By Patrick L. Kennedy

A smart pill no bigger than a blueberry can withstand the stomach’s acidic fluids, detect signs of gastrointestinal trouble, and send warning signals to an ordinary smart phone, Assistant Professor Rabia Yazicigil (ECE) and colleagues reported in Nature. The fruit of a multi-institution, cross-disciplinary effort, this novel technology might make a world of difference for the seven million people who suffer from the inflammatory bowel diseases (IBD) Crohn’s disease and ulcerative colitis.

“This could change the way we diagnose and monitor these conditions,” says Yazicigil, a senior author on the paper. Her team at BU led the design of the miniaturized ultra-low-power chip inside the pill, while collaborators at MIT engineered the bacterial biosensors and designed the pill casing. Yazicigil’s doctoral student Mandy Liu helped to test and validate the integrated system in live large animal models.

Diarrhea and fatigue are just some of the symptoms that follow an IBD flare-up. Long-term effects include malnutrition and even the risk of colon cancer. In the Nature study, the BU-MIT team’s smart capsule succeeded in detecting nitric oxide, thiosulfate, tetrathionate and reactive oxygen species in the digestive system of Yorkshire pigs weighing up to 180 pounds.

Rabia Yazicigil (ECE) and doctoral student Mandy Liu show off the smart capsule.

“These molecules are key biomarkers for inflammation,” says Yazicigil, suggesting an IBD flare-up may be imminent. “The pill has engineered living bacteria that light up in response to these molecules.”

That instantaneous reaction is key to more efficient IBD management, because the biomarkers only crop up for a short time, and they don’t show up in a colonoscopy. Instead of undergoing that invasive annual procedure and all its attendant discomforts, future IBD patients can give their own gut a regular check by simply (and safely) swallowing the smart pill, Yazicigil hopes. As the capsule passes through the digestive tract, it runs on a tiny battery, thanks to the energy-efficient sensor readout circuit that was custom designed in her BU lab. “It processes and sends the bioluminescent signals wirelessly to your smart phone or a computer, monitoring your condition in real time in a very accurate way.”

The Nature study represents the successful convergence of several areas of expertise, Yazicigil says, from the bacteria engineering to the capsule’s acid-resistant casing to the miniaturization of the capsule through fully integrated photodetector and sensor readout circuits. “It’s a hard thing to do, detecting these weak signals while consuming low power,” she says.

“We played to the strengths of the biology and the electronics,” says Yazicigil’s colleague Miguel Jimenez, an MIT research scientist who is joining BU’s biomedical engineering faculty this fall. “Our tiny pill shows what is possible when we can bridge bacterial sensing with wireless communication.”

“Our bacterial probes can measure the dynamic microenvironment in the gut, which defines how gut bacteria build communities and ultimately impact on our health. This proves the power of synthetic biology to leverage the information-processing abilities of living cells to prevent disease in difficult-to-access environments.” says Maria Eugenia Inda, the postdoctoral fellow leading the project in the Lu lab – SynBio center, MIT.

In addition to the study published in Nature, Yazicigil’s doctoral student Mandy Liu published a paper on the electronics aspect of the project in the Journal of Solid-State Circuits, the IEEE’s flagship journal for chip design.

Other collaborators on the Nature study hailed from Brigham and Women’s Hospital, the University of Chicago, and Analog Devices. Funding for the work came from the Leona M. and Harry B. Helmsley Charitable Trust, the Pew Charitable Trusts, the Translational Research Institute of Space Health, the MIT Department of Mechanical Engineering, the MIT Karl van Tassel Career Development Professorship, and the Catalyst Foundation.