Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2012 Jan 17;84(2):793-821.
doi: 10.1021/ac2029024. Epub 2011 Nov 23.

High-Q optical sensors for chemical and biological analysis

Matthew S Luchansky  1 , Ryan C Bailey
Affiliations
Review

High-Q optical sensors for chemical and biological analysis

Matthew S Luchansky et al. Anal Chem. .
No abstract available

PubMed Disclaimer

Figures

Figure 1
Figure 1
Whispering gallery mode (WGM) sensing. (A) For a non-planar WGM microsphere geometry, light is coupled into a spheroid-on-a-stem structure from an adjacent, carefully aligned optical fiber. Light from a tunable laser propagates by total internal reflection through the fiber, and coupling to the microsphere occurs at resonant wavelengths (Equation 1). A photodetector records the resonance wavelength as a dip in the transmission spectrum. Adapted with permission from ref . © 2008 National Academy of Sciences, U.S.A. (B) Planar WGM microrings can be fabricated in silicon-on-insulator, allowing straightforward coupling form a linear waveguide to the ring. Interaction of molecules with a microring (in this case proteins binding to a capture antibody) causes a change in the local refractive index. When the resonance condition is met, light (~1560 nm) is coupled from the linear waveguide into the microring and constructively interferes to set up a standing wave. Attenuations in the transmission spectrum collected at the output of the linear waveguide coincide with the resonance wavelength. Changes in refractive index shift the resonance wavelength, as depicted by the shift from the black to red transmission spectrum. Adapted from ref . © 2009 American Chemical Society.
Figure 2
Figure 2
High-Q geometries, as visualized by scanning electron microscopy. (A) Glass microsphere formed by heating a tapered optical fiber by Vollmer et al. Reproduced with permission from ref . © 2008 National Academy of Sciences, U.S.A. (B) Silica microtoroid fabricated by lithography, etching, and thermal reflow by Armani et al. Reproduced by permission from ref . © 2007 American Association for the Advancement of Science. (C) Silver-coated surface-plasmon-polariton WGM microdisk fabricated by Min et al. Reproduced by permission from ref . © 2009 Nature Publishing Group. (D) Silicon microring resonator inside lithographically defined annular opening in perfluoropolymer cladding by Luchansky et al. Reproduced by permission from ref . © 2010 Elsevier. (E) Liquid core optofluidic ring resonator fabricated from glass microcapillary by Zhu et al., with adjacent optical fiber taper for coupling. Adapted from ref . © 2007 American Chemical Society. (F) Hurricane microresonator device, showing association with gold nanoparticles by Koch et al. Reproduced by permission from ref . © 2010 Elsevier. (G) Coupling region of 140-µm slot microring resonator by Carlborg et al. Reproduced by permission from ref . © 2010 The Royal Society of Chemistry. (H) 1-D photonic crystals fabricated in silicon-on-oxide in a multiplexed geometry by Mandal et al. Reproduced by permission from ref . © 2009 The Royal Society of Chemistry. (I) Grating structure of TiO2/SiO2-coated replica-molded polymer photonic crystal by Huang et al. Adapted from ref . © 2011 American Chemical Society.
Figure 3
Figure 3
Surface functionalization methods for microring arrays. (A) Use of 6-channel PDMS microfluidics for differential capture antibody functionalization of 6 groups of 4 microrings each. Adapted from ref . © 2010 American Chemical Society. (B) Non-contact piezoelectric (inkjet) method for spotting of air-stable glycans on individual microrings. Fluorescently labeled streptavidin alignment calibration is shown here. Reproduced by permission from ref . © 2011 The Royal Society of Chemistry. (C) One-step self-assembly of a DNA-encoded antibody library (DEAL) on individual DNA-functionalized microrings. DNA can be spotted robustly on microrings and retains functionality when dried, allowing subsequent direction of antibody loading. Adapted from ref . © 2011 American Chemical Society.
Figure 4
Figure 4
Sensor characterization by evanescent field profiling. (A) Real-time plot showing the cumulative growth of 72 polyelectrolyte bilayers on a silicon microring. Inset shows sequential addition of 3 representative bilayers of polyallylamine HCl (PAH) and polystyrene sulfonate (PSS). The relative shift for each layer models the exponential decay of the evanescent field with increasing distance from the sensor surface, yielding a 1/e distance of 63 nm. (B) Protein multilayer growth plot displaying relative shift per biotin-antibody/streptavidin bilayer. After reaching a peak response of 250 pm at bilayer 8 as initial holes (incomplete surface coverage) of protein monolayer are annealed, subsequent layers show exponential signal decay as they are deposited farther from the ring surface. Error bars represent the standard deviation for n=4 rings. Reproduced by permission from ref . © 2010 Elsevier.
Figure 5
Figure 5
Strategies for increased specificity and signal enhancement. (A) A sandwich immunoassay for the cytokine interleukin-2 (IL-2) utilizes a secondary antibody for added specificity and to amplify the primary signal. The surface can be regenerated with a low-pH rinse. Adapted from ref . © 2010 American Chemical Society. (B) Similarly, the use of a secondary antibody specific for the DNA:RNA heteroduplex (S9.6) amplifies the signal associated with miRNA 24-1 binding. Adapted from ref . © 2011 American Chemical Society. (C) A tertiary enhancement step can be used to amplify the signal further. In this case, streptavidin-conjugated 100-nm beads bind to a biotinylated secondary antibody in a three-step assay for the cardiac biomarker C-reactive protein (CRP). A low CRP concentration (blue curve) that was difficult to quantitate with a sandwich assay becomes easily observable with bead-based signal enhancement. Adapted by permission from ref . © 2011 The Royal Society of Chemistry.
Figure 6
Figure 6
Photonic crystal enhanced microscopy (PCEM) for cellular attachment imaging. (A) By illuminating a photonic crystal surface from below with a laser that is scanned through a range of incident angles, a transmission spectrum is obtained for each 0.61-µm2 pixel to find the angle of minimum transmission (AMT). On-cell pixels have a reduced angle of minimum transmission relative to off-cell pixels. (B) Lidstone et al. use PCEM to image the attachment of hepatic carcinoma cells by mapping the AMT on a pixel-by-pixel basis with a CCD camera. (C) The morphology of cardiomyocte attachment visualized by a PCEM surface plot corresponds with optical microscopy observations (gray-scale inset). Adapted by permission from ref . © 2011 The Royal Society of Chemistry.
Figure 7
Figure 7
Multiplexing applications of high-Q sensors. (A) DNA-encoded antibody libraries allow for rapid, parallel capture agent affinity profiling on a microring resonator array platform. In this case, 6 anti-prostate specific antigen (PSA) antibodies are screened in parallel with a kinetic titration (PSA concentrations, in ng/mL, noted above arrows) to allow rational selection of the best antibodies from multiple vendors. Real-time analysis allows for the calculation of association and dissociation rates. Adapted from ref . © 2011 American Chemical Society. (B) Microring resonator sensor arrays also allow for multiplexed cytokine profiling for T cell differentiation analysis. Normalized cytokine secretion levels for three differentiated primary T cell subsets (Th0, Th1, and Th2) were determined by one-step sandwich immunoassays. Control cultures on the left are compared to PMA/ionomycin-stimulated (Stim) cultures on the right, with a comparison of secretion levels by a paired difference t-test (*/** indicate significance at 95%/99%). Adapted from ref . © 2011 American Chemical Society. (C) These 96-, 384-, and 1536-well photonic crystal microplates permit high-throughput screening assays. Reproduced by permission from ref . © 2011 The Royal Society of Chemistry. (D) As an example of multiplexing applications of photonic crystal microplates, a 384-well high-throughput screen of protein-protein modulators correctly reveals rapamycin as necessary for FRB binding to immobilized FKBP12. Among the 320 compounds screened, a large peak wavelength value (PWV) only occurs in the presence of rapamycin. Reproduced by permission from ref . © 2009 American Chemical Society.
Figure 8
Figure 8
Single nanoparticle detection and sizing. Zhu et al. utilize silicon microtoroids to detect and analyze single nanoparticles. (A) The fiber-coupled microtoroid and finite-element-method simulation of the WGM field profile in a toroidal cross-section are shown. (B) SEM allows for visualization of a 300-nm particle deposited on the high-Q resonator. Nanoparticle deposition causes scattering that breaks the symmetry in the microtoroid, lifting the degeneracy in the WGM modes that propagate in opposite directions in the toroid. (C) The resulting mode splitting doublet is the basis for single particle detection and sizing, and a representative transmission spectrum shows both symmetric (left) and asymmetric (right) modes. (D) Five transmission spectra show the splitting changes that accompany the deposition of successive KCl particles (zero to four particles, from top to bottom). Corresponding particle deposition images for particle counting are shown at the right. Reproduced by permission from ref . © 2010 Nature Publishing Group.
Figure 9
Figure 9
Optical trapping and manipulation of particles. (A) CCD images of a racetrack microring and its adjacent bus waveguide (a) show the optical switching process for 3-µm polystyrene particles. (b) Initially, a string of particles is trapped on the bus waveguide. (c) The trapped particles are diverted to the microring at the resonance wavelength. Optical switching can be performed by moving from on-resonance to off-resonance wavelengths. (d) At off-resonance wavelengths, already-trapped particles remain on the ring, but the next group of particles is not diverted to the ring. (e) More particles can be diverted onto the ring upon return to the resonance wavelength. Reproduced by permission from ref . © 2010 The Royal Society of Chemistry. (B) Similar experiments by Lin et al. were used to trap polystyrene particles on much smaller (5–10-µm) microrings. Particle velocities and revolution frequencies were measured for trapped particles recirculating the microring. (C) The cross-section of a 10-µm microring and its accompanying WGM intensity below a trapped microsphere is shown. 3D-finite-difference time-domain (FDTD) simulations of electromagnetic field strength (in A/m) were performed at 1 W input power in the waveguide. The FDTD simulations show that the intensity on top of the ring follows a Gaussian distribution. Sections B and C reproduced by permission from ref . © 2010 American Chemical Society.
Figure 10
Figure 10
Additional applications of high-Q devices: Compact silicon lasers and thermal imaging. (A) An electrically pumped microring resonator laser by Liang et al. is shown with an adjacent SOI bus waveguide, with the expanded view at right showing the fundamental transverse electrical mode localized toward the edge of the device. Stimulated emission is bidirectional. The inset at lower left is a cross-sectional SEM showing the metal layers and contacts. (B) Reduction of device diameter and improvements in facet reflectivity (R) will further reduce lasing thresholds, with 400 µA lasing threshold possible with a 4.5-µm device (red dot). The inset shows the top view of a 15-µm device. Sections A and B reproduced by permission from ref . © 2010 Nature Publishing Group. (C) Another interesting application of high-Q sensors is the creation of microphotonic thermal detectors. A representative silicon nitride resonator thermal detector device and adjacent waveguide is shown. (D) To demonstrate thermal sensitivity, the transmission through the adjacent waveguide is shown to vary with thermal fluctuations induced by a chopped CO2 laser signal. Sections C and D reproduced by permission from ref . © 2007 Nature Publishing Group.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. It is worth noting that label-free sensors often involve a specific capture agent such as an antibody, complementary DNA probe, or aptamer that causes the detection methodology to be no longer rigorously label-free. However, the biosensing community has firmly established the designation of “label-free” to include sensors that may require specific recognition elements but do not require fluorescent or enzymatic tags, and that broader definition of “label-free” will be used in this review.

    1. Vollmer F, Arnold S. Nat. Methods. 2008;5:591–596. - PubMed
    1. Luchansky MS, Washburn AL, Martin TA, Iqbal M, Gunn LC, Bailey RC. Biosens. Bioelectron. 2010;26:1283–1291. - PMC - PubMed
    1. Cunningham BT. JALA. 2010;15:120–135. - PMC - PubMed
    1. Qavi AJ, Washburn AL, Byeon J-Y, Bailey RC. Anal. Bioanal. Chem. 2009;394:121–135. - PMC - PubMed

Publication types