Wearable biosensors integrating flexible substrates with biosensing components demonstrate remarkable advantages including lightweight construction, stretchability, and biocompatibility, enabling conformal skin attachment or textile integration for continuous, noninvasive physiological monitoring. Sweat, containing abundant biomarkers such as glucose, lactate, uric acid, and electrolytes, holds significant potential for disease diagnosis, health management, and sports medicine applications. However, conventional sweat analysis techniques, such as electrochemical methods (susceptible to signal interference and electrode passivation) and colorimetric approaches (limited sensitivity and stability), exhibit inherent limitations. Surface-enhanced Raman scattering (SERS) technology has emerged as an optimal solution owing to its ultra-high sensitivity, multiplexing capability, and compatibility with aqueous samples. While traditional rigid SERS substrates lack mechanical flexibility for wearable applications, flexible SERS platforms combine stretchability, skin conformability, and biocompatibility, allowing seamless integration with flexible electronics for dynamic monitoring. Despite recent progress in flexible SERS-based sweat sensors, precise multiplexed quantification remains challenging due to spectral overlap and dependence on bulky instrumentation.

To address these challenges, Prof. Lin's team at Fujian Normal University developed an innovative wearable sweat sensor incorporating a flexible SERS substrate with paper-based microfluidics. This advanced design enables highly sensitive multiplexed quantification of uric acid, glucose, and pH in sweat while maintaining excellent skin conformability for prolonged dynamic monitoring. By employing a handheld Raman spectrometer, the system overcomes the limitations of conventional laboratory equipment, offering a lightweight and versatile solution for in situ, real-time, and high-precision health monitoring. The relevant research results are published in Photonics Research as the Cover, Volume 13, Issue 8, 2025. [Nan Wang, Youliang Weng, Yi Liu, Yangmin Wu, Shuohong Weng, Yi Shen, Shangyuan Feng, Duo Lin, "Wearable nanoplasmonic sensor based on surface-enhanced Raman scattering for multiplexed analysis of sweat," Photonics Res. 13, 2316 (2025)].

This study presents a multilayered integrated design that innovatively combines high-sensitivity SERS detection with a flexible wearable platform. A cellulose paper substrate functionalized with silver nanoparticles (AgNPs) was developed, achieving both exceptional mechanical properties and detection sensitivity. The three-dimensional porous structure of cellulose paper not only provides excellent flexibility and skin conformability (36-hour continuous wearability), but also serves as an ideal platform for AgNPs loading, generating abundant electromagnetic "hot spots" with remarkable Raman enhancement.

Leveraging capillary action in paper-based microfluidics for pump-free sweat collection/transport and the high SERS activity of AgNPs, the sensor enables in situ detection of key sweat biomarkers: pH (4-7.5), uric acid (LOD=17μM), and glucose (LOD=1μM). Experimental results demonstrate stable detection within 15 minutes with spike recovery rates of 95%-116%. When coupled with a portable Raman spectrometer, the system maintains laboratory-grade precision (RSD<8%) while overcoming the limitations of conventional benchtop instruments. Long-term wear tests confirm the sensor causes no skin irritation, offering a reliable point-of-care solution for personalized health monitoring (Fig. 1).

Figure 1. Schematic diagram of wearable sweat nano-plasma sensor based on flexible SERS substrate.

To further enhance the sensor's performance and expand its applicability across diverse physiological states, future research will focus on three key technological advancements: (1) development of an integrated microneedle/iontophoresis system for smart sweat stimulation, (2) establishment of a smartphone-based Bluetooth wireless monitoring platform, and (3) optimization of detection sensitivity and data analysis through AI algorithms. These innovations will enable high-precision detection at sub-micromolar levels even under resting or low-sweat conditions, thereby broadening its potential applications in sports medicine, chronic disease management, and beyond.