Tza-Huei (Jeff) Wang spends his days working with tiny droplets of fluid. Really tiny. Some of his lab’s devices analyze droplets that are one-millionth of a liter. Others use a far smaller scale: one-trillionth of a liter.
Why would anyone want to isolate such minute volumes of fluid? Because microfluidics, as Wang’s field is known, allows rapid, precise analysis of many kinds of biological processes.
Over the last decade, Wang’s lab has developed devices that might someday make it far easier for clinicians to identify infectious pathogens and to diagnose early-stage cancers. And because some of these devices have the potential to be cheap and portable, they might transform health care in low-resource countries that have few traditional hospital laboratories.
“With microfluidics,” Wang says, “you can control the microenvironments you want to look at. You have precise temporal and spatial control. You have resolution even down to the single-cell level. It’s a very elegant approach.”
To translate his lab’s technologies into real-world clinical progress, Wang has built collaborations with a broad team of physicians and epidemiologists at Johns Hopkins and beyond.
One of Wang’s highest-profile recent projects involves a portable device that can rapidly confirm an infection with gonorrhea — and identify within 15 minutes whether the gonorrhea will respond to traditional antibiotics. In a typical hospital lab, that process takes two to four days. But with Wang’s device, a patient can receive a diagnosis and start treatment, all within a 45-minute clinical visit.
“It’s a huge benefit to start treating the patient during that initial visit,” says Charlotte Gaydos, a professor of infectious diseases at the school of medicine, who has collaborated with Wang for more than seven years. “Usually, you’re waiting several days for results to come back, and during that time, there’s a risk of further transmission of infection.”
Wang, Gaydos and their colleagues have tested their device in the emergency department at The Johns Hopkins Hospital and at several clinics in Baltimore. They have also piloted the system in rural areas of Uganda, where antibiotic-resistant gonorrhea is becoming prevalent.
At each site, Wang has worked to make sure that the device actually fits into the local clinical workflow. “Ten years ago,” he says, “some people were very, very frustrated with microfluidics because we’d invented all of these very elegant, very powerful microchips, but they couldn’t be used easily in clinical settings. People didn’t see a lot of actual real-world products.”
To avoid that pitfall, Wang — a professor of mechanical engineering with joint appointments in biomedical engineering, medicine and oncology —teaches his graduate students and postdocs to have long, deep conversations with their physician collaborators. “Don’t just read their papers,” he says. “Go and visit their clinics and see how the work actually happens.”
Using that collaborative approach, Wang’s lab has developed an array of devices for detecting cancer and analyzing pathogens. With Johns Hopkins oncologist Stephen Meltzer, Wang has developed a new technique for detecting precancerous changes in the esophagus. With pathologist Karen Carroll he has developed a microfluidic platform that can accurately identify any of dozens of pathogens in a tiny specimen of urine. Like the gonorrhea device, this platform can deliver extremely fast reports about the pathogens’ sensitivity to antibiotics.
Wang says that his visits to the Ugandan clinical sites in 2019 were among the most valuable experiences of his time at Johns Hopkins. “While I was there,” he says, “I heard about a problem I’d never even thought about. Clinics in Uganda sometimes get shipments of counterfeit antibiotics, and they can’t tell what’s real. So that might be my next project: a portable device for the rapid authentication of medicines.”