What’s Going on Inside You? These Inventions Keep Track 

When Sameer Sonkusale was in high school about 35 years ago, his father brought him on work trips along India’s expanding railway routes, which cover tens of thousands of miles. Father and son would live in a special train car that was dropped off at the end of a line where new tracks were being laid, sometimes deep in a forest. The trips lasted for months at a time, whenever school schedules allowed.

Sonkusale’s father was trained as a chemist, but he had taught himself electrical engineering to work on the communication network for the railroad.

“He was always curious and learning, much like me,” said Sonkusale, who is now a professor of electrical and computer engineering at Tufts.

Sonkusale loved reading his father’s books on electrical engineering and ultimately pursued formal training in the field. Then by some poetic fate, he did the reverse of what his father had once done: As a trained electrical engineer, he taught himself the fields of chemistry, biology, and medicine to push the limits of his research.

Today Sonkusale is known for his forays into other disciplines, which have led to fascinating innovations. He and his research team have created tiny backpacks for birds that measure the stress they’re experiencing due to climate change; a smart bandage that detects a wound’s progress and delivers medicine to prevent infection and accelerate healing; and a T-shirt with woven threads that can “read” your sweat to track markers of athletic performance.

He has also developed a floss pick that can detect indicators of stress, hormonal changes, and cardiovascular disease in your saliva; a sensor that can be attached to a leaf to track a plant’s response to the environment; and an electronic “nose” that can detect gases in minute quantities, such as those that may leak from gas pipes.

Each project started with a conversation with someone working in a field very different from his own.

“I don’t like to go to conferences and seminars in my own field,” he explained. “More often than not, I find that when I talk to someone outside my discipline about their challenges—in chemistry, biology, medicine—I realize I can apply knowledge of tools and methods that can help them get to a solution. The most interesting problems are always at the boundaries between disciplines.”

Trained as an electrical engineer, Professor Sameer Sonkusale taught himself chemistry, biology and medicine to expand the impact of his research. Photo: Andy Kwok

Monitoring health from home

It was one such encounter that led to a collaboration with Professor Ayanna Thomas in the Department of Psychology and Professor David Hammer in the Department of Education. Together with other faculty in electrical and computer engineering, they were interested in learning how stress can affect problem-solving and learning.

The challenge was how to measure stress in student volunteers as they were given different topics and tasks to learn. The researchers initially collected saliva samples and sent them to a lab to measure the stress hormone cortisol, which took two to three days. There was no way to measure continuously so the test subjects could adapt their learning strategies in real time.

“We didn’t want measurement to create an additional source of stress, so we thought, can we make a sensing device that becomes part of your day-to-day routine?” Sonkusale said. “Flossing seemed like a natural fit to take a daily sample.”

Can your floss detect that you’re stressed? This special dental floss pick can draw in saliva, then be inserted into a device that displays a readout of levels of cortisol, a stress hormone. Photo: Andy Kwok

He came up with the design of a cortisol-sensing dental floss pick. The saliva is drawn into the pick by capillary action through a very narrow channel in the floss. When the pick handle is inserted into a small box-shaped device about the size of a soda can, a readout of cortisol levels is presented on a screen. Press your finger on the side of the box and it also reads your heart rate and blood oxygen level.

To detect the cortisol, Sonkusale and his team used a material called an electropolymerized molecularly imprinted polymer (eMIP). The polymer—a plastic-like substance made by a chain of chemicals—is formed around the cortisol, similar to how you might make a plaster cast of your hand. After removing the cortisol, you are left with an open space, or binding site, that can pick up any free-floating cortisol found in saliva, sweat, or other fluids.

One can create these eMIP molds around any molecule, not just cortisol.

“The eMIP approach is a game changer,” said Sonkusale. “If you discover a new marker for stress or any other disease or condition, you can just create a polymer cast in a very short period of time.”

Specially designed baby pacifiers can monitor the emergence of infections in infants. Photo: Andy Kwok

Sonkusale and his team of researchers saw an opportunity to turn this approach into something that could have many applications.

Passive devices like dental floss picks and baby pacifiers can collect the fluids, and when ready, they can be inserted into the detection box to read out whatever is being tracked. Right now, the devices can track stress through cortisol, and the pacifiers can also monitor the emergence of infections in infants.

“Just like people are now using glucose monitoring to adjust their diet and lifestyle, the device could give you a better understanding of how biological markers of stress and other conditions respond to food, diet, sleep, and environment—things that you can take an active role in managing,” said Sonkusale.

Taking an inventory of the gut

One of the most remarkable inventions from the Sonkusale lab looks like an ordinary capsule the size of a vitamin pill. After it’s swallowed, the 3D-printed capsule—which contains a sponge-like material—absorbs small samples from the gut as the capsule passes through the gastrointestinal tract.

The gut microbiome is made up of trillions of microorganisms—bacteria, viruses, and fungi—that live in the large and small intestine. This swarm of microorganisms may be as much an integral part of our bodies as any organ, influencing and maintaining equilibrium in everything from metabolism and immunity to brain function.

More than 2,000 species of microbiota have been found in the gut. While the vast majority of these appear to be beneficial, some may be harmful. An imbalance of the microbiota, termed “dysbiosis,” can be associated with inflammation, susceptibility to infections, and even the worsening of diseases such as cancer.

Sonkusale believes that being able to noninvasively profile which microbiota populate a person’s gut will be a major step toward unraveling the role and possible therapeutic potential of those organisms. 

The development of the capsule has made use of expertise from many corners of Tufts. Ruben Del-Rio-Ruiz, then a postdoctoral researcher in the Sonkusale lab, worked with research scholar Débora Regina Romualdo Da Silva and Professor Giovanni Widmer at Cummings School of Veterinary Medicine at Tufts University to conduct preclinical studies in animals and analyze the samples collected from different parts of the gut by the ingestible capsules.

“We’re picking up hundreds of species of bacteria from the small intestine,” said Widmer, who uses high-throughput DNA sequencing to identify the bacteria sequestered in the capsules.

The device has now moved to human studies, this time with the help of Tufts Distinguished Professor Alice H. Lichtenstein, who is a senior scientist at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University. Her team is looking at whether the capsule can detect changes in people’s microbiomes depending on their diet.

Martin Son, senior director of Technology Commercialization at Tufts, thought the new technology would be a great project for students in the Master of Science in Innovation & Management (MSIM) program at Tufts Gordon Institute. Every semester, students conduct in-depth research on Tufts technology to determine whether an innovation has market potential and could be a candidate for a startup.

Zoe Watson, EG24, and Sofia Paschenti, EG25, were drawn to the microbiome project when they were graduate students. “It was very personal from the get-go, for myself and Sofia,” said Watson. “We both had people close to us who had irritable bowel syndrome and celiac disease—conditions which could be affected by the gut microbiome.”

Their research landed on an initial target market to diagnose a condition called small intestine bacterial overgrowth, or SIBO. SIBO affects about one of every 10 people, and an even higher percentage of people with irritable bowel syndrome, Crohn’s disease, and other gastrointestinal illnesses. An accurate diagnosis could help direct treatment such as antibiotics and diet, relieving uncomfortable or painful symptoms like bloating, cramps, and nausea.

Watson and Paschenti launched a startup called Microvitality to develop the capsule for this market, and potentially to support research, diagnostics, and treatment of other conditions.

“The capsule will allow us to better understand the system of microbiota that inhabit different parts of our gut, which tends to be unique for each individual,” said Lichtenstein. “Ultimately we want to know if we can manipulate diet to alter the gut microbiota so that we can encourage growth of the more favorable organisms and minimize growth of the less favorable ones.”

Widmer and Sonkusale think that a more targeted approach to microbiome manipulation might be possible using a variation of the capsule that would deliver probiotics rather than collect resident bacteria.

Microneedles link diagnosis and treatment

In the world of medicine, getting the right dose of treatment is often a matter of trial and error, involving time and human decision-making. Sonkusale sees an opportunity to make the process virtually instantaneous, at least in select cases, by making devices that adjust delivery of a medication while simultaneously tracking how the patient responds to treatment.

The approach harnesses the engineering concept of the closed loop. A closed loop refers to any system that measures the results of its own output and feeds that information back so the system can adapt instantly to changing conditions and optimize performance. A good example of a closed loop is the cruise control in your car. Set for a specific speed, cruise control will adjust power from the engine to maintain the set speed while adapting to changing conditions, such as climbing hills or differences in wind speed.

Researchers in Sonkusale's lab have developed a translucent plastic prototype device about the size of a box of Tic Tacs, tethered to a microneedle patch about the size of a large postage stamp. Inside the device is a reservoir that holds the drug in liquid form and a tiny pump that can push the liquid through the microneedles in precise amounts.

“The prototype can’t adjust the medication based on the patient’s response by itself yet, but it is an active delivery system that can have useful applications for something like pain management,” said Danilo Dos Santos, a research assistant professor working with Sonkusale. “A physician can remotely change the dosage of a treatment like ketamine based on patient feedback, but also limit its delivery to avoid risk of addiction.”

“The goal is for the next generation of active or closed loop delivery to be about the size of a smartwatch,” said Dos Santos. A microneedle patch would be on the back of the “watch” (or around the wristband), and a screen interface would allow the patient or physician to schedule regular doses. The device could be tremendously helpful for people taking several medications, for example, since it could eliminate the need to keep track of multiple drugs and multiple doses every day, and it can be managed by a caregiver.

“The idea is to put the patch on, load the prescription timing in an app, and then just forget about it—you’ll never miss a medication,” said Sonkusale.

While active and closed loop devices are being developed in the lab, a passive delivery microneedle patch is already being commercialized by the startup company Anodyne Nanotech. Anodyne emerged in much the same way that Microvitality came about—through the Tufts Gordon Institute MSIM program.

In contrast to the hollow microneedles used in patches for active delivery of drugs, passive delivery microneedle patches contain a solid form of the drug embedded in the needles, which slowly leaches out over time.

Sonkusale says that these efforts will ultimately converge on a closed loop drug delivery system, through which the microneedle patch will not only deliver a drug but will also use sensors to pick up markers of disease that indicate how well the person is responding to treatment and feed that information back to the delivery pump.

“This is something that I have always talked about—the notion that medicine needs to be personalized, not just based on age, weight, or even genetics, but also on how someone metabolizes and reacts to the drug in the moment,” he said. “The treatment needs to adapt in real time to how they are responding to it. You can imagine, for example, someone with epilepsy could have a drug [like benzodiazepine] to be ramped up just before the onset of a seizure, based on some feedback received by the drug delivery patch.”