Effects of Aptamer-Functionalized Multivalent DNA Nanostructures on Small-Molecule Detection in Wearable Sweat Sensors

The merits of an ideal wearable sensor are high sensitivity, excellent stability, and user-friendly operation, typically requiring room-temperature storage and sample-to-answer detection capability. Here, we developed aptamer-functionalized multivalent fluorescent DNA nanostructures (Ap-MFDNs) and demonstrated that they can improve the detection sensitivity for sweat biomarkers, i.e., cortisol, lactate, and uric acid, compared with monovalent probes. The results showed that the multivalent binding strategy exhibited varying effects on enhancing the detection sensitivity for different small molecules, which was particularly evident for cortisol. Molecular docking was employed to help understand these differences. Meanwhile, we demonstrated that the Ap-MFDNs can be stored as a lyophilized powder under appropriate ionic strength. Based on the multivalent DNA nanostructures, we designed corresponding wearable sensors for direct detection of the above three targets in human sweat with the aid of smartphones. The detection range of the wearable sensor can cover the physiological levels of the three small molecules in sweat. Therefore, multivalent DNA nanostructures have the potential to improve the performance of wearable sensors.