A Modular and Customizable Aptamer Transducer Designed for Feed-Forward Coupling with Catalytic Amplifiers

Aptamer biosensing has attracted recent attention due to its potential for sensing applications in the medical, environmental, and food safety industries.1 Additionally, aptasensors can be designed as point-of-care devices making them useful where lab equipment is less accessible.1 Many studies have aimed to develop aptasensors with improved sensitivity and selectivity, while relatively few have focused on aptasensor modularity.1 Here, we introduce a modular Aptamer Transducer (AT) that can be incorporated with a variety of DNA reaction networks by producing a customized output strand. Modularity of the AT was accomplished by separation of the aptamer input and output domains on a sensing substrate. Aptamer-ligand binding allows a structure switching element to be activated to initiate strand displacement with fuel strands and release the customized output ssDNA sequence. The well-known 23-mer adenosine binding DNA aptamer was incorporated into the AT design and shown to accommodate sequence designs for targeted reporter complexes, with the limit of detection down to 5 μM.2 Further, adenosine AT output was customized for two linear catalytic amplification reaction networks developed by Zhang et al. and Kotani et al. The ATs were able to trigger feed-forward signaling to these catalytic amplifiers without the need for amplifier reaction network redesign, further supporting modularity of the device.3,4 Future study of the AT will aim to improve the device sensitivity, reduce network leakage, and incorporate other aptamers. Through continued AT device improvement, future reaction networks could employ concurrent solution based multiplexed sensing using two or more aptamers.