Selectivity issues in affinity-based biochemical sensors: Determining the ratio of similar biomolecules in binary mixtures

Abstract

We consider selectivity of affinity-based nanosensors utilizing resonance shift due to the presence of adsorbed analyte. Among such devices we analyze mass-based sensors utilizing mechanical resonance in e.g. micro or nanocantilevers and all-optical refractometric sensors utilizing surface plasmon polariton resonance. The sensitivity of such devices can be extremely high, reaching single-molecule level, however their selectivity is limited by the differences in mass in the first case or in refractive index values between different analytes in the second. The typical approach is to use some kind of receptors on the sensor surface with highly specific binding of a targeted analyte. The properties of a given biomolecule, for instance protein, will vary between its different conformations due to different arrangements of their atoms in space. Since the conformation of a molecule is critically important for its function, it is of interest to determine the ratio between different conformational isomers in a given sample. In general, different conformations of a biomolecule may have different affinity toward binding sites on the surface of an affinity-based nanosensor, as well as different surface-volume ratios. We argue that the analysis of adsorption kinetics ensures sufficient data to discriminate between different conformations in a mixture.