Long-term monitoring in a microfluidic system to study tumour spheroid response to chronic and cycling hypoxia

Grist, Samantha M.; Nasseri, S. Soroush; Laplatine, Loïc; Schmok, Jonathan C.; Yao, Dickson; Hua, Jessica; Chrostowski, Lukas; Cheung, Karen C.

doi:10.1038/s41598-019-54001-8

Cited by 55 publications

(64 citation statements)

References 80 publications

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“…The use of reagents and biomarker probes including fluorescent protein reporters that are known to work well in 2D cell monolayer models may or may not exhibit the same protein expression or performance in 3D cell model systems due to physical barriers, oxygen content and nutrient levels within the core of a spheroid, and other environmental conditions (Edmondson et al 2014;Wenzel et al 2014;Grist et al 2019). Therefore, HCS practitioners need to review and verify these potential caveats during assay development and validation experiments before proceeding.…”

Section: Reagents and Probes For 3d Cell Imagingmentioning

confidence: 99%

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Factors to consider when interrogating 3D culture models with plate readers or automated microscopes

Trask

2021

In Vitro Cell.Dev.Biol.-Animal

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Along with the increased use of more physiologically relevant three-dimensional cell culture models comes the responsibility of researchers to validate new assay methods that measure events in structures that are physically larger and more complex compared to monolayers of cells. It should not be assumed that assays designed using monolayers of cells will work for cells cultured as larger three-dimensional masses. The size and barriers for penetration of molecules through the layers of cells result in a different microenvironment for the cells in the outer layer compared to the center of three-dimensional structures. Diffusion rates for nutrients and oxygen may limit metabolic activity which is often measured as a marker for cell viability. For assays that lyse cells, the penetration of reagents to achieve uniform cell lysis must be considered. For live cell fluorescent imaging assays, the diffusion of fluorescent probes and penetration of photons of light for probe excitation and fluorescent emission must be considered. This review will provide an overview of factors to consider when implementing assays to interrogate three dimensional cell culture models.

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Section: Reagents and Probes For 3d Cell Imagingmentioning

confidence: 99%

“… 2014 ; Grist et al . 2019 ). Therefore, HCS practitioners need to review and verify these potential caveats during assay development and validation experiments before proceeding.…”

Section: Considering Limitations Of Models That Incorporate Microfluimentioning

confidence: 99%

Factors to consider when interrogating 3D culture models with plate readers or automated microscopes

Trask

2021

In Vitro Cell.Dev.Biol.-Animal

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“…To achieve this, Grist and colleagues developed a microfluidic platform, in which breast tumor cell (MCF-7) spheroids in alginate hydrogel core-shell beads were cultured. All tumor spheroids were periodically exposed to 0%, 3% and 10% oxygen [54]. They discovered oxygen profile-dependent swelling and shrinking of individual cells within the tumor spheroids.…”

Section: Reconstituting the Biochemical Microenvironment On-chipmentioning

confidence: 99%

Technological Advances in Tumor-On-Chip Technology: From Bench to Bedside

Bērziņa

Harrison

Taly

et al. 2021

Cancers

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Tumor-on-chip technology has cemented its importance as an in vitro tumor model for cancer research. Its ability to recapitulate different elements of the in vivo tumor microenvironment makes it promising for translational medicine, with potential application in enabling personalized anti-cancer therapies. Here, we provide an overview of the current technological advances for tumor-on-chip generation. To further elevate the functionalities of the technology, these approaches need to be coupled with effective analysis tools. This aspect of tumor-on-chip technology is often neglected in the current literature. We address this shortcoming by reviewing state-of-the-art on-chip analysis tools for microfluidic tumor models. Lastly, we focus on the current progress in tumor-on-chip devices using patient-derived samples and evaluate their potential for clinical research and personalized medicine applications.

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“…A spheroid has the geometrical property similar to solid tumor in vivo, providing the native properties of gradient oxygen situation [70]. For the study of hypoxia in tumor spheroids, Ilana Berger Fridman et al [71] developed a multi-layer microfluidic device to generate 3D breast tumor spheroids under the microenvironment of five levels of oxygen concentrations with high throughput.…”

Section: Hypoxia Modelmentioning

confidence: 99%

Diversity Models and Applications of 3D Breast Tumor-on-a-Chip

Song

et al. 2021

Micromachines

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Breast disease is one of the critical diseases that plague females, as is known, breast cancer has high mortality, despite significant pathophysiological progress during the past few years. Novel diagnostic and therapeutic approaches are needed to break the stalemate. An organ-on-chip approach is considered due to its ability to repeat the real conditions found in the body on microfluidic chips, offsetting the shortcomings of traditional 2D culture and animal tests. In recent years, the organ-on-chip approach has shown diversity, recreating the structure and functional units of the real organs/tissues. The applications were also developed rapidly from the laboratory to the industrialized market. This review focuses on breast tumor-on-a-chip approaches concerning the diversity models and applications. The models are summarized and categorized by typical biological reconstitution, considering the design and fabrication of the various breast models. The breast tumor-on-a-chip approach is a typical representative of organ chips, which are one of the precedents in the market. The applications are roughly divided into two categories: fundamental mechanism research and biological medicine. Finally, we discuss the prospect and deficiencies of the emerging technology. It has excellent prospects in all of the application fields, however there exist some deficiencies for promotion, such as the stability of the structure and function, and uniformity for quantity production.

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Long-term monitoring in a microfluidic system to study tumour spheroid response to chronic and cycling hypoxia

Cited by 55 publications

References 80 publications

Factors to consider when interrogating 3D culture models with plate readers or automated microscopes

Factors to consider when interrogating 3D culture models with plate readers or automated microscopes

Technological Advances in Tumor-On-Chip Technology: From Bench to Bedside

Diversity Models and Applications of 3D Breast Tumor-on-a-Chip

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