The PC-based Bactobridge H^TM comprises module blocks, each containing up to 20 conductivity measuring test tubes maintained at a controlled temperature and time, which can be pre-set by the user through a Windows 95/NT software application called BactoWatch. The Bactobridge H^TM and its associated system, includes a PC workstation that can electronically link up to 15 Bactobridge H^TM Modules with a total of 300 conductivity measuring test tubes. In the "1 Per Reaction Protocol", there are 10 Sets of "Control and Reactant" conductivity measuring test tubes per module, which allows up to 150 independent tests to be conducted, simultaneously. In the "2 Per Module Protocol" there is "2 Control" conductivity-measuring test tubes per module which allows up to 270 dependent tests to be conducted, simultaneously.

A Windows 95 version of the BactoWatch software program controls the "four modes" of operation of the Bactobridge H^TM (heating module, initializing and performing test and test complete). BactoWatch displays in it’s "Active Window", - what mode of operation - the Bactobridge H^TM. Module is in during all stages of the "Test Run".

After the test has been running for approximately 10 minutes, if desired, histograms can be viewed by selecting the "Histogram" command on the toolbar or from the "Histogram Menu", select "Show Histogram". Histograms can only be viewed during the "Performing Test" mode of operation. The "Histogram" shows the current reading for all conductivity measuring test tubes in relation to each other for that test. The scale will automatically change as the largest reading gets bigger or smaller. So the largest reading will generally appear to be the whole height of the graph. Remember that the purpose of the Histogram is to show 'current state relative performance'. Graphs show conductivity measuring test tube histories (traces) against other conductivity measuring test tube histories (not necessarily from the same test). Indeed traces from previous tests (i.e., test stored on the hard drive) can be shown on the same graph and a single trace can be shown on multiple graphs.

The major advantage of the Bactobridge H^TM over existing technologies is that there is no long incubation period necessary to grow bacteria. Accurate and quantitative bacterial level determinations can be conducted very rapidly. As an incubation instrument with associated computers, users will be able to detect the presence or absence of specific microorganisms within minutes after collection of samples. For instance, the metabolic activity of 1,500 E-coli was detected within 15 minutes, while with an inoculum of less than 5 x 10 organisms the initial activity was detected in approximately 45 minutes.

To overcome the disadvantages and limitations of current laboratory technologies, by design, the Bactobridge H^TM uses a conductivity measuring system. Electrically matched pair of conductivity test tubes is placed in a measuring bridge and it's associated circuitry. The control conductivity test tube contains an inert medium and the reaction conductivity test tube contains the medium and the sample to be tested. The changes in the electrical impedance (conductance of the medium) are then measured. Hence by using a selective differential medium both quantitative and qualitative microbiological data collection and analysis can be achieved. Inoculations of 5 x 10 microorganisms per ml or more will cause an offset in the balanced impedance bridge circuit of the Bactobridge H^TM and produce an electrical current (conductivity) curve that follows the integral of the viable count curve. Conductance curves of metabolic activity show linear slopes for the concentrations of E-coli and Salmonella.

The Bactobridge H^TM has been cleared by the FDA for in vitro analysis of cancer cell responses to anti-cancer drugs [510(K) #936123]. Inoculations of cancer cell suspensions into the conductivity measuring tubes causes an offset in the balance of the impedance bridge facilitating conductivity measurements (of the medium) to detect early cell metabolism and subsequent cell division. Current methodologies utilized for tumor cell sensitivity are based on tumor cell culture with inherent limitations related to minimum specimen volume and time required for analysis (days); thus the possibility for tumor cell mutation exists and the ultimate test tissue may not represent the tumor in vivo. Bactobridge generated tumor cell analysis requires hours rather than days for testing. The tumor tested represents a closer correlation to tumor behavior in vivo. Reduced turnaround time will result in reduced laboratory costs with subsequent positive effect on patient management and total health care costs.

Tumor cell evaluation shows that utilizing the conductance pathway of metabolizing tumors within the closed system of the reaction cell can provide a convenient indicator of alterations in the cellular milieu (following exposure to anticancer drugs); and, that the Bactobridge H utilizing bridge technologies and principles of conductance/impedance will display resultant characteristic patterns correlating with drug sensitivity, in real time. We expect that each tumor type will produce subtle but specific conductance curves. We also expect that some tumor types may not be viable candidates for evaluation by the Bactobridge. The scope of testing for each individual sample will be defined by the viable cell count following processing. Optimization requires the identification of the requirements of each specific tumor type for media, incubator parameters, and sufficient data to have statistical predictability power. These factors are dependent on tumor biology specific for each tumor type.

Currently, immuno and colony forming assays are often used to determine the effects of various anti-cancer drugs on biopsied tumor cells. The problem is they are limited in revealing information about biological mechanisms. The Bactobridge provides a vehicle for developing safety test for selective proof of bacterial contamination and endotoxins. The Bactobridge can be used to replace the need for genetic modification of patient cells to test for contamination to avoid side effects.

The Bactobridge can be used to monitor rapid changes in cell environments and simultaneously monitor cellular responses to antibiotics as they occur. The immediate effects of environmental changes on microbial metabolism are often dramatic and generally occur long before changes in growth rate (measured by photometry) can be detected.

In recent years Researchers such as Dr. Victor Ling, have determined that a multi-drug resistance/p-glycoprotein (pgp) is the gene/protein responsible for chemotherapy failure in the treatment of many cancers, including breast cancer. Traditional immunoassays can take from 2-3 weeks before results are known and in certain cases, colon, breast and lung cancer cells won’t grow, in-vitro. Dr. Ling has stated that the results of his experiments have shown that if normal, non-transformed, primary cells are removed from a person and grown in-vitro these cells that originally did not express detectable drug resistance, within hours demonstrated hundreds-of-fold induction of mdr.

In point of fact, according to Researchers at the Southern California Medical Oncology Association "drug resistance is a multi-factorial phenomenon". Chemosensitivity assays measure the net effect of many or all of these mechanisms mdr/pgp does not. On average, in studies inclusive of 4,000 patients, patients were found to be seven fold more likely to respond to treatment containing in-vitro active drugs than to treatment comprised of in-vitro "inactive drugs".

Of great significance in the study of human malignancy is the fact that all tumors induced by virus contain the same new tumor specific antigens. Tumors induced by different viruses have different antigens although they too have some antigens in common with other tumors induced by closely related viruses. This is particularly true of some of the RNA viruses, which are considerably larger then DNA viruses.

Briefly, it is not surprising that cell surface transplant antigens are altered in malignancy; these changes are reflected not only in the normal antigens but also in the formation of new tumor specific antigens. Although such tumor specific antigens are probably not confined to the surface, it is on the intact cell that they are most readily observed. The effect of malignancy on normal transplantation antigens appears to be primarily one of simplification - particularly where the tumor cell has lost most of its biological specificity and has reverted to an undifferentiated form. Of the variety of normal transplantation antigens present on the surface of a single cell (H-2 antigens in the mouse, H-LA in man, etc. - antigens determined by the major histocompatibility locus) none appears to be completely absent, all may be reduced in degree of representation on the cell surface.

In addition, the tumor cell may show new antigenic specificities that were not present on the normal cell. Experimental tumors found to have tumor specific transplantation antigens include all of the virus-induced tumors, all of the chemical carcinogen induced tumor, many of the physical agents induced tumors, and some "spontaneous" tumors.

The truth of the matter is, many tumors resist full penetration by anti-cancer agents. Such resistance may help to explain why drugs that eradicate tumor cells in the laboratory often fail to eliminate malignancies in the body. To eradicate tumors, anti-cancer agents must be dispersed throughout the growths in concentrations high enough to eliminate deadly cells.

One of the first problems, a blood transported drug encounters en-route to cancer cells is an uneven distribution of blood vessels. Furthermore, the aberrant branching and twisting of the vasculature often contribute to an observable slowing of the blood flow - a phenomenon that is exacerbated by the unusual viscosity of blood in tumors. The relative lack of oxygen in tumors may lead cancer cells to secrete high levels of lactic acid.

Although a number of drugs break down or fail to work in an acidic environment, some drugs actually work better in acidic or hypoxic environments. The Bactobridge can be used to determine which works best in either environment. Research conducted at Harvard University and the Massachusetts General Hospital suggests that combining anti-vascular therapies with therapies that are designed to attack cancer cells could well improve the effectiveness of both types of treatments.

They believe to be more precise, investigators will have to increase perfusion in poorly vascularized areas, increase permeability of tumor vessels, reduce interstitial pressure and increase the rate of interstitial transport.

Senior Researchers at the University of Maryland Cancer Center have been quoted as saying, "starting with the right drug is very important to the patient." "This is extremely vital for instance, if a patient has failed first-line chemotherapy, the chance that he or she will respond to secondary chemotherapy regimes is reduced significantly". Many chemotherapeutic drugs are known to induce cross-resistance and multiple drug resistance, and by that generate additional mechanisms that interfere with either palliative or curative therapy. Then there is the issue of pain and suffering and the unnecessary expenditures for not only the chemotherapeutic drugs but the antiemetic and hydration fluids and pain medications while theses patient are going through ineffective therapy that should not have been administered".

Selecting the right drug the first time is very important for another reason. A failed attempt can cost $7,000 to $25,000 to say nothing of the emotional burden it places on the patient (source: J. Marvin Figenbaum, Chairman, President and CEO of Nu-Tech Bio-Med, Inc. a NASDAQ traded Company.

In 1981, Ommaya et al , Director of Neurosurgery at the National Institutes of Health was able to obtain quantitative sensitivity data in less than four hours of working time after surgical biopsy of the tumor using the Bactobridge. Single cell suspensions of human gliomas, one epidermal cancer of the mouth, and two drug resistant cell lines were treated with various anti-cancer agents and resultant changes in electrical impedance were measured as indices of cancer cell sensitivity to the drug. Results suggest that the impedance changes measure a true sensitivity of cancer cells to chemotherapy and may reflect alteration in cellular metabolism associated with a cessation of cell division.

The Company's healthcare information network can help physicians distinguish between patients at high risk for re-occurrence who should get therapy from those who do not need therapy after therapy. The value of this information could be enormous. Up to 15% of all cancers defy classification by visual examination. In fact, the diagnosis of "metastatic cancer of unknown primary site" is the eighth most common cancer diagnosis. Furthermore, visual examination of tumor provides very little information about the growth rate and the type of treatment to which they will respond.

In 1985, Gatter et al submitted data on 120 patients to Pathologist at Oxford University, an internationally recognized medical center, who thought 53 cancers were lymphomas, 43 were carcinomas and 24 were unclassifiable. Further review revealed, 80 cases of lymphomas (including 29 formerly classified as carcinomas) and 27 as carcinoma (only one quarter of these were originally diagnosed correctly).

The implications from this are clear, for poorly differentiated tumors, morphological assessment alone errs so often (in nearly 50 percent of cases overall), that failure to perform immunohistologic studies is difficult to defend ethically or legally.