Sensitive Quantification of MicroRNA in Blood through Multi-amplification Toehold-Mediated DNA-Strand-Displacement Paper-Spray Mass Spectrometry (TSD-PS MS)

Angew Chem Int Ed Engl. 2022 Feb 21;61(9):e202113051. doi: 10.1002/anie.202113051. Epub 2022 Jan 14.

Abstract

Accurate quantification of disease-signature microRNAs (miRNAs) in biomedical samples is in high demand for clinical diagnosis but still challenging because of the low abundance of miRNAs and complicating interferences in the milieus. Here, we report a multi-amplification strategy based on paper-spray mass spectrometry (PS MS) for the analysis of miRNAs in blood. A toehold-mediated DNA-strand-displacement reaction (TSD) is employed to amplify the signal chain and to ensure the specificity. The signal chain is then cleaved by UV light to release signal molecules for detection. Moreover, the paper spray method can efficiently filter out interfering substances in the blood and further enhance the sensitivity of detection. This concept is successfully demonstrated in the prototypical detection of the cancer biomarker miRNA-141 in blood and serum. The proposed TSD-PS MS approach provides an efficient method for the sensitive detection of oligonucleotides at low concentration in complicated milieus.

Keywords: Light-assisted detection; Mass spectrometry; Multi-amplification; Paper spray; microRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers, Tumor / blood*
  • Biosensing Techniques
  • DNA / chemistry*
  • Humans
  • Mass Spectrometry
  • MicroRNAs / blood*
  • Neoplasms / blood*
  • Neoplasms / pathology
  • Nucleic Acid Amplification Techniques*
  • Paper*

Substances

  • Biomarkers, Tumor
  • MIRN141 microRNA, human
  • MicroRNAs
  • DNA