Label-Free Colorimetric Biosensors Based on Aptamers and Gold Nanoparticles: A Critical Review

Taking advantage of the adsorption of single-stranded DNA oligonucleotides by gold nanoparticles (AuNPs) and the protection effect of the adsorbed DNA against salt-induced aggregation of AuNPs, a label-free colorimetric sensor for the detection of DNA was reported in 2004. Since then, the range of target molecules has extended from complementary nucleic acids to metal ions and small molecules by using aptamers. In the presence of target molecules, a blue color arising from aggregated AuNPs is expected. However, these sensors only considered aptamer binding to its target, and the adsorption of aptamers by AuNPs, while the target/AuNP interactions were ignored. We recently found that target adsorption can often dominate the system. In this Review, we list literature examples of using this label-free strategy for sensing aptamer targets. Seven target analytes are discussed in detail. For As(III), dopamine, melamine, kanamycin, adenosine, and ATP, target adsorption dominated, and the same color change was observed even with non-aptamer sequences. Only in the case of K+ detection, did the effect of specific aptamer binding dominate, attributable to weak K+/AuNP interactions. These examples call for a careful evaluation of target adsorption and the use of non-aptamer control sequences in validating these sensors.