The CellCAT Division will develop two approaches to cell imaging that will employ technologies developed separately by consultants Dr. David Prelewitz and Conrad Schneiker.
Current technology limitations force scientists to decide, a priori, what part of the cell they will visualize. The small area is brought into focus and can be viewed live, but the rest of the cell is not visible. This best-guess approach means that critical cellular activities, interactions and structural changes can be missed, just by the field of view being at the wrong place, at the wrong time. Using a new approach that is based on phase information rather than simply wavelength and intensity, the entire cell may be imaged in three dimensions at one time and high resolution, creating a comprehensive view of the cellular system and its processes at the same moment in time.
The system will not require fluorescent dyes and cellular activity may be viewed without knowing in advance where to look. Most traditional methods of cellular imaging depend on use of markers that bind chemically or immunochemically to a particular cell structure of interest, and comprise an optical dye such as a fluorophore. These materials are illuminated at one wavelength and are optically read at a second wavelength; this shift in color permits use of color filters that block the illumination color, thus reducing the effects of scattered light that would otherwise render the image useless. The problem with these fluorophores is that they are chemically reactive and while not always toxic to the cell, they certainly alter its behavior. The breakthrough promised by CellCAT is to image the cell without any markers. This is enabled by use of a completely different characteristic of light, its phase. A completely coherent laser light source emits light with a waveform that is almost perfectly aligned at the source. As the light passes through a cell, even though the cell is transparent, sub-cellular bodies that have different makeup, density, water content, or chemistry, will slow the light going through them to a different degree than other volumes in the cell. If all this “phase shift” information is collected from one point of reference, and combined with like information from other points of reference, a complex mathematical software program can re-build a three dimensional image of the cell itself. Again, no dyes are used and the image is in real time. As a result, changes in cell behavior due to outside effects such as adding a proposed pharmacological agent can be observed in real time, in 3-D, and without the unwanted effects of fluorescent dyes or other markers. Changes throughout the cell, from the shape of the nucleus, the patterns of the microtubules and overall cell size can be measured at high precision. This combination of powerful elements has not been achievable in the past with other microscopic platforms.
CellCat technology is expected to permit visualization the cell's structural components and their relative viscosity (gel formations and membranes), its cytoskeletal system of microtubules, and its phase and spectral data. This is accomplished with low power laser technology and advanced software analytics that allow for the collection and reconstruction of phase data gathered from the cell.
Schematic diagram of the core CellCAT imaging system
Technology Applications and Market Potential
There is a large unmet market need for this advance in imaging capability. Research organizations in industry, government and academia spend billions annually in imaging and cell handling equipment, biomarkers, and software to conduct research in cell sciences. CellTraffix will develop these hardware systems to augment today’s confocal microscopes.
The company will also develop the software to capture, access, store, and retrieve the high content data files. Development of a next-generation therapeutic agent begins with computational methods that model the interaction between a known cellular receptor and numerous classes of chemical compounds. These candidate compounds can number in the thousands, and as the development process proceeds, each succeeding step becomes significantly more expensive. A pharmaceutical company that can winnow the huge number of compounds down to a few, without unintentionally dropping a promising candidate, will win in the marketplace. The ability to directly observe the reaction of a cell, and potentially to observe the specific chain of events that occurs as a reaction to exposure to a candidate compound, will significantly increase the efficiency of the development process for that company. The advantage is compounded; it represents large cost savings and much faster time to market.
Several well known institutions have been contacted by CellTraffix in order to collaborate and secure non-dilutive government and private foundation grants for building and using the CellCAT system, with commercial rights flowing back to the Company. Collaborators include the University of Rochester’s Center for Cellular and Analytical Imaging and commitments from Lawrence Berkeley National Labs (Life Science Division), the UCLA (Neuropsychology Department), USC Biomedical Engineering Center (an NSF funded biomedical engineering center), University of Alberta at Edmonton (Department of Oncology) and the Institute for Medical Science and Technology at Edmonton, Scotland. CellTraffix intends to eventually license the equipment hardware to one or more existing microscope system manufacturers with appropriate infrastructure, including in-place distribution and marketing capabilities. CellTraffix will also develop and sell software packages of varying complexity and capability to enable sophisticated analysis of the cell images to the level of sophistication desired by the users.
The Company also owns or holds exclusive licenses for the following intellectual property relative to the CellCAT technology:
- US 6,815,688 Devices for Guiding and Manipulating Electron Beams
- US 6,943,356 Improved Tips for Nanoscanning Electron Microscope
- US 6,700,127 Point Source for Producing Electron Beams
- US 7,279,686 Integrated Sub-Nanometer-Scale Electron Beam Systems
- US 7,282,716 Digital Imaging Assembly and Methods Thereof
- US 7,006,219 Biological Imager
- US 6,369,932 System and Method for Recovering Phase Information of a Wave Front
- US 6,545,790 System and Method for Recovering Phase Information of a Wave Front
- US 6,906,839 System and Method for Recovering Phase Information of a Wave Front
CellTraffix also has a number of additional patent applications pending that it expects to ultimately issue relating to CellCAT.