Adjustable and Versatile 3D Tumor Spheroid Culture Platform with Interfacial Elastomeric Wells

An, Hyun Ji; Kim, Hyo Sil; Kwon, Jung Ah; Song, Jihwan; Choi, Inhee

doi:10.1021/acsami.9b21471

Cited by 24 publications

(20 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Various interaction forces, especially the cell–cell interaction energy ( G cell–cell ) and the cell–surface interaction energy ( G cell–cell–surface ) between seeded cells and agarose well, contribute significantly to the aggregation of the cells to form spheroids . Consequently, the total energy of the system can be expressed as …”

Section: Resultsmentioning

confidence: 99%

Developing μSpherePlatform Using a Commercial Hairbrush: An Agarose 3D Culture Platform for Deep-Tissue Imaging of Prostate Cancer

Krishnan

Chelvam

2021

ACS Appl. Bio Mater.

View full text Add to dashboard Cite

Prostate-specific membrane antigen (PSMA) is a viable diagnostic biomarker for the detection and treatment of prostate cancer. Although numerous imaging techniques and fluorescent probes have been developed, targeted imaging and intraoperative surgery continue to remain as a proof-of-concept with a severe lack of tools having high affinity and penetrative capacity. In vitro three-dimensional cell culture has gained immense interest in cancer research and drug discovery programs as it yields important physiological information and serves an excellent model for bioimaging and penetration analysis studies. Current techniques employed in spheroid formation include liquid overlay and hanging drop methods, both of which are low-yielding and technically demanding. We describe for the first time a simple-to-use platform, μSpherePlatform, an inexpensive, high-throughput method yielding morphologically homogeneous spheroids in bulk for analyzing penetrative capacity and imaging ability of PCa diagnostics. Microwell arrays made of agarose have been fabricated using a commercial hairbrush as a master template. This procedure has been described in detail, and arrays of spheroids (100−120 spheroids/6-well plate) with >95% success rates have been produced from PCa cell lines (LNCaP and DU-145). A PSMA-targeted fluorescent conjugate was synthesized and evaluated in the spheroids developed using μSpherePlatform by multiphoton imaging. A synthetic 3D scaffold strategy is reported herein, which (1) correlates perfectly with the in vivo model, (2) is amenable for automated analysis, (3) shows a negligible lot to lot variation, (4) is simplistic, ( 5) is useful for high-throughput assays, ( 6) is extremely compatible with imaging techniques, (7) generates PCa spheroids within 48 h, and (8) forms large size-controllable spheroids of diameter 500−1300 μm. The μSpherePlatform thus provides a significant contribution to multimodal analyses of cancer diagnostics and deep-tissue imaging studies.

show abstract

Section: Resultsmentioning

confidence: 99%

Developing μSpherePlatform Using a Commercial Hairbrush: An Agarose 3D Culture Platform for Deep-Tissue Imaging of Prostate Cancer

Krishnan

Chelvam

2021

ACS Appl. Bio Mater.

View full text Add to dashboard Cite

show abstract

“…The methods of 3D cell spheroid formation mainly include hanging-drop approaches [89,90], spinner flask approaches, micropatterned plates and magnetic levitation approaches [91]. Recently, an interesting work involving a rapid and efficient method for the formation of 3D cell culture spheroids was described [92]. Based on the phenomenon of interfacial reactions between two immiscible liquid solutions with different densities and surface tensions, spherical wells in elastomeric PDMS can be formed and adjusted by the density and surface tension of the dropped solutions.…”

Section: Spheroid Culturesmentioning

confidence: 99%

“…The results of in situ drug testing and monitoring of ROS levels were performed using 3D tumor spheroids located in PDMS wells, demonstrating that this platform can be used to study the responses of tumor cells to drugs. Furthermore, the system can also be used as a general tool for in situ drug screening of cancer and is easily implemented in practical applications [92]. In addition, Li et al [63] successfully constructed a mechanical cue-based simultaneous 2D and 3D multicellular culture system.…”

Section: Spheroid Culturesmentioning

confidence: 99%

Functions and clinical significance of mechanical tumor microenvironment: cancer cell sensing, mechanobiology and metastasis

Zhou

Wang

Zhang

et al. 2022

Cancer Communications

View full text Add to dashboard Cite

Dynamic and heterogeneous interaction between tumor cells and the surrounding microenvironment fuels the occurrence, progression, invasion, and metastasis of solid tumors. In this process, the tumor microenvironment (TME) fractures cellular and matrix architecture normality through biochemical and mechanical means, abetting tumorigenesis and treatment resistance. Tumor cells sense and respond to the strength, direction, and duration of mechanical cues in the TME by various mechanotransduction pathways. However, far less understood is the comprehensive perspective of the functions and mechanisms of mechanotransduction. Due to the great therapeutic difficulties brought by the mechanical changes in the TME, emerging studies have focused on targeting the adverse mechanical factors in the TME to attenuate disease rather than conventionally targeting tumor cells themselves, which has been proven to be a potential therapeutic approach. In this review, we discussed the origins and roles of mechanical factors in the TME, cell sensing, mechano‐biological coupling and signal transduction, in vitro construction of the tumor mechanical microenvironment, applications and clinical significance in the TME.

show abstract

“…However, it is still challenging to observe cell spheroids in situ on this platform because certain materials used on this platform have obvious nonspecific adsorption properties for compounds (such as polydimethylsiloxane, multi-layer polymer polymers, modified inorganic materials, etc. ) In addition, each cell spheroid must be processed separately on this platform, which greatly limits their applicability in HTS. As a result, increasing attention has been attracted to further develop droplet microarrays and engineering techniques to simplify the culture process, optimize methods of drug input, improve the accuracy and reproducibility of screening processes, and provide a greater support for precision medicine. − …”

Section: Introductionmentioning

confidence: 99%

Acoustic Droplet-Assisted Superhydrophilic–Superhydrophobic Microarray Platform for High-Throughput Screening of Patient-Derived Tumor Spheroids

Xia

Chen

et al. 2021

ACS Appl. Mater. Interfaces

View full text Add to dashboard Cite

Cell-based high-throughput screening is a key step in the current disease-based research, drug development, and precision medicine. However, it is challenging to establish a rapid culture and screening platform for rare cells (patient-derived) due to the obvious differences between the traditional 2D cell model and the tumor microenvironment, as well as the lack of a lowconsumption screening platform for low numbers of cells. Here, we developed an acoustic drop-assisted superhydrophilic−superhydrophobic microarray platform for the rapid culture and screening of a few cells. By employing hydrophilic and hydrophobic microarrays, we can automatically distribute the cell suspension into uniform droplets, and these cells can spontaneously form compact 3D cell spheroids within 36 h (similar to the microenvironment of tumors in vivo). By using the acoustic droplet ejection device, we can accurately inject a drug solution with a volume of ∼pL to ∼nL into the droplet, and the whole process can be completed within 20 ms (one print). By using three different cell lines (Caco-2, MCF-7, and HeLa) to optimize the platform, the culture and screening of five patients' colon cancer were subsequently realized. Using three conventional chemotherapeutics (5-fluorouracil, cetuximab, and panitumumab) of various concentrations, the best treatment was screened out and compared with the actual treatment effect of the patients, and the results were extremely similar. As a proof-of-concept application, we have proved that our platform can quickly cultivate patient samples and effectively screen the best treatment methods, highlighting its wide application in precision medicine, basic tumor research, and drug development.

show abstract

Adjustable and Versatile 3D Tumor Spheroid Culture Platform with Interfacial Elastomeric Wells

Cited by 24 publications

References 34 publications

Developing μSpherePlatform Using a Commercial Hairbrush: An Agarose 3D Culture Platform for Deep-Tissue Imaging of Prostate Cancer

Developing μSpherePlatform Using a Commercial Hairbrush: An Agarose 3D Culture Platform for Deep-Tissue Imaging of Prostate Cancer

Functions and clinical significance of mechanical tumor microenvironment: cancer cell sensing, mechanobiology and metastasis

Acoustic Droplet-Assisted Superhydrophilic–Superhydrophobic Microarray Platform for High-Throughput Screening of Patient-Derived Tumor Spheroids

Contact Info

Product

Resources

About