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Label-Free Detection of Single Protein Using a Nanoplasmonic-Photonic Hybrid Microcavity

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Microparticle Photophysics Lab, Polytechnic Institute of NYU, Brooklyn, New York 11201, United States
Department of Physics, Fordham University, Bronx, New York 10458, United States
§ Department of Biological Sciences, NYC College of Technology, Brooklyn, New York 11201, United States
Cite this: Nano Lett. 2013, 13, 7, 3347–3351
Publication Date (Web):June 18, 2013
Copyright © 2013 American Chemical Society

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    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.

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