Impact of Conformational Transitions on SPR Signals-Theoretical Treatment and Application in Small Analytes/Aptamer Recognition

Surface plasmon resonance (SPR) is a powerful technique for label-free and real-time characterization of molecular interactions at interfaces. However, the detection of small molecules still remains a challenge. Here, we report on the direct detection of a low-molecular-weight compound by its receptor presented as a monolayer. Moreover, the signal observed is more than twice the expected mass-weighted response. To establish the origin of the signal enhancement, we present herein a theoretical model that simulates the maximal SPR response by taking into account the aptamer conformational change. We demonstrated that the variation of layer thickness is not the only parameter to be considered. We highlighted that the conformational transition of the aptamer also induces a deviation of the refractive index increment (RII) of the target/aptamer complex from the sum of the MI of individual entities. This nonadditivity of the RII significantly contributes to the magnitude of the signal. We also propose the prediction of the maximal SPR response as a function of the penetration depth, the ratio of the mass-weighted RII of the partners, the sensing layer thickness, and the correction of the complex RII. This model provides new insights into parameters to be considered for the analysis of SPR signals.