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Around 170,000 tons of cheese are produced in Switzerland per year (40% of the total Swiss milk production) with a value of around CHF 600 million ($674 million). Agroscope, a Swiss federal research institute, produces microbes necessary to manufacture and preserve the great diversity and uniqueness of Helvetic cheese and fermented milk products. Over 12,000 different microbial strains of 350 different species have been collected and are produced at Agroscope. Over 90,000 liquid bacterial culture samples, in addition to 115,000 freeze-dried cultures, are sold annually. The cultures are also used to produce Appellation d’Origine Protégée cheeses, a Swiss excellency. Only 12 Swiss cheeses are under this designation, and they keep alive the great passion and quality from the region in which they are produced.

Ueli von Ah, PhD, head of Agroscope’s Biotechnology Research Group, supervises the federal research station for dairy technology; his team ensures the production, safety, and efficiency of the starter cultures used by the Swiss dairy manufacturers. He gave us an insight into how the production of bacterial cultures is supported and facilitated by Securecell’s technological platforms.

Production of microbial cultures

Production of the microbial cultures starts in six 0.5-L bioreactors. There, fermentation is manually initiated, and measurements are successively and automatically managed and controlled by Lucullus® (Securecell AG). The production is then automatically upscaled into 5-L bioreactors, fully integrated into Lucullus®. After fermentation and separation of the biomass in the 5-L bioreactors, cryoprotective media is added, and then yield and activity of the strains are evaluated after freeze-drying.

Dr. von Ah uses Lucullus® to increase the cultures’ production performance and control the fermentation processes. Lucullus® is a Process Information Management System (PIMS) that aligns and stores all data from disparate sources of the entire bioprocess environment in one place. Operations, process control, data collection, and analysis are planned and executed. The harmonization of the different devices and data is made easy by integrated workflows and a high degree of automation.

“All the processed data are transferred to the central hub automatically without any issue. All information is centrally managed, easily accessible, and ready to be directly applied,” says Dr. von Ah.

During the fermentation process, sugars and acids have to be monitored as they are strong indicators of biomass production. It is possible to plan and control the fermentation rate and advancement by measuring those two parameters. This automatic process control can be implemented with the help of Numera®, Securecell’s automated PAT sample, and sampling management system.

Numera®, autosampler, and HPLC at work
Numera®, autosampler, and HPLC at work

At Agroscope, Numera® automatically performs sampling every two hours from four 5-L bioreactors. Numera® avoids the hassle of manually preparing and collecting samples and allows real-time control of the media recipe, quick adjustment of the concentration of sugars, and better biomass production.

Media preparation

The media recipes for liquid and freeze-dried culture media are developed using the Lucullus® media tool. The media tool offers a raw materials and media database, a recipe library, sample information, and a barcode generator to keep track of samples. The system offers complete media traceability. All the parameters can be shared safely on-site and off-site.

“Lucullus® is a really powerful tool, and it has incredibly advanced features and tools. Lucullus® implements the traceability: I can identify all the steps from the freeze-drying batch to the conserve from which I have started the process,” states Dr. von Ah.

The entry of offline data into the staging area

Cell culture data are automatically imported into Lucullus® and displayed for analysis online, offline, or even remotely. There is no accurate soft sensor available to measure the biomass produced at Agroscope; this process requires offline measurements that are successively and automatically imported into Lucullus® for additional automatic processing.

 

Securecell empowers biopharma and biotech for full bioprocess development automation. Discover more at bit.ly/HighTechSwissCheese.