Start-up to use genes to build better chips

The Palo Alto, Calif.-based company is using methods that will allow researchers to build semiconductors or other components by combining inorganic substances like cadmium sulfide with a vast library of genetically engineered organisms. Formerly known as Semzyme, Cambrios is officially unveiling its new name, strategies and venture backers this week.

In the vast majority of situations, combining a metal with a living virus or bacteria won't result in a breakthrough, but occasionally the chemical interaction between the metal and a protein from the organism produces elegant--and potentially commercially attractive--films or crystals, said CEO Mike Knapp. A seashell, after all, is chalk that has reacted with specialized proteins.

"This is the way evolution works. You try lots of stuff and see what works," he said. "Proteins can manipulate things. We wouldn't survive as humans if our proteins didn't manipulate things atom by atom."

Researchers have long discussed techniques for adopting processes found in nature, but practical advances in nanotechnology appear to be inching closer to reality. U.K.-based Nanomagnetics is examining ways to make tiny, uniform memory cells out of proteins. Japan's Matsushita is conducting similar research. Other companies are looking at ways to harness photosynthesis for energy production.

In academia, the University of Bristol created the Centre for Organised Matter Chemistry under Professor Steven Mann, who pioneered research in this area in the early 1990s. Montana State held a conference on biomineralization this week.

"Generally, people are looking for applications," said Eric Mayes, CEO of Nanomagnetics. "It is mainly academics in the area" right now.

Although it has only eight employees, Cambrios is one of the companies at the center of the research activity in this area. The company grew out of work performed by two of the pioneers in the field, Angela Belcher, a professor of material science at the Massachusetts Institute of Technology, and Evelyn Wu, an electrical and computer engineering professor at the University of California, Santa Cruz. (One of Belcher's graduate research projects examined how proteins control the growth and structure of abalone shells. She also studied under Mann.)

Scientific advisors include other academics, such as Stanford University's Fabian Pease, an expert in integrated circuits who is also well-versed in how to obtain grants from the Department of Defense and its DARPA research wing, said Knapp.

Cambrios recently received $1.8 million in early round venture funding from Arch Ventures, Alloy Ventures and Oxford Bioscience Partners and has begun to seek investors for a second round of funding. It also opened offices in Palo Alto.

Coli formula, here I come
The company's modus operandi can be likened to the old adage about throwing spaghetti on the wall and seeing what sticks.

The first stage of the process involves creating billions of random genetic variants of a bacteriophage, or virus, that attacks the E. coli bacteria. "We morph the genetic material of a parasite of a bacteria," Knapp said. (Though E. coli is commonly associated with food poisoning, researchers like to work with it because it's fairly well understood. "It is the workhorse of the biomolecular world," Knapp said.)

Altering the genome in an individual bacteriophage causes the virus to produce a novel protein. "Each bacteriophage has one protein but there are billions of bacteriophages," Knapp said. Researchers then examine how this huge, lab-generated library of proteins interacts with a foreign substance, often different types of metals.

Because of the number of different viruses and their respective proteins, the protein-substance encounters are not set up as individual meetings. Instead, the inorganic material is brought into contact with all of the different proteins at once. The proteins that don't stick or react to the metal or other foreign substance are washed away. "Bonding is the first step in how to manipulate these systems," Knapp explained.

Subsequent experiments then winnow the field to the most interesting results. The end results are varied: the same inorganic material will produce different types of crystals with a change in proteins Creating new substances out of a reaction between a protein and a metal comes as a result of the catalytic process many observe in high school chemistry. The big difference, Knapp said, is that most people don't associate proteins with this process, just inorganic minerals and elements.

A second technique involves combining inorganic materials with variants of a tube-shaped virus, known as M13, that measures 880 nanometers long and 6 nanometers in diameter. Instead of trying to form a third substance, researchers look to see whether the inorganic materials will bond into a coating around the virus.

In essence, researchers are forming fossils of the virus. The procedure could someday be employed to create nanowires, strands of atoms, generally made of pure silicon, that can be used to conduct electricity or light.

This process could also be used to create nanowires out of different substances or even composite nanowires that contain chemically distinct bands of varying materials. In January, Belcher's lab produced nanowires out of cadmium sulfide with this method.

The reactive and template methods are reflected in Cambrios' name, which derives from the Cambrian period. The period, which took place between 543 million and 490 million years ago, saw an incredible profusion of new life forms and genetic activity. The modern world also has many fossils from that age.

Cambrios is now at the point where it needs to begin to catalog materials that could become commercially viable. It also needs to develop a list of potential applications. One early commercial use could come in thin films. At present, putting different films together can require high temperatures and clean-rooms. Biological methods could cut costs by allowing manufacturers to conduct the process at lower temperatures, Knapp theorized. Materials employed for making electronic devices (gold, silicon, germanium) and magnetic (cobalt-platinum, iron-platinum) are amenable to these processes.

Some of these substances could also be used in new types of pixels. Another business idea is to develop bioelectrical tools that could be sold to larger, established manufacturers. As part of the tools push, the company signed an agreement with Dyax, a bioscience company specializing in designer proteins, to use that company's technology in electronics.

"We're trying to put together proof of concepts," Knapp said. "What we have to do next is bring out materials that are functional, demonstrable and relevant."