High-Throughput Microfluidic Labyrinth for the Label-free Isolation of Circulating Tumor Cells.

Abstract

We present "Labyrinth," a label-free microfluidic device to isolate circulating tumor cells (CTCs) using the combination of long loops and sharp corners to focus both CTCs and white blood cells (WBCs) at a high throughput of 2.5 mL/min. The high yield (>90%) and purity (600 WBCs/mL) of Labyrinth enabled us to profile gene expression in CTCs. As proof of principle, we used previously established cancer stem cell gene signatures to profile single cells isolated from the blood of breast cancer patients. We observed heterogeneous subpopulations of CTCs expressing genes for stem cells, epithelial cells, mesenchymal cells, and cells transitioning between epithelial and mesenchymal. Labyrinth offers a cell-surface marker-independent single-cell isolation platform to study heterogeneous CTC subpopulations.

• Authors: Eric Lin, Lianette Rivera-Báez, Shamileh Fouladdel, Hyeun Joong Yoon, Stephanie Guthrie, Jacob Wieger, Yadwinder Deol, Evan Keller, Vaibhav Sahai, Diane M Simeone, Monika L Burness, Ebrahim Azizi, Max S Wicha, Sunitha Nagrath
• Journal: Cell systems (Cell Syst) Vol. 5 Issue 3 Pg. 295-304.e4 (09 27 2017) ISSN: 2405-4712 [Print] United States
• PMID: 28941584 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Topics

• Breast Neoplasms (blood)
• Cell Count
• Cell Line, Tumor
• Cell Separation (instrumentation, methods)
• Epithelial Cells (metabolism)
• Epithelial-Mesenchymal Transition
• Female
• High-Throughput Screening Assays (methods)
• Humans
• Leukocytes (metabolism)
• Microfluidic Analytical Techniques (instrumentation)
• Microfluidics (methods)
• Neoplastic Cells, Circulating (metabolism)
• Single-Cell Analysis (instrumentation, methods)