Systematic prevention of bubble formation and accumulation for long-term culture of pancreatic islet cells in microfluidic device

Wang, Yong; Lee, Dongyoung; Zhang, Lisa; Jeon, Hae Jeong; Mendoza-Elias, Joshua E.; Harvat, Tricia A.; Hassan, Sarah; Zhou, Amanda; Eddington, David T.; Oberholzer, José

doi:10.1007/s10544-011-9618-3

Cited by 59 publications

(40 citation statements)

References 20 publications

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“…For example, there are limitations associated with performing experimental studies on biological cells in closed microflow devices. Some of the problems arise directly from unfavorable properties of the materials used in device fabrication [38], such as the lack of optical transparency (silicon) and oxygen permeability (glass, silicon), while others are connected to limited compatibility of living cells with microfluidic channel confinement during culture, for example due to gas bubble formation [39]. HCF devices can overcome many of these limitations, and can help to develop new experimental methodologies.…”

Section: Discussionmentioning

confidence: 99%

Hydrodynamic Flow Confinement Technology in Microfluidic Perfusion Devices

2012

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Abstract:Hydrodynamically confined flow device technology is a young research area with high practical application potential in surface processing, assay development, and in various areas of single cell research. Several variants have been developed, and most recently, theoretical and conceptual studies, as well as fully developed automated systems, were presented. In this article we review concepts, fabrication strategies, and application areas of hydrodynamically confined flow (HCF) devices.

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Section: Discussionmentioning

confidence: 99%

Hydrodynamic Flow Confinement Technology in Microfluidic Perfusion Devices

2012

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“…Second, 50 µL 99.5% ethanol (Wako, Japan) loaded in 200 µL pipet tips were used to wet the microchannels in the PDMS chip by capillary flow and gravity flow 17,138 . The microchannels were then washed with ultrapure water.…”

Section: Cell Seeding and Electrotaxis Experimentsmentioning

confidence: 99%

Voltage-gated ion channels mediate the electrotaxis of glioblastoma cells in a hybrid PMMA/PDMS microdevice

Tsai

IJspeert

Shen

2020

Preprint

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Transformed astrocytes in the most aggressive form cause glioblastoma, the most common cancer in central nervous system with high mortality. The physiological electric field by neuronal local field potentials and tissue polarity may guide the infiltration of glioblastoma cells through the electrotaxis process. However, microenvironments with multiplex gradients are difficult to create. In this work, we have developed a hybrid microfluidic platform to study glioblastoma electrotaxis in controlled microenvironments with high throughput quantitative analysis by a machine learning-powered single cell tracking software. By equalizing the hydrostatic pressure difference between inlets and outlets of the microchannel, uniform single cells can be seeded reliably inside the microdevice. The electrotaxis of two glioblastoma models, T98G and U-251MG, require optimal laminin-containing extracellular matrix and exhibits opposite directional and electro-alignment tendencies. Calcium signaling is a key contributor in glioblastoma pathophysiology but its role in glioblastoma electrotaxis is still an open question. Anodal T98G electrotaxis and cathodal U-251MG electrotaxis require the presence of extracellular calcium cations. U-251MG electrotaxis is dependent on the P/Q-type voltage-gated calcium channel (VGCC) and T98G is dependent on the R-type VGCC. U-251MG and T98G electrotaxis are also mediated by A-type (rapidly inactivating) voltage-gated potassium channels and acidsensing sodium channels. The involvement of multiple ion channels suggests that the glioblastoma electrotaxis is complex and patient-specific ion channel expression can be critical to develop personalized therapeutics to fight against cancer metastasis. The hybrid microfluidic design and machine learning-powered single cell analysis provide a simple and flexible platform for quantitative investigation of complicated biological systems.

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“…For example, when cells are cultured in a micro uidic device, the bubbles generated may inhibit the ow of the culture medium, thereby generating different microenvironmental conditions such as pH and oxygen concentration locally in the device. Previous research has proposed removal of bubbles by bubble trap [21,22], surface modi cation of PDMS [23,24], and lter [25], and stable long-term perfusion has been realized. Owing to the recent developments in microfabrication technology, developers can easily create simple designs independently, thereby adding various functions with added values to micro uidic devices.…”

Section: Nanoparticles Immobilized In the Micro Uidic Devicementioning

confidence: 99%

Immobilized Monolayer Nanoparticles in a Microfluidic Device for Surface Enhanced Raman Scattering Measurement

Hase

Ishigaki

Shibusawa

et al. 2017

ABE

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Micro uidic devices are powerful bioapplication tools for cellular experiments in particular, as they can regulate physical and chemical parameters such as the ow rate, shear stress, oxygen, and molecular concentrations in a culture medium to mimic physiological and pathological microenvironments in vitro. However, as cell cultures take place in enclosed spaces, culture samples have to be removed repeatedly to monitor cell-derived metabolites and proteins in order to maintain the cellular microenvironment. We report a simple method for obtaining surface enhanced Raman scattering (SERS) spectra through self-assembly of a nanoparticle monolayer on polydimethylsiloxane (PDMS), which is commonly used in highly biocompatible micro uidic devices. Silica nanoparticles were stabilized as a hexagonal close packed structure on an O 2 plasma-processed PDMS membrane, and was coated with silver using vapor deposition to create an SERS plate. When this SERS plate was installed in a micro uidic device, the nanoparticles did not peel off even after long-term uid immersion. The SERS spectra exhibited stable SERS generation and an enhancement factor of more than 1.5 × 10 6 of the Raman signals from rhodamine 6G compared to the signals without nanoparticles. The SERS spectra of lactate and ATP were obtained, and Raman shifts due to the different masses of 12 C-and 13 C-lactate were observed, suggesting that the proposed method can be applied to determine the cellular metabolic ux in micro uidic devices. We also obtained cell membrane-derived SERS spectra by culturing murine mammary carcinoma 4T1 cells directly on the nanoparticle membrane. PDMS has high biocompatibility and is often used for fabricating micro uidic devices. Through tight binding of the nanoparticles to the O 2 plasma-treated PDMS, the chemical reaction products or the metabolites from cells can be measured for a long duration, while maintaining the microenvironment. We anticipate that this technology can be utilized as a useful tool for analyzing cellular metabolic functions and imaging cellular distributions without staining in various pathological models created in micro uidic devices.

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Systematic prevention of bubble formation and accumulation for long-term culture of pancreatic islet cells in microfluidic device

Cited by 59 publications

References 20 publications

Hydrodynamic Flow Confinement Technology in Microfluidic Perfusion Devices

Hydrodynamic Flow Confinement Technology in Microfluidic Perfusion Devices

Voltage-gated ion channels mediate the electrotaxis of glioblastoma cells in a hybrid PMMA/PDMS microdevice

Immobilized Monolayer Nanoparticles in a Microfluidic Device for Surface Enhanced Raman Scattering Measurement

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