bioRxiv Science⌕ Search

bioRxiv · 10.1101/2024.10.10.617430

Step-by-step methodology for building a capsule to sample small intestine content

Abstract

BackgroundResearch on the intestinal microbiome has been hindered by limited access to intestinal content. Recently, a few capsule prototypes have demonstrated their potential for sampling intestinal material while using the natural pathway. However, access to these capsules is restricted because most of them are not yet commercially available. Pigs offer significant potential to inform human research due to the many physiological similarities between the two species. The unique features of pig anatomy have made it difficult to conduct research using swallowable devices. This article provides a detailed account of the manufacturing process and composition of a capsule, along with all the necessary steps for successfully sampling small intestine content in pigs. ResultsThe capsule moves passively through the digestive tract, relying solely on intestinal peristalsis for propulsion. Engineered to open when it encounters a pH level greater than 6, the upper part dissolves, allowing intestinal fluids to enter the inner chamber. This triggers a plunger to expand, drawing luminal content into the storage chamber. Once the plunger mechanism is fully extended the capsule is automatically sealed. The capsule has a size of a 0 hard capsule and consists of two main components: a dissolvable exterior with an enteric coating and a 3D-printed bottom part. The printing files of the 3D-printed bottom part are provided for replication. In vitro testing shows that the capsule can withstand two hours in an acidic medium and successfully samples within an hour of being transferred to a neutral medium. When tested in vivo in pigs, the capsule successfully collected intestinal content from the upper and middle sections of the small intestine. ConclusionsThis article provides essential details for the rapid development of a cost-effective tool that has been already validated for non-invasive sampling of small intestine content in pigs. By providing access to the exact production steps and printing files, this article empowers others to innovate and expand upon this foundational work. This open-source approach opens up new avenues for intestinal research, making it more accessible and adaptable for a wide range of studies in both animal and human models.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Ollagnier, C., Tretola, M., Garcia Vinado, I., Morel, B.. 2024-10-12. Step-by-step methodology for building a capsule to sample small intestine content. https://doi.org/10.1101/2024.10.10.617430

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Surfactant-Assisted Colorimetric Signal Enhancement in Paper-Based Glucose Sensing

Paper-based colorimetric sensors offer a low-cost and accessible platform for point-of-care (POC) analysis, but enzyme activity loss during coating and drying can weaken analytical signals and require high enzyme loadings or complex immobilization procedures. Although surfactants are widely used to improve wettability in paper-based assays, their potential contribution to colorimetric performance beyond these effects remains unclear. Here, we investigated surfactant-assisted colorimetric signal enhancement in a glucose assay implemented on a 96-puddle paper plate (96-PPP) and identified Tween 20 as the most effective surfactant. Its effect on detection performance became more pronounced as glucose oxidase (GOx) loading decreased; at 0.1 mg/mL GOx, Tween 20 lowered the limit of detection (LoD) from 0.113 to 0.034 mg/mL (approximately 3.3-fold) over a working range of 0-5 mg/mL, despite no statistically significant change in the measured contact angle at this loading. Tween 20 had no appreciable effect on the reaction in solution but preserved 95% of the apparent reaction rate constant after drying, compared with 11% without it, and atomic force microscopy (AFM) revealed a more dispersed dried enzyme morphology on mica. Tween 20-containing sensors also showed slower signal decay during repeated wetting-drying cycles and thermal stress, retained 77% (vs 26%) of the response at 400 mM NaCl, and exhibited within-PPP and between-batch coefficients of variation (CVs) below 10% (vs 12.3-19.5%), while maintaining glucose selectivity over potentially interfering molecules. These results indicate that Tween 20 enhances paper-based glucose sensing beyond wettability, in part by retaining enzyme cascade activity during drying, although the contributions of the individual enzymes and the underlying mechanism remain to be established.

bioengineering↗

Engineering CAR-T cells to remodel the mucin-rich cancer cell glycocalyx

The dense glycocalyx of cancer cells can restrict immune-cell access to surface antigens and limit CAR-T cell activity. Here, we show that mucin density and epitope position determine how glycocalyx remodeling affects CAR-T cell recognition and killing. We identify KLK5 as a human protease that cleaves tumor-associated mucins, increases access to membrane-proximal antigens, and enhances CAR-T cell function. We then engineer CAR-T cells to display or secrete KLK5, enabling remodeling of the tumor glycocalyx during antigen recognition. KLK5-engineered CAR-T cells improved tumor control across multiple xenograft models, and KLK5-secreting MUC17 CAR-T cells produced the strongest in vivo benefit, prolonging survival compared with conventional MUC17 CAR-T cells. These findings show that CAR-T cells can be engineered to breach the mucin-rich glycocalyx while preserving accessible target epitopes.

bioengineering↗

Wall stiffening is a primary contributor to motility loss in Crohn's disease: an electromechanical modeling study

Fibrotic strictures are among the most disabling complications of Crohn's disease, permanently narrowing the bowel and impairing motility, yet no approved therapy reverses them. Chronic inflammation alters pacemaker-network coupling, smooth-muscle excitability, and calcium-dependent contractility, while fibrosis thickens the bowel wall, narrows the lumen, and changes tissue mechanics. The relative contributions of these coupled electrical, contractile, and structural alterations to motility loss remain unclear. To address this gap, we develop an integrated electromechanical finite-element framework for fibrostenosing Crohn's disease that couples a fibrosis-driven growth model with a FitzHugh-Nagumo electromechanical model. A full-factorial 25 design of experiments is used to quantify the relative effects of electrical diffusivity, excitation threshold, peak active stress, wall stiffness, and hypertrophic remodeling on cyclic lumen-volume deformation. Motility is quantified by the standard deviation of lumen volume over one contraction cycle. Within the parameter ranges examined, increased wall stiffness emerged as the dominant contributor to motility loss, followed by impaired smooth-muscle contractility. Changes in excitation threshold, hypertrophic remodeling, and electrical diffusivity produced substantially smaller effects. Pairwise interactions were small relative to the dominant main effects, indicating that the mechanisms contributed largely through their individual effects. Our findings suggest that limiting wall stiffening while preserving smooth-muscle contractile function may provide a therapeutic strategy for maintaining intestinal motility in fibrostenosing Crohn's disease.

bioengineering↗