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

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.