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

• Published in: Lab on a chip Vol. 14; no. 1; p. 78
• Main Authors: Earhart, Christopher M, Hughes, Casey E, Gaster, Richard S, Ooi, Chin Chun, Wilson, Robert J, Zhou, Lisa Y, Humke, Eric W, Xu, Lingyun, Wong, Dawson J, Willingham, Stephen B, Schwartz, Erich J, Weissman, Irving L, Jeffrey, Stefanie S, Neal, Joel W, Rohatgi, Rajat, Wakelee, Heather A, Wang, Shan X
• Format: Journal Article
• Language: English
• Published: England 07-01-2014
• Subjects: Antibodies, Immobilized - chemistry; Antibodies, Immobilized - immunology; Antigens, Neoplasm - immunology; Antigens, Neoplasm - metabolism; Carcinoma, Non-Small-Cell Lung - metabolism; Carcinoma, Non-Small-Cell Lung - pathology; Cell Adhesion Molecules - immunology; Cell Adhesion Molecules - metabolism; Cell Line, Tumor; Cell Separation - instrumentation; Cell Separation - methods; Epithelial Cell Adhesion Molecule; Fluorescein-5-isothiocyanate - chemistry; Humans; Keratins - immunology; Keratins - metabolism; Lung Neoplasms - metabolism; Lung Neoplasms - pathology; Magnetics; Magnetite Nanoparticles - chemistry; MCF-7 Cells; Microfluidic Analytical Techniques - instrumentation; Microfluidic Analytical Techniques - methods; Mutation; Neoplastic Cells, Circulating - metabolism; Receptor, Epidermal Growth Factor - genetics; Receptor, Epidermal Growth Factor - immunology; Receptor, Epidermal Growth Factor - metabolism
• ISSN: 1473-0189
• DOI: 10.1039/c3lc50580d

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.