High-purity Isolation for Genotyping Rare Cancer Cells from Blood Using a Microfluidic Chip Cell Sorter

Anticancer Res. 2022 Jan;42(1):407-417. doi: 10.21873/anticanres.15499.

Abstract

Background/aim: A multistep sorting method for enrichment of rare cells, such as circulating tumor cells, in the blood without cumbersome pretreatments required by most flow cytometry-based methods, which lead to high cost and decreased detection efficiency, was developed.

Materials and methods: After only hemolysis and cell staining, cancer cells are enriched by repetitive sorting (3×) based on nuclear-positive, cytokeratin-positive, and CD45-negative expression.

Results: Experiments using spikes of PC-9 cells showed a mean recovery of 65% and mean purity of 83%, which was retained up to 72 hours after blood draw using preservative tubes. Significant differences in expression level of programmed death-ligand 1 or vimentin were observed between high- and low-expressing cell lines, concurrently with enrichment. Next-generation sequencing analysis of recovered PC-9, A549, and MDA-MB231 cells successfully detected all known mutations.

Conclusion: This novel isolation method applicable for preserved samples with sufficient recovery and purity may be substantially beneficial for recovering cells for subsequent molecular analysis.

Keywords: Cancer cell; PD-L1; circulating tumor cell; liquid biopsy; microfluidic chip cell sorter; multistep sorting.

MeSH terms

  • A549 Cells
  • Flow Cytometry
  • Genotyping Techniques*
  • Hemolysis
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Leukocyte Common Antigens / genetics*
  • Microfluidic Analytical Techniques*
  • Neoplasms / blood*
  • Neoplasms / genetics
  • Neoplasms / pathology
  • Neoplastic Cells, Circulating / metabolism
  • Neoplastic Cells, Circulating / pathology

Substances

  • Leukocyte Common Antigens