“…In the early stage of disease development, the levels of diagnostically relevant biomarkers (e.g., circulating tumor DNAs, ctDNAs) are generally very low. , For this reason, methods capable of sensitively and selectively detecting biomolecules of interest are of cardinal importance in biomarker screening and early diagnosis. Among various bioanalytical methods, electrochemical biosensing not only combines the high sensitivity of electroanalytical techniques with the high selectivity of molecular-recognition processes but also offers the benefits of low cost, fast response, and good portability, − thus holding great potential in bioanalytical applications. To improve the detection sensitivity, however, most of the reported electrochemical biosensors rely on the use of either natural enzymes (e.g., alkaline phosphatase, ALP) , or complex nanomaterials (e.g., surface-functionalized metal nanoparticles, NPs) − for signal amplification, which limits their application scope because of the poor stability (e.g., temperature and pH sensitivity) and high cost of natural enzymes and the laborious and lengthy operations involved in the synthesis and postfunctionalization of nanomaterials. , Therefore, the challenge in electrochemical biosensing lies, to a large extent, in simplifying the amplification strategy without compromising the detection sensitivity and cost-effectiveness.…”