An automated real-time microfluidic platform to probe single NK cell heterogeneity and cytotoxicity on-chip

Abstract Cytotoxicity is a vital effector mechanism used by immune cells to combat pathogens and cancer cells. While conventional cytotoxicity assays rely on averaged end-point measures, crucial insights on the dynamics and heterogeneity of effector and target cell interactions cannot be extracted,...

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Autores principales:	Nikita Subedi, Laura C. Van Eyndhoven, Ayla M. Hokke, Lars Houben, Mark C. Van Turnhout, Carlijn V. C. Bouten, Klaus Eyer, Jurjen Tel
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/87160ca70d764539bc92b8e660f8164f
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spelling	oai:doaj.org-article:87160ca70d764539bc92b8e660f8164f2021-12-02T15:09:16ZAn automated real-time microfluidic platform to probe single NK cell heterogeneity and cytotoxicity on-chip10.1038/s41598-021-96609-92045-2322https://doaj.org/article/87160ca70d764539bc92b8e660f8164f2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96609-9https://doaj.org/toc/2045-2322Abstract Cytotoxicity is a vital effector mechanism used by immune cells to combat pathogens and cancer cells. While conventional cytotoxicity assays rely on averaged end-point measures, crucial insights on the dynamics and heterogeneity of effector and target cell interactions cannot be extracted, emphasizing the need for dynamic single-cell analysis. Here, we present a fully automated droplet-based microfluidic platform that allowed the real-time monitoring of effector-target cell interactions and killing, allowing the screening of over 60,000 droplets identifying 2000 individual cellular interactions monitored over 10 h. During the course of incubation, we observed that the dynamics of cytotoxicity within the Natural Killer (NK) cell population varies significantly over the time. Around 20% of the total NK cells in droplets showed positive cytotoxicity against paired K562 cells, most of which was exhibited within first 4 h of cellular interaction. Using our single cell analysis platform, we demonstrated that the population of NK cells is composed of individual cells with different strength in their effector functions, a behavior masked in conventional studies. Moreover, the versatility of our platform will allow the dynamic and resolved study of interactions between immune cell types and the finding and characterization of functional sub-populations, opening novel ways towards both fundamental and translational research.Nikita SubediLaura C. Van EyndhovenAyla M. HokkeLars HoubenMark C. Van TurnhoutCarlijn V. C. BoutenKlaus EyerJurjen TelNature 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 Nikita Subedi Laura C. Van Eyndhoven Ayla M. Hokke Lars Houben Mark C. Van Turnhout Carlijn V. C. Bouten Klaus Eyer Jurjen Tel An automated real-time microfluidic platform to probe single NK cell heterogeneity and cytotoxicity on-chip
description	Abstract Cytotoxicity is a vital effector mechanism used by immune cells to combat pathogens and cancer cells. While conventional cytotoxicity assays rely on averaged end-point measures, crucial insights on the dynamics and heterogeneity of effector and target cell interactions cannot be extracted, emphasizing the need for dynamic single-cell analysis. Here, we present a fully automated droplet-based microfluidic platform that allowed the real-time monitoring of effector-target cell interactions and killing, allowing the screening of over 60,000 droplets identifying 2000 individual cellular interactions monitored over 10 h. During the course of incubation, we observed that the dynamics of cytotoxicity within the Natural Killer (NK) cell population varies significantly over the time. Around 20% of the total NK cells in droplets showed positive cytotoxicity against paired K562 cells, most of which was exhibited within first 4 h of cellular interaction. Using our single cell analysis platform, we demonstrated that the population of NK cells is composed of individual cells with different strength in their effector functions, a behavior masked in conventional studies. Moreover, the versatility of our platform will allow the dynamic and resolved study of interactions between immune cell types and the finding and characterization of functional sub-populations, opening novel ways towards both fundamental and translational research.
format	article
author	Nikita Subedi Laura C. Van Eyndhoven Ayla M. Hokke Lars Houben Mark C. Van Turnhout Carlijn V. C. Bouten Klaus Eyer Jurjen Tel
author_facet	Nikita Subedi Laura C. Van Eyndhoven Ayla M. Hokke Lars Houben Mark C. Van Turnhout Carlijn V. C. Bouten Klaus Eyer Jurjen Tel
author_sort	Nikita Subedi
title	An automated real-time microfluidic platform to probe single NK cell heterogeneity and cytotoxicity on-chip
title_short	An automated real-time microfluidic platform to probe single NK cell heterogeneity and cytotoxicity on-chip
title_full	An automated real-time microfluidic platform to probe single NK cell heterogeneity and cytotoxicity on-chip
title_fullStr	An automated real-time microfluidic platform to probe single NK cell heterogeneity and cytotoxicity on-chip
title_full_unstemmed	An automated real-time microfluidic platform to probe single NK cell heterogeneity and cytotoxicity on-chip
title_sort	automated real-time microfluidic platform to probe single nk cell heterogeneity and cytotoxicity on-chip
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/87160ca70d764539bc92b8e660f8164f
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An automated real-time microfluidic platform to probe single NK cell heterogeneity and cytotoxicity on-chip

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