Microfluidic, label-free enrichment of prostate cancer cells in blood based on acoustophoresis Journal Article


Authors: Augustsson, P.; Magnusson, C.; Nordin, M.; Lilja, H.; Laurell, T.
Article Title: Microfluidic, label-free enrichment of prostate cancer cells in blood based on acoustophoresis
Abstract: Circulating tumor cells (CTC) are shed in peripheral blood at advanced metastatic stages of solid cancers. Surface-marker-based detection of CTC predicts recurrence and survival in colorectal, breast, and prostate cancer. However, scarcity and variation in size, morphology, expression profile, and antigen exposure impairs reliable detection and characterization of CTC. We have developed a noncontact, label-free microfluidic acoustophoresis method to separate prostate cancer cells from white blood cells (WBC) through forces generated by ultrasonic resonances in microfluidic channels. Implementation of cell prealignment in a temperature-stabilized (±0.5 °C) acoustophoresis microchannel dramatically enhanced the discriminatory capacity and enabled the separation of 5 μm microspheres from 7 μm microspheres with 99% purity. Next, we determined the feasibility of employing label-free microfluidic acoustophoresis to discriminate and divert tumor cells from WBCs using erythrocyte-lysed blood from healthy volunteers spiked with tumor cells from three prostate cancer cell-lines (DU145, PC3, LNCaP). For cells fixed with paraformaldehyde, cancer cell recovery ranged from 93.6% to 97.9% with purity ranging from 97.4% to 98.4%. There was no detectable loss of cell viability or cell proliferation subsequent to the exposure of viable tumor cells to acoustophoresis. For nonfixed, viable cells, tumor cell recovery ranged from 72.5% to 93.9% with purity ranging from 79.6% to 99.7%. These data contribute proof-in-principle that label-free microfluidic acoustophoresis can be used to enrich both viable and fixed cancer cells from WBCs with very high recovery and purity. © 2012 American Chemical Society.
Keywords: methodology; cell proliferation; cytology; metabolism; cell viability; cell survival; cell line, tumor; tumor antigen; prostatic neoplasms; blood; antigens, neoplasm; instrumentation; neoplastic cells, circulating; tumors; prostate tumor; microfluidics; tumor cell line; cell adhesion molecules; temperature; molecular biology; cell separation; circulating tumor cells; leukocyte; tumor embolism; prostate cancers; diseases; cd45 antigen; cancer cells; acoustophoresis; separation; microfluidic analytical techniques; cell adhesion molecule; tumor cells; cells; recovery; antigens, cd45; leukocytes; peripheral blood; solid cancer; cell lines; microspheres; microfluidic analysis; expression profile; label free; microfluidic channel; non-contact; paraformaldehydes; pre-alignment; prostate cancer cells; reliable detection; ultrasonic resonances; viable cells; white blood cells; acetal resins; temperature control; ultrasonic applications; tumor associated antigen ga733; tumor-associated antigen ga733
Journal Title: Analytical Chemistry
Volume: 84
Issue: 18
ISSN: 0003-2700
Publisher: American Chemical Society  
Date Published: 2012-09-18
Start Page: 7954
End Page: 7962
Language: English
DOI: 10.1021/ac301723s
PROVIDER: scopus
PMCID: PMC3445767
PUBMED: 22897670
DOI/URL:
Notes: --- - "Export Date: 1 October 2012" - "CODEN: ANCHA" - "Source: Scopus"
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  1. Hans Gosta Lilja
    345 Lilja