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MIT Researchers Develop Ingestible, Jell-O-Like Pill to Monitor the Stomach for a Month

A team of engineers at MIT have developed an ingestible, Jell-O-like pill that, upon reaching the stomach, rapidly swells to the size of a soft, squishy ping-pong ball large enough to stay in the stomach for a prolonged period of time.

The ingestible hydrogel device as a small pill can swell to a large soft sphere, and de-swell to a floppy membrane. (Image credit: Xinyue Liu, Shaoting Lin)

The inflatable pill is fitted inside a sensor that continuously monitors the stomach’s temperature for up to 30 days. If the pill has to be taken out of the stomach, a patient can drink a solution of calcium that makes the pill to shrink fast to its original size and pass safely out of the body.

The new pill is composed of two types of hydrogels—mixtures of water and polymers that look like the consistency of Jell-O. The combination allows the pill to rapidly swell in the stomach while remaining resistant to the churning acidic atmosphere in the stomach.

The hydrogel-based design is longer lasting, softer, and more biocompatible than present-day ingestible sensors, which either can only persist in the stomach for a few days, or are composed of metals or hard plastics that are orders of magnitude stiffer than the gastrointestinal tract.

The dream is to have a Jell-O-like smart pill, that once swallowed stays in the stomach and monitors the patient’s health for a long time such as a month.

Xuanhe Zhao, Associate Professor of Mechanical Engineering, MIT.

Zhao and senior collaborator Giovanni Traverso, a visiting scientist who will join the MIT faculty in 2019, together with lead authors Xinyue Liu, Christoph Steiger, and Shaoting Lin, have recently published their results in Nature Communications.

Pills, ping-pongs, and pufferfish

The new inflatable pill’s design is inspired by the pufferfish or blowfish’s defense mechanisms. Typically a slow-moving species, the pufferfish will rapidly inflate when threatened, like a spiky balloon. It achieves this by quickly sucking in a large quantity of water.

The puffer’s robust, fast-inflating body was precisely what Zhao was aiming to replicate in hydrogel form. The team had been seeking for ways to design a hydrogel-based pill to transport sensors into the stomach and remain there to monitor, for instance, disease states or vital signs for a comparatively long period of time.

They understood that if a pill were sufficiently small to be swallowed and passed down the esophagus, it would also be sufficiently small to pass out of the stomach, via an opening called the pylorus. To keep it from leaving the stomach, the team would have to design the pill to rapidly swell to the size of a ping-pong ball.

Currently, when people try to design these highly swellable gels, they usually use diffusion, letting water gradually diffuse into the hydrogel network,” Liu says. “But to swell to the size of a ping-pong ball takes hours, or even days. It’s longer than the emptying time of the stomach.”

The scientists instead sought for ways to design a hydrogel pill that could inflate a lot more rapidly, at a rate matching that of an alarmed pufferfish.

An ingestible tracker

The design, they eventually created, resembled a small, Jell-O-like capsule, composed of two hydrogel materials. The inner material is made up of sodium polyacrylate—superabsorbent particles that are used in commercial products such as diapers for their ability to quickly soak up liquid and inflate.

The scientists understood, however, that if the pill were composed only of these particles, it would instantly break apart and exit the stomach as individual beads. So they engineered a second, protective hydrogel layer to encapsulate the rapid-swelling particles. This outer membrane is composed of many nanoscopic, crystalline chains, each folded over another, in an almost impenetrable, gridlock pattern—an “anti-fatigue” feature that the scientists reported in a previous paper.

You would have to crack through many crystalline domains to break this membrane,” Lin says. “That’s what makes this hydrogel extremely robust, and at the same time, soft.”

In the lab, the scientists dipped the pill in different solutions of water and fluid that resembles gastric juices, and discovered the pill inflated to 100 times its original size in about 15 minutes—a lot faster than current swellable hydrogels. Once inflated, Zhao says the pill is about the softness of Jell-O or tofu, yet amazingly sturdy.

To put the pill’s toughness to test, the scientists mechanically squeezed it numerous times, at forces even greater than what the pill would endure from standard contractions in the stomach.

The stomach applies thousands to millions of cycles of load to grind food down,” Lin explains. “And we found that even when we make a small cut in the membrane, and then stretch and squeeze it thousands of times, the cut does not grow larger. Our design is very robust.”

The scientists further established that a solution of calcium ions, at a concentration more than what is found in milk, can shrink the swollen particles. This causes the pill to deflate and exit the stomach.

Finally, Steiger and Traverso embedded tiny, commercial temperature sensors into a number of pills, and fed the pills to pigs, which possess stomachs and gastrointestinal tracts quite similar to humans. The team later reclaimed the temperature sensors from the pigs’ stool and plotted the temperature measurements of the sensors over time. They learned that the sensor was able to correctly track the animals’ day-to-day activity patterns up to 30 days.

Ingestible electronics is an emerging area to monitor important physiological conditions and biomarkers,” says Hanqing Jiang, a professor of mechanical and aerospace engineering at Arizona State University, who was not a part of the research. “Conventional ingestible electronics are made of non-bio-friendly materials. Professor Zhao’s group is making a big leap on the development of biocompatible and soft but tough gel-based ingestible devices, which significantly extends the horizon of ingestible electronics. It also represents a new application of tough hydrogels that the group has been devoted to for years.”

Going forward, the scientists predict the pill may safely deliver a variety of different sensors to the stomach to track, for example, pH levels, or signs of certain viruses or bacteria. Miniature cameras may also be fitted into the pills to image the progress of ulcers or tumors, over the course of a number of weeks. Zhao says the pill might also be employed as a safer, more comfortable substitute to the gastric balloon diet, a form of diet control in which a balloon is threaded via a patient’s esophagus and into the stomach, with the help of an endoscope.

With our design, you wouldn’t need to go through a painful process to implant a rigid balloon. Maybe you can take a few of these pills instead, to help fill out your stomach, and lose weight. We see many possibilities for this hydrogel device.

Xuanhe Zhao, Associate Professor of Mechanical Engineering, MIT.

This study received support, in part, from the National Science Foundation, National Institutes of Health, and the Bill and Melinda Gates Foundation.

Jell-O-like, expanding pill

Jell-O-like, expanding pill. (Video credit: MIT)

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