Microsystems for Cell Cultures

A topical collection in Biosensors (ISSN 2079-6374). This collection belongs to the section "Nano- and Micro-Technologies in Biosensors".

Viewed by 19206

Editors

Institute of Microtechnology, Technische Universität Braunschweig, 38124 Braunschweig, Germany
Interests: nano/microfabrication; microfluidics; lab/organ-on-chip; optoelectronics; cell biology
Institute of Microtechnology & Center of Pharmaceutical Engineering, Technische Universität Braunschweig, 38106 Braunschweig, Germany
Interests: organ-on-chip; lab-on-chip; tissue barriers; electrochemical sensors; stem cells; neuropsychiatric disorders

Topical Collection Information

Dear Colleagues,

Microsystems are being increasingly utilized in biotechnological, biomedical, and pharmaceutical research and development as a replacement for in vitro cell cultures and animal experiments. Platforms such as organ-on-chip (OoC) can be designed to recapitulate biochemical and biophysical conditions and replicate the natural microenvironment of living cells and tissues. In addition to OoC platforms, microbioreactors have become versatile bioprocess engineering tools used for microbial and mammalian cell cultivation. Such cell culture technologies are often equipped with miniaturized sensors that provide feedback, allow process monitoring and control, and ensure the necessary cell culture conditions are maintained. This Topical Collection aims to assemble a collection of novel microsystems for cell cultivation. Advances in the areas of system design, sensor integration, as well as target applications are welcome.

Prof. Dr. Iordania Constantinou
Dr. Thomas E. Winkler
Collection Editors

Manuscript Submission Information

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Keywords

  • microsystems
  • cell culture
  • microfluidic
  • microbioreactor
  • organ-on-chip
  • single-cell cultivation

Published Papers (7 papers)

2023

Jump to: 2022, 2021

17 pages, 2583 KiB  
Article
Development of a Redox-Polymer-Based Electrochemical Glucose Biosensor Suitable for Integration in Microfluidic 3D Cell Culture Systems
by L. Navarro-Nateras, Jancarlo Diaz-Gonzalez, Diana Aguas-Chantes, Lucy L. Coria-Oriundo, Fernando Battaglini, José Luis Ventura-Gallegos, Alejandro Zentella-Dehesa, Goldie Oza, L. G. Arriaga and Jannu R. Casanova-Moreno
Biosensors 2023, 13(6), 582; https://0-doi-org.brum.beds.ac.uk/10.3390/bios13060582 - 27 May 2023
Cited by 1 | Viewed by 1954
Abstract
The inclusion of online, in situ biosensors in microfluidic cell cultures is important to monitor and characterize a physiologically mimicking environment. This work presents the performance of second-generation electrochemical enzymatic biosensors to detect glucose in cell culture media. Glutaraldehyde and ethylene glycol diglycidyl [...] Read more.
The inclusion of online, in situ biosensors in microfluidic cell cultures is important to monitor and characterize a physiologically mimicking environment. This work presents the performance of second-generation electrochemical enzymatic biosensors to detect glucose in cell culture media. Glutaraldehyde and ethylene glycol diglycidyl ether (EGDGE) were tested as cross-linkers to immobilize glucose oxidase and an osmium-modified redox polymer on the surface of carbon electrodes. Tests employing screen printed electrodes showed adequate performance in a Roswell Park Memorial Institute (RPMI-1640) media spiked with fetal bovine serum (FBS). Comparable first-generation sensors were shown to be heavily affected by complex biological media. This difference is explained in terms of the respective charge transfer mechanisms. Under the tested conditions, electron hopping between Os redox centers was less vulnerable than H2O2 diffusion to biofouling by the substances present in the cell culture matrix. By employing pencil leads as electrodes, the incorporation of these electrodes in a polydimethylsiloxane (PDMS) microfluidic channel was achieved simply and at a low cost. Under flow conditions, electrodes fabricated using EGDGE presented the best performance with a limit of detection of 0.5 mM, a linear range up to 10 mM, and a sensitivity of 4.69 μA mM−1 cm−2. Full article
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2022

Jump to: 2023, 2021

18 pages, 4410 KiB  
Article
Large Area Microfluidic Bioreactor for Production of Recombinant Protein
by Natalia Bourguignon, Paola Karp, Carolina Attallah, Daniel A. Chamorro, Marcos Oggero, Ross Booth, Sol Ferrero, Shekhar Bhansali, Maximiliano S. Pérez, Betiana Lerner and Gustavo Helguera
Biosensors 2022, 12(7), 526; https://0-doi-org.brum.beds.ac.uk/10.3390/bios12070526 - 14 Jul 2022
Cited by 2 | Viewed by 2240
Abstract
To produce innovative biopharmaceuticals, highly flexible, adaptable, robust, and affordable bioprocess platforms for bioreactors are essential. In this article, we describe the development of a large-area microfluidic bioreactor (LM bioreactor) for mammalian cell culture that works at laminar flow and perfusion conditions. The [...] Read more.
To produce innovative biopharmaceuticals, highly flexible, adaptable, robust, and affordable bioprocess platforms for bioreactors are essential. In this article, we describe the development of a large-area microfluidic bioreactor (LM bioreactor) for mammalian cell culture that works at laminar flow and perfusion conditions. The 184 cm2 32 cisterns LM bioreactor is the largest polydimethylsiloxane (PDMS) microfluidic device fabricated by photopolymer flexographic master mold methodology, reaching a final volume of 2.8 mL. The LM bioreactor was connected to a syringe pump system for culture media perfusion, and the cells’ culture was monitored by photomicrograph imaging. CHO-ahIFN-α2b adherent cell line expressing the anti-hIFN-a2b recombinant scFv-Fc monoclonal antibody (mAb) for the treatment of systemic lupus erythematosus were cultured on the LM bioreactor. Cell culture and mAb production in the LM bioreactor could be sustained for 18 days. Moreover, the anti-hIFN-a2b produced in the LM bioreactor showed higher affinity and neutralizing antiproliferative activity compared to those mAbs produced in the control condition. We demonstrate for the first-time, a large area microfluidic bioreactor for mammalian cell culture that enables a controlled microenvironment suitable for the development of high-quality biologics with potential for therapeutic use. Full article
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19 pages, 3048 KiB  
Article
Microsensor in Microbioreactors: Full Bioprocess Characterization in a Novel Capillary-Wave Microbioreactor
by Kevin Viebrock, Dominik Rabl, Sven Meinen, Paul Wunder, Jan-Angelus Meyer, Lasse Jannis Frey, Detlev Rasch, Andreas Dietzel, Torsten Mayr and Rainer Krull
Biosensors 2022, 12(7), 512; https://0-doi-org.brum.beds.ac.uk/10.3390/bios12070512 - 11 Jul 2022
Viewed by 2583
Abstract
Microbioreactors (MBRs) with a volume below 1 mL are promising alternatives to established cultivation platforms such as shake flasks, lab-scale bioreactors and microtiter plates. Their main advantages are simple automatization and parallelization and the saving of expensive media components and test substances. These [...] Read more.
Microbioreactors (MBRs) with a volume below 1 mL are promising alternatives to established cultivation platforms such as shake flasks, lab-scale bioreactors and microtiter plates. Their main advantages are simple automatization and parallelization and the saving of expensive media components and test substances. These advantages are particularly pronounced in small-scale MBRs with a volume below 10 µL. However, most described small-scale MBRs are lacking in process information from integrated sensors due to limited space and sensor technology. Therefore, a novel capillary-wave microbioreactor (cwMBR) with a volume of only 7 µL has the potential to close this gap, as it combines a small volume with integrated sensors for biomass, pH, dissolved oxygen (DO) and glucose concentration. In the cwMBR, pH and DO are measured by established luminescent optical sensors on the bottom of the cwMBR. The novel glucose sensor is based on a modified oxygen sensor, which measures the oxygen uptake of glucose oxidase (GOx) in the presence of glucose up to a concentration of 15 mM. Furthermore, absorbance measurement allows biomass determination. The optical sensors enabled the characterization of an Escherichia coli batch cultivation over 8 h in the cwMBR as proof of concept for further bioprocesses. Hence, the cwMBR with integrated optical sensors has the potential for a wide range of microscale bioprocesses, including cell-based assays, screening applications and process development. Full article
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10 pages, 2087 KiB  
Article
Easy-to-Operate Co-Flow Step Emulsification Device for High-Throughput Three-Dimensional Cell Culture
by Chunyang Wei, Chengzhuang Yu, Shanshan Li, Tiejun Li, Jiyu Meng and Junwei Li
Biosensors 2022, 12(5), 350; https://0-doi-org.brum.beds.ac.uk/10.3390/bios12050350 - 18 May 2022
Viewed by 2123
Abstract
Cell culture plays an essential role in tissue engineering and high-throughput drug screening. Compared with two-dimensional (2D) in vitro culture, three-dimensional (3D) in vitro culture can mimic cells in vivo more accurately, including complex cellular organizations, heterogeneity, and cell–extracellular matrix (ECM) interactions. This [...] Read more.
Cell culture plays an essential role in tissue engineering and high-throughput drug screening. Compared with two-dimensional (2D) in vitro culture, three-dimensional (3D) in vitro culture can mimic cells in vivo more accurately, including complex cellular organizations, heterogeneity, and cell–extracellular matrix (ECM) interactions. This article presents a droplet-based microfluidic chip that integrates cell distribution, 3D in vitro cell culture, and in situ cell monitoring in a single device. Using the microfluidic “co-flow step emulsification” approach, we have successfully prepared close-packed droplet arrays with an ultra-high-volume fraction (72%) which can prevent cells from adhering to the chip surface so as to achieve a 3D cell culture and make scalable and high-throughput cell culture possible. The proposed device could produce droplets from 55.29 ± 1.52 to 95.64 ± 3.35 μm, enabling the diverse encapsulation of cells of different sizes and quantities. Furthermore, the cost for each microfluidic CFSE chip is approximately USD 3, making it a low-cost approach for 3D cell culture. The proposed device is successfully applied in the 3D culture of saccharomyces cerevisiae cells with an occurrence rate for proliferation of 80.34 ± 3.77%. With low-cost, easy-to-operate, high-throughput, and miniaturization characteristics, the proposed device meets the requirements for 3D in vitro cell culture and is expected to be applied in biological fields such as drug toxicology and pharmacokinetics. Full article
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2 pages, 489 KiB  
Editorial
Microsystems for Cell Cultures
by Iordania Constantinou
Biosensors 2022, 12(4), 190; https://0-doi-org.brum.beds.ac.uk/10.3390/bios12040190 - 23 Mar 2022
Cited by 1 | Viewed by 1590
Abstract
Microfabricated systems are increasingly being utilized in biotechnological, biomedical, and pharmaceutical research and development as replacements for traditional in vitro cell cultures, bioreactors, and animal experiments (Figure 1) [...] Full article
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2021

Jump to: 2023, 2022

33 pages, 15799 KiB  
Protocol
How to Perform a Microfluidic Cultivation Experiment—A Guideline to Success
by Sarah Täuber, Julian Schmitz, Luisa Blöbaum, Niklas Fante, Heiko Steinhoff and Alexander Grünberger
Biosensors 2021, 11(12), 485; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11120485 - 29 Nov 2021
Cited by 8 | Viewed by 3483
Abstract
As a result of the steadily ongoing development of microfluidic cultivation (MC) devices, a plethora of setups is used in biological laboratories for the cultivation and analysis of different organisms. Because of their biocompatibility and ease of fabrication, polydimethylsiloxane (PDMS)-glass-based devices are most [...] Read more.
As a result of the steadily ongoing development of microfluidic cultivation (MC) devices, a plethora of setups is used in biological laboratories for the cultivation and analysis of different organisms. Because of their biocompatibility and ease of fabrication, polydimethylsiloxane (PDMS)-glass-based devices are most prominent. Especially the successful and reproducible cultivation of cells in microfluidic systems, ranging from bacteria over algae and fungi to mammalians, is a fundamental step for further quantitative biological analysis. In combination with live-cell imaging, MC devices allow the cultivation of small cell clusters (or even single cells) under defined environmental conditions and with high spatio-temporal resolution. Yet, most setups in use are custom made and only few standardised setups are available, making trouble-free application and inter-laboratory transfer tricky. Therefore, we provide a guideline to overcome the most frequently occurring challenges during a MC experiment to allow untrained users to learn the application of continuous-flow-based MC devices. By giving a concise overview of the respective workflow, we give the reader a general understanding of the whole procedure and its most common pitfalls. Additionally, we complement the listing of challenges with solutions to overcome these hurdles. On selected case studies, covering successful and reproducible growth of cells in MC devices, we demonstrate detailed solutions to solve occurring challenges as a blueprint for further troubleshooting. Since developer and end-user of MC devices are often different persons, we believe that our guideline will help to enhance a broader applicability of MC in the field of life science and eventually promote the ongoing advancement of MC. Full article
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16 pages, 4695 KiB  
Article
Parallelizable Microfluidic Platform to Model and Assess In Vitro Cellular Barriers: Technology and Application to Study the Interaction of 3D Tumor Spheroids with Cellular Barriers
by Arya Lekshmi Nair, Lena Mesch, Ingo Schulz, Holger Becker, Julia Raible, Heiko Kiessling, Simon Werner, Ulrich Rothbauer, Christian Schmees, Marius Busche, Sebastian Trennheuser, Gert Fricker and Martin Stelzle
Biosensors 2021, 11(9), 314; https://0-doi-org.brum.beds.ac.uk/10.3390/bios11090314 - 03 Sep 2021
Cited by 9 | Viewed by 3402
Abstract
Endothelial and epithelial cellular barriers play a vital role in the selective transport of solutes and other molecules. The properties and function of these barriers are often affected in case of inflammation and disease. Modelling cellular barriers in vitro can greatly facilitate studies [...] Read more.
Endothelial and epithelial cellular barriers play a vital role in the selective transport of solutes and other molecules. The properties and function of these barriers are often affected in case of inflammation and disease. Modelling cellular barriers in vitro can greatly facilitate studies of inflammation, disease mechanisms and progression, and in addition, can be exploited for drug screening and discovery. Here, we report on a parallelizable microfluidic platform in a multiwell plate format with ten independent cell culture chambers to support the modelling of cellular barriers co-cultured with 3D tumor spheroids. The microfluidic platform was fabricated by microinjection molding. Electrodes integrated into the chip in combination with a FT-impedance measurement system enabled transepithelial/transendothelial electrical resistance (TEER) measurements to rapidly assess real-time barrier tightness. The fluidic layout supports the tubeless and parallelized operation of up to ten distinct cultures under continuous unidirectional flow/perfusion. The capabilities of the system were demonstrated with a co-culture of 3D tumor spheroids and cellular barriers showing the growth and interaction of HT29 spheroids with a cellular barrier of MDCK cells. Full article
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