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

Analytical Chemistry
Cecilia MagnussonHans Lilja

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 eosinophi...Continue Reading

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Citations

Jun 25, 2019·Microsystems & Nanoengineering·Mengxi WuTony Jun Huang
Jun 17, 2020·Cytometry. Part a : the Journal of the International Society for Analytical Cytology·Franziska OlmStefan Scheding
Apr 27, 2021·Analytical Chemistry·Weifei ZhangJin-Ming Lin
Jul 10, 2021·The Journal of the Acoustical Society of America·William Naundrup Bodé, Henrik Bruus
Apr 30, 2020·Analytical Chemistry·Jiaxiang YinXingyu Jiang
Sep 11, 2021·Scientific Reports·Elnaz Attar Jannesar, Hossein Hamzehpour
Dec 17, 2021·Analytical Chemistry·Eva Undvall AnandThomas Laurell

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