Microfluidic platforms for cell cultures and investigations

Coluccio, Maria Laura; Perozziello, Gerardo; Malara, Natalia; Parrotta, Elvira Immacolata; Zhang, Peng; Gentile, Francesco; Limongi, Tania; Raj, Pushparani Michael; Cuda, Gianni; Candeloro, Patrizio; Fabrizio, E. Di

doi:10.1016/j.mee.2019.01.004

Cited by 161 publications

(110 citation statements)

References 162 publications

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“…Cultures have been mainly carried out on 2D platforms, such as petri dishes, microtiter plates, and flasks, in which the organisms are placed onto a flat surface that is different from in vivo 3D environment [2]. Although the conventional 2D culture techniques generated a wealth of new scientific and technological results with significant and transformative potential, they fail to provide an accurate structure, function, or physiology of living organisms and even worse can alter their gene expression, metabolism, production, and morphology compared to those in 3D [1][2][3][4]. These organisms inherently respond to a variety of chemical and physical cues from their 3D microenvironment differently than 2D cues while performing the fundamental cellular processes such as proliferation, differentiation, apoptosis, and migration.…”

Section: Introductionmentioning

confidence: 99%

“…High-throughput culturing tools and trapping methods for C. elegans have historically developed separately, and the techniques developed for those applications are usually incompatible with each other [11,12]. Even the latest advances in a 3D controlled environment do not accurately replicate their natural habitats and do not show any significant difference in culturing compared to the standard 2D method [3].…”

Section: Introductionmentioning

confidence: 99%

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Paper-Supported High-Throughput 3D Culturing, Trapping, and Monitoring of Caenorhabditis Elegans

2020

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We developed an innovative paper-based platform for high-throughput culturing, trapping, and monitoring of C. elegans. A 96-well array was readily fabricated by placing a nutrient-replenished paper substrate on a micromachined 96-well plastic frame, providing high-throughput 3D culturing environments and in situ analysis of the worms. The paper allows C. elegans to pass through the porous and aquatic paper matrix until the worms grow and reach the next developmental stages with the increased body size comparable to the paper pores. When the diameter of C. elegans becomes larger than the pore size of the paper substrate, the worms are trapped and immobilized for further high-throughput imaging and analysis. This work will offer a simple yet powerful technique for high-throughput sorting and monitoring of C. elegans at a different larval stage by controlling and choosing different pore sizes of paper. Furthermore, we developed another type of 3D culturing system by using paper-like transparent polycarbonate substrates for higher resolution imaging. The device used the multi-laminate structure of the polycarbonate layers as a scaffold to mimic the worm’s 3D natural habitats. Since the substrate is thin, mechanically strong, and largely porous, the layered structure allowed C. elegans to move and behave freely in 3D and promoted the efficient growth of both C. elegans and their primary food, E. coli. The transparency of the structure facilitated visualization of the worms under a microscope. Development, fertility, and dynamic behavior of C. elegans in the 3D culture platform outperformed those of the standard 2D cultivation technique.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Paper-Supported High-Throughput 3D Culturing, Trapping, and Monitoring of Caenorhabditis Elegans

2020

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“…Moreover, in organs‐on‐chips, the right choice of surface functionalization method provides the means for culturing the desired cells in 2D or 3D and achieving fully confluent functional cells in a short time frame . Biofunctionalization techniques in microfluidic channels determine the durability and stability of the final product against temperature, harsh chemical conditions and degradation as well as high shear forces …”

Section: Introductionmentioning

confidence: 99%

Biofunctionalization of Glass‐ and Paper‐Based Microfluidic Devices: A Review

Shakeri

Jarad

Leung

et al. 2019

Adv Materials Inter

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Biofunctionalization of microchannels is of great concern in the fabrication of microfluidic devices. Different substrates such as glass slides, papers, polymers, and beads require different biofunctionalization approaches granting the utilization of microfluidics in several biomedical applications. Covalent immobilization of biomolecules inside the microchannels is achieved by chemical modification of the surface such as silanization or introducing different coupling agents. Although creating biointerfaces that are covalently bonded to the microchannel surface necessitates multiple steps of surface modification and incubation times, it bestows a robust biointerface capable of withstanding high shear stresses and harsh conditions without dissipating the biofunctionality. Regarding the applications that do not require robustness and long‐term stability, noncovalent attachment of biomolecules such as van der Waals and hydrophobic interactions are adequate to successfully create a functional biointerface. This review summarizes the various biofunctionalization approaches used in the most common microfluidic substrates: glass and paper. In addition, several biofunctionalization examples are proposed and described in detail along with their associated applications.

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“…The advantages of MBR systems have in the past been used for high throughput screening, strain engineering and bioprocess development . To closely mimic the microenvironment of cells, the design of MBR can be tailored for specific applications, including cytotoxicity testing and drug development . In a microfluidic setup, they are also used as cell culturing and analytical devices, in clinical embryology or tissue engineering .…”

Section: Introductionmentioning

confidence: 99%

“…[7][8][9][10] To closely mimic the microenvironment of cells, the design of MBR can be tailored for specific applications, including cytotoxicity testing and drug development. 11,12 In a microfluidic setup, they are also used as cell culturing and analytical devices, in clinical embryology or tissue engineering. 13,14 Nowadays, advancing developments in manufacturing techniques enable increasingly smaller reactor setups to optimally use the advantages of miniaturization.…”

mentioning

confidence: 99%

Novel electrodynamic oscillation technique enables enhanced mass transfer and mixing for cultivation in micro‐bioreactor

Frey

Vorländer

Rasch

et al. 2019

Biotechnology Progress

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Micro‐bioreactors (MBRs) have become an indispensable part for modern bioprocess development enabling automated experiments in parallel while reducing material cost. Novel developments aim to further intensify the advantages as dimensions are being reduced. However, one factor hindering the scale‐down of cultivation systems is to provide adequate mixing and mass transfer. Here, vertical oscillation is demonstrated as an effective method for mixing of MBRs with a reaction volume of 20 μL providing adequate mass transfer. Electrodynamic exciters are used to transduce kinetic energy onto the cultivation broth avoiding additional moving parts inside the applied model MBR. The induced vertical vibration leads to oscillation of the liquid surface corresponding to the frequency and displacement. On this basis, the resonance frequency of the fluid was identified as the most decisive factor for mixing performance. Applying this vertical oscillation method outstanding mixing times below 1 s and exceptionally high oxygen transport with volumetric mass transfer coefficients (kLa) above 1,000/hr can be successfully achieved and controlled. To evaluate the applicability of this vertical oscillation mixing for low volume MBR systems, cultivations of Escherichia coli BL21 as proof‐of‐concept were performed. The dissolved oxygen was successfully online monitored to assure any avoidance of oxygen limitations during the cultivation. The here presented data illustrate the high potential of the vertical oscillation technique as a flexible measure to adapt mixing times and oxygen transfer according to experimental demands. Thus, the mixing technique is a promising tool for various biological and chemical micro‐scale applications still enabling adequate mass transfer.

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Microfluidic platforms for cell cultures and investigations

Cited by 161 publications

References 162 publications

Paper-Supported High-Throughput 3D Culturing, Trapping, and Monitoring of Caenorhabditis Elegans

Paper-Supported High-Throughput 3D Culturing, Trapping, and Monitoring of Caenorhabditis Elegans

Biofunctionalization of Glass‐ and Paper‐Based Microfluidic Devices: A Review

Novel electrodynamic oscillation technique enables enhanced mass transfer and mixing for cultivation in micro‐bioreactor

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