Spiral shape microfluidic channel for selective isolating of heterogenic circulating tumor cells

Biosens Bioelectron. 2018 Mar 15:101:311-316. doi: 10.1016/j.bios.2017.10.036. Epub 2017 Oct 17.

Abstract

Detecting heterogenic tumor cells that are traveling in our body through blood stream for the tumor metastasis is one way for cancer prognosis. Due to the heterogeneity of circulating tumor cells (CTCs), further identification of tumor cell types should be accompanied with CTCs isolation from blood cells in peripheral blood sample. Both negative enrichment and recollection of isolated CTCs are required in the downstream analysis, which are time-consuming, labor-intensive, and massive equipment required. To solve these limitations, we have developed a simple and disposable spiral shape microfluidic channel that can separate all CTCs from blood cells, and at the same time, can identify the types of CTCs based on epithelial cell adhesion molecule (EpCAM) expression level. Two different types of tumor cells, MCF-7 and MDA-MB-231, both from the same origin of breast carcinoma cells, were used to demonstrate the functionality of the developed system. The spiral channel system could capture the EpCAM positive and negative CTCs with 96.3% and 81.2% purity, respectively, while both EpCAM positive and negative CTCs were differently positioned along the microfluidic channel. The average selectivity of EpCAM positive and negative CTCs is 6.1:4.8. In addition, the throughput of the system was optimized at a sample flow rate of 150µl/min. The developed system successfully demonstrated its potential to identify biomarkers, including EpCAM, for detecting the heterogenic CTCs.

Keywords: Circulating tumor cells (CTCs); Epithelial cell adhesion molecule (EpCAM); Heterogeneity of CTCs; Magnetic activated cell sorting (MACS); Spiral shape microfluidic channel.

MeSH terms

  • Biosensing Techniques / instrumentation*
  • Breast Neoplasms / pathology*
  • Cell Line, Tumor
  • Cell Separation / instrumentation*
  • Epithelial Cell Adhesion Molecule / analysis
  • Equipment Design
  • Female
  • Humans
  • MCF-7 Cells
  • Magnetics / instrumentation
  • Microfluidic Analytical Techniques / instrumentation*
  • Neoplastic Cells, Circulating / pathology*

Substances

  • Epithelial Cell Adhesion Molecule