Tracking the dynamics of circulating tumour cell phenotypes using nanoparticle-mediated magnetic ranking.

Profiling the heterogeneous phenotypes of rare circulating tumour cells (CTCs) in whole blood is critical to unravelling the complex and dynamic properties of these potential clinical markers. This task is challenging because these cells are present at parts per billion levels among normal blood cells. Here we report a new nanoparticle-enabled method for CTC characterization, called magnetic ranking cytometry, which profiles CTCs on the basis of their surface expression phenotype. We achieve this using a microfluidic chip that successfully processes whole blood samples. The approach classifies CTCs with single-cell resolution in accordance with their expression of phenotypic surface markers, which is read out using magnetic nanoparticles. We deploy this new technique to reveal the dynamic phenotypes of CTCs in unprocessed blood from mice as a function of tumour growth and aggressiveness. We also test magnetic ranking cytometry using blood samples collected from cancer patients.

[1]  A W Partin,et al.  Prognostic significance of Gleason score 3+4 versus Gleason score 4+3 tumor at radical prostatectomy. , 2000, Urology.

[2]  Paul H. Bessette,et al.  Marker-specific sorting of rare cells using dielectrophoresis. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[3]  S. Digumarthy,et al.  Isolation of rare circulating tumour cells in cancer patients by microchip technology , 2007, Nature.

[4]  B. Gillette.  Getting more for less , 2007 .

[5]  Paul I. Okagbare,et al.  Highly efficient circulating tumor cell isolation from whole blood and label-free enumeration using polymer-based microfluidics with an integrated conductivity sensor. , 2008, Journal of the American Chemical Society.

[6]  D. Radisky,et al.  Immune-induced epithelial to mesenchymal transition in vivo generates breast cancer stem cells. , 2009, Cancer research.

[7]  Mark M Davis,et al.  Isolating highly enriched populations of circulating epithelial cells and other rare cells from blood using a magnetic sweeper device , 2009, Proceedings of the National Academy of Sciences.

[8]  K. Isselbacher,et al.  Isolation of circulating tumor cells using a microvortex-generating herringbone-chip , 2010, Proceedings of the National Academy of Sciences.

[9]  Yi-Kuen Lee,et al.  Highly efficient capture of circulating tumor cells by using nanostructured silicon substrates with integrated chaotic micromixers. , 2011, Angewandte Chemie.

[10]  N. Normanno,et al.  Circulating tumour cells , 2011, Nature Reviews Cancer.

[11]  Ren Sun,et al.  Genetic analysis of H1N1 influenza virus from throat swab samples in a microfluidic system for point-of-care diagnostics. , 2011, Journal of the American Chemical Society.

[12]  R. Weinberg,et al.  A Perspective on Cancer Cell Metastasis , 2011, Science.

[13]  Daniel T Chiu,et al.  Sensitive and high-throughput isolation of rare cells from peripheral blood with ensemble-decision aliquot ranking. , 2012, Angewandte Chemie.

[14]  Cesar M. Castro,et al.  Ultrasensitive Clinical Enumeration of Rare Cells ex Vivo Using a Micro-Hall Detector , 2012, Science Translational Medicine.

[15]  Weian Zhao,et al.  Bioinspired multivalent DNA network for capture and release of cells , 2012, Proceedings of the National Academy of Sciences.

[16]  David J. Beebe,et al.  Circulating Tumor Cells: Getting More from Less , 2012, Science Translational Medicine.

[17]  E. Waller,et al.  Translational Applications of Flow Cytometry in Clinical Practice , 2012, The Journal of Immunology.

[18]  M. Tiwari,et al.  A novel 3D integrated platform for the high-resolution study of cell migration plasticity. , 2013, Macromolecular bioscience.

[19]  Sridhar Ramaswamy,et al.  Circulating Breast Tumor Cells Exhibit Dynamic Changes in Epithelial and Mesenchymal Composition , 2013, Science.

[20]  Mehmet Toner,et al.  Inertial Focusing for Tumor Antigen–Dependent and –Independent Sorting of Rare Circulating Tumor Cells , 2013, Science Translational Medicine.

[21]  Massimo Cristofanilli,et al.  Circulating Breast Tumor Cells Exhibit Dynamic Changes in Epithelial and Mesenchymal Composition , 2013 .

[22]  Mehmet Toner,et al.  Discontinuous nanoporous membranes reduce non-specific fouling for immunoaffinity cell capture. , 2013, Small.

[23]  K. Pantel,et al.  Challenges in circulating tumour cell research , 2014, Nature Reviews Cancer.

[24]  Adam H Mepham,et al.  Nanoparticle-mediated binning and profiling of heterogeneous circulating tumor cell subpopulations. , 2015, Angewandte Chemie.

[25]  Eugene J. Lim,et al.  Tunable Nanostructured Coating for the Capture and Selective Release of Viable Circulating Tumor Cells , 2015, Advanced materials.

[26]  John X. J. Zhang,et al.  Microscale Magnetic Field Modulation for Enhanced Capture and Distribution of Rare Circulating Tumor Cells , 2015, Scientific Reports.

[27]  Shana O Kelley,et al.  Beyond the Capture of Circulating Tumor Cells: Next-Generation Devices and Materials. , 2016, Angewandte Chemie.

[28]  John W. Park,et al.  Circulating Tumor Cells , 2017, Methods in Molecular Biology.