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A Microfluidic Hanging-Drop-Based Islet Perifusion System for Studying Glucose-Stimulated Insulin Secretion From Multiple Individual Pancreatic Islets

Islet perifusion systems can be used to monitor the highly dynamic insulin release of pancreatic islets in glucose-stimulated insulin secretion (GSIS) assays. Here, we present a new generation of the microfluidic hanging-drop-based islet perifusion platform that was developed to study the alteration...

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Autores principales: Wu Jin, Patricia, Rousset, Nassim, Hierlemann, Andreas, Misun, Patrick M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149801/
https://www.ncbi.nlm.nih.gov/pubmed/34055765
http://dx.doi.org/10.3389/fbioe.2021.674431
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author Wu Jin, Patricia
Rousset, Nassim
Hierlemann, Andreas
Misun, Patrick M.
author_facet Wu Jin, Patricia
Rousset, Nassim
Hierlemann, Andreas
Misun, Patrick M.
author_sort Wu Jin, Patricia
collection PubMed
description Islet perifusion systems can be used to monitor the highly dynamic insulin release of pancreatic islets in glucose-stimulated insulin secretion (GSIS) assays. Here, we present a new generation of the microfluidic hanging-drop-based islet perifusion platform that was developed to study the alterations in insulin secretion dynamics from single pancreatic islet microtissues at high temporal resolution. The platform was completely redesigned to increase experimental throughput and to reduce operational complexity. The experimental throughput was increased fourfold by implementing a network of interconnected hanging drops, which allows for performing GSIS assays with four individual islet microtissues in parallel with a sampling interval of 30 s. We introduced a self-regulating drop-height mechanism that enables continuous flow and maintains a constant liquid volume in the chip, which enables simple and robust operation. Upon glucose stimulation, reproducible biphasic insulin release was simultaneously observed from all islets in the system. The measured insulin concentrations showed low sample-to-sample variation as a consequence of precise liquid handling with stable drop volumes, equal flow rates in the channels, and accurately controlled sampling volumes in all four drops. The presented device will be a valuable tool in islet and diabetes research for studying dynamic insulin secretion from individual pancreatic islets.
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spelling pubmed-81498012021-05-27 A Microfluidic Hanging-Drop-Based Islet Perifusion System for Studying Glucose-Stimulated Insulin Secretion From Multiple Individual Pancreatic Islets Wu Jin, Patricia Rousset, Nassim Hierlemann, Andreas Misun, Patrick M. Front Bioeng Biotechnol Bioengineering and Biotechnology Islet perifusion systems can be used to monitor the highly dynamic insulin release of pancreatic islets in glucose-stimulated insulin secretion (GSIS) assays. Here, we present a new generation of the microfluidic hanging-drop-based islet perifusion platform that was developed to study the alterations in insulin secretion dynamics from single pancreatic islet microtissues at high temporal resolution. The platform was completely redesigned to increase experimental throughput and to reduce operational complexity. The experimental throughput was increased fourfold by implementing a network of interconnected hanging drops, which allows for performing GSIS assays with four individual islet microtissues in parallel with a sampling interval of 30 s. We introduced a self-regulating drop-height mechanism that enables continuous flow and maintains a constant liquid volume in the chip, which enables simple and robust operation. Upon glucose stimulation, reproducible biphasic insulin release was simultaneously observed from all islets in the system. The measured insulin concentrations showed low sample-to-sample variation as a consequence of precise liquid handling with stable drop volumes, equal flow rates in the channels, and accurately controlled sampling volumes in all four drops. The presented device will be a valuable tool in islet and diabetes research for studying dynamic insulin secretion from individual pancreatic islets. Frontiers Media S.A. 2021-05-12 /pmc/articles/PMC8149801/ /pubmed/34055765 http://dx.doi.org/10.3389/fbioe.2021.674431 Text en Copyright © 2021 Wu Jin, Rousset, Hierlemann and Misun. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Bioengineering and Biotechnology
Wu Jin, Patricia
Rousset, Nassim
Hierlemann, Andreas
Misun, Patrick M.
A Microfluidic Hanging-Drop-Based Islet Perifusion System for Studying Glucose-Stimulated Insulin Secretion From Multiple Individual Pancreatic Islets
title A Microfluidic Hanging-Drop-Based Islet Perifusion System for Studying Glucose-Stimulated Insulin Secretion From Multiple Individual Pancreatic Islets
title_full A Microfluidic Hanging-Drop-Based Islet Perifusion System for Studying Glucose-Stimulated Insulin Secretion From Multiple Individual Pancreatic Islets
title_fullStr A Microfluidic Hanging-Drop-Based Islet Perifusion System for Studying Glucose-Stimulated Insulin Secretion From Multiple Individual Pancreatic Islets
title_full_unstemmed A Microfluidic Hanging-Drop-Based Islet Perifusion System for Studying Glucose-Stimulated Insulin Secretion From Multiple Individual Pancreatic Islets
title_short A Microfluidic Hanging-Drop-Based Islet Perifusion System for Studying Glucose-Stimulated Insulin Secretion From Multiple Individual Pancreatic Islets
title_sort microfluidic hanging-drop-based islet perifusion system for studying glucose-stimulated insulin secretion from multiple individual pancreatic islets
topic Bioengineering and Biotechnology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8149801/
https://www.ncbi.nlm.nih.gov/pubmed/34055765
http://dx.doi.org/10.3389/fbioe.2021.674431
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