Using microfluidic tests to identify infection

Good health care comes through good networks. When a little girl in the United States has a stubborn stomachache or a fever, her pediatrician checks her over and sends a sample to a laboratory for processing and accurate diagnosis. Results come back by mail or fax, and her parents get a prescription that can be easily filled by a local drugstore. In the meantime, the child has as much ginger ale as she can drink, a comfortable bed, and help standing by at the hospital switchboard. Everything’s in place, ready to catch her before she gets too sick to save.

There's no single solution that can give all that to the children who live in developing countries. But networks of solutions will catch those children just as effectively. One of PATH’s new technologies, an innovative tool for diagnosing disease, may take the world one big step closer to the safety net developing-world children need.

A credit card that buys lives

PATH is working with two teams to develop a point-of-care, microfluidics-based diagnostic tool—the “lab-on-a-card” to those who live outside the research laboratory. The first team includes the University of Washington, Washington University, and Micronics; the second, the University of Washington, Micronics, and Nanogen. Both teams are examples of that combination of private- and public-sector resources that has become an indispensable tool for bringing equitable health care to low-resource regions.

The lab-on-a-card is a credit card-sized piece of plastic that is riddled with tiny channels and chambers filled with the chemicals and reagents needed to translate a stool or blood sample into a diagnosis. Inject a sample into one end and place the card in a small, portable device that provides a little extra agitation and pretty soon—less than 20 minutes, in most cases—the clinician knows what to treat and how.

The right tool in the right place

A small, local health care center will be able to use the card, and health care workers without a lot of training can collect samples and bring them back to the center without having to use any high-tech equipment to keep them cool and clean. Once a sample is in the card, it will be protected from contamination. Processing happens immediately, so the sample won’t degrade in the destructive heat present in so many developing-world settings.

Most of the tests that can give results this quickly and in extreme conditions can answer only a single question—identify a single pathogen—at a time. The lab-on-a-card is a much better diagnostic, able to test for multiple pathogens at once. And that matters a lot when antibiotics are in short supply, when there’s no supportive care, when the wrong treatment could mean a life-threatening delay. It matters even more, for families and communities, when a child is carrying bacteria or a virus that’s capable of spreading quickly from person to person. Then, fast treatment with the right antibiotic can be the only way to halt an outbreak.

But how does it work?

The simple version is, it works through capillary action—something you probably last heard about in high school chemistry class. Dip a tiny straw into a drop of water, and the vacuum inside the tube will suck the water up. Paper towels work on this principle.

When you inject a sample into the card, capillary action gets it started through the microchannels in the plastic in just the same way. Additional pumping draws the sample along until it reacts with the chemicals that will tell the doctor what’s going on. In contrast, a standard laboratory would place a bit of the sample into a Petri dish, carefully protected from contamination, and then into a high-tech incubator geared to help the bacteria grow. That takes a lot of skill, expensive equipment, and time—24 hours to several days to get results.

Right now, the team is developing a processing device to go with the card that looks much like an iPod—cleanly and sturdily constructed, handheld, simple to navigate. The cards themselves are disposable, so there’s no risk of contamination, even when testing is carried out in less-than-ideal conditions. No manual intervention is required, other than connecting the card to the processor. The results should be just as reliable as those produced by conventional methods, and the cost should be much lower.

Deadly diarrhea and fast-moving fevers

Childhood diarrhea and rapid-onset fever are the first two illnesses that the teams are targeting with the lab-on-a-card. More than three million people, the majority in the developing world, die each year of infection with any of a myriad of bacteria that can colonize the intestinal tract, causing severe illness and diarrhea. Some of these cases can be easily treated with oral rehydration, but health workers need a way to identify children who need immediate antibiotics to survive. Halting an outbreak, once it’s gotten a toehold in a community, also depends on quick and accurate identification of the bug that’s causing the disease.

Fever can also be caused by a broad spectrum of organisms, making it hard to know just what’s gone wrong in a particular case. In many developing countries, people who have very high temperatures are most likely to be treated for malaria; other diseases that also manifest as fever are often missed and can cause death in a very short period of time, too short to allow multiple courses of treatment if the first diagnosis turns out to be wrong.

A version of the lab-on-a-card that will help reduce the threat of diarrheal disease has already been tested extensively in research labs in the United States. We hope to have it in field tests (the last step in the testing phase) by 2007. The fever panel will be close behind.

Global response

Will these two tests change the world? Not in an afternoon. But they’ll save lives every day—and they’re part of a long-term strategy for solving health problems that are truly global: creating solutions and systems that are as unique as the needs they meet.

Photo: PATH (Patrick McKern).