Smart capsules for sensing and sampling the gut: status, challenges and prospects

Abstract

Smart capsules are developing at a tremendous pace with a promise to become effective clinical tools for the diagnosis and monitoring of gut health. This field emerged in the early 2000s with a successful translation of an endoscopic capsule from laboratory prototype to a commercially viable clinical device. Recently, this field has accelerated and expanded into various domains beyond imaging, including the measurement of gut physiological parameters such as temperature, pH, pressure and gas sensing, and the development of sampling devices for better insight into gut health. In this review, the status of smart capsules for sensing gut parameters is presented to provide a broad picture of these state-of-the-art devices while focusing on the technical and clinical challenges the devices need to overcome to realise their value in clinical settings. Smart capsules are developed to perform sensing operations throughout the length of the gut to better understand the body's response under various conditions. Furthermore, the prospects of such sensing devices are discussed that might help readers, especially health practitioners, to adapt to this inevitable transformation in healthcare. As a compliment to gut sensing smart capsules, significant amount of effort has been put into the development of robotic capsules to collect tissue biopsy and gut microbiota samples to perform in-depth analysis after capsule retrieval which will be a game changer for gut health diagnosis, and this advancement is also covered in this review. The expansion of smart capsules to robotic capsules for gut microbiota collection has opened new avenues for research with a great promise to revolutionise human health diagnosis, monitoring and intervention.

Keywords: colonic microflora; enteric bacterial microflora; gastrointesinal endoscopy; intestinal bacteria; small intestine.

Figure 1

(A) Human GI (digestive) tract with each distinct segment of the gut identified. (B) Temperature and gas profiles of the gut, measured internally, which shows the daily response in each segment.

Figure 2

Representation of microbial population across the lumen and mucosa layer in both the small intestine and colon. The villi structure is only present in the small intestine along with a mucus layer whereas the colon contains two mucus layers. Reproduced from Fellows and Varga-Weisz licensed under CC BY 4.0.

Figure 3

Gut sensing devices for measuring various gut parameters. (A) alphaOne pH monitoring capsule by the Jinshan group and (B) Bravo reflex capsule by Medtronic are used to record acid reflux episodes to diagnose gastro-oesophageal reflux disease by attachment to the oesophageal wall. (C) Heidelberg pH capsule for upper GI tract use to determine achlorhydria by holding it inside the stomach. (D) SmartPill by Medtronic to measure pH, temperature and pressure throughout the gut that can also generate a transit profile. (E) Laboratory prototype to measure pH. (F) Atmo Gas Capsule by Atmo Biosciences to measure gases from inside the gut that simultaneously generates the gas profile (results) on a phone application. (G) VitalSense by Philips Respironics and (H) eCelsius by BodyCap used to measure core body temperature. (I) Capsule prototype to measure peristaltic pressure. (J) Capsule to measure gases in the gut.

Figure 4

Tools for tissue biopsy. (A) Cylindrical razors to cut a targeted tissue sample. (B) A barb-based design to penetrate the gut wall to extract a tissue sample. (C) A scissor-shaped razor to clamp tissue inside the jaws. The razor used magnetic actuation to eject from the capsule shell and cut the targeted tissue with scissor motion that could be visualised with the camera module. (D) The elaboration of tissue extraction method using the scissor-shaped razor.

Figure 5

Passive sampling devices that use an enteric pH coating which dissolves by reacting with the target fluid allowing microbiota and digesta sample collection. (A) Osmotic pill sampler that continuously samples the microorganisms throughout its passage till recovery (reproduced from Rezaei et al licensed under CC BY 4.0). (B) and (C) Collects the sample mainly from small intestine and secure it from contamination inside the colon by sealing the inlet through hydrogel (reproduced from Nejati et al with permission from the Royal Society of Chemistry). (D) IMBA capsule with explanation of the collection process with timings in various regions throughout the gut (reproduced from Jin et al 2019 AGA Institute). (E) Bistable mechanism to collect and store the sample (reproduced from Salem et al 2018 IEEE). PDMS, polydimethylsiloxane.

Figure 6

Active and dynamic sampling devices that use wireless triggering mechanism (except G) to collect microbiota and digesta samples. (A) A compact capsule with three separate channels to store the content (reproduced from Park et al 2022 IEEE). (B) A dynamic sampling capsule that brushes the intestinal wall to collect microbiota (reproduced from Finocchiaro et al 2021 IEEE). (C) A magnetic capsule with a hinge mechanism to collect digesta and microbiota sample with blind activation based on predicted transit time (reproduced from Shokrollahi et al 2021 IEEE). (D) A flexible capsule triggered with a magnet to collect the surrounding fluid with suction (reproduced from Du et al 2018 IEEE). (E) A commercial prototype with sophisticated external magnetic control mechanism to drag the capsule to the target-site and on-board camera to visualise the collection site (reproduced from Ding et al 151). (F) Another dynamic sampling mechanism that scrapes the microbiota from intestinal wall. The capsule can be triggered by wireless transceiver (reproduced from Rehan et al licensed under CC BY-NC-ND 4.0). (G) A standalone capsule that uses on-board camera (optical detection) to identify the target location and collect the sample based on an internal microcontroller signal (reproduced from Yau et al 2021 Crohn’s & Colitis Foundation.). (H) A dynamic sampling device that focusses on collecting the microbiota from gut lining (reproduced from Rehan et al 2020 John Wiley & Sons). Dynamic sampling devices that focus on collecting the microbiota from the gut lining are shown in (B), (F) and (H).

Figure 7

Future of smart capsule technology for monitoring gut health and disease detection for early intervention of health issues.