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Time-Resolved Non-Invasive Metabolomic Monitoring of Microfluidic Spheroid And Monolayer Cell Cultures By NMR

preprint
submitted on 17.04.2020 and posted on 20.04.2020 by Bishnubrata Patra, Manvendra Sharma, William Hale, Marcel Utz
We present a quantitative NMR study comparing the metabolic activity in a spheroid and a monolayer of the same number of MCF-7 cells. Both cultures were carried out under hypoxic conditions on microfluidic devices with 2.5 µL sample volume. NMR spectra were obtained by periodically inserting the devices into a dedicated micro-NMR probe. The results demonstrate that quantitative, non-invasive metabolomic monitoring of microfluidic cultures with as few as 1250 individual cells is possible. Metabolite concentrations in the cultures were found to change linearly with time. The consumption rates of D-Glucose and the production rates of L-Lactic acid were approximately 2.5 times larger in the monolayer than in the spheroid. In contrast to the spheroids,
monolayers exhibited significant production of L-Alanine and L-Glutamine. Due to its non-invasive nature, metabolic monitoring by NMR can complement destructive fluorescent-based assays that are commonly used for read-out in microfluidic cultures.

Funding

EU H2020 #737043 TISuMR

History

Email Address of Submitting Author

marcel.utz@gmx.net

Institution

University of Southampton

Country

United Kingdom

ORCID For Submitting Author

0000-0003-2274-9672

Declaration of Conflict of Interest

no conflict of interest

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