By Mary Welch

In 1996, Jon Faiz Kayyem wanted money for the company that he ran from his garage. "I needed to prove my idea but before I could raise any money; I had to explain to the potential investors what genomics was. No one knew."

Since then, genomics has become a household word and Kayyem's company, Clinical Micro Sensors Inc. (CMS), has moved out of the garage. CMS, which now employs 70 people, is involved in the field of mass applied genomics - the widespread application of genetic knowledge to medicine and industry.

The Pasadena, Calif.-based company is developing DNA testing units and disposable biochip cartridges, combining universal platform design and advanced bioelectronic technology in convenient benchtop and hand-held formats.

"I was working on my post-doctoral studies at Cal Tech and working with electrons that flow through DNA, Kayyem said. "It was when Affymetrix was spun off and the whole biochip world became very exciting. I wanted to use electronic reading off the chip rather than optical fluorescence, which is what the other companies were focusing on. The basic technology is much less complex and lets us build portable and hand-held devices, which is our goal."

CMS' eSensor technology relies on bioelectronics to detect, among other targets, single nucleotide polymorphisms (SNPs). Bioelectronics is the formation of electronic circuit elements using assemblies of organic molecules on surfaces. The technology uses the complementary binding properties of DNA and RNA to assemble an electronic circuit element, which creates a detectable electronic signal when the target DNA or RNA is present.

The system employs small DNA biochips containing electronically active electrodes coated with specific DNA probes. These probes on the chips' surface "capture" specific target DNA present in the sample, which generates a unique, characteristic electrical signal. Each CMS chip can detect several different DNA sequences at once from a single patient sample.

In a recent study, 56 patient samples with genetic profiles unknown to CMS, and 10 with known profiles, were analyzed. The patients were undergoing testing for hereditary hemochromatosis at the University of Wisconsin Hospital and Clinics in Madison. These samples included mutations coding for the C282Y and H63D amino acid changes, which are the most common defects responsible for hereditary hemochromatosis.

The eSensor technology successfully identified the states of all 66 patient samples.

The technology identified patients with normal DNA, those harboring the disease-causing mutations, and those classified as carriers of hereditary hemochromatosis.

CMS doesn't anticipate beginning the regulatory process until next year after it has manufactured its first eSensor product. Toward that aim, the company hired Edward Cook as vice president, manufacturing and product development.

Hereditary hemochromatosis, an iron-overload disease, is a potentially fatal disorder affecting millions. There are more than 1 million afflicted in the U.S., and some 32 million more are silent "carriers" of the genetic mutations, which may be passed on to their children. Because it has non-specific symptoms, it is often overlooked by physicians.

Left untreated, excess iron that builds up may lead to cirrhosis, diabetes and even heart irregularities. Liver cancer is the leading cause of death from the disease.

The company wasn't planning on having this indication become the initial focus of its efforts, Kayyem said. "We were going in other directions, but since people have started hearing about the trial's results, we have had a lot of phone calls interested in the study and the technology. It may cause us to re-think our plan."

The company also intends to first focus on non-clinical applications, such as agriculture, animal husbandry and food safety testing.

"That would give customers a feel for the technology and we can work with the regulatory bodies more effectively," he said.

CMS also intends to take its DNA testing into non-laboratory settings as well. "We want to have the test be hand-held so that it can be given in the field or in an office," Kayyem said.

Now that CMS has finished its first large, blinded-study, raising money is easier than when Kayyem first rounded up investors. He raised $6 million in that first attempt in 1996, and another $15 million in 1998. That second round attracted Motorola Inc., of Chicago, which is a minority owner of CMS. Another prominent investor is Los Angeles-based Smart Technology Ventures.

CMS is finishing up its third round of financing and Motorola and Smart Technology Ventures are both participating again.

"We've come a long way from when I had to tell people what genomics was," Kayyem said.

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