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Integrated sorting and detection of circulating tumor cells in blood using microfluidic cell sorting and surface plasmon resonance

Published online by Cambridge University Press:  16 December 2014

Joshua S. Holt ,
Alvaro Mendoza ,
David Lawrence  and
Nathaniel C. Cady
Joshua S. Holt
Affiliation:
SUNY College of Nanoscale Science & Engineering Albany, NY 12203, U.S.A.
Alvaro Mendoza
Affiliation:
Wadsworth Center, NYS Dept. of Health Albany, NY 12201, U.S.A.
David Lawrence
Affiliation:
Wadsworth Center, NYS Dept. of Health Albany, NY 12201, U.S.A.
Nathaniel C. Cady
Affiliation:
SUNY College of Nanoscale Science & Engineering Albany, NY 12203, U.S.A.
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Abstract

Metastatic tumors can spread via release of circulating tumor cells (CTCs) into the bloodstream. Early detection of these CTCs could greatly improve cancer survival rates by enabling diagnosis, and therefore treatment, before secondary tumors arise. However, tumor cells are typically present in very low concentrations, making them difficult to detect in a fluid dominated by red blood cells (RBCs), leukocytes and serum proteins. Separation of CTCs from blood plasma, leukocytes and RBCs is predicted to improve cell capture via antibody-based methods and reduce interference in capture/detection assays. Previously, members of our team have demonstrated microfluidic, size-based separation of blood components, but have yet to integrate this sorting capability with an affinity-based detection technology. To this end, we have developed a microfluidic platform to separate CTCs from mouse blood and detect them using grating coupled surface plasmon resonance (GCSPR). We have implemented a size-based sorting array, which separates objects based upon their diameter, within a microfluidic channel. Separation of beads (2 μm, 6 μm, 10 μm) has been demonstrated, as well as separation of white blood cells and CTCs from blood. The resulting stream of large blood cells (including CTCs) is then directed onto an integrated SPR grating for affinity based capture and detection. Using GCSPR vs. conventional SPR enables detection of multiple cell types across the grating in an array-based format. We have demonstrated differential capture and detection of cells on GCSPR gratings following size-based separation of blood. Using capture antibodies specific to unique CTC surface proteins enables identification of cell types and may provide prognostic capability, beyond the diagnostic capacity of this system.

Keywords

sensorfluidicsbiomedical
Type
Articles
Information
MRS Online Proceedings Library (OPL) , Volume 1686: Micro- and Nanofluidic Systems for Materials Synthesis, Device Assembly and Bioanalysis , 2014 , mrss14-1686-v09-02
Copyright
Copyright © Materials Research Society 2014 

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References

REFERENCES

Alemar, J., & Schuur, E. R. (2013). Progress in using circulating tumor cell information to improve metastatic breast cancer therapy. Journal of oncology, 2013, 702732. doi:10.1155/2013/702732 CrossRefGoogle ScholarPubMed
Davis, J. a, Inglis, D. W., Morton, K. J., Lawrence, D. a, Huang, L. R., Chou, S. Y., … Austin, R. H. (2006). Deterministic hydrodynamics: taking blood apart. Proceedings of the National Academy of Sciences of the United States of America, 103(40), 14779–84. doi:10.1073/pnas.0605967103 Google Scholar
Lanza, D., Ma, J., Guest, I., Uk-Lim, C., Glinskii, A., Glinskii, G., & Sell, S. (2012). Tumor-derived mesenchymal stem cells and orthotopic site increase the tumor initiation potential of putative mouse mammary cancer stem cells derived from MMTV-PyMT mice. Tumour Biology, 33(6), 1997–2005.10.1007/s13277-012-0459-3CrossRefGoogle ScholarPubMed
Lianidou, E. S., & Markou, A. (2011). Circulating tumor cells in breast cancer: detection systems, molecular characterization, and future challenges. Clinical chemistry, 57(9), 1242–55. doi:10.1373/clinchem.2011.165068 CrossRefGoogle ScholarPubMed
Lin, H. K., Zheng, S., Williams, A. J., Balic, M., Groshen, S., Scher, H. I., … Cote, R. J. (2010). Portable filter-based microdevice for detection and characterization of circulating tumor cells. Clinical cancer research : an official journal of the American Association for Cancer Research, 16(20), 5011–8. doi:10.1158/1078-0432.CCR-10-1105 CrossRefGoogle ScholarPubMed
Ma, J., Lanza, D., Guest, I., Uk-Lim, C., Glinskii, A., Glinskii, G., & Sell, S. (2012). Characterization of mammary cancer stem cells in the MMTV-PyMT mouse model. Tumour Biology, 33(6), 1983–1996.10.1007/s13277-012-0458-4CrossRefGoogle ScholarPubMed
Mosier, A. P., Kaloyeros, A. E., & Cady, N. C. (2012). A novel microfluidic device for the in situ optical and mechanical analysis of bacterial biofilms. Journal of microbiological methods, 91(1), 198–204. doi:10.1016/j.mimet.2012.07.006 CrossRefGoogle ScholarPubMed
Rice, J. M., Stern, L. J., Guignon, E. F., Lawrence, D. a, & Lynes, M. a. (2012). Antigen-specific T cell phenotyping microarrays using grating coupled surface plasmon resonance imaging and surface plasmon coupled emission. Biosensors & bioelectronics, 31(1), 264–9. doi:10.1016/j.bios.2011.10.029 CrossRefGoogle ScholarPubMed