Biosensors for viral and bacterial pathogen detection: From biological recognition elements to small-molecule engineering of electrochemical interfaces

Abstract

Infectious diseases pose a serious threat to global public health, and the COVID-19 pandemic has clearly demonstrated the critical need for rapid, accurate, and accessible diagnostic tools. Portable point-of-care analytical systems provide an alternative to conventional laboratory methods such as ELISA and PCR, enabling rapid pathogen identification outside centralized facilities, which is essential for timely diagnosis and treatment decisions. Beyond initial detection, such systems also hold potential for quantitative monitoring of viral or bacterial load, relevant for assessing disease stage and therapy effectiveness. Electrochemical biosensing platforms most favorably combine the required analytical performance with broad possibilities for miniaturization, automation, and scaling. However, despite the exponential growth in publications, clinical translation and commercialization of such devices remain limited by insufficient stability and reproducibility of the bioreceptor layer, uncontrolled interfacial orientation, and matrix effects in complex biological samples. This review provides a critical analysis of current approaches to the directed structuring of the bioreceptor layer in electrochemical sensors, comparing biological recognition elements (antibodies, DNA/RNA probes) with synthetic and biomimetic alternatives (aptamers, engineered peptides, and molecularly imprinted polymers). Particular attention is given to the multifaceted roles of small organic molecules as structural elements — cross-linkers for oriented immobilization, redox mediators and electrocatalysts for signal transduction, and independent low-molecular-weight recognition ligands — for the design of next-generation electrochemical test platforms with operational characteristics tunable at the molecular level.