Microneedles From Shape-Preserving Crosslinked Poly(Vinyl Alcohol) Hydrogels: Minimising Interference in Transdermal Proteomics

Hydrogel-forming microneedle array patches (HFMAPs) enable minimally invasive interstitial fluid (ISF) sampling for biomarker detection. However, optimising their formulation to enhance biomarker recovery and minimise analytical interference while maintaining mechanical properties remains a challenge. This study presents interference-free HFMAPs fabricated from shape-preserving polyvinyl alcohol and polyvinyl pyrrolidone (PVA-PVP) hydrogel. Two formulations are developed with PVA-PVP without chitosan (PP) and with chitosan (PPChi) using micromoulding and evaluated for mechanical strength, insertion efficiency, ISF absorption, and biomarker recovery. The impact of washing to remove interference and chitosan modification on IgG sampling is assessed ex vivo, while in vivo studies measure ISF uptake and skin response. Both formulations exhibit sufficient mechanical strength for insertion, with washed patches maintaining tip sharpness despite minor shrinkage. Formulated HFMAPs absorb over 5 µL of ISF and facilitate quantifiable IgG detection ex vivo, whereas chitosan-modified patches reduce IgG recovery due to biomarker-hydrogel interactions. In vivo, all formulations absorb over 1.5 µL of ISF within 2 h, obtaining sufficient samples for subsequent analysis. Proteomic study reveale 50 to 200 proteins, with chitosan affecting abundance but not the total number detected. These findings support HFMAPs as a promising tool for non-invasive transdermal sampling of protein biomarkers, enabling subsequent proteomic analysis.