Microslit on a chip: A simplified filter to capture circulating tumor cells enlarged with microbeads

PLoS One. 2019 Oct 24;14(10):e0223193. doi: 10.1371/journal.pone.0223193. eCollection 2019.

Abstract

Microchips are widely used to separate circulating tumor cells (CTCs) from whole blood by virtues of sophisticated manipulation for microparticles. Here, we present a chip with an 8 μm high and 27.9 mm wide slit to capture cancer cells bound to 3 μm beads. Apart from a higher purity and recovery rate, the slit design allows for simplified fabrication, easy cell imaging, less clogging, lower chamber pressure and, therefore, higher throughput. The beads were conjugated with anti-epithelial cell adhesion molecules (anti-EpCAM) to selectively bind to breast cancer cells (MCF-7) used to spike the whole blood. The diameter of the cell-bead construct was in average 23.1 μm, making them separable from other cells in the blood. As a result, the cancer cells were separated from 5 mL of whole blood with a purity of 52.0% and a recovery rate of 91.1%, and also we confirmed that the device can be applicable to clinical samples of human breast cancer patients. The simple design with microslit, by eliminating any high-aspect ratio features, is expected to reduce possible defects on the chip and, therefore, more suitable for mass production without false separation outputs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / blood*
  • Breast Neoplasms / blood*
  • Breast Neoplasms / genetics
  • Female
  • Humans
  • MCF-7 Cells
  • Microfluidic Analytical Techniques*
  • Microspheres
  • Neoplastic Cells, Circulating*
  • Precancerous Conditions / blood
  • Precancerous Conditions / genetics

Substances

  • Antigens, Neoplasm

Grants and funding

This research was supported by the National Research Foundation of Korea (NRF) (Grant No. NRF-2017M3A9E9072667) funded by the Ministry of Science and ICT and by Samsung Advanced Institute of Technology (SAIT). At the time of the study, Samsung Electronics, Ltd. employed authors Tae Seok Sim and Jeong-Gun Lee. The specific roles of these authors are articulated in the ‘author contributions’ section. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.