Label-free detection of single nanoparticles and biological molecules using microtoroid optical resonators
Single-molecule detection is one of the fundamental challenges of modern biology. Such experiments often use labels that can be expensive, difficult to produce, and for small analytes, might perturb the molecular events being studied. Analyte size plays an important role in determining detectability. Here we use laser-frequency locking in the context of sensing to improve the signal-to-noise ratio of microtoroid optical resonators to the extent that single nanoparticles 2.5 nm in radius, and 15.5 kDa molecules are detected in aqueous solution, thereby bringing these detectors to the size limits needed for detecting the key macromolecules of the cell. Our results, covering several orders of magnitude of particle radius (100 nm to 2 nm), agree with the 'reactive' model prediction for the frequency shift of the resonator upon particle binding. This confirms that the main contribution of the frequency shift for the resonator upon particle binding is an increase in the effective path length due to part of the evanescent field coupling into the adsorbed particle. We anticipate that our results will enable many applications, including more sensitive medical diagnostics and fundamental studies of single receptor–ligand and protein–protein interactions in real time.
Additional Information© 2016 CIOMP. This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 Unported License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/. Received: 6 March 2015; revised: 24 July 2015; accepted: 5 August 2015; accepted article preview online 22 August 2015. Published online 1 January 2016. We thank Raymond Deshaies for the ribosomes, Carver Mead for the frequency locking suggestion, Richard Murray for discussions on feedback control, Andrew Raubitschek for the exosomes, Stephen Holler and Mark Oxborrow for COMSOL assistance, and Scott Fraser, Rob Phillips, and Kerry Vahala for comments and discussion of the manuscript.
Published - lsa20161a.pdf
Supplemental Material - lsa20161x1.pdf