Review of microfluidic microbioreactor technology for high-throughput submerged microbiological cultivation

Hegab, Hanaa M.; ElMekawy, Ahmed; Stakenborg, Tim

doi:10.1063/1.4799966

Cited by 69 publications

(48 citation statements)

References 57 publications

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“…Furthermore, the set up time and complex fluid manifolds make it challenging for large-scale applications. 11-12 For example, it is not possible to rapidly change medium through the microfluidic system without influencing or interrupting the created 3-D microenvironment. Thus, a microfluidic model system that can control 3-D microenvironments in large-scale arrays for long culturing times (weeks and above) and with a simple user-interface (as simple as changing the medium of a culture dish) would be a major stepping stone for in depth tissue engineering studies.…”

Section: Introductionmentioning

confidence: 99%

A microfluidic platform for generating large-scale nearly identical human microphysiological vascularized tissue arrays

et al. 2013

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This paper reports a polydimethylsiloxane microfluidic model system that can develop an array of nearly identical human microtissues with interconnected vascular networks. The microfluidic system design is based on an analogy with an electric circuit, applying resistive circuit concepts to design pressure dividers in serially-connected microtissue chambers. A long microchannel (550, 620 and 775 mm) creates a resistive circuit with a large hydraulic resistance. Two media reservoirs with a large cross-sectional area and of different heights are connected to the entrance and exit of the long microchannel to serve as a pressure source, and create a near constant pressure drop along the long microchannel. Microtissue chambers (0.12 μl) serve as a two-terminal resistive component with an input impedance > 50-fold larger than the long microchannel. Connecting each microtissue chamber to two different positions along the long microchannel creates a series of pressure dividers. Each microtissue chamber enables a controlled pressure drop of a segment of the microchannel without altering the hydrodynamic behaviour of the microchannel. The result is a controlled and predictable microphysiological environment within the microchamber. Interstitial flow, a mechanical cue for stimulating vasculogenesis, was verified by finite element simulation and experiments. The simplicity of this design enabled the development of multiple microtissue arrays (5, 12, and 30 microtissues) by co-culturing endothelial cells, stromal cells, and fibrin within the microchambers over two and three week periods. This methodology enables the culturing of a large array of microtissues with interconnected vascular networks for biological studies and applications such as drug development.

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Section: Introductionmentioning

confidence: 99%

A microfluidic platform for generating large-scale nearly identical human microphysiological vascularized tissue arrays

et al. 2013

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“…[1][2][3] Microchannels are essential parts of such systems and are exploited as micro-heat exchangers, microbioreactors, concentrators, mixers, and separators. [4][5][6][7] As alternative materials from the a) Author to whom correspondence should be addressed. Electronic mail: chemnet75@korea.kr.…”

Section: Introductionmentioning

confidence: 99%

Deformation properties between fluid and periodic circular obstacles in polydimethylsiloxane microchannels: Experimental and numerical investigations under various conditions

2013

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Understanding the mechanical properties of optically transparent polydimethylsiloxane (PDMS) microchannels was essential to the design of polymer-based microdevices. In this experiment, PDMS microchannels were filled with a 100 lM solution of rhodamine 6G dye at very low Reynolds numbers ($10 À3 ). The deformation of PDMS microchannels created by pressure-driven flow was investigated by fluorescence microscopy and quantified the deformation by the linear relationship between dye layer thickness and intensity. A line scan across the channel determined the microchannel deformation at several channel positions. Scaling analysis widely used to justify PDMS bulging approximation was allowed when the applied flow rate was as high as 2.0 ll/min. The three physical parameters (i.e., flow rate, PDMS wall thickness, and mixing ratio) and the design parameter (i.e., channel aspect ratio ¼ channel height/channel width) were considered as critical parameters and provided the different features of pressure distributions within polymer-based microchannel devices. The investigations of the four parameters performed on flexible materials were carried out by comparison of experiment and finite element method (FEM) results. The measured Young's modulus from PDMS tensile test specimens at various circumstances provided reliable results for the finite element method. A thin channel wall, less cross-linker, high flow rate, and low aspect ratio microchannel were inclined to have a significant PDMS bulging. Among them, various mixing ratios related to material property and aspect ratios were one of the significant factors to determine PDMS bulging properties. The measured deformations were larger than the numerical simulation but were within corresponding values predicted by the finite element method in most cases. V C 2013 AIP Publishing LLC. [http://dx

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“…[10][11][12][19][20][21][22][23][24][25][26][27][28][29] Some of them report on partial 3D cell culture patterning by arrays of posts, [10][11][12] requiring delicate injection pressure control 10 and, therefore, preventing wide spread application. At the same time, PDMS has several other disadvantages.…”

Section: Introductionmentioning

confidence: 99%

Hydrogel-based microfluidic incubator for microorganism cultivation and analyses

et al. 2015

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This work presents an array of microfluidic chambers for on-chip culturing of microorganisms in static and continuous shear-free operation modes. The unique design comprises an in-situ polymerized hydrogel that forms gas and reagent permeable culture wells in a glass chip. Utilizing a hydrophilic substrate increases usability by autonomous capillary priming. The thin gel barrier enables efficient oxygen supply and facilitates on-chip analysis by chemical access through the gel without introducing a disturbing flow to the culture. Trapping the suspended microorganisms inside a gel well allows for a much simpler fabrication than in conventional trapping devices as the minimal feature size does not depend on cell size. Nutrients and drugs are provided on-chip in the gel for a self-contained and user-friendly handling. Rapid antibiotic testing in static cultures with strains of Enterococcus faecalis and Escherichia coli is presented. Cell seeding and diffusive medium supply is provided by phaseguide technology, enabling simple operation of continuous culturing with a great flexibility. Cells of Saccharomyces cerevisiae are utilized as a model to demonstrate continuous on-chip culturing.

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Review of microfluidic microbioreactor technology for high-throughput submerged microbiological cultivation

Cited by 69 publications

References 57 publications

A microfluidic platform for generating large-scale nearly identical human microphysiological vascularized tissue arrays

A microfluidic platform for generating large-scale nearly identical human microphysiological vascularized tissue arrays

Deformation properties between fluid and periodic circular obstacles in polydimethylsiloxane microchannels: Experimental and numerical investigations under various conditions

Hydrogel-based microfluidic incubator for microorganism cultivation and analyses

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