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.

Highlights

  • circulating tumor cells (CTCs) are generally seen as a prognostic indicator for patients with various metastatic carcinomas [1] and can act as a predictor of metastatic diseases [2], a disease which is more than 90% responsible for cancer related deaths [3]

  • Microslit on a chip: A simplified filter to capture circulating tumor cells enlarged with microbeads including easy, fast and cost-effective fabrication process as well as relevance of biological studies via biocompatibility, transparency, low autofluorescence and semipermeability

  • We presented a novel CTC separation method showing both high purity and high recovery rate

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Summary

Introduction

CTCs are generally seen as a prognostic indicator for patients with various metastatic carcinomas [1] and can act as a predictor of metastatic diseases [2], a disease which is more than 90% responsible for cancer related deaths [3]. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript

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