Electrochemical Biosensors Employing Hybridization Chain Reaction: From Structural Design to Applications

Abstract Electrochemical biosensors are one of the most emerging sensor technologies for many applications including disease diagnosis, environmental monitoring, and food safety, etc. They often rely on amplification strategies to achieve ultrasensitivity for the specific analytes of interest, as they feature extremely low abundance, such as ctDNA and other protein‐type cancer biomarkers. Among all the amplification strategies, hybridization chain reaction (HCR) is extremely cost‐effective, simple, enzyme‐free, and reacts under isothermal conditions, thus often employed in the electrochemical biosensors towards the goal of sensitivity enhancement. By coupling HCR and electrochemistry, it has proved to benefit a great variety of analytes, including ions, small molecules, nucleic acids, proteins, and cells, etc. Given the recent advance of HCR‐amplified electrochemical biosensors, here one aims to review the significant achievements of this platform over the past 10 years, covering their design in HCR constructs in response to the respective targets, and their challenges and opportunities.