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A mesofluidic multiplex immunosensor for detection of circulating cytokeratin-positive cells in the blood of breast cancer patients

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Abstract

We have recently reported the analytical performance of an immunosensor comprising one mm-scale parallel plate laminar flow chamber and applied to capture MCF7 breast cancer cells (Ehrhart et al., Biosens. Bioelectr. 24, 467, 2008). Herein we present a new multiplex immunosensor embodying four parallel plate laminar flow chambers that fit onto a standard, functionalized, microscopy glass slide. The four surfaces are coated with long alkyl chain spacers of 21-aminohenicosyl trichlorosilane (AHTS) and then grafted with a monoclonal anti-human epithelial cell adhesion molecule (EpCAM) antibody specific of target cells to immobilize. We first demonstrate a significantly (P < 0.01) improved capacity of each of the four flow chambers of the multiplex immunosensor to capture MCF7 cells compared to the previous single chamber device. Second, in addition to an increase of cell immobilization, the multiplex device offers a versatile tool easily grafted with various purified antibodies onto the four surfaces. Third, we obtained high cell capture rate and efficiency of various numbers of MCF7 cells spiked in buffer containing an equal number of background leukocytes. And fourth, we demonstrate isolation efficiency of circulating tumor cells (CTCs) from peripheral blood drawn from a small cohort of patients with localized or metastatic breast cancer. This new multiplex immunosensor could be tested for its potential to capture different subpopulations of CTCs.

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Acknowledgements

The authors thank Pr. Joseph Zyss, head of the Institut d’Alembert, for supporting this project, Julie Morisot for technical assistance and Dr Helise Stabile for initiating automated image acquisition. They also thank the laboratory SATIE UMR 8029 CNRS (Systèmes et Applications des Technologies de l’Information et de l’Energie) for providing computing means. This study was supported by the Agence Nationale de la Recherche (grant #ANR-EMPB CAPCELL 2006-06).

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Authors and Affiliations

  1. CyToCap, ENS Cachan—Institut d’Alembert, 61 Avenue du Président Wilson, 94235, Cachan cedex, France

    François Breton & Phuong-Lan Tran

  2. Institut des Sciences Moléculaires, UMR 5255 CNRS, Université Bordeaux 1, 33405, Talence cedex, France

    Bernard Bennetau & Laurent Thomas

  3. INSERM U735, Génétique Moléculaire des cancers d’origine épithéliale, Centre René Huguenin, 92210, Saint-Cloud, France

    Rosette Lidereau

  4. UMR 8006 CNRS, Procédés et Ingénierie en Mécanique et Matériaux, Arts et Métiers ParisTech, 151 boulevard de l’hôpital, 75013, Paris, France

    Gilles Regnier

  5. UMR 8200 CNRS, Stabilité génétique et Oncogenèse, Institut Gustave Roussy, Université Paris-Sud 11, 94805, Villejuif cedex, France

    Jean-Claude Ehrhart

  6. UMR 8113 CNRS, Biotechnologie et Pharmacologie appliquée, ENS Cachan—Institut d’Alembert, 94235, Cachan cedex, France

    Patrick Tauc

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  1. François Breton
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  2. Bernard Bennetau
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Correspondence to Phuong-Lan Tran.

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Breton, F., Bennetau, B., Lidereau, R. et al. A mesofluidic multiplex immunosensor for detection of circulating cytokeratin-positive cells in the blood of breast cancer patients. Biomed Microdevices 13, 1–9 (2011). https://doi.org/10.1007/s10544-010-9465-7

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