Sensors that detect ranges of chemical concentrations

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A key part of survival for all organisms is being able to sense conditions in their environments. Researchers at the University of California Santa Barbara and University of Rome Tor Vergata have taken lessons from nature to create biosensors that are highly precise (ideal for monitoring the concentration of highly toxic drugs used to treat many cancers) or, conversely, that can detect a very large change in target concentrations (ideal to monitor HIV virus progression). Biosensors are used, among other purposes, to detect highly toxic levels of drugs used to treat cancer, or to detect the changing levels of viruses in the blood. The way that organisms detect biomolecules is by having receptor or binding sites on protein or nucleic acid molecules (receptors) to which specific biomolecules become chemically bound (these are termed "ligands"). Most human-made sensors rely on just one binding site, which confines their precision to a fixed, well-defined "dynamic range" of target concentrations. Specifically, the useful dynamic range of typical biomolecule binding events spans an 81-fold range of target concentrations. However, sometimes precision levels are needed at a very narrow range of 2- to 5-fold concentrations, or at very broad ranges such as over 6,500-fold concentrations. The key breakthrough underlying their new approach came by observing that living organisms monitor their enviornments in an optimized way by "combining in a very elegant way multiple receptors, each displaying a different affinity for their common target" (Estrada 2012). That is, they respond to either wide or narrow changes in target concentrations. The biosensors being tested by the researchers use multiple binding sites which can detect concentrations in narrow or broad ranges, or even in a bi-modal range of high and low concentrations. According to Vallée-Bélisle et al. (2012), "By engineering a structure-switching mechanism to tune the affinity of a receptor molecule, we first generated a set of receptor variants displaying similar specificities but different target affinities. Using combinations of these receptor variants (signaling and nonsignaling), we then rationally extended (to 900000-fold), narrowed (to 5-fold), and edited (three-state) the normally 81-fold dynamic range of a representative biosensor."Sources: Estrada A. 2012. Chemists mimic nature to design better medical tests. EurekAlert! February 14, 2012. Vallée-Bélisle A; Ricchi F; Plaxco KW. 2012. Engineering biosensors with extended, narrowed, or arbitrarily edited dynamic range. Journal of the American Chemical Society 134:2876-2879

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