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WIREs Nanomed Nanobiotechnol
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Using nanoparticles to push the limits of detection

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Abstract The size‐dependent chemical and physical properties of nanoparticles inspire the design of unique assays and the use of new detection schemes while also offering the opportunity to vastly improve the results achieved when using traditional signal transduction methods. Herein, the most commonly exploited nanoparticle amplification schemes are organized and reviewed on the basis of the detection methods used to monitor the nanoparticle property of interest. The topics covered include the improved signal photostability and brightness of semiconductor quantum dots, the increased extinction coefficient of noble metal nanoparticles, the advantages of having a magnetic label on individual target molecules to facilitate separation, the multiplexing that is enabled with ‘barcoded’ nanoparticles, and the greatly amplified signals that can be achieved on the basis of conductivity changes, generated current, or simply by adding a ‘massive’ nanoparticle onto a small molecule target. Common approaches emerge among different nanoparticle materials and detection schemes, and it is also clear that there is still significant opportunity to use nanoparticles in as‐yet‐unimagined ways to further improve assay and sensor limits of detection Copyright © 2009 John Wiley & Sons, Inc. This article is categorized under: Nanotechnology Approaches to Biology > Cells at the Nanoscale

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Figure showing the localization of PEG‐g‐PEI coated QDs with (a) longer and (b) shorter PEG chain lengths. (Reprinted, with permission, from Ref. 5. Copyright 2007 American Chemical Society.).

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(a) Schematic representation of the sandwich hybridization that occurs between two sets of probe DNA and target DNA, resulting in the aggregation of the nanoparticles. (b) AFM images of nanoparticle aggregates induced by the addition of target DNA at various concentrations; a: 10 nM (91.3 ± 6.6 nm), b: 1 nM (86.8 ± 3.9 nm), c: 100 pM (80.6 ± 3.1 nm), and d: 10 pM (75.0 ± 4.3 nm). The particle size increases with the concentration of target DNA. Scale bar: 1µm. (Reprinted, with permission, from Ref. 66. Copyright 2006 Springer.).

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(a) Schematic representation of SECM imaging of DNA hybridization on a microarray. The attachment of the streptavidin–gold nanoparticles and the silver precipitation at a spot where hybridization has occurred results in an SECM positive feedback. The gray circles represent biotin molecules, whereas the ovals and the empty circles are the streptavidin molecules and the gold nanoparticles, respectively. The silver particles deposited onto the streptavidin–gold nanoparticle conjugates are shown by the filled circles. (b) A SECM image of six spots of the same probe on a microarray surface. (Reprinted, with permission, from Ref. 53. Copyright 2001 American Chemical Society.).

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Scheme depicting the analytical procedure for using the Pt‐NPs in the analysis of (a) DNA and (b) thrombin. (Reprinted, with permission, from Ref. 51. Copyright 2005 American Chemical Society.).

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Multitarget electrical DNA detection protocol based on different inorganic colloid nanocrystal tracers. (a) Introduction of probe‐modified magnetic beads. (b) Hybridization with the DNA targets. (c) Second hybridization with the QD‐labeled probes. (d) Dissolution of QDs and electrochemical detection. (Reprinted, with permission, from Ref. 44. Copyright 2003 American Chemical Society.).

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Scheme showing concept behind electrical detection of DNA. (Reprinted, with permission, from Ref. 29. Copyright 2006 AAAS.).

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Reflectance (a) and fluorescence (b) images of striped nanobarcodes with five different patterns. On the basis of selective labeling, only three nanobarcode populations are visible in the fluorescence image. (Reprinted, with permission, from Ref. 19. Copyright 2003 Springer.).

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Fe3O4 nanoparticle size effects on magnetic behavior. (a) TEM images of nanoparticles, (b) and (c) size‐dependent T2 characteristics, (d) T2 values as a function of size, and (e) magnetization as a function of size. (Reprinted, with permission, from Ref. 14. Copyright 2005 American Chemical Society.).

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Scheme showing the stepwise extraction of different cell populations using magnetic nanoparticles. (Reprinted, with permission, from Ref. 12. Copyright 2007 American Chemical Society.).

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