Biosensing by WGM Microspherical Resonators

Abstract

Whispering gallery mode (WGM) microresonators, thanks to their unique properties, have allowed researchers to achieve important results in both fundamental research and engineering applications. Among the various geometries, microspheres are the simplest 3D WGM resonators; the total optical loss in such resonators can be extremely low, and the resulting extraordinarily high Q values of 10⁸-10⁸ lead to high energy density, narrow resonant-wavelength lines and a lengthy cavity ringdown. They can also be coated in order to better control their properties or to increase their functionality. Their very high sensitivity to changes in the surrounding medium has been exploited for several sensing applications: protein adsorption, trace gas detection, impurity detection in liquids, structural health monitoring of composite materials, detection of electric fields, pressure sensing, and so on. In the present paper, after a general introduction to WGM resonators, attention is focused on spherical microresonators, either in bulk or in bubble format, to their fabrication, characterization and functionalization. The state of the art in the area of biosensing is presented, and the perspectives of further developments are discussed.

Keywords: biosensing; microresonator; microsphere; photonics; whispering gallery modes.

Figure 1

Experimental set-up for visualizing the directional emission of an asymmetric resonant cavity (ARC) in aqueous solution. (a) Setup components: 1. imaging system; 2. photodetector; 3. spatial filter; 4. rotation stage, with ARC and the chamber with GFP in PBS buffer; 5. 10× objective; 6. quarter-wave plate for polarization control; 7. fiber collimator; (b) Polar histogram of refractive escape for six-pole boundary ARC; (c) Ray-tracing simulation; (d) Real color image of directional emission by GFP fluorescence imaging of an ARC with a 63-$\mathsf{\mu }$m diameter. Reprinted with permission from [16].

Figure 2

(a) WGM supported on the total internal reflection of an optical wave; (b) Spherical coordinates in a WGM spherical resonator.

Figure 3

Scheme of a waveguide/fiber to microsphere coupling system: (a) lateral and (b) cross-sectional view. Reprinted with permission from [42].

Figure 4

Sketch of the two basic geometries for optically-integrated WGM sensors: (a) top view of a microring with two port waveguides: O, output port; I, input port; T, through port; (b) cross-section of a microdisk with vertical coupling with a buried waveguide (A Si₃N₄ layer, B SiO₂ layer); (c) cross-section of a microdisk with vertical coupling, non-buried waveguide.

Figure 5

Sketch of hybrid WGM sensors: (a) microsphere coupled with a waveguide; (b) LCORR-anti-resonant reflecting optical waveguides (ARROW) system and cross-section viewed from the LCORR (liquid core optical ring resonator) on top of an ARROW.

Figure 6

Sketch of a long period fiber grating (LPG) exciting the cladding mode followed by a ‘thick’ taper where coupling with the resonator takes place.

Figure 7

Chemical structures and abbreviations of the silanes mentioned in this review.

Figure 8

Functionalization of a WGMR for an aptasensor: after activation of the surface with piranha solution, silanization with 3-mercaptopropyltrimethoxysilane (MPTMS); and thiol bonding to the thrombin aptamer.

Figure 9

(a) Schematic WGMR transmission line shape before (blue) and after (red) a resonant shift; (b) Resonant shift versus time (sensorgram).

Figure 10

An experimental setup for WGMR biosensing, which includes the controls of the flow of water and analyte-containing solutions past the microsphere. Reprinted with permission from [141].

Figure 11

(A) Top view of some 500 barium-titanate (38 $\mathsf{\mu }$m in diameter) microspheres immersed in a 10-$\mathsf{\mu }$mL PBS droplet. (B) Sketch of the WGM droplet assay. The light from the excited resonators is imaged from below (4× objective) and detected by an APD. (C) In active mixing mode, a 125-$\mathsf{\mu }$m diameter glass rod is rotated at 5000 rpm in the PBS droplet. Reprinted with permission from [142].

Figure 12

Experimental setup of the WGM plasmon-enhanced biosensing platform. (a) A prism coupler is used to excite WGMs in a glass microsphere. The liquid sample cell is made in PDMS. The inset shows a plasmonic nanorod enabling detection of single oligonucleotides. (b) Photo of the spherical WGMR, with a diameter in the range of 60–100 $\mathsf{\mu }$m. (c) Example spectra for TE(black) and TM(red) polarization obtained with an ≈79 $\mathsf{\mu }$m microsphere in water, exhibiting typical experimental Q values around 5 × 10⁶. Reprinted with permission from [146].

Figure 13

Mosaic image taken by the Zeiss Axio Observer microscope following the sample scan along the microcapillary Z axis. The analysis reveals that the bubble fluorescence intensity is around three-fold higher than that of the microcapillary.