PARK RIDGE, ILL. - Biochip development, which peaked two years ago during the national anthrax scare, has begun paying unexpected dividends, as research work in the area is yielding a new breed of so-called "protein chips" that could help with early detection of cancer, Alzheimer's disease, and HIV (human immunodeficiency virus).

Researchers at a start-up nanotechnology company last week took a first step in commercializing the technology when they acquired a new protein-chip-based detection system that they hope to integrate into desktop products within a year.

Nanosphere, Inc. (Northbrook, IL) said that the new detection technology exhibits about one million times more sensitivity than conventional methods in the detection of prostate-specific antigen, a protein linked to prostate cancer. The announcement followed the September 26th publication of the technology's foundation in the journal Science by one of the company's founders.

Nanosphere's pronouncements put the company in lock-step with other members of the world's technical community, many of whom have been accelerating their efforts in the development of protein chips.

"Protein chips are the next generation of biochip technology," noted Darrell Chandler, technical group leader for Argonne National Laboratory's Biochip Technology Center (Argonne, Ill.). "DNA chips were the first generation, and now a lot of people are working very hard on protein chips because they provide the ability to diagnose diseases based on certain protein signatures."

Looking for proteins

Researchers at Argonne said last week that their Biochip Technology Center has developed protein chips that can be connected to a CCD (charge-coupled device) camera or CMOS chip, and could one day serve in handheld protein chip-based diagnostic devices.

"Ultimately, we can foresee putting the chip into a cartridge, and having the cartridge fit into a Palm pilot or a similar device," Chandler said.

Similarly, researchers at Pacific Northwest National Laboratory (Richland, WA) are developing protein chips that allow researchers to screen for multiple proteins simultaneously. They plan to use the technology to identify new protein markers that could serve as a screen for the presence of breast cancer.

Some researchers, such as those at Argonne, are developing systems that work in conjunction with optical detection techniques and don't need to be directly connected to electronics. Argonne's chips, which are essentially glass slides, employ an array of tiny gel elements, or "nano test tubes," onto which researchers cram tens of thousands of proteins in a square area measuring a half-centimeter on a side. Argonne has demonstrated the technology in portable biochip readers that optically examine the slides as a means of detecting biological agents or chemicals.

Argonne's approach differs from that of Nanosphere, Inc., which plans to employ an electrical technique that uses silicon protein chips containing gold nanoparticles. The chips include contact pads and on-board circuitry made from a combination of chromium and gold. Invented by a Northwestern University professor who is also a company founder, the technology is already being used to detect strands of DNA, and will now be used to detect protein markers, as well.

Nanosphere uses the technique to measure bonding between DNA strands in, for example, a drop of blood. DNA strands in the sample combine with similar strands in the silicon substrate and in the gold nanoparticles, which measure about 15 nm wide. To check for bonding, researchers measure the electrical resistance across two gold particles, located microns from one another.

When no bonding is present, resistance is high, and electrical current barely conducts across the gap between the particles. But by laying a capture strand of DNA across the gap and then applying a blood sample, researchers can create an electrical bridge. The resulting change in conduction signals the presence of the DNA or protein that they're looking for.

The company's engineers said that the electronic technique shows promise for high volume production of handheld detection devices.

"Electronics allow you to put gold electrodes onto a silicon base, which can be manufactured in high quantities," said William Cork, chief technical officer for Nanosphere. "With electronics, the costs go down because the complexity goes down."

The start-up company said it has used the silicon-and-gold configuration in its Verigene ID desktop system, which was unveiled over the summer and is currently undergoing clinical trials. Nanosphere's engineers designed the system using an off-the-shelf single-board computer from Ampro Computers, Inc. (San Jose, CA) and an in-house-developed "glue logic" board. The glue logic board integrates all the I/O, including touch screen drivers, along with FPGAs and software interfaces.

Security aid

Nanosphere's biochips, like those made by other researchers, can also be used for identification of DNA from such pathogens as anthrax, smallpox, and tuberculosis. Many researchers are working with government agencies on biochips that can be used to detect the deadly contaminants in military and civilian settings.

Nanosphere engineers said they plan to initially sell their Verigene ID desktop system for $30,000, and their Verigene Mobile system for approximately $5,000 when it reaches the market.

"But if we get an order for 10,000 units from the Defense Department, the prices would drop fast," Cork said.

In medical settings, Cork said that the protein chips offer vastly greater sensitivity than existing protein detection methods used by today's medical community.

"Today, there are a lot of applications where the detection of proteins is fairly routine," Cork said. "But this offers far greater sensitivity than those tests, and it gives more diagnostic information than has ever been available before."

For cancer victims, or for those with the potential of contracting certain cancers, the new technology reportedly could detect cancer much earlier - possibly ten times sooner than it is detected today.

"There is concurrence (within the research community) that we could detect it earlier," Cork said. "How much earlier we still don't know for sure."

Researchers said that the protein chip techniques could also be used for earlier detection of Alzheimer's Disease and HIV.

"The real value of the protein chips will definitely be in life science research," said Chandler of Argonne. "Discovery of the proteins will come first, and then we'll create tools to do the diagnostics."