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Singled out: Diagnostic device developed by New Haven biotech can find one cell in a million

By Abram Katz, Register Science Editor

The body is trillions of cells, its blood is billions of cells. Within that multitude, one cell in the circulatory system may be an early warning sign of cancer or a valuable diagnostic tool.

The problem, of course, is how to pinpoint that one cell of interest from all the other somatic cells, blood cells, proteins, enzymes, antibodies and the other heavy traffic pumping through the vessels.

Using the conventional method of microscope, stain and human eye, the process would be orders of magnitude more difficult that picking a needle out of a haystack.

Now, a New Haven biotechnology company has made the job easier with an integrated robotic microscope, computer and system of fluorescent markers.


The Ikoniscope, made by Ikonisys of Science Park, has been approved for two uses by the U.S. Food and Drug Administration and already has been sold to about two dozen laboratories.

The FDA allows the blue and orange Ikoniscope to be used for testing in bladder cancer and during a pregnancy. Each new use must receive FDA approval, said Dr. Petros Tsipouras, chairman and chief executive officer of Ikonisys.

The Ikoniscope can pinpoint and characterize 1 cell in 100,000, said Triantafyllos Tafas, chief technology officer of Ikonisys.

While the significance of finding single abnormal cells is not yet clear, the Ikoniscope can locate fetal cells circulating in a mother-to-be, and perform a noninvasive alternative to an amniocentesis test. There is about 1 fetal cell in every 1 million maternal blood cells, Tafas said.

The blood sample would first be exposed to segments of DNA assembled to lock onto chromosome 21. These segments would also be linked to a fluorescent dye.

Maternal cells would contain one pair of chromosome 21. So should the fetal cell. However, if the fetal cell contains three copies of chromosome 21, the baby will be born with Down syndrome.

Maternal blood is exposed to the DNA probes and then inserted on a slide into the Ikoniscope. Several slides can be loaded into a cartridge that is inserted into the machine.

Instructions and commands are entered through a computer monitor on the front of the device. Computers in the machines can be configured in several ways, including one in which satellite machines feed into one master Ikoniscope.

Inside the machine, the microscope automatically scans all of the cells on each slide. Using a sophisticated pattern-recognition algorithm, the computer analyzes and sorts every slide.

All cells should show a light signal of at least two copies of chromosome 21. A cell or two might emit a signal of three copies.

Information about the light emitted from the cells is stored in a massive memory bank.

The computer then scans each image, pixel by pixel. First it examines the cells at low power and eliminates all of the "uninteresting" cells. In this case, that would include all cells with two points of light, indicating two copies of chromosome 21.

Cells with abnormal signals, either more than two copies, fewer than two, or some other unexpected light pattern, are then scanned again at high power.

After more computing, the machine presents images of cells with three copies of chromosome 21, if there are any, and all questionable results.

Ikonisys also has an approved test to identify bladder cancer cells circulating in the blood.

The technique is similar, but uses a different DNA probe. Cancer cells generally have multiple copies of chromosomes, a sure signal of abnormality. Probes can recognize bladder cells, and find any that contain extra copies of chromosomes.

Tafas said Ikonisys is interested in pursuing prostate cancer diagnosis, which is currently based on clinical exams and the amount of prostate specific antigen (PSA) in the patient’s blood.

Elevated PSA levels are ambiguous, however. PSA results include a high number of false positives — finding cancer where none exists — subjecting men to unnecessary biopsies. PSA tests also miss a high percentage of real cancers.

So, what does elevated PSA mean in the absence of prostate cancer cells? Does a finding of prostate cancer cells in concert with a high PSA score constitute a clear diagnosis?

Ikonisys plans to study these and other questions in collaboration with Oxford University, Tsipouras said.

Another basic question is what does an isolated abnormal cell mean, Tafas said. The immune system constantly locates and destroys haywire cells that might otherwise lead to cancer. Consequently, it is possible that very small numbers of isolated cancer cells might be normal, he said.

The answer will require more study.

Meanwhile, the Ikonisys system also could be used to judge the efficacy of cancer therapy, Tafas said. An effective therapy should yield few cancer cells in circulation. A poor one would leave more.

The rapid throughput of Ikoniscope technology is valuable in many areas of biological research, Tsipouras said. So, Ikonisys has received FDA approval to establish a research laboratory here. The lab should be operational in mid-January.

As an FDA-approved device, Ikonisys has to monitor the use of every bolt, screw, electrical component, wire and everything else that goes into the machine. The company keeps an extensive paper trail of parts and lots. One type of screw cannot be substituted for another without a great deal of complication.

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