Electrochemical Surface-enhanced Raman Spectroscopy Research Articles

Targeted fentanyl screening utilizing electrochemical surface-enhanced Raman spectroscopy (EC-SERS) applied to authentic seized drug casework samples

Effective and rapid screening methods for seized drug analysis are crucial to ensure the safety of first responders and laboratory personnel, while reducing overall analysis time and improving reliability. The drug landscape has been overwhelmed by fentanyl and fentanyl analogs that are extremely potent and generally present in low concentrations with other drugs and diluents. We have previously reported the use of electrochemical surface-enhanced Raman spectroscopy (EC-SERS) as a novel screening method for detecting fentanyl and fentanyl analogs in the presence of commonly encountered analytes. Herein, we present the application of this targeted method to authentic seized drug casework samples to assess the performance and fit-for-purpose of the developed method to accurately identify fentanyl and fentanyl-like substances. Authentic sample sets contained a wide range of analytes, and a varying number of compounds present in each sample, representing both true positive and true negative samples. EC-SERS results were compared to the ground-truth as established by gas chromatography-mass spectrometry (GC–MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS), as well as the results of chemical color tests. Application to authentic samples allowed for identification of fentanyl and fentanyl analogs. The targeted approach was shown to provide preferential enhancement of the fentanyl signal. The overall accuracy for the targeted screening method for the presence of a fentanyl/fentanyl-like substance was 87.5 % and the fentanyl samples averaged between 6 wt% to 9 wt% fentanyl or fentanyl analog. EC-SERS provided an alternative fentanyl screening approach demonstrating results within minutes and the absence of false positives.

Ultraminiaturized Microfluidic Electrochemical Surface‐Enhanced Raman Scattering Chip for Analysis of Neurotransmitters Fabricated by Ship‐in‐a‐Bottle Integration

Electrochemical surface‐enhanced Raman scattering (EC‐SERS) is a promising technique for the diagnosis of trace amounts of neurotransmitters, because it can elucidate neurotransmitters’ behavior on electrodes to deduce their functions in the human body. However, the current EC‐SERS devices need several tens of milliliters of analyte solution to collect enough signal for analysis. Miniaturization of EC‐SERS devices is crucial for the early diagnosis of disease and point‐of‐care testing. Herein, a new type of EC‐SERS sensor based on 3D microfluidic chips for the analysis of neurotransmitters in ultrasmall volumes is proposed. The microfluidic EC‐SERS chip is fabricated by a ship‐in‐a‐bottle technique based on hybrid laser processing. The working electrode is modified using silver/zinc oxide materials, enabling the formation of a unique “candy apple” structure. To assess the fabricated microfluidic EC‐SERS chips, ascorbic acid is analyzed using the ingenious microfluidic EC‐SERS chips to elucidate its redox reaction by EC‐SERS spectroscopy. Significantly, a sub‐10 μL volume of analyte solution is sufficient for EC‐SERS analysis, which is several orders smaller in volume than the requirements of current EC‐SERS devices. The unprecedented microfluidic EC‐SERS chips fabricated by the ship‐in‐a‐bottle integration technique can be used in portable and smart analyzers for next‐generation biomedicines and catalysts.

Potential controlled redox cycling of 4-aminothiophenol by coupling plasmon mediated chemical reaction with electrochemical reaction

The plasmon-mediated chemical reaction (PMCR) is a promising new direction for photocatalysis. By harvesting light through photon-electron interactions using nanostructures of plasmonic metals, chemical reactions of immobilized molecules on the metal surface can be activated. As demonstrated in recent years, the electrode potential (E) applied to the metal surface also provides a unique means for electrosynthesis by changing the local electrostatic field and controlling the electron transfer and redistribution in the molecules immobilized on the electrode surface. Here, as a case study, we studied the E-modulated PMCR of 4-aminothiophenol (4-ATP) confined in the nano junction formed between the gold nanoparticle (AuNP) and gold nanoelectrode (AuNE) by using the time-resolved electrochemical-surface-enhanced Raman spectroscopy (EC-SERS), a powerful tool to track the chemical reaction in-situ on the plasmonic metal surfaces in solution. We demonstrated that the negative E can effectively suppress the plasmon-mediated photo-oxidation of 4-ATP to 4,4-dimercaptoazobenzene (DMAB) and meanwhile activate the EC reduction of DMAB to 4-ATP. We are able to use E to regulate the competition between photo-oxidation and EC reduction and achieve the redox cycling between 4-ATP and DMAB in continuous E cycles. By analyzing the E-modulated dynamic SERS signal changes, we also found the applied E could affect the SERS changes through two intertwined nonreaction and reaction mechanisms. This approach can improve our understanding of the photon-electron-molecule interactions and the interplay between PMCR and EC reactions in plasmonic molecular junctions.

Silver nanoparticles - laser induced graphene (Ag NPs - LIG) hybrid electrodes for sensitive electrochemical-surface enhanced Raman spectroscopy (EC-SERS) detection.

This paper presents a novel approach for the fabrication of low cost Electrochemical-Surface Enhanced Raman Scattering (EC-SERS) sensing platforms. Laser Induced Graphene (LIG) electrodes were readily fabricated by direct laser writing of polyimide tapes and functionalized with silver nanoparticles (Ag NPs) to obtain hybrid Ag NPs - LIG electrodes suitable for EC-SERS analysis. Detection was achieved by coupling a handheld potentiostat with a Raman spectrograph, enabling measurement of SERS spectra of target analytes generated during voltage sweeps in the 0.0 to -1.0 V interval range. The sensing capabilities of the fabricated system were first tested with model molecule 4-aminobenzenethiol (4-ABT). Following sensitive detection of 4-ABT, EC-SERS analysis of food contaminant melamine in milk and antibiotic difloxacin hydrochloride (DIF) in river water was demonstrated, achieving sensitive detection of both analytes without pre-treatment steps. The easiness of fabrication, versatility of design, rapid analysis time and potential miniaturization of the system make Ag NPs - LIG electrodes suitable for a large range of in situ applications in the field of food monitoring and for environmental analysis.

EC-SERS detection of thiabendazole in apple juice using activated screen-printed electrodes

Thiabendazole (TBZ), a benzimidazole fungicide used for post-harvest treatment, may be a trace contaminant of food matrices. In this work, we report the first EC-SERS (electrochemical-surface enhanced Raman spectroscopy) detection of TBZ in spiked apple juice using electrochemically (EC) roughened, gold-based screen-printed electrodes (AuSPEs) and portable instrumentation. Polarizing the substrate (−0.8 V vs Ag/AgCl) improves the recorded SERS signal of TBZ, allowing to reach a limit of detection (LOD) in juice of 0.061 ppm with a relatively wide linear range (0.5–10 μM) and good intermediate precision (%RSD < 10). The recovery of TBZ from unprocessed juice was found to be more than 82 %. Furthermore, a proof-of-concept integration of AuSPEs with a miniaturized flow cell for the preconcentration of TBZ and the controlled delivery of sample and reagents has been demonstrated. This approach paves the way for integrated, portable analytical systems applicable for on-site sample collection, processing, and analysis.

Computational Model for Electrochemical Surface-Enhanced Raman Scattering: Key Role of the Surface Charges and Synergy between Electromagnetic and Charge-Transfer Enhancement Mechanisms.

We present a computational model for electrochemical surface-enhanced Raman scattering (EC-SERS). The surface excess of charge induced by the electrode potential (Vel) was introduced by applying an external electric field to a set of clusters [Agn]q with (n, q) of (19, ±1) or (20, 0) on which a molecule adsorbs. Using DFT/TD-DFT calculations, these metal-molecule complexes were classified by the adsorbate partial charge, and the main Vel-dependent properties were simultaneously studied with the aid of vibronic resonance Raman computations, namely, changes on the vibrational wavenumbers, relative intensities, and enhancement factors (EFs) for all SERS mechanisms: chemical or nonresonant, and resonance Raman with bright states of the adsorbate, charge-transfer (CT) states, and plasmon-like excitations on the metal cluster. We selected two molecules to test our model, pyridine, for which Vel has a remarkable effect, and 9,10-bis((E)-2-(pyridin-4-yl)vinyl)anthracene, which is almost insensitive to the applied bias. The results nicely reproduced most of the experimental observations, while the limitations of our approach were critically evaluated. We detected that accounting explicitly for the surface charges is key for EC-SERS models and that the highest calculated EFs, up to 107 to 108, are obtained by interstate coupling of bright local excitations of the metal cluster and CT states. These results highlight the importance of nonadiabatic effects in SERS and the capabilities of EC-SERS as a technique with potential to study excited-state coupling by tuning the CT and plasmon-like states by manipulating Vel.

(Invited) In Situ Electrochemical Raman Spectroscopy for Nanoscale to Macroscale Electrochemical Processes

Raman spectroscopy has been increasingly applied in studying the electrochemical processes, including adsorption and reaction, under in situ or operando condition, because Raman spectroscopy can conveniently work in aqueous solution and provide fingerprint molecular information. In this talk, I will present the recent work in my group on developing various electrochemical Raman spectroscopy for in-situ and operando studies of electrochemical systems at the limits of time and spatial resolution and sensitivityWith the help of the plasmonic enhancement at the tip of a plasmonic material, electrochemical tip-enhanced Raman spectroscopy (EC-TERS) offers itself as the only nanospectroscopy for investigating the electrochemical interface with unprecedent spatial resolution and explicit chemical fingerprint information. We developed the electrochemical TERS both based on STM and AFM using the water immersion objective and homemade optical instrument. EC-TERS was applied to obtain the molecular fingerprint information of surface adsorption and electrochemical reaction on single crystal surfaces and monitor the plasmon-driven reaction at the nanoscale.Aiming at addressing the challenge of monitoring the highly dynamic changing electrochemical interfaces under potential control and presence of the electrolyte, a transient electrochemical surface-enhanced Raman spectroscopy (TEC-SERS) was developed to monitor the structural evolution of surface species at a time resolution that equals the transient electrochemical methods (e.g. cyclic voltammetry and chronoamperometry), allowing the precise correlation of Raman signal with the molecular signature information and the electrochemical current signal. He observed an interesting two-step reaction processes that are impossible to observe by conventional steady state SERS methods. A wide-field Raman imaging system was developed to offer a high imaging speed to monitor the spatial and temporal change at every point over the whole electrode surface simultaneously. The heterogeneity of electrocatalytic reaction on the electrode surface was observed. This technique offers the possibility to spatially correlate electrochemical behavior and the particular surface sites where the reaction happens.

Ni-Catalyzed Plasmonic Oxygen Evolution at Near-Neutral Conditions

The oxygen evolution reaction is essential in the solar production of chemical fuels, green hydrogen. Plasmonic metal-semiconductor systems can be potentially used for the production. Hot electrons generated by localized surface plasmon resonance are rapidly injected into the semiconductor, and concentrated hot holes oxidize water on the catalysts for oxygen evolution. Using Ni-modified Au/TiO2, in situ electrochemical surface-enhanced Raman spectroscopy was performed over the pH range of 7–13. Significantly enhanced photocurrents at near-neutral conditions were generated with low-energy photons (1.58 eV). The results prove that nickel-based catalysts accelerated the four-electron multistep reaction via plasmon-assisted water oxidation.

Dual-Approach Electrochemical Surface-Enhanced Raman Scattering Detection of Mycobacterium tuberculosis in Patient-Derived Biological Specimens: Proof of Concept for a Generalizable Method to Detect and Identify Bacterial Pathogens.

The recent surge in infectious disease-causing pathogens, resulting in global catastrophe, has merited a pivotal quest toward point-of-care (POC) diagnostics. Mycobacterium tuberculosis (MTB) is still the top bacterium-based infectious disease-causing pathogen worldwide. In a concerted effort toward simplifying and decentralizing the discriminatory screening of MTB causing pathogens, electrochemical surface-enhanced Raman scattering (EC-SERS) was adopted to create a customized screening tool. The development strategy combined five key factors, including (i) a simplified Tollens'-based chemical synthesis method for bulk supply of silver nanoparticles, (ii) the deliberate surface modification of nanoparticles with carefully selected polyelectrolytes to resemble the conditioning layer usually found on a natural substratum, (iii) uniform SERS-active films formed through simple unprogrammed assembly, (iv) the controlled manipulation of the local electric field through applied voltage using a technique that does not conform to the limitations of classical EC-SERS, and (v) the inherent specificity of the target-specific SERS vibrational signature. The EC-SERS platform was able to discriminatively detect and identify TB-derived mycobacteria, including three clinically relevant MTB strains, TB-H37Rv, TB-HN878, and TB-CDC1551. Moreover, a customized voltage stepping protocol, compatible with either the inclusion of a short preincubation step or with in situ EC-SERS is illustrated. From the obtained SERS vibrational signatures, a band indicating a mode unique to TB-derived/TB-affiliated mycobacteria and thus not observed for other bacterial types used in this study was illustrated. Furthermore, provisional investigation, done as prelude for assessing the potential for translational adaptability of the EC-SERS technique toward POC clinical settings for sputum and urine specimens, was carried out.

An Electrochromic Ag-Decorated WO3-x Film with Adjustable Defect States for Electrochemical Surface-Enhanced Raman Spectroscopy.

Electrochemical surface-enhanced Raman scattering (EC-SERS) spectroscopy is an ultrasensitive spectro-electrochemistry technique that provides mechanistic and dynamic information on electrochemical interfaces at the molecular level. However, the plasmon-mediated photocatalysis hinders the intrinsic electrochemical behavior of molecules at electrochemical interfaces. This work aimed to develop a facile method for constructing a reliable EC-SERS substrate that can be used to study the molecular dynamics at electrochemical interfaces. Herein, a novel Ag-WO3−x electrochromic heterostructure was synthesized for EC-SERS. Especially, the use of electrochromic WO3−x film suppresses the influence of hot-electrons-induced catalysis while offering a reliable SERS effect. Based on this finding, the real electrochemical behavior of p-aminothiophenol (PATP) on Ag nanoparticles (NPs) surface was revealed for the first time. We are confident that metal-semiconductor electrochromic heterostructures could be developed into reliable substrates for EC-SERS analysis. Furthermore, the results obtained in this work provide new insights not only into the chemical mechanism of SERS, but also into the hot-electron transfer mechanism in metal-semiconductor heterostructures.

Ultrasensitive MERS-CoV Biosensor Composed of Multi-functional DNA 3 Way-Junction Probe based on Electrochemical-Surface Enhanced Raman Spectroscopy (EC-SERS) Dual Detection System

Professor Taek Lee, associate professor, Biomedical Engineering Lab, Department of Chemical Engineering, Kwangwoon University, South Korea, is working on the development of biosensors and in vitro diagnostic devices, nucleic acid nanoengineering-based therapy and biomolecular-based bioelectronics for computation. Middle East respiratory syndrome coronavirus (MERS-CoV) is the novel coronavirus that causes Middle East respiratory syndrome (MERS). Lee is investigating the potential of aptamers to be used in the detection of viruses such as MERS-CoV. This could assist with diagnosis and treatment and protect peoples' health. In a world first, Lee and the team developed a MERS aptamer using the SELEX technique and then created the world's first MERS-nanovesicle biosensor composed of multi-functional DNA aptamer/graphene-MoS2 nanocomposite based on electrochemical and surface-enhanced Raman spectroscopy. The biosensor can detect the virus in a buffer solution and in saliva and the researchers believe it could be applicable to the detection of other viruses such as COVID-19. So far, the team has developed 30 types of aptamer that have potential to be used in biosensors and the researchers hope their work to establish a rapid virus detection system using fast SELEX and biosensor fabrication techniques will benefit health and wellbeing.

Forensic Identification of Fentanyl and its Analogs by Electrochemical-Surface Enhanced Raman Spectroscopy (EC-SERS) for the Screening of Seized Drugs of Abuse

Reliable identification of fentanyl and fentanyl analogs present in seized drug samples is imperative to the safety of first responders and laboratory personnel and informs the future analysis process and handling procedures. The electrochemical-surface enhanced Raman spectroscopy (EC-SERS) method developed in this work allows the in-situ preparation of the SERS substrate providing a rapid, efficient, and accurate approach to detect fentanyl, even at low percent by weight concentrations common in seized drugs. Optimization of the electrochemical potentials suitable for the SERS substrate preparation and adsorption of the analyte was achieved using multi-pulse amperometric detection. This method demonstrated large enhancement of the SERS response. This method was applied to six fentanyl analogs with substitutions to the amide group, representing small changes in the fentanyl core structure. Identification of these analogs through differences in the EC-SERS spectra was evident. Interference studies incorporating analytes frequently encountered with fentanyl including heroin, cocaine, methamphetamine, naltrexone, and naloxone were assessed and found to offer limited to no interference. The limits of detection of the fentanyl compounds were in the low to mid nanograms per milliliter range, with the most sensitive compound detected at 10 ng/ml. Application of the method to simulated drug mixtures was performed to determine fit-for-purpose. In all mixtures with fentanyl as the minor contributor, fentanyl was correctly identified, including mixture samples comprised of 5 and 1% fentanyl. This approach represents the first in-situ EC-SERS analysis of fentanyl and its analogs and provides accurate and efficient screening for fentanyl in seized drug samples.

Electrochemical surface-enhanced Raman spectroscopy (EC-SERS): a tool for the identification of polyphenolic components in natural lake pigments.

The identification of natural organic pigments is important for the conservation, preservation, and historical interpretation of artwork. Due to the fugitive nature of the natural dye components in pigments, their analysis can be complicated by issues such as low concentration and sample complexity. In addition, these pigments are exceedingly diverse, and often represent complex mixtures which are difficult to analyse without a separation step. A particularly challenging class of dyes is the natural yellow polyphenols (i.e. quercetin, rhamnetin, emodin, etc.). Several techniques have been used successfully for the identification of phenolic compounds in a complex mixture, but the majority of these methods require advanced instrumentation and one or more separation steps. In addition, these methods may lack the sensitivity needed to detect minute amounts of pigment remaining in faded artwork. As a result, there is a need for innovative methods of analysis which can be applied to the interpretation of artworks containing natural dyes. In this work, cost-effective screen printed electrodes (SPEs) modified with silver nanoparticles (AgNP) were used to amplify the electrochemical SERS response of phenolic compounds. In particular, application of a voltage to the SERS substrate allows for a fine-tuning of the SERS signal, and was successfully used to separately characterize dye components in two natural yellow lake pigments, Reseda Lake and Stil de Grain. To our knowledge, this work represents the first electrochemical surface-enhanced Raman spectroscopy (EC-SERS) study of polyphenolic dye mixtures, and is the first application of EC-SERS for natural pigment analysis. This work establishes EC-SERS as a useful technique for the identification of complex natural dyes which may find potential use in the cultural heritage realm.

Identification of the molecular pathways of RuO2 electroreduction by in-situ electrochemical surface-enhanced Raman spectroscopy

RuO2 is one of the most promising catalysts for oxygen evolution reaction (OER), a key reaction in water electrolysis. However, the fundamental insights about the structural evolution of RuO2 under different electrochemical environments remain unclear. Herein, the molecular reaction pathways of the electroreduction of RuOx in alkaline and neutral conditions are identified using in-situ electrochemical surface-enhanced Raman spectroscopy. Au@RuO2 core–shell nanostructures are fabricated to amplify the Raman signals of species adsorbed on RuOx surfaces. Using such core–shell nanostructures, direct spectroscopic evidences of OH intermediate during the RuO2 electroreduction process are obtained, which is further confirmed by D2O isotopic substitution experiments. A molecular pathway that RuO2 is reduced to Ru through a two-step reduction process has been proposed. This work provides insightful information on the structural evolution of RuOx with electrochemical environments.

Plasmonic photoelectrochemical dimerization and reduction of p-halo-nitrobenzene on AgNPs@Ag electrode

Electrochemical surface-enhanced Raman spectroscopy (EC-SERS) can provide the fingerprint information at the molecular level during electrochemical processes and the laser used in the EC-SERS process can simultaneously induce the plasmon-mediated chemical reaction (PMCR). In this work, EC-SERS has been used to understand the plasmonic effects on the selective dimerization reduction route of para-halonitrobenzene on the AgNPs@Ag electrode. Para-iodonitrobenzene (pINB) was first chosen as the probe molecule for photoelectrochemical reductions and investigated in acidic and neutral electrolyte solutions. The density functional theory (DFT) calculations confirmed that the electrochemical reduction of pINB produces 2-amino-5-iodophenol in HClO4 and p,p’-diiodoazobenzene (DIAB) in neutral electrolyte. However, when the PMCR is introduced in the electroreduction of pINB, the route of reduction path can be altered to the reduction product DIAB. Thus DIAB was generated firstly both in acidic and neutral conditions by PMCR and then reduced to p-iodoaniline. Finally, all the para chloro- and bromo- nitrobenzene can generate the p,p’-dihalo-azobenzene dimer by the PMCR under acidic conditions. Therefore, the plasmonic photoelectrochemical dimerization and reduction reactions can give us an idea to introduce the light on the selectivity of chemical reactions on plasmonic noble electrodes of nanostructures to alter the reduction pathway. This is practically significant for obtaining highly selective reduction products.

Fast Screening of Dithiocarbamate, Chloronicotinyl and Organophosphate Pesticides By Raman Spectroelectrochemistry Based on EC-SERS Effect

Electrochemical surface-enhanced Raman scattering (EC-SERS) effect is an outstanding procedure that ensures the enhancement of Raman signal by the electrochemical activation of the electrode surface. In that way, activation of metallic screen-printed electrodes (SPEs) by electrochemical routes leads to the generation of reproducible nanostructures with excellent SERS properties [1,2] and opens new gates for analytical applications.In this work, detection of thiram, imidacloprid and chlorpyrifos pesticides is achieved by the development of a new procedure. This methodology offers a quick and easy protocol which consists of three steps: (1) preconcentration of the sample, (2) electrochemical activation of SPE and (3) Raman detection of pesticides (Figure 1).Figure 1. Raman spectrum of thiram obtained following the proposed procedure.Analysis of tap water samples provides suitable results that demonstrate the capabilities of the proposed method. In that way, Raman spectroelectrochemistry based on EC-SERS effect avoids the complicated instrumentation, tedious pretreatment protocols or time-consuming measurement procedures used in other methods, and offers an interesting alternative in fields as environmental and food safety.

Double fingerprint characterization of uracil and 5-fluorouracil

Time Resolved Raman spectroelectrochemistry (TR-Raman-SEC) has been used for the first time to obtain two different Raman spectra of one single analyte in the same experiment. This double detection has been accomplished thanks to the use of electrochemical surface enhanced Raman scattering (EC-SERS) and electrochemical surface oxidation enhanced Raman scattering (EC-SOERS) in the same experiment. These two Raman enhancement phenomena can provide a broad insight into the interaction between analyte and substrate surface when they are combined. To prove the possibilities of this methodology, a Raman spectroelectrochemistry study of uracil (U) and 5-fluorouracil (5-FU), two analytes with relevance in medicine and biochemistry, have been performed. Density functional theory (DFT) calculations has been carried out to shed more light on the interaction of these molecules with silver substrates in acidic media.

Preface to the special issue dedicated to Professor Richard P. Van Duyne (1945–2019)

Preface to the special issue dedicated to Professor Richard P. Van Duyne (1945–2019)

Fabrication of high quality electrochemical SERS (EC-SERS) substrates using physical vapour deposition.

Screen-printed electrodes (SPEs) are an efficient and inexpensive substrate for electrochemical surface-enhanced Raman spectroscopy (EC-SERS) studies. Traditionally, the working electrode of the SPE is modified with either a colloidal paste of metal nanoparticles or an electrodeposited metallic film. These methods can be time-consuming and often produce non-uniform nanostructured films. Physical vapour deposition (PVD) is presented in this work as an efficient and effective alternative method for the production of SERS-active SPEs. SPEs coated with silver thin films via PVD show consistent and strong EC-SERS enhancement for the detection of two probe molecules, 4-aminothiophenol (p-ATP) and 5-(pyridine-4-yl)-1,3,4-oxadiazole-2-thiol (PYOT). The EC-SERS signal intensity for p-ATP and PYOT had coefficients of variation of 8.2% and 5.5%, respectively. More generally, these substrates show promise for reliable enhancement of molecules spanning diverse analytical applications.

Integrated EC-SERS Chip with Uniform Nanostructured EC-SERS Active Working Electrode for Rapid Detection of Uric Acid.

Toxemia of pregnancy is a very dangerous disease for pregnant women. The mortality rate of toxemia of pregnancy is close to 10% to 15%. Early detection of pregnancy toxemia is to monitoring uric acid concentration in urine. The current mainstream method for detecting uric acid requires an enzyme (urate oxidase), which needs to be stored in a low-temperature environment, and the method requires complex chemical steps, which takes a longer time and more samples. In this study, we propose an integrated miniature three-electrode electrochemical surface-enhanced Raman spectroscopy chip (EC-SERS chip) suitable for rapid EC-SERS detection applications. The integrated microfluidic reservoir on the chip makes it easy to use, which is very suitable for rapid detection applications. The SERS active working electrode for the proposed integrated EC-SERS chip is a nanocone array polycarbonate (PC) substrate decorated with an evenly distributed and tightly packed array of gold nanospheres. It showed good uniformity and can be easily reproduced. The integrated EC-SERS chip is very small compared to the traditional electrochemical cell, which reduces the sample volume required for the testing. In addition, the chip is for one-time use only. It eliminates the need to clean electrochemical cells for reuse, thereby reducing the possibility of contamination and inaccurate detection. Various low-concentration Rhodamine 6G (R6G) solutions were tested to verify the performance of the developed EC-SERS chip. Experimental results showed that the proposed EC-SERS chip has a strong enhancement factor of up to 8.5 × 106 and a very good EC-SERS uniformity (the relative standard deviation of EC-SERS intensity is as low as 1.41%). The EC-SERS chip developed has been further tested for the detection of uric acid in synthetic urine. The results showed that the EC-SERS signal intensity has a highly linear relationship with the logarithm of the uric acid concentration in synthetic urine, which indicates that the developed EC-SERS chip is suitable for the quantitative detection of uric acid in synthetic urine. Therefore, the developed EC-SERS chip is very promising to be used in routine and early diagnosis of pregnancy toxemia and may be used in many other medical tests, food safety, and biotechnology applications.