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Sci Rep. 2015 May 18;5:9980. doi: 10.1038/srep09980.

Single-cell Migration Chip for Chemotaxis-based Microfluidic Selection of Heterogeneous Cell Populations.

Author information

1
1] Department of Electrical Engineering and Computer Science, University of Michigan, 1301 Beal Avenue, Ann Arbor, MI 48109-2122, USA [2] University of Michigan Comprehensive Cancer Center, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA.
2
1] Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI [2] Medical Scientist Training Program, University of Michigan Medical School, Ann Arbor, MI.
3
Department of Biomedical Engineering, University of Michigan, 2200 Bonisteel Blvd, Ann Arbor, MI 48109, USA.
4
University of Michigan Comprehensive Cancer Center, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA.
5
1] Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, MI [2] Department of Internal Medicine and Comprehensive Cancer Center, University of Michigan, 1500 E. Medical Center Drive, Ann Arbor, MI 48109, USA.
6
1] Department of Electrical Engineering and Computer Science, University of Michigan, 1301 Beal Avenue, Ann Arbor, MI 48109-2122, USA [2] Department of Biomedical Engineering, University of Michigan, 2200 Bonisteel Blvd, Ann Arbor, MI 48109, USA.

Abstract

Tumor cell migration toward and intravasation into capillaries is an early and key event in cancer metastasis, yet not all cancer cells are imbued with the same capability to do so. This heterogeneity within a tumor is a fundamental property of cancer. Tools to help us understand what molecular characteristics allow a certain subpopulation of cells to spread from the primary tumor are thus critical for overcoming metastasis. Conventional in vitro migration platforms treat populations in aggregate, which leads to a masking of intrinsic differences among cells. Some migration assays reported recently have single-cell resolution, but these platforms do not provide for selective retrieval of the distinct migrating and non-migrating cell populations for further analysis. Thus, to study the intrinsic differences in cells responsible for chemotactic heterogeneity, we developed a single-cell migration platform so that individual cells' migration behavior can be studied and the heterogeneous population sorted based upon chemotactic phenotype. Furthermore, after migration, the highly chemotactic and non-chemotactic cells were retrieved and proved viable for later molecular analysis of their differences. Moreover, we modified the migration channel to resemble lymphatic capillaries to better understand how certain cancer cells are able to move through geometrically confining spaces.

PMID:
25984707
PMCID:
PMC4435023
DOI:
10.1038/srep09980
[Indexed for MEDLINE]
Free PMC Article

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