Electrochemical determination of microRNAs based on isothermal strand-displacement polymerase reaction coupled with multienzyme functionalized magnetic micro-carriers

Biosens Bioelectron. 2016 Jun 15:80:344-351. doi: 10.1016/j.bios.2015.12.064. Epub 2015 Dec 21.

Abstract

MicroRNAs (miRNAs) show great potential for disease diagnostics due to their specific molecular profiles. Detection of miRNAs remains challenging and often requires sophisticated platforms. Here we report a multienzyme-functionalized magnetic microcarriers-assisted isothermal strand-displacement polymerase reaction (ISDPR) for quantitative detection of miRNAs. Magnetic micro-carriers (MMCs) were functionalized with molecular beacons to enable miRNAs recognition and magnetic separation. The target miRNAs triggered a phi29-mediated ISDPR, which can produce biotin-modified sequences on the MMCs. Streptavidin-alkaline phosphatase was then conjugated to the MMC surface through biotin-streptavidin interactions. In the presence of 2-phospho-L-ascorbic acid, miRNAs were quantitatively determined on a screen-printed carbon electrode from the anodic current of the enzymatic product. We show that this method enables detection of miRNAs as low as 9 fM and allows the discrimination of one base mismatched sequence. The proposed method was also successfully applied to analyze miRNAs in clinical tumor samples. This paper reports a new strategy for miRNAs analysis with high sensitivity, simplicity, and low cost. It would be particularly useful for rapid point-of-care testing of miRNAs in clinical laboratory.

Keywords: Electrochemical sensing assay; Magnetic microcarriers; MicroRNA; Signal amplification.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biosensing Techniques / methods
  • Biotin / chemistry
  • Breast / pathology
  • Breast Neoplasms / diagnosis
  • Breast Neoplasms / genetics*
  • Electrochemical Techniques / methods*
  • Female
  • Humans
  • Limit of Detection
  • Magnets / chemistry
  • MicroRNAs / analysis*
  • Nanoparticles / chemistry
  • Nanoparticles / ultrastructure
  • Nucleic Acid Amplification Techniques / methods
  • Sensitivity and Specificity
  • Streptavidin / chemistry

Substances

  • MIRN21 microRNA, human
  • MicroRNAs
  • Biotin
  • Streptavidin