Label-free determination of adenosine and mercury ions according to force mapping-based force-to-color variety

Single molecule force spectroscopy based on atomic force microscopy (AFM) is a simple and sensitive technique to probe molecular recognition forces. Here we demonstrate that visual color-intensity analysis of single molecule force mapping (SMFM) can be employed as a quick and convenient force-to-color detection towards the presence of various dissolved analytes in very low concentrations. To achieve this aim, analyte-specific single-strand DNA aptamers are first bound to an AFM tip. The measured forces between the functionalized tip and a suitable substrate, namely either a clean surface or a surface functionalized with the complementary DNA oligomer, change when a critical concentration of the analyte is reached. The current SMFM-based visual biosensing shows improved developments like higher sensitivity, lower detection limits, quicker detection, and much simple readout. The color of the obtained force maps reveals the force intensity, which gives a highly selective and immediate visual force-to-color response towards the presence of adenosine (above ∼0.1 nM) and Hg²⁺ (∼10 pM). The strategies shown in this work will be helpful to design and fabricate aptasensors for biomedical analysis as well as to understand the molecular interactions between DNA hybridization.