Generation of nitric oxide gradients in microfluidic devices for cell culture using spatially controlled chemical reactions

Chen, Yinghua; Peng, Chien-Chung; Cheng, Yung-Ju; Wu, Jingen; Tung, Yi-Chung

doi:10.1063/1.4829775

Cited by 8 publications

(6 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…27 The device can generate chemical gradients, using a well-developed channel design based on the arrangements of serpentine channels, and can generate an oxygen gradient, using a previously developed spatially confined chemical reaction method. 23,24,28 As a result, the designed device can be simply actuated by syringe pumps without bulky gas cylinders and sophisticated flow control schemes, which greatly reduce the instrumentation complexity. Due to the spatial confinement of chemical reactions, the usage of chemicals can be minimized without altering the compositions of the culture medium.…”

Section: Introductionmentioning

confidence: 99%

A polydimethylsiloxane–polycarbonate hybrid microfluidic device capable of generating perpendicular chemical and oxygen gradients for cell culture studies

et al. 2014

Self Cite

View full text Add to dashboard Cite

This paper reports a polydimethylsiloxane-polycarbonate (PDMS-PC) hybrid microfluidic device capable of performing cell culture under combinations of chemical and oxygen gradients. The microfluidic device is constructed of two PDMS layers with microfluidic channel patterns separated by a thin PDMS membrane. The top layer contains an embedded PC film and a serpentine channel for a spatially confined oxygen scavenging chemical reaction to generate an oxygen gradient in the bottom layer for cell culture. Using the chemical reaction method, the device can be operated with a small amount of chemicals, without bulky gas cylinders and sophisticated flow control schemes. Furthermore, it can be directly used in conventional incubators with syringe pumps to simplify the system setup. The bottom layer contains arrangements of serpentine channels for chemical gradient generation and a cell culture chamber in the downstream. The generated chemical and oxygen gradients are experimentally characterized using a fluorescein solution and an oxygen-sensitive fluorescent dye, respectively. For demonstration, a 48 hour cell-based drug test and a cell migration assay using human lung adenocarcinoma epithelial cells (A549) are conducted under various combinations of the chemical and oxygen gradients in the experiments. The drug testing results show an increase in A549 cell apoptosis due to the hypoxia-activated cytotoxicity of tirapazamine (TPZ) and also suggest great cell compatibility and gradient controllability of the device. In addition, the A549 cell migration assay results demonstrate an aerotactic behavior of the A549 cells and suggest that the oxygen gradient plays an essential role in guiding cell migration. The migration results, under combinations of chemokine and oxygen gradients, cannot be simply superposed with single gradient results. The device is promising to advance the control of in vitro microenvironments, to better study cellular responses under various physiological conditions for biomedical applications.

show abstract

Section: Introductionmentioning

confidence: 99%

A polydimethylsiloxane–polycarbonate hybrid microfluidic device capable of generating perpendicular chemical and oxygen gradients for cell culture studies

et al. 2014

Self Cite

View full text Add to dashboard Cite

show abstract

“…With the help of the device developed in this paper, cell culture under oxygen gradients can be performed in a facile manner that greatly promotes cell studies under oxygen gradients. Furthermore, a similar operation principle can be applied to generate other physiologically relevant gaseous gradients, such as carbon dioxide and nitric oxide, for in vitro cell culture studies 17 . These capabilities demonstrate that the PDMS-PC microfluidic device shows great potential for various cell culture applications, including drug testing and cell proliferation and migration assays, to advance in vitro cell culture studies.…”

Section: Discussionmentioning

confidence: 99%

Polydimethylsiloxane-polycarbonate Microfluidic Devices for Cell Migration Studies Under Perpendicular Chemical and Oxygen Gradients

Chiang

Yeh

Peng

et al. 2017

JoVE

Self Cite

View full text Add to dashboard Cite

This paper reports a microfluidic device made of polydimethylsiloxane (PDMS) with an embedded polycarbonate (PC) thin film to study cell migration under combinations of chemical and oxygen gradients. Both chemical and oxygen gradients can greatly affect cell migration in vivo; however, due to technical limitations, very little research has been performed to investigate their effects in vitro. The device developed in this research takes advantage of a series of serpentine-shaped channels to generate the desired chemical gradients and exploits a spatially confined chemical reaction method for oxygen gradient generation. The directions of the chemical and oxygen gradients are perpendicular to each other to enable straightforward migration result interpretation. In order to efficiently generate the oxygen gradients with minimal chemical consumption, the embedded PC thin film is utilized as a gas diffusion barrier. The developed microfluidic device can be actuated by syringe pumps and placed into a conventional cell incubator during cell migration experiments to allow for setup simplification and optimized cell culture conditions. In cell experiments, we used the device to study migrations of adenocarcinomic human alveolar basal epithelial cells, A549, under combinations of chemokine (stromal cell-derived factor, SDF-1α) and oxygen gradients. The experimental results show that the device can stably generate perpendicular chemokine and oxygen gradients and is compatible with cells. The migration study results indicate that oxygen gradients may play an essential role in guiding cell migration, and cellular behavior under combinations of gradients cannot be predicted from those under single gradients. The device provides a powerful and practical tool for researchers to study interactions between chemical and oxygen gradients in cell culture, which can promote better cell migration studies in more in vivo-like microenvironments.

show abstract

“…receiver output signals can approximately restore to the same concentration level of input signal via adjusting C VII Amp . After validating the microfluidic design in COMSOL, the device can then be fabricated in polydimethylsiloxane (PDMS) via soft lithography [41], [42]. We envision that a syringe, connected with a species reservoir and a computer, is placed next to each inlet, and its injection is controlled by this computer via digital commands.…”

Section: An End-to-end Microfluidic MC Implementationmentioning

confidence: 99%

Chemical Reactions-Based Microfluidic Transmitter and Receiver Design for Molecular Communication

Bi¹,

Deng²,

Pierobon³

et al. 2020

IEEE Trans. Commun.

View full text Add to dashboard Cite

show abstract

Generation of nitric oxide gradients in microfluidic devices for cell culture using spatially controlled chemical reactions

Cited by 8 publications

References 32 publications

A polydimethylsiloxane–polycarbonate hybrid microfluidic device capable of generating perpendicular chemical and oxygen gradients for cell culture studies

A polydimethylsiloxane–polycarbonate hybrid microfluidic device capable of generating perpendicular chemical and oxygen gradients for cell culture studies

Polydimethylsiloxane-polycarbonate Microfluidic Devices for Cell Migration Studies Under Perpendicular Chemical and Oxygen Gradients

Chemical Reactions-Based Microfluidic Transmitter and Receiver Design for Molecular Communication

Contact Info

Product

Resources

About