Design of a microfluidic device for immunoaffinity-based isolation of circulating tumor cells with minimal clogging

Abstract

Combining bioaffinity-based techniques with microfluidics is an effective strategy for the selective isolation of rare circulating tumor cells (CTCs) among peripheral blood cells. In this scope, designing a microfluidic channel with high cell-surface interaction is crucial, which can be realized by increasing surface area via micropillars. In such microfluidic channels, the interpillar distance represents a critical design parameter, and the value is decided considering the trade-off between the possibility of clogging and CTC capture efficiency. In this study, a curvilinear microfluidic channel with a wide (150 µm) interpillar distance was developed to prevent clogging while maintaining high CTC capture efficiency. Computational fluid dynamics was used to compare the residence time of particles in the designed channels. For the proof-of-concept study, microfabricated channels were biofunctionalized for immunoaffinity-based isolation of CTCs, using anti-EpCAM antibodies. Enhanced CTC capture was enabled through the micropillars inside the channels helping the increased encounters between the cells and the antibody-functionalized surface. The curvilinear channel effectively isolated cells from MCF-7 breast cancer cell line among white blood cells, with more than 85% capture efficiency. The rate of non-specific binding of white blood cells remained below 20%. This study demonstrated the ability to increase the interactions between particles and surfaces without requiring a dense layout of the micropillars inside the microchannel, therefore minimizing the clogging possibility of the channel without sacrificing performance.

Keywords

• Microfluidic channel
• Micropillar
• Computational fluid dynamics
• Circulating Tumor Cell (CTC) isolation
• Immunoaffinity binding