CellCAT Core Technology

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.

 

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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.

 
Commercial Strategy
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.
 
Intellectual Property

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.
 
CellSelect Core Technology

CellTraffix has pioneered core platform technologies for the selection and manipulation of a broad range of Target Cells found in the bloodstream for modification, collection, or elimination.  Target Cells include circulating tumor cells, adult stem cells, and immunological cells.

Unlike existing products that use antibodies or other molecular tools in non-physiologic approaches, the CellSelect system manipulates Target Cells by mimicking the mechanisms of cell trafficking employed by the body itself.

 

Real-time microscopic image of a common mode of cell trafficking in the body.  Target Cells (in this case, leukocytes) are captured from the free stream and made to adhere to the blood vessel wall.  The body facilitates capture and rolling of cells using the specialized adhesion protein Selectin.  CellSelect technology mimics this mechanism of cell trafficking.

The core platform technology involves a flow-mediated adhesion system, built on a biocompatible device substrate.  This system utilizes a class of molecules called selectins for adhering and rolling Target Cells either in vitro (in benchtop research kits or clinical diagnostics) or in vivo (in implantable devices), replicating the cellular trafficking mechanisms of the human body.  Once Target Cells adhere and begin rolling, they can either be purified and removed, or therapeutically modified using a secondary set of Signalling Molecules commingled on the device surface.

Real-time image of CellSelect device capturing Target Cells from free-flow with Selectin.  Cells undergo adhesion and rolling for either later harvest (for adult stem cell donation) or modification and release (for metastatic cancer cell killing).In the therapeutic applications, Target Cells are released from the device after modification and return to circulation.  Key aspects of the core technology include proprietary cell capture coatings on the substrate, specialized tuning of the surface to adhere specific Target Cells, Target Cell rolling dynamics, prototype device design, and Cell Modification utilizing secondary Signalling Molecules.


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Multi-step process of CellSelect technology:  Target Cells in a blood or other biological sample specifically adhere to immobilized Adhesion Molecules affixed to the interior surface of the device.  Optional  secondary Signalling Molecules can cause the Target Cell to be therapeutically manipulated or killed.
This powerful platform technology lends itself to the development of a wide range of potential products.

 
Technology Applications

The ability of CellSelect technology to actively capture and manipulate Target Cells holds much promise for research grade and clinical kits, as well as therapeutic delivery systems for cancer metastasis, stem cell therapies, and immunological diseases. 

For example, device substrates specifically tuned to adhere metastatic cancer cells also utilize apoptosis-inducing Signalling Molecules that result in the death of the metastatic cell after leaving the device surface.  In this manner CellSelect technology opens significant opportunities for CellTraffix to become a leader in the large and growing oncology market against secondary tumor formation.

In additional cancer therapies, CellTraffix seeks to provide solutions for adult stem cell transplantation.  CellSelect technology holds potential to provide modes of harvest and isolation of superior stem cell populations from Bone Marrow or Whole Blood donation product.  Moreover, the ability of CellSelect to both adhere certain cell populations for harvest and therapeutically modify other cell populations with Signalling Molecules, means that CellSelect products will benefit both allogeneic and autologous recipients, whose risk involves either graft versus host disease (allogeneic) or reintroduction of cancer (autologous).


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Schematic of CelTraffix prototype device for use in processing Bone Marrow donation following traditional cancer therapies.  Bone Marrow or Whole Blood donation product is flowed through CellSelect device specially tuned to remove or initiate cell-death in undesired cells, including T-cells and Circulating Cancer Cells.
Additionally, recent clinical advances in adult stem cell-based therapies such as the successful removal, reprogramming, and reintroduction of cells into a patient, highlight the powerful potential of adult stem cells as a new therapeutic target for a range of diseases, including diabetes and cardiovascular diseases.

 
Commercial Strategy
CellTraffix is focused on continued development of its core technology to produce research and diagnostic kits targeting oncology and stem cell applications. These products have relatively low barriers to entry in terms of cost and time to market. The Company will also work towards developing a series of viable prototype devices (including both ex vivo and in vivo designs) for metastatic cancer prevention. We further plan to engage select pharmaceutical companies for partnering discussions to continue device development and fund product approval.
 
Collaborations
Partnerships with both academic and industrial/private sector entities contribute to ongoing development of CellSelect technologies. 

For example, CellTraffix collaborates with the University of Rochester in key research activities including adhesion and isolation of Target Cell populations from mixed cell samples, induced killing of cancer cells, and development of superior surface chemistries for immobilization of adhesion molecules. 

CellTraffix has recently completed proof-of-concept experiments in which prototype devices were successfully implanted into live rats, resulting in targeted capture and enrichment of viable adult stem cells from blood circulation.  Results of these and other studies in prominent peer-reviewed journals provide excellent public exposure for CellTraffix’ patented CellSelect technologies.
 
Intellectual Property
CellTraffix has exclusively in-licensed a portfolio of patents, applications and know-how from both the University of Rochester and Biomed Solutions (investor in CellTraffix). The portfolio contains US patents and applications along with their corresponding international counterparts. The portfolio covers devices for adhering, rolling and modifying targeted cells. The Company plans to continue to file new patentable inventions as appropriate to protect its core technology.
 
Partnering Opportunities
CellTraffix plans to engage in commercial discussions with select parties once key development milestones are reached. The Company intends to pursue both co-development and/or joint-licensing relationships for therapeutic applications. This approach will yield financial benefits in the form of joint funding of programs, early upfront payments and milestones, and additionally allow CellTraffix to leverage the competencies of these partners.