Scientists have long struggled with how to study the gut's vast nervous system — often called the body's 'second brain' — without damaging it. Current research methods are invasive and often require complex surgeries that make it difficult to study normal gut function.
"If you look at how we do any study trying to map neural function in the gut, it is all extremely crude," said Khalil Ramadi , a NYU researcher who has developed a new approach to this challenge. "We just don't have good tools for it."
A team led by Ramadi — assistant professor of bioengineering at NYU Tandon School of Engineering and Director of the Laboratory for Advanced Neuroengineering and Translational Medicine at NYU Abu Dhabi (NYUAD) — has created ingestible devices called ICOPS (Ingestible Controlled Optogenetic Stimulation) that deliver targeted light stimulation directly to the gut.
The technology allows researchers to precisely illuminate specific regions of the intestinal tract, activating specific nerve cells. It could be used to observe how those cells control digestion, for example, and reveal new targets for treating conditions like gastroparesis, where the stomach empties too slowly, or metabolic diseases and eating disorders. The approach represents a dramatic improvement over current methods, which typically involve invasive surgical procedures to implant optical fibers .
The device enables optogenetics, a technique that makes specific cells light-sensitive. Scientists first modify target neurons to respond to light stimulation, then the patient swallows the LED-equipped pill.
"You can go in, transfect a certain subset of cells to be light sensitive, and then swallow this light pill whenever you want to activate those cells," Ramadi explained.
In a paper published in Advanced Materials Technologies , the researchers demonstrate how these devices could control the enteric nervous system — the network of neurons that governs gut function — without surgery.
While optogenetics has been used for brain research since the early 2000s, this marks the first non-invasive platform for wireless optical stimulation of the gut, opening new possibilities for mapping neural circuits that were previously inaccessible to researchers.
ICOPS represents the latest in Ramadi's portfolio of ingestible technologies, which includes FLASH , a capsule that uses electrical stimulation to activate gut neurons, and IMAG , a magnetic field-based device for tracking pill location in the gut. While these other devices have shown that neural activation can lead to hormonal changes affecting metabolism, ICOPS adds optogenetic control for greater precision.
A key innovation is that ICOPS operates without a battery, instead receiving power wirelessly through magnetic induction from an external transmitter. This battery-free design was necessary for the device to be small enough for testing in rats.
"What makes this capsule unique is that it was entirely fabricated in-house using 3D printing, without the need for cleanroom facilities," said Mohamed Elsherif, a Postdoctoral Associate in Ramadi's lab and the paper's lead author. "This allowed us to integrate micro-LEDs and custom coils in a scalable way, making it the first rodent-scale ingestible capsule for non-invasive optical stimulation. Crucially, it can operate wirelessly in freely moving animals, enabling studies that were not possible with traditional tethered or invasive approaches."
The implications extend beyond research. The technology could lead to new treatments for gut motility disorders. "We don't really have very good prokinetic or antikinetic agents," Ramadi said, referring to drugs that speed up or slow down gut movement. "We have stuff that overall slows or accelerates motility, but not targeted ones."
Neural activation in specific gut regions can also trigger hormonal changes affecting metabolism, potentially offering new approaches to treating metabolic diseases and eating disorders.
The devices travel through the digestive system naturally over one to two days. Beyond light therapy, the platform could enable electrical stimulation and targeted drug delivery. While clinical applications likely remain a decade away, the research represents a significant step toward understanding the gut's complex neural networks.
In addition to Ramadi and Elsherif, the paper's authors are Rawan Badr El-Din, Zhansaya Makhambetova, Heba Naser, Rahul Singh, Keonghwan Oh, and Revathi Sukesan from NYUAD's Division of Engineering; Maylis Boitet from NYUAD's Core Technology Platforms Operations; and Sohmyung Ha from NYUAD's Division of Engineering and NYU Tandon.
