Nanopore-Based Single-Molecule Detection Using Self-Assembling Nanoparticle Probes for Enhanced Biomarker Screening

The ability to detect biomarkers with precision at the single-molecule level in biological fluids could revolutionise disease diagnosis, monitoring, and treatment. Nanopore technology has gained prominence, initially for sequencing and now for screening applications. While labelling can enhance nanopore sensing selectivity, challenges remain, particularly in distinguishing between bound and unbound targets. This study presents highly sensitive molecular probes made from nanoparticles (NPs) that self-assemble and dimerise when bound to a biological target. Both single and paired NPs can be successfully detected using nanopore sensing, with potential applications in pathogen detection and analysis. This technology is expected to advance sensitive, selective diagnostic strategies that require minimal sample volume, without the need for processing or amplification.