Ingestible Biosensor Pill for At-Home Monitoring of Intestinal Inflammation

Inspired by the firefly, Mass General Brigham researchers evaluated an ingestible capsule in preclinical models, finding that it accurately diagnosed acute mesenteric ischemia 90% of the time

Researchers led by investigators at Mass General Brigham and Massachusetts Institute of Technology have validated an ingestible capsule in preclinical models for the diagnosis of acute mesenteric ischemia, a condition caused by blocked or reduced blood flow to the intestines. The research is published in Science Robotics.

Acute mesenteric ischemia accounts for less than 1.5% of emergency department visits for abdominal pain but has a mortality rate of 55%, due in part to how difficult it can be to diagnose the condition early.

“Acute mesenteric ischemia is a potentially deadly but often underdiagnosed condition. Its early symptoms can resemble common gastrointestinal problems, and current diagnostic tools such as imaging tests are invasive, costly, and often too slow to enable timely treatment,” said senior author Giovanni Traverso, MB, BChir, PhD, MBBCH, a gastroenterologist in the Division of Gastroenterology, Hepatology, and Endoscopy in the Mass General Brigham Department of Medicine. “We aimed to create a faster, safer, and more accessible way to detect this condition before permanent intestinal damage occurs.”

Traverso and his team’s battery-powered swallowable capsule, called FIREFLI (Finding Ischemia via Reflectance of LIght), was inspired by the firefly, which emits light via pH-sensitive luciferase, an enzyme that catalyzes a light-emitting reaction called bioluminescence. FIREFLI generates light after activation by the small intestine’s pH. The emitted light illuminates the surrounding tissue, with ischemic tissue (deprived of oxygen and nutrients) demonstrating significantly lower luminance. These data are then transmitted wirelessly to an external mobile device which could someday allow clinicians to diagnose acute mesenteric ischemia.

In studies conducted in nine pigs, FIREFLI correctly identified acute mesenteric ischemia 90% of the time overall—it was excellent at correctly identifying animals with the condition (98% sensitivity) but was somewhat less effective at ruling out those that didn’t have it (85% specificity), leading to some false positives.

“This work brings together engineering, biology, and medicine to make an invisible medical emergency detectable quickly and noninvasively,” said Traverso. “The approach could enable faster triage in emergency departments, reduce unnecessary invasive testing in patients whose abdominal symptoms are not caused by ischemia, expand access to diagnostic care in clinics that lack advanced imaging technology, and lay the groundwork for future ‘smart’ capsules that combine sensing, wireless communication, and even targeted therapy delivery.”

Authorship: In addition to Traverso, Mass General Brigham authors include J. Chen, A. Alexiev, A. Sergnese, A. Hayward, C. Rosen, N. Shalabi, and S. Owyang. Additional authors include N. Fabian, A. Pettinari, Y. Cai, V. Perepelook, K. Schmidt, A. Guevara, B. Laidlaw, I. Moon, B. Markowitz, I. Ballinger, and Z. Yang.

Disclosures: Complete details of all relationships for profit and not for profit for Traverso can be found at the following link: www.dropbox.com/sh/szi7vnr4a2ajb56/AABs5N5i0q9AfT1IqIJAE-T5a?dl=0.

Funding: This work was funded in part by 1) The Karl van Tassel (1925) Career Development Professorship, Department of Mechanical Engineering, Massachusetts Institute of Technology (MIT). 2) The Division of Gastroenterology, Brigham and Women’s Hospital. 3) Advanced Research Projects Agency for Health (ARPA-H) under Award Number D24AC00040-00. 4) Defense Advanced Research Projects Agency (DARPA) under agreement number FA8650-21-2-7120 awarded to G.T. The views and conclusions contained herein are those of the authors and should not be interpreted as necessarily representing official policies or endorsements, either expressed or implied, of ARPA-H, DARPA, or the US Government. J.C. is supported by the Natural Science and Engineering Research Council of Canada Postgraduate Scholarship-Doctoral. S.O. is supported by the NIH through NIDDK 1F32DK139701-01 and NIDDK T32DK135449.

Paper cited: Chen J et al. “An Ingestible Capsule for Luminance-Based Diagnosis of Mesenteric Ischemia” Science Robotics DOI: 10.1126/scirobotics.adx1367