Magnetic Large‐Mesoporous Nanoreactors Enable Enzymatically Regulated Background‐Free and Persistently Signalling Diseases Diagnosis

Abstract

Diverse diseases and increasing prevalence pose a serious threat to public health. Point-of-care testing (POCT) techniques have imposed superior requirements over sensitivity, selectivity, robustness, affordability, and highthroughput. However, transient signal, complex sample pretreatment, and low signal-to-noise ratio make POCT severely limited in detection accuracy, efficiency, and sensitivity. Here, an enzyme-assisted magnetic large-mesoporous nanoreactor (FS) is constructed for achieving persistent-chemiluminescence signal output and eliminating matrix interference in disease diagnosis. The core-shell structured FS synthesized via an interface coassembly method exhibits uniform size, large and open mesopores (≈22 nm), and intrinsic magnetic separability. Such unique FS acts as efficient nanoreactor for confined cascade reactions enable efficient persistent-chemiluminescence (pCL) signal transduction and high-SNR chromogenic analysis of diverse biomarkers. The developed pCL assays facilitate high-sensitive determination of chronic disease biomarkers glucose and uric acid with detection limits (DL) of 5.4 mg L −1 and 151.2 ng L −1 , respectively. The proposed chromogenic immunoassay enables an ultrasensitive and visual determination of alpha-fetoprotein with a DL of 1.2 ng L −1 , which is superior to previously published immunoassays. The feasibility of the developed methods for real-world applications are demonstrated in 159 clinical serum samples, and the determination results agree well with the clinical data. The proposed technique is expected to promote highly sensitive disease diagnosis in primary medical institutions and resource-limited areas since not relying on expensive automatic sampling and testing instruments. The good flexibility of the customizable nanoreactor makes it a powerful tool for developing various POCT techniques for rapid, sensitive, and accurate diseases diagnosis.

Spatially Confined Nanoreactors Designed for Biological Applications

“…Li et al synthesized an enzyme-assisted magnetic large-mesoporous nanoreactor by in situ growth of a large mesoporous silica shell on a Fe 3 O 4 core via an interfacial co-assembly method. [47] By anchoring diverse biological macromolecules inside using 3glyoxypropyl trimethoxysilane as a bridging ligand, the nanoreactor was developed as customizable nanoprobes and applied for point-of-care testing, which achieved highly sensitive quantification of chronic disease biomarkers (glucose and uric acid) (Figure 3A), with detection limits of 5.4 mg L −1 for glucose and 151.2 ng L −1 for uric acid in serum. The feasibility of this method was further validated in 159 clinical serum samples, showing excellent agreement with clinical results.…”

“…Molecular detection [ 43] Disease diagnosis [ 47] Cancer therapy [ 52] Protein identification [ 58] >50 Oxidoreductase, proteins…”

“…A) Schematic diagram for the fabrication of the enzyme-assisted magnetic large-mesoporous nanoreactor (FS) for disease diagnosis and the enlarged field-emission scanning electron microscope image of the ultrathin slice of a single FS displayed the large and open mesopores of≈22nm which contributes to a fast adsorption and collection of analytes in complex samples. Reproduced with permission [47]. Copyright 2022, Wiley-VCH.…”

Construction of Magnetic Core–Large Mesoporous Satellite Immunosensor for Long‐Lasting Chemiluminescence and Highly Sensitive Tumor Marker Determination

“…[18] In particular, mesoporous materials, such as mesoporous silica nanospheres (MSNs), have attracted widespread attention in CL assay for enhanced signal intensity and improved detection sensitivity due to their unique properties (e.g., adjustable pore size, large pore volume, easily modifiable surface, and high specific surface area). [19][20][21] For example, Gu et al exploited a novel chemiluminescent biosensor by encapsulating chemiluminescent label molecules into ordered MSNs with specific DNA gates for ultra-sensitive detection of nuclease activity and bacteria. [22] The sensitivity and selectivity of chemiluminescence assay could be further improved by regulating the pore size to selectively couple guest molecules with different sizes on their surface or interior.…”

Coaxial Electrohydrodynamic Printing of Microscale Core–Shell Conductive Features for Integrated Fabrication of Flexible Transparent Electronics

“…Flexible electronics have attracted extensive attention owing to their unique electrical/thermal/optical/sensing capability under mechanical deformation conditions, which have found a broad spectrum of applications in health monitoring, , disease treatment, , Internet of thing, , soft robots, virtual reality, and augmented reality. , To simultaneously achieve large flexibility and specific functionality, a reliable encapsulating layer is commonly required to protect microscale conductive features from external physical/chemical exposure, electrical interconnects, or mechanical damage …”