Platform helps accelerate synthetic and metabolic workflows

Biosyntia is an industrial biotech company, focusing especially on developing more natural and sustainable processes for producing active ingredients used in beauty and nutrition such as vitamins and antioxidants. Investing in the right technology is key to helping the company achieve its goals — and by integrating Sphere Fluidics’ Pico-Mine platform, Biosyntia is now exploring genetic diversity faster than ever before.

Ultrahigh-throughput, droplet-based screening had long been on Biosyntia’s radar for its immense potential in cell factory development and Biosyntia’s synergistic expertise in biosensor development. Having explored various companies over several years to help bring this technology in-house, a partnership was born with Sphere Fluidics and its groundbreaking Pico-Mine platform. Designed to support earlier-stage research using picodroplet technology, Pico-Mine is designed to provide:

• semi-automated platform capabilities;
• flexibility for workflows and assays to help find valuable and rare biological variants among large cell populations;
• radically increased throughput; and
• reduced cost across a wide range of applications helping save on resources.
   

One of Biosyntia’s technologies for developing state-of-the-art cell factories for precision fermentation is the use of genetically encoded biosensors. However, uses of traditional tools, such as flow cytometry, are based on sensing internal product concentrations only. Pico-Mine droplet-based screening allows miniaturisation of a fermentation process to the nanolitre scale with direct sensing of extracellular product concentrations, and easy single-cell isolation of improved producing strains.

Within the first months of using Pico-Mine with Biosyntia’s proprietary B7 biosensor, the company has already been able to identify improved genetic variants of its B7 production strain, which are currently in the process of being upscaled for precision fermentation of sustainable and natural B7 vitamin (Bio-B7). It is able to explore genetic diversity faster than ever before, identifying the one-in-a-million cells from large mutant libraries that show improved production phenotypes.

“Droplet screening is a game changer, and with Pico-Mine from Sphere Fluidics in our lab we are now able to test 1000-fold more strains within the same timeframe and with a fraction of the resources,” said David Lennox-Hvenekilde, senior scientist and droplet screening lead at Biosyntia. “We are already seeing super-exciting results and expect many more to come.”

Pico-Mine offers droplet microfluidic technology in an easy-to-use platform, allowing researchers with no experience in microfluidics to run experiments in just a matter of weeks and therefore making it possible for scientists to quickly integrate the platform into their workflows and projects. In addition to its ease of use, due to its semiautomated design, there are many different experiments researchers can do with the set-up to expand research capabilities and stay at the forefront of single-cell research and implement effectively.

Pico-Mine is allowing Biosyntia to develop novel industrially relevant cell factories, with next steps to scale this technology to a wide array of further molecules, not limited to B vitamins. Droplet-based ultrahigh-throughput screening will play a cornerstone role in Biosyntia’s R&D strategy going forward to aid in reaching the company’s goals of European bio-based production of greener and more sustainable nutritional ingredients.

“We are truly excited about having the droplet technology in-house to substantially accelerate the improvement of strains for precision fermentation of nutritional ingredients,” said Hans Genee, CSO and co-founder of Biosyntia. “From what I have already seen, I expect to see significant impact across a wider portfolio of projects.”

Biosyntia’s updated workflow integrating Pico-Mine with its proprietary B7 biosensor has enabled the company to rapidly identify improved genetic variants of its B7 production strain. For a larger image, click here.

Flexible but simple, Pico-Mine lets users mix and match functions to build the workflow they need for every project, without requiring microfluidics expertise. The high-throughput, low-cost picodroplet technology allows both cell-by-cell assessment and rapid, low-stress processing of cells — all at tiny volumes — which should enable precise measurement of large libraries in hours. Pico-Mine biochips meanwhile allow a wide range of functions to be combined to execute even complex workflows, and Sphere Fluidics can provide custom biochips too if the user needs something slightly different.