Enhanced detection of HBV and HCV using Cas13a-FLAP and FGoAI platforms.
Xijuan Gu, Tianyi Wang, Lingwei Wu, Jiayun Guan, Xiaoxia Kang, Wenjun Ming, Yidan Zhu, Qian Xu, Yuling Qin, Li Wu
Abstract
Open AccessHepatitis viruses continue to pose a major global health burden, underscoring the critical role of early diagnosis in achieving effective disease control. Here, a ratiometric fluorescence biosensor based on Cas13a and fluorescent RNA aptamers was developed for the highly efficient detection of hepatitis viruses. The integrated system consists of three functionally coupled modules: (i) duplex-specific nuclease (DSN)-enabled target recognition and sequence-specific cleavage, (ii) Cas13a-activated collateral degradation, and (iii) fluorescent RNA aptamer-based ratiometric biosensor. The proof-of-concept evaluation established limits of detection of 7.4 copies per µL for the hepatitis B virus (HBV) gene and 2.9 copies per µL for the hepatitis C virus (HCV) gene, respectively. Subsequently, image discrimination was performed using a portable fluorescence imaging device. By innovatively merging classical image processing with AI algorithms, the system achieved significantly enhanced stability and anti-interference capability in image analysis. As a result, the efficiency of this platform was successfully validated through the analysis of clinical samples, achieving a specificity of 100% and a sensitivity of over 96.3%, thereby demonstrating its high diagnostic accuracy. The proposed strategy demonstrates significant potential as a sensitive and highly specific diagnostic platform for hepatitis virus detection.