With security tightened and concern about identity heightened, the computerized tagging of molecules with other molecules is an idea whose time has come. A. Prasanna de Silva and colleagues present an appropriate strategy, which bears the grand title of molecular computational identification, or MCID (Nature Mater. doi:10.1038/nmat1733; 2006).
In essence, the technique involves using a series of single-input 'logic gates' — in this case, fluorescent dyes — that respond differently to various chemical stimuli, and whose combined response is unique to a particular molecule. That might be useful to those in the pharmaceutical industry, for example, who need to be able to keep close tabs on libraries of different, but structurally related, compounds.
The authors set about finding fluorescent molecules that reproduce the effects of five different logic gates when exposed to the H+ ion, which is responsible for acidity in water. Two of these gates, PASS 1 and PASS 0, produce a positive or a negative response regardless of the input and are trivial: they are, respectively, a fluorescent dye immobilized on a polymer bead, and no tag molecule at all.
For the YES gate, a molecule was chosen in which a process known as photoinduced electron transfer hinders fluorescence. When H+ ions are present, they interact with electrons that would otherwise be transferred, so the molecule fluoresces. By using tag molecules with subtly different structures, the H+ concentration at which this effect kicks in can be altered, and different colours of fluorescence can be created.
Similar principles apply to the authors' NOT gate, which is activated when the concentration of H+ is low. Pictured is an array of tag beads that has been immersed in hydrochloric acid (where the H+ concentration is high; top image) or the alkali sodium hydroxide (with a lower level of H+ ions; bottom image). The disappearance of twoYES beads (bottom left) and the appearance of two NOT beads (middle) is clearly visible.
The technique can be easily extended to multiple-input gates, as the authors demonstrate with a tag molecule that acts as an AND gate. It fluoresces only in the presence of both H+ and the sodium ion Na+. Other distinguishable input stimuli are calcium, caesium and zinc ions, glucose molecules, and even heat and light.
The various available inputs, gates, switching thresholds and output colours could make MCID a sophisticated cataloguing tool, say the authors. Molecules and other nanoscale objects, like so much in today's world, may soon become familiar with computerized ID.
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Webb, R. Playing molecular tag. Nature 443, 39 (2006). https://doi.org/10.1038/443039a