Small intestinal sampling capsule for inflammatory bowel disease type detection and management

Authors: NEJATI, SINA - Purdue University; WANG, JIANGSHAN - Purdue University; HEREDIA, ULISSES - Purdue University; SEDAGHAT, SOTOUDEH - Purdue University; WOODHOUSE, IAN - Purdue University; Johnson, Jay; VERMA, MOHIT - Purdue University; RAHIMI, RAHIMI - Purdue University

Submitted to: Lab on a Chip
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/29/2021
Publication Date: 11/26/2021
Citation: Nejati, S., Wang, J., Heredia, U., Sedaghat, S., Woodhouse, I., Johnson, J.S., Verma, M., Rahimi, R. 2021. Small intestinal sampling capsule for inflammatory bowel disease type detection and management. Lab on a Chip. 22(1):57-70. https://doi.org/10.1039/D1LC00451D.
DOI: https://doi.org/10.1039/D1LC00451D

Interpretive Summary: The ability to non-invasively assess biomarkers associated with intestinal health is lacking in both humans and pigs. In humans, non-invasive technologies to assess intestinal health would be beneficial in diagnosing diseases such as Crohn’s disease and ulcerative colitis. In pigs, this technology would be beneficial for repeated and non-invasive sampling of intestinal contents for biomarker analyses. Traditionally, pigs must be euthanized, and intestinal sections are manually collected to evaluate intestinal physiology and microbiome. However, while this process is often a necessary step in swine intestinal health research, it leads to the use of a greater number of animals in research efforts due to an inability to perform repeated non-invasive sampling. To address these issues in both humans and pigs, we have developed and tested a battery free non-invasive smart capsule device that can allow for targeted sampling of intestinal biomarkers throughout the intestine. The battery free smart capsule is composed of a 3D printed casing with a superabsorbent hydrogel inside the capsule, which captures the biomarkers of interest. The capsule is then naturally passed and collected to evaluate the biomarkers. This capsule has been extensively tested and validated for use in both humans and pigs.

Technical Abstract: Although serum and fecal biomarkers (e.g., lactoferrin, and calprotectin) have been used in management and distinction between inflammatory bowel disease (IBD) and irritable bowel syndrome (IBS), none are proven to be a differential diagnostic tool between Crohn’s disease (CD) and ulcerative colitis (UC). The main challenge with laboratory-based biomarkers in the stool test is the inability to indicate the location of the disease/inflammation in the gastrointestinal (GI) tract due to the homogenous nature of the collected fecal sample. For the first time, we have designed and developed a battery-free smart capsule that will allow targeted sampling of inflammatory biomarkers inside the gut lumen of the small intestine. The capsule is designed to provide a simple and non-invasive complementary tool to fecal biomarker analysis to differentiate the type of IBD by pinpointing the site of inflammatory biomarkers secretion (e.g., small or large bowel) throughout the GI tract. The capsule takes advantage of the rapid change from an acidic environment in the stomach to higher pH levels in the small intestine to dissolve a pH-sensitive polymeric coating as a means to activate the sampling process of the capsule within the small intestine. A swelling poly-2-hydroxyethyl methacrylate hydrogel is placed inside the capsule as a milieu to collect the sampled GI fluid while also providing the required mechanical actuation to close the capsule once the sampling is completed. The hydrogel component along with the collected GI fluid can be easily obtained from the capsule through the screw-cap design for further extraction into a buffer solution. As a proof of concept, the capsule’s performance in sampling and extraction of bovine serum albumin (BSA) and calprotectin- a key biomarker of inflammation- was assessed within the physiologically relevant range. The ratio of extracted biomarkers relative to that in the initial sampling environment remained constant (~3%) and independent of the sampling matrix in both in vitro and ex vivo studies. It is believed that the demonstrated technology will provide immediate impact in more effective IBD type differential diagnostic and treatment strategies by providing a non-invasive assessment of inflammation biomarkers profile throughout the digestive tract.