Time-resolved non-invasive metabolomic monitoring of a single cancer spheroid by microfluidic NMR
Time-resolved non-invasive metabolomic monitoring of a single cancer spheroid by microfluidic NMR
We present a quantitative study of the metabolic activity of a single spheroid culture of human cancer cells. NMR (nuclear magnetic resonance) spectroscopy is an ideal tool for observation of live systems due to its non-invasive nature. However, limited sensitivity has so far hindered its application in microfluidic culture systems. We have used an optimised micro-NMR platform to observe metabolic changes from a single spheroid. NMR spectra were obtained by directly inserting microfluidic devices containing spheroids ranging from 150µm to 300 µm in diameter in 2.5µL of culture medium into a dedicated NMR probe. Metabolite concentrations were found to change linearly with time, with rates approximately proportional to the number of cells in the spheroid. The results demonstrate that quantitative monitoring of a single spheroid with ≤2500 cells is possible. A change in spheroid size by 600 cells leads to a clearly detectable change in the L-Lactic acid production rate (p = 3.5×10−3). The consumption of D-Glucose and production of L-Lactic acid were approximately 2.5 times slower in spheroids compared to monolayer culture of the same number of cells. Moreover, while cells in monolayer culture were found to produce L-Alanine and L-Glutamine, spheroids showed slight consumption in both cases
Patra, Bishnubrata
3bfe5fe9-78ef-4026-9f42-2dd75cfea3b2
Sharma, Manvendra
e249236d-221d-4e59-8440-011f6863f891
Hale, William G
d98f9d64-00f9-447e-9783-185185a0b3c6
Utz, Marcel
c84ed64c-9e89-4051-af39-d401e423891b
December 2021
Patra, Bishnubrata
3bfe5fe9-78ef-4026-9f42-2dd75cfea3b2
Sharma, Manvendra
e249236d-221d-4e59-8440-011f6863f891
Hale, William G
d98f9d64-00f9-447e-9783-185185a0b3c6
Utz, Marcel
c84ed64c-9e89-4051-af39-d401e423891b
Patra, Bishnubrata, Sharma, Manvendra, Hale, William G and Utz, Marcel
(2021)
Time-resolved non-invasive metabolomic monitoring of a single cancer spheroid by microfluidic NMR.
Scientific Reports, 11 (1), [53].
(doi:10.1038/s41598-020-79693-1).
Abstract
We present a quantitative study of the metabolic activity of a single spheroid culture of human cancer cells. NMR (nuclear magnetic resonance) spectroscopy is an ideal tool for observation of live systems due to its non-invasive nature. However, limited sensitivity has so far hindered its application in microfluidic culture systems. We have used an optimised micro-NMR platform to observe metabolic changes from a single spheroid. NMR spectra were obtained by directly inserting microfluidic devices containing spheroids ranging from 150µm to 300 µm in diameter in 2.5µL of culture medium into a dedicated NMR probe. Metabolite concentrations were found to change linearly with time, with rates approximately proportional to the number of cells in the spheroid. The results demonstrate that quantitative monitoring of a single spheroid with ≤2500 cells is possible. A change in spheroid size by 600 cells leads to a clearly detectable change in the L-Lactic acid production rate (p = 3.5×10−3). The consumption of D-Glucose and production of L-Lactic acid were approximately 2.5 times slower in spheroids compared to monolayer culture of the same number of cells. Moreover, while cells in monolayer culture were found to produce L-Alanine and L-Glutamine, spheroids showed slight consumption in both cases
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More information
Accepted/In Press date: 27 November 2020
Published date: December 2021
Additional Information:
Funding Information:
The datasets for the current study are available in the University of Southampton Institutional repository (https ://doi.org/10.5258/SOTON/D1329). We thank Ms. Sylwia Ostrowska and Mr. Jacob Keeley for help with the pH calibration and for performing a T1measurement of the growth medium. This work was supported by the European Commission through the Horizon 2020 Future and Emerging Technologies programme, Project TISuMR (Grant number 737043).
Publisher Copyright:
© 2021, The Author(s).
Identifiers
Local EPrints ID: 445751
URI: http://eprints.soton.ac.uk/id/eprint/445751
ISSN: 2045-2322
PURE UUID: 79c7981a-5ed3-4f06-a6ff-3b681c4ef4e1
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Date deposited: 07 Jan 2021 17:31
Last modified: 17 Mar 2024 03:30
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Author:
Bishnubrata Patra
Author:
Manvendra Sharma
Author:
William G Hale
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