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Microfluidic, Label-Free Enrichment of Prostate Cancer Cells in Blood Based on Acoustophoresis

Augustsson, Per LU ; Magnusson, Cecilia LU ; Nordin, Maria LU ; Lilja, Hans LU and Laurell, Thomas LU (2012) In Analytical Chemistry 84(18). p.7954-7962
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Analytical Chemistry
volume
84
issue
18
pages
7954 - 7962
publisher
The American Chemical Society
external identifiers
  • wos:000308829700054
  • pmid:22897670
  • scopus:84866391645
ISSN
1520-6882
DOI
10.1021/ac301723s
language
English
LU publication?
yes
id
d2024168-cdd6-4142-9a3c-8a1a3a6c7634 (old id 4145520)
date added to LUP
2013-11-07 09:13:06
date last changed
2017-10-22 04:51:13
@article{d2024168-cdd6-4142-9a3c-8a1a3a6c7634,
  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.},
  author       = {Augustsson, Per and Magnusson, Cecilia and Nordin, Maria and Lilja, Hans and Laurell, Thomas},
  issn         = {1520-6882},
  language     = {eng},
  number       = {18},
  pages        = {7954--7962},
  publisher    = {The American Chemical Society},
  series       = {Analytical Chemistry},
  title        = {Microfluidic, Label-Free Enrichment of Prostate Cancer Cells in Blood Based on Acoustophoresis},
  url          = {http://dx.doi.org/10.1021/ac301723s},
  volume       = {84},
  year         = {2012},
}