Microenvironment-regulated Fe single-atom nanozyme with neutral-pH peroxidase-mimicking activity for paper-based...

Single-atom nanozymes (SANs) with peroxidase (POD)-mimicking activity have attracted considerable attention for biomarker detection. However, the POD-mimicking activity is typically restricted to acidic environments, hindering its practical applications.

This work reported a pH-regulated Fe single-atom nanozyme engineered via polyacids functioning as Brønsted acids. The polyacids can effectively modulate the local microenvironment pH around Fe single sites, ensuring high POD-mimicking activity in a neutral pH reaction system. The Fe SAN integrated into a microfluidic paper-based analytical device (μPAD) enables the efficient and simultaneous detection of five biomarkers (glucose, cholesterol, galactose, choline, and acetylcholine) without altering the solution pH, via cascade-amplified colorimetric reaction. The proposed μPAD exhibits wide linear detection ranges and low limits of detection, as determined by smartphone-based RGB image analysis.

This work provides a generalizable strategy to overcome pH limitations of SANs, offering the potential to establish a portable, high-performance, and interpretable platform for multiplex biomarker analysis in clinical diagnostics.