Digital Detection of Nanoparticles: Viral Diagnostics and Multiplexed Protein and Nucleic Acid Assays
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Digital Detection of Nanoparticles: Viral Diagnostics and Multiplexed Protein and Nucleic Acid Assays M. S. Ünlü Boston University, Department of Electrical and Computer Engineering, Department of Biomedical Engineering and Photonics Center Boston, MA 02215, U.S.A. ABSTRACT Synthetic nanoparticles have made significant impact across a broad range of technological applications including optical nanoantennas, ultra-sensitive imaging and sensing, and diagnostics and therapeutics. Natural nanoparticles such as viruses and pollutants are major concerns for human health. High-throughput characterization of nanoparticles in terms of their size and shape is crucial for practical applications of synthetic nanoparticles and highly sensitive pathogen identification. Recently, we have demonstrated Interferometric Reflectance Imaging Sensor (IRIS) with the ability to detect single nanoscale particles [1,2]. In single-particle modality of IRIS (SP-IRIS), the interference of light reflected from the sensor surface is modified by the presence of particles producing a distinct signal that reveals the size of the particle. In our approach, the dielectric layered structure acts as an optical antenna optimizing the elastic scattering characteristics of nanoparticles for sensitive detection and analysis. We have demonstrated identification of virus particles in complex samples for various viruses in multiplexed format. Size discrimination of the imaged nanoparticles (virions) allows differentiation between modified viruses having different genome lengths and facilitates a reduction in the counting of non-specifically bound particles to achieve a limit-of-detection (LOD) of 5x103 pfu/mL for the Ebola and Marburg VSV pseudotypes. We have demonstrated the simultaneous detection of multiple viruses in serum or whole blood as well as in samples contaminated with high levels of bacteria [3]. Single nanoparticle detection with IRIS has shown promising results for protein [4] and DNA arrays with attomolar detection sensitivity. INTRODUCTION Sensitive and specific detection at the single particle limit has crucial importance for understanding and preventing the negative consequences of the nanoparticles as well as developing devices for diagnostic and therapeutic applications. Over the last decade, various technologies have been developed for single nanoparticle characterization [2, 5-7]. Challenges remain for developing a practical detection and characterization tool with the capability of rapidly analyzing complex samples with particles with different sizes, shapes and chemical constituents. We have demonstrated the use of optical interference on a thin dielectric film for single particle detection. The idea of thin film interference has been studied since 19th century [8] and applied to biochemical sensors more than 20 years ago [9]. We have developed the concept of Interferometric Reflectance Imaging Sensor (IRIS) [10,11] for multiplexed biodetection using functionalized immunocapture surfaces on reflecting substrates with thin dielectric la
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