Abstract
The quantitative and qualitative analysis of circulating tumor cells (CTCs) has the potential to improve the clinical management of several cancers, including prostate cancer. As such, there is much interest in the isolation of CTCs from the peripheral blood of cancer patients. We report the design, fabrication, and proof-of-principle testing of an integrated permalloy-based microfluidic chip for immunomagnetic isolation of blood-borne prostate cancer cells using an antibody targeting prostate surface membrane antigen (PSMA). The preliminary results using spiked blood samples indicate that the proposed device is consistently capable of isolating prostate cancer cells with high sensitivity (up to 98 %) at clinically relevant low concentrations (down to 20 cells/mL) and an acceptable throughput (100 μL/min).
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References
C. Alix-Panabières, K. Pantel, Clin. Chem. 59(1), 110–118 (2013)
C. Alix-Panabières, K. Pantel, Nat. Rev. Cancer 14(9), 623–631 (2014)
E. Antonarakis et al., N. Engl. J. Med. 371, 1028–1038 (2014)
E. Antonarakis et al., JAMA Oncol. 1(5), 582–591 (2015)
K. Bouchelouche, P. Choyke, J. Capala, Discov Med. 9(44), 55–61 (2010)
T. Buchheit, S. Goods, P. Kotula, P. Hiava, Mater. Sci. Eng. A 432(1–2), 149–157 (2006)
C. Chaffer, R. Weinberg, Science 331(6024), 1559–1564 (2011)
S. Chang, Rev Urol. 6(10), S13–S18 (2004)
J. Chung, Development of a cell cross flow system (Victoria, BC, 2010)
J. de Bono et al., Clin. Cancer Res. 14(9), 6302–6309 (2008)
G. Deng et al., Breast Cancer Res. 10, R69 (2008)
D. Emerson, K. Cieślicki, R. Barber, Lab Chip 6(3), 447–454 (2006)
H. Esmaeilsabzali et al., Biotechnol. Adv. 31(7), 1063–1084 (2013)
J. Gleghorn et al., Lab Chip 10(1), 27–29 (2010)
T. Gorges et al., BMC Cancer. 12(178) (2012)
A. Grützkau, A. Radbruch, Cytometry A. 77, 643–647 (2010)
D. Haber, V. Velculescu, Cancer Discov. 4(6), 650–661 (2014)
G. Hatch, R. Stelter, J. Magn. Magn. Mater 225(1–2), 262–276 (2001)
J. Horoszewicz et al., Cancer Res. 43(4), 1809–1818 (1983)
K. Hoshino et al., Lab Chip 11, 3449–3457 (2011)
R. Kalluri, R. Weinberg, J. Clin. Invest. 119(6), 1420–1428 (2009)
N. Karabacak et al., Nat. Protoc. 9(3), 694–710 (2014)
S. Kim et al., Anal. Chem. 85(5), 2779–2786 (2013)
B. Kirby et al., PLoS One 7(4), e35976 (2012)
W. Liu et al., Lab Chip 9(16), 2381–2390 (2009)
H. Liu, P. Li, J. Van Lew, Int J Hydrogen Energ. 35(17), 9186–9198 (2010)
J. Luo et al., J. Electrochem. Soc. 152(1), C36–C41 (2005)
S. Maheswaran, D. Harber, Curr Opin Genet Dev. 20(1), 96–99 (2010)
K. McCloskey, J. Chalmers, M. Zborowski, Anal. Chem. 75(24), 6868–6874 (2003)
N. Pamme, Lab Chip 6(1), 24–38 (2005)
K. Pantel, M. Speicher, Oncogene (2015). doi:10.1038/onc.2015.192
B. Plouffe, S. Murthy, L. Lewis, Rep. Prog. Phys. 78(1), 016601 (2015)
A. Powell et al., PLoS ONE 7(5), e33788 (2012)
J. Ross et al., Clin. Cancer Res. 9(17), 6357–6362 (2003)
K. Sakaki et al., Biomed. Microdevices 11(6), 1317–1330 (2009)
C. Scheel, R. Weinberg, Semin. Cancer Biol. 22(5–6), 396–403 (2012)
J. Schenck, Prog. Biophys. Mol. Biol. 87(2–3), 185–204 (2005)
S. Sieben et al., J. Magn. Magn. Mater. 225(1), 175–179 (2001)
R. Siegel, K. Miller, A. Jemal, CA Cancer J Clin. 65(1), 5–29 (2015)
A. Singh, J. Settleman, Oncogene 29(34), 4741–4751 (2010)
A. Stroock et al., Science. 295(5555), 647–651 (2002)
D. Suzman, E. Antonarakis, Ther Adv Med Oncol. 6(4), 167–179 (2014)
A. Talasaz et al., Proc Natl Acad Sci U S A. 106(10), 3970–3975 (2009)
A. Tibbe, M. Miller, L. Terstappen, Cytometry A. 71(3), 154–162 (2007)
X. Wang, A. Mujumdar, C. Yap, J. Appl. Phys. 102(7) (2007)
G. Whitesides et al., Annu. Rev. Biomed. Eng. 3, 335–373 (2001)
A. Wognum, P. Lansdorp, S. T. Inc, Tetrameric antibody complexes for blocking non-specific labeling of antigens. Canada, Patent No. CA2411392 A1 (2003)
T. Yap, C. Swanton, C. J. de Bono, EPMA J. 3(1) (2012)
Acknowledgment
This work made use of the 4D LABS shared facilities supported by the Canada Foundation for Innovation (CFI), British Columbia Knowledge Development Fund (BCKDF), Western Economic Diversification Canada (WD), and Simon Fraser University (SFU). We would also like to acknowledge CMC Microsystems for the provision of products and services, including CAD and simulation tools, which facilitated this research. This work was supported in part by a Discovery Grant, RGPIN/298219-2012 (Park), from the Natural Science and Engineering Research Council of Canada (NSERC).
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All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted (Protocol#: 1056E-12, University Animal Care Committee, Simon Fraser University).
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The authors declare that they have no conflict of interest.
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Esmaeilsabzali, H., Beischlag, T.V., Cox, M.E. et al. An integrated microfluidic chip for immunomagnetic detection and isolation of rare prostate cancer cells from blood. Biomed Microdevices 18, 22 (2016). https://doi.org/10.1007/s10544-016-0041-7
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DOI: https://doi.org/10.1007/s10544-016-0041-7