Ingestible Osmotic Pill for In Vivo Sampling of Gut Microbiomes

Abstract

Technologies capable of noninvasively sampling different locations in the gut upstream of the colon enable new insights into the role of organ-specific microbiota in human health. Herein, an ingestible, biocompatible, battery-less, 3D-printed microengineered pill with an integrated osmotic sampler and microfluidic channels for in vivo sampling of the gut lumen and its microbiome upstream of the colon is discussed. The pill's sampling performance is characterized using realistic in vitro models and validated in vivo in pigs and primates. Herein, the results show that the bacterial populations recovered from the pill's microfluidic channels closely resemble the bacterial population demographics of the microenvironment to which the pill is exposed. Herein, it is believed that such lab-on-a-pill devices revolutionize the understanding of the spatial diversity of the gut microbiome and its response to medical conditions and treatments.

A toolbox for the comprehensive analysis of small volume human intestinal samples that can be used with gastrointestinal sampling capsules

“…Volumes of gastrointestinal samples, obtained from gastrointestinal sampling devices, are maximally 200 µL 14 . To obtain as much information as possible, we developed a workflow in which analyses were combined to allow the most efficient workup of the samples.…”

“…Detailed knowledge on the fate of fibres inside the human intestinal tract is however still very limited, due to the lack of convenient non-invasive methods to study the fate of dietary fibres inside the digestive tract in vivo. New gastrointestinal sampling capsules are being developed, which sample luminal content at a specific location in the intestinal lumen 11 , 14 , 15 . Application of these devices pose several methodological challenges, because of their retrieval time delay and their small volume.…”

“…Nevertheless, due to the novelty of these devices, no associated analytical methodologies have been published. The current challenges are the small sampling volumes of around maximum 200 µL 14 , and the time delay between sampling and harvesting at body temperature since excretion of the capsule from the body can take up to days 12 . Therefore, at the moment of actuation, the sample needs to be stabilised to block further metabolism so that a representative sample is obtained.…”

Current Sampling Methods for Gut Microbiota: A Call for More Precise Devices

“…Aspirated intestinal fluid can be collected after the capsule is discharged from the body. Recently, Rezaei Nejad et al also reported a 3D-printed pill for aspirating small intestinal fluid (Rezaei Nejad et al, 2019). This pill comprises a semipermeable membrane to separate the helical channels and salt chamber.…”

Orally ingestible medical devices for gut engineering

“…Also, the device can be controlled magnetically (Fig. 5D ii) [93]. The authors claimed that such a design promotes continuous sampling throughout the entire intestine as shown in Fig.…”