The core of our platform technology is based on the design for novel devices employing a cell adhesion matrix (CAM, a porous layer of extracellular matrix polymer coated with blood-borne adhesion molecules) that mimics the interstitial microenvironment, in which tumor cells are invading from primary site. For cancer detection, we have used the cell adhesion matrix (CAM) technology to achieve two goals: enrichment and discrimination of circulating viable tumor cells from non-viable tumor cells and the vastly greater number of normal cells in blood.

Figure 2 (below) shows the two novel aspects of the CAM technology:

1. a one-step, one-million fold enrichment of rare (cancer) cells that can enable approximately one-hundred times better cancer detection sensitivity using current technologies
2. introduction of a new way of identifying cancer cells using the ability of cancer cells to bind and digest CAM fragments.

Figure 2: Detection of rare cancer cells in the blood using Vitatex´ CAM technology.
I. Cancer cells are rare cells in blood, numbering one in millions of cells, but are distinguishiable from normal cells by their invasive characteristics.
II. Only live tumor cells have binding affinity to the CAM film. The CAM surface can specifically trap cancer cells leaving normal and dead tumor cells in solution.
III. Cancer cells not only bind to the CAM surface, they also ingest the CAM. When the CAM is fluorescently labeled, only invasive cancer cells exhibit positive fluorescence from ingested and concentrated labeled CAM fragments (CAM+; the proclivity to degrade and ingest CAM is one of the hallmarks of invasive and metastatic cells).
IV. When the remaining CAM outside the cells is digested with CAM-degrading enzymes, cancer cells with internal CAM fragments become labeled. This cell identification method provides a unique opportunity of identifying cancer cells present in the blood.

Vita-Tech™ is the result of 20 years of R&D at Dr. Wen-Tien Chen´s laboratory on the invadopodia hypothesis. Our CAM-initiated cell separation technologies are based on an invasive behavior exhibited by tumor cells: such cells, which express cell adhesion receptors and integrins on "invadopodia" (surface protrusions of cancer cells) adhere rapidly and tightly to CAM. In turn, invadopodia carry a battery of proteolytic enzymes, allowing tumor cells to digest and invade surrounding interstitial microenvironment.

Normal blood cells lack such integrins and are non-adherent. Dead tumor cells also fail to adhere in this active process. Figure 3 shows the dynamic association of invadopodia of invasive tumor cells with the CAM.

Figure 3 - Invadopodia: membrane protrusions of an invasive tumor cell involving in the invasion into the connective tissue.
A. Side view of an invadopodium
B. Top view of breast carcinoma cells labeled with fluorescent monoclonal antibody directed against an invadopodia antigen.
C. Super-imposed image of breast carcinoma cells labeled with fluorescent monoclonal antibody directed against an invadopodia antigen and their underlying red fluorescent CAM film. Invadopodia move outward as cells spread and remove (degrade) the underlying CAM, leaving black areas under the cell body.

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