# Ion‑Mediated Structural Engineering of Hydrogel Interfaces for Tunable Mechanical and Analyte Diffusion Properties in Electrochemical Biosensors

## TL;DR

This paper introduces a new method to control hydrogel properties using ions, enabling better biosensors for glucose monitoring in sweat and interstitial fluid.

## Contribution

A novel ion-mediated strategy is introduced to tune hydrogel structure, enabling independent control of mechanical strength and analyte diffusion.

## Key findings

- Hydrogels with pore sizes from 65 nm to 2.5 µm and moduli of 50–140 kPa were fabricated.
- Two glucose biosensors were demonstrated with tailored performance for sweat and interstitial fluid.
- Ion combinations were shown to systematically affect hydrogel mechanical and diffusion properties.

## Abstract

Advanced hydrogel interfaces exhibiting finely tuned mechanical characteristics and porosity are essential in wearable and implantable biosensors, mitigating tissue–device mismatches and controlling target analyte transport in biofluids. This work presents an ion‐mediated structural engineering approach designed to meticulously regulate the porous architecture and mechanical robustness of poly(vinyl alcohol)–alginate hydrogels (PAH) through straightforward ionic modulation, effectively addressing inherent trade‐offs between mechanical strength and analyte diffusion. Utilizing three complementary ionic mechanisms—salting‐out, calcium ion chelation, and sequence‐directed biomineralization—hydrogels with tailored porous microstructures are fabricated. The resulting hydrogels exhibit pore sizes ranging from 65 nm to 2.5 µm, mechanical moduli of 50–140 kPa, and controlled analyte diffusion behaviors. Leveraging this structural tunability, two exemplary glucose biosensors are demonstrated: a highly porous hydrogel‐integrated wearable biosensor designed for rapid and sensitive glucose monitoring in sweat, and a densely structured hydrogel‐integrated implantable biosensor optimized for robust and continuous glucose tracking in interstitial fluid. This innovative methodology elucidates critical interconnections between the hydrogel's ion‐mediated microstructural architecture, its mechanical robustness and tunable diffusion characteristics, and the resulting biosensing performance optimized for wearable and implantable applications, thereby advancing the design paradigm for next‐generation personalized biosensor interfaces.

An ion‐mediated structural engineering strategy enables versatile modulation of PVA–Alginate hydrogel microstructure. We systematically examine how different ion combinations affect hydrogel mechanical properties and analyte diffusivity. Applying this novel strategy to hydrogel as the outer membrane in an electrochemical glucose biosensor allows precise tailoring of the linear dynamic range to match desired analyte concentration ranges.