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      Nanostructured Optical Photonic Crystal Biosensor for HIV Viral Load Measurement

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          Abstract

          Detecting and quantifying biomarkers and viruses in biological samples have broad applications in early disease diagnosis and treatment monitoring. We have demonstrated a label-free optical sensing mechanism using nanostructured photonic crystals (PC) to capture and quantify intact viruses (HIV-1) from biologically relevant samples. The nanostructured surface of the PC biosensor resonantly reflects a narrow wavelength band during illumination with a broadband light source. Surface-adsorbed biotarget induces a shift in the resonant Peak Wavelength Value (PWV) that is detectable with <10 pm wavelength resolution, enabling detection of both biomolecular layers and small number of viruses that sparsely populate the transducer surface. We have successfully captured and detected HIV-1 in serum and phosphate buffered saline (PBS) samples with viral loads ranging from 10 4 to 10 8 copies/mL. The surface density of immobilized biomolecular layers used in the sensor functionalization process, including 3-mercaptopropyltrimethoxysilane (3-MPS), N-gamma-Maleimidobutyryl-oxysuccinimide ester (GMBS), NeutrAvidin, anti-gp120, and bovine serum albumin (BSA) were also quantified by the PC biosensor.

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          Most cited references 40

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          Biosensing with plasmonic nanosensors.

          Recent developments have greatly improved the sensitivity of optical sensors based on metal nanoparticle arrays and single nanoparticles. We introduce the localized surface plasmon resonance (LSPR) sensor and describe how its exquisite sensitivity to size, shape and environment can be harnessed to detect molecular binding events and changes in molecular conformation. We then describe recent progress in three areas representing the most significant challenges: pushing sensitivity towards the single-molecule detection limit, combining LSPR with complementary molecular identification techniques such as surface-enhanced Raman spectroscopy, and practical development of sensors and instrumentation for routine use and high-throughput detection. This review highlights several exceptionally promising research directions and discusses how diverse applications of plasmonic nanoparticles can be integrated in the near future.
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            Chaotic mixer for microchannels.

            It is difficult to mix solutions in microchannels. Under typical operating conditions, flows in these channels are laminar-the spontaneous fluctuations of velocity that tend to homogenize fluids in turbulent flows are absent, and molecular diffusion across the channels is slow. We present a passive method for mixing streams of steady pressure-driven flows in microchannels at low Reynolds number. Using this method, the length of the channel required for mixing grows only logarithmically with the Péclet number, and hydrodynamic dispersion along the channel is reduced relative to that in a simple, smooth channel. This method uses bas-relief structures on the floor of the channel that are easily fabricated with commonly used methods of planar lithography.
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              Translating biomolecular recognition into nanomechanics.

              We report the specific transduction, via surface stress changes, of DNA hybridization and receptor-ligand binding into a direct nanomechanical response of microfabricated cantilevers. Cantilevers in an array were functionalized with a selection of biomolecules. The differential deflection of the cantilevers was found to provide a true molecular recognition signal despite large nonspecific responses of individual cantilevers. Hybridization of complementary oligonucleotides shows that a single base mismatch between two 12-mer oligonucleotides is clearly detectable. Similar experiments on protein A-immunoglobulin interactions demonstrate the wide-ranging applicability of nanomechanical transduction to detect biomolecular recognition.
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                Author and article information

                Journal
                Sci Rep
                Sci Rep
                Scientific Reports
                Nature Publishing Group
                2045-2322
                28 February 2014
                2014
                : 4
                Affiliations
                [1 ]Bio-Acoustic MEMS in Medicine (BAMM) Laboratory, Division of Biomedical Engineering, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School , Boston, MA, USA
                [2 ]Department of Electrical & Computer Engineering, and Department of Bioengineering, University of Illinois at Urbana-Champaign , IL, USA
                [3 ]Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School , MA, USA
                [4 ]Harvard-MIT Division of Health Sciences and Technology , Cambridge, MA, USA
                Author notes
                Article
                srep04116
                10.1038/srep04116
                3937800
                24576941
                Copyright © 2014, Macmillan Publishers Limited. All rights reserved

                This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported License. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/3.0/

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