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Double emulsion-pretreated microwell culture for the in vitro production of multicellular spheroids and their in situ analysis

Multicellular spheroids have served as a promising preclinical model for drug efficacy testing and disease modeling. Many microfluidic technologies, including those based on water–oil–water double emulsions, have been introduced for the production of spheroids. However, sustained culture and the in...

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Autores principales: Qu, Fuyang, Zhao, Shirui, Cheng, Guangyao, Rahman, Habibur, Xiao, Qinru, Chan, Renee Wan Yi, Ho, Yi-Ping
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433470/
https://www.ncbi.nlm.nih.gov/pubmed/34567752
http://dx.doi.org/10.1038/s41378-021-00267-w
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author Qu, Fuyang
Zhao, Shirui
Cheng, Guangyao
Rahman, Habibur
Xiao, Qinru
Chan, Renee Wan Yi
Ho, Yi-Ping
author_facet Qu, Fuyang
Zhao, Shirui
Cheng, Guangyao
Rahman, Habibur
Xiao, Qinru
Chan, Renee Wan Yi
Ho, Yi-Ping
author_sort Qu, Fuyang
collection PubMed
description Multicellular spheroids have served as a promising preclinical model for drug efficacy testing and disease modeling. Many microfluidic technologies, including those based on water–oil–water double emulsions, have been introduced for the production of spheroids. However, sustained culture and the in situ characterization of the generated spheroids are currently unavailable for the double emulsion-based spheroid model. This study presents a streamlined workflow, termed the double emulsion-pretreated microwell culture (DEPMiC), incorporating the features of (1) effective initiation of uniform-sized multicellular spheroids by the pretreatment of double emulsions produced by microfluidics without the requirement of biomaterial scaffolds; (2) sustained maintenance and culture of the produced spheroids with facile removal of the oil confinement; and (3) in situ characterization of individual spheroids localized in microwells by a built-in analytical station. Characterized by microscopic observations and Raman spectroscopy, the DEPMiC cultivated spheroids accumulated elevated lipid ordering on the apical membrane, similar to that observed in their Matrigel counterparts. Made possible by the proposed technological advancement, this study subsequently examined the drug responses of these in vitro-generated multicellular spheroids. The developed DEPMiC platform is expected to generate health benefits in personalized cancer treatment by offering a pre-animal tool to dissect heterogeneity from individual tumor spheroids.
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spelling pubmed-84334702021-09-24 Double emulsion-pretreated microwell culture for the in vitro production of multicellular spheroids and their in situ analysis Qu, Fuyang Zhao, Shirui Cheng, Guangyao Rahman, Habibur Xiao, Qinru Chan, Renee Wan Yi Ho, Yi-Ping Microsyst Nanoeng Article Multicellular spheroids have served as a promising preclinical model for drug efficacy testing and disease modeling. Many microfluidic technologies, including those based on water–oil–water double emulsions, have been introduced for the production of spheroids. However, sustained culture and the in situ characterization of the generated spheroids are currently unavailable for the double emulsion-based spheroid model. This study presents a streamlined workflow, termed the double emulsion-pretreated microwell culture (DEPMiC), incorporating the features of (1) effective initiation of uniform-sized multicellular spheroids by the pretreatment of double emulsions produced by microfluidics without the requirement of biomaterial scaffolds; (2) sustained maintenance and culture of the produced spheroids with facile removal of the oil confinement; and (3) in situ characterization of individual spheroids localized in microwells by a built-in analytical station. Characterized by microscopic observations and Raman spectroscopy, the DEPMiC cultivated spheroids accumulated elevated lipid ordering on the apical membrane, similar to that observed in their Matrigel counterparts. Made possible by the proposed technological advancement, this study subsequently examined the drug responses of these in vitro-generated multicellular spheroids. The developed DEPMiC platform is expected to generate health benefits in personalized cancer treatment by offering a pre-animal tool to dissect heterogeneity from individual tumor spheroids. Nature Publishing Group UK 2021-05-24 /pmc/articles/PMC8433470/ /pubmed/34567752 http://dx.doi.org/10.1038/s41378-021-00267-w Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Qu, Fuyang
Zhao, Shirui
Cheng, Guangyao
Rahman, Habibur
Xiao, Qinru
Chan, Renee Wan Yi
Ho, Yi-Ping
Double emulsion-pretreated microwell culture for the in vitro production of multicellular spheroids and their in situ analysis
title Double emulsion-pretreated microwell culture for the in vitro production of multicellular spheroids and their in situ analysis
title_full Double emulsion-pretreated microwell culture for the in vitro production of multicellular spheroids and their in situ analysis
title_fullStr Double emulsion-pretreated microwell culture for the in vitro production of multicellular spheroids and their in situ analysis
title_full_unstemmed Double emulsion-pretreated microwell culture for the in vitro production of multicellular spheroids and their in situ analysis
title_short Double emulsion-pretreated microwell culture for the in vitro production of multicellular spheroids and their in situ analysis
title_sort double emulsion-pretreated microwell culture for the in vitro production of multicellular spheroids and their in situ analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8433470/
https://www.ncbi.nlm.nih.gov/pubmed/34567752
http://dx.doi.org/10.1038/s41378-021-00267-w
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