In Situ Sampling and Monitoring Cell-Free DNA of the Epstein-Barr Virus from Dermal Interstitial Fluid Using Wearable Microneedle Patches

ACS Appl Mater Interfaces. 2019 Oct 23;11(42):38448-38458. doi: 10.1021/acsami.9b12244. Epub 2019 Oct 8.

Abstract

Using polymerase chain reaction and genotyping, Epstein-Barr virus cell-free DNA (EBV Cf DNA) was detectable in interstitial fluid (ISF). Microneedles offer a minimally invasive approach to capture such Cf DNA. However, a key challenge of microneedles lies in the ability to specifically isolate biomarkers within a short time. We introduced a hydrogel microneedle patch for rapid and easy capture of EBV Cf DNA from ISF in situ around 15 min, with a maximum capture efficiency of 93.6%. Then, quantification of EBV Cf DNA was achieved by electrochemical recombinase polymerase amplification wearable flexible microfluidics, with a detection limit of 3.7 × 102 copies/μL. Animal tests supported the performance of microneedles for EBV Cf DNA capture. Collectively, these data showed that the microneedle patch may have broad implications for patients with Cf DNA-related disease and cancer metastasis in minimally invasive manners.

Keywords: Epstein−Barr virus; cell-free DNA; flexible microfluidics; microneedle patch; wearable device.

MeSH terms

  • Animals
  • Cell Survival / drug effects
  • Cell-Free Nucleic Acids / analysis*
  • Cell-Free Nucleic Acids / metabolism
  • Electrochemical Techniques / instrumentation
  • Electrochemical Techniques / methods*
  • Extracellular Fluid / metabolism*
  • Female
  • Gold / chemistry
  • HeLa Cells
  • Herpesvirus 4, Human / genetics*
  • Humans
  • Hydrogels / chemistry
  • Hydrogels / pharmacology
  • Limit of Detection
  • Mice
  • Mice, Nude
  • Microfluidics
  • Nanowires / chemistry
  • Needles
  • Polymerase Chain Reaction
  • Wearable Electronic Devices*

Substances

  • Cell-Free Nucleic Acids
  • Hydrogels
  • Gold