Reagent-Free Wearable Electrochemical Monitoring of Cytokines in Interstitial Fluid Using PB/MIP Hydrogel Microneedle Patches
Abstract
Inflammatory cytokines such as interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are central to acute-phase responses and are increasingly implicated in cardiovascular and systemic inflammatory progression, yet current monitoring remains largely episodic and blood-based. We present a reagent-free, wearable electrochemical platform that enables direct cytokine quantification in dermal interstitial fluid (ISF) using an on-chip Prussian Blue (PB) redox transducer overlaid with a signal-off o-phenylenediamine molecularly imprinted polymer (MIP) and integrated with a biocompatible hydrogel microneedle (HMN) array for minimally invasive ISF sampling.
The PB/MIP (e-MIP) sensor was configured for inflammatory biomarker detection in ISF, specifically IL-6 and TNF-α, and evaluated across in vitro and ex vivo conditions. In ex vivo porcine skin measurements performed in artificial ISF, the device preserved calibration linearity for IL-6 and TNF-α across clinically relevant concentration ranges. The integrated wearable platform achieved
limits of detection ≤0.41 pg mL
⁻
¹
for both IL-6 and TNF-α in the porcine skin model, supporting high-sensitivity cytokine readout under skin-relevant transport conditions.
To assess in vivo utility for dynamic inflammation tracking, HMN-integrated patches were applied to lipopolysaccharide (LPS)-challenged rats, with IL-6 selected as a representative cytokine due to its rapid acute-phase kinetics. The wearable e-MIP captured time-resolved IL-6…
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