Disulfide-Cleavage-Triggered Nanomicelles for Highly Specific Glutathione Detection: Integration of Solution and 3D Paper-Based Sensing with Proof-of-Concept in Lung Fluid Samples

Glutathione (GSH) is an important antioxidant in organisms. The microemulsion shows several benefits for the entrapment of dyes, including a high fluorescent intensity, easy preparation, and a long shelf life. We have designed a nanomicellar material in which Triton-X 100 and a cosurfactant of bis(6-hydroxylhexyl) disulfide, S2, mediated the aggregation of nanomicelles with a particle size of approximately 200 nm, to encapsulate the fluorescent dyes of curcumine-BF2 (Cur-BF2) and dansyl boronic acid (DA), namely, TSC and TSD. The well-constructed nanomicelles demonstrated a strong emission band at 587 and 525 nm, respectively, for both sensing platforms in aqueous solution. Because of the excellently optimized number of surfactants and cosurfactants to form nanomicelles with particle sizes of around 10–30 nm, the presence of GSH induced the cleavage of a disulfide bond of S2 encapsulated in nanomicelles, leading to loosening of the aggregated nanomicelles. Consequently, the fluorescence intensity of the dye encapsulated in nanomicelles was remarkably decreased corresponding to the concentration of GSH. In an ongoing research into the convenient sensing approach, TSD nanomicelle-fabricated 3D-paper-based microfluidic devices (TSD@3D-μPADs) have been developed for GSH detection in ELF samples using a distance-based assay for discrimination of pulmonary diseases. The length of the FL darkness distance of ELF sampling in cancer patients was pronouncedly more substantial than that of noncancer participants (p < 0.0001 for n = 20). To increase the readability, TSD@3D-μPADs were designed in a microfluidic pattern as a channel model to count the number of nonbrightness channels, which proved to be a high-potential analysis in POC diagnosis (p < 0.0001 for n = 15). Moreover, these microfluidic devices showed superior stability for long-term storage.