Nano-dimensionality effect on electrochemical aptamer-based sensor performance for MUC1 liquid biopsy

The modularity of electrochemical aptamer-based (E-AB) sensors has made them useful candidates for real-time and specific determination of molecular targets (irrespective of their chemical reactivity). In this work, we have emphasized the role of the electrode surface's morphological dimensions on the E-AB sensor's performance for the detection of breast cancer biomarker MUC1 in the human serum sample. To accomplish this, bottom-up approaches were utilized for the synthesis of one- and three-dimensional gold substrates (with 0.072 cm² and 0.079 cm² ECSAs, respectively) that were later used in the construction of E-AB sensors, and the results were compared to a planar gold electrode (two-dimensional with an ECSA of 0.02 cm²). The selection of a regular gold electrode as the two-dimensional substrate was essential to make the study relevant and comparable with the widely used type of electrode that is commonly used in the fabrication of E-AB sensors. Our data show that the E-AB sensor based on the three-dimensional gold substrate with a limit of detection (LOD) of 6.8 nM did not significantly improve the regular electrode (two-dimensional) with a LOD of 7.8 nM, whereas the one-dimensional gold substrate proved to be the most electrochemically sensitive surface with a LOD of 3.5 nM. This enhancement is likely due to the attributes of the surface organization. Therefore, our findings suggest that a large surface area alone does not necessarily guarantee a better sensitivity unless causing a fruitful contribution to the aptamers' surface organization.