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Updated: May 7, 2026

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Enhancing the miRNA Detection Sensitivity of DNA Origami Book Biosensors Using Lock Modifications and a Polymer

Ivana Domljanovic1,2, Samet Kocabey1,3, Guillermo P Acuna3,2

  • 1Laboratory of Experimental and Translational Oncology, Department of Oncology, Microbiology and Immunology, Faculty of Science and Medicine, University of Fribourg, Chemin du Musée 18, PER17, Fribourg, 1700, Switzerland.

Small (Weinheim an Der Bergstrasse, Germany)
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Summary

This study presents a DNA origami biosensor for rapid and sensitive microRNA detection in human serum and plasma. Modifications enhance sensitivity, enabling early cancer diagnostics and liquid biopsy applications.

Keywords:
DNA origami biosensorFRETbreast cancermiRNAquenching

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Area of Science:

  • Nanotechnology
  • Molecular Diagnostics
  • Biotechnology

Background:

  • DNA origami offers a programmable platform for sensitive and specific molecular diagnostics.
  • MicroRNA detection is crucial for early disease diagnosis and personalized medicine.

Purpose of the Study:

  • To validate a dynamic DNA origami book biosensor for direct microRNA-21 (miR-21) detection in complex biological fluids.
  • To enhance biosensor sensitivity and specificity through modifications to the lock mechanism and polymer addition.
  • To demonstrate the potential for simultaneous microRNA detection in clinical samples for liquid biopsy applications.

Main Methods:

  • Utilized a DNA origami book biosensor with Förster resonance energy transfer (FRET) and fluorescence quenching optical readouts.
  • Engineered lock mechanisms using fluorine-modified bases and locked nucleic acid (LNA).
  • Incorporated diethylene glycol (DEG), a biocompatible polymer, to improve detection sensitivity.

Main Results:

  • Achieved direct detection of miR-21 in human serum and plasma with high specificity.
  • Demonstrated rapid detection (within 10 min) with low limits of detection (LoD) in buffer (0.69 pm with LNA), serum (8.86 pm), and plasma (23.24 pm) without amplification.
  • Successfully performed simultaneous detection of miR-21 and miR-7a in clinical plasma samples.

Conclusions:

  • The DNA origami biosensor platform is effective for sensitive and specific microRNA detection in complex biological samples.
  • Modifications to the lock mechanism and the addition of polymers significantly enhance biosensor performance.
  • The platform shows great promise for personalized diagnostics and liquid biopsy, enabling diverse microRNA biomarker profiling.