Capture and Release of Cancer Cells by Combining On-Chip Purification and Off-Chip Enzymatic Treatment

ACS Appl Mater Interfaces. 2015 Nov 4;7(43):24001-7. doi: 10.1021/acsami.5b06791. Epub 2015 Oct 21.

Abstract

As "liquid biopsies", circulating tumor cells (CTCs) have been thought to hold significant insights for cancer diagnosis and treatment. Despite the advances of microfluidic techniques that improve the capture of CTCs to a certain extent, recovering the captured CTCs with enhanced purity at the same time remains a challenge. Here, by combining on-chip purification and off-chip enzymatic treatment, we demonstrate a two-stage strategy to enhance the purity of captured cancer cells from blood samples. The on-chip purification introduces a stirring flow to increase the capture sensitivity and decrease nonspecifically bounded cells. The off-chip enzymatic treatment enables the cancer cells to be released from the attached magnetic beads, further improving the purity and enabling next reculture. For the proof-of-concept study, spiked cancer cells are successfully obtained from unprocessed whole blood with high recovery rate (∼68%) and purity (∼61%), facilitating subsequent RNA expression analysis.

Keywords: aptamers; circulating tumor cells; hepatocellular carcinoma; microfluidics; release.

MeSH terms

  • Animals
  • Aptamers, Nucleotide / chemistry
  • Carcinoma, Hepatocellular / enzymology
  • Carcinoma, Hepatocellular / pathology*
  • Cattle
  • Cell Line, Tumor
  • Cell Separation / methods*
  • Computer Simulation
  • Dimethylpolysiloxanes / chemistry
  • Enzymes / chemistry*
  • Finite Element Analysis
  • Humans
  • Liver Neoplasms / enzymology
  • Liver Neoplasms / pathology*
  • Magnetics
  • Microfluidic Analytical Techniques / methods
  • Microfluidics
  • Neoplastic Cells, Circulating / metabolism*
  • Protein Array Analysis / methods*
  • Reproducibility of Results

Substances

  • Aptamers, Nucleotide
  • Dimethylpolysiloxanes
  • Enzymes
  • baysilon