Recent Advances and Perspective in Electrically Regulated Surface‐Enhanced Raman Spectroscopy

Surface‐enhanced Raman spectroscopy (SERS) has emerged as a distinctive fingerprinting technique, offering a broad spectrum of applications encompassing environmental monitoring, chemical detection, and biomolecular analysis. Electrically modulated SERS (E‐SERS) stands as a technique which leverages an electric field to finely control the Raman signal based on the foundational principles of SERS. Through the manipulation of the physicochemical attributes of a metal or 2D material substrate, E‐SERS brings about an enhancement of the SERS signal. This enhancement occurs through a charge transfer process and modulation of the plasma resonance. This article showcases recent strides in the domain of E‐SERS, encompassing advancements such as the integration of paired integrated electrodes, piezoelectric materials, and pyroelectric materials in the construction of substrates. An exhaustive analysis of the mechanism underpinning the enhancement of the Raman signal is undertaken, alongside an exploration of the prominent attributes characterizing diverse methods for conditioning Raman signals. Elucidations are provided on the significance of employed electric fields in the augmentation of SERS and their manifold applications in drug identification, chemical detection, and catalysis. In summation, a delineation of challenges and perspectives inherent to E‐SERS substrates is presented, delineating a path for prospective comprehensive exploration within this auspicious realm of research.


Introduction
Raman spectroscopy is a powerful analytical technique used to investigate the vibrational modes of molecules.It was discovered in 1928 by the Indian physicist Sir C.V. Raman, who observed that when light interacts with a material, a small fraction of where G 1 is the enhancement factor of the excitation field, ω 0 is the frequency of the incident light, E 0 ω 0 ð Þis the intensity of the incident light, and E loc λ ex ð Þ is the intensity of the localized EM field varying with λ ex .G 2 is the enhancement factor at the Raman emission wavelength λ R , which is the enhancement factor of the emission field.The Raman signal enhancement is best when the plasma resonance absorption peak of the metallic material matches the laser wavelength and the emission wavelength, that is, G 1 ¼ G 2 .The SERS enhancement factor is proportional to the fourth power of the local electric field (jEj 4 ). [6]The CM in SERS involves the charge transfer between the molecule of interest and the metal nanostructures.This charge transfer induces a change in the electronic structure of the molecule, promoting an increase in the molecular polarization rate.The polarizability tensor α σρ can be expressed by the following equation.(5)   where A represents the Raman vibrational process in which electrons move from the ground state jIi to the excited state jKi and then rejump to the ground state jIi.The polarizability is related to the degree of overlap of the vibrational wavefunction from the ground state to the excited state.B represents the charge transfer leap from the ground state jIi of a molecule to the unfulfilled energy state jMi of a metal.When the frequency of the jump ω IM is equal to the excitation frequency of the laser ω, a resonance enhancement occurs and the pull-full signal is maximized.C represents a jump from the unfilled energy state jMi of a metal to the excited state jKi of a molecule, which results in a resonance enhancement when the jump frequency ω MK is equal to the excitation frequency ω of the laser, at which point the Raman signal is at its maximum.It is worth noting that B and C produce selective enhancement of certain characteristic vibrational modes of the molecule. [7]It is important to note that in practical SERS experiments, both the EM and CM can contribute simultaneously to the observed enhancement, making it challenging to separate their individual contributions. [8,9]M modulation is the main strategy for modulating "hotspots" by changing the morphology and structural properties of metallic nanoparticles to align them with the plasmon resonance wavelength corresponding to the excitation light.[12] On the other hand, CM modulation techniques predominantly aim at enhancing the efficiency of charge transfer between the substrate and the probing molecule through the manipulation of energy levels.Notably, these techniques involve the modulation of energy bands in nonmetallic nanomaterials.15][16][17] Among these strategies, certain regulatory approaches prove economically burdensome and unsuitable for practical application, while others exhibit intricate nature and bear limited reproducibility.However, the avenue of electrical modulation offers a means to realize virtually all the aforementioned modulation techniques through straightforward operations.Generally speaking, E-SERS materializes through the imposition of an external electric field onto the substrate or the stimulation of the substrate's inherent electric field.Both the application of an external field and the stimulation of a spontaneous field yield alterations in the local electric field existing amidst the metal nanostructures of the substrate, as well as perturbations in the valence and conduction bands of the semiconductor, alongside adjustments to the Fermi energy levels of the metal.Furthermore, the accumulation of molecules can also be accomplished by electrophoretic migration of metal nanoparticles and probe molecules within the electric field.This demonstrates the strong advantages of E-SERS.
In this review, we provide a timely overview of the progress of E-SERS research.E-SERS is described in two main categories according to the principle, namely, applied electric field and self-generated electric field.The former category encompasses diverse manifestations such as applied direct current and applied alternating current.In contrast, the latter category incorporates methodologies harnessing material-induced piezoelectric effects, thermoelectric effects, pyroelectric effect, and triboelectric effect, among others. [18]A thorough exploration of the enhancement mechanism governing Raman signals is undertaken, concomitant with a comprehensive elucidation of the defining characteristics inherent to varied methodologies.The pivotal role ascribed to applied electric fields in heightening SERS enhancement finds ample illustration, underpinning their manifold applications encompassing drug identification, chemical detection, and catalytic processes.These insights are underscored vividly through judicious integration of apt visual aids and illustrative instances.Concluding the discourse, an expose on the challenges and prospects intrinsic to these E-SERS substrates is presented.This review paves the way for an impending and profound exploration within the domain of this promising field.

Principle for E-SERS
One of the means of E-SERS is to apply an external electric field directly on the substrate (Figure 2A).The application of the electric field brings more free electrons to the substrate, which can promote charge transfer between the substrate and the molecules, resulting in a significant enhancement of the Raman signal.The change of free electron density on the substrate metal nanoparticles leads to the shift of the plasma resonance peaks, which results in a directional modulation of the Raman signal intensity.In addition, applying an electric potential to a particular structure can generate dielectric electrophoresis and dipole-dipole interactions, leading to the concentration of nanoparticles in regions of high electric field strength and the formation of high-density hotspots. [19,20]The application of oscillating electric fields induces synchronous vibrations of molecules, alters their dipole moments, and induces unique chemical bonding behaviors for specific molecules, thus allowing for specific differentiation of target molecules.Oscillating electric fields can also quickly and efficiently deposit a variety of probe molecules and aggregate them on hotspots to enhance the Raman signal.Another approach to E-SERS is to utilize the spontaneous electric field of the SERS substrate material (Figure 2B). [21,22]Some substrate materials have self-generated electric properties in response to external stimuli, including piezoelectric, friction electric, thermoelectric, and pyroelectric materials. [23]These materials generate internal electric fields under conditions of mechanical deformation, mechanical friction, and controlled temperature changes in response to various forms of stimuli.In some of these materials, the generation of internal electric fields results in electrons being injected into the active layer of the SERS, enhancing the EM field in the vicinity of the metallic nanostructures, which ultimately leads to the enhancement of the Raman signal.In addition, the generation of internal electric field affects the charge transfer efficiency between the substrate material and the metal nanoparticles and allows the modulation of the metal Fermi energy levels to improve the resonance excitation efficiency between molecules. [24,25]n summary, E-SERS is an effective and versatile technique for improving the sensitivity and selectivity of Raman spectroscopy.Electrical modulation is based on the application of an external electric field or excitation of a spontaneous electric field, which leads to changes in the vibrational properties of the analyte molecules.These changes result in enhanced Raman scattering intensity and can be used in a wide range of areas such as chemical sensing, catalysis, and surface analysis.

External Electric Field
The modulation of the external electric field on SERS is a complex phenomenon that involves factors such as the strength of the electric field (positive or negative), as well as the application of alternating current (AC) power to alter the frequency of the field.To achieve maximum enhancement, the resonance frequency of the molecule must be in accordance with the frequency of the electric field.The effects of the electric field on the Raman frequency of a molecule can be exploited to investigate its properties.Moreover, the electric field can also induce an enrichment effect on probe molecules, which can be utilized to adjust the intensity of the SERS signal.
James H. Rice et al. from University College Dublin combine graphene oxide (GO) with diphenylalanine peptide nanotubes (FF-PNTs) and applied external electrical fields to further enhance the SERS effect (Figure 3A). [26]It is found that the applied electric field ranging from 5 to 25 V could increase the Raman intensity efficiently and achieve the strongest enhancement factor up to 10 times, while if exceeds it results in the reduced Raman signal (Figure 3B).Studies show that the variation of the Raman intensity should be associated with the pyroelectricity of FF-PNT.The effect might be activated after applying the electric field, and the producing electrons might enhance the charge-transfer processes between the FF-PNTs and GO.However, the pyroelectric effect of the FF-PNTs would reduce as the temperature increases beyond 55 °C, and the substrate heats up to 60 °C when the electric field is above 25 V mm À1 .Thus, the increased Raman signal is attributed to the more efficient charge transfer that decreases the difference in energy, and too high an electric field would drive out of resonance the energy levels, decreasing charge-transfer efficiency.Based on this mechanism, the composite SERS substrate realizes the detection of biomolecules with low-Raman cross sections at nanomolar concentration.
In the same year, James H. Rice et al. reported the alignment of a template consisting of silver nanoparticles on peptide nanotubes and contact with microfabricated chips in dry environment (Figure 3C). [27]It is shown that the application of a longitudinal electric field can tune the density of states of diphenylalanine peptide nanotube (FF-PNT) from semiconductor to metal, thus enabling effective charge transfer from nanotube to metal nanoparticles.This leads to an enhancement of the hot electron density of states (Figure 3D).The oscillating electric field can cause synchronous vibrations of FF-PNT molecules under high voltage and bias, thus changing their dipole moments.Moreover, the applied electric field can enhance the local electric field generated by Ag NPs, causing the electrons to be perturbed from the equilibrium position.These two causes lead to the fluctuation of Raman intensity.The study found that the same approach can be used to enhance the Raman scattering intensity of small Raman cross-section molecules (such as glucose and DNA-based molecules).
The applied electric field can also control the resonance by changing the free electron density and thus causing the displacement of the absorption peak, which in turn affect the intensity of the Raman signal. [28]SERS-based system for electrically modulated plasma switching was developed by Xiaodong Chen et al.Researcher used a five-fold stellate polyhedral gold nanoparticle (FSPAuNP) as a sensitive single-particle working electrode whose potential can be used to control plasmon resonance.When a bias of À0.5 V is applied to Ag/AgCl, a clear polypyrrole(PPy) Raman spectrum appears.In contrast, the peak carbon-carbon intensity decreases sharply at a bias of þ0.5 V (red curve).The FSPAuNP device can switch the Raman signal "ON" and "OFF" under controlled conditions.When a negative voltage is applied, the free electron density decreases and the absorption peak is blueshifted to match the incident laser (532 nm).In contrast, when a positive voltage is applied, the free electron density increases and the absorption peak is redshifted, making it more difficult to resonate with the incident laser, resulting in a very weak Raman signal.Ilya N. Kurochkin et al. demonstrated that the action of gradient electric fields on nanoparticles can concentrate them in regions of high electric field intensity and induce their coagulation, thus having an effect on the SERS signal. [29]It was found that in the initial moments under electric field conditions, the SERS signal matched the background signal and no aggregation of nanoparticles was observed.With time delay, silver particles concentrate between the electrodes (in the region of maximum electric field gradient) and form aggregates.The formation of branched fractal aggregates leads to the concentration of hotspots in the detection area.As a result, a strong SERS signal with all characteristic peaks can be observed.In the absence of voltage, the signal intensity fluctuates around the background value.Moreover, the SERS signal intensity of the conjugated particles varies with the electric field intensity in a "sawtooth" shape.It is shown that this dependence originates from the dynamic structure of the aggregates formed under the action of the electric field.The aggregates of nanoparticles are anisotropic and oriented along the magnetic field lines.As they grow, they can close the circuit (short circuit) and cause rapid local heating of the environment, formation of air or vapor bubbles, and aggregate disruption.Aggregation disruption leads to a significant reduction in the intensity of the conjugated SERS signal.
Nikhil V. Medhekar et al used electrode pairs to study the influence of low-frequency (5 mHz to 1 kHz) oscillating electric fields on the SERS spectra of thiophenol. [30]The experimental apparatus consisted of a nanotextured, metalized surface to achieve SERS, with an integrated microscale electrode pair for applying the external field, as shown in Figure 4.This applied electric field is shown to affect SERS peak intensities and influence specific vibrational modes of the analyte.The applied electric field perturbs the polar analyte, thereby altering the scattering cross section.Peaks related to the sulfurous bond which binds the molecule to the silver nanotexture exhibit strong and distinguishable responses to the applied field, due to varying bending and stretching mechanics.During Raman measurements, an oscillating voltage was applied across the electrode pair on either side of the nanoisland array.It should be noted that no static (i.e., direct current) fields were applied for two reasons: 1) static fields are known to electrochemically degrade silver nano-structures and result in the dissociation of the adsorbed analytes and 2) the motivation of this work is to develop a platform for SERS enhancement with multivariate parametric control, by adding the strength, frequency, and phase of an external electric field to the SERS accumulation parameters.When there is no external electric field, C─S bond is aligned at a θ angle to the normal of the silver surface.When an oscillating field is applied to the silver island, the field strength perpendicular to the surface will increase (since the electric field lines are always perpendicular to the conducting surface).This will cause the rotation of the benzene ring and C─S bond to align with the field.At lower electric field strengths (2.5 and 5.0 kV mm À1 ), the benzene rings can be realigned to compensate for this application area by bending the C─S bonds.At higher electric fields (10.0 kV mm À1 ), the C─S bond resists further bending and the bond and the benzene ring itself can be deformed in the direction of the applied field to achieve equilibrium, as shown in Figure 2C.The bending of the C─S bond affects the 462 cm À1 peak.The deformation of the C─S bond and the change in orientation of the benzene ring affect the 420 cm À1 peak.The bending of the C─S bond and the resulting deformation of the bound benzene ring under strong electric fields are correlated with each other.These results highlight that the spectral variations are strongly correlated to field-induced molecular reorientation and the relationship between the molecular orientation and the EM field of the incident laser.
Subsequently, the group achieved the identification of thiophene from a mixture of structurally similar benzyl mercaptans using oscillating electric fields of different frequencies. [31]ERS substrates were prepared by photolithography of SERS-compatible silicon wafers, and then silver was plated on their surfaces using oblique angle deposition (OAD) technique to form discrete silver nanoislands with diameters of about 20-40 nm.It was found that under the influence of an oscillating electric field, this particular bond can be distinguished not only by its Raman shift, but also by its dependence on frequency.For example, the 469 cm À1 peak intensity in the Raman spectrum of thiophene increases sharply at 100 mHz and decreases at 1 Hz.The 417 cm À1 peak shows a similar trend, but with weaker intensity, it becomes stable at frequencies above 1 kHz.The unique behavior of the thiophene fingerprint peaks (417 and 469 cm À1 ) can be easily used to determine the presence of this molecule in the mixture.The anchoring C─S bond of thiophenol subject to bending forces (related to the 462 cm À1 peak) at lower electric field strengths.C) Higher electric fields subject the thiophenol molecule to stronger bending and potential stretching forces (related to the 420 cm À1 peak) (not to scale).Adapted with permission from ref. [31].Copyright 2011, American Chemical Society.
To investigate the regulation of the gate and bias voltages on SERS substrate, the graphene/Ag NP composite structure was fabricated on a field-effect transistor. [32]It is observed that when the gate voltage set as 60 V, the Raman and fluorescence signals are further enhanced using R6G as probe molecules.However, the intensity of that is significantly suppressed, when the gate voltage is set as À60 V.It is thought that turning gate voltage could turn the Fermi level of Ag NP.More hot electrons generated and transfer from the Ag NP to graphene after adding the positive gate voltages, which would obtain the stronger SERS and fluorescence signals.When the negative gate voltage was set, the positive holes are accumulated on the surface of graphene, resulting in the hot electrons transferring to graphene and recombining with the holes, which would reduce the Raman and fluorescence signals on the contrary.Besides, the electrons by increasing bias voltages were also added to investigate the reference.It demonstrates that the signals of SERS and fluorescence cannot be enhanced with the increasing bias voltages at gate voltage 60 V or signals on the contrary.Besides, the electrons by increasing bias voltages wtain the stro is not plasmonic hot electrons, they are carriers driven by bias voltages.
In addition, photocurrent can be used to estimate the charge transfer amplitude of SERS system.Jeong Ho Cho et al. developed a method to estimate in situ the magnitude of charge transfer by measuring the photocurrent generated in a hybrid system consisting of a physically adsorbed R6 G layer and a 2D material (Figure 5). [33]hyh-Chyang Luo et al. developed a platform using electrochemical surface-enhanced Raman scattering (EC-SERS) technique, which can directly measure the redox state of conducting polymers in liquids and thus enable indirect detection of oxidants in electrolyte solutions (Figure 6A). [34]Conducting polymers hydroxymethyl poly (3,4-ethylenedioxythiophene) or poly (EDOTOH) were coated onto gold nanoparticle-coated ITO glass as SERS-active substrates.The Raman peak intensity decreased with the oxidation of the poly (EDOT-OH) film, and the Raman intensity of the conducting polymer decreased more rapidly when the oxidizing agent was present.When the cathodic potential is applied, the active substrate returns to the preoxidation state.Real-time SERS spectra of homogeneous poly (EDOT-OH) films on AuNPs at a rate of 20 mV s À1 and a potential range of À0.5 to 0.5 V under applied cyclic potentials show that the Raman characteristic peaks of the polymers increase with decreasing applied potentials.When the applied potential is À0.5 to 0 V, there is a dominant peak at 1421 cm À1 and a dominant peak at 1503 cm À1 , representing the symmetric and asymmetric C α ═C β stretching bands, respectively.The intensity of the main peak at 1421 cm À1 is greatly enhanced by the cathodic potential, which is mainly due to the neutral state of polysilicon (EDOT-OH) rather than the doped state.When the applied membrane potential is 1.1 V, the membrane is either overoxidized or degraded.The SERS spectra of poly (EDOT-OH) films were measured when À0.5 to 1.1 V cycle potential was applied.The spectral intensity gradually decreased after each cycle and the intensity was not reversible.Therefore poly (EDOT-OH) films have to be in a certain anode voltage range to ensure stable detection of oxidants.For different oxidants (H 2 O 2 , ammonium persulfate (APS) and iron (III) chloride (FeCl 3 )), all showed similar results.This work provides new ideas for continuous monitoring of the redox state of conducting polymers and quantitative analysis of oxidant concentrations.
Robert Hołyst et al. from the Institute of Physical Chemistry of the Polish Academy of Sciences developed a method for rapid and efficient deposition of analytes on SERS substrates based on alternating electric fields. [35]The tetrafluoroethylene (PTFE) is formed into a separate unit in the shape of a cube with a pocket shape (Figure 6B).The SERS substrate is used as the electrode.The counter electrode is made of a glass covered with indium tin oxide (ITO).A PTFE septum of 200 μm thickness is attached to the counter electrode to avoid the flow of Faraday current.Both electrodes are connected to a function generator that provides the desired voltage waveform.The SERS substrate was immersed in a mixture of 1:4 v/v ethanol and water for 10 s.Then, two electrodes were placed in the deposition cell by connecting them to the power supply through a copper strip.Then, 50 μL of the deposited analyte solution was placed into the pocket between the SERS substrate and the PTFE separator.A squarewave voltage from 10 to 0 v or from 0 to 10 v was applied and oscillated for .The wavelength and the power of Raman excitation beam were 532 nm and 1 mW, respectively.Adapted with permission from ref. [34].Copyright 2015, American Chemical Society.
5 min.Finally, the SERS substrate was removed from the deposition cell and dried in the open air.It was shown that the intensity of the SERS signal increases with increasing deposition voltage when PMBA (10 À6 M) is placed at voltages from 0.1 to 10 V and frequencies of 10 kHz.The analysis of high-voltage applications from 100 V to 1000 V showed the opposite effect, that is, the SERS signal decreased with increasing voltage.The application of high voltages leads to high ion densities in the electric double layer (EDL) and consequent nonlinear effects, such as ion aggregation and spatial site resistance between ionic species.In addition, when the frequency is too low, the period of applied voltage is much longer than the time of EDL formation.During most of the time, the electric field is completely shielded and the molecules cannot move in a directional manner.For very high frequencies, the molecules do not have enough time to move and almost no molecules can reach the SERS surface.Therefore, it is important to adjust the appropriate frequency to suit the characteristics of the analyte under study.

Spontaneous Electric Field
In contrast to the direct application of electric fields, thermoelectricity, pyroelectricity, piezoelectricity, and frictional electricity utilize external stimuli to induce electric field excitation.These stimuli include, but are not limited to, temperature gradients, mechanical stress, and EM forces.This approach provides a natural advantage over applied electric fields by allowing the utilization of energy that would typically be lost in nature, such as the kinetic energy of water in rivers and the temperature gradients generated by human respiration.Therefore, the study of the SERS field considers the great relevance of thermoelectric, pyroelectric, piezoelectric, and frictional effects.
The piezoelectric effect describes the generation of an electric charge in certain crystalline materials in response to applied mechanical stress.It arises due to the displacement of ions within the crystal lattice upon mechanical deformation. [36]is effect can be described by the direct piezoelectric effect, where mechanical stress generates an electric field, and the converse piezoelectric effect, where an applied electric field induces mechanical deformation.The governing principles involve the noncentrosymmetry of the crystal structure, leading to the polarization of the material and its ability to respond electromechanically.The thermoelectric effect refers to the direct conversion of a temperature gradient into an electrical voltage, and vice versa, in certain materials known as thermoelectric materials. [37]This phenomenon is governed by the Seebeck effect, wherein an electric field is established when there is a temperature gradient across a thermoelectric material.The principles of thermoelectricity involve the concept of energy bands and electron transport in semiconductors.The pyroelectric effect describes the spontaneous polarization and consequent electric charge generation in certain materials when subjected to temperature variations.It occurs in materials lacking an inversion center in their crystal structure, leading to a net electric dipole moment.Temperature-induced changes in the spontaneous polarization give rise to the pyroelectric effect.The principles of the pyroelectric effect are associated with the concept of ferroelectricity, where the presence of a spontaneous electric polarization is reversible by an external electric field.The triboelectric effect is the phenomenon of generating electric charges when two dissimilar materials come into contact and then separate, causing electron transfer between the materials.It is primarily governed by the principles of contact electrification and charge redistribution at the material interfaces.The triboelectric series ranks materials based on their tendency to gain or lose electrons during contact, leading to positive or negative surface charges.The triboelectric effect finds application in self-powered sensors, wearable electronics, and energy harvesting from mechanical motion.
In electric field-modulated SERS setups, the SERS substrates have to be not only nanoscopically engineered but also electrically conductive, and the measurement needs to be performed in an electrical device or electrochemical cell. [38]To avoid the complexity of the instrumental setup in SERS test, Qi An et al. combined an energy conversion film and Ag nanowire layer.This middle layer is a polymeric composite piezoelectric film that fabricated reduced graphene oxide (rGO) doped in the piezoelectric polymer poly (vinylidene fluoride-co-hexafluoropropylene) (PVDF-HFP).This substrate could converts film deformation into stored electrical energy and present a prolonged negative electric potential for tens of seconds on the substrate surface.It is also found that the negatively charged polymeric layer injected electrons into the Ag nanowire layer, enhancing the intensity of the hotspot.On the contrary, the theoretical simulation shows that the positively charged substrate decreased the electric field in the Ag nanowire layer and results in decreasing SERS signals on experimental observation.
To further investigate the electric-field boosted SERS effect in a simple device, Qi An et al. proposed a triboelectrically active substrate, which strengthens the SERS signals of Au-Ag binary metal nanostructures by threefold (Figure 7). [39]The triboelectricity is easily generated by simply rubbing the SERS substrate using a piece of copper foil.The advantage compared to piezoelectric E-SERS substrates is that the charge generation processes are induced by gentle rubbing motion during Raman measurements, which would not defocus laser irradiation as film deformation and simplifies the operation of the measurement.James H. Rice et al. developed a PVDF/LiNbO3 piezoelectric film. [40]It is believed that the charge generated by the applied mechanical stress can be transferred to the analyte molecules, resulting in an enhanced CM mechanism.
Brian J. Rodriguez et al. developed a self-excited SERS substrate combining piezoelectric quasi-1D peptide nanotubes and plasmonic metal nanoparticles (Figure 8). [41]The substrate is mechanically bent to obtain the piezoelectric effect.During the bending of the substrate, the strain expected to be applied to the FF-PNT activates the piezoelectric potential by converting the FF-PNT deformation into stored electrical energy, which generates a negative potential on the FF-PNT surface.The surface potential then injects electrical energy into the plasmonically active metal nanostructures.Theoretical calculations show that the SERS signal level is enhanced as the net surface charge increases.Examination of the experimental data leads to the conclusion that the SERS intensity increases when the generated stress increases to 0.12 GPa, and the SERS signal intensity decreases when the substrate is bent beyond this value.In the ideal model, the SERS enhancement further reaches a maximum when about 20 electron charges are added to an Ag NP (due to Ag NP).However, as the pressure continues to be applied, the hole concentration gradually increases enough to "pull back" the electrons on the AgNP, resulting in a weakening of the SERS intensity.It was found that piezoelectric-based electric fields induce internal electric fields in Ag NP, and these internal electric fields work in concert.Usually, the effect of adding a positive charge to the FF-PNT surface leads to an enhancement of the SERS signal.In contrast, when negative charges occur on the FF-PNT surface, Figure 7. A-C) Schematic illustration of the fabrication process for the E-SERS substrate.D) The operation principle of the E-SERS substrate: a relative movement between the copper film and the noble metal interface gives rise to the transfer of electrons from copper to gold; then the negative surface charges induce the polarization of the rGO fillers; the polarized charges are preserved in the high-dielectric matrix and assisted in immobilizing and preserving the surface charges after the removal of the copper contacts, which in turn result in prolonged preservation of the surface charges; the prolonged interfacial E-fields finally lead to charge injection from rGOto the noble metal structure and boost the EM field therein.Bottom right: The measured Raman intensities from the charged and discharged substrates, respectively.Adapted with permission from ref. [40].Copyright 2019, Elsevier.
the SERS signal decreases.A maximum SERS signal is generated when 20 positive charges occur on the FF-PNT surface.Further addition of positive charges decreases the SERS signal intensity, resulting in a reduction of the piezoelectric synergistic electric field and the internal electric field of Ag NPs.
Zhen Li et al. proposed a regulation strategy based on thermoelectric effect.A thermoelectric SERS substrate consisting of GaN films and Ag NPs was developed.After applying a temperature gradient to this substrate, the formed thermoelectric potential can modulate the charge exchange between GaN and Ag NPs, thus distributing the Fermi energy level of Ag NPs in a wide range and thus improving the probability of resonant electron leap with the detected molecule. [42]When the Fermi energy level of n-type GaN is higher than that of Ag, its work function is 4.26 eV.At the heterogeneous interface of Ag/GaN, the energy band of GaN bends upward, leading to the directional transfer of charge from GaN to Ag.The bottom of the n-type GaN conduction band is higher than the Ag Fermi energy level, leading to the formation of a Schottky barrier between GaN and Ag, as shown in Figure 9A.During the heating process, according to the electrical results, the GaN film surface generates a relatively persistent thermal potential, and the negative potential causes the energy band and Fermi energy level of GaN to move upward (Figure 9B).At this time, the height of the Schottky barrier between GaN and Ag will increase in the heterogeneous interface, and more electrons will flow from GaN to Ag NPs.This resulted in a 4.7-fold enhancement of the Raman signal (Figure 9C).It was shown that the enhanced SERS signal due to the thermal potential should be attributed to the CM factor rather than the EM effect.Subsequently, to verify the generality of the thermoelectric effect on SERS, Zhen Li et al. developed a thermoelectric SERS substrate composed of ZnO nanorod arrays and metal nanoparticles (Figure 9D). [43]According to Seebeck's theorem, due to the high concentration and kinetic energy during heating, electrons at the bottom diffuse to the top, which leads to the accumulation of holes at the bottom and electrons at the top.As a result, an electric field is generated in the ZnO NRs from the bottom to the top, causing the ZnO energy band and Fermi energy level to tilt downward at the bottom (positive potential) and upward at the top (negative potential).During the cooling process, the energy level of ZnO at the bottom tilts upward and the energy level of ZnO at the top tilts downward.The tiltable energy band of ZnO improves the energy level overlap between CB/VB and the lowest unoccupied orbital (LUMO)/highest occupied orbital (HOMO) of the molecule, further improving the charge transfer resonance efficiency.As a result, the SERS effect of ZnO NRs is further enhanced.It is shown that the change in electron density caused by the thermal potential will cause the Fermi energy level of Ag to change from positive to negative over a wide range of distribution.This will increase the probability of resonance between the Fermi energy level and molecular LUMO/HOMO and thus increase the probability of charge transfer leap.In AZA substrates, Ag NPs/ZnO NRs have a greater change in electron density at larger thermal potentials compared to Ag NPs/ZnO NRs; this gives rise to a more extensive change in Ag at the Fermi level.Therefore, it can be reasonably said that the AZA substrate exhibits a greater CM effect on the overall SERS signal.In addition, the group developed E-SERS substrates based on pyroelectric materials (PMN-PT) combined with plasmonic silver nanoparticles (Ag NP). [44]The SERS signal intensity was enhanced by more than 100 times after the positive and negative thermoelectric potentials were applied (Figure 9E).Moreover, this work attributes the enhancement to a CM mechanism induced by charge transfer through theoretical calculations and experimental verification.It can be seen that in the process of Raman signal enhancement by the electric field excited by the applied temperature gradient, scientists prefer to attribute the enhancement factor to CM.
In contrast to directly affecting the energy level of the substrate material, Zhong Lin Wang et al. developed a device that uses the voltage generated by frictional electricity to achieve enrichment of the molecules to be measured (Figure 10). [45]The device uses a triboelectric nanogenerator (TENG) to provide electrostatic driving force for the enrichment of molecules on the SERS substrate.The TENG acts to generate an electric field in solution that provides sufficient driving force for the movement of the target molecules.The preconcentrator consists of a platinum wire electrode, a PDMS cavity, and a transparent indium tin oxide (ITO) conductive glass.Silver nanoparticles with an average diameter of 80 nm are dropped onto the ITO electrode as the SERS-active substrate.When the TENG is rotated, the upper and lower electrodes generate opposite charges, creating a strong electric field.Under the force of the electric field, the charged molecules move toward the negative electrode (SERS-active substrate), resulting in an enhanced SERS signal of the molecules.It was found that the output characteristics of TENG are high voltage and low current.The open-circuit voltage is up to 2000 V, while the short-circuit current is only 5.5 μA.TENG applies a voltage of 2.2 V to the pre-enrichment device and a current of 5.2 μA through it.This allows the molecules to be enriched faster under strong electric fields, and the low current achieves a natural suppression of other side reactions.In this system, the detection limit of Nile blue (NB, a positively charged molecule) reaches 10 À15 M and the enrichment time is reduced to 30 s. Unlike other ways of enriching molecules with an applied electric field, this system can be self-powered in the field without an applied voltage.
Chao Zhang et al. designed a light-energy-excited pyroelectric nanogenerator as a SERS substrate (Figure 11).The AgNWs solution was spun onto the PVDF membrane, and then graphene was transferred to cover the AgNWs to synthesize the graphene-@AgNWS hybrid structure acting as the PVDF membrane. [46]ue to its high dielectric constant and low dielectric loss, pyroelectric PVDF membranes can convert transient polarization caused by thermal absorption into electrical energy.The pyroelectric NG can adjust the local thermoelectric charge on the surface of the plasma layer by optical drive and can be further used as the SERS base to significantly enhance the Raman signal.In this system, the preservation time of potential could be up to 100 s, which provided enough time for SERS detection in situ.In addition, the process of superhot electron transfer providing energy for catalytic reactions is also studied.Under laser irradiation, the collective oscillation of free electrons produces a highly concentrated electric field.As the plasmon decays, hot electrons with high kinetic energy are produced.This can further effectively prevent the recombination of hot electrons and hole pairs induced by the plasmon effect by inducing the pyroelectric field through polarization after sunlight irradiation.As a result, more hot electrons will be transferred from AgNWs to graphene, increasing the local thermoelectric charge density at the active site and used for excellent catalytic properties.
Yan-Yan Song et al. modulated SERS using magnets to provide piezoelectric potential with adjustable pressure (Figure 12). [47]Controlled enhancement of piezoelectric potential is achieved by integrating asymmetric gold-decorated zinc oxide nanorods (ZnO NRs) together, using magnets to provide adjustable pressure.Due to the spatially oriented separation of electron-hole pairs on asymmetric NRs, the local hotspot intensity of Au tip was significantly improved, and SERS signal was increased by 6.7 times.The results show that in addition to the conventional properties of noble metal/semiconductor Schottky junction, asymmetric Au/ZnO NRs have the following special advantages in enhancing Raman signals.1) ZnO piezoelectric material can directly generate charge carriers under mechanical stress; 2) Au NPs provided a large number of hotspots for SERS enhanced; and 3) unique 1D asymmetric NRs promoted efficient spatial separation and migration of charge carriers.

Perspective and Conclusions
In this review, we have discussed the recent advances in E-SERS, which is an emerging technique that combines the high sensitivity and selectivity of SERS with the versatility and flexibility of electric field modulation.We have categorized the E-SERS methods into two types: applied electric field and spontaneous electric field.We have summarized the principles, advantages, and applications of each type of E-SERS method, with reference to the recently published related works.
Electrically modulated SERS offers higher sensitivity compared to traditional SERS techniques, enabling the detection of low-concentration analytes.Besides, the strength and direction of the electric field can be controlled and adjusted externally, providing a means to optimize and tailor the SERS enhancement effect for specific analytes or applications.By adjusting the electric field, specific molecular vibrations can be targeted, allowing for selective detection of certain molecules in complex samples.These methods can achieve self-powered and flexible E-SERS detection without external power sources or complex equipment.They can be applied to monitor the environmental pollutants, biological molecules, and chemical reactions in situ and in real time.
Despite the significant progress made in the field of E-SERS, there are still several challenges that need to be addressed.Some of them are as follows.1) The design and fabrication of novel E-SERS substrates with high stability, reproducibility, and uniformity.The development of E-SERS substrates with enhanced performance and reproducibility is crucial for the widespread adoption of this technique.Future research should focus on exploring new materials, surface structures, and fabrication techniques to create substrates that exhibit exceptional stability and uniformity.For instance, investigating plasmonic nanostructures with precise control over size, shape, and interparticle spacing can lead to improved E-SERS substrates with reproducible enhancements.Moreover, incorporating advanced nanomaterials, such as 2D materials or metal-organic frameworks, into the substrate design can offer enhanced stability and reproducibility.2) The optimization of the experimental conditions and parameters for E-SERS measurements, such as potential range, scan rate, temperature gradient, friction force, etc.To unleash the full potential of E-SERS, it is essential to optimize experimental conditions and parameters.Researchers should systematically study the effects of key parameters, such as potential range, temperature gradient, and friction force, on E-SERS performance.Understanding the underlying mechanisms governing these effects will enable precise control and tuning of E-SERS enhancements.3) The development of theoretical models and numerical simulations for E-SERS enhancement mechanisms and electric field distributions.Theoretical models and simulations play a vital role in unraveling the complex interactions underlying E-SERS enhancements.Researchers should work on refining existing models and developing new ones to gain deeper insights into the underlying physical and chemical processes.Incorporating factors such as plasmon-exciton interactions, charge-transfer phenomena, and EM field distributions can provide a comprehensive understanding of the E-SERS enhancement mechanisms.Furthermore, coupling experimental data with numerical simulations can facilitate the rational design of highly efficient E-SERS systems.4) The integration of E-SERS with other techniques, such as electrochemistry, microscopy, spectroscopy, etc., to achieve multifunctional and multidimensional analysis.Combining E-SERS with complementary techniques can enhance its analytical capabilities and broaden its applications.Integrating E-SERS with electrochemistry can enable real-time monitoring of electrochemical reactions at the nanoscale.Coupling E-SERS with various microscopy techniques, such as scanning probe microscopy or super-resolution imaging, can provide spatially resolved chemical information.Additionally, combining E-SERS with different spectroscopic methods can offer multidimensional molecular insights, facilitating comprehensive analysis in complex samples.5) The exploration of new applications of E-SERS in various fields, such as catalysis, energy conversion and storage, biomedicine, nanotechnology, etc.The versatility of E-SERS makes it highly promising for applications in diverse fields.Researchers should actively explore and demonstrate the potential of E-SERS in catalysis, energy conversion and storage, biomedicine, nanotechnology, and beyond.For example, studying catalytic reactions on E-SERS-active surfaces can provide valuable mechanistic insights.E-SERS can also be employed for in situ monitoring of electrochemical energy storage devices, leading to improved device performance.In biomedicine, E-SERS can play a critical role in sensitive and specific molecular sensing for disease diagnostics and therapeutics.Furthermore, exploring the use of E-SERS in nanotechnology can pave the way for advanced nanoscale devices and sensors.
In conclusion, E-SERS is a promising technique that has the potential to significantly impact the field of molecular sensing and analysis.The ability to regulate the applied electric field provides a unique opportunity to study the relationship between the electric field and the SERS signal, and the use of other electrical phenomena can further enhance the SERS signal.Despite the challenges that still need to be addressed, the recent progress in E-SERS has opened up new avenues for research and has the potential to lead to the development of more sensitive and robust sensing techniques.We hope that this review article can provide a comprehensive overview of the current state-of-the-art of E-SERS and inspire more research interest and innovation in this emerging field.

Figure 2 .
Figure 2. A) Applied electric field-modulated SERS signal and B) self-generated power-modulated SERS signal.

Figure 3 .
Figure 3. A) Schematic illustration of the substrate design used in the study.The inset in panel a shows Raman spectra from the analyte molecule TMPyP at a relatively low concentration of ∼10 À11 M on the FF-PNT/GO template with an applied electric field of 25 V mm À1 .B) Normalized SERS spectra recorded at 0 and 25 V mm À1 .C) Schematic sketch of the template design that is used in the study.D) SERS sensing of biomolecules on the template using an externally applied electric field.SERS measurements of glucose.Adapted with permission from refs.[27,28].Copyright 2019, American Chemical Society and 2019, Springer Nature.

Figure 4 .
Figure 4. Electric field-induced thiophenol molecular kinetics.A) Schematic representation of typical thiophenol binding to silver nanostructures.B) The anchoring C─S bond of thiophenol subject to bending forces (related to the 462 cm À1 peak) at lower electric field strengths.C) Higher electric fields subject the thiophenol molecule to stronger bending and potential stretching forces (related to the 420 cm À1 peak) (not to scale).Adapted with permission from ref.[31].Copyright 2011, American Chemical Society.

Figure 5 .
Figure5.A) Schematic illustration of Raman and photoinduced charge transfer measurement of Rhodamine 6G (R6G) film coated on two different kinds of hexagonal atomic layers.MoS 2 and WSe 2 films fabricated on SiO 2 /Si substrate were dipped to %100 μM aqueous R6G solution.B) Raman spectra of monolayer R6G film adsorbed on the monolayer graphene (red line), MoS 2 (blue line), and WSe 2 (green line) substrates, respectively.Dashed black line corresponds to 1250 cm À1 .The wavelength and the power of Raman excitation beam were 532 nm and 1 mW, respectively.Adapted with permission from ref.[34].Copyright 2015, American Chemical Society.

Figure 6 .
Figure 6.A) Setup of electrochemical surface-enhanced Raman scattering (EC-SERS) with an automapping stage where the laser beam moves 2 μm every 30 s in 6 Â 6 μm 2 to monitor the bonding state change with time during polymer oxidation.B) System for analyte deposition in the electric field.50 μL of analyte solution was placed into the pocket between SERS substrate and counter electrode covered with separator (200 μm PTFE foil).Electrodes were connected to the source of voltage (function generator) using copper tape.Adapted with permission from refs.[35,36].Copyright 2019, American Chemical Society and 2020, Biosensors and Bioelectronics.

Figure 8 .
Figure 8. Schematics of the device used to flex the substrate and a SERS experiment with a flexed FF-PNT/Ag NP substrate.Adapted with permission from ref.[42].Copyright 2020, American Chemical Society.

Figure 9 .
Figure 9. A,B) Schematic diagram of GA structure and principle.C) Changes in the intensity of 10 À7 M R6G SERS during the heating process.D) Schematic description of the AZA substrate.E) Raman spectra of R6G (10 À11 M) measured during the cooling processes.F) Enhancement factors of SERS signals of R6G during the heating and cooling processes for different substrates.Adapted with permission from refs.[43,44].Copyright 2022, American Chemical Society and 2022, Springer Nature.

Figure 10 .
Figure 10.Schematic setup of triboelectric preconcentration device in SERS.A) An electric field provided by TENG is applied between the top Pt wire electrode and the ITO electrode including the SERS substrate, most of the charged molecules are attracted along an electric field (pink lines) and then concentrated onto the ITO electrode resulting in amplification of the SERS signal for the molecules.SEM images of B) PTFE and C) Ag nanoparticles.D) Working schematic diagram of the triboelectric preconcentration of charged molecules.E) SERS measurements of NB molecules with or without TENG.Adapted with permission from ref. [46].Copyright 2022, Elsevier.

Figure 11 .
Figure 11.A) Schematic diagram of pyroelectric NG.SERS signals and local electric filed intensity improved by the pyroelectric effect.B) SERS spectra (R6G, 10 À7 M) comparison before and after sunlight illumination.C) SERS spectra (R6G, 10 À7 M) detected at every 20 s after stopping illumination.D) SERS intensity of the Raman peak at 610 cm À1 during the repeated five cycles.E) SERS spectra (CV, 10 À7 M) comparison before and after sunlight illumination.Adapted with permission from ref. [47].Copyright 2021, Elsevier.

Figure 12 .
Figure 12.A) Synthesis of Au/ZnO NR arrays.B) Flexible SERS substrate was attached on the surface of runner's forehead for monitoring the degree of exercise fatigue by analyzing the perspiration components.C) SERS and D) E-SERS performance of the device and the composition of the functional layer of the substrate.Adapted with permission from ref. [48].Copyright 2021, American Chemical Society.