[Paper Review] Single-molecule DNA Bases Discrimination in Oligonucleotides by Controllable Trapping in Plasmonic Nanoholes

Jian‐An Huang, Mansoureh Z. Mousavi+7 more|arXiv (Cornell University)|May 6, 2019

Nanopore and Nanochannel Transport Studies92 references57 citations

TL;DR

The paper demonstrates single-molecule SERS discrimination of all four DNA bases by trapping a gold nanoparticle in plasmonic nanoholes to extend residence time, enabling labeling-free base identification in oligonucleotides.

ABSTRACT

Surface-enhanced Raman spectroscopy (SERS) sensing of DNA sequences by plasmonic nanopores could pave a way to new generation single-molecule sequencing platforms. The SERS discrimination of single DNA bases depends critically on the time that a DNA strand resides within the plasmonic hot spot. However, DNA molecules flow through the nanopores so rapidly that the SERS signals collected are not sufficient for single-molecule analysis. In this work, we report an approach to control the time that molecules reside in the hot spot by physically adsorbing them onto a gold nanoparticle and then trapping the single nanoparticle in a plasmonic nanohole. By trapping the nanoparticle for up to minutes, we demonstrate single-molecule SERS detection of all 4 DNA bases as well as discrimination of single nucleobases in a single oligonucleotide. Our method can be extended easily to label-free sensing of single-molecule amino acids and proteins.

Motivation & Objective

• Motivate nanopore-based SERS for single-molecule DNA sequencing.
• Address rapid translocation that limits SERS signal quality by increasing molecule residence time in the hot spot.
• Demonstrate controllable trapping of a gold nanoparticle in a plasmonic nanohole to enable single-molecule base discrimination.

Proposed method

• Physically adsorb DNA molecules onto a gold nanoparticle to form a localized SERS-active system.
• Trap the nanoparticle inside a plasmonic nanohole to controllably extend exposure time to the hot spot.
• Record SERS signals to discriminate all four DNA bases at the single-molecule level.
• Apply the approach to discriminate single nucleobases within a single oligonucleotide.

Experimental results

Research questions

• RQ1 Can single-molecule SERS discrimination of all DNA bases be achieved by increasing residence time in a plasmonic hot spot?
• RQ2 Does trapping a nanoparticle in a plasmonic nanohole allow discrimination of bases within single oligonucleotides without labeling?
• RQ3 Is the method extendable to other biomolecules such as amino acids and proteins?

Key findings

• Single-molecule SERS detection of all four DNA bases demonstrated.
• Controllable trapping yields residence times up to minutes in the hot spot.
• Successful discrimination of single nucleobases within a single oligonucleotide.
• Method suggests easy extension to label-free sensing of amino acids and proteins.