3D-printed MOF-hydrogel microarray for multiplexed miRNA detection and early herb-induced liver injury warning

Area of Science:

• Biomedical Engineering
• Molecular Diagnostics
• Toxicology

Background:

• Herb-induced liver injury (HILI) lacks sensitive and timely biomarkers beyond ALT/AST.
• Circulating microRNAs (miRNAs) like miR-122 and miR-194 show promise for liver injury detection.
• Detecting low-abundance analytes requires advanced sensing technologies.

Purpose of the Study:

• To develop a highly sensitive and rapid diagnostic platform for early HILI detection.
• To validate a novel circulating miRNA biomarker panel (miR-122 and miR-194) for HILI.
• To integrate advanced materials and fabrication techniques for a high-throughput sensor array.

Main Methods:

• Fabrication of a 3D-printed multifunctional metal-organic framework (MOF)-hydrogel microarray (3D-MHMA).
• Integration of UiO-66-NH2 MOF nanoparticles for target enrichment and fluorescence quenching.
• Utilized a catalytic hairpin assembly-hybridization chain reaction (CHA-HCR) cascade for signal amplification.
• 3D bioprinting for creating a high-throughput, spatially encoded sensor array.

Main Results:

• Achieved ultra-sensitive detection of miR-122 and miR-194 with a limit of detection of 2.61 fM.
• Demonstrated reliable miRNA profiling in cellular and animal models of triptolide-induced liver injury.
• Showcased that miRNA release significantly preceded ALT/AST elevation, providing an early diagnostic window (AUC >0.9).

Conclusions:

• The 3D-MHMA platform coupled with miR-122/miR-194 biomarkers enables early HILI detection.
• This integrated solution offers a superior diagnostic window compared to conventional methods.
• Presents a promising approach for early warning systems in clinical toxicology and personalized medicine.