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

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

doi:10.1016/j.cels.2017.08.012

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

Cell Syst. 2017 Sep 27;5(3):295-304.e4. doi: 10.1016/j.cels.2017.08.012. Epub 2017 Sep 20.

Affiliations

¹ Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Translational Oncology Program, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
² Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA; Translational Oncology Program, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA.
³ Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA; Translational Oncology Program, University of Michigan, Ann Arbor, MI 48109, USA.
⁴ Department of Surgery, University of Michigan, Ann Arbor, MI 48109, USA; Translational Oncology Program, University of Michigan, Ann Arbor, MI 48109, USA; Department of Molecular and Integrative Physiology, University of Michigan, Ann Arbor, MI 48109, USA.
⁵ Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA; Translational Oncology Program, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: mwicha@med.umich.edu.
⁶ Department of Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Translational Oncology Program, University of Michigan, Ann Arbor, MI 48109, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI 48109, USA. Electronic address: snagrath@umich.edu.

PMID: 28941584
DOI: 10.1016/j.cels.2017.08.012

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.

Keywords: breast cancer; circulating tumor cells; epithelial mesenchymal transition; heterogeneity of cancer; label-free separation; mesenchymal epithelial transition; microfluidics; pancreatic cancer; single-cell gene analysis of CTCs.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Breast Neoplasms / blood
Cell Count
Cell Line, Tumor
Cell Separation / instrumentation
Cell Separation / 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
Single-Cell Analysis / methods

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

Authors

Affiliations

Abstract

Publication types

MeSH terms

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