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data needs to be related to data obtained from established ensemble-averaging techniques. Second, it should be shown that the method is generally applicable and works for biorecognition reactions other than the extremely strong biotinavidin interaction probed here. Protein antibodies are of particular importance as capture molecules, but they are considerably larger than biotin, which might impair sensitivity. Finally, it would be extremely valuable if the method could be parallelized, meaning that numerous nanoparticles are measured
simultaneously whilst retaining single-molecule sensitivity. This would dramatically increase the speed and dynamic range of the approach, which could in turn lead to new and powerful methods for ultrasensitive medical diagnostics7 and drug screening. Ultimately, the technique could help unravel the heterogeneity of biomolecular interactions8, which is normally hidden by ensemble averaging, or it could be used to quantify molecular interactions in highly connedvolumes, perhaps even inside livingcells.
Mikael Kll is at the Department of Applied Physics, Chalmers University of Technology, 412 96 Goteborg, Sweden.e-mail: [email protected]
References
1. Zijlstra, P., Paulo, P.M.R. & Orrit, M. Nature Nanotech. 7, 379382 (2012).
2. Atwater, H.A. & Polman, A. Nature Mater. 9, 205213 (2010).3. Soukolis, C. M. & Wegener, M. Nature Photon. 9, 523530 (2011).4. Homola, J. Chem. Rev. 108, 462493 (2008).5. Stewart, M.E. etal. Chem. Rev. 108, 494521 (2008).6. Ament, I. etal. Nano Lett. 12, 10921095 (2012).7. Giljohann, D.A. & Mirkin, C.A. Nature 462, 461462 (2009).8. Henzler-Wildman, K. & Kern, D. Nature 450, 964972 (2007).
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