A Novel Microfluidic Method Utilizing a Hydrofoil Structure to Improve Circulating Tumor Cell Enrichment: Design and Analytical Validation.

Gürhan Özkayar,Özge Zorlu,Taylan Töral,Ender Yildirim,Yağmur Demircan Yalçın,Ebru Özgür,Şebnem Şahin,Haluk Külah,Ege Mutlu

doi:10.3390/mi11110981

Gürhan Özkayar, Özge Zorlu + Show 7 more

Open Access

https://doi.org/10.3390/mi11110981

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Abstract

Being one of the major pillars of liquid biopsy, isolation and characterization of circulating tumor cells (CTCs) during cancer management provides critical information on the evolution of cancer and has great potential to increase the success of therapies. In this article, we define a novel strategy to effectively enrich CTCs from whole blood based on size, utilizing a spiral microfluidic channel embedded with a hydrofoil structure at the downstream of the spiral channel. The hydrofoil increases the distance between the streams of CTCs and peripheral blood cells, which are already distributed about two focal axes by the spiral channel, thereby improving the resolution of the separation. Analytical validation of the system has been carried out using Michigan Cancer Foundation-7 (MCF7) breast cancer cell lines spiked into blood samples from healthy donors, and the performance of the system in terms of white blood cell (WBC) depletion, CTC recovery rate and cell viability has been shown in single or two-step process: by passing the sample once or twice through the microfluidic chip. Single step process yielded high recovery (77.1%), viable (84.7%) CTCs. When the collected cell suspension is re-processed by the same chip, recovery decreases to 65.5%, while the WBC depletion increases to 88.3%, improving the purity. Cell viability of >80% was preserved after two-step process. The novel microfluidic chip is a good candidate for CTC isolation applications requiring high recovery rate and viability, including functional downstream analyses for variety of cancer types.

Highlights

Despite emerging detection technologies and new therapy regimes, cancer is the main health issue all over the world
The hydrofoil increases the distance between the streams of circulating tumor cells (CTCs) and peripheral blood cells (PBCs), which are already distributed about two focal axes by the spiral channel, thereby improving the performance
To investigate the effect of hydrodynamic forces generated during the passage of the cell suspension through the chip on the viability of CTCs, a pure Michigan Cancer Foundation-7 (MCF7) cell suspension was processed by the microfluidic chip using the same protocol explained above

Summary

Introduction

Despite emerging detection technologies and new therapy regimes, cancer is the main health issue all over the world. A variety of techniques is available for CTC isolation from blood, each having its own advantages and inadequacies These technologies can be basically classified in two groups: (i) those that are based on the differences in physical properties of CTCs and PBCs, including size, deformability, and electrical properties, and (ii) the others that are based on the differences in surface biological signatures [16,17]. Technologies that are based on the differences in physical properties of CTCs and PBCs apply either a mechanical filtration through porous filters or hydrodynamic enrichment that employs state-of the art microfluidic technologies [19] These technologies offer the advantages of label-free isolation of CTCs from whole blood. WBC depletion ratio, CTC recovery rate, and cell viability have been investigated

Principle of Particle Focusing in Spiral Microfluidic Channels

Device Design and Simulations

Viability Analysis

Flow Rate Optimization

Effect on Cell Viability

Conclusions