Strong Surface-enhanced Raman Scattering Signals Research Articles

Confined growth of Ag nanogap shells emitting stable Raman label signals for SERS liquid biopsy of pancreatic cancer

To develop a reliable surface-enhanced Raman scattering (SERS) immunoassay as a new liquid biopsy modality, SERS nanoprobes emitting strong and stable signals are necessary. However, Ag nanoparticles used as SERS nanoprobes are prone to rapid fading of SERS signals by oxidation. This has driven the development of a new strategy for Ag-based SERS nanoprobes emitting stable and strong SERS signals over time. Herein, Ag nanogap shells entrapping Raman labels are created in the confined pores of mesoporous silica nanoparticles (AgNSM) through a rapid single-step reaction for SERS liquid biopsy. Each AgNSM nanoprobe possesses multiple nanogaps of 1.58 nm to entrap Raman labels, allowing superior long-term SERS signal stability and large enhancement of 1.5 × 106. AgNSM nanoprobes conjugated with an antibody specific for carbohydrate antigen (CA)19-9 are employed in the SERS sandwich immunoassay including antibody-conjugated magnetic nanoparticles for CA19-9 detection, showing a two orders of magnitude lower limit of detection (0.025 U mL−1) than an enzyme-linked immunosorbent assay (0.3 U mL−1). The AgNSM nanoprobe immunoassay accurately quantifies CA19-9 levels from clinical serum samples of early and advanced pancreatic cancer. AgNSM nanoprobes with stable SERS signals provide a new route to SERS liquid biopsy for effective detection of blood biomarkers.

Gold-decorated laser-induced graphene for wearable biosensing and joule heating applications

BackgroundLaser-induced graphene from polyimide (PI) substrate has attracted much attention due to its controllable morphology and patternable structure. However, the property of polyimide-derived graphene (PDG) should be further improved to meet the requirement of next-generation flexible devices. MethodsIn this article, Au-modified PDG has been fabricated via the CO2 laser scribing on the common PI substrate. The obtained PDG with a foam-like morphology can provide large accessible sites for the deposition of Au nanoparticles (ANPs) by thermal evaporation. Significant findingsThe ANP-PDG devices have been utilized as electrochemical and surface-enhanced Raman scattering (SERS) sensors for the detection of dopamine (DA), Rhodamine 6G (R6G), and Adenine (Ad), respectively. The properties of the electrothermal heater based on the ANP-PDG films are also investigated. Due to the high conductivity and unique plasmonic effect of ANPs, the ANP-PDG displays higher electrocatalytic activity and stronger SERS signals than that of bare PDG film. The ANP-PDG also can reach higher steady-state temperatures (Ts) compared to the bare PDG heater. Furthermore, the ANP-PDG devices precisely defined on the PI substrate reveal great mechanical flexibility and the sheet resistance is very stable without obvious change, which can be applied for next-generation flexible electronics.

TbMOF@Au catalytic determination of trace malathion with aptamer SERS/RRS/Abs assay.

Terbium metal-organic framework (TbMOF) was prepared by microwave method with 1,3,5-benzenetricarboxylic acid as ligand. With HAuCl4 as precursor and NaBH4 as reducing agent, TbMOF-loaded gold nanoparticles (AuNPs) catalyst (TbMOF@Au1) was prepared rapidly and characterized by transmission electron microscope (TEM), X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy. It was found that TbMOF@Au1 has a strong catalytic effect on the HAuCl4-Cys nanoreaction, and the produced AuNPs have a strong resonant Rayleigh scattering (RRS) peak and surface plasmon resonance absorption (Abs) peak at 370nm and 550nm, respectively. With the addition of the molecular probe Victoria blue 4R (VB4r), AuNPs have a strong surface-enhanced Raman scattering (SERS) effect, the target analyte molecules are trapped in between the nanoparticles and a hot spot effect created in the process resulting in an extremely high SERS signal. A new SERS/RRS/Abs triple-mode analysis method for Malathion (MAL) was established by coupling this new TbMOF@Au1 catalytic indicator reaction with MAL aptamer (Apt) reaction, and its SERS detection limit was 0.21ng/mL. The SERS quantitative analysis method has been applied to the analysis of fruit samples with the recovery of 92.6-106.6% and the precision of 2.72-8.16%.

Nanogold sol plasmon discattering assay for trace carbendazim in tea coupled aptamer with Au3+-glyoxal-carbon dot nanocatalytic reaction.

Carbendazim (CBZ) is a broad-spectrum fungicide, which is toxic to mammals. Therefore, it is very necessary to establish a sensitive detection for food safety. An experiment found that CDFe exhibited excellent catalysis for the nano-indicator reaction of HAuCl4-glyoxal to produce gold nanoparticles (AuNPs) and that the generated AuNPs have a very strong surface-enhanced Raman scattering (SERS) effect at 1613 cm-1 in the presence of Victoria blue B molecular probes, and resonance Rayleigh scattering (RRS) signals at 370 nm. The aptamer (Apt) suppressed the catalysis of CDFe to cause the SERS and RRS signals decreasing. With the addition of CBZ, the specific Apt reaction occurred to restore the catalysis of CDFe, and resulting in a linear increase in the signals of RRS and SERS. As a result, this new nanocatalytic amplification indicator reaction was coupled with a specific Apt reaction of carbendazim (CBZ), to construct a new CDFe catalytic amplification-aptamer SERS/RRS discattering assay for ultratrace CBZ, which was used to analyze CBZ in tea samples with satisfactory results. In addition, this biosensoring platform can be also used to assay profenofos.

Multiplex SERS detection of polycyclic aromatic hydrocarbon (PAH) pollutants in water samples using gold nanostars and machine learning analysis.

Polycyclic aromatic hydrocarbons (PAHs) have attracted a lot of environmental concern because of their carcinogenic and mutagenic properties, and the fact they can easily contaminate natural resources such as drinking water and river water. This study presents a simple and sensitive point-of-care SERS detection of PAHs combined with machine learning algorithms to predict the PAH content more precisely and accurately in real-life samples such as drinking water and river water. We first synthesized multibranched sharp-spiked surfactant-free gold nanostars (GNSs) that can generate strong surface-enhanced Raman scattering (SERS) signals, which were further coated with cetyltrimethylammonium bromide (CTAB) for long-term stability of the GNSs as well as to trap PAHs. We utilized CTAB-capped GNSs for solution-based 'mix and detect' SERS sensing of various PAHs including pyrene (PY), nitro-pyrene (NP), anthracene (ANT), benzo[a]pyrene (BAP), and triphenylene (TP) spiked in drinking water and river water using a portable Raman module. Very low limits of detection (LOD) were achieved in the nanomolar range for the PAHs investigated. More importantly, the detected SERS signal was reproducible for over 90 days after synthesis. Furthermore, we analyzed the SERS data using artificial intelligence (AI) with machine learning algorithms based on the convolutional neural network (CNN) model in order to discriminate the PAHs in samples more precisely and accurately. Using a CNN classification model, we achieved a high prediction accuracy of 90% in the nanomolar detection range and an f1 score (harmonic mean of precision and recall) of 94%, and using a CNN regression model, achieved an RMSEconc = 1.07 × 10-1 μM. Overall, our SERS platform can be effectively and efficiently used for the accurate detection of PAHs in real-life samples, thus opening up a new, sensitive, selective, and practical approach for point-of-need SERS diagnosis of small molecules in complex practical environments.

Graphene-Based Surface-Enhanced Raman Scattering (SERS) Sensing: Bibliometrics Based Analysis and Review

Surface-enhanced Raman scattering (SERS) has received increasing attention from researchers since it was first discovered on rough silver electrode surfaces in 1974 and has promising applications in life sciences, food safety, and environmental monitoring. The discovery of graphene has stirred considerable waves in the scientific community, attracting widespread attention in theoretical research and applications. Graphene exhibits the properties of a semi-metallic material and has also been found to have Raman enhancement effects such as in metals. At the same time, it quenches the fluorescence background and improves the ratio of a Raman signal to a fluorescence signal. However, graphene single-component substrates exhibit only limited SERS effects and are difficult to use for trace detection applications. The common SERS substrates based on noble metals such as Au and Ag can produce strong electromagnetic enhancement, which results in strong SERS signals from molecules adsorbed on the surface. However, these substrates are less stable and face the challenge of long-term use. The combination of noble metals and graphene to obtain composite structures was an effective solution to the problem of poor stability and sensitivity of SERS substrates. Therefore, graphene-based SERS has been a popular topic within the last decade. This review presents a statistically based analysis of graphene-based SERS using bibliometrics. Journal and category analysis were used to understand the historical progress of the topic. Geographical distribution was used to understand the contribution of different countries and institutions to the topic. In addition, this review describes the different directions under this topic based on keyword analysis and keyword co-occurrence. The studies on this topic do not show a significant divergence. The researchers’ attention has gradually shifted from investigating materials science and chemistry to practical sensing applications. At the end of the review, we summarize the main contents of this topic. In addition, several perspectives are presented based on bibliometric analysis.

Spectrally multiplexed assay using gap enhanced nanoparticle for detection of a myocardial infarction biomarker panel

Multiplexed assays are essential for the detection of biomarker panels. Differentiating signals from different biomarkers in a single test zone makes the detection more efficient. In this paper, a new method is designed for the synthesis of gap-enhanced nanoparticles (GeNPs) using Raman reporter molecules (RRM) and 6-amino-1-hexanethiol (6-AHT) as the spacer. The GeNPs show a nanometer-size gap, generate strong surface-enhanced Raman scattering (SERS) attributed to the gap, and exhibit discriminative spectral peaks. The strong Au–S bonds on both core and shell sides and the covalent bond between RRM and 6-AHT led to a stable structure, which ensured the stable SERS signal generation from the GeNPs. Using the GeNPs, a spectrally multiplexed assay for the detection of a biomarker panel is developed. The biomarker panel is composed of cardiac troponin I (cTnI), copeptin, and heart-type fatty acid-binding protein (h-FABP), which improves myocardial infarction (MI) diagnostic performance. A paper-based platform that is more amenable to point-of-care diagnostic analysis is used. The developed single biomarker assay achieves limits of detection of 0.01 ng mL−1, 0.86 ng mL−1, 0.004 ng mL−1 for cTnI, h-FABP, and copeptin in buffer solutions. The dynamic range of the assay in human serum samples also covers the clinically relevant range of the biomarkers. The cross interference in the multiplexed assay is low. These results show the strong potential of the developed GeNPs in multiplexed detection of biomarkers and the developed simple-to-use multiplexed assay in the diagnosis of MI at the point of care.

A sensitive and simple competitive nanozyme-linked apta-sorbent assay for the dual-mode detection of ochratoxin A.

The enzyme-linked apta-sorbent assay (ELASA) is widely used for the detection of small-molecule compounds as a result of low cost and reagent stability of aptamers. However, enzyme labels used in ELASA still suffer from some drawbacks, such as high production cost and limited stability. To overcome the drawbacks, we reported a nanozyme-linked apta-sorbent assay (NLASA) coupled with surface-enhanced Raman scattering (SERS)-colorimetric dual-mode detection. For nanozyme labels, Pd-Pt bimetallic nanocrystals (Pd-Pt NRs) could catalyze 3,3',5,5'-tetramethylbenzidine (TMB) to blue TMB2+, whose color variation could not only be distinguished by naked eyes but also had a strong SERS signal. The NLASA method was employed to detect ochratoxin A (OTA) with a limit of detection values of 0.097 nM (0.039 ppb) and 0.042 nM (0.017 ppb) via the colorimetric and SERS methods, respectively. This method was applied for the determination of OTA in wine and grape samples, and the detection results were in a satisfied agreement with those determined by the high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method. The proposed NLASA method provided a rapid and sensitive detection for OTA and could also be broadened for other small-molecules.

Multimodal Gold Nanostars as SERS Tags for Optically-Driven Doxorubicin Release Study in Cancer Cells.

Surface Enhanced Raman Scattering (SERS) active gold nanostars represent an opportunity in the field of bioimaging and drug delivery. The combination of gold surface chemical versatility with the possibility to tune the optical properties changing the nanoparticles shape constitutes a multimodal approach for the investigation of the behavior of these carriers inside living cells. In this work, SERS active star-shaped nanoparticles were functionalized with doxorubicin molecules and covered with immuno-mimetic thiolated polyethylene glycol (PEG). Doxorubicin-conjugate gold nanoparticles show an intense Raman enhancement, a good stability in physiological conditions, and a low cytotoxicity. The strong adsorption of the anticancer drug doxorubicin in close contact with the gold nanostars surface enables their use as SERS tag imaging probes in vivo. Upon laser irradiation of the nanoparticles, a strong SERS signal is generated by the doxorubicin molecules close to the nanostars surface, enabling the localization of the nanoparticles inside the cells. After long time irradiation, the SERS signal drops, indicating the thermally driven delivery of the drug inside the cell. Therefore, the combination of SERS and laser scanning confocal microscopy is a powerful technique for the real-time analysis of drug release in living cells.

An ultrasensitive surface-enhanced Raman scattering sensor for the detection of hydrazine via the Schiff base reaction

The development of convenient assays for the determination of hydrazine (N2H4) has drawn significant attention due to the high toxicity of this substance. Herein, we developed a concise, rapid and ultrasensitive surface-enhanced Raman scattering (SERS) sensor for N2H4 detection based on alpha-cyclodextrin-silver nanoparticles (α-CD-AgNPs) modified by 4-mercaptobenzaldehyde (4-MBA). The 4-MBA molecules can specifically capture the N2H4 molecules and undergo a Schiff base reaction. As a result, this induces the aggregation of nanoparticles and generates a new characteristic peak at 1529 cm–1 that is attributed to CN and CC vibrations. Compared with noble metal nanoparticles, 4-MBA not only formed AgS bonds but could also be fixed in the cavity of cyclodextrin to produce a more stable and stronger SERS signal. The SERS intensity at 1529 cm–1 and the logarithm of the concentration of N2H4 presented a good linear relationship from 10–9 to 10–7 M with an unprecedented limit of detection (LOD) of 38 pM. The proposed SERS sensor exhibited satisfactory selectivity and reproducibility and was applied to detect N2H4 in real and complex water samples. We expect this assay to be a promising alternative tool for the on-site detection of N2H4.

Facile fabrication of PS/Cu2S/Ag sandwich structure as SERS substrate for ultra-sensitive detection

In this work, a serials of PS(polystyrene)/Cu2S/Ag sandwich substrates were successfully constructed using the magnetic sputtering method by adjusting the Ag sputtering time (0 min, 2 min, 4 min, 6 min, 8 min and 10 min) and used as the surface-enhanced Raman scattering (SERS) substrates. When the Ag sputtering time was 6 min, the strongest SERS signal was observed. The optimized SERS substrate has strong SERS activity on 4-mercaptobenzoic acid (4-MBA), the minimum detection limit was 10−13 M and the enhancement factor was as high as 4.7 × 107. In addition, the SERS signals were highly reproducible with small standard deviation. The SERS enhancement mechanism of the PS/Cu2S/Ag system was attributed to the synergistic effect of the chemical mechanism and the electromagnetic enhancement mechanism. This strategy has find a new way for manufacturing SERS activity sensor with high sensitivity and reproducibility.

Determination of Dichlorvos in Pears by Surface-Enhanced Raman Scattering (SERS) with Catalysis by Platinum Coated Gold Nanoparticles

A surface-enhanced Raman scattering (SERS) sensor is reported for the determination of dichlorvos, an organophosphate pesticide (OP), in pears. Platinum coated gold nanoparticles (Au@PtNPs) were used as secondary catalysts to provide signal amplification. Acetylcholinesterase (AChE) catalyzed the hydrolysis of acetylthiocholine to form thiocholine. Thiocholine causes the accumulation of Au@PtNPs, which changes the particle size and prevents their peroxidase-mimicking activity. Dynamic light scattering was used to characterize the particle size. Following the addition of dichlorvos, the AChE activity was inhibited, the production of thiocholine and aggregation were reduced, and the peroxidase mimicing property was retained. In the presence of 3,3′,5,5′-tetramethylbenzidine (TMB), a blue product was produced that provided strong SERS signals. The SERS method showed a linear relationship for dichlorvos concentrations from 20 to 2000 µg/L. The developed protocol had a limit of detection of 20 µg/L. This SERS sensor assay was successfully applied for the quantification of dichlorvos in pears with satisfactory recoveries from 80.25 to 94.86%.

Plasmonic Ag nanocube enhanced SERS biosensor for sensitive detection of oral cancer DNA based on nicking endonuclease signal amplification and heated electrode

Surface-enhanced Raman scattering (SERS) biosensing has attracted great attention due to its multiplexed capability, high sensitivity, and rapid readout. In this study, plasmonic Ag nanocube (AgNC) enhanced SERS biosensing platform was proposed by coupling nicking endonuclease-assisted target recycling signal amplification with heated electrode for sensitive detection of DNA species related to oral cancer. SERS tags were manufactured by signal DNA (sDNA) conjugating onto the surfaces of AgNCs, and 4-mercaptobenzoic acid (4-MBA) assembled on the surfaces of AgNC/sDNA as a Raman reporter. The sharp feature of edges and corners of AgNCs with high electromagnetic field provided SER hot spots with high quality, and stronger SERS signal could be achieved. In addition, the activity of nicking endonuclease Nt.BstNBI could be greatly enhanced by elevating the temperature of the surface of the heated Au electrode (HAuE) during Nt.BstNBI-assisted target recycling amplification process, resulting in dramatic amplification of target DNA detection. All of these contributed to the high sensitivity of the developed SERS biosensor. A limit of detection (LOD) of 3.1 fM (S/N = 3) could be obtained with an electrode temperature of 45 °C. This proposed SERS biosensor was anticipated to act as a promising biosensing platform for early clinical diagnosis of oral cancer.

Strawberry-like SiO2/Ag nanocomposites immersed filter paper as SERS substrate for acrylamide detection

In this work, based on the strawberry-like SiO2/Ag nanocomposites (SANC) immersed filter paper, a newly surface-enhanced Raman scattering (SERS) substrate was constructed for the detection of acrylamide (AAm) in food products. To construct filter paper-based SANC (F-SANC) SERS substrates, SiO2 nanoparticles (SNP) were firstly synthesized and acted as carriers. After that, the in-situ preparation of silver nanoparticles (Ag NP) on SNP surface was carried out to form the strawberry-like three-dimensional (3D) structure of SANC. Finally, SANC were entangled into the filter paper to produce nanoarchitecture, thus providing enhanced plasmon resonance between SANC with strong SERS signal. Under the optimized conditions, the method exhibited good performance toward AAm with a vast linear response from 0.1 nM to 50 μM (R = 0.9935), limit of detection (LOD) of 0.02 nM (S/N = 3), and the recoveries of 80.5%~105.6% for practical samples. This strategy showed good robustness in the rapid and sensitive detection of AAm, which could be a promising strategy in food analysis and verification.

Flexible and ultrasensitive surface-enhanced Raman scattering substrates for the pesticide detection

In this paper, a simplified method for preparing surface-enhanced Raman scattering (SERS) substrates with spin-coating is reported. The green chemical synthesis of Ag nanoparticles (NPs) is environmentally friendly without complex instruments. The Ag NPs are coated on a polydimethylsiloxane (PDMS) film by spin coating for detecting pesticides. By this method, we can get the substrate with high sensitivity. The results showed that the substrate has a strong SERS signal even the concentration of thiram (pesticide) is down to 10−9 M. Compared with the allowed residue dose in food security (10−5 M), the detection limit of thiram is lower. On the other hand, PDMS has the advantage of flexibility and transparency, it can meet the demands of the detection of analytes on irregular objects.

Improved surface-enhanced Raman scattering (SERS) sensitivity to molybdenum oxide nanosheets via the lightning rod effect with application in detecting methylene blue

MoO2 nanomaterials show a superior surface-enhanced Raman scattering (SERS) property due to their high concentration of free electrons and low resistivity. However, the physical process of semiconductor-based SERS is still elusive because there are many factors that affect the local electromagnetic field intensity and the subsequent Raman intensity of the molecules in close proximity to the semiconductor nanomaterials. Herein, we investigate the important contribution of surface morphology to molybdenum oxide SERS. The MoO3/MoO2 nanosheets (NSs) are synthesized by oxidizing MoO2 NS, and the surface roughness of MoO3 can be controlled through adjusting the oxidization time. Compared with the MoO2 NS before oxidization, the MoO3/MoO2 NSs exhibit a much stronger SERS signal, which favors their application as a SERS substrate to detect trace amounts of methylene blue molecules. The minimum detectable concentration is up to 10−9 M and the maximum enhancement factor is about 1.4 × 105. Meanwhile, excellent signal reproducibility is also observed using the MoO3/MoO2 NSs as the SERS substrate. A simulated electric field distribution shows that a stronger electric field enhancement is formed due to the lightning rod effect in the gap of corrugated MoO3 NSs. These results demonstrate that the surface topography of molybdenum oxide may play a more important role than their oxidation state in SERS signal enhancement.

SERS Substrate with Silk Nanoribbons as Interlayer Template.

The formation of hot spots is an effective approach to improve the performance of surface-enhanced Raman scattering (SERS). Silk nanoribbons (SNRs), with a height of about 1-2 nm, and Au nanoparticles (AuNPs) were assembled by electrostatic interactions to introduce sandwich hot spot structures. These sandwich structures were optimized by tuning the ratio of SNRs and AuNPs, resulting in strong SERS signals with a sensitivity of 10-13 M and enhancement factor (EF) of 5.8 × 106. Improved SERS spectrum uniformity with relative standard deviation (RSD) about 11.2% was also achieved due to the homogeneous distribution of these hot spot structures. The inherent biocompatibility of SNRs and facile fabrication processes utilized endowed the SERS substrates significant benefits toward biomedical applications, confirmed by cytocompatibility and improved SERS bioimaging capacity in vitro. The results of this study suggest the feasibility of forming high performance bioimaging systems through the use of naturally derived materials with special nanostructures.

Surface-enhanced Raman scattering by composite structure of gold nanocube-PMMA-gold film

In this study, we experimentally prepared composite structures of 170 nm gold nanocube, poly(methyl methacrylate) (PMMA) spacer layers with different thicknesses, and 50 nm gold film as substrates for surface plasmons excitation and surface-enhanced Raman scattering (SERS). The SERS spectra of gold nanocube and the composite structure were studied by using a 633 nm laser as an excitation source and rhodamine 6G (R6G) as the Raman probe molecule with 5.625 µg/mL gold nanocube aqueous solution. It was found that the composite structures produced much stronger SERS signals than that with the single gold nanocube structure. The relationship between the intensities of SERS Raman peaks and the PMMA spacer layer thicknessess of the composite structures was found to have the same trend as that between the Raman enhancement factor and PMMA spacer layer thickness obtained by the finite element method simulation. Furthermore, a R6G concentration as low as 10−12 M could be detected by the composite structure.

A novel gold nanosol SERS quantitative analysis method for trace Na+ based on carbon dot catalysis

The Ca-doped carbon dots (CDCa) exhibited strong catalysis of HAuCl4-H2O2 reaction to produce gold nanoparticle (AuNP), using Vitoria blue 4R (VB4r) as molecular probe, it appeared a strong surface enhanced Raman scattering (SERS) peak at 1615 cm−1 in the AuNP nanosol substrate. When catalyst CDCa increased, the SERS peak enhanced linearly owing to AuNPs increasing, that is, the AuNP concentration is linear to SERS signal. Potassium pyroantimonate (PA) ligand can adsorb on CDCa surface to inhibit the catalysis and cause the SERS peak decreasing. The analyte of Na+ reacts with PA to produce the stable precipitate of [Na2(PA)] and free CDCa catalyst. The more Na+, the more CDCa released, and the stronger SERS signal due to more AuNP substrate. Accordingly, a SERS quantitative analysis method for Na+ was developed based on CDCa catalytic SERS reaction, with a linear range of 0.004–0.043 μmol/L, and a detection limit of 0.0019 μmol/L Na.

Self-Healing Plasmonic Metal Liquid as a Quantitative Surface-Enhanced Raman Scattering Analyzer in Two-Liquid-Phase Systems.

Liquid-state interfacial plasmonic systems are emerging as an alternative for the quantitation and practicability of the surface-enhanced Raman scattering (SERS) technique in analytical science, especially for complex liquid-phase systems. Here we show a general strategy for the three-dimensional (3D) self-assembly of gold nanoparticle (GNP) arrays on a spherical oil-water (O-W) interface, denoted as a plasmonic metal liquid (PML). The PML has excellent self-healing and shape-adaptive features; it can be transferred into containers of any shape; and it presents fast, quantitative, and multiplex SERS capability. Accurate control of nanoparticle density (PD) on the 3D interface enables tunable SERS strength. In situ synchrotron radiation small angle X-ray scattering (SR-SAXS) provides evidence that the interfacial PD is quantifiable and can be precisely regulated in the range of 24-216 particles/μm2, which produces optimizable Raman enhancement. The strongest SERS signal is achieved at 167 particles/μm2 with GNP diameters of approximately 64 nm. In particular, the O phase acts not only as the assembly media for spherical PML arrays but also as the extracting agent for targets with different natures in complex media. Moreover, the O phase with continuous-phase features generates inherent and sharp SERS fingerprints and provides an effective internal standard (IS) for calibrating the fluctuation of samples and measuring conditions. By virtue of the triple roles of the O phase, the PML platform exhibits excellent mechanical stability, detection sensitivity, and signal reproducibility. This study demonstrates the concept of a fast and quantitative liquid-state SERS platform in common cuvettes on a portable Raman device that is as simple as a spectrophotometer.