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使用光刻微滤器进行循环肿瘤细胞分离的系统研究。

The systematic study of circulating tumor cell isolation using lithographic microfilters.

作者信息

Adams Daniel L, Zhu Peixuan, Makarova Olga V, Martin Stuart S, Charpentier Monica, Chumsri Saranya, Li Shuhong, Amstutz Platte, Tang Cha-Mei

机构信息

Creatv MicroTech, Inc., 9900 Belward Campus Drive, Suite 330, Rockville, MD 20850, USA.

Creatv MicroTech, Inc., 2242 W. Harrison Street, Suite 109B, Chicago, IL 60612-3515, USA.

出版信息

RSC Adv. 2014;9:4334-4342. doi: 10.1039/C3RA46839A.

Abstract

Circulating tumor cells (CTCs) disseminated into peripheral blood from a primary, or metastatic, tumor can be used for early detection, diagnosis and monitoring of solid malignancies. CTC isolation by size exclusion techniques have long interested researchers as a simple broad based approach, which is methodologically diverse for use in both genomic and protein detection platforms. Though a variety of these microfiltration systems are employed academically and commercially, the limited ability to easily alter microfilter designs has hindered the optimization for CTC capture. To overcome this problem, we studied a unique photo-definable material with a scalable and mass producible photolithographic fabrication method. We use this fabrication method to systematically study and optimize the parameters necessary for CTC isolation using a microfiltration approach, followed by a comparison to a "standard" filtration membrane. We demonstrate that properly designed microfilters can capture MCF-7 cancer cells at rate of 98 ± 2% if they consist of uniform patterned distributions, ≥160 000 pores, and 7 μm pore diameters.

摘要

从原发性或转移性肿瘤扩散到外周血中的循环肿瘤细胞(CTC)可用于实体恶性肿瘤的早期检测、诊断和监测。长期以来,通过尺寸排阻技术分离CTC一直是研究人员感兴趣的一种简单的广泛方法,该方法在基因组和蛋白质检测平台上的使用方法多样。尽管这些微滤系统在学术和商业上都有多种应用,但微滤器设计难以轻易改变的局限性阻碍了CTC捕获的优化。为了克服这个问题,我们研究了一种独特的可光定义材料,并采用了可扩展且可大规模生产的光刻制造方法。我们使用这种制造方法系统地研究和优化使用微滤方法分离CTC所需的参数,然后与“标准”滤膜进行比较。我们证明,如果微滤器由均匀的图案分布、≥160000个孔和7μm的孔径组成,经过适当设计的微滤器能够以98±2%的速率捕获MCF-7癌细胞。

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