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.

We report the label-free detection and sizing by a microcavity of the smallest individual RNA virus, MS2, with a mass only $1% of InfluenzaA (6 vs. 512 ag). Although detection of such a small bio-nano-particle has been beyond the reach of a bare spherical microcavity, it was accomplished with ease (S/N ¼ 8, Q ¼ 4 Â 10 5) using a single dipole stimulated plasmonic-nanoshell as a microcavity wavelength shift enhancer, providing an enhancement of $70Â, in agreement with theory. Unique wavelength shift statistics are recorded consistent with an ultra-uniform genetically programmed substance that is drawn to the plasmonic hot spots by light-forces. V

The enhancement of Raman signal is observed on excitation through a single microsphere. The dependence of the enhancement ratio (ER) on various parameters viz., numerical aperture (NA) of the microscopic objective lens, pump wavelength, size and refractive index of the microsphere has been studied. The enhancement has been explained due to interaction of the increased field of the photonic nanojet emerging from the single microsphere. The photonic nanojet induced ER of Raman peaks of silicon wafer and cadmium ditelluride is reported here. It is observed for the first time that by suitable selection of the experimental parameters, it is possible to enhance the Raman signal by approximately two orders of magnitude.

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