Recent developments in surface-enhanced Raman spectroscopy in the field of chemical, biochemical and clinical application– a critical review

ABSTRACT

To comprehend the complex messages of science, we require visual senses for better understanding. It is evident that our visualisation falls short at minute levels. Surface Enhanced Raman Spectroscopy (SERS) facilitates the temporal identification and characterisation of the molecular composition, structure, and dynamics of a given sample. This technology promises to be an effective solution for many undiscovered and unaccounted outcomes in the chemical, biochemical, and clinical fields. Hence, early detection of large panels of bio targets, contaminants, and toxins is assessed with high levels of sensitivity and multiplexity, tracing to the extent of Nano (10^–9) levels. Over the past decade, nanomaterials-based SERS has emerged, shedding light on the importance of different dimensions of nanomaterials, primarily in the development of SERS sensing for various applications. SERS Nano probes offer remarkable improvements by focusing and imaging, utilising the Raman scattering efficiency, wherein molecules are absorbed on a nanostructured surface. This article elucidates the SERS principle, classification based on sensing dimensions, and its application in the field of food safety and drug monitoring, detecting various proteins, viruses, and bacteria, both in-vitro and in-vivo imaging, cancer biomarker detection, as well as detecting nutrients, pesticides, and foodborne pathogens by SERS. It serves as a collective review of recent advancements that have flourished in the past few years, highlighting concepts, issues, and challenges with the prior motive of incorporating and stimulating wider interest in developing SERS nanomaterial applications for chemical engineering.

KEYWORDS:

• Surface enhanced Raman spectroscopy
• nanotechnology
• nano probe
• biphotonic
• chemical imaging
• chemical sensing

1. Introduction

Raman spectroscopy is a technique that has been around for more than 80 years. In recent years, it has become an important tool in the field of material science as it allows scientists to detect and identify molecules based on their unique molecular vibrations. The technique is used to identify organic and inorganic compounds, as well as crystals, minerals, and polymers. It has an advantage over traditional IR spectroscopy by reducing sample preparation time. Initially, due to the difficulty in predicting Raman scattering, it was not widely used [1]. In 1974, three scientists from Southampton University observed Raman scattering of pyridine on a silver electrode that displayed a wide range of inelastic light scattering. From there, the term ‘Surface Enhanced Raman Spectroscopy’ (SERS) was coined [2]. SERS can enhance signals up to ${10}^6$ or more, enabling researchers to quantify minute details and detect biomarkers, dust, and other fine particles.

The mechanism enabling the function of Raman spectroscopy involves electromagnetic and chemical enhancement. Together, these two mechanisms provide a focal point where SERS can be utilised for various purposes [3]. There are two techniques of Raman spectroscopy – intrinsic and extrinsic. In intrinsic SERS, a unique spectrum directly measures the target molecules, thereby providing qualitative analysis. Applications include detection of glucose, amino acids, protein structure, antioxidants and DNA, though it is very insensitive to some molecules. Extrinsic SERS is an indirect method to analyse targets where nanoparticles are functionalised with a ligand [4].

The achievement of SERS depends on the substrate and SERS activity. The substrate must meet certain requirements to function properly: it must have high SERS activity and sensitivity, be rich in reproducibility, be stable, maintain a size of around 50 nm, and have interparticle spacing of less than 10 nm. Additionally, the substrate should be uniform to avoid miscalculations, and a clean substrate should be used to avoid impurities [5].

In this article, we will discuss what Raman spectroscopy is, how it works, some practical applications of this technique, and also explore recent advances in SERS.

2. Surface-enhanced Raman spectroscopy

Surface-enhanced Raman spectroscopy (SERS) combines the sensitivity of a molecule with the specificity of a chemical, enabling structural and molecular detection of analytes at low concentrations. The exploration of various ideas for implementing potent, reproducible, and sensitive active surfaces in SERS is discussed [6].

2.1. Principle and mechanism

The basis of SERS lies in monochromatic light irradiating the analyte after interacting with a metal plasmonic surface. This interaction provides us with information about the energies of molecular vibrations and rotations. The success of SERS is dependent on this interaction between the adsorbed analyte and metallic plasmonic surfaces such as Au, Ag, and Cu [7]. These metals exhibit Localized Surface Plasmon Resonance within the wavelength range in which Raman scattering occurs.

SERS follows two principles:

• Electromagnetic – The excitation of plasmonic surfaces.

• Chemical – The formation of complexes with charge-transfer.

The electromagnetic (EM) process begins when the substrate meets a metallic layer with free electrons, which is then exposed to monochromatic light. This light, interacting with the metallic nanoparticle, results in significant amplification, particularly in areas inducing an oscillating dipole on molecules adjacent to the nanoparticles [8]. Therefore, physical interaction between the substrate and analyte is essential to maximise enhancement. By enhancing highly localised regions, alterations in interparticle spacing, size, and nanoparticle form occur. However, there is a lack of control over hotspot creation, substrate homogeneity, and stability [9].

For chemical enhancement, molecules should be directly adsorbed onto the surface, resulting in the formation of complexes. Subsequently, monochromatic light irradiates the metallic plasmonic surface, yielding results. Experimental parameters and organisation should be periodically reviewed [10]. Analytes require compatible parameters such as SERS substrate and monochromatic light. Developing specific SERS applications demands skilled workers and research grants. The SERS technique simplifies many real-world problems and processes [11].

Chemical enhancement can also influence the SERS effect alongside electromagnetic augmentation. Charge transfer between adsorbed molecules and the metal surface drives changes in molecular structure and electrical configuration. These modifications may alter the frequency of vibration of Raman-active bonds, resulting in enhanced Raman scattering signals. Although the precise nature of chemical amplification in SERS is still under investigation, its impact on some SERS data is significant [12].

This improvement is thought to result from several processes, including the formation of charge-transfer complexes between molecules and the metal surface, the creation of new electronic states at the molecule-metal interface, and modifications to molecule polarisability. While research on the precise processes driving chemical augmentation in SERS continues, its potential ramifications are significant [13]. It has considerable potential in areas such as catalysis, electrochemistry, and the study of biological macromolecules, as it enables the detection and characterisation of molecules at incredibly low concentrations, even down to single-molecule levels. Unlocking SERS’ full potential in diverse scientific and technical applications requires an understanding of and ability to utilise chemical enhancement in SERS. The SERS enhancement factor (EF) is calculated in multiple ways [10]; however, the simplest method is often employed.

(1) $\mathit{EF}=\frac{{\mathit{I}}_{\mathit{sers}}/N_{\mathit{sers}}}{I_{\mathit{nor}}/N_{\mathit{nor}}}$(1)

where,

$I_{\mathit{sers}}$ – SERS intensity

$N_{\mathit{sers}}$ – Number of molecules adsorbed to the surface in SERS excited volume

$I_{\mathit{nor}}$ – Non-SERS intensity

$N_{\mathit{nor}}$ – Number of molecules adsorbed to the surface in non-SERS excitation volume.

The equation was derived from the study ‘Nanoparticle Properties and Synthesis Effects on Surface-Enhanced Raman Scattering Enhancement Factor’ [14]. The enhancement factor (EF) quantifies the combined effects of electromagnetic and chemical enhancement. Table 1 illustrates the various types of Surface Enhanced Raman Spectroscopy (SERS), along with their application fields and mechanisms.

Table 1. Different types of SERS with its application, applied field and mechanism.

Type of Surface Enhanced Spectroscopy	Application	Applied Field	Mechanism	Reference
Colloidal SERS	Chemical and biological sensing	Liquid phase	Electromagnetic enhancement by plasmonic nanoparticles in colloidal suspension	[15]
Substrate-based SERS	Trace analysis, biosensing, environmental monitoring	Solid phase	Electromagnetic enhancement by plasmonic substrates (e.g. metal nanoparticles on surfaces)	[16]
Tip-enhanced Raman Spectroscopy (TERS)	Nanoscale imaging and analysis	Near-field scanning microscopy (NSOM)	Electromagnetic enhancement at the sharp metal tip scanning sample surface	[17]
Shell-isolated SERS	Biochemical analysis, medical diagnostics	Liquid phase	Electromagnetic enhancement with core-shell nanoparticles	[18]
Electrochemical SERS	Electrochemical interfaces, sensing	Electrochemical cell	Synergy between chemical enhancement at electrode surfaces and electromagnetic enhancement	[19]
Nano-gap SERS	Single-molecule detection, plasmonics	Sub-nanometer gaps	Enhanced electromagnetic fields in the nano-gap regions between metal nanoparticles	[20]
Surface-Enhanced Fluorescence (SEF)	Biological imaging and detection	Liquid phase	Enhanced fluorescence emission from fluorophores placed near plasmonic nanoparticles	[21]
Surface-Enhanced Hyper-Raman (SEHRS)	Vibrational modes beyond Raman selection rules	Solid phase	Hyper-Raman scattering combined with plasmonic enhancement	[22]
Nanoporous SERS	Gas and vapor sensing	Gas phase	Plasmonic enhancement in nanoporous materials for gas molecule interactions	[23]
Graphene-enhanced SERS	Chemical and biological sensing	Solid phase	Electromagnetic enhancement by graphene plasmons	[24]
Surface-Enhanced Coherent Anti-Stokes Raman Scattering (SECARS)	Vibrational imaging, biomedical applications	Solid and liquid phase	Coherent anti-Stokes Raman scattering with plasmonic enhancement	[25]
Bimetallic SERS	Trace analysis, catalysis	Solid phase	Synergy between two different metal nanoparticles for enhanced Raman signals	[26]
DNA-based SERS	Genetic analysis, bioassays	Liquid phase	DNA-assembled nanoparticle clusters for signal enhancement	[27]
Hotspot-engineered SERS	Sensing, single-molecule detection	Solid and liquid phase	Precisely controlled hotspots on nanostructured substrates for maximum enhancement	[28]
Self-assembled monolayers SERS (SAM-SERS)	Chemical and biological sensing	Solid phase	Plasmonic enhancement at self-assembled monolayers (SAMs) on metal surfaces	[29]
SERS in microfluidic systems	Lab-on-a-chip applications, analytical chemistry	Liquid phase	Integration of SERS with microfluidic channels for enhanced analysis	[30]

3. Applications

SERS has evolved and established a firm application in all disciplines, including chemical, clinical, biomedical, pharmaceutical, and electrochemistry. New and potential innovations have drawn the attention of researchers to this spectrum of studies. This article compiles recent advancements made in recent years [31]. Table 2 will provide various applications of SERS along with their advantages. This method utilises the phenomenon known as surface Plasmon resonance, which occurs when molecules adhere to or are close to nanostructured metal surfaces. These surfaces are commonly made of silver or gold. The identification and measurement of analytes at incredibly low concentrations are made possible by the enhanced signal, which offers insightful information molecular vibrations.

Table 2. Various application of SERS along with its mechanism and advantage.

Application Types	Application Field	Mechanism	Advantage	Reference
Trace Analysis	Environmental Monitoring	Electromagnetic Enhancement	Sensitivity to detect trace amounts of pollutants	[32]
Food Safety Monitoring	Agriculture/Food Industry	Plasmonic Enhancement	Rapid and sensitive detection of food contaminants	[33]
Biomedical Diagnostics	Medicine/Healthcare	Chemical Enhancement	Early detection of diseases through molecular fingerprinting	[34]
Explosive Detection	Security/Defense	Charge Transfer Mechanism	High sensitivity to identify trace amounts of explosive materials	[35]
Catalysis Studies	Chemical Research	Hotspot-Induced Enhancement	Studying reaction mechanisms on catalytic surfaces	[36]
Forensic Analysis	Law Enforcement	Surface-Induced Enhancement	Identifying trace evidence from crime scenes	[37]
Nanomaterial Characterization	Nanotechnology	Surface Plasmon Resonance	Understanding the properties of nanoparticles	[38]
Drug Delivery Monitoring	Pharmaceutical Research	Adsorption-Enhanced Enhancement	Monitoring drug release from nanocarriers in real-time	[34]
Environmental Sensing	Air/Water Quality Monitoring	Chemical Adsorption	Detecting pollutants in the environment with high specificity	[39]
Art Conservation	Museums/Archaeology	Substrate-Induced Enhancement	Non-destructive analysis of artworks for preservation purposes	[40]
Nanotoxicology	Environmental Health	Nanoparticle-Induced Enhancement	Assessing the potential toxicity of nanoparticles on living organisms	[38]
Counterfeit Detection	Anti-Counterfeiting	Molecular Fingerprinting	Distinguishing genuine products from counterfeit ones	[41]
Disease Biomarker Identification	Medical Research	SERS-Tagging Technique	Identifying specific biomarkers associated with diseases	[42]
Environmental Remediation	Pollution Control	Surface-Enhanced Photocatalysis	Degradation of pollutants using enhanced photocatalytic processes	[39]
Quality Control in Manufacturing	Industrial Production	SERS Imaging	Non-destructive assessment of product quality during the manufacturing process	[43]
Microbial Identification	Microbiology	SERS-Active Nanoprobes	Rapid and accurate identification of microbial species	[44]
Drug Metabolism Studies	Pharmaceutical Development	Intracellular SERS	Studying drug metabolism within living cells	[34]
Fuel Analysis	Energy Sector	SERS Substrate Arrays	Characterising fuel components for improved efficiency	[45]
Soil Nutrient Analysis	Agriculture/Environmental Sciences	In Situ SERS	Assessing soil nutrients and health in real-time	[46]
Water Contaminant Monitoring	Water Treatment	SERS-Based Sensors	Continuous monitoring of water quality for contaminants	[47]

SERS is used in analytical chemistry for the trace-level identification of a wide range of chemicals, including pharmaceutical compounds, biological components, and environmental contaminants. Due to its exceptional sensitivity, even single molecules may be identified, allowing researchers to characterise complex combinations with unmatched accuracy. This has implications for professions like forensics, where trace quantities of chemicals can aid in criminal investigations [48]. In biomedical research, SERS has the potential to improve medical imaging and diagnostics. By examining the biomarkers found in human fluids, researchers are exploring its potential for early disease diagnosis. Diagnostic tests can be made more specialised by targeting specific compounds of interest with SERS-based nanosensors. Additionally, SERS imaging methods offer the opportunity for non-invasive imaging at the microscopic and molecular scale, which could revolutionise our understanding of biological mechanisms and disease development [49].

SERS is valuable for materials research as it can shed light on surface characteristics and molecular interactions. With the use of SERS, scientists can investigate catalytic reactions, structural self-assembly, and degradation processes, which will aid in creating better materials and coatings for use in industrial applications. SERS also helps identify and measure contaminants in soil, water, and air for environmental monitoring. It is a useful tool for ensuring environmental standards are met and protecting public health due to its ability to quickly detect and measure different chemical components [50]. Figure 1 represents the application of Surface Enhanced Raman Spectroscopy in different fields.

Figure 1. Application of surface enhanced raman spectroscopy in different fields.

The use of SERS is broad and constantly growing, encompassing fields such as analytical chemistry, medicinal research, materials study, and environmental surveillance. Professionals and investigators seeking to understand the complexities of molecules and their interactions in various scenarios will find it to be an invaluable tool due to its sensitivity, specificity, and ability to provide information at the molecular level [49].

3.1. Chemical application

SERS, or surface-enhanced Raman spectroscopy, has emerged as a transformative tool for chemical investigation. It enables the identification of molecules at extremely low concentrations while maintaining sensitivity and selectivity. This capability stems from the remarkable amplification of Raman signals on nanostructured metal surfaces. Various branches of chemistry have harnessed this feature, employing SERS to elucidate chemical structures, investigate surface reactions, and explore catalytic processes. Particularly in pharmaceutical analysis, SERS plays a crucial role in characterising drug interactions and chemicals. Moreover, SERS serves as a cornerstone of environmental monitoring, aiding in the identification of trace contaminants. Essentially, SERS empowers scientists to explore the molecular world with unprecedented sensitivity, paving the way for both fundamental research and practical applications [51]. Figure 2 illustrates the diverse applications of Surface Enhanced Raman Spectroscopy.

Figure 2. Types of surface enhanced raman spectroscopy (SERS).

3.1.1. Detection of pesticides

The importance of agriculture cannot be overstated, both in industries and developing nations. It serves as the foundation of a country and contributes significantly to the economy, either directly or indirectly. Rapid on-site screening and inspection of fruits, vegetables, their freshness, and quality, along with monitoring plant growth, diseases, and harmful residues including pesticides and prohibited additives, are essential. Improvements in fast detection techniques are imperative as they directly or indirectly affect the quality of life, especially considering recent concerns about food safety [52]. Figure 3 illustrates the detection methods for different types of pesticides using SERS.

Figure 3. Detection methods for different types of pesticides by SERS.

SERS analysis is utilised to identify pesticides, their concentration, and composition. One common technique involves the mixing of colloidal metallic nanoparticles with analytes. This method has been applied to chlortoluron, atrazine, diuron, and terbuthylazine, achieving detection limits between 10 and 20 picograms. The SERS substrates used were Ag-quantum dots of sponge-shaped structures [53]. Another intriguing technique for quick and extremely sensitive trace monitoring of the herbicide paraquat in water utilises a SERS-based microdroplet sensor [54].

Shell-isolated nanoparticles (SHINs) have been recently employed for obtaining quick and reliable results. Sprinkling AuNPs, known as smart dust, over the surface being probed visualised pesticide residues of methyl para-thion in fruits [55]. There has also been discussion about creating a reproducible, recyclable SERS-active substrate made of TiO₂ nanotube arrays coated with AuNPs to detect pesticides like methyl-parathion and the herbicide 4-chlorophenol, as well as other compounds. The substrates are cleaned by photodegradation under ultraviolet irradiation. This improvement in substrate cleaning is vital for enhancing reproducibility and stability [56]. Table 3 provides information about various detection methods for pesticides.

Table 3. Detection methods for various types of pesticides by SERS.

Type of Pesticide	Pesticide	Detection Methods	Materials for Detection	References
Organophosphates	Malathion	SERS-active substrates	Silver nanoparticles	[57]
Organophosphates	Chlorpyrifos	Nanosphere-based SERS	Gold nanoparticles	[58]
Organophosphates	Parathion	SERS with silver nanorods	Graphene-based SERS substrates	[59]
Organophosphates	Diazinon	SERS with nanowire substrates	Silver-coated nanostructures	[60]
Organophosphates	Dichlorvos	SERS using metal island films	Silver nanoparticles	[61]
Organophosphates	Methamidophos	SERS-active nanostructured materials	Platinum-coated nanoparticles	[62]
Pyrethroids	Permethrin	SERS coupled with chemometrics	Palladium-decorated nanostructures	[63]
Pyrethroids	Cypermethrin	SERS with surface-modified nanoparticles	Silver nanocubes	[64]
Pyrethroids	Deltamethrin	SERS using bimetallic nanostructures	Gold-coated silver nanoparticles	[65]
Pyrethroids	Fenvalerate	SERS with plasmonic nanomaterials	Gold nanostars	[66]
Carbamates	Carbaryl	SERS-based immunoassay	Silver-coated nanowires	[67]
Carbamates	Methomyl	SERS in combination with magnetic nanoparticles	Magnetic core-shell nanostructures	[68]
Carbamates	Aldicarb	SERS using silicon-based substrates	Silicon nanowires	[69]
Carbamates	Carbofuran	SERS with metal organic frameworks (MOFs)	MOF-coated metal nanoparticles	[68]
Neonicotinoids	Imidacloprid	SERS with carbon-based nanomaterials	Carbon nanotubes	[70]
Neonicotinoids	Clothianidin	SERS using hybrid plasmonic nanomaterials	Gold-coated magnetic nanoparticles	[71]
Neonicotinoids	Thiamethoxam	SERS coupled with microfluidic devices	Silver-coated nanospheres	[69]
Neonicotinoids	Acetamiprid	SERS with functionalised metal nanoparticles	Functionalised silver nanoparticles	[69]
Triazines	Atrazine	SERS with metal oxide nanostructures	Titanium dioxide nanotubes	[72]
Triazines	Simazine	SERS with semiconductor nanomaterials	Zinc oxide nanoparticles	[73]
Triazines	Prometryn	SERS combined with nanoimprinting	Polymer-based nanostructures	[70]
Triazines	Terbuthylazine	SERS with plasmonic-enhanced substrates	Gold-coated silicon nanoparticles	[71]
Organochlorines	DDT (Dichlorodiphenyltrichloroethane)	SERS with metal-dielectric nanostructures	Silica-coated gold nanoparticles	[71]
Organochlorines	Lindane	SERS using hollow metal nanocubes	Hollow gold nanocubes	[71]
Organochlorines	Aldrin	SERS with self-assembled monolayers	Silver-coated silica nanospheres	[69]
Organochlorines	Dieldrin	SERS with metal nanoparticle clusters	Gold nanoclusters	[71]

In this application, SERS capitalises on the distinctive spectrum fingerprints that result from interactions between various pesticide compounds and plasmonic nanostructures. SERS can enhance the Raman signals produced by pesticides by functionalising these tiny structures or nanoparticles with certain receptors or compounds that bind to them [74]. This yields a unique and recognisable spectral pattern, even in the presence of low amounts of the pesticide. Early warning systems and accurate pesticide usage monitoring are made possible by SERS’s extraordinary sensitivity in detecting pesticides. By minimising pesticide residues on crops, this can assist farmers in maximising their pesticide applications, lowering environmental pollution, and ensuring food safety. Additionally, SERS can help regulatory bodies enforce safety standards and pesticide residue limitations, thus protecting the environment and the general population [75].

3.1.2. Molecular vibrational spectroscopy

SERS is a powerful analytical method that enables the investigation of molecular vibrations and interactions at the nanoscale, making it a type of molecular vibration spectroscopy. SERS combines conventional Raman spectroscopy with the remarkable signal amplification resulting from molecules interacting with plasmonic nanostructures. This dramatic increase in Raman scattering intensity due to the interaction allows for the identification and characterisation of analytes, even at trace levels [76]. When metallic nanoparticles, such as silver or gold, tightly bind to the molecules of interest in SERS, the phenomenon of localised surface Plasmon resonance occurs. This leads to the formation of localised electromagnetic ‘hotspots’ on the surface of the nanoparticle, amplifying the Raman signals of neighbouring molecules by many orders of magnitude. These enhanced signals provide valuable information on molecular vibrations, revealing details about chemical composition, interactions, and molecular structure.

The method finds applications in various disciplines, including chemistry, biology, materials science, and environmental monitoring. Researchers can investigate molecular dynamics in constrained settings, study biomolecular behaviour on surfaces, and analyse chemical processes at the nanoscale. SERS has the capability to identify and analyse single molecules, pushing the limits of sensitivity and resolution in spectroscopic methods. Recent advancements in nanofabrication, plasmonics, and instrumentation have further enhanced the capabilities of SERS [77].

To target specific vibrational modes and enable selective analysis of molecules, researchers are developing customised nanostructures. When combined with other methods like microscopy and microfluidics, SERS facilitates the detection of dynamic processes in situ and in real-time. Molecular vibration spectroscopy using SERS has transformed the field of spectroscopy by providing scientists with a powerful tool for detecting molecular vibrations and interactions with unprecedented sensitivity and accuracy. Its ability to reveal molecular-level features in complex systems makes it a valuable technology for a wide range of scientific and technological applications [78].

3.1.3. Trace detection

A state-of-the-art development in analytical chemistry is trace detection by SERS, which enables the identification and quantification of target molecules in minute quantities with unmatched sensitivity and selectivity. In this application, plasmonic effects are utilised to construct metallic nanostructures, often made of silver or gold, to generate localised electromagnetic ‘hotspots’ on their surfaces. When these hotspots are in close proximity to the nanostructures, Raman scattering signals are significantly enhanced. These nanostructures are functionalised with molecular probes that exhibit a high affinity for the target analyte as part of the trace detection procedure employing SERS. Due to the local electromagnetic field augmentation induced by the target molecules adhering to the functionalised nanoparticle surfaces, the Raman scattering signal is dramatically increased. Consequently, a very distinct and precise spectral fingerprint is produced, which can be recorded and analysed to detect the target molecule even in very small amounts [79].

Applications for SERS-based trace detection can be found in a wide range of industries, including security, forensics, environmental monitoring, and biological research. Its ability to identify low quantities of compounds has revolutionised the way we approach safety, diagnostics, and quality control. It now serves as a potent tool for enhancing our understanding of complex samples and preserving the integrity of various goods and environments. While there are still challenges with standardisation and reproducibility, ongoing advancements in plasmonics, equipment, and nanofabrication methods are enhancing and expanding the capabilities of SERS for trace detection, creating new opportunities for accurate and reliable analysis. SERS’ remarkable sensitivity in trace detection is one of its key features [80]. Raman signals can be amplified by a factor of up to 10¹⁴ owing to the plasmonic nanostructures’ enhancement of the electromagnetic field, enabling the detection of even a few molecules of the target substance. This sensitivity is crucial for locating tiny levels of chemicals in complex backgrounds.

SERS utilises the unique spectral fingerprints of various molecules to enable the simultaneous detection of multiple analytes in a single experiment. Researchers can generate a ‘barcode’ of signals that identify distinct target molecules by functionalising the nanostructures with diverse chemical probes. This multiplexing capability is highly advantageous for thorough and rapid analysis. In many analytical procedures, trace detection can be hindered by the presence of interfering chemicals. The distinct spectrum fingerprints of SERS and the ability to tailor the characteristics of the nanostructures can mitigate interference, enhancing the selectivity of the analysis. This is particularly beneficial when working with complex samples consisting of multiple components.

3.1.4. Chemical kinetics

Chemical kinetics is a field in which SERS serves as a potent tool, providing unique insights into the rates, mechanisms, and pathways of chemical reactions at the molecular level. Due to its exceptional sensitivity and ability to provide real-time information, SERS has proven to be extremely valuable in unravelling complex kinetic processes [81]. SERS allows scientists to monitor the progression of reactants and products in situ and in real-time, offering crucial information on reaction kinetics, transition states, and intermediates.

The utility of SERS in chemical kinetics is particularly evident when analysing rapid or transient processes, where conventional techniques may fall short. It enables precise identification and quantification of reactants and products, as well as the detection of transient intermediates, by facilitating direct observation of the vibrational modes of the molecules involved in the process. Additionally, SERS can monitor changes in molecular structures and conformations throughout a reaction, providing valuable insights into reaction mechanisms [82].

This application of SERS has broad implications, spanning from investigations of photochemical and photophysical processes to catalysis and surface chemistry. It enables scientists to optimise reaction conditions, enhance catalysts, and comprehend the intricacies of chemical transformations. In sectors such as materials science, energy conversion, and pharmaceutical research, where a comprehensive understanding of reaction kinetics is crucial, the role of SERS technology in elucidating chemical kinetics will continue to grow in importance [83].

Furthermore, SERS is highly adaptable and can be employed for a variety of reactions, including liquid-liquid, liquid-solid, and gas-solid processes. It provides researchers with the opportunity to study chemical kinetics in diverse settings and conditions, offering insights into how reactions occur on different surfaces or interfaces. SERS is not only utilised to elucidate reaction mechanisms but also to investigate how external influences impact chemical kinetics. SERS experiments facilitate the manipulation and monitoring of changes in temperature, pressure, and concentration, allowing scientists to explore how these factors influence reaction rates and pathways. This information is crucial for designing and optimising chemical processes under specific conditions [84].

3.2. Biochemical application

This section of the article discusses biochemical applications, primarily focusing on food safety and drug monitoring. It involves substrate analysis and aids in the detection of pathogens, antibodies, adulterations, and other toxins [85].

3.2.1. Food safety

Ensuring food safety should be in one of the topmost priority to ensure a healthy population to some level; efficient analysis should be performed to reach this standard. Traditional food analysis depends on liquid or as chromatography which involves labour, time intensive procedures, maintenance etc. SERS offers high sensitivity, quick, affordable methods is being utilised in various food and agricultural analysis [86]. Fingerprinting is one major tool based on SERS vibrations. SERS provides the capacity to detect minute concentrations of dangerous compounds, even in matrices that are complex, in the context of food safety. For example, SERS may identify allergens like peanuts or gluten at concentrations that are far lower than those that cause allergic responses. In order to reduce possible health hazards, it can also detect pollutants like pesticides, heavy metals, and poisons early on.

Colloidal nanostructures are used to analyse and detect the presence of colourants, adulterants. This had various drawbacks due to its affinity to analyte, low reproducibility Researches are ongoing to improve the sensitivity and decrease matrix interference and also creating an in-situ environment [5]. SERS’s flexibility includes the ability to identify food adulteration, which is important for maintaining the genuineness of expensive goods like olive oil or honey. By examining the distinct molecular makeup of the samples, researchers and regulators using SERS may distinguish between genuine and counterfeit goods. This is crucial for maintaining industry standards and safeguarding customers.

Additionally, SERS’ non-destructive nature makes it particularly useful for applications involving food safety since it enables examination of samples without compromising their integrity. This is essential when working with priceless or irreplaceable objects, such as rare ingredients or meals from a particular culture. Standardisation and assuring uniform findings across laboratories are obstacles that must be addressed, although continual improvements in SERS technology are progressively overcoming these problems. The processing and analysis of samples may be streamlined by integrating SERS with microfluidic systems, making it even more appropriate for routine food safety testing. SERS is a quick, sensitive, and precise technology for identifying pollutants, allergens, and adulterants, which offers significant promise for revolutionising food safety procedures. Technology has the ability to improve regulatory oversight, protect public health, and uphold consumer confidence in the world’s food supply chain as it develops and becomes more widely available [87].

3.2.2. Drug monitoring

The advancement of drug delivery and monitoring systems represents a significant development in the biomedical field, particularly in enhancing precision and clarity in addressing biological issues. One notable advancement is the development of Site-Specific, Targeted Drug Delivery Systems, aimed at improving the effectiveness of therapies while minimising adverse effects on other organs [88]. For example, in cancer therapy, where conventional medications with high toxicity levels often lead to severe side effects, targeted drug delivery systems hold promise for inhibiting tumour growth with greater specificity [89]. Erlotinib, an anti-EGFR sensor, exemplifies the application of SERS in monitoring side effects and patient responses in pancreatic and lung cancer cells [90]. By measuring erlotinib’s composition and concentration at the nano-level through the interaction between the sensor and the drug on gold colloidal nanostructures, SERS-based sensors offer a valuable tool for precise drug monitoring.

Quantitative analysis plays a crucial role in evaluating the connection between drug delivery and therapeutic impact. Traditional drug delivery systems often provide only qualitative analysis, but SERS technology overcomes this limitation by enabling quantitative analysis [91]. However, achieving precise drug quantities remains challenging, necessitating the development of specialised Nano probes to enhance resolution and provide clear imaging contrast [88]. Moreover, Magnetic Resonance Imaging (MRI) emerges as a suitable option for monitoring drug delivery, as it can generate high-resolution images with excellent temporal and spatial arrangement, allowing for clear visualisation of drug distribution [92]. By integrating SERS and MRI technologies, researchers can potentially achieve both quantitative analysis and precise imaging, enhancing the effectiveness and safety of drug delivery systems.

3.2.3. Detection of lateral flow assay strips

Lateral flow immunoassay assay is a straightforward and effective technology combining immunology and chromatography. It is a rapid diagnostic test which provides the results within 15 minutes unlike diagnostic labs that require long incubation time. The extract containing the analyte is passed without any external force through polymeric zones of various reagents containing antibodies or binders that detect and traps the analytes [93]. All of these are placed in a pad encapsulated into a plastic cassette that protects and holds the device. This biomolecule detection is user-friendly, inexpensive, time-efficient, Quantitative analysis is done by biomarker and qualitative by naked eye [94]. At hospitals when the availability and affordability is crucial, tests for acute illness in emergency situations, Lateral Flow Immunoassay tests can be put to good use. Developing and under developing can gain advantage from this due to its low cost. An appealing solution for problems such as analysis in capabilities, low sensitivity [95], is through incorporating SERS and nanoparticles. Numerus laser emitted photons and metal nanoparticle are available to analyse numerous targets. Detection based on SERS, electrochemical, fluorescent, magnetic with linear or dual types has exponentially increased the structural improvements, membrane manipulation, and antibody immobilisation of the Lateral flow assay [96].

3.2.4. Microbial analysis

SERS has emerged as a powerful technology for microbial investigation, offering rapid and highly accurate identification of microorganisms such as bacteria, viruses, and fungi. SERS exploits the unique spectral fingerprints generated by these microorganisms when they interact with SERS-active substrates or nanoparticles. These Raman spectra serve as molecular signatures, facilitating species-level identification and finding applications across various fields including microbiology, food safety, environmental monitoring, and clinical diagnostics [97].

One of the key advantages of SERS-based microbial analysis is its ability to provide rapid data without the need for labour-intensive culture procedures. This versatility makes it invaluable for ensuring microbiological safety and understanding microbial diversity in diverse contexts, including clinical specimens and environmental samples. Moreover, SERS can offer identification within minutes, enabling swift decision-making in urgent situations such as clinical diagnostics or food safety assessments [98].

Furthermore, SERS exhibits high selectivity, enabling it to differentiate between closely related microbial species or strains with varying biochemical characteristics. This capability is crucial for accurate identification and characterisation of microorganisms. SERS can also be utilised in environmental monitoring to detect and classify microorganisms in air, water, or soil samples, facilitating early detection of hazardous toxins or diseases and assessing the impact of microbial populations on environmental health. In the food industry, SERS can rapidly identify harmful pathogens or spoilage microorganisms, ensuring the safety and quality of food products [99].

Despite its potential, SERS-based microbiological analysis faces challenges such as optimising experimental settings for different microbial species and standardising microbiological SERS spectra. Nonetheless, ongoing research in bioinformatics and SERS technology aims to address these challenges, positioning SERS as a standard tool for microbial investigation across various sectors involving microorganisms as technology continues to advance [100].

3.3. Clinical application

The integration of electrophoresis with SERS UV detection represents a powerful approach utilised in the detection of various biomolecules such as proteins, DNA, and cancer biomarkers [101]. This method typically involves electrophoretic separation of biomolecules followed by SERS UV detection, which allows for sensitive and specific identification of target molecules. One significant application of SERS in this context is its potential for tracking therapy outcomes and guiding treatment plans in clinical settings. By employing SERS probes that selectively attach to specific molecules involved in disease progression or therapy, clinicians can monitor real-time changes in these molecules within a patient’s body. This real-time monitoring provides valuable information on the efficacy of therapies, allowing for prompt adjustments as needed to optimise treatment outcomes [101].

Furthermore, the development of medical imaging technology holds promise for SERS-based imaging approaches. SERS imaging enables visualisation of cellular and molecular structures with high resolution and specificity, providing unprecedented insights into biological processes. This technology could lead to innovations in understanding disease processes and the development of novel treatments [102]. Overall, the clinical use of SERS has the potential to revolutionise healthcare delivery by facilitating early and precise diagnosis of illnesses, guiding individualised treatment plans, and enhancing our understanding of complex biological systems. As technology continues to advance, SERS is poised to make significant contributions to improving healthcare outcomes for patients.

3.3.1. Detection of proteins

Protein detection is a fundamental aspect of biological research, and resonance Raman spectroscopy (RRS) is one technique utilised for this purpose, capable of detecting proteins and other biological components such as DNA, tyrosine, and tryptophan. Among the various methods available for protein detection, the ‘Western-SERS’ method, introduced by Han et al. in 2008, has gained widespread adoption. Protein electrophoresis is a commonly employed technique for protein separation based on size and charge differences [103]. This process typically takes at least a week to complete and allows researchers to identify the proteins present in a sample and assess whether they are intact or degraded. Proteins play crucial roles in biological systems, serving as building blocks for tissues, enzymes, and hormones. During digestion, proteins are broken down into individual amino acids, which are then utilised for various metabolic processes.

In protein electrophoresis, the process begins with treating a sample of blood or serum with sodium dodecyl sulphate (SDS), which breaks down proteins into smaller fragments. These fragments are then separated by gel electrophoresis as they migrate through an electrical field. Smaller proteins move more quickly through the gel than larger ones due to reduced resistance. Following separation, proteins are typically stained with a dye and visualised under ultraviolet light to track their migration through the gel. Antibodies specific to particular proteins can also be employed to detect their presence in the sample, enabling targeted analysis [104]. Overall, protein electrophoresis combined with techniques such as RRS and Western-SERS provides powerful tools for protein detection and analysis, contributing to our understanding of biological processes and diseases.

3.3.2. Detection of cancer biomarker

In order to detect colon and rectal cancer early, CEA (Carcinoembryonic Antigen) has been employed in the past. According to multiple clinical trials, elevated CEA readings have been discovered in a variety of malignant tumours, including breast, lung, and other cancer types. SERS has significant potential in several fields, including early illness diagnosis and personalised therapy. Researchers are creating SERS-based biosensors that can detect biomarkers linked to a variety of illnesses, including cancer, infectious diseases, and metabolic disorders, by utilising the high sensitivity and specificity of SERS [105]. These biosensors may diagnose a condition quickly and precisely, often at a time when more traditional techniques would be unable to do so. Additionally, SERS enables multiplexed detection, increasing diagnostic effectiveness by allowing the simultaneous study of many biomarkers from a single sample. As a result, CEA is a flexible tumour marker. It has great clinical utility in the differential diagnosis, disease monitoring, and curative impact assessment of malignant tumours, even though it cannot be utilised as a precise indicator for the identification of some malignant tumours [106].

For the purpose of detecting CEA, researchers have developed a number of novel materials with SERS activity. For instance, the surfaces of hollow gold nanoparticles show strong SERS activity. Magnetic beads support immune complexes, which is more significant. High sensitivity and reproducibility immunoassays for cancer markers can be performed using magnetic beads. This technique is more sensitive than ELISA and can detect CEA right away [107]. Picogram-level detection is also possible. To create a 3D biocompatible aluminium-based quantum structure for CEA determination, Ganesan et al. used an ultrashort pulsed laser. Sandwich immunoassay and molecularly imprinted approaches have also been developed for the quantitative evaluation of CEA, with detection limits as low as the nanogram range [108].

3.3.3. Bio-chemical analysis

In the realm of biological investigation, SERS has emerged as a groundbreaking technology, enabling researchers to unravel intricate details of biomolecules, their interactions, and structural alterations with unparalleled accuracy. This method leverages the vibrational signatures of molecules, offering insights into complex biological systems, by harnessing the exceptional signal enhancement provided by plasmonic nanostructures. SERS plays a vital role in elucidating biomolecular structures and conformational changes in biochemical studies. Biomolecules such as proteins, nucleic acids, and lipids interact with metal-enhanced surfaces, generating distinctive Raman spectra that divulge information about their secondary and tertiary structures. Understanding biological and molecular processes is pivotal for drug development and research on protein-ligand interactions, in particular [109].

The remarkable sensitivity of SERS facilitates the investigation of single-molecule interactions, pushing the boundaries of detection limits. This enables the detection of previously imperceptible phenomena and transient intermediates for analysis. SERS also offers deep insights into dynamic processes, such as cellular responses to stimuli or drug absorption, in real-time, by operating in complex biological environments such as cell membranes or living cells. SERS’s specificity enables the identification of disease markers and biomarkers at incredibly low concentrations in applications like disease diagnosis. This holds promise for personalised therapy methods and early disease detection. SERS can also be integrated with microfluidics to enhance the efficiency of point-of-care devices for rapid on-site diagnostics [110].

While certain technical challenges exist, such as repeatability and standardisation, ongoing advancements in nanofabrication methods and signal enhancement techniques are addressing these issues. Collaborations between researchers in spectroscopy, nanotechnology, and biochemistry are driving the development of state-of-the-art SERS-based techniques for a comprehensive understanding of biochemical processes. By offering a potent, label-free, and non-invasive means of probing the molecular realm within living systems, SERS has revolutionised biochemical analysis. It serves as an indispensable tool for expanding our knowledge of biology, biomedicine, and pharmacology, owing to its ability to provide structural information, explore connections, and investigate dynamic processes [111].

3.3.4. Tissue analysis

SERS has emerged as a transformative technique in tissue analysis, offering unparalleled insights into tissue composition, pathology, and disease progression. By utilising SERS, scientists and medical professionals can extract precise molecular data from tissue samples with exceptional sensitivity and specificity. This enables differentiation between healthy and diseased tissue, characterisation of distinct tissue types, and evaluation of treatment efficacy by leveraging unique molecular fingerprints present within tissues [112]. One of the primary advantages of SERS in tissue analysis is its capability to generate molecular fingerprints of tissues, even within complex biological matrices. It can identify various biomolecules such as lipids, proteins, nucleic acids, and metabolites, facilitating comprehensive evaluation of tissue composition and health. For instance, in cancer research, SERS can aid in delineating tumour margins, identifying cancer-specific markers, and monitoring treatment effectiveness. Furthermore, SERS enables pharmacokinetic investigations and personalised treatment plans by examining the distribution of medications or therapeutic agents within tissues [113].

SERS-based tissue analysis offers particular advantages due to its non-destructive nature. Unlike conventional tissue analysis methods that require staining or destructive sample processing, SERS can be applied to tissue samples without compromising their integrity. This preservation of the original tissue structure facilitates further histological analyses. Additionally, SERS can operate without the need for labels, eliminating the requirement for additional chemical agents or markers, reducing the risk of artefacts, and simplifying sample preparation [114].

The versatility of SERS extends to various fields of tissue analysis. In neuroscience, SERS can examine brain tissue and cerebrospinal fluid, aiding in the study of neurodegenerative diseases such as Alzheimer’s and Parkinson’s. It also assists in evaluating the integration of transplanted tissues with their host environment and assessing the biological suitability of tissue-engineered constructs in regenerative medicine. While challenges such as tissue heterogeneity and repeatability persist, SERS is continually advancing in tissue analysis applications. Through enhancements in conventional staining techniques and the provision of more comprehensive characterisation of tissue components, SERS has the potential to revolutionise histopathology. Ultimately, SERS holds promise for significantly advancing disease diagnosis and therapy, deepening our understanding of tissue biology, and ultimately enhancing patient care [115].

3.4. Machine learning and artificial intelligence in SERS

Similar to the majority of spectroscopic methods, Raman necessitates sophisticated data processing in order to get significant insights from spectra. High accuracy, sensitivity, and selectivity vibrational fingerprint recognition has been achieved by the use of several multivariate data processing methods and linear regression techniques to analyse the optically rich and complex signal. For the purpose of automating data analysis, such data analysis usually made use of artificial intelligence (AI) [116]. In terms of data science, artificial intelligence (AI) refers to the application of a computer system that makes use of a mathematical model that the user has painstakingly created. An artificial intelligence system must be able to extract pertinent characteristics, patterns, or information from the data on its own. When vibrational spectroscopy is used in conjunction with AI to analyse vibrational fingerprints, this is typically the case. Machine learning is the term used to describe these capabilities of an AI system. SERS has a number of qualities that make it perfect for use in machine learning data processing. Since Raman’s limited sensitivity was resolved by the use of plasmonic materials, SERS can identify single molecules [117].

By lowering noise and raising the signal-to-noise ratio, machine learning (ML) techniques can assist SERS spectra become more high-quality and facilitate the identification of significant spectral characteristics. The identification and classification of intricate spectral patterns using ML models facilitates the identification of particular molecules or compounds in SERS spectra. ML algorithms can help with the interpretation of complicated spectra by helping to detect and assign peaks to particular chemical vibrations or functional groups [118]. It is possible to develop machine learning algorithms to associate SERS spectra with particular analyte concentrations, enabling the quantitative detection of compounds in intricate mixtures. In order to establish the link between spectral characteristics and concentrations and enable precise quantification, machine learning (ML) can help construct calibration curves [119]. In order to help identify outliers or unidentified substances, machine learning algorithms have the ability to identify anomalous or unexpected characteristics in SERS spectra. Surface-enhanced Raman spectroscopy in conjunction with machine learning has great potential to advance analytical capabilities by allowing for more selective and sensitive molecular detection. This can help a variety of fields, including materials science, biomedical diagnostics, and environmental monitoring [120].

3.5. Semiconductor-based materials for SERS

SERS amplifies the Raman scattering signal of molecules adsorbed on or close to certain surfaces. SERS is frequently used to boost signals from molecules on metallic surfaces, such as gold or silver nanoparticles, but because of its potential in a variety of fields, including material science, biomedical research, and nanotechnology, its application to semiconductor-based materials has attracted a lot of attention recently [121]. More and more semiconductor materials, including metal oxides, metal sulphides, metal tellurides, metal halides, and some single element semiconductors, have been shown to be SERS-active substrates. The inherent nature of semiconductor enhanced Raman scattering has been called into question since several of these novel SERS-active semiconductors have enhancement factors that have never been seen before or have broken records. However, because material preparation and characteristics vary widely, it is challenging to compare the findings of several experiments [122].

Semiconductor surfaces offer superior surface bonding for analyte collection, expanding the range of systems and behaviours that may be investigated. When compared to traditional metals, semiconductor materials and their structures have higher thermodynamic stability. Additionally, semiconductor materials are very stable in a variety of detecting situations due to their resilience [123]. These semiconductor substrates exhibit a remarkable variety of structural configurations, such as multi-dimensional Nano films, quantum dots, wires, sheets, and three-dimensional nanostructures, all of which might be tailored to suit specific requirements. Semiconductor materials are categorised according to their completely occupied valence band and unoccupied conduction band, which are easily manipulated by adjusting the size, shape, material, and doping of the nanoparticles [124]. Since semiconductor materials are essentially friendly, they have been widely suggested as a potential interface for biomolecule immobilisation. Moreover, semiconductors sustain the bioactivity of biomolecules by forming coordination interactions with their carboxyl and amine groups. For research and biological response simulations, semiconductor enhanced Raman scattering is a promising option [125].

According to CT theory, electrons can move from the metal to the molecule or from the molecule to the metal during the Charge Transfer (CT) process, which mostly takes place between the molecule and substrate. Semiconductors are being added to research systems more frequently as a result of the growth and development of nanotechnology, and there may be two ways in which molecules and semiconductors might be improved [126]. The first is the propagation route and CT resonance enhancement. The SERS enhancement in a system of molecules and semiconductors has been thoroughly and methodically explored, and it is believed to have gone through a specific transition phase. SERS is ‘given’ the power of this transition process in order to increase molecular signals [127].

4. Challenges and future perspectives

SERS technology-based biomarker detection has made rapid and substantial advancements in recent years, particularly in conjunction with nanotechnology, which is poised to usher in a new era of chemical sensing and imaging with enhanced accuracy and specificity [128]. SERS technology is increasingly pivotal in diagnostics, encompassing tumour diagnosis, assessment of organelle functionality, virus detection, and identification of cellular activities. Despite these strides, SERS technological advancements still face several challenges. One significant challenge is the inconsistency in SERS substrate preparation, resulting in variable experimental data, which, in turn, affects the application and promotion of SERS [106]. Efforts to address this issue and improve the reproducibility of SERS experiments are ongoing, with researchers exploring novel fabrication techniques and refining substrate materials to achieve greater consistency and reliability in SERS measurements. As these challenges are addressed and SERS technology continues to evolve, it holds immense promise for revolutionising various areas of diagnostics and biomedical research.

4.1. Challenges

It is imperative to design new universal SERS-active nanostructures with high sensitivity, specificity, biocompatibility, and minimal interference for biomarker identification. Ideal SERS-active nanostructures should not induce spectral alterations that are difficult to replicate. Furthermore, there is a need to develop additional types of SERS-active substrates and establish new methods for SERS-enhanced substrate preparation, in addition to refining and advancing existing techniques [129]. The development of new SERS testing technologies suitable for medical diagnostics is essential. By integrating SERS technology with biomedical technologies, particularly non-destructive detection and analysis methods, the full potential of SERS technology in disease-related biomarker detection, characterised by high sensitivity and specificity, can be realised. This will lead to the emergence of novel SERS detection technologies and the comprehensive analysis of biomarker information [130].

Efforts should be made to establish rapid and efficient protein bioconjugation techniques. Insufficient exploration of the adsorption behaviour and structure of biomarkers in contact with substrates has resulted in inadequate interpretation of protein signals. Therefore, SERS technology should be utilised as a tool to investigate the composition and function of biomarkers [131]. Additionally, extracting information from target molecules in complex systems is crucial. Many techniques focus solely on typical SERS signals and overlook the quantitative structure-activity relationship of the entire spectrum, as well as signal processing and analysis. Therefore, adopting new methodologies and developing logic trees for complex systems will aid in the analysis and resolution of real-world issues [106].

4.2. Future perspective

The influence of Surface-Enhanced Raman Spectroscopy (SERS) is poised to continue evolving and growing tremendously, driven by remarkable advancements and diverse applications across numerous scientific domains. Leveraging its vibrational fingerprint spectra, SERS offers distinct advantages over traditional optical spectroscopic methods like fluorescence and UV absorption spectroscopy, providing exceptionally high sensitivity and rich chemical information. Notably, SERS enables fail-safe multiplex detection of analytes in complex media, a capability not achievable with many other spectroscopic techniques. Recent developments have showcased the utility of SERS as a Point-of-Care (POC) technique in various chemical, biochemical, food, and agricultural applications [132].

Technological integration with SERS sensors heralds a new era of smart plant sensors, facilitating the creation of nanotechnology-based sensors capable of converting the presence of plant chemicals into digital signals for monitoring equipment. Moreover, the development of flexible wearable nanoelectronic circuit-based sensor networks, wirelessly implanted on plant leaves or fruits, holds promise for real-time monitoring of plant nutrition and stress [133]. Combining these nanoelectronic sensors with flexible membrane-based SERS sensors could offer additional advantages. SERS and integrated sensors based on nanophotonics technology may expedite the identification of desirable agricultural traits for high-throughput screening of chemical phenotypes [134]. Furthermore, advancements in SERS technology extend benefits to other areas such as material science, medicine, and biological processes.

SERS also can offer advanced performance as compared with other competing analytical techniques as SERS has outstanding sensitivity and can identify individual molecules. Analytes in trace levels can be detected thanks to the significantly magnified signals produced by the increase of Raman signals caused by plasmonic effects on metallic surfaces. SERS provides molecular fingerprinting capabilities, which are similar to those of traditional Raman spectroscopy and allow compounds to be identified and characterised using their distinct vibrational spectra. This precision comes in very handy when figuring out complicated mixes [135]. Multiplexing is made possible by SERS, allowing for the simultaneous detection of many analytes in a single sample. This capacity is essential in many areas, including environmental monitoring and biological diagnostics. Adsorbed molecules on the surface provide SERS signals, which frequently lessen background interference from the sample matrix. The selectivity of SERS for target analytes is improved by this feature. SERS’s quick measuring capabilities make real-time monitoring possible. This characteristic is very helpful in areas like biological and chemical detection [136].

By providing accurate insights into chemical interactions at the nanoscale, SERS is poised to revolutionise the development of novel nanomaterials, catalysts, and energy storage technologies. Its ability to identify biomarkers at ultra-low concentrations holds enormous promise for personalised medicine, enabling early illness detection and customised therapies. Moreover, the combination of SERS with microfluidics and lab-on-a-chip technologies is paving the way for rapid on-site diagnostics [137]. In environmental monitoring, SERS will play a crucial role in identifying and mitigating pollutants, safeguarding ecosystems.

As nanotechnology continues to advance and plasmonic nanoparticles become more accessible and affordable, SERS is positioned to become a staple tool in laboratories and companies worldwide. The synergy between artificial intelligence and SERS aims to enhance its user-friendliness and effectiveness, automating data processing and uncovering hidden insights in complex spectra. In summary, the future of SERS is characterised by its expanding adaptability, accessibility, and impact across scientific disciplines and industries, offering solutions to some of the most pressing challenges of our time [138].

5. Conclusion

This review provides an insightful overview of recent advancements in Surface-Enhanced Raman Spectroscopy (SERS) over the past decade, highlighting its applications in chemical, biochemical, and clinical fields. Notably, SERS technology has shown promise in the detection of viruses, pathogens, and adulterants in food safety, with potential for further improvement through enhanced SERS substrates that facilitate easier fabrication and better signal repeatability. Moving forward, the development of low-cost, reliable, and portable Raman systems, coupled with more dependable and repeatable SERS substrate platforms, is expected to significantly increase the utilisation of SERS sensors for food analytics and research in the coming years. While proof-of-concept studies for the detection of nucleic acids using SERS are promising, efforts should be directed towards selectively capturing target nucleic acids on SERS sensors with high specificity and utilising affordable and portable Raman spectrometers for readout. Achieving this will require the integration of sensors and a readily implementable nano-bio interface. The rich information provided by SERS is influenced by various processes, including molecular resonances, charge-transfer transitions, and phenomena like ballistic electrons. Understanding these contributions is crucial as they contribute to the extreme enhancements observed with SERS. The electromagnetic properties of nanostructures play a significant role in these enhancements, making them a focal point of SERS research.

Author contributions

B Senthil Rathi: Conceptualisation, Methodology, Formal Analysis, Investigation, Supervision, Writing- Original draft preparation. Kalaiarasi N: Resources, Writing- Original draft preparation, Writing- Review & Editing. Lay Sheng Ewe: Supervision, Validation, Writing- Review & Editing. V Kishore: Investigation, Resources, Writing- Original draft preparation Weng Kean Yew: Supervision, Data Curation, Visualisation, Writing- Review & Editing Sriananda Ganesh T: Resources, Formal analysis, Critical review, Writing – review and editing.Sujatha S:Resources, Formal analysis, Critical review, Writing – review and editing. Theresa Kasthuri Dinah S: Visualisation, Writing- Review & Editing. Kaavyaa K: Data Curation, Writing- Review & Editing.

Disclosure statement

No potential conflict of interest was reported by the author(s).