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WIREs Nanomed Nanobiotechnol
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Plasmonic biosensors

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The unique optical properties of plasmon resonant nanostructures enable exploration of nanoscale environments using relatively simple optical characterization techniques. For this reason, the field of plasmonics continues to garner the attention of the biosensing community. Biosensors based on propagating surface plasmon resonances (SPRs) in films are the most well‐recognized plasmonic biosensors, but there is great potential for the new, developing technologies to surpass the robustness and popularity of film‐based SPR sensing. This review surveys the current plasmonic biosensor landscape with emphasis on the basic operating principles of each plasmonic sensing technique and the practical considerations when developing a sensing platform with the various techniques. The ‘gold standard’ film SPR technique is reviewed briefly, but special emphasis is devoted to the up‐and‐coming localized surface plasmon resonance and plasmonically coupled sensor technology. WIREs Nanomed Nanobiotechnol 2015, 7:152–168. doi: 10.1002/wnan.1314 This article is categorized under: Diagnostic Tools > Biosensing Diagnostic Tools > Diagnostic Nanodevices
A surface plasmon resonance (SPR) can be excited in thin gold film using the Kretschmann configuration (a, S: Source, D: Detector) and detected as a sharp decrease in the intensity of the reflected beam occurring at the SPR angle or wavelength (b). Film SPR is often used to study biomolecular interactions (c). Target analyte binding by the film‐immobilized receptors is detected by a shift in the film SPR. This SPR shift can be monitored over time as target analyte is introduced into the flow cell and then washed away. Kinetic parameters describing the molecular interaction can be calculated from the resulting SPR sensorgram (d). (Reprinted with permission from Ref . Copyright 2000 Elsevier)
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Gold nanoparticles (NPs) in close proximity to gold film create localized regions of field enhancement that can be used for stimulated surface enhanced resonance Raman scattering (SERRS, a). The NP‐film SERRS hot spots are generated with 100% yield, as is indicated by the fact that each NP in the laser scatter image (b) also appears in the SERRS image (c). A SERRS spectrum with characteristic peaks from a Raman reporter molecule can be collected from each film‐coupled NP (d). (Reprinted with permission from Ref . Copyright 2010 ACS)
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A gold nanoparticle (NP) can become plasmonically coupled to nearby gold film, which can be conceptualized optically by the formation of a virtual NP dimer with one half of the dimer being an effective mirror image of the real NP above the film (a). Molecular spacer layers (b) are used to control the nanoscale separation distance between the NPs and film. As the NP‐film separation distance increases a blue shift in the film‐coupled NP localized surface plasmon resonance (LSPR) occurs, which is characteristic of a plasmon ruler (c, d). NP‐film plasmon rulers are created efficiently with 100% yield (e, f), and so it is possible to create a high density of plasmon rulers over a large surface area (g, h) for characterization with ensemble spectroscopic measurements. (Reprinted with permission from Refs . Copyright 2012, 2008, 2010, 2012 ACS)
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A plasmonically coupled nanoparticle (NP) dimer designed to detect DNA is depicted in (a). When target DNA is present the separation distance between the NPs increases and produces a blue shift in the coupled localized surface plasmon resonance of the NP dimer (b). The NP dimer in the inset dark field images (b) is indicated by an arrow. (Reprinted with permission from Ref . Copyright 2013 Wiley)
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Plasmonic nanopores (a) exhibit extraordinary optical transmission (EOT) when illuminated collinearly due to excited plasmonic modes defined by the grating order of the nanopore array. A handheld miniature nanopore array sensing device is shown in (b and c). An example of nanopore sensing in shown in (d–f) where the presence of a virus (red plot) is detected by a shift in the wavelength of the EOT from a nanopore sensing array containing antibodies targeting the virus (blue plot). (a–c) (Reprinted with permission from Ref . Copyright 2014 NPG) (d–f) (Reprinted with permission from Ref . Copyright 2010 ACS)
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A lateral flow assay using colloidal gold for colorimetric, visual detection is depicted in (a, C: Control, T: Test). The assay demonstrated a qualitative increase in signal in the Test region with increasing target concentration (b). (Reprinted with permission from Ref . Copyright 2010 Elsevier)
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A transmitted localized surface plasmon spectroscopy (T‐LSPR) measurement is depicted in (a, S: Source, D: Detector) as an extinction measurement, where the collective LSPR of an ensemble of plasmon resonant nanoparticles (NPs) immobilized on a transparent substrate is measured using a spectrophotometer and a collinear optical path. The photo in (b) shows a visual representation of a simple T‐LSPR experiment. Glass slides with immobilized gold nanoisland films show drastic color changes with annealing of the gold coating and addition of polymer layers to the nanoislands. (Reprinted with permission from Ref . Copyright 2014 ACS). A multiplexed T‐LSPR device is shown in (c) that contains microchannels for delivery of solutions to separate T‐LSPR sensing arrays. (Reprinted with permission from Ref . Copyright 2014 ACS)
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Localized surface plasmon resonances (LSPRs) from plasmon resonant nanoparticles (NPs) are sensitive to the refractive index of their surroundings. A plasmon resonant NP functionalized with receptor molecules will display a red shift in the scattering spectrum of its LSPR as it binds target analyte.
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Single nanoparticles (NPs) can be spectroscopically characterized using a dark field microscope (a). The localized surface plasmon resonance (LSPR) of a NP shifts when protein attaches to the surface of the NP (b). This LSPR shift was tracked over time to reveal step‐wise attachment of single proteins to the NP being analyzed (c, d). (Reprinted with permission from Ref . Copyright 2012 ACS)
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