Smart Sampling Capsule for Small Intestinal Bacteria Overgrowth Detection

Small intestinal bacterial overgrowth (SIBO) is the condition when the bacteria in the upper gastrointestinal tract grow excessively beyond 10⁵ colony forming units (CFU)/mL. The high population of bacteria then leads to malabsorption, indigestion, constipation, and a decrease in the efficiency of the immune system. Currently available techniques for the diagnosis of SIBO rely on jejunal aspiration and breath tests for measuring the hydrogen and methane produced through the bacterial metabolism of carbohydrates. However, these approaches commonly suffer from invasiveness, high expense, and poor accuracy by yielding false-positive results. Here, to sidestep the issues associated with discomfort to the patient, contamination, and unreliable results, we designed and developed a new 3D-printed sampling device to site-selectively collect small intestinal bacteria. The capsule's pH-responsive enteric coating served as an actuation mechanism to open the device in the region of the small intestine to facilitate bacteria collection while maintaining its integrity in the highly acidic environment of the stomach. A water-soluble glue was used to maintain the compression of a biocompatible polyetheretherketone (PEEK) spring, which was then inserted inside the capsule. When the enteric coating disintegrated and the GI tract fluid collected, the water-soluble glue was dissolved, causing the spring to expand. Upon expansion, the bonded flexible disc on top of the spring effectively sealed the capsule preventing contamination from the lower GI tract. Once the device has been discharged, the device could be readily opened to collect the small intestinal bacteria and quantify the CFU/mL. To achieve the least amount of deformation after the expansion of the spring, various materials were tested under compression for different time points and the length variation was recorded. Additionally, a series of systematic force profile studies was performed with different glue thicknesses to identify the exerted force for proper sealing of the device as well as understand the duration of the sampling. To demonstrate the non-selective sampling capability of the device, different dye concentrations as well as two bacterial strains including Escherichia coli and Pseudomonas aeruginosa with different concentrations were investigated. The results showed an excellent matching concentration between the collected sample and the sampling environment. The targeted bacterial sampling performance and spring-assisted sealing mechanism were validated using both realistic in vitro GI tract models with bacteria cultures and ex vivo with dissected porcine small intestines. Here, it is envisioned that such smart sampling capsule technology will offer new ways to gather specific bacteria from the small intestine to identify the potential for SIBO disease more accurately.