High spatial resolution nanoslit SERS for single-molecule nucleobase sensing

Abstract

Solid-state nanopores promise a scalable platform for single-molecule DNA analysis. Direct, real-time identification of nucleobases in DNA strands is still limited by the sensitivity and the spatial resolution of established ionic sensing strategies. Here, we study a different but promising strategy based on optical spectroscopy. We use an optically engineered elongated nanopore structure, a plasmonic nanoslit, to locally enable single-molecule surface enhanced Raman spectroscopy (SERS). Combining SERS with nanopore fluidics facilitates both the electrokinetic capture of DNA analytes and their local identification through direct Raman spectroscopic fingerprinting of four nucleobases. By studying the stochastic fluctuation process of DNA analytes that are temporarily adsorbed inside the pores, we have observed asynchronous spectroscopic behavior of different nucleobases, both individual and incorporated in DNA strands. These results provide evidences for the single-molecule sensitivity and the sub-nanometer spatial resolution of plasmonic nanoslit SERS.

Surface-enhanced Raman spectroscopy: benefits, trade-offs and future developments

“…For the traditional SERS substrates, there are increasing efforts towards the development of non-typical substrate congurations like nanoholes, gratings, or other nanoapertures, which may be advantageous for SERS dynamic sensing applications at the single molecule level, especially in the eld of life science. 117,118 We would also like to bring the readers' attention to the current efforts towards nding new materials with SERS enhancement approaching that of gold and silver. For example, Mo-doped Ta 2 O 5 , WO 3 with oxygen vacancies, nanostructured TiN, 119,120 and metal telluride have been observed to show SERS in the visible region, 39,44,119,121 while having very good chemical stability.…”

Speculation of Nano-gap Sensor for DNA sequencing technology: A Review on Synthetic Nanopores

“…(b) The measurement setup of nanopore device with nanoslit cavity to enhance Raman signal. They showed distinct Raman peak shift for 4 four different nucleotides [91].…”

“…Nanoslit structure has also been introduced in Raman spectroscopy to promote optical signal showing the distinct spectrum shift of four different bases (see Fig. 8b) [91]. The nanoslit was fabricated by nanomachining processes; starting from electron beam lithography to create pattern of nanoslit, KOH anisotropic wet etching to make inverse pyramidal cavity shape, BHF etching to open the nanoslit structure and Au sputtering.…”

Raman Scattering: From Structural Biology to Medical Applications

“…Great enhancement of the Raman signal from analyte that was fixed on a silver electrode was discovered in the middle of the 1970s. Currently, an array of different nanoparticles with various coating is used for DNA and RNA detection and even sequencing [163][164][165].…”