Oligonucleotide Discrimination Enabled by Tannic Acid-Coordinated Film-Coated Solid-State Nanopores

Discrimination of nucleotides serves as the basis for DNA sequencing using solid-state nanopores. However, the translocation of DNA is usually too fast to be detected, not to mention nucleotide discrimination. Here, we utilized polyphenolic TA and Fe³⁺, an attractive metal-organic thin film, and achieved a fast and robust surface coating for silicon nitride nanopores. The hydrophilic coating layer can greatly reduce the low-frequency noise of an original unstable nanopore, and the nanopore size can be finely tuned in situ at the nanoscale by simply adjusting the relative ratio of Fe³⁺ and TA monomers. Moreover, the hydrogen bonding interaction formed between the hydroxyl groups provided by TA and the phosphate groups of DNAs significantly increases the residence time of a short double-strand (100 bp) DNA. More importantly, we take advantage of the different strengths of hydrogen bonding interactions between the hydroxyl groups provided by TA and the analytes to discriminate between two oligonucleotide samples (oligodeoxycytidine and oligodeoxyadenosine) with similar sizes and lengths, of which the current signal patterns are significantly different using the coated nanopore. The results shed light on expanding the biochemical functionality of surface coatings on solid-state nanopores for future biomedical applications.