Microfluidics-Based Single-Cell Research for Intercellular Interaction

Pang, Long; Ding, Jing; Liu, Xi-Xian; Kou, Zhixuan; Guo, Lulu; Xu, Xi; Fan, Shih-Kang

doi:10.3389/fcell.2021.680307

Cited by 17 publications

(9 citation statements)

References 138 publications

(140 reference statements)

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“…However, when moving to micrometer-sized objects in fibers, the same behavior cannot be expected because of the large hindrance of particles within micrometer-sized fibers, thus resulting in fibers having heterogeneous properties along their length; fibers loaded with equally spaced particles represent a suitable alternative to address this challenge. By replacing particles with cells, the fibers introduced here would represent a novel-controlled in vitro platform for cell–cell interactions , and cell-drug interactions, overcoming some limitations of current techniques where the distribution of cells cannot be controlled, thus leading to inaccurate results.…”

Section: Discussionmentioning

confidence: 99%

Continuous Manufacturing of Microfluidic Fibers Embedded with Ordered Microparticles via Ionic Gelation

Maisto

McDowall

Adams

et al. 2022

ACS Appl. Eng. Mater.

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Fibers loaded with either particles or cells are widely employed across a variety of fields, including material science, tissue engineering, and pharmaceutical research. However, the concentration of such objects along the fiber length remains stochastic, thus resulting in fibers having heterogeneous properties along their length. We here introduce a new class of material featuring fibers loaded with “equally spaced” microparticles. The fibers were obtained thanks to the combination between the recently discovered viscoelastic particle ordering phenomenon and the well-established process of fiber synthesis via ex situ ionic gelation. We employed a simple experimental apparatus made of a syringe pump connected to a 100 μm tube ending in a calcium chloride bath. The liquid forming the fiber was an aqueous solution of hyaluronic acid and sodium alginate. We studied the effect of volumetric flow rate, sodium alginate concentration, and spinning speed on the fiber diameter and the particle-spacing in the fiber. We also discussed the advantages of this type of fiber over the existing ones and suggested potential applications across several fields.

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Section: Discussionmentioning

confidence: 99%

Continuous Manufacturing of Microfluidic Fibers Embedded with Ordered Microparticles via Ionic Gelation

Maisto

McDowall

Adams

et al. 2022

ACS Appl. Eng. Mater.

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“…While the droplets insulate cells from contamination, perfluorocarbon oils provide air permeability and allow the cells to exchange air with the outside world. Bacteria, yeast, and mammalian cells ( Huebner et al, 2007 ; Köster et al, 2008 ; Pang et al, 2021 ; Seiler et al, 2022 ) have been proven able to survive encapsulated in droplets for a long time and retain good cell activity after resuscitation, which can be used for various biological measurements. Compared with traditional culture methods, fewer reagents are consumed, but vitality is slightly decreased ( Nakagawa et al, 2021 ).…”

Section: Single-cell Analysis Technique Based On Droplet Microfluidicsmentioning

confidence: 99%

Droplets microfluidics platform—A tool for single cell research

Cheng

et al. 2023

Front. Bioeng. Biotechnol.

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Cells are the most basic structural and functional units of living organisms. Studies of cell growth, differentiation, apoptosis, and cell-cell interactions can help scientists understand the mysteries of living systems. However, there is considerable heterogeneity among cells. Great differences between individuals can be found even within the same cell cluster. Cell heterogeneity can only be clearly expressed and distinguished at the level of single cells. The development of droplet microfluidics technology opens up a new chapter for single-cell analysis. Microfluidic chips can produce many nanoscale monodisperse droplets, which can be used as small isolated micro-laboratories for various high-throughput, precise single-cell analyses. Moreover, gel droplets with good biocompatibility can be used in single-cell cultures and coupled with biomolecules for various downstream analyses of cellular metabolites. The droplets are also maneuverable; through physical and chemical forces, droplets can be divided, fused, and sorted to realize single-cell screening and other related studies. This review describes the channel design, droplet generation, and control technology of droplet microfluidics and gives a detailed overview of the application of droplet microfluidics in single-cell culture, single-cell screening, single-cell detection, and other aspects. Moreover, we provide a recent review of the application of droplet microfluidics in tumor single-cell immunoassays, describe in detail the advantages of microfluidics in tumor research, and predict the development of droplet microfluidics at the single-cell level.

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“…Thus, microfluidic miniaturized device models require highly skilled research and laboratories for the design of a standard mold or protocol to obtain success in high-throughput microfluidic devices. Finally, as it happened in Transwell models, these systems exhibit several limitations in terms of recapitulating morphology, metabolism and expression profiles of cells as well as 3D cellular organization, working most of the studies in 2D configuration because of the intrinsic geometry of microfluidic devices ( He et al, 2014 ; Coluccio et al, 2019 ; Pang et al, 2021 ). In this regard, many efforts have been driven to develop 3D extracellular matrix on microfluidic systems for specific applications, e.g., neural stem cells differentiation and regeneration, organoids-on-a-chip, and in brain, liver and cancer models ( Wang et al, 2017 ; Mofazzal Jahromi et al, 2019 ; Zhao et al, 2021 ; Dai et al, 2022 ).…”

Section: In Vitro Bbb Models Overviewmentioning

confidence: 99%

On the quest of reliable 3D dynamic in vitro blood-brain barrier models using polymer hollow fiber membranes: Pitfalls, progress, and future perspectives

Mantecón-Oria

Rivero

Diban

et al. 2022

Front. Bioeng. Biotechnol.

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With the increasing concern of neurodegenerative diseases, the development of new therapies and effective pharmaceuticals targeted to central nervous system (CNS) illnesses is crucial for ensuring social and economic sustainability in an ageing world. Unfortunately, many promising treatments at the initial stages of the pharmaceutical development process, that is at the in vitro screening stages, do not finally show the expected results at the clinical level due to their inability to cross the human blood-brain barrier (BBB), highlighting the inefficiency of in vitro BBB models to recapitulate the real functionality of the human BBB. In the last decades research has focused on the development of in vitro BBB models from basic 2D monolayer cultures to 3D cell co-cultures employing different system configurations. Particularly, the use of polymeric hollow fiber membranes (HFs) as scaffolds plays a key role in perfusing 3D dynamic in vitro BBB (DIV-BBB) models. Their incorporation into a perfusion bioreactor system may potentially enhance the vascularization and oxygenation of 3D cell cultures improving cell communication and the exchange of nutrients and metabolites through the microporous membranes. The quest for developing a benchmark 3D dynamic in vitro blood brain barrier model requires the critical assessment of the different aspects that limits the technology. This article will focus on identifying the advantages and main limitations of the HFs in terms of polymer materials, microscopic porous morphology, and other practical issues that play an important role to adequately mimic the physiological environment and recapitulate BBB architecture. Based on this study, we consider that future strategic advances of this technology to become fully implemented as a gold standard DIV-BBB model will require the exploration of novel polymers and/or composite materials, and the optimization of the morphology of the membranes towards thinner HFs (<50 μm) with higher porosities and surface pore sizes of 1–2 µm to facilitate the intercommunication via regulatory factors between the cell co-culture models of the BBB.

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Microfluidics-Based Single-Cell Research for Intercellular Interaction

Cited by 17 publications

References 138 publications

Continuous Manufacturing of Microfluidic Fibers Embedded with Ordered Microparticles via Ionic Gelation

Continuous Manufacturing of Microfluidic Fibers Embedded with Ordered Microparticles via Ionic Gelation

Droplets microfluidics platform—A tool for single cell research

On the quest of reliable 3D dynamic in vitro blood-brain barrier models using polymer hollow fiber membranes: Pitfalls, progress, and future perspectives

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