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Ultrasensitive miR-451 Detection via DNAzyme-Mediated Etching with In Situ Single-Nanoparticle LSPR Monitoring.

Xingyu Zi^1,2, Kuilin Liu^1,2, Jianqi Wang^1,2

¹College of Electronic Information and Optical Engineering, Nankai University, Tianjin 300350, China.

Analytical Chemistry

|May 28, 2026

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A novel biosensing platform detects microRNA-451 (miR-451), a colorectal cancer biomarker, with ultrasensitive precision. This method combines amplification with nanoparticle monitoring for improved minimally invasive diagnostics.

Area of Science:

Biomedical Engineering
Nanotechnology
Molecular Diagnostics

Background:

MicroRNA-451 (miR-451) is a biomarker associated with colorectal cancer (CRC).
Minimally invasive detection methods for biomarkers like miR-451 are crucial for early diagnosis and monitoring.
Existing detection methods may lack the sensitivity or specificity required for complex biological samples.

Purpose of the Study:

To develop an ultrasensitive biosensing platform for detecting miR-451.
To couple off-chip hybridization chain reaction (HCR) amplification with in situ single-nanoparticle localized surface plasmon resonance (LSPR) monitoring.
To enable precise quantification of miR-451 in complex biological matrices.

Main Methods:

Utilized off-chip HCR to amplify miR-451 signals, generating DNA duplexes with G-quadruplex (G4) sequences.

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Employed hemin-G4 DNAzymes to catalyze the etching of silver shells on Au@Ag core-shell nanoparticles (Au@AgNPs) immobilized in a microfluidic chip.

Monitored spectral shifts (LSPR redshift) of individual nanoparticles before and after etching to quantify miR-451, minimizing sampling errors.

Main Results:

Achieved an ultrasensitive limit of detection (LOD) of 40.96 aM for miR-451.
Demonstrated a wide linear detection range from 100 aM to 100 pM.
Exhibited high specificity against nontarget and mismatched sequences.
Successfully evaluated applicability in fetal bovine serum and human serum, with RT-qPCR providing auxiliary verification.

Conclusions:

The developed biosensing platform offers ultrasensitive and specific detection of miR-451.
The combination of HCR amplification and in situ LSPR monitoring provides a robust approach for miRNA analysis.
This platform holds significant potential for minimally invasive diagnostics of colorectal cancer and other diseases in complex biological samples.