Case study

InsightCell

Online monitoring of living cells metabolism by nuclear magnetic resonance

Cloud tag

Background

Bruker is a developer, manufacturer and distributor of high-performance scientific instruments and analytical and diagnostic solutions that enable our customers to explore life and materials at microscopic, molecular and cellular levels.

Challenges

In the context of vaccine production, the monitoring of bioprocesses is mandatory for quality control, but is generally only ensured by measurements of a limited number of standard variables (e.g. oxygen consumption, pH variation, or measurement of certain metabolites) but give no information on the dynamic of the metabolic activity of production cells.

Being able to monitor dynamically, and in real-time, cells in fermentation systems would allow to understand reactions and anticipate potential issues in production, as well as optimize processes.

Solution

The solution consists in using the established InsightMR™ technology from Bruker, designed originally for the monitoring chemical reactions on-line, under real process conditions.

For metabolites monitoring in biological processes, the culture could flow from the bioreactor to the NMR spectrometer, in a closed circuit, allowing temperature stability. To test this approach, we used a simple culture of Saccharomyces Cerevisiae yeast, focusing on metabolic pathways that are common to all eukaryotic cells, performing continuous 1H NMR analysis for 6 hours.

Results

The system stability and the metabolites detection sensibility was performed by analysis Saccharomyces Cerevisiae in the RPMI culture media. This media is reach in diverse metabolites and is usually used for culturing of eukaryotic cells. All amino acids were detected, as well as glucose, myo-Inositol and choline.

Only, vitamins, which were at submicromolar concentration, were under the detection limit.
The InsightMRTM software allowed us to monitor metabolites evolution and we have been able to characterize the metabolic activity of Saccharomyces Cerevisiae, observing glucose consumption, while acetate and ethanol were abundantly produced during fermentation.
This “proof of concept” study has confirm that the InsightMRTM technology can be used for the monitoring of living cells, offering a new tool for the dynamic monitoring of bioprocesses.

Outlook

Based on our expertise in NMR metabolomics, from wet lab to data interpretation, as well as in microbiology and bioprocesses, we can leverage this technology to help companies interested in improving their bioproduction processes.

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