Wearable biosensors have the potential for developing individualized health evaluation and detection systems owing to their ability to provide continuous real-time physiological data. Among various wearable biosensors, localized surface plasmon resonance (LSPR)-based wearable sensors can be versatile in various practical applications owing to their sensitive interactions with specific analytes. Understanding and analyzing endocrine responses to stress is particularly crucial for evaluating human performance, diagnosing stress-related diseases, and monitoring mental health, as stress takes a serious toll on physiological health and psychological well-being. Cortisol is an essential biomarker of stress because of the close relationship between cortisol concentration in the human body and stress level. In this study, a flexible LSPR biosensor was manufactured to detect cortisol levels in the human body by depositing gold nanoparticle (AuNP) layers on a 3-aminopropyltriethoxysilane (APTES)-functionalized poly (dimethylsiloxane) (PDMS) substrate. Subsequently, an aptamer was immobilized on the surface of the LSPR substrate, enabling highly sensitive and selective cortisol capture owing to its specific cortisol recognition. The biosensor exhibited excellent detection ability in cortisol solutions of various concentrations ranging from 0.1 to 1000 nM with a detection limit of 0.1 nM. The flexible LSPR biosensor also demonstrated good stability under various mechanical deformations. Furthermore, the cortisol levels of the flexible LSPR biosensor were also measured in the human epidermis before and after exercise as well as in the morning and afternoon. Our biosensors, which combine easily manufactured flexible sensors with sensitive cortisol-detecting molecules to measure human stress levels, could be versatile candidates for human-friendly products.

Surface-enhanced Raman spectroscopy (SERS) detection in microfluidics is an interesting topic because of its high sensitivity, miniaturization, and ability to perform online detection. However, the difficulties in generating SERS-based microfluidic devices with uniform signal reproducibility and high sensitivity have hindered their widespread application. In addition, the recyclability of the SERS-based microfluidic devices can contribute to their broad commercialization, but the possible contamination in the detection area and cumbersome cleaning procedures remain a challenge. In this study, we describe a repeatable SERS-based microfluidic device comprising a disposable SERS substrate and a reusable microfluidic channel. The microfluidic channel was prepared via mechanical processing, and the SERS substrate was fabricated by nanoimprint lithography and electrodeposition. The SERS substrate and microfluidic channel can be attached easily because they were assembled using screws. The SERS substrate achieved an excellent SERS enhancement factor greater than 10⁸ over a large sample area, signal uniformity, and substrate-to-substrate reproducibility. This guaranteed reliable and sensitive signals in every experiment. Furthermore, the disposable SERS substrate contributed exact detection of target molecules. Finally, their practical application was demonstrated with the repeated use of the microfluidic device by detecting a specific micro-RNA, (miR-34a) at a concentration as low as 5 fM.

To achieve an effective surface-enhanced Raman scattering (SERS) sensor with periodically distributed “hot spots” on wafer-scale substrates, we propose a hybrid approach combining physical nano-imprint lithography and a chemical deposition method to form a silver microbead array. Nano-imprint lithography (NIL) can lead to mass-production and high throughput, but is not appropriate for generating strong “hot-spots.” However, when we apply electrochemical deposition to an NIL substrate and the reaction time was increased to 45 s, periodical “hot-spots” between the microbeads were generated on the substrates. It contributed to increasing the enhancement factor (EF) and lowering the detection limit of the substrates to 4.40 × 10⁶ and 1.0 × 10⁻¹¹ M, respectively. In addition, this synthetic method exhibited good substrate-to-substrate reproducibility (RSD < 9.4%). Our research suggests a new opportunity for expanding the SERS application.