Progress of Microneedle Electrochemical Biosensors for Interstitial Fluid Detection and Monitoring
Xinxing Gong, Yeru Wen, Yimin Pang, Song Liu, Quan Yuan
Abstract
Comprehensive Summary Microneedle electrochemical biosensors have emerged as a crucial technology for non‐invasive biomarker detection, offering minimally invasive and real‐time monitoring capabilities. These biosensors utilize a microneedle array to extract interstitial fluid, and integrate biological recognition elements ( e.g. , enzymes, antibodies) and electrochemical signal converters ( e.g ., current, resistance) to enable rapid and sensitive detection of various biomarkers like blood glucose, lactic acid, and electrolytes. Despite the commercialization of this technology in continuous blood glucose monitoring, challenges persist, including the need to balance needle length and mechanical strength, ensure long‐term stability against biological contamination and enzyme inactivation, and optimize large‐scale manufacturing processes. Future advancements are anticipated through interdisciplinary collaborations, leveraging artificial intelligence for data analysis and exploring biodegradable materials, to facilitate the transition of microneedle electrochemical sensors from research settings to clinical use and advance the field of personalized medicine. This review examines the historical development, design, manufacturing processes, sensing mechanisms, biomarker detection capabilities, and integration potential of microneedle electrochemical biosensors, while also addressing their application prospects and technical hurdles. Key Scientists In 1998, Mark R. Prausnitz's team at the Georgia Institute of Technology first pioneered the use of microneedle arrays for transdermal drug delivery, establishing the groundwork for the application of this technology in the field. [1] Subsequently, in 2004, E.V. Mukerjee's team conducted the first comprehensive investigation into microneedle arrays for percutaneous interstitial fluid (ISF) extraction and in‐situ analysis, opening up a new avenue for biofluid extraction and analysis. [2] In 2010, Mark A. F. Kendall's team introduced a surface‐modified micro‐projection array for direct capture of disease‐specific biomarkers from the skin dermis for detection. Joseph Wang and Roger Narayan's team is dedicated to advancing the practical application of microneedle electrochemical biosensors in personal health monitoring and medical integrating devices through minimally invasive or non‐invasive monitoring of various biomarkers. [3‐5] In 2022, a microneedle‐based electrochemical biosensor was proposed by Sam Emaminejad's team for continuous and real‐time monitoring of drug pharmacokinetics. [6] In 2024, Kelley and colleagues first developed an implantable biosensor utilizing active reset technology for continuous, real‐time monitoring of protein biomarkers in live animals, enabling rapid protein dissociation via high‐frequency oscillation for real‐time monitoring. Meanwhile, Shi et al . proposed a hydrogel‐based one‐component organic electronic device for closed‐loop antiepileptic therapy, integrating electrical recording and drug release functions to predict pathological conditions. [7]