Affinity-based electrochemical sensors for biomolecular detection in whole blood

The detection and/or quantification of biomarkers in blood is important for the early detection, diagnosis, and treatment of a variety of diseases and medical conditions. Among the different types of sensors for detecting molecular biomarkers, such as proteins, nucleic acids, and small-molecule drugs, affinity-based electrochemical sensors offer the advantages of high analytical sensitivity and specificity, fast detection times, simple operation, and portability. However, biomolecular detection in whole blood is challenging due to its highly complex matrix, necessitating sample purification (i.e., centrifugation), which involves the use of bulky, expensive equipment and tedious sample-handling procedures. To address these challenges, various strategies have been employed, such as purifying the blood sample directly on the sensor, employing micro-/nanoparticles to enhance the detection signal, and coating the electrode surface with blocking agents to reduce nonspecific binding, to improve the analytical performance of affinity-based electrochemical sensors without requiring sample pre-processing steps or laboratory equipment. In this article, we present an overview of affinity-based electrochemical sensor technologies that employ these strategies for biomolecular detection in whole blood. Graphical abstract