Time-resolved non-invasive metabolomic monitoring of a single cancer spheroid by microfluidic NMR

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 a...

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Autores principales:	Bishnubrata Patra, Manvendra Sharma, William Hale, Marcel Utz
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/36803785c8414c4f97f0b765608eed58
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spelling	oai:doaj.org-article:36803785c8414c4f97f0b765608eed582021-12-02T15:13:59ZTime-resolved non-invasive metabolomic monitoring of a single cancer spheroid by microfluidic NMR10.1038/s41598-020-79693-12045-2322https://doaj.org/article/36803785c8414c4f97f0b765608eed582021-01-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79693-1https://doaj.org/toc/2045-2322Abstract 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 150 $$\upmu$$ μ m to 300 $$\upmu$$ μ m in diameter in 2.5 $$\upmu$$ μ L 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 $$\le$$ ≤ 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 ( $$p=3.5\times 10^{-3}$$ 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.Bishnubrata PatraManvendra SharmaWilliam HaleMarcel UtzNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Bishnubrata Patra Manvendra Sharma William Hale Marcel Utz Time-resolved non-invasive metabolomic monitoring of a single cancer spheroid by microfluidic NMR
description	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 150 $$\upmu$$ μ m to 300 $$\upmu$$ μ m in diameter in 2.5 $$\upmu$$ μ L 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 $$\le$$ ≤ 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 ( $$p=3.5\times 10^{-3}$$ 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.
format	article
author	Bishnubrata Patra Manvendra Sharma William Hale Marcel Utz
author_facet	Bishnubrata Patra Manvendra Sharma William Hale Marcel Utz
author_sort	Bishnubrata Patra
title	Time-resolved non-invasive metabolomic monitoring of a single cancer spheroid by microfluidic NMR
title_short	Time-resolved non-invasive metabolomic monitoring of a single cancer spheroid by microfluidic NMR
title_full	Time-resolved non-invasive metabolomic monitoring of a single cancer spheroid by microfluidic NMR
title_fullStr	Time-resolved non-invasive metabolomic monitoring of a single cancer spheroid by microfluidic NMR
title_full_unstemmed	Time-resolved non-invasive metabolomic monitoring of a single cancer spheroid by microfluidic NMR
title_sort	time-resolved non-invasive metabolomic monitoring of a single cancer spheroid by microfluidic nmr
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/36803785c8414c4f97f0b765608eed58
work_keys_str_mv	AT bishnubratapatra timeresolvednoninvasivemetabolomicmonitoringofasinglecancerspheroidbymicrofluidicnmr AT manvendrasharma timeresolvednoninvasivemetabolomicmonitoringofasinglecancerspheroidbymicrofluidicnmr AT williamhale timeresolvednoninvasivemetabolomicmonitoringofasinglecancerspheroidbymicrofluidicnmr AT marcelutz timeresolvednoninvasivemetabolomicmonitoringofasinglecancerspheroidbymicrofluidicnmr
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Time-resolved non-invasive metabolomic monitoring of a single cancer spheroid by microfluidic NMR

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