An active-matrix digital microfluidic platform for simultaneous short- and long-read viral genomic surveillance

Abstract

The outbreak frequency and geographic distribution of viral pathogens are continuously expanding, making enhanced genomic surveillance an urgent global public health need. Parallel library preparation combining next-generation sequencing (NGS) and third-generation sequencing (TGS) can substantially improve the coverage and resolution of genomic surveillance, representing a key strategy for strengthening surveillance. Here we developed a complete sample-to-result system integrating a programmable active-matrix digital microfluidic (AM-DMF) chip with a bioinformatics analysis pipeline. Compared with conventional manual protocols used in public health laboratories, our system reduces reagent consumption by 72%, shortens library preparation time by 45% and decreases the inter-batch coefficient of variation (CV) by 20%. In 20 RT-qPCR-confirmed clinical samples, the system achieved complete concordance for viral identification and assigned serotypes/genotypes consistent with sequencing-based phylogenetic analysis. This system is field-deployable and enables rapid virus serotyping as well as in-depth genomic surveillance. TeaserA digital microfluidic platform integrating short- and long-read sequencing enables rapid comprehensive viral genome analysis.