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Single-molecule detection

Breaking the concentration barrier

Nature Nanotechnology volume 8, pages 480–482 (2013)Cite this article

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The combination of a plasmonic nanoantenna and a nanoaperture has merged fluorescence enhancement and spatial confinement to enable single-molecule detection at biologically relevant concentrations.

Detecting a single molecule is the ultimate goal in chemical analysis and constitutes the basis of innovative technological solutions in the biosciences, and for DNA sequencing in particular1. To detect a single molecule the observation volume must host only one molecule of interest during the measurement. The maximum concentration that can be detected by optical means is constrained by the size of the observation volume, which in turn is limited by diffraction. This implies that it is impossible to carry out single-molecule detection at concentrations exceeding the picomolar to low-nanomolar range, because the observation volume becomes populated by more than one fluorescent molecule as concentration increases. This concentration barrier has hampered the widespread use of single-molecule techniques for studying biomolecular interactions, such as protein–protein and enzyme–substrate interactions, whose dissociation constant is in the micromolar range (that is, reaction partners have to be present at that concentration to obtain a significant fraction of the biomolecular complex). Now, writing in Nature Nanotechnology, Jérôme Wenger and colleagues at Aix-Marseille Université in France, alongside collaborators at the ICFO-Institut de Ciencies Fotoniques and ICREA-Institució Catalana de Recerca i Estudis Avançats in Spain, describe a system that brings two complementary nanophotonic approaches together to achieve single-molecule detection with a high signal-to-noise ratio at a micromolar concentration2.

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Figure 1: Nanophotonic approaches to enhance single-molecule detection.

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  1. Philip Tinnefeld is at the Institute for Physical and Theoretical Chemistry, TU Braunschweig, Braunschweig University of Technology, 38106 Braunschweig, Germany,

    Philip Tinnefeld

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  1. Philip Tinnefeld
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Correspondence to Philip Tinnefeld.

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Tinnefeld, P. Breaking the concentration barrier. Nature Nanotech 8, 480–482 (2013). https://doi.org/10.1038/nnano.2013.122

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