Credit: GETTY

The properties of molecules are traditionally inferred from bulk measurements. But, some 20 years ago, fluorescence spectroscopy made it possible to look at the behaviour of single molecules, and thus investigate properties that are averaged out in bulk studies. In these experiments, however, a fluorescent label must be attached to the target molecule, which limits the scope of the approach. Andrea Armani and colleagues report that single molecules can now be detected without fancy labels (Science doi: 10.1126/science.1145002; 2007).

The alternative to amplifying the signal of a single molecule by attaching a label — as required in fluorescence spectroscopy — is to sample the unmodified molecule many times over. This can be done using a high-quality optical microcavity — a device in which light is confined and circles at discrete frequencies. Armani et al. use silica toroids of about 80 μm diameter; light circulating in such a structure passes a molecule sitting on its surface more than 100,000 times, enough for even a single molecule to leave a signature.

The microtoroid sensor exploits the time that the light spends in the cavity in two ways. On the one hand, the long confinement time results in narrow resonance lines, and therefore good resolving power for small shifts in the resonant wavelength (which occur because the presence of the molecule increases the path length of the light). On the other hand, the molecule is heated by the high-intensity light inside the cavity; the molecule, in turn, heats up the cavity, leading to a more pronounced shift.

As well as achieving single-molecule sensitivity, Armani and co-workers can make their technique selective to specific molecules by sensitizing the resonator surface — for example, by coating it with antibodies. Such specificity, together with the possibility of operating the device in an aqueous environment, opens the door to biological applications, in which the sensor could be used to sensitively determine concentrations of marker molecules. Using the biomolecule interleukin-2 as an example, the authors show that concentrations from micromolar to attomolar — an impressive twelve orders of magnitude — could be detected.