Please tell us about yourself

What recourse does an entrepreneur have when there is no venture capital for a start-up with a truly promising invention? At San Diego’s Biological Dynamics, 27-year-old founder Raj Krishnan’s solution is to win entrepreneur and student competitions—and so far he has won 13 awards, nine of them this year, including most recently a $40,000 first prize in the UC San Diego Entrepreneur Challenge, where the judges were impressed with his presentation skills. “We went to the competitions because venture capital is extremely hard to find now, and we have been fortunate. It enables us now to protect our IP and pay bills,” Krishnan says.

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Raj Krishnan talks eagerly about the prospects of someday making a cancer diagnosis no more troubling to a patient than telling someone they have caught a common cold. And the bioengineering Ph.D. student at University of California San Diego says he may have found a way to make that happen. Krishnan’s team of fellow UCSD students and professor Michael J. Heller believe they have found a simple and cost-effective way of detecting cancer at its outset.

Nowadays finding a cancer at an early stage usually means it can be cured. But there hasn’t been any method of detecting cancer in its earliest stages. Symptoms usually aren’t apparent until the cancer has reached a late stage of growth.

Tell us about your work

As cancer cells begin to grow, an increased amount of DNA circulates in the blood. Krishnan says this increase in “cell-free” DNA is believed to be of cancerous origin. In the 1970s, scientists noted that people with tumors have a lot of free DNA in their blood, but serious studies have only been done lately. “There still hasn’t been an easy method to isolate the DNA without degrading it,” says Krishnan. “Ours is the first that doesn’t do that, and it’s a very clear and very easy separation.”

Krishnan’s research efforts have been directed at creating technology to identify abnormal amounts of cell-free high molecular weight DNA in the blood. High molecular weight DNA is widely considered a good secondary biomarker for almost every type of cancer, but separating nanoparticles of DNA that circulate in extremely small amounts has been problematic, to say the least. This DNA is thought to be of 5-50 nanometers in size, which means it is smaller than the wavelength of light. “It’s very difficult to find in blood. The analogy of needle in the haystack has been used, but I’d say it’s more like looking for a needle on the whole farm,” says UCSD’s Heller, a professor of bioengineering. Krishnan discovered it can be done by generating an electric field through a microelectrode array.

Until recently, using AC (alternating current) electric field techniques to separate nanoparticles such as DNA from blood would have been considered impossible because of the salt concentration and constituents in the blood. But Krishnan has been able to demonstrate that this can be accomplished under certain conditions, proving that some widely held aspects of the previous theory were incorrect. Krishnan’s Eureka moment happened about two years ago, when he was running experiments on a microelectrode array. “Late that night I decided I had nothing better to do, and I would just run that experiment. As I had set it all up I needed only to push a button and leave the room; if nothing happened, there was no harm. When I came back to the room, I went ‘Oh my God! Nothing was supposed to happen!’ but it had happened,” says Krishnan. He had managed to isolate the DNA— even in blood samples with extremely high salt concentrations.

UCSD’s Heller was astonished. “I said to him first he must not have been doing it right,” laughs professor Heller, a former co-founder of Nanogen and now co-founder of Biological Dynamics. “All I did differently was try something when most people would have just accepted the answer as being impossible because the theory said so,” Krishnan says. The professor and graduate student spent six months finding out what happened and why nobody else had seen it.

How did you end up in such an offbeat, unconventional and unique career?

Rajaram Krishnan was born in India. He lived in Calcutta, and later spent three years in Indonesia until his family moved to San Jose, CA, when he was eleven years old. He says he loves basketball, video games, books, traveling, and puzzles. At UCLA he first tried computer science but found it too monotonous, and chose bioengineering because he was really good at mathematics, chemistry and physics. “I didn’t want to be stuck in a cubicle in 10 years designing a smaller cell phone. I realized the best way I could have an impact was by building tools that doctors use,” he says. He received a B.S. in electrical engineering from UCLA in 2004, after which he moved to UCSD, where he received an M.S. in bioengineering in 2006.

Krishnan, professor Heller, and fellow grad students David Charlot and Roy Lefkowitz founded Biological Dynamics to move their diagnostic technology to clinics. The start-up company’s business plan calls for developing two products, a blood analyzing system priced around $20,000, and one-time disposable electrode cartridges priced around $20. They have secured their findings with patent applications, and they hope to soon begin making the devices. In laboratories at UCSD’s Moores Cancer Center, Krishnan and the rest of the team encounter late-stage cancer patients every day. “I just hope what we do would become something that could save a lot of lives,” says Krishnan.