ABSTRACT
Interactions between whispering gallery modes (WGMs) and small nanoparticles are commonly modeled by treating the particle as a point dipole scatterer. This approach is assumed to be accurate as long as the nanoparticle radius, a, is small compared to the WGM wavelength λ. In this Letter, however, we show that the large field gradients associated with the evanescent decay of a WGM causes the dipole theory to significantly underestimate the interaction strength and, hence, the induced WGM resonance shift, even for particles as small as aâ¼λ/10. To mitigate this issue, we employ a renormalized Born approximation to more accurately determine nanoparticle-induced resonance shifts and, hence, enable improved particle sizing. The domain of validity of this approximation is investigated, and supporting experimental results are presented.
ABSTRACT
Recently we reported the detection and sizing of the smallest RNA virus MS2 with a mass of 6 ag from the resonance frequency shift of a whispering gallery mode-nanoshell hybrid resonator (WGM-h) upon adsorption on the nanoshell and anticipated that single protein above 0.4 ag should be detectable but with considerably smaller signals. Here, we report the detection of single thyroid cancer marker (Thyroglobulin, Tg) and bovine serum albumin (BSA) proteins with masses of only 1 ag and 0.11 ag (66 kDa), respectively. However, the wavelength shifts are enhanced beyond those anticipated in our earlier work by 240% for Tg and 1500% for BSA. This surprising sensitivity is traced to a short-range reactive field near the surface of our Au nanoshell receptor due to intrinsic random bumps of protein size, leading to an unanticipated increase in sensitivity to single protein, which grows larger as the protein diminishes in size. As a consequence of the largest signal-to-noise ratio in our BSA experiments (S/N ≈ 13), we conservatively estimated a new protein limit of detection for our WGM-h of 5 kDa.
Subject(s)
Gold/chemistry , Metal Nanoparticles/chemistry , Microchemistry/instrumentation , Protein Array Analysis/instrumentation , Proteins/analysis , Proteins/chemistry , Surface Plasmon Resonance/instrumentation , Equipment Design , Equipment Failure Analysis , Miniaturization , Staining and Labeling , Systems IntegrationABSTRACT
The state of adsorbed protein molecules can be examined by comparing the shifts in a narrow line resonance wavelength of transverse electric (TE) and transverse magnetic (TM) whispering gallery modes (WGM) when the molecules adsorb onto a transparent microsphere that houses WGM. In adsorption of bovine serum albumin (BSA) onto an aminopropyl-modified silica microsphere, the TM/TE shift ratio indicated highly anisotropic polarizability of BSA in the direction normal to the surface, most likely ascribed to anchoring the heart-shaped protein molecule by one of its tips. The polarization-dependent resonance shift was confirmed when the surrounding refractive index was uniformly changed by adding salt, which would simulate adsorption of large objects.
Subject(s)
Coated Materials, Biocompatible/chemistry , Materials Testing/methods , Serum Albumin, Bovine/chemistry , Serum Albumin, Bovine/ultrastructure , Silicon Dioxide/chemistry , Adsorption , Electromagnetic Fields , Magnetics , Microspheres , Protein Binding , Protein Conformation , Surface PropertiesABSTRACT
We optically characterize nanolayer (<150 nm) formation in situ on a silica microsphere in an aqueous environment by simultaneously following the shifts of whispering-gallery modes at two wavelengths. This approach was inspired by layer perturbation theory, which indicates that these two measurements can be used to determine independently both the thickness and the optical dielectric constant. The theory is verified for extreme cases and used to characterize a biophysically relevant hydrogel nanolayer with an extremely small excess refractive index of 0.0012.
