Researchers from Purdue University have developed a 3D printed capsule that’s capable of sampling bacteria inside the human stomach.
Designed to perform the role of a colonoscopy, the printed pill is able to capture bacteria (known as biome), not just in the colon, but the entire gastrointestinal tract. The “gut-oscopy” technique could be deployed alongside existing colonoscopy processes in order to better understand intestinal diseases.
“If a colonoscopy or camera pill sees blood, it can’t sample that area to investigate further, said Rahim Rahimi, Assistant Professor of Materials Engineering at Purdue. “You could just sample bacteria from a person’s fecal matter, but bacteria can vary a lot throughout the GI tract. Our approach could be complementary.”
“It’s all about being able to take samples of bacteria anywhere in the gut. That was impossible before.”
Colonoscopies and 3D printed pills
Over the past decade, studies have identified links between biological imbalances (dysbiosis) in the stomach and diseases such as diabetes, obesity, and metabolic syndrome. The presence of specific bacterial species can also alter the metabolism of certain drugs, such as chemotherapeutic agents and antiviral medication. As a result, microbiome sampling is important to understanding microbiota-drug interactions, and it provides the potential for developing patient-specific medication delivery.
The majority of pre-existing research has been conducted using ex-situ sampling methods that rely on the collection of fecal matter. As only a fraction of gut bacteria from fecal specimens is culturable, major efforts have been made to enable the direct sampling of microorganisms from the GI tract. The tract itself is 9 meters long, and its diameter varies by patient, so direct sampling has many challenges. Current colonoscopy and gastroscopy methods are limited to sampling at certain sections, and can be invasive, causing patient non-compliance.
Smart functional capsules provide an alternative approach, by taking bacteria from targeted locations along the GI tract. PillCam Capsule Endoscopy (CE) technology has already been commercialized, and is widely used as a non-invasive alternative to traditional endoscopies. Despite the PillCam’s video diagnostic abilities, it still lacks the ability to collect and store samples inside the capsule. Battery-driven sampling capsules have also been developed, but malfunctions have stranded the devices inside patients during testing.
“Passive actuation” sampling offers a more compact, safer and cheaper option. In passive designs, the capsule moves through the GI tract via peristalsis motion, with an average speed of 1–2 cm min−1. Previous attempts at creating passive capsules have varied in form. A multicenter study in 2015, successfully created a passive pill in the form of a compressed mesh sponge, but this was retrieved via a piece of string, causing discomfort to the patient.
The Purdue team’s new capsule design
In a novel approach, the Purdue team has created a capsule that uses the swelling property of a highly absorbent hydrogel to collect bio organisms. Hydrogels are super-absorbent and can soak up 150–300 times their weight in aqueous conditions, making them ideal for storing bacteria. Incorporating the absorbency of hydrogels into the pill enabled the device to be non-invasive, and enter previously unreachable areas of the GI tract.
The tablet itself consists of four components: a biodegradable enteric coating, 3D printed housing, sampling hydrogel, and a gas permeable PDMS membrane. Utilizing a Form 2 3D printer, the research team fabricated the pills with a biocompatible photocurable polymer. Each capsule, measuring 9mm in diameter and 15mm in length, contained the sampling hydrogel as well as the 1 mm thick membrane.
In practice, the pill is swallowed, and its biodegradable enteric coating delays it from being activated until it reaches its target location. Once there, the coating dissolves, allowing GI fluids to fill the device. As the dehydrated hydrogel expands inside the pill, it pushes the PDMS membrane onto the capsule’s aperture, acting to seal the device once full.
Testing the efficacy of the Purdue pill
In order to evaluate their newly-developed pills, the team conducted a series of leak tests and in vitro bacteria sampling. To assess the device’s sealing mechanism, an assembled capsule and a separate hydrogel were separately submerged in sodium chloride solution and DI water for eight hours. Red food coloring was also added, so that the level of absorbency between the two hydrogels could be easily identified.
Summary UV-visible spectroscopy measurements showed no fresh media inside the capsule over the course of the experiment. The level of absorption in the sealed capsule and pure DI water proved to be comparable, and remained stable over time. As a result, the test confirmed that no exchange of fluids took place between the hydrogel within the sealed capsule, and the sodium chloride solution.
To validate the device’s ability to sample bacteria, the researchers submerged the capsules in culture solution to simulate the GI environment. Three fully-assembled capsules and a set of bare hydrogel samples were immersed into three different solutions for one hour each. The conditions were designed to be hostile to the bacteria, and to challenge the survivability of the biome in their 3D printed pill.
Cross section SEM images later confirmed the presence of bacteria on the surface of the hydrogel, and that E. coli were able to attach onto the gel’s solid polymer network. Further testing involved using a combination of bleach and the antibiotic Tobramycin, to simulate the harshest plausible environment. In all conditions, the bare hydrogels had a lower number of viable bacteria compared to that extracted from within the sealed capsules.
Although fewer viable bacteria samples were maintained under the bleach evaluations, a significant amount still survived, further proving that the hydrogel provided a nurturing habitat. The Purdue team believes that the pill’s low cost and simple design could enable its widespread future application in clinical settings. In the meantime, the researchers will focus on targeting specific sample locations and conducting in vivo testing using animal models.
Previous 3D printed capsules
3D printed pills represent an important tool for scientists, as they provide a non-intrusive method of examining and affecting the insides of the human body.
A research project led by Tufts University, also 3D printed a capsule with the aim of sampling bacteria in the gut. The pill proved capable of spatially targeting microbiomes in the intestinal tracts of animals.
Scientists from the University College London (UCL) discovered an unexpected chemical reaction while 3D printing pills. Experiments revealed that heart pressure drug Amlodipine was undetectable when fabricated with other medications.
A team from St. John’s University, New York, produced 3D printed tablets that could deter opioid abusers from misusing pharmaceuticals. The egg-shaped tablets, dubbed “egglets”, were developed to deliberately make them difficult to take recreationally.
The researchers’ findings are detailed in their paper titled “Smart capsule for non-invasive sampling and studying of the gastrointestinal microbiome,” which was published in the RSC Advances journal. The report was co-authored by Jose Fernando Waimin, Sina Nejati, Hongjie Jiang, Jake Qiu, Jianghsan Wang, Mohit S. Verma and Rahim Rahimi.
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Featured image shows a GIF of the Purdue researchers’ 3D printed capsule. GIF via Purdue University, Kapwing.