skip to main content


Title: Machine learning for composition analysis of ssDNA using chemical enhancement in SERS

Surface-enhanced Raman spectroscopy (SERS) is an attractive method for bio-chemical sensing due to its potential for single molecule sensitivity and the prospect of DNA composition analysis. In this manuscript we leverage metal specific chemical enhancement effect to detect differences in SERS spectra of 200-base length single-stranded DNA (ssDNA) molecules adsorbed on gold or silver nanorod substrates, and then develop and train a linear regression as well as neural network models to predict the composition of ssDNA. Our results indicate that employing substrates of different metals that host a given adsorbed molecule leads to distinct SERS spectra, allowing to probe metal-molecule interactions under distinct chemical enhancement regimes. Leveraging this difference and combining spectra from different metals as an input for PCA (Principal Component Analysis) and NN (Neural Network) models, allows to significantly lower the detection errors compared to manual feature-choosing analysis as well as compared to the case where data from single metal is used. Furthermore, we show that NN model provides superior performance in the presence of complex noise and data dispersion factors that affect SERS signals collected from metal substrates fabricated on different days.

 
more » « less
Award ID(s):
1704085 1707641 1807890 1901844
PAR ID:
10184764
Author(s) / Creator(s):
; ; ;
Publisher / Repository:
Optical Society of America
Date Published:
Journal Name:
Biomedical Optics Express
Volume:
11
Issue:
9
ISSN:
2156-7085
Format(s):
Medium: X Size: Article No. 5092
Size(s):
Article No. 5092
Sponsoring Org:
National Science Foundation
More Like this
  1. null (Ed.)
    Abstract Surface-enhanced Raman scattering (SERS) process results in a tremendous increase of Raman scattering cross section of molecules adsorbed to plasmonic metals and influenced by numerous physico-chemical factors such as geometry and optical properties of the metal surface, orientation of chemisorbed molecules and chemical environment. While SERS holds promise for single molecule sensitivity and optical sensing of DNA sequences, more detailed understanding of the rich physico-chemical interplay between various factors is needed to enhance predictive power of existing and future SERS-based DNA sensing platforms. In this work, we report on experimental results indicating that SERS spectra of adsorbed single-stranded DNA (ssDNA) isomers depend on the order on which individual bases appear in the 3-base long ssDNA due to intramolecular interaction between DNA bases. Furthermore, we experimentally demonstrate that the effect holds under more general conditions when the molecules do not experience chemical enhancement due to resonant charge transfer effect and also under standard Raman scattering without electromagnetic or chemical enhancements. Our numerical simulations qualitatively support the experimental findings and indicate that base permutation results in modification of both Raman and chemically enhanced Raman spectra. 
    more » « less
  2. Nanohybrids of graphene and two-dimensional (2D) layered transition metal dichalcogenides (TMD) nanostructures can provide a promising substrate for extraordinary surface-enhanced Raman spectroscopy (SERS) due to the combined electromagnetic enhancement on TMD nanostructures via localized surface plasmonic resonance (LSPR) and chemical enhancement on graphene. In these nanohybrid SERS substrates, the LSPR on TMD nanostructures is affected by the TMD morphology. Herein, we report the first successful growth of MoS2 nanodonuts (N-donuts) on graphene using a vapor transport process on graphene. Using Rhodamine 6G (R6G) as a probe, SERS spectra were compared on MoS2 N-donuts/graphene nanohybrids substrates. A remarkably high R6G SERS sensitivity up to 2 × 10−12 M has been obtained, which can be attributed to the more robust LSPR effect than in other TMD nanostructures such as nanodiscs as suggested by the finite-difference time-domain simulation. This result demonstrates that non-metallic TMD/graphene nanohybrids substrates can have SERS sensitivity up to one order of magnitude higher than that reported on the plasmonic metal nanostructures/2D materials SERS substrates, providing a promising scheme for high-sensitivity, low-cost applications for biosensing. 
    more » « less
  3. Surface-enhanced Raman scattering (SERS) provides orders of magnitude of enhancements to weak Raman scattering. The improved sensitivity and chemical information conveyed in the spectral signatures make SERS a valuable analysis technique. Most of SERS enhancements come from the electromagnetic enhancement mechanism, and changes in spectral signatures are usually attributed to the chemical enhancement mechanism. As the electromagnetic mechanism has been well studied, we will give an overview of models related to the chemical mechanism, which explain the Raman response in terms of electronic transitions or induced electron densities. In the first class of models based on electronic transitions, chemical enhancements are attributed to changes in transitions of the molecule and new charge transfer transitions. The second class of models relate chemical enhancements to charge flows near the molecule–metal interface by partitioning the induced electron density of the SERS system in real space. Selected examples will be given to illustrate the two classes of models, and connections between the models are demonstrated for prototypical SERS systems. 
    more » « less
  4. Abstract

    Two‐dimensional transition metal dichalcogenides (TMDs)/graphene van der Waals (vdW) heterostructures integrate the superior light–solid interaction in TMDs and charge mobility in graphene, and therefore are promising for surface‐enhanced Raman spectroscopy (SERS). Herein, a novel TMD (MoS2and WS2) nanodome/graphene vdW heterostructure SERS substrate, on which an extraordinary SERS sensitivity is achieved, is reported. Using fluorescent Rhodamine 6G (R6G) as probe molecules, the SERS sensitivity is in the range of 10−11to 10−12mon the TMD nanodomes/graphene vdW heterostructure substrates using 532 nm Raman excitation, which is comparable to the best sensitivity reported so far using plasmonic metal nanostructures/graphene SERS substrates, and is more than three orders of magnitude higher than that on single‐layer TMD and graphene substrates. Density functional theory simulation reveals enhanced electric dipole moments and dipole–dipole interaction at the TMD/graphene vdW interface, yielding an effective means to facilitate an external electrostatic perturbation on the graphene surface and charge transfer. This not only promotes chemical enhancement on SERS, but also enables electromagnetic enhancement of SERS through the excitation of localized surface plasmonic resonance on the TMD nanodomes. This TMD nanodome/graphene vdW heterostructure is therefore promising for commercial applications in high‐performance optoelectronics and sensing.

     
    more » « less
  5. Escherichia coli single-stranded (ss)DNA binding (SSB) protein mediates genome maintenance processes by regulating access to ssDNA. This homotetrameric protein wraps ssDNA in multiple distinct binding modes that may be used selectively in different DNA processes, and whose detailed wrapping topologies remain speculative. Here, we used single-molecule force and fluorescence spectroscopy to investigate E. coli SSB binding to ssDNA. Stretching a single ssDNA-SSB complex reveals discrete states that correlate with known binding modes, the likely ssDNA conformations and diffusion dynamics in each, and the kinetic pathways by which the protein wraps ssDNA and is dissociated. The data allow us to construct an energy landscape for the ssDNA-SSB complex, revealing that unwrapping energy costs increase the more ssDNA is unraveled. Our findings provide insights into the mechanism by which proteins gain access to ssDNA bound by SSB, as demonstrated by experiments in which SSB is displaced by the E. coli recombinase RecA.

     
    more » « less