DOI: 10.1073/pnas.2611528123 ISSN: 0027-8424

A strain-insensitive multiplexed soft microneedle patch for robust interstitial fluid biomarker monitoring

Zheng Qiao, Shuwen Chen, Shuoyan Liu, Leigh Edward Madden, Shicheng Fan, Lanfeng Liang, Mui Hoon Nai, Baobao Lin, Zixiong Wu, Zhijie Li, David Lawrence Becker, Changsheng Wu, Chwee Teck Lim

Wearable microneedle sensors analyze biomarkers in situ from interstitial fluids (ISF), enabling minimally invasive, precise, and continuous monitoring of metabolic diseases. However, conventional designs either lack adequate conformability to skin or suffer from electrode fractures during skin penetration and body motion, leading to signal instability that undermines reliable multiparameter acquisition. Here, we present a fully integrated system with a soft microneedle sensor array featuring nano-hill topographies on strain-resilient electrodes to delocalize strain via geometric confinement. This design reduces signal variability by 14-fold compared to conventional designs, enabling stable, simultaneous in situ monitoring of multiple ISF biomarkers. It achieves clinical-grade accuracy for continuous glucose monitoring (mean absolute relative difference of 10.8%) and captures dynamic synchronized variations in glucose, local tissue pH, and temperature in a living subject in real time. The system integrates a reusable electronic module with a disposable microneedle array with a sensor footprint of just 1.8 cm 2 . By combining high signal stability with multiparameter synchrony in a compact form factor, this system offers a practical solution for reliable, real-time ISF analysis under dynamic in vivo conditions.

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