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Hybrid microfluidic sorting of rare cells based on high throughput inertial focusing and high accuracy acoustic manipulation.

Yinning ZhouZhichao MaYe Ai
Published in: RSC advances (2019)
The ability to isolate rare circulating tumor cells (CTCs) from blood samples is essential to perform liquid biopsy as a routine diagnostic and prognostic test. Both label-free and surface biomarker-based cell sorting technologies have been developed to address the demand in high-integrity isolation of rare CTCs for cancer research. Label-free cell sorting mainly relies on the size difference between CTCs and blood cells; thus, it lacks sufficient sorting specificity. Surface biomarker-based cell sorting is highly specific; however, it requires expensive, labor-intensive, and time-consuming labeling due to the use of multiple sets of surface biomarkers. Because of the complex nature and high heterogeneity of tumorigenesis, it is difficult to rely on a single sorting process for high-integrity rare cell isolation. In this study, for the first time, we present a hybrid microfluidic cell sorting method combining high throughput size-dependent inertial focusing for size-based pre-enrichment and high accuracy fluorescence activated acoustic sorting for single cell isolation. After one single hybrid sorting process, we have demonstrated at least 2500-fold purity enrichment of MCF-7 breast cancer cells spiked in diluted whole blood samples with cell viability maintained at 91 ± 1% (viability before sorting was 94 ± 2%). This developed hybrid microfluidic cell sorting technique provides a promising solution for rare cell isolation needed in a variety of biological research and clinical applications.
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