Ultra-sensitive DNA detection with single-base mismatch resolution using graded hollow-core optical microcavity functionalized by polyA-AuNPs

A graded hollow-core optical microcavity (GHCOM) functionalized by polyA-AuNPs is proposed and demonstrated for DNA hybridization detection with ultra-low limit of detection (LoD) and high specificity. The GHCOM with wall thickness of ∼2 μm and Q factor of 7.8 × 10⁶ is fabricated, featuring a graded longitudinal shape which enhances light-matter interaction near sensing interface of the microcavity. Whispering gallery mode (WGM) oscillation is excited and traced spectrally for monitoring DNA hybridization in real-time. PolyA-AuNPs are functionalized onto the surface of the GHCOM to increase biological binding sites on sensor surface and hybridization efficiency between DNA molecules. DNA hybridization detection of concentration ranging from 1 fM to 1 pM is achieved, with measured DNA biosensing sensitivity of 2.38pm/lg fM and LoD of∼ 583 aM. Specific single-base mismatch detection of 19-base target DNA is also achieved by optical spectra detection of WGM oscillation. The proposed label-free DNA biosensor has advantageous of high sensitivity, high specificity and robustness, having important application values in bioengineering and disease diagnosis.