# Plasmon-enhanced Single Molecule Detection with Microcavities

Label-free detection of single molecules has been a dream of biologists and biotechnologists. We have come one step closer towards achieving this goal by coupling optical resonators to nanoplasmonic structures. We use whispering gallery modes (WGM) in optical microsphere resonators to excite plasmon resonances in 55 nm gold nanoparticles. Strong electromagnetic field enhancements (hotspots, in red) are observed at the nanoparticle site without significant losses to the quality factor of the resonator. When a molecule binds to the hotspot location it tunes the resonance frequency in proportion to the encountered field strength. The hotspots can provide large sensitivity enhancements – bringing label-free single molecule detection within reach, see right. Such single molecule detection capability is essential for designing the next generation of biosensors and to elucidate intricate mechanisms of molecular machines. We demonstrate this new sensing concept in collaboration with Pennsylvania State University and MIT [5,7].

This entirely new approach to enhancing the sensitivity of microcavity biosensors utilizes the fact that the frequency shift signal Dw produced by a protein binding to the microcavity is in proportion to the intensity $|E|^2$ encountered at the binding site $r_0$: $$\frac{\Delta \omega}{\omega} = \frac{\Delta W_\text{particle}}{W_\text{total}} = \frac{-\alpha \vec{E}\left(\vec{r}_0\right)^2}{2\int \epsilon \vec{E}\left(\vec{r}_0\right)^2 \mathrm{d} V}$$ where $a$ is the polarizability of the bound biomolecule and $\epsilon$ is the permittivity of the microcavity. Any mechanism that can amplify the field intensity at the binding site while maintaining high Q factor will produce a boost in the frequency shift signal, dramatically increasing the sensitivity for single molecule detection.

Hot spots of high field intensities can be generated by evanescent coupling of the microcavity to a plasmonic nanoantenna such as a simple gold nanoparticle. Evanescent excitation of plasmon resonances, for example in a gold nanorod, can produce very large field enhancements. Many other nanoantenna geometries can be explored for this purpose and their designs are similar to nanostructures that are investigated in surface enhanced Raman spectroscopy (SERS). Examples for nanoantennas commonly investigated in SERS are nanoparticle dimers or nanoshell dimers as well as bowtie antennas. Different from SERS, which seeks to enhance the far-field scattering signal, microcavity biosensing relies entirely on enhancing the near-field intensity. In fact it is necessary to minimize the scattering loss to maintain high Q factor which is required for sensitive detection. Through careful choice of WGM wavelength it is indeed possible to enhance the near field intensity at the nanoantenna site while minimizing scattering loss. Indeed, our first experimental reports indicate dramatic sensitivity enhancements in hybrid high Q photonic-plasmonic resonators [5-7].

Our first demonstrations of this plasmon-enhanced microcavity detection scheme utilized a random nanoparticle layer coupled to WGM of a microsphrer cavity to generate hot spots of high field intensity. In theory, optimized plasmon coupling can produce localized near field enhancements up to three orders in magnitude, bringing label-free single molecule detection within reach. We furthermore propose to use the large near field enhancements in a random nanoparticle layer to optically trap single protein molecules at sites of highest sensitivity (hotspots), producing femto-molar sensitivity levels in only ml-scale sample volumes[7].

• [1] F. Vollmer, L. Yang, “Label-free Biodetection with High-Q Microcavities: A Review of Biosensing Mechanisms for Integrated Devices”, Nanophotonics, online early view, (2012).
• [2] M. Baaske, F. Vollmer, “Optical Resonator Biosensors: Molecular Diagnostic and Nanoparticle Detection on an Integrated Platform”,ChemPhysChem 13, 427 – 436 (2012).
• [3] K. Wilson, F. Vollmer, “Whispering Gallery Mode Resonator Biosensors”, Encyclopedia of Nanotechnology, Springer, 2012.
• [4] F. Vollmer, S. Roy, “Optical Resonator based Biomolecular Sensors and Logic Devices”, Journal of the Indian Institute of Science 92, 233-251 (2012)
• [5] M.A. Santiago-Cordoba, S.V. Boriskina, M.C. Demirel, F. Vollmer, “Plasmonic nanoparticle-based protein detection by optical shift of a resonant microcavity”, Applied Physics Letters 99, 073701 (2011). Cover article.
• [6] K. Kim, W. Lee, Y Oh, M. Baaske, M. Foreman, Donghyun Kim, Frank Vollmer, “Efficient localization of whispering gallery modes on a nanopost antenna array for plasmon-enhanced DNA detection”, submitted to ACS Nano (2012)
• [7] M.A. Santiago-Cordoba, M. Cetinkaya, S.V. Boriskina, M.C. Demirel, F. Vollmer, “Ultrasensitive detection of a protein by optical trapping in a photonic-plasmonic microcavity” Journal of Biophotonics 5, 629–638 (2012). Editor’s choice.
• [8] A. Webster and F. Vollmer, “Interference of conically scattered light in surface plasmon resonance”, submitted (2012).
• [9] G. Sarau, B. Lahiri, P. Banzer, P. Gupta, A. Bhattacharya, F. Vollmer, and S. Christiansen, “Enhanced Raman Scattering of Graphene using Arrays of Split Ring Resonators”, submitted to Small (2012)
• [10] Y. Wu, D. Zhang, Y. Peng, F. Vollmer, “Enhanced Label-free DNA Detection by a DNA Catalytic Network Using Whispering Gallery Mode Resonators“, submitted (2012)
• [11] S. Roy, P. Sethi, J. Topolancik, and F. Vollmer, “All-Optical Reversible Logic Gates with Optically Controlled Bacteriorhodopsin Protein-Coated Microresonators”, Advances in Optical Technologies, 2012, Article ID 727206, 12 pages (2012)
• [12] K.A. Wilson, C.A. Finch, P. Anderson, F. Vollmer, J.J. Hickman, “Whispering gallery mode biosensor quantification of fibronectin adsorption kinetics onto alkylsilane monolayers and interpretation of resultant cellular response”, Biomaterials 33, 225-236 (2011)