Electrochemical aptamer (EA) sensors based on aptamer-cDNA duplex probes (cDNA: complementary DNA) and target induced strand displacement (TISD) recognition are sensitive, selective and capable of detecting a wide variety of target analytes. While substantial research efforts have focused on engineering of new signaling mechanisms for the improvement of sensor sensitivity, little attention was paid to the enhancement of sensor response rate. Typically, the previous TISD based EA sensors exhibited relatively long response times larger than 30 min, which mainly resulted from the suboptimal aptamer-cDNA probe structure in which most of aptamer bases were paired to the cDNA bases. In an effort to improve the response rate of this type of sensors, we report here the rational engineering of a quickly responsive and sensitive aptamer-cDNA probe by employing the conception of bivalent interaction in supramolecular chemistry. We design a bivalent cDNA strand through linking two short monovalent cDNA sequences, and it is simultaneously hybridized to two electrode-immobilized aptamer probes to form a bivalent binding (BB) aptamer-cDNA probe. This class of BB probe possesses the advantages of less aptamer bases paired to the cDNA bases for quick response rate and good structural stability for high sensor sensitivity. By use of the rationally designed BB aptamer-cDNA probe, a TISD based EA sensor against ATP with significantly enhanced response rate (with a displacement equilibrium time of 4 min) and high sensitivity was successfully constructed. We believe that our BB probe conception will help guide future designs and applications of TISD based EA sensors.

基于适体-cDNA双链探针（cDNA：互补DNA）和目标诱导链置换（TISD）识别的电化学适体（EA）传感器灵敏，选择性强，能够检测多种目标分析物。尽管大量的研究工作集中在设计新的信号机制以提高传感器灵敏度，但很少有人关注传感器响应率的提高。通常，以前基于TISD的EA传感器表现出相对较长的响应时间（大于30分钟），这主要是由于亚适体-cDNA探针结构欠佳而导致的，其中大多数适体碱基与cDNA碱基配对。为了提高此类传感器的响应率，我们在这里报告了通过利用超分子化学中的二价相互作用的概念对快速响应和敏感的适体-cDNA探针进行的合理工程设计。我们通过连接两个短的单价cDNA序列设计一个二价cDNA链，并将其同时与两个电极固定的适体探针杂交，以形成一个二价结合（BB）适体-cDNA探针。此类BB探针具有与cDNA碱基配对较少的适体碱基的优点，以实现快速响应速度和良好的结构稳定性，从而具有较高的传感器灵敏度。通过使用合理设计的BB适体-cDNA探针，成功构建了基于TISD的针对ATP的EA传感器，该传感器具有显着提高的响应速度（位移平衡时间为4分钟）和高灵敏度。