novel retinal tracking and imaging instrumentation. Adaptive optics has been integrated into systems that use scanning laser ophthalmoscopy (AOSLO) and spectral-domain optical coherence tomography (AO-SDOCT). AO systems couple a wave-front sensor and a deformable mirror to actively correct distortions caused mainly by the tear film, cornea, and lens. In both instruments, AO improves the transverse resolution that can be achieved. The AOSLO system produces a high-magnification scan that can resolve cones, capillaries, and other retinal structures of interest. SDOCT systems already have micron-level depth resolution, and with AO, have improved transverse resolution and brightness.

The bio-medical optics group is currently working with world class ophthalmologists and scientists, including Cindy Toth at Duke University, Ann Fulton at Children's Hospital Boston, and Steve Burns at Indiana University. Planned clinical tests will involve retinal pathologies such as age-related macular degeneration and retinopathy of prematurity. The research will provide a greater understanding of the etiology, characteristics, and progression of retinal diseases, and may lead to advanced laser and pharmacological treatments based upon improved understanding of the molecular disease pathways.

Terahertz Science and Technology

The portion of the electromagnetic spectrum between 50 and 5000 microns (5 to 0.05 THz) has received much attention from the international scientific community. Lying between laser sources at the short wavelength end and electronic oscillators at the long wavelength end, few tools are available to explore the response of materials to radiation in this range. The ability of these long wavelengths to pass through many common materials has spawned a number of research programs devoted to detect hidden illicit substances such as weapons, explosives, and drugs.

PSI scientists David Cook and Seonkyung Lee have been exploring the fundamental spectroscopy of many materials in the THz spectral region using a time-domain THz spectrometer designed and built in our laboratories. Based on rectification of a femtosecond visible laser, a broad-band pulse of THz radiation is used to capture the absorption, reflection, and scattering properties of samples. PSI has developed procedures for quantitative spectroscopy of solid-phase materials and produced the first databases of many controlled substances of interest to national security applications.

THz quantum cascade gain laser coupled to an external cavity (THz ECQCL)

Tunable, narrow-linewidth laser sources in the THz spectral region remains an elusive goal and the subject of intense international competition. Joel Hensley, David Cook, and Krishnan Parameswaran of PSI are collaborating with Prof. Alessandro Tredicucci, of the Scuola Normale Superiore, Pisa, Italy. Prof. Tredicucci and co-workers developed the first THz wavelength Quantum Cascade Laser (QCL) and PSI has been evaluating these devices in LIDAR systems for stand-off detection.

The THz spectral region also contains absorption features in gases, including nuclear fine-structure transitions from atomic gases such as oxygen. In collaboration with Prof. Tredicucci, Joel Hensley is developing an absorption sensor for atomic oxygen that will be deployed at NASA Ames to measure concentrations in high-temperature, high-speed flow facilities that are used to evaluate materials for atmospheric re-entry. The application requires a tunable source and PSI is designing an external cavity around the THz QCL emitter.

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