Capture of Circulating Tumour Cell Clusters Using Straight Microfluidic Chips.

Arutha Kulasinghe,Jian Zhou,Liz Kenny,Ian Papautsky,Chamindie Punyadeera

doi:10.3390/cancers11010089

Abstract

Circulating tumour cells (CTCs) are the metastatic precursors to distant disease in head and neck cancers (HNCs). Whilst the prognostic and predictive value of single CTCs have been well documented, the role of CTC clusters, which potentially have a higher metastatic capacity are limited. In this study, the authors used a novel straight microfluidic chip to focus and capture CTCs. The chip offers high cell recoveries with clinically relevant numbers (10–500 cells/mL) without the need for further purification. Single CTCs were identified in 10/21 patient samples (range 2–24 CTCs/mL), CTC clusters in 9/21 patient samples (range 1–6 CTC clusters/mL) and circulating tumour microemboli (CTM) in 2/21 samples. This study demonstrated that CTC clusters contain EGFR amplified single CTCs within the cluster volume. This novel microfluidic chip demonstrates the efficient sorting and preservation of single CTCs, CTC clusters and CTMs. The authors intend to expand this study to a larger cohort to determine the clinical implication of the CTC subsets in HNC.

Highlights

Cancer metastasis remains the major cause of cancer-related deaths, yet little is known about the transient cell populations responsible for the formation of distant disease
We investigated the presence of Circulating tumour cells (CTCs) and circulating tumour microemboli (CTM) in head and neck cancers (HNC)
Due to the strong size-dependence of inertial migration, we can precisely control the channel length to select larger CTCs and clusters, leading to separation from white blood cells (WBCs). The former are collected from the inner outlet (IO) and the waste cells exit the channel from the outer outlet (OO)

Summary

Introduction

Cancer metastasis remains the major cause of cancer-related deaths, yet little is known about the transient cell populations responsible for the formation of distant disease. In 1954, Watanabe described the role of CTC clusters leading to metastases more readily than single CTCs [2]. Since these findings, the field has gained significant traction in technologies for isolating rare cancer cells from patient bloods [3,4,5]. The field has gained significant traction in technologies for isolating rare cancer cells from patient bloods [3,4,5] To this end, the first FDA-approved CellSearch platform This technology pre-selects for epithelial cell adhesion molecule expression (EpCAM) on cells before characterising cells for pan-cytokeratin, CD45 and DAPI [6]. The reliance on a single marker for CTC isolation showed

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Conclusion