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A microfluidic platform for cultivating ovarian cancer spheroids and testing their responses to chemotherapies
Microsystems & Nanoengineering ( IF 7.3 ) Pub Date : 2020-10-19 , DOI: 10.1038/s41378-020-00201-6
Neda Dadgar 1 , Alan M Gonzalez-Suarez 1 , Pouria Fattahi 1 , Xiaonan Hou 2 , John S Weroha 2 , Alexandre Gaspar-Maia 3 , Gulnaz Stybayeva 1 , Alexander Revzin 1
Affiliation  

There is increasing interest in utilizing in vitro cultures as patient avatars to develop personalized treatment for cancer. Typical cultures utilize Matrigel-coated plates and media to promote the proliferation of cancer cells as spheroids or tumor explants. However, standard culture conditions operate in large volumes and require a high concentration of cancer cells to initiate this process. Other limitations include variability in the ability to successfully establish a stable line and inconsistency in the dimensions of these microcancers for in vivo drug response measurements. This paper explored the utility of microfluidics in the cultivation of cancer cell spheroids. Six patient-derived xenograft (PDX) tumors of high-grade serous ovarian cancer were used as the source material to demonstrate that viability and epithelial marker expression in the microfluidic cultures was superior to that of Matrigel or large volume 3D cultures. To further demonstrate the potential for miniaturization and multiplexing, we fabricated multichamber microfluidic devices with integrated microvalves to enable serial seeding of several chambers followed by parallel testing of several drug concentrations. These valve-enabled microfluidic devices permitted the formation of spheroids and testing of seven drug concentrations with as few as 100,000 cancer cells per device. Overall, we demonstrate the feasibility of maintaining difficul-to-culture primary cancer cells and testing drugs in a microfluidic device. This microfluidic platform may be ideal for drug testing and personalized therapy when tumor material is limited, such as following the acquisition of biopsy specimens obtained by fine-needle aspiration.



中文翻译:


用于培养卵巢癌球体并测试其对化疗反应的微流体平台



人们越来越有兴趣利用体外培养物作为患者化身来开发癌症的个性化治疗。典型的培养物利用基质胶包被的板和培养基来促进癌细胞作为球体或肿瘤外植体的增殖。然而,标准培养条件需要大量操作,并且需要高浓度的癌细胞来启动该过程。其他限制包括成功建立稳定线的能力的可变性以及用于体内药物反应测量的这些微癌的尺寸的不一致。本文探讨了微流体在癌细胞球体培养中的应用。使用 6 个高级别浆液性卵巢癌患者来源的异种移植 (PDX) 肿瘤作为源材料,证明微流体培养物中的活力和上皮标记物表达优于 Matrigel 或大体积 3D 培养物。为了进一步证明小型化和多路复用的潜力,我们制造了带有集成微阀的多室微流体装置,以便能够连续接种多个室,然后并行测试多个药物浓度。这些支持阀门的微流体装置允许形成球体并测试七种药物浓度,每个装置仅包含 100,000 个癌细胞。总的来说,我们证明了在微流体装置中维持难以培养的原代癌细胞和测试药物的可行性。当肿瘤材料有限时,例如通过细针抽吸获得活检标本后,该微流体平台可能是药物测试和个性化治疗的理想选择。

更新日期:2020-10-19
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