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Small Research, Large Potential Brian Zukas '12 researches lab-on-a-chip technology By Suki Casanave '86G See related stories

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MENTOR, MENTEE: Niva Gupta, left, and Brian Zukas '12, who has become a mentor to other students.

It was the drill that made her do a double-take. Niva Gupta's microfluidics lab is a jumble of test tubes and beakers and silicone tubing. But a drill? The associate professor of chemical engineering knew exactly who was responsible for the wayward piece of power equipment—and she knew there would be a good story behind it.

When Gupta had agreed to let Brian Zukas '12 work in her lab, he was only a sophomore. She was impressed by his focus and enthusiasm. But she was skeptical about his experience. "He hadn't done much in this field," she says. Within days, she knew she'd made the right decision. "He was very quick at transforming thought into a product or device," says Gupta. "He was very resourceful and a good experimentalist." Which explains why she sometimes discovered Rube Goldberg-style creations in her lab.

The drill, it turns out, was just the thing to help Zukas create smaller droplets for his experiment. "I was shocked to see the drill attached to the needle," says Gupta, laughing. "But it was a great idea."

Creating the perfect droplet size was just one small step in the NSF-funded microfluidics research underway in Gupta's lab. The technology, as its name suggests, deals with the flow of liquid in very small channels—typically at the submillimeter level. It's a field with potential applications in many different industries—one familiar example is inkjet printing. But Gupta and her team have their sights set on the field of medicine. "Imagine," says Zukas, "using just a nanoliter of blood on a chip that costs maybe 50 cents to make. You could detect a whole host of diseases, testing huge numbers of people in third-world countries for relatively little cost."

The medical applications of this lab-on-a-chip technology, with its on-site diagnostic potential—no expensive tests, easy access, instant analysis—hold tremendous promise, notes Gupta. "We know that diseased cells don't deform as easily as healthy ones," she explains. "Running a blood sample inside a very small channel, similar to what happens when blood is forced through capillaries in the body, allows you to see the rigidity of the cells, which helps to determine how diseased a person is." The technology also holds promise for dispensing drugs. In fact, this winter marked the first successful clinical trial with an implantable, microchip-based device, which was used to deliver an osteoporosis drug to test subjects. Based on research at MIT and tested at Microchips, Inc., these programmable chips could also be used for other diseases, including cancer and multiple sclerosis, as well as chronic conditions like diabetes. "Widespread application of such devices is a long way off," says Gupta, "but the field is exploding, and new applications are being discovered all the time."

Gupta's focus, meanwhile, is on developing numerical models to help confirm a correlation between empirical data and theory. "In medicine you don't have the luxury of testing every possibility," she says, pointing out that every cell type is different and so is the way they might interact with different channel sizes. But a computer can run an infinite number of variations. "I'm trying to bring a fundamental science outlook to the use of microchannels for detecting disease," says Gupta.

Perry Smith/UNH Photographic Services BASIC RESEARCH: Brian Zukas '12, left, and Logan Mower '13 in UNH's microfluids lab.

Which is where Zukas comes in. His experiments are matched with computer simulations developed by graduate student Robert Carroll '10. "Our work helps confirm that Robert's numerical models are applicable to real-world situations," says Zukas. That combination sets UNH apart, according to Gupta. "Very few labs do both the theory and the experiments," she says.

Creating credit-card-sized labs-on-a-chip starts with basic experiments to determine how cells might behave: Will they deform? Will they rupture? How fast will they flow? So even before he started fooling with drills and droplets, Zukas spent nearly a year creating the right recipe for his simulated cells. "You can actually eat this," he says, grinning, as he mixes sodium alginate, a seaweed substance that forms the beads at the center of his microcapsules. Surrounded by an elastic protein membrane, these beads are designed to roughly simulate red blood cells, but getting the "cell" to hang together wasn't easy, notes Zukas. "Some days, they'd just keep dissolving on me," he says. "Or they'd break. I did endless tests to figure it out."

Zukas attributes his patience partly to his childhood love for Legos. He was constantly dismantling his creations, building and rebuilding, looking for better solutions. At UNH, Zukas transferred his problem-solving passion to the lab. "I don't think I would have had this opportunity in a larger program," he says. "Or it would have been a lot harder to access. When I heard about the emphasis on undergraduate research at UNH, I knew it was something I wanted to do—and it's definitely been one of the most intellectually rewarding experiences I've had."

Although she is losing Zukas, who graduated in May, Gupta is thrilled that he has been able to mentor a new crop of lab assistants, including Logan Mower '13 and Chris Blais '15, who will carry on his work. Zukas has also worked with two Pinkerton Academy students, one of whom will enroll in UNH's chemical engineering program next fall. "Brian is a role model for these students," says Gupta of her protege, who has presented his work at both the 2011 and the 2012 Undergraduate Research Conferences. With a research presentation grant, he was also able to attend the national conference of the American Institute of Chemical Engineers, where his work took third place out of 60 entrants.

Sitting now in front of a computer, Zukas is eager to show off the final step of the testing process—a video of a microcapsule moving through simulated capillaries. Captured on high-speed film, the split-second journey plays out slowly: a dark spot moves steadily across the screen, the unassuming star of its own 10-second drama. First, it's a bullet-shaped blob squeezing through a narrow 1 mm channel. "Now it's crossing the expansion joint into the larger channel," says Zukas, watching as the deformed microcapsule "cell" returns to its original spherical shape. When Zukas captured this slow-motion journey for the first time, he was ecstatic, rushing to Gupta's office to tell her the news. Months of painstaking experimentation, patient trial and error, had come, finally, to this: a small miracle in black and white. The promise of things to come. ~

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