SlipChip Helps Isolate, Grow Individual Gut Microbe Strains

Photograph of a glass SlipChip for growing microbes, shown next to a US quarter (left). Fluorescent in situ hybridization image of the target organism (right, top). Transmission electron microscopy image of a single cell of the target organism (right, bottom). Credit: Liang Ma (Ismagilov group) and Roland Hatzenpichler/Caltech

The world around us, and certainly within us, is full of bacteria. Within our very guts are millions of individual strains that may have beneficial functions for our bodies, be cause of disease, or simply be resident microbes living peacefully in a hospitable environment. Studying specific species among such a large set of bacteria is difficult because some strains are considerably more numerous, eclipsing others that are difficult to detect and isolate. This has greatly impeded research into the gut’s microbiome. Researchers at Caltech have developed a new method that relies on a microfluidic device, called SlipChip, that can help isolate and culture specific bacteria for laboratory work.

Fluorescence images showing that RNA sequences from the target organism (red and green) are present in every cell (blue, overlay). The overlay validates that this is a pure culture of a single microbial species—and that the single species is the target organism.

The SlipChip, also developed at Caltech, can help isolate specific bacterial strains from a sample into separate compartments. Once there, the researchers are able to split the contents of the compartments, using one half to identify the strain using DNA sequencing, while the other is kept alive for further cultivation and experimentation.

More info from Caltech:

To validate the new methodology, the researchers isolated one specific bacterium from the Human Microbiome Project’s “Most Wanted” list. The investigators used the SlipChip to grow this bacterium in a tiny volume of the washing fluid that was used to collect the gut bacteria sample from a volunteer. Since bacteria often depend on nutrients and signals from the extracellular environment to support growth, the substances from this fluid were used to recreate this environment within the tiny SlipChip compartment—a key to successfully growing the difficult organism in the lab.

After growing a pure culture of the previously unidentified bacterium, Ismagilov and his colleagues obtained enough genetic material to sequence a high-quality draft genome of the organism. Although a genomic sequence of the new organism is a useful tool, further studies are needed to learn how this species of microbe is involved in human health, Ismagilov says.

In the future, the new SlipChip technique may be used to isolate additional previously uncultured microbes, allowing researchers to focus their efforts on important targets, such as those that may be relevant to energy applications and the production of probiotics. The technique, says Ismagilov, allows researchers to target specific microbes in a way that was not previously possible.

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