Rational Development of Co‐Doped Mesoporous Ceria with High Peroxidase‐Mimicking Activity at Neutral pH for Paper‐Based Colorimetric Detection of Multiple Biomarkers

Abstract

Peroxidase-mimicking nanozymes have been extensively studied, however, their application is limited by the requirement for an acidic pH. Herein, the development of Co-doped mesoporous cerium oxide (Co-m-ceria) is reported, which operates optimally at a near-neutral pH and exhibits a peroxidaselike catalytic efficiency that is 600-times higher than that of pristine m-ceria. Density functional theory (DFT) calculations for the application of pristine and various metal-doped m-ceria in peroxidase-like reactions under different pH environments are conducted to select Co as the appropriate dopant. The high peroxidase-like activity of Co-m-ceria under neutral conditions and its mesoporous nature enable its application in a one-pot cascade reaction system, wherein biomarkers of oxidative enzymes can be detected without altering the pH. Five different oxidative enzymes are immobilized in the pores of Co-m-ceria at high loadings, followed by incorporation of the enzymecontaining Co-m-ceria in paper microfluidic devices for the convenient and simultaneous detection of multiple biomarkers. The Co-m-ceria-incorporated paper microfluidic device enables the selective and sensitive determination of multiple biomarkers using a smartphone-acquired image. This study demonstrates the potential of the rational design of nanozymes and their application in paper microfluidic devices, laying the groundwork for future applications of nanozymes in point-of-care testing environments.

Insights on catalytic mechanism of CeO2 as multiple nanozymes

“…The above investigations indicated a correlation between the structural defects of ceria nanozymes and their catalytic activity as peroxidase mimics [31,55,[96][97][98][99][100]. The high catalytic activity was found on the CeO 2 nanozymes featured with the high level of the surface Ce 3+ fraction and large surface area.…”

“…Further calculations suggest that the dissociative chemisorption of H 2 O 2 on CeO 2 is the ratedetermined step (Figs. 4(b) and 4(c)) [97]. The kinetic energy barrier of this step is 1.14 eV on the defective CeO 2 surface, where the oxygen vacancy located on the third layer gives the best catalytic performance.…”

Amorphous Fe-Containing Phosphotungstates Featuring Efficient Peroxidase-like Activity at Neutral pH: Toward Portable Swabs for Pesticide Detection with Tandem Catalytic Amplification

“…Lee's group developed Co-doped mesoporous ceria based on density functional theory analysis for multiple biomarker detection in neutral environments. 10 However, a suitable dopant−matrix match remains difficult to achieve. Another method is the addition of extra chemical reagents (e.g., adenosine triphosphate) or energy sources (e.g., light) to facilitate charge conversion during reactions.…”

“…It is known that a majority of natural enzymes show the best catalytic performance at physiological pH . However, almost all of the peroxidase mimics explored currently, from the first reported Fe 3 O 4 to the latest single-atom nanozyme, are restricted to acidic conditions. − The pH mismatch between peroxidase mimics in acidic environments and bioenzymes under neutral conditions significantly hinders the development of enzyme–nanozyme catalytic systems especially for biochemical sensing.…”

Biosensor Based on Peroxidase-Mimetic Nanozyme and Lactate Oxidase for Accurate L-Lactate Analysis in Beverages

“…The first nanozyme was described back in 1970 by Breslow et al [ 16 ]. From that time, hundred different types, structures, and properties nanozymes were synthesized, characterized, and successfully used in sensor technology [ 17 , 18 , 19 , 20 ]. Despite the large number of lactate biosensors created on the basis of different nanocomposites, increasing their sensitivity and their adaptation for the analysis of the target analyte in complex mixtures of real samples is still an urgent task.…”