Abstract

AbstractSolid‐state nanopores are implemented in new and promising platforms that are capable of sensing fundamental biomolecular constituents at the single‐molecule level. However, several limitations and drawbacks remain. For example, the current strategies based on both electrical and optical sensing suffer from low analyte capture rates and challenging nanofabrication procedures. In addition, their limited discrimination power hinders their application in the detection of complex molecular constructs. In contrast, Raman spectroscopy has recently demonstrated the ability to discriminate both nucleotides and amino acids. Herein, a plasmonic nanoassembly is proposed supporting nanopores at high density, in the order of 100 pores per µm2. These findings demonstrate that the device has a high capture rate in the range of a few fm. The pore size is ≈10 nm in diameter and provides an amplification of the electromagnetic field exceeding 103 in intensity at 785 nm. Owing to these features, single‐molecule detection is achieved by means of surface‐enhanced Raman scattering from a solution containing 50 fm DNA molecules (≈4.4 kilobase pairs). Notably, the reported spectra show an average number of 2.5 Raman counts per nucleotide. From this perspective, this number is not far from what is necessary to discriminate the DNA sequence.

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