Isolation and mutational analysis of circulating tumor cells from lung cancer patients with magnetic sifters and biochips

使用磁筛和生物芯片对肺癌患者循环肿瘤细胞进行分离和突变分析

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作者:Christopher M Earhart, Casey E Hughes, Richard S Gaster, Chin Chun Ooi, Robert J Wilson, Lisa Y Zhou, Eric W Humke, Lingyun Xu, Dawson J Wong, Stephen B Willingham, Erich J Schwartz, Irving L Weissman, Stefanie S Jeffrey, Joel W Neal, Rajat Rohatgi, Heather A Wakelee, Shan X Wang

Abstract

Detection and characterization of circulating tumor cells (CTCs) may reveal insights into the diagnosis and treatment of malignant disease. Technologies for isolating CTCs developed thus far suffer from one or more limitations, such as low throughput, inability to release captured cells, and reliance on expensive instrumentation for enrichment or subsequent characterization. We report a continuing development of a magnetic separation device, the magnetic sifter, which is a miniature microfluidic chip with a dense array of magnetic pores. It offers high efficiency capture of tumor cells, labeled with magnetic nanoparticles, from whole blood with high throughput and efficient release of captured cells. For subsequent characterization of CTCs, an assay, using a protein chip with giant magnetoresistive nanosensors, has been implemented for mutational analysis of CTCs enriched with the magnetic sifter. The use of these magnetic technologies, which are separate devices, may lead the way to routine preparation and characterization of "liquid biopsies" from cancer patients.

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