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Harnessing microfluidics for high throughput microbiology R&D

The BioMillenia technology platform is based on microfluidics, a technology platform widely used in life sciences, but not necessarily in microbiology. There are some commercial developments of the technology, for example NGS or dPCR platforms, but it’s a very new application in the field of microbiology.

Culturing bacteria from environmental samples is notoriously difficult and requires great effort in optimization and adaptation of culture parameters, different media compositions and atmospheric conditions, and all greatly depending on the starting sample being used. In a laboratory context, this means employing many people, using a lot of space, a variety of incubation conditions and financial means to access that novel space for natural product discovery.

Using microfluidics to parallelise bacteria cultures

One of BioMillenia’s founders did some early work showing that the combination of microbial culture and biochemical assays can be used for bioprospection of bacteria from environmental samples. It was a very intriguing concept to look at droplet microfluidics, because now petri dishes and microlitre plates could be replaced with tiny droplets.

This allows us to parallelise the culture of bacteria independent from plates or petri dishes with a focus that was not possible to achieve before. We can generate 100 million droplets on our one platform in a single day, meaning that if we do single-cell encapsulations, we can hold 30 million parallel donor bacterial cultures in such macroenvironments.

We have consistently found that we can maintain a much higher microbial diversity of the original environmental sample using the cultural environment created with those tiny droplets. With a variety of starting materials – plant, animal, soil, water, humans – a comparison of the input bacterial sample and what is retrieved as a live culture shows much higher diversity than the usual microbiology methods.

There is a certain amount of know-how that we have developed in-house which increases the diversity of microbes in those cultures. The other key development is our ability to isolate the original droplets from within 100 million. We can do this, for example, based on the bacteria’s genotypic traits. Then we can also run assays in the droplets to identify specific traits of the bacteria based on enzymatic assays and reactivities, on molecules that those microbes secrete, and ELISA-type binding assays.

There are plenty of examples where we are attempting to develop the technology to broaden its applicability. There is a constant drive for innovation with the platform, as there has not been much use of microfluidics in the microbiology field.

One of the challenges is increasing the volume of throughput and parallel use of samples. Another area that we are seeking to improve is the differing atmospheric conditions utilised, such as implementing a fully anaerobic workflow for the culturing of more oxygen sensitive organisms.

Transitioning from a platform to a product company

We have previously been a technology platform company, but what is important now is to transition into a product company, so that we can apply the platform to developing new microbiome-based products.

The first area that we have chosen for this is the area of skin care, and we are actively working on projects to improve skin care products based on microbiome discoveries. It’s well known that unbalanced microbiome can lead to certain irritations and even diseases. This applies to many different areas such as digestive and immune health. As the skin is the largest immune organ, anything wrong there is certainly affected by the microbiome.

We try to identify the indications that an unbalance microbiome cause disruptions and irritations. We are looking for bacterial strains and products that can fight off certain pathobiont like Staphylococcus aureus, or finding nonchemical solutions to treat dandruff.

For a start-up company like ours, it’s important to have a fast track to the market. In skin care regulatory conditions are not as stringent as in other areas where our platform could play an important role. Also, in skin care we see a lot of correction in the market and also a lot of interest from potential partner companies.

Microbiome discoveries which drive Pharma R&D

The microbiome and the human host co-evolved over thousands of years, and so about 50 percent of the metabolites which are flowing through our body are not human cell derived but bacteria cell derived. To me, it’s logical that there is an impact of what microbes produce as compounds on human health and the destruction of the microbiome, also might lead to certain destruction of essential compounds, which might be needed.

I think the future will see a lot of work and intriguing discoveries into how compounds delivered by the human microbiome also affects disease stages – something which has started but is only just beginning. R&D in pharma is an area where it’s clear the microbiome plays a crucial role for the treatment and/or prevention of certain diseases.

With our technology platform we can identify strains and isolate them easily. We can then culture them and look for mechanistic interactions which could deliver a lot of ground-breaking work and collaborations, not least in the pharma field.

 

Dirk Loffert is CEO and co-founder of BioMillenia, France. He presented at the 6th Microbiome R&D & Business Collaboration Forum. 

 

 

The 7th Microbiome R&D & Business Collaboration Forum: USA allows you to discover how companies are successfully translating microbiome research into products, as well as to understand the regulatory hurdles and other obstacles to the microbiome market. Click here to view the agenda.

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