Clinical-Scale Cell-Surface-Marker Independent Acoustic Microfluidic Enrichment of Tumor Cells from Blood

Overview

Journal Anal Chem

Specialty Chemistry

Date 2017 Nov 1

PMID 29087172

Citations 21

Authors

Cecilia Magnusson

Per Augustsson

Andreas Lenshof

Yvonne Ceder

Thomas Laurell

Hans Lilja

Affiliations

Soon will be listed here.

Abstract

Enumeration of circulating tumor cells (CTCs) predicts overall survival and treatment response in metastatic cancer, but as many commercialized assays isolate CTCs positive for epithelial cell markers alone, CTCs with little or no epithelial cell adhesion molecule (EpCAM) expression stay undetected. Therefore, CTC enrichment and isolation by label-free methods based on biophysical rather than biochemical properties could provide a more representative spectrum of CTCs. Here, we report on a clinical-scale automated acoustic microfluidic platform processing 5 mL of erythrocyte-depleted paraformaldehyde (PFA)-fixed blood (diluted 1:2) at a flow rate of 75 μL/min, recovering 43/50 (86 ± 2.3%) breast cancer cell line cells (MCF7), with 0.11% cancer cell purity and 162-fold enrichment in close to 2 h based on intrinsic biophysical cell properties. Adjustments of the voltage settings aimed at higher cancer cell purity in the central outlet provided 0.72% cancer cell purity and 1445-fold enrichment that resulted in 62 ± 8.7% cancer cell recovery. Similar rates of cancer-cell recovery, cancer-cell purity, and fold-enrichment were seen with both prostate cancer (DU145, PC3) and breast cancer (MCF7) cell line cells. We identified eosinophil granulocytes as the predominant white blood cell (WBC) contaminant (85%) in the enriched cancer-cell fraction. Processing of viable cancer cells in erythrocyte-depleted blood provided slightly reduced results as to fixed cells (77% cancer cells in the enriched cancer cell fraction, with 0.2% WBC contamination). We demonstrate feasibility of enriching either PFA-fixed or viable cancer cells with a clinical-scale acoustic microfluidic platform that can be adjusted to meet requirements for either high cancer-cell recovery or higher purity and can process 5 mL blood samples in close to 2 h.

Citing Articles

Two-Step Acoustic Cell Separation Based on Cell Size and Acoustic Impedance─toward Isolation of Viable Circulating Tumor Cells.

Magnusson C, Rezayati Charan M, Augustsson P Anal Chem. 2025; 97(4):2120-2126.

PMID: 39818757 PMC: 11800186. DOI: 10.1021/acs.analchem.4c04911.

Recent Advances in Dielectrophoretic Manipulation and Separation of Microparticles and Biological Cells.

Yao J, Zhao K, Lou J, Zhang K Biosensors (Basel). 2024; 14(9).

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Acoustofluidic Actuation of Living Cells.

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Acoustic Enrichment of Heterogeneous Circulating Tumor Cells and Clusters from Metastatic Prostate Cancer Patients.

Magnusson C, Augustsson P, Undvall Anand E, Lenshof A, Josefsson A, Welen K Anal Chem. 2024; 96(18):6914-6921.

PMID: 38655666 PMC: 11079855. DOI: 10.1021/acs.analchem.3c05371.

The integrated on-chip isolation and detection of circulating tumour cells.

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