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This paper aims to provide a detailed review of weak interaction biosensors and several common biosensor methods for magnifying signals, as well as judiciously guide readers through selecting an appropriate detecting system and signal amplification method according to their research and application purpose.

This paper classifies the weak interactions between biomolecules, summarizes the common signal amplification methods used in biosensor design and compares the performance of different kinds of biosensors. It highlights a potential electrochemical signal amplification method: the G protein signaling cascade amplification system.

Developed biosensors which, based on various principles, have their own strengths and weaknesses have met the basic detection requirements for weak interaction between biomolecules: the selectivity, sensitivity and detection limit of biosensors have been consistently improving with the use of new signal amplification methods. However, most of the weak interaction biosensors stop at the research stage; there are only a minority realization of final commercial application.

This paper evaluates the status of research and application of weak interaction biosensors systematically. The G protein signaling cascade amplification system proposal offers a new avenue for the research and development of electrochemical biosensors.