Threading Precision: Progress and Emerging Trends in Aptamer-Based Nanopore Sensing

In recent years, nanopore technology has enhanced analyte detection, enabled higher resolution and achieved single-molecule sensing capability. Aptamer-conjugated nanopore sensing technology combines the high specificity of aptamers with the single-molecule resolution of nanopores. By anchoring aptamers to biological, solid-state or hybrid nanopores, target binding events produce distinct electrical signatures that allow sensitive and label-free detection. This approach enables real-time monitoring of small molecules, proteins, and even pathogens, with promising applications in diagnostics, drug screening, environmental monitoring, etc. Hybrid biological/solid state devices produce robust signals and are suitable for PoC applications. The aptamers "magic bullets" have also been exploited to develop single-molecule antigen detection using nanopores, which offers a promising alternative for accurate virus testing to contain their transmission. Chemical conjugation of aptamers to nanopore interfaces improves selectivity for peptides/amino acids and expands robustness for practical samples. Aptamer-based nanopipettes offer high analytical precision by enabling label-free, real-time detection of target molecules in ultra-small sample volumes. This review maps aptamer-nanopore integration across biological, solid-state, and hybrid platforms. It also explores various types of aptamers integrated into nanopore platforms that cater to precise, single-molecule recognition, paving the way for highly sensitive, portable diagnostics and next-generation therapeutic monitoring tools.