Surface-Enhanced Raman Scattering Probing the Translocation of DNA and Amino Acid through Plasmonic Nanopores

Abstract

DNA and amino acids are important biomolecules in living organisms. Probing such biomolecules with structural characters can provide valuable information for life study. Here, gold plasmonic nanopores (GPNs) with high SERS activity (a local enhancement factor higher than 109) are synthesized at the tip of a glass nanopipette. An electric field drives individual molecules to translocate through the GPNs, which enables in situ collection of the surface-enhanced Raman scattering (SERS). Nonresonant biomolecules, including nucleobases, amino acids, and oligonucleotides (DNA), with single nucleobase differences can be distinguished. The intensity of SERS is tunable by modulating the affinity between DNA and the GPNs. The present study shows the feasibility of applying a plasmonic nanopore to DNA and protein detection, which may also provide an easy way for tracking single molecule translocation by developing a well-defined single plasmonic nanopore.

In situsolid-state nanopore fabrication

“…These methods can be based on the detection of fluorescent labels, 77,78 light scattering, 79 and surface enhanced Raman spectroscopy. [80][81][82] Optical based detection strategies are often enhanced by integrating plasmonic nanostructres with the nanopore. [83][84][85][86] Given the ability of these alternate sensing modalities to overcome several of the fundamental limitations of ionic current based sensing, they will likely continue to attract interest in the coming years.…”

“…These sensing strategies can be based on the detection of fluorescent labels, 77,116 light scattering, 79 and surface enhanced Raman spectroscopy. 80,81 However, the need for precise alignment of the optical path with the nanopore remains a bottleneck for these experiments. Nanopores fabricated via laser etching partially overcome this issue by creating pores that are self-aligned with the optical path (although stage drift can be problematic and result in misalignment).…”

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].…”

“…A new approach in DNA/RNA sequencing is based on the combination of biological/solid-state nanopores with electrochemical measurements. While the DNA molecule goes through the gold SERS-active nanopore it produces a series of specific Raman signals that correspond to the bases in nanopore [165]. This DNA sequence research tool can be used for third generation sequencing (single-molecule reading), however, at the moment it does not have sufficient resolution to compete with other methods such as Oxford Nanopore, and it is now at the development and optimization stage while using oligonucleotides.…”

Nanopipette‐based electrochemical SERS platforms: Using electrodeposition to produce versatile and adaptable plasmonic substrates

“…[24,[27][28][29][30] Nanopipettes can also be used to inject reductants into a solution of gold salts, producing highly enhancing Au structures. [31] In all cases, however, the resulting nanostructures are not electronically connected, thus precluding dynamical control over the surface potential, which has been recently identified as an essential parameter to modulate surface-analyte affinity, [32][33][34][35] and consequentially the adsorption of analytes onto the hotspots. [36,37] In this paper, we take a different approach to render nanopipettes SERS active, converting nanopipettes into nanoelectrodes and using electrodeposition methods.…”