Better Reception, Better Signal! Investigating the Impact of Electrochemical Immunosensor Architecture on Sensitivity

Abstract

Enhancing digital healthcare monitoring to allow for the detection of biological species such as viruses, hormones, and early warning disease biomarkers requires sensors with ultra-low limits of detection, a broad linear range of performance, and high selectivity. Furthermore, these requirements are needed when analysing for target analyte species present in low concentration levels, as well as, for example, when pursuing non-invasive detection applications in saliva- or sweat-based analyte solutions. These analyte solutions can be complex, containing a variety of non-specific species and molecules. Therefore, focusing on the sensor architecture, surface functionalization, and the transduction method is of great importance when addressing these complex solutions.[2] Maximising the available surface area of the transducing sensor facilitates greater numbers of binding events between the receptor and target analyte of interest being possible.[1] This in turn increases sensitivity for identifying and quantifying the target analyte distinct from other species present, or in low concentrations in the solution. Evaluating different geometries, supporting structures, and the materials in the sensor electrode’s design can determine which architecture, in combination with the transduction technique and immobilized molecules, can enhance the overall performance of the sensor and attain ultra-low levels of detection. Additionally, while reliability in the bio-functionalization of the electrode surface is crucial, it is equally vital that the method of fabricating the electrodes geometry is repeatable. Repeatability in this regard further decreases sensor to sensor variability and signal outputs, especially if the sensor is to become commercially viable. In this work, custom micropillar-array silicon (Si) chips (MASCs) are commercially fabricated, thus providing the advantage of having a highly repeatable architecture and being commercially viable as a sensing design. The MASCs were used as a supporting structure to increase the available surface area, compared to a planar chip, for immobilising biorecognition elements, therefore increasing the sensitivity to potential binding events between the receptor and target analyte. The MASCs were coated with gold (Au) to facilitate the supporting surface acting as a transducing sensor, utilizing electrochemical impedance spectroscopy (EIS) as the primary transduction technique. The study evaluates the sensitivity and linear range of the MASCs comparatively against planar Au-coated Si chips, characterizing the design and performance of the sensors via EIS, cyclic voltammetry (CV), differential pulse voltammetry (DPV), fluorescent microscopy (FM), and scanning electron microscopy (SEM). With this study, a label-free transduction technique was harnessed for biosensing, addressing performance issues by developing different sensor architectures, leveraging a robust biofunctionalization protocol, and comparatively developing sensors whose design considerations accommodate goals of commercial viability and a robust, adaptable biosensing platform for future research prospectives.