Editorial Feature

Sensing Molecules with Surface Enhanced Raman Spectroscopy


Surface Enhanced Raman Spectroscopy (SERS) is a type of Raman Spectroscopy, and an ultrasensitive analytical tool used for both chemical and biological analysis. It allows for label-free, non-destructive, direct detection of molecules through their Raman fingerprint. In this article, we examine how SERS is used to detect biological and chemical molecules.

It is used across a wide range of industries including analytical testing, trace material analysis, medical testing, drug discovery, and point of care testing. The development of portable Raman spectrometers has meant that the use of SERS can now also be used for field testing in forensics and biological and chemical threat detection.

Surface Enhanced Raman Spectroscopy

SERS was first discovered by Martin Fleischmann and his team from the University of Southampton in the 1970s, as a way of improving sensitivity when using Raman spectroscopy.

It works through the enhancement of Raman scattering through laser excitation of roughened metal surfaces and nanoparticles in colloidal solutions. The laser excitation creates a highly localized light field. When a molecule is absorbed or lies close to the enhanced field at the surface, an enhancement in the Raman signal is observed and recorded.

The most common nanoparticle types used in SERS are gold and silver nanospheres, but other shapes such as nanorods, nanostars, nanocubes, and nanowires can also be produced through a polymer-mediated polyol process.

Nanoparticles can be hollowed or capped using a number of chemical methods. The shape and size of nanoparticles affect SERS enhancement, and this is something that laboratories are still researching today.

Drug and Chemical Detection

One of the main uses of SERS is for drug and chemical detection. It can be used to analyze drugs for safety purposes, to detect illicit and legal drugs and can also be used to detect chemical threats. The detection of drugs and chemicals can be done directly through SERS alone, or by combining it with another analytical technique such as UPLC to clean up biological samples first.

With Raman and SERS being made portable, the use of SERS in field testing for forensics and chemical threat detection has greatly increased. Previous methods of analysis, such as using liquid chromatography and mass spectrometry, have lengthy sample preparation times, and SERS is providing a portable, sensitive, and fast alternative.

SERS for DNA Detection

There are many different methods of detecting DNA using SERS, including DNA hybridization, asymmetry signal amplification method, and gene chips methods.

SERS is used in DNA detection to identify DNA sequences, tell apart DNA from RNA in mixtures and to monitor hybridization of individual DNA in microfluidics. SERS can be utilized to target DNA and RNA sequences using both gold and silver nanoparticles, as well as Raman-active dyes.

DNA detection by SERS allows for gene detection of diseases such as Ebola, Hepatitis, HIV, and Bacillus Anthracis. SERS has an advantage over fluorescence techniques for gene detection because there are no markers which could overlap the gene markers like there are with fluorescence detection methods. There are already several Raman dyes commercially available which can be used for gene detection.

Protein Detection

SERS can be used to detect proteins by identifying their amino acid residues and polypeptide skeleton structure. SERS-based antigen-antibody reactions can also detect functional proteins.

Protein and lipid bilayers are dynamic three-dimensional structures that make use of the fact that SERS is a label-free way of characterization. SERS spectra also allow for deep biophysical characterization of the biomolecules near metallic surfaces.

SERS for protein detection is used in clinical diagnosis to detect specific disease-related protein biomarkers. The potential uses for SERS in biosensing are vast and include detection for diseases such as diabetes, cancer, Alzheimer’s, and Parkinson’s.

Clinical Diagnostics of Tissues

For many years immunofluorescence staining has been the gold standard for clinical diagnostics of tissues, but the fluorescent dyes used are highly toxic, so analysis cannot be carried out in vivo. Raman spectroscopy is a chemically specific, label-free diagnostic technique, so offers a solution to this problem. The fact that SERS is a fast, label-free technique has also proved to be a great advantage for point-of-care tests for therapeutic drug monitoring.

Environmental Sensing

Heavy metal cations and toxic anions are the two categories of toxic areas that SERS can analyze in the environment. Metal ions such as arsenic, mercury, lead, chromium, cadmium, and copper cause a variety of diseases and even sometimes death.

The toxic metals can be released naturally through volcanic emissions and the breakdown of metal-rich rocks, as well as from human activities such as combustion of coals, chemical and electronics manufacturing, and solid waste incineration.

SERS sensors cannot directly detect Monoatomic heavy metal ions, due to the fact they contain no chemical bonds to be able to generate Raman scattering, so only inorganic oxyanions and oxycations can be directly detected by their characteristic Raman vibration bands

Pathogen detection

As well as being used to detect contaminants in food, SERS is a technique that is rising in popularity to detect foodborne pathogens such as E. coli, Salmonella, and Staphylococcus Aureus.

A quick and effective method to detect foodborne pathogens is needed for both food safety and human health, which SERS provides over traditional pathogen detection methods. The two main ways to detect food pathogens include using silver colloid substrates, as well as biomarkers such as dipicolinic acid.

Traditional methods of detecting pathogens are lengthy processes with multiple steps that include the inoculation of microbes on agar plates, culturing and differentiating them. Faster techniques such as immunoassays and PCR are available, but they have limited detection of low concentrations of pathogens.

Infrared spectroscopy can be used to provide a fingerprint map of pathogens at low levels. However, unlike SERS, it is unable to detect pathogens when they are in solutions.


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Louise Saul

Written by

Louise Saul

Louise pursued her passion for science by studying for a BSc (Hons) Biochemistry degree at Sheffield Hallam University, where she gained a first class degree. She has since gained a M.Sc. by research and has worked in a number of scientific organizations.


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