Enzyme-containing-hydrogel/TiO2 hybrid photonic crystal for label-free detection of small molecules

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Abstract

Label-free optical biosensing is a promising key technology in medical diagnosis and biomedical science. The refractive-index (RI) sensitivity of photonic-crystal (PhC)-based biosensors can facilitate rapid, simple, and label-free sensing of biomolecules, with a compact measurement setup. However, the top-down fabrication of highly reproducible PhCs is expensive. Moreover, their RI sensitivity is not sufficient to detect the RI changes caused by small molecules such as glucose. Here, we propose a highly reproducible enzyme-containing-hydrogel/TiO2 hybrid-PhC–based sensing system for label-free small-molecule detection. Our hybrid PhC can detect small molecules by utilizing the reflection-spectrum responses of TiO2-based PhCs to the RI changes of the hydrogel on the surface, caused by the shrinking and swelling of the hydrogel in response to a reaction between the immobilized enzyme and target substrate. In this report, we demonstrate the rapid and simple detection of glucose, using a GOx-containing hybrid PhC. Our hybrid PhC can selectively and rapidly detect 1 nM glucose, with a compact setup, from the shrinking of the hydrogel caused by the oxidation of glucose by GOx. Our sensing system is expected to pave the way for the application of PhC-based biosensors in the detection of small molecules.

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Kawasaki, D., & Endo, T. (2025). Enzyme-containing-hydrogel/TiO2 hybrid photonic crystal for label-free detection of small molecules. Scientific Reports, 15(1). https://doi.org/10.1038/s41598-025-99063-z

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