Flexible Toolbox of High-Precision Microfluidic Modules for Versatile Droplet-Based Applications

Although the enormous potential of droplet-based microfluidics has been successfully demonstrated in the past two decades for medical, pharmaceutical, and academic applications, its inherent potential has not been fully exploited until now. Nevertheless, the cultivation of biological cells and 3D ce...

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Main Authors: Mario Saupe, Stefan Wiedemeier, Gunter Gastrock, Robert Römer, Karen Lemke
Format: Article
Language:English
Published: MDPI AG 2024-02-01
Series:Micromachines
Subjects:
Online Access:https://www.mdpi.com/2072-666X/15/2/250
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author Mario Saupe
Stefan Wiedemeier
Gunter Gastrock
Robert Römer
Karen Lemke
author_facet Mario Saupe
Stefan Wiedemeier
Gunter Gastrock
Robert Römer
Karen Lemke
author_sort Mario Saupe
collection DOAJ
description Although the enormous potential of droplet-based microfluidics has been successfully demonstrated in the past two decades for medical, pharmaceutical, and academic applications, its inherent potential has not been fully exploited until now. Nevertheless, the cultivation of biological cells and 3D cell structures like spheroids and organoids, located in serially arranged droplets in micro-channels, has a range of benefits compared to established cultivation techniques based on, e.g., microplates and microchips. To exploit the enormous potential of the droplet-based cell cultivation technique, a number of basic functions have to be fulfilled. In this paper, we describe microfluidic modules to realize the following basic functions with high precision: (i) droplet generation, (ii) mixing of cell suspensions and cell culture media in the droplets, (iii) droplet content detection, and (iv) active fluid injection into serially arranged droplets. The robustness of the functionality of the Two-Fluid Probe is further investigated regarding its droplet generation using different flow rates. Advantages and disadvantages in comparison to chip-based solutions are discussed. New chip-based modules like the gradient, the piezo valve-based conditioning, the analysis, and the microscopy module are characterized in detail and their high-precision functionalities are demonstrated. These microfluidic modules are micro-machined, and as the surfaces of their micro-channels are plasma-treated, we are able to perform cell cultivation experiments using any kind of cell culture media, but without needing to use surfactants. This is even more considerable when droplets are used to investigate cell cultures like stem cells or cancer cells as cell suspensions, as 3D cell structures, or as tissue fragments over days or even weeks for versatile applications.
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spelling doaj.art-4f6c5abb367142218db220e68cd5364c2024-02-23T15:27:47ZengMDPI AGMicromachines2072-666X2024-02-0115225010.3390/mi15020250Flexible Toolbox of High-Precision Microfluidic Modules for Versatile Droplet-Based ApplicationsMario Saupe0Stefan Wiedemeier1Gunter Gastrock2Robert Römer3Karen Lemke4Institute for Bioprocessing and Analytical Measurement Techniques e.V., 37308 Heilbad Heiligenstadt, GermanyInstitute for Bioprocessing and Analytical Measurement Techniques e.V., 37308 Heilbad Heiligenstadt, GermanyInstitute for Bioprocessing and Analytical Measurement Techniques e.V., 37308 Heilbad Heiligenstadt, GermanyInstitute for Bioprocessing and Analytical Measurement Techniques e.V., 37308 Heilbad Heiligenstadt, GermanyInstitute for Bioprocessing and Analytical Measurement Techniques e.V., 37308 Heilbad Heiligenstadt, GermanyAlthough the enormous potential of droplet-based microfluidics has been successfully demonstrated in the past two decades for medical, pharmaceutical, and academic applications, its inherent potential has not been fully exploited until now. Nevertheless, the cultivation of biological cells and 3D cell structures like spheroids and organoids, located in serially arranged droplets in micro-channels, has a range of benefits compared to established cultivation techniques based on, e.g., microplates and microchips. To exploit the enormous potential of the droplet-based cell cultivation technique, a number of basic functions have to be fulfilled. In this paper, we describe microfluidic modules to realize the following basic functions with high precision: (i) droplet generation, (ii) mixing of cell suspensions and cell culture media in the droplets, (iii) droplet content detection, and (iv) active fluid injection into serially arranged droplets. The robustness of the functionality of the Two-Fluid Probe is further investigated regarding its droplet generation using different flow rates. Advantages and disadvantages in comparison to chip-based solutions are discussed. New chip-based modules like the gradient, the piezo valve-based conditioning, the analysis, and the microscopy module are characterized in detail and their high-precision functionalities are demonstrated. These microfluidic modules are micro-machined, and as the surfaces of their micro-channels are plasma-treated, we are able to perform cell cultivation experiments using any kind of cell culture media, but without needing to use surfactants. This is even more considerable when droplets are used to investigate cell cultures like stem cells or cancer cells as cell suspensions, as 3D cell structures, or as tissue fragments over days or even weeks for versatile applications.https://www.mdpi.com/2072-666X/15/2/250droplet-based microfluidicshigh throughputdroplet generationmixingmergingactive fluid injection
spellingShingle Mario Saupe
Stefan Wiedemeier
Gunter Gastrock
Robert Römer
Karen Lemke
Flexible Toolbox of High-Precision Microfluidic Modules for Versatile Droplet-Based Applications
Micromachines
droplet-based microfluidics
high throughput
droplet generation
mixing
merging
active fluid injection
title Flexible Toolbox of High-Precision Microfluidic Modules for Versatile Droplet-Based Applications
title_full Flexible Toolbox of High-Precision Microfluidic Modules for Versatile Droplet-Based Applications
title_fullStr Flexible Toolbox of High-Precision Microfluidic Modules for Versatile Droplet-Based Applications
title_full_unstemmed Flexible Toolbox of High-Precision Microfluidic Modules for Versatile Droplet-Based Applications
title_short Flexible Toolbox of High-Precision Microfluidic Modules for Versatile Droplet-Based Applications
title_sort flexible toolbox of high precision microfluidic modules for versatile droplet based applications
topic droplet-based microfluidics
high throughput
droplet generation
mixing
merging
active fluid injection
url https://www.mdpi.com/2072-666X/15/2/250
work_keys_str_mv AT mariosaupe flexibletoolboxofhighprecisionmicrofluidicmodulesforversatiledropletbasedapplications
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AT guntergastrock flexibletoolboxofhighprecisionmicrofluidicmodulesforversatiledropletbasedapplications
AT robertromer flexibletoolboxofhighprecisionmicrofluidicmodulesforversatiledropletbasedapplications
AT karenlemke flexibletoolboxofhighprecisionmicrofluidicmodulesforversatiledropletbasedapplications