A Conversation with Nanogen Co-founders

Birndorf is currently Nanogen’s Chairman and CEO. Heller, a professor of bioengineering and electrical and computer engineering at the University of California, San Diego, continues his affiliation with Nanogen as a consultant.

NGP. When Nanogen was founded, how did the idea for the technology come about?

MH. I started working on this technology around 1990. The idea a lot of people were thinking about was to take things people were doing in the lab – nucleic acid hybridization, gel electrophoresis, PCR – and do them in a parallel manner. I also had a background in detection, in putting fluorescent and chemiluminescent dyes on DNA and wanted to do something in the DNA field. A friend of mine had a small biotech company, and he rented me an office. I had some resources, not a lot but enough to keep me going for a couple of years, and I was experimenting with electronic movement of DNA. I got some patents filed and went to see Howard at Enterprise Partners. He really liked the electronic array; he thought that looked like something you could run with.

HB. I believed personalized medicine was going to be coming into the forefront, and this technology looked like it had the potential to penetrate the diagnostics marketplace. I was very excited – and I remain very excited – about the potential of electronic array technology to deliver a robust platform for advanced diagnostics.

NGP. What were some of the hurdles you faced?

MH. Getting the chips made and getting them to perform was a hurdle. Normally, no one pours salty water on a silicon chip. We spent a lot of time developing a permeation layer that would protect the DNA during electrolysis. And of course building any highly integrated device is a challenge, and for diagnostics purposes things need to work perfectly. So getting the instrument to where it needed to be took a lot of effort, but the new instrument (NanoChip® 400) is really nice.

NGP. From the beginning, were you thinking beyond microarrays for diagnosis? Were the fabrication applications obvious to you?

MH. Definitely. Right away, in the first patents and papers we published, we realized that we could move around anything on the chip – other molecules, proteins, polymers, other particles, even cells. We were always thinking beyond genotyping.

NGP. What advantages does electronic “pick and place” offer over other available methods for nanofabrication?

MH. Number one is that it’s scalable. You can start with nanomaterials and finish with something you can see. The technology allows you the ability to manipulate any kind of material, and it’s also fast. In seconds, you can put down a layer of components and then build up.

NGP. How can Nanogen’s technology facilitate progress in developing nanomedical applications?

MH. First, the system may be able to help make drug delivery devices – what people call “motherships” – circulating devices the size of red blood cells that package drugs, imaging agents, antibodies to target them to specific tissues or cell types, perhaps circuits that could communicate back to physicians. A second application might be the construction of small medical devices – “lab on a chip” diagnostics. Nanogen is working toward smaller microarrays right now. A lot of this sounds like science fiction, and it won’t happen tomorrow, but it’s coming.

NGP. What has been the impact of the National Nanotech Initiative in the United States?

MH. It’s been very helpful. It’s brought nanotechnology to everyone’s attention. And nanotech is big throughout the world, of course. There is some hype, but there is also huge potential.