For lab chips, the future is plastic

Development of an economically feasible "lab on a chip" is getting a boost from the efforts of two Northern California companies. The breakthrough is the work of competitors Soane Biosciences (Hayward) and Caliper Technologies Corp. (Palo Alto), now running neck and neck in the race to develop low-cost, disposable lab chips made with injection-molded plastic.

Soane demonstrated its plastic LabCard for chemical analysis at the High Performance Capillary Electrophoresis Conference (Anaheim, CA) in late January. Caliper recently entered into an agreement with Dow Chemical Co. (Midland, MI) to develop a plastic version of its LabChip.

Until now, most experimental lab chips have been micromachined on glass, silicon, or other substrates, resulting in a chip too pricey to throw away. While good for certain research applications, including high-throughput drug discovery, such micromachined chips have not been adaptable to disposable diagnostic use.

Injection-molded plastic lab chips, such as this example from Soane Biosciences, promise low cost and disposability.

"As a group, the micromachined diagnostics being developed today are overwhelmingly aimed at the nucleic acids analysis and nucleic acids diagnostics markets," says Michael Knapp, PhD, Caliper's vice president for science and technology. "Some day that will be a very large market, but today it's very small. So researchers in that field are developing technology for a speculative market, perhaps hoping to accelerate the development of that market. In the meantime, there are many other analytical applications for in vitro diagnostic products that already account for a very large market." It's this ripe existing diagnostics market that Caliper and Soane plan to exploit.

The companies' chips, each about the size of a 35-mm slide, use microfluidic integrated circuitry to microscopically perform all the liquid handling and biochemical processing needed for sample analysis. They perform sample processing and accommodate a variety of ligand-binding assays and molecular separation methods, including electrophoresis, chromatography, and molecular sieving. "The chips' channel structures and active fluid-flow controls provide a framework for performing almost any analytical task you can imagine," Knapp says.

Another benefit of the chips' design is that each test consumes only minuscule volumes of sample and reagent. Sample volumes can be as small as 10 pl, a critical advantage when only a small amount of sample is available. "You can't take a 25-ml sample from a neonate, because that may approach the total volume of available blood," Knapp observes.

Both companies have expressed interest in partnering with multiple diagnostics manufacturers through the use of nonexclusive agreements.

"Every major diagnostics manufacturer is very actively looking at this field with an eye toward making investments," confirms Herbert Hooper, PhD, Soane's vice president for research and development. Soane has already partnered with Hitachi Chemical (Tokyo) to develop an immunodiagnostic system for the Japanese market using its disposable plastic LabCards.

Caliper has yet to sign an agreement with a diagnostics manufacturer. But progress toward commercialization of Caliper's technology took a leap forward last October, when the company signed an agreement with Hoffman-LaRoche, Inc. (Nutley, NJ), to develop a high-throughput drug-discovery system based on LabChips. Soane is collaborating with an unnamed pharmacetical company on a similar drug-discovery project.

According to the companies' experts, almost any immunodiagnostic or DNA-based test could conceivably be run on a chip. But they acknowledge that such chips will never replace large, high-throughput conventional analyzers for routine, high-volume tests. The cost-effective candidate tests are those for which an immediate quantitative result would provide a significant health benefit. Point-of-care tests for use in emergency-care settings--such as cardiac marker panels--offer an obvious target for future product development.

"In chest pain evaluation," Hooper explains, "being able to accurately diagnose acute myocardial infarction [AMI] early can result in enormous health-care savings." A point-of-care cardiac marker panel would enable physicians and emergency medical technicians "to release patients who have not suffered AMI, to ensure that patients who have had AMI are not released inappropriately, and also to begin administration of therapy more quickly," Hooper adds.

Knapp agrees that point-of-care testing is the hottest diagnostic market for the new disposable chip technology. Using these chips, he says, "People can get diagnostically relevant chemical and biochemical information whenever and wherever they need it--even if there is no trained technician around. I think that's the nearest-term diagnostic product opportunity."

Penetrating the point-of-care market, however, will hinge on the availability of an analyzer inexpensive enough for sale to physicians' offices. Both companies say development of such an analyzer is quite feasible. Because all liquid handling takes place within the chip, says Knapp, the analyzer for reading the chips is "unbelievably simple."

The interface between the chip and the analyzer consists solely of electrodes, which exert electrokinetic forces to move fluids through the chip. Both companies are designing analyzers with light-based sensing systems. Current prototypes are based on fluorescent detection and spectral discrimination.

Even the early prototype models currently in existence are only about the size of a VCR. Caliper plans to launch an analyzer of about that size for the research market by the end of the year, with a price tag of about $5000 to $6000. But a handheld Caliper model for a different range of applications is in development as well. Soane expects to have products on the market for life science research within two years.

Both Caliper and Soane plan to debut their technologies with products for the unregulated life science and analytic research markets. The products will have applications in molecular biology, biochemistry, organic chemistry, and cell biology.

Products for the medical diagnostics market will follow. Asked to guess when a chip-based immunodiagnostic system might debut for the U.S. market, Hooper says, "I think we're looking at a three-year time frame."--Jenevieve Blair Polin