Microarrays, labs-on-chip enlist for early avian-virus diagnosis

Avian flu is already en route to the United States, Stohr said, via the same circuitous avenue that influenza has always taken. Today the disease cannot be transmitted from human to human, but WHO and other agencies fear that inevitably, people working with poultry in affected parts of the world will bring a human virus into the mix. When it merges with the DNA of the avian flu, a new strain will arise that can pass from person to person.

H5N1 has killed 60 of the 120 people infected so far. By contrast, the killer influenza of 1918 left 50 million dead for 1 billion infected worldwide.

The special H5N1 flu microarray funded by the National Institutes of Health is theoretically capable of one-hour turnaround, potentially speeding testing with a handheld flu chip "reader" that is being crafted by University of Colorado spin-off InDevR LLC in Boulder (http://indevr.net). But initially, it will take the researchers several weeks to evaluate the results of their first avian flu microarray.

The device is designed "to rapidly identify a particular strain in hours instead of days," said University of Colorado professor Kathy Rowlen, the chief scientist at InDevR. "This was our first microarray to be tested at the CDC. We exposed the microarray to a sample from a patient infected with H5N1. Now we are going to see how well our microarray can identify a real sample."

InDevR is developing a field-portable instrument that rapidly spots avian virus in body fluids, air and drinking water. Right now, samples must be amplified externally, then applied to the chip before being read with a microscope. InDevR's goal is an inexpensive portable reader, with internal amplification, into which a sample from a patient can be injected.

Microarrays have been around for several years, but they usually require hospital equipment to inspect the results of batch operations from many patients. Delivering a diagnosis on the spot merges the two functions of collecting the samples and testing them, making it a while-you-wait operation that almost anyone can perform. Such easy-to-use devices for mitigating the effects of pandemic flu could be here within a year.

"We have a microarray too, but ours is embedded inside our microfluidic chip," said Stefano Lo Priore, business development manager at STMicroelectronics. "We have already proven that our chip can identify RNA just as well as DNA, so we are ready to identify viruses too."

STMicroelectronics is already delivering its first In-Check parts (see http://eet.com/news/ latest/showArticle.jhtml?articleID=170100873) to customers that Lo Priore identified as "partners who identify genetic sequences." The plan, he said, "is to begin trials next year and have a clinically proven product by the end of 2006."

The entire lab-on-a-chip measures only 1 x 3 inches yet contains all the necessary mechanical, thermal, electrical and fluidic connections to perform polymerase chain reaction on an internal microarray, with a complete electronic system about the size of a shoebox. OEMs can use the chip to build field-portable devices that even nonmedical personnel could use for on-the-spot testing, ST said.

Diagnostic devices made with In-Check can be preconfigured for avian flu, according to the company, preventing a pandemic by delivering fast results.

"All you have to do is take a sample of a body fluid and extract its DNA — which is done off the chip for now," said Lo Priore. "Then you mix the extracted DNA with the proper reagent and inject it into our microfluidic chip, and our system takes over the test from there. All these operations can be done in about an hour, whereas in a large hospital this kind of test would probably be done overnight."

According to Lo Priore, on-the-spot tests would ease containment by shortening the quarantine for the uninfected to while-you-wait. Such testing at airports, train stations, hospitals, doctor's offices — even the grocery store — could modernize the venerable vaccinate-and-quarantine strategy. Distributed testing networks "could be anywhere, from a doctor's office to a tent in a Third World country," said Lo Priore. "This would completely change how you quarantine people, since we could tell within an hour whether someone had the flu or not."

The fast results would help the CDC track the spread of infection. New mutations could also be tracked in real-time, enabling fast development of custom vaccines to provide first responders with more-effective treatments.

"We are looking into the possibility of having a product [specifically designed] for the avian flu right now, but we are in the very early stages," Lo Priore said. Adapting the system to avian flu detection would merely require repopulating the microarray with that specific virus' marker RNA. "I think that many [electronics] companies are looking into preparing products for a possible outbreak of the avian flu, but I don't know of any announcements yet," he added.

Within a year, ST promises to have its subsystem — a pc board with all chips installed — available for OEMs to create handheld devices to detect bacterial or viral infections. In partnership with Mobidiag (Helsinki, Finland), ST is testing its biochip's ability to detect the common bacterial infections sepsis, pneumonia and meningitis. Mobidiag wants to use the chip eventually for devices that provide rapid point-of-care diagnosis of high-incidence outpatient diseases, such as respiratory and urinary-tract infections.

"We are gearing up to deliver turnkey systems with the microarray already populated with the DNA or RNA you want to identify," said Lo Priore.

STMicroelectronics says its lab-on-chip sells for $10 to $15, depending on the application. But since the device is built with traditional chip-making methods, economies of scale could drive down the price. "The possibility for scaling and for quality control . . . resonates well with the potential partners with which we are negotiating," Lo Priore said.