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Magneto-plasmonic Nanoparticle Platform for Capture, Separation and Enumeration of Rare Cells
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Detection of disseminated tumor cells or tumor biomarkers in human fluids such as blood, urine, and saliva can provide an accessible tool for cancer detection and therapy monitoring. In particular, accurate quantitation of cancer cells in the bloodstream can help to determine prognosis and monitor the effectiveness of cancer therapy. However, the challenge of detecting circulating tumor cells (CTCs) is their rare occurrence, estimated as one to few CTCs among millions of leukocytes and billions of erythrocytes. Here we address this challenging problem by developing nanoparticle probes with multiple functionalities. Integration of multiple components in a single nanostructure is a challenging task. Most of the existing approaches to synthesis of hybrid nanoparticles require cumbersome multi-step protocols and result in nanostructures with limited tunability of physical and optical properties. Here, we developed a new type of nanoparticles which consist of primary 6 nm iron oxide core-gold shell nanoparticles that form highly uniform spherical assemblies with sizes that can be varied from ca. 70 to 180 nm. The magneto-plasmonic nanoclusters exhibit strong red-NIR absorbance and superparamagnetic properties with a high magnetic moment in an external magnetic field. We conjugated the nanoclusters with monoclonal antibodies specific for tumor biomarkers of breast, colon and skin cancers and demonstrated molecular specific optical and photoacoustic (PA) imaging with high sensitivity. We carried out experiments in whole blood from a normal volunteer spiked with various amounts of cancer cells. It was shown that cell capture efficiency exhibits a linear behavior from 5 to 500 cells per 2.5 mL of the whole blood. Furthermore, we demonstrated that molecular targeted nanoclusters can be used for simultaneous magnetic capture and PA detection of cancer cells in whole blood with greater than 90% capturing efficiency with no laborious processing steps that are commonly used in other cancer cell capture and enumeration assays. The magneto-plasmonic nanoparticle platform is being tested in blood samples of cancer patients with metastatic disease with a very good capture efficiency as compared to FDA approved CellSearch system. Our immunotargeted nanoparticles can be easily adapted to a variety of biomarkers, targeting both surface receptor molecules and intracellular biomarkers of epithelialderived cancer cells. In this presentation we will explore the opportunities afforded by the hybrid magneto-plasmonic nanoparticles and PA imaging for the development of a low cost simple and nearly real-time assays for capture, separation and enumeration of rare cells.

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