Responsive Moiré Hydrogel-IOL Platform for Intraocular Biomarker Monitoring of Neurodegenerative Diseases

Bioresponsive hydrogels are smart materials that respond to external stimuli and have strong potential as biosensors because they enable real-time and label-free detection. In this study, we propose a moiré pattern-based sensing platform using bioresponsive hydrogels.
The platform consists of two line gratings with different pitch sizes. One is a hydrogel grating whose pitch changes in response to external stimuli, and the other is a reference grating with a constant pitch. Stimulus-induced volume changes in the hydrogel alter the pitch of the hydrogel grating, which subsequently modulates the pitch of the resulting moiré patterns, referred to as the moiré signal. These moiré signals can be measured in real time without labeling using a customized moiré microscopy system and signal-processing method.
After confirming that pH-induced hydrogel swelling could be monitored through moiré pattern changes, we applied the system to detect disease-related biomarkers using responsive hydrogels that shrink upon interaction with target molecules. Secreted phosphoprotein 1 (SPP1) and acetylcholinesterase (AChE) were selected as model analytes, and the proposed platform successfully detected biomarker-induced hydrogel responses. In both cases, changes in the hydrogel grating pitch were measured with substantially higher sensitivity by moiré pattern analysis than by direct optical measurement.
Furthermore, target-induced moiré signal changes were successfully detected in in vivo environments using a custom-designed intraocular lens incorporating the hydrogel grating. These results demonstrate the potential of the proposed platform for detecting various biomarkers in intraocular aqueous humor after implantation.