A PDMS-Based Microfluidic Hanging Drop Chip for Embryoid Body Formation

Wu, Huei-Wen; Hsiao, Yi-Hsing; Chen, Chihchen; Yet, Shaw‐Fang; Hsu, Chia-Hsien

doi:10.3390/molecules21070882

Cited by 32 publications

(21 citation statements)

References 27 publications

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“…Besides, in most of the microfluidic-based culture systems [ 46 , 47 , 48 ], the cell suspension is introduced at the inlet. After the suspension fills the device, the cells take several minutes to deposit on microwell bottoms.…”

Section: Discussionmentioning

confidence: 99%

A Dynamic Hanging-Drop System for Mesenchymal Stem Cell Culture

Huang

Tzeng

Chen

et al. 2020

IJMS

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There have been many microfluid technologies combined with hanging-drop for cell culture gotten developed in the past decade. A common problem within these devices is that the cell suspension introduced at the central inlet could cause a number of cells in each microwell to not regularize. Also, the instability of droplets during the spheroid formation remains an unsolved ordeal. In this study, we designed a microfluidic-based hanging-drop culture system with the design of taper-tube that can increase the stability of droplets while enhancing the rate of liquid exchange. A ring is surrounding the taper-tube. The ring can hold the cells to enable us to seed an adequate amount of cells before perfusion. Moreover, during the period of cell culture, the mechanical force around the cell is relatively low to prevent stem cells from differentiate and maintain the phenotype. As a result of our hanging system design, cells are designed to accumulate at the bottom of the droplet. This method enhances convenience for observation activities and analysis of experiments. Thus, this microfluid chip can be used as an in vitro platform representing in vivo physiological conditions, and can be useful in regenerative therapy.

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Section: Discussionmentioning

confidence: 99%

A Dynamic Hanging-Drop System for Mesenchymal Stem Cell Culture

Huang

Tzeng

Chen

et al. 2020

IJMS

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“…The growing spheroids secrete their own ECM, for example, generating scaffold‐free 3D cellular constructs that may better represent in vivo‐like cell behaviour when compared with 2D monolayer cell cultures. Such scaffold‐free 3D constructs can be maintained by continuous supply of nutrients and may also provide standardization, reproducibility, size uniformity and high‐throughput compatibility, all of which are necessary for preclinical and therapeutic drug testing (van Duinen et al, 2015; Wu, Hsiao, Chen, Yet, & Hsu, 2016). In a recent modification of a microfluidic scaffold‐free 3D cell culture platform, Frey, Misun, Fluri, Hengstler, & Hierlemann (2014) were able to grow multiple spheroids of different cell types with interconnected hanging drops within a microfluidic device.…”

Section: Microfluidic Devices For 3d Cell Culturementioning

confidence: 99%

Three‐dimensional in vitro cell culture devices using patient‐derived cells for high‐throughput screening of drug combinations

et al. 2020

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Drug discovery using traditional animal models is often inefficient because test animal models cannot accurately represent human responses, particularly in terms of toxicology and pathophysiology. For these reasons, there is an urgent need to develop in vitro human disease models to accelerate new drug development. This is especially the case for precision medicine, where current in vitro and ex vivo models are not sufficient to predict individual drug efficacy and safety across the enormous heterogeneity of populations and individuals. In addition, model cell lines cultured under non‐physiological conditions do not recapitulate the complex microenvironment of patient tissues. Precision medicine using patient‐derived cells and drug combination therapies may be a promising solution to overcome these limitations. Three‐dimensional (3D) cell culture models can simultaneously simulate complex in vivo tissue microenvironments and be miniaturized for large‐scale screening of drug combinations using limited available patient‐derived cells. Recently, microfluidic and microarray platforms have been developed to mimic multiple human organs and human‐specific disease states, and are becoming more commonly used in high‐throughput drug screening. Herein, we highlight the current status of microfluidic‐based 3D cell culture devices, such as organ/body‐on‐chip systems, as well as microarray‐based 3D cell culture platforms, which can be combined with patient‐derived cells. Miniaturized cell culture systems using patient‐derived cells represent promising tools for identifying new drug combinations and also biological mechanisms that underlie drug synergies.

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“…As one way of solving these problems, microfluidic handing drop devices [11][12][13][14] have been presented, which link all hanging drop arrays to microchannels and connect them to fluidic pumps. However, because these methods have been applied to the spheroid array network that has been designed to use a multi-spheroid interaction, the spheroids in the microfluidic hanging drop devices may interfere with each other due to the interconnected microchannel structure.…”

Section: 044109-1mentioning

confidence: 99%

High-throughput culture and embedment of spheroid array using droplet contact-based spheroid transfer

2018

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Spheroids are one of the most representative models of 3D cell culture, which can be easily formed using conventional hanging drop method. However, medium change and spheroid transferring process are the bottlenecks that reduce the throughput of the entire process in the hanging drop culture. In addition, the embedment of spheroid into hydrogel still depends on the individual pipetting process. To overcome these issues, we present poly(dimethylsiloxane) (PDMS)based simple devices which can exploit droplet contact-based spheroid transfer using a drop array chip (DAC) having an array of well structures and peripheral rims. When the upper spheroid-containing drops were in contact with the lower liquid drops, the air-liquid interface disappeared at the merged surface and the spheroids settled down due to gravitational force. This method was applied to repetitive medium change and live/dead staining of spheroids cultured with the hanging drop method. To simultaneously embed the spheroids into the corresponding collagen hydrogel drops, a PDMS-based pillar array chip (PAC) was contacted in advance with the spheroid-containing DAC. The contacted PAC then contained the spheroids trapped in small drops of liquid reduced in volume to around 0.5 ll. Consequently, the spheroids were embedded into the collagen drops at once by contacting the spheroid-containing PAC with the collagen-loaded DAC. The embedded spheroids using the DAC-PAC contacting method showed a reliable invasion behavior compared to the embedded spheroids using conventional manual pipetting.

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A PDMS-Based Microfluidic Hanging Drop Chip for Embryoid Body Formation

Cited by 32 publications

References 27 publications

A Dynamic Hanging-Drop System for Mesenchymal Stem Cell Culture

A Dynamic Hanging-Drop System for Mesenchymal Stem Cell Culture

Three‐dimensional in vitro cell culture devices using patient‐derived cells for high‐throughput screening of drug combinations

High-throughput culture and embedment of spheroid array using droplet contact-based spheroid transfer

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