Challenges and Advances of Interstitial Skin Fluid Wearable Smart Sensors on Emerging Microneedle Platforms

Interstitial skin fluid (ISF) holds great potential in bioassays as its components are similar to blood, offering a noninvasive alternative for disease diagnosis, prevention, and treatment. Microneedles (MNs), a novel biomedical tool, enable minimally invasive and painless extraction of ISF. This perspective systematically examines the latest advancements in MN-based ISF extraction and sensing. It elaborates on the differences between blood and ISF in molecular concentration and lag time, and compares MN-based sensing with conventional detection methods. Multiple biosensing principles, including electrochemical, fluorescence, colorimetry, and SERS, are detailed, and their metrics are evaluated in terms of LOD, specificity, response time, stability, and signal-to-noise ratio. The limitations of MNs, such as extraction efficiency, biological contamination, microdetection, and signal drift, are discussed, along with potential solutions. The application of MNs in wearable health monitoring, covering real-time monitoring, wireless data transmission, sensor miniaturization, closed-loop drug monitoring and delivery systems and commercialized MN detection products, is explored. Although challenges remain in sensor stability and device-clinical integration, the development of MN-and ISF-based detection devices is promising, and with further research, they are expected to revolutionize personal medical health monitoring.