The present and future of ingestible sensors – The new taste of science

The present and future of ingestible sensors – The new taste of science

By Subhra Pradhan

What is an ingestible sensor?

In simple terms, they are ingestible electronic devices, roughly the size of a medicine capsule, composed of biocompatible materials that make up a power supply, microprocessor, controller, sensors, etc., giving the device the ability to telecommunicate for use in the healthcare industry for disease diagnostics and monitoring.

Importantly, as they are noninvasive, this real-time healthcare technology can have far-reaching implications, well beyond what current sensors are capable of. The technology of ingestible sensors is the next step following wearable sensors. The ingestible sensor market size has been estimated at roughly $491 million in 2016, and this could increase at a compound annual growth rate of as much as 19% through 2024. It is a disruptive technology in the field of disease diagnostics, monitoring, and management. Hence, the field of “intelligent pills” is well worth exploring.

Bacteria on a chip:

In a May 2018 article in the journal Science, researchers presented a novel ingestible micro-bio-electronic device (IMBED) that can be used to monitor gut health. As a proof of concept, the group designed a “heme-sensitive probiotic biosensor” that can be used to detect gastrointestinal (GI) bleeding. While previous generations of ingestible sensors measured mostly pH, temperature, pressure, and adherence to medication, this is the first time that the technology was pushed towards specific diagnostics.

Bacteria can be seen as nano-biosensors, as they can sense a plethora of external physical and chemical parameters through specific genetic pathways. In this intelligent pill, scientists used the heme-sensing genetic components of Lactococcus lactis and Escherichia coli O157:H7 bacteria to sense blood in the extracellular environment and modified it to produce an output signal as bioluminescence (Photorhabdus luminescens luxCDABE). The system was then introduced into a gut-friendly bacterial strain. The pill device runs on a battery that is powered by stomach acid. This prototype was tested on both mice and pigs in which GI bleeding was induced, and the ingested device was able to detect heme, the iron-holding molecule in hemoglobin, as its nano-bioluminescent signal was processed and transmitted to an Android app. How? Briefly, the bioluminescence was detected and converted into digital code by a low-power chip-based luminometer present within the device. The codes were transmitted outside the body wirelessly for display and quantitation. The luminometer consists of very efficient phototransistors to detect the photon flux. In this particular prototype, the photo-current was measured wirelessly for two hours. The real-time data was visualized and processed on an Android phone with custom application software. The device could readily detect blood in the environment.

Bacteria engineered to detect specific molecules are placed in four wells on the custom-designed sensor, which is attached to a microprocessor that converts the sensory information to a wireless signal. Image: Melanie Gonick/MIT

Currently, it is recognized that the pills need to be resized, as their dimensions (roughly 1.5 inches) hinder human trials. This concept was also extrapolated to detect other molecules like acyl-homoserine lactones using non-pathogenic E. coli Nissle 1917. These IMBEDs show great promise in detecting small intra-gut molecules that are difficult to detect using traditional fecal testing. These technologies are a brilliant amalgamation of fundamental biology, electronics, and engineering that will most definitely aid in our comprehension of gut issues.

Gut gas sensors:

We can imagine the gut as a hot soup of life, inside which food is digested and broken down, chemicals and gases are exchanged between cells, and food particles undergo chemical and physical interactions. Thus, real-time sensing of the gut environment can provide us with a plethora of never-before-seen gut events. Among them, gut gases can be measured as a proxy for bacterial biomass and chemical analytes present in the gut. Hence, gut gas analysis could be perfect for developing biomarkers for GI tract disorders. A study published in Nature Electronics in January 2018 by Australian scientists demonstrated the first pilot human trial on gut gas–sensing digital pills, providing some powerful new insights into gut activity.

A close up of the swallowable sensor. Photo: Peter Clarke/RMIT University

This study could have major ramifications in the field of gut diagnostics, as it is estimated that nearly one in five people around the world will suffer from GI tract disorders. This digital pill has gas sensors for oxygen, hydrogen, and carbon dioxide, and the data generated can be accessed through smartphone-based application software. The structural components of the pill include a gas-permeable membrane, a reed switch, microprocessors, and wireless transmitters. Furthermore, studies have shown that these capsules do not have any retention problems. The study revealed some very novel gut activity such as the production of oxidizing chemicals to combat foreign molecules and the presence of oxygen in the colon, findings that directly contradict previous knowledge.

Professor Kourosh Kalantar-zadeh, study lead and a co-inventor of the capsule, comments that “trials showed the presence of high concentrations of oxygen in the colon under an extremely high-fiber diet. This contradicts the old belief that the colon is always oxygen free. This new information could help us better understand how debilitating diseases like colon cancer occur.”

The trial was performed on seven healthy individuals on specific diets comprised of either high or low fiber. Results clearly show accurate food fermentation onset times. The group is now reported to be on the path to commercialization and marketing of the technology and the product. They have partnered with Planet Innovation and established the company Atmo Biosciences to perform Phase II clinical trials. This could revolutionize our understanding of the gut, gastrointestinal biomolecules, food retention time, digestion, food absorption or lack thereof, microbiome composition, and much more, all in real time and in a noninvasive manner.

The capsule moves through the gastrointestinal system and transmits information via a handheld device and mobile app. Photo: Atmo Biosciences

Adherence to medication monitoring:

Abilify MyCite is the first pill containing a digital tracking system that has been approved by the U.S. Food and Drug Administration that can be used by physicians to monitor medicine ingestion in patients suffering from mental disorders. As adherence is essential and often an issue with some patients, this new intelligent pill allows for stricter monitoring and management of medication adherence programs. The capsule comes with an embedded sensor, wearable patch, and software app. The software can alert doctors whenever a patient is not in compliance with medication regimes. Moreover, the data is available easily through web portals via a smartphone. This is a cooperative effort by Otsuka Pharmaceuticals and Proteus Digital Health.

Future directions:

Ingestible sensors are still a new concept, and the idea of swallowing a sensor containing all the electronic components remains a psychological challenge. Strict safety guidelines must be maintained by the pharmaceutical companies and regulatory authorities. The field must also surmount the huge hurdle of massive expenditures linked to product development, as these technologies require invention of new integrated technologies, an issue that could slow the speed of development. Nevertheless, the information that can be obtained through this ingestible technology has a huge potential to shed light on newly discovered functionalities of the gut. We currently lack an in-depth comprehension of how gastric juices, electrolytes, hormones, and other gut metabolites coordinate together to establish a healthy gut. Hence, we can safely assume that these highly integrated ingestible sensors are the future of our gut health.

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