An engineered pill (aka lab-on-a-pill) for spatial sampling of microbiome and other contents in the gut
Tufts researchers have developed a device which traverses the gut and collects samples of the microbiome in a way that permits correlation of samples with particular locations from which they were sampled.
More than 1,000 species of bacteria inhabit the healthy gut. The vast majority of these bacteria have a beneficial, supportive role in digestion and protection against disease. When the natural balance of the microbiome is disturbed, a condition called “dysbiosis” occurs, which can be associated with inflammation, susceptibility to infections, and even the exacerbation of other diseases such as cancer. Research is increasingly unveiling specific microbiome metabolites that have beneficial or protective effects against disease.
Current methods of sampling the microbiome involve primarily the analysis of fecal DNA and metabolites, but the approach provides little information of the environment upstream of the distal colon, where bacterial species can vary significantly.
A 3D printed ingestible pill that samples bacteria found in the gut also known as the microbiome as it passes through the gastrointestinal tract (GI).
The device is manufactured with microfluidic channels that can sample different stages of the GI tract. The surface of the pill is covered with a pH sensitive coating, so that it does not absorb any samples until it enters the small intestine (bypassing the stomach) where the coating dissolves. A semi-permeable membrane separates two chambers in the pill – one containing helical channels that take up the bacteria and the other containing a calcium salt-filled chamber. The salt chamber helps create an osmotic flow across the membrane which pulls the bacteria into the helical channels. A small magnet in the pill enables one to hold it at certain locations in the gut for more spatially targeted sampling using a magnet outside the body. A fluorescent dye in the salt chamber helps locate the pill after it exits the GI tract.
Osmotic pill sampler design and working principle. a) A 3D schematic of the overall design of the pill, b) fabricated osmotic pill samplers, c) proof of concept, the pill samples of a water solution containing blue food dye (the sample did not penetrate the salt chamber), d) the pill surface and the fluorescent dye in the pill are detectable under UV light, e) scanning electron microscope (SEM) images of the osmotic membrane used in the pill, f) marked inlet at the top chamber is designed for initiating the pill (priming), and g) overall working principle of the osmotic pill sampler in an enteric capsule
The pill has been studied extensively in vitro and in vivo and found to provide accurate identification of bacterial populations and their relative abundance. It has been tested in pigs and primates, though additional clinical trials will be needed to determine if the pill can be used routinely in humans for clinical care.
Principal coordinate analysis of bacterial populations sampled with pills. Results from two experiments in pigs and two experiments in vitro (experiments 2 and 3) are represented with dotted and empty symbols, respectively. Symbol shape indicates whether sample originated from the pill's collection channel (○, “in”) or was collected from the matrix from which the pill was recovered (□, “out”). Color indicates organ for in vivo experiments and species origin of fecal sample for in vitro experiments. Two different mouse feces were used in experiment 2 and 3, explaining the distance between white and red datapoints.
IP STATUS PCT Publication No. WO2019178084 (September 19, 2019)