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WIREs Nanomed Nanobiotechnol
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Current trends in nanobiosensor technology

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Abstract The development of tools and processes used to fabricate, measure, and image nanoscale objects has lead to a wide range of work devoted to producing sensors that interact with extremely small numbers (or an extremely small concentration) of analyte molecules. These advances are particularly exciting in the context of biosensing, where the demands for low concentration detection and high specificity are great. Nanoscale biosensors, or nanobiosensors, provide researchers with an unprecedented level of sensitivity, often to the single molecule level. The use of biomolecule‐functionalized surfaces can dramatically boost the specificity of the detection system, but can also yield reproducibility problems and increased complexity. Several nanobiosensor architectures based on mechanical devices, optical resonators, functionalized nanoparticles, nanowires, nanotubes, and nanofibers have been demonstrated in the lab. As nanobiosensor technology becomes more refined and reliable, it is likely it will eventually make its way from the lab to the clinic, where future lab‐on‐a‐chip devices incorporating an array of nanobiosensors could be used for rapid screening of a wide variety of analytes at low cost using small samples of patient material. WIREs Nanomed Nanobiotechnol 2011 3 229–246 DOI: 10.1002/wnan.136 This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > Diagnostic Nanodevices Diagnostic Tools > In Vitro Nanoparticle-Based Sensing

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Illustration of several mechanical device configurations. (a) A resonating mechanical device (cantilever) that indicates a change in resonator mass (due to bound analyte) by a shift in resonant frequency. (b) A static deflection device formed from two materials with different thermal expansion coefficients that bends due to a change in temperature. (c and d) Static deflection devices that bend due to analyte binding causing a surface stress. (Reprinted with permission from Ref 51. Copyright 2008 The Royal Society of Chemistry)

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(a) Diagram illustrating binding of streptavidin to a biotin‐functionalized CNT sensor. (b) Frequency shift of a quartz crystal microbalance mass sensor as streptavidin solution is introduced to the functionalized nanobiosensor. Note that the response is specific to the streptavidin solution; negligible response is seen with solutions of other biomolecules. (c) Electrical response of the CNT‐based nanobiosensor as streptavidin solution is introduced at increasing concentrations. Again, the response is specific to streptavidin. (Reprinted with permission from Ref 154. Copyright 2003 National Academy of Sciences)

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(a) Optical microscopy image of a metal electrode array used as interface to nanowire biosensors (field of view is 350 × 400 µm). (b) An individual silicon nanowire bridging two electrodes (scale bar is 2 µm). (Reprinted with permission from Ref 142. Copyright 2005 Macmillan Publishers Ltd)

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Illustration showing DNA‐functionalized Au nanoparticles aggregating upon hybridization with complementary strands. (Reprinted with permission from Ref 116. Copyright 2006 Wiley‐VCH Verlag GmbH & Co. KGaA)

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Illustration of a LCORR sensing system. (a) Illustration of a potential method to multiplex multiple LCORRs using a single laser (to excite multiple cavities) and multiple detectors. (b) Illustration of a laser coupled to an optical resonator cavity formed by the wall of a glass capillary. (Reprinted with permission from Ref 89. Copyright 2006 Optical Society of America)

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Illustration of a WGM biosensor. (a) Light is coupled into a microsphere evanescently via a tapered optical fiber. Certain wavelengths of light will resonate in the cavity, causing dips in transmission through the optical fiber at those wavelengths. (b) Binding of molecules on the cavity surface will cause a shift in the resonant frequency spectrum of the cavity, and thus the resonant frequency dips monitored at the detector will shift. (c) As more analyte binds to the surface, this resonant frequency shift will increase. (Reprinted with permission from Ref 82. Copyright 2008 Macmillan Publishers Ltd)

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(a) Illustration of a mechanical cantilever resonator containing an embedded microfluidic channel. (b) Illustration showing a decrease in resonant frequency as the density inside the embedded channel increases. If molecules that selectively bind to the channel walls are present, they will accumulate in the channel, causing an increased density in the channel that can be detected as a frequency shift. (c) If a single particle is cycled through the channel, it will cause a frequency shift that varies with the particle's position along the cantilever. This allows the measurement of the mass of single, isolated, unbound particles in solution. (Reprinted with permission from Ref 72. Copyright 2007 Macmillan Publishers Ltd)

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Frequency shifts of a NEMS resonator due to binding of AcV1 antibody (green) and baculovirus particles (red). (Reprinted with permission from Ref 58. Copyright 2004 American Institute of Physics)

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Diagnostic Tools > Diagnostic Nanodevices
Diagnostic Tools > In Vitro Nanoparticle-Based Sensing
Diagnostic Tools > Biosensing

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