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.

An electrochemical method based on CRISPR-Cas12a and enzymatic reaction for the highly sensitive detection of tumor marker MUC1 mucin

“…25 Due to the mechanism of highly specific recognition of exogenous DNA by CRISPR-Cas12a, aptamer sensors based on the CRISPR-Cas12a system have high selectivity in the detection of nucleic acid and non-nucleic acid targets. [26][27][28][29] In order to improve the analytical sensitivity of the sensors, techniques such as Hybridization Chain Reaction (HCR), 30 Strand Displacement Reaction (SDA), 31 Loop-mediated Isothermal Amplification (LAMP) 32 and Rolling-Circle Amplification (RCA) 33 have been successively introduced, but it is still difficult to meet the requirements for the detection of ultratrace analysts in samples. The enzyme catalytic reaction used in the bioassay involves making use of the efficient catalytic activity of the enzyme to catalyze the cycle of the reaction in which the substrate is involved, to continuously in situ generate detectable probes around the detector.…”

Hybridization Chain Reaction-Based Electrochemical Biosensors by Integrating the Advantages of Homogeneous Reaction and Heterogeneous Detection

“…In comparison with other sensing devices, electrochemical biosensors exhibit the advantages of high sensitivity, low cost, excellent specificity, and easy miniaturization [10,11]. Moreover, the combination of HCR with other DNA amplification techniques, such as CHA, nuclease-assisted target recycling, and strand-displacement amplification (SDA), has further improved the detection sensitivity [12]. Although HCR-based strategies have exhibited good development momentum in the design of biosensors, most of the HCR-based electrochemical bioassays require the immobilization of DNA initiators on the electrode surface, which will suffer from some intrinsic shortcomings such as complex immobilization processes and low HCR efficiency due to the local steric hindrance [13][14][15].…”