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使用代表血管的多间隙微流控装置对单个肿瘤细胞迁移和变形进行定量观察和成像。

A quantitative observation and imaging of single tumor cell migration and deformation using a multi-gap microfluidic device representing the blood vessel.

作者信息

Chaw K C, Manimaran M, Tay Francis E H, Swaminathan S

机构信息

Institute of Bioengineering and Nanotechnology 31 Biopolis Way, The Nanos #04-01, 138669, Singapore.

出版信息

Microvasc Res. 2006 Nov;72(3):153-60. doi: 10.1016/j.mvr.2006.06.003. Epub 2006 Nov 1.

Abstract

A microfluidic device was developed for quantifying the migratory and deformability capabilities of a single tumor cell using direct imaging. It was fabricated using photolithography and is made of polydimethysiloxane. Chemotaxis approach was used for directing cell movement, using 10 microm microgaps to restrict the migration to a single cell. Each cell's migration rate is quantified as a measure of its distance traveled over time taken. Real-time recording of cell deformation under physiological flow was performed, and the elongation index and surface area change of the cells were compared. Three human tumor cell lines viz. HepG2, HeLa and MDA-MB-435S were used to verify the operation and methodology of the device. Their migration rates ranged from 5 to 15 microm/h, consistent with other scientific reports. By reducing the microgap width to 3 microm, it was found that the cells moved along the row of microgaps but were unable to migrate across the microgaps. Subsequent deformation of the cells through the gaps further showed that their migratory capability might be governed by their deformation ability and the deformation stress on their membranes. The strategy of targeting cancer cell membrane for rupture may provide a therapy for metastasis. Being a valuable tool for rapid quantification of a single cell's migratory capability, this device should be helpful for pharmacologic and drug screening, investigation of factors that regulate cell migration and deformation.

摘要

开发了一种微流控装置,用于通过直接成像来量化单个肿瘤细胞的迁移和变形能力。该装置采用光刻技术制造,由聚二甲基硅氧烷制成。采用趋化方法引导细胞运动,利用10微米的微间隙将迁移限制为单个细胞。每个细胞的迁移速率通过其在一定时间内移动的距离来量化。对细胞在生理流动下的变形进行实时记录,并比较细胞的伸长指数和表面积变化。使用三种人类肿瘤细胞系,即HepG2、HeLa和MDA-MB-435S来验证该装置的操作和方法。它们的迁移速率在5至15微米/小时之间,与其他科学报告一致。通过将微间隙宽度减小到3微米,发现细胞沿着微间隙行移动,但无法穿过微间隙迁移。随后细胞通过间隙的变形进一步表明,它们 的迁移能力可能受其变形能力和细胞膜上的变形应力控制。靶向癌细胞膜破裂的策略可能为转移提供一种治疗方法。作为一种快速量化单个细胞迁移能力的有价值工具,该装置应有助于药理和药物筛选,以及对调节细胞迁移和变形的因素进行研究。

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