Abstract
DNA biosensors have attracted considerable attention due to their great potential in environmental monitoring and medical diagnosis. Despite the great achievements, the single function and uncontrollability of the sensors restrict their further application. Therefore, it is necessary to construct controllable nanodevices with both sensing and responding capabilities to external stimuli. Herein, we develop a strategy to engineer structure-switching biosensors which can respond to external stimuli while preserving the sensing capability. The engineered nanodevice consists of an actuation module and a sensing module. Initially, the sensing module is disabled by a blocker strand which acts as an allosteric switch. Once the stimuli-responsive actuation module displaces the blocker DNA, the sensing module is activated. Based on the strategy, the engineered nanodevice could recognize both the target and external stimuli. As a demonstration of this strategy, a controllable Hg2+ sensor was designed, in which a 'YES', 'AND', and 'OR' logic gate is employed as the actuation module respectively to facilitate recognition of oligonucleotide inputs. The modular nature of the proposed strategy makes it easily generalizable to other structure-switching sensors. As a demonstration of this, we successfully apply it to the ATP sensor. The proposed strategy has potential in the fields of programmable biosensing, disease diagnosis, DNA computing, and intelligent nanodevices.