Researchers from MIT, Boston University and elsewhere report a blueberry-sized smart pill that could be a game-changer for diagnosing and treating intestinal diseases. That’s because it’s the first ingestion-compatible technology that can automatically detect and report in real time key biomolecules that may indicate a problem.
This work was published in the August 10 issue of the magazine nature. Other authors of the paper are researchers at Brigham and Women’s Hospital in Boston, the University of Chicago, and Analog Devices.
This new study significantly advances earlier research reported in the journal 2018 science. The current pill is about one-sixth the size of the prototype reported in 2017. science, Comply with safe and ingestible dosage forms on the market. It is also designed to detect key biomolecules such as nitric oxide and hydrogen sulfide byproducts, which are important signals and mediators of inflammation associated with intestinal disease.
Current techniques for diagnosing diseases within the gut can be invasive (think colonoscopies or other endoscopic procedures) and fail to detect molecular biomarkers of disease in real time. The latter is a problem because some important biomarkers are very short-lived, so they disappear before current technology can detect them.
The new pill, which has been successfully tested on pigs, combines specially designed live bacteria with electronics and tiny batteries. When bacteria sense a molecule of interest, they produce light (the bacteria themselves have also been successfully tested in vitro in animals and in mice). The pill electronics then convert the light into a wireless signal that can be transmitted through the body to a smartphone or other computer in real time as the pill travels through the intestines.
“The inner workings of the human gut remain one of the last frontiers of science. Our new drugs could unlock a wealth of information about body function, the body’s relationship to the environment, and the effects of disease and therapeutic intervention,” says MIT Bioengineering , said Timothy Lu, associate professor of electrical engineering and computer science. Lu, who is also affiliated with MIT’s Materials Research Laboratory and Senti Biosciences, is the paper’s senior author. nature.
potential impact
Approximately 7 million people worldwide suffer from inflammatory bowel disease (IBD) such as colitis or Crohn’s disease.
“One of the most challenging aspects of monitoring IBD is predicting the clinical symptoms that often occur in these patients and deciding on medical management of their disease. Currently, we do not have strong biomarkers to predict upcoming inflammatory episodes, so Patients often develop severe symptoms that require hospitalization for proper management.” He was not involved in the study. “This system could be a game-changer in IBD management in terms of early diagnosis, stopping disease flare-ups and optimizing treatment plans.”
In their study, the researchers showed that the smart pill can detect nitric oxide, a short-lived molecule associated with many inflammatory bowel diseases. Importantly, the sensor can also detect varying concentrations of nitric oxide. “This will allow us to differentiate between normal conditions and disease,” said Maria Eugenia Inda, a Pew postdoctoral fellow in MIT’s Departments of Electrical Engineering and Computer Science (EECS) and Bioengineering (BE). This is also important because biomarker levels vary widely between patients.
Understanding the gut
The team says the pill could be tweaked to detect other key biomarkers. As a result, Inda is also excited about the system’s potential to allow scientists to better understand the gut microbiome, or the delicate environment of microorganisms key to digesting food.
Right now, the gut is like a black box. “We still don’t fully understand it because it’s difficult to access and study. We lack the tools to explore it,” she said. “Understanding more about the chemical environment of the gut could help us prevent disease by identifying factors that cause inflammation before it occurs.”
Beyond the gut, the team’s combination of microbes and electronics could have broad applications for health monitoring. “We leveraged the strengths of biology and electronics, and our little pill shows what can happen when we can deliver bacteria to When sensing is connected to wireless communications, anything is possible.” Inda and Jimenez are co-first authors of the paper.
“With this development, we describe a unique gastrointestinal assessment platform that we anticipate can help many people,” said Giova, associate professor at MechE, a gastroenterologist at Brigham and Women’s Hospital and one of the study’s senior authors. Giovanni Traverso said. study.
a wonderful journey
Inda compared the research to the 1966 film “The Fantastic Journey,” which follows four scientists who shrink themselves to fit in a tiny submarine that travels through a patient’s arteries to treat problems with his brain. “We scientists couldn’t do that,” she smiles, “but now we can send bacteria to do something similar. Rapid advances in synthetic biology allow us to harness the information-processing power of living cells to diagnose this inaccessible diseases in the environment.”
Co-authors Inda, Jimenez, Traverso and Lu nature The authors of the paper are Christoph Steiger and Alison MechE, Hayward, Adam Wentworth, and Wiam Madani, MIT Koch Institute for Integrative Cancer Research, and Brigham and Women’s Hospital (BWH); Nhi Phan and Jenna Ahn, Koch Institute; Qijun Liu, Department of Electrical and Computer Engineering, Boston University (also first author of the 2022 Electronics paper), Arslan Riaz, Timur Zirtiloglu, and Rabia Yazicigil; Kaitlyn Wong and Ronan McNally, BWH; Keiko Ishida, Koch Institute and BWH; MechE, Koch Institute, and MIT Niora Fabian, Department of Comparative Medicine (DCM); Josh Jenkins and Johannes Kuosmanen, MechE and the Koch Institute; Yong Lai, BE and EECS; Alison Hayward, MechE, the Koch Institute, BWH and DCM; Mark Mimi, University of Chicago (Mark Mimee); Phillip Nadeau of Analog Devices; Anantha Chandrakasan, dean of the MIT School of Engineering and EECS professor.
This work was supported by the Leona M. and Harry B. Helmsley Charitable Trusts, the Pew Charitable Trusts, the Space Health Translational Institute, the MIT Department of Mechanical Engineering, and the MIT Karl van Tassel (1925) Career Development Professor Positions and Catalyst Foundation.