Observing π-Au Interaction between Aromatic Molecules and Single Au Nanodimers with a Subnanometer Gap by SERS.

Interface interaction between aromatic molecules and noble metals plays a prominent role in fundamental science and technological applications. However, probing π-metal interactions under ambient conditions remains challenging, as it requires characterization techniques to have high sensitivity and molecular specificity without any restrictions on the sample. Herein, the interactions between polycyclic aromatic hydrocarbon (PAH) molecules and Au nanodimers with a subnanometer gap are investigated by surface-enhanced Raman spectroscopy (SERS). A cleaner and stronger plasmonic field of subnanometer gap Au nanodimer structures was constructed through solvent extraction. High sensitivity and strong π-Au interaction between PAHs and Au nanodimers are observed. Additionally, the density functional theory calculation confirmed the interactions of PAHs physically absorbed on the Au surface; the binding energy and differential charge further theoretically indicated the correlation between the sensitivity and the number of PAH rings, which is consistent with SERS experimental results. This work provides a new method to understand the interactions between aromatic molecules and noble metal surfaces in an ambient environment, also paving the way for designing the interfaces in the fields of catalysis, sensors, and molecular electronics.

Ag supraparticles with 3D hot spots to actively capture molecules for sensitive detection by surface enhanced Raman spectroscopy.

To achieve highly sensitive detection using surface-enhanced Raman spectroscopy (SERS), it is imperative to fabricate a substrate with a high density of hot spots and facilitate the entry of target molecules into these hot spot regions. However, steric hindrance arising from the presence of surfactants and ligands on the SERS substrate may impede the access of target molecules to the hot spots. Here, we fabricate non-close-packed three-dimensional (3D) supraparticles with high-density hot spots to actively capture molecules. The formation of 3D supraparticles is attributed to the minimization of free energy during the gradual contraction of the droplet. The numerous capillaries present in non-close-packed supraparticles induce the movement of target molecules into the hot spot region through capillary force along with the solution. The results demonstrate that the SERS enhancement effect of 3D supraparticles is at least one order of magnitude higher than that of multi-layered nanoparticle structures formed under natural drying conditions. In addition, the SERS performance of 3D supraparticles is evaluated with diverse target molecules, including antimicrobial agents and drugs. Hence, this work provides a new idea for the preparation of non-close-packed substrates for SERS sensitive detection.

Extending Plasmonic Enhancement Limit with Blocked Electron Tunneling by Monolayer Hexagonal Boron Nitride.

Fabricating ultrasmall nanogaps for significant electromagnetic enhancement is a long-standing goal of surface-enhanced Raman scattering (SERS) research. However, such electromagnetic enhancement is limited by quantum plasmonics as the gap size decreases below the quantum tunneling regime. Here, hexagonal boron nitride (h-BN) is sandwiched as a gap spacer in a nanoparticle-on-mirror (NPoM) structure, effectively blocking electron tunneling. Layer-dependent scattering spectra and theoretical modeling confirm that the electron tunneling effect is screened by monolayer h-BN in a nanocavity. The layer-dependent SERS enhancement factor of h-BN in the NPoM system monotonically increases as the number of layers decreases, which agrees with the prediction by the classical electromagnetic model but not the quantum-corrected model. The ultimate plasmonic enhancement limits are extended in the classical framework in a single-atom-layer gap. These results provide deep insights into the quantum mechanical effects in plasmonic systems, enabling the potential novel applications based on quantum plasmonic.

Three-Phase Catassembly of 10 nm Au Nanoparticles for Sensitive and Stable Surface-Enhanced Raman Scattering Detection.

Interfacial self-assembly with the advantage of providing large-area, high-density plasmonic hot spots is conducive to achieving high sensitivity and stable surface-enhanced Raman scattering (SERS) sensing. However, rapid and simple assembly of highly repeatable large-scale multilayers with small nanoparticles remains a challenge. Here, we proposed a catassembly approach, where the "catassembly" means the increase in the rate and control of nanoparticle assembly dynamics. The catassembly approach was dropping heated Au sols onto oil chloroform (CHCl3), which triggers a rapid assembly of plasmonic multilayers within 15 s at the oil-water-air (O/W/A) interface. A mixture of heated sol and CHCl3 constructs a continuous liquid-air interfacial tension gradient; thus, the plasmonic multilayer film can form rapidly without adding functional ligands. Also, the dynamic assembly process of the three-phase catassembly ranging from cluster to interfacial film formation was observed through experimental characterization and COMSOL simulation. Importantly, the plasmonic multilayers of 10 nm Au NPs for SERS sensing demonstrated high sensitivity with the 1 nM level for crystal violet molecules and excellent stability with an RSD of about 10.0%, which is comparable to the detection level of 50 nm Au NPs with layer-by-layer assembly, as well as breaking the traditional and intrinsic understanding of small particles of plasmon properties. These plasmonic multilayers of 10 nm Au NPs through the three-phase catassembly method illustrate high SERS sensitivity and stability, paving the way for small-nanoparticle SERS sensing applications.

Development of a MoS2/Ag NP Nanopocket to Trap Target Molecules for Surface-Enhanced Raman Scattering Detection with Long-Term Stability and High Sensitivity.

Surface-enhanced Raman scattering (SERS) substrates mostly achieve highly sensitive detection by designing various hot spots; however, how to guide molecules to hot spots and prevent them from leaving has not been thoroughly considered and studied. Here, a composite MoS2/Ag NP nanopocket detector composed of MoS2 covered with a Ag NP film was fabricated to develop a general SERS method for actively capturing target molecules into hotspots. A finite element method (FEM) simulation of the multiphysics model was used to analyze the distributions of electric field enhancements and hydrodynamic processes in solution and air of the MoS2/Ag NP nanopocket. The results revealed that covering MoS2 slowed the evaporation of the solution, extended the window period for SERS detection, and enhanced the electric field in comparison with the monolayer Ag NP film. Therefore, in the process of dynamic detection, the MoS2/Ag NP nanopocket can provide an efficient and stable signal within 8 min, increasing the high sensitivity and long-term stability of the SERS method. Furthermore, a MoS2/Ag NP nanopocket detector was applied to detect antitumor drugs and monitor hypoxanthine structural changes in serum, which demonstrated long-term stability and high sensitivity for SERS analysis. This MoS2/Ag NP nanopocket detector paves the way for developing the SERS method in various fields.

Insight into the Heterogeneity of Longitudinal Plasmonic Field in a Nanocavity Using an Intercalated Two-Dimensional Atomic Crystal Probe with a ∼7 ŠResolution.

Quantitative measurement of the plasmonic field distribution is of great significance for optimizing highly efficient optical nanodevices. However, the quantitative and precise measurement of the plasmonic field distribution is still an enormous challenge. In this work, we design a unique nanoruler with a ∼7 Šspatial resolution, which is based on a two-dimensional atomic crystal where the intercalated monolayer WS2 is a surface-enhanced Raman scattering (SERS) probe and four layers of MoS2 are a reference layer in a nanoparticle-on-mirror (NPoM) structure to quantitatively and directionally probe the longitudinal plasmonic field distribution at high permittivity by the quantitative SERS intensity of WS2 located in different layers. A subnanometer two-dimensional atomic crystal was used as a spacer layer to overcome the randomness of the molecular adsorption and Raman vibration direction. Combined with comprehensive theoretical derivation, numerical calculations, and spectroscopic measurements, it is shown that the longitudinal plasmonic field in an individual nanocavity is heterogeneously distributed with an unexpectedly large intensity gradient. We analyze the SERS enhancement factor on the horizontal component, which shows a great attenuation trend in the nanocavity and further provides precise insight into the horizontal component distribution of the longitudinal plasmonic field. We also provide a direct experimental verification that the longitudinal plasmonic field decays more slowly in high dielectric constant materials. These precise experimental insights into the plasmonic field using a two-dimensional atomic crystal itself as a Raman probe may propel understanding of the nanostructure optical response and applications based on the plasmonic field distribution.

Controlling the Shrinkage of 3D Hot Spot Droplets as a Microreactor for Quantitative SERS Detection of Anticancer Drugs in Serum Using a Handheld Raman Spectrometer.

Quantitative measurement is one of the ultimate targets for surface-enhanced Raman spectroscopy (SERS), but it suffers from difficulties in controlling the uniformity of hot spots and placing the target molecules in the hot spot space. Here, a convenient approach of three-phase equilibrium controlling the shrinkage of three-dimensional (3D) hot spot droplets has been demonstrated for the quantitative detection of the anticancer drug 5-fluorouracil (5-FU) in serum using a handheld Raman spectrometer. Droplet shrinkage, triggered by the shaking of aqueous nanoparticle (NP) colloids with immiscible oil chloroform (CHCl3) after the addition of negative ions and acetone, not only brings the nanoparticles in close proximity but can also act as a microreactor to enhance the spatial enrichment capability of the analyte in plasmonic sites and thereby realize simultaneously controlling 3D hot spots and placing target molecules in hot spots. Moreover, the shrinking process of Ag colloid droplets has been investigated using a high-speed camera, an in situ transmission electron microscope (in situ TEM), and a dark-field microscope (DFM), demonstrating the high stability and uniformity of nanoparticles in droplets. The shrunk Ag NP droplets exhibit excellent SERS sensitivity and reproducibility for the quantitative analysis of 5-FU over a large range of 50-1000 ppb. Hence, it is promising for quantitative analysis of complex systems and long-term monitoring of bioreactions.

Floating Ag-NPs@Cu-NW bundles fabricated on copper mesh for highly sensitive SERS detection of uric acid in pretreatment-free urine.

The rapid and sensitive detection of ultra-trace marker molecules from biological samples is of great significance for the wide application of surface-enhanced Raman spectroscopy (SERS) methods in clinical diagnosis and disease monitoring. However, the cumbersome biological sample processing procedures and the poor enrichment of target analytes in hot spots hinder the practical applications of SERS methods. In this paper, we synthesized a novel floating SERS substrate by a simple one-step oxidation process, annealing and in situ chemical etching to form Ag-NPs@Cu-NW bundles on copper mesh (CM). In particular, under spontaneous bottom-up capillary action, the pressure difference at different nanogaps drives uric acid molecules to actively enter hot spots, so that the Ag-NPs@Cu-NW bundle nanostructure with the advantages of a light weight CM is capable of preventing the common coffee-ring effect and enhancing the spatial enrichment of analytes. Therefore, this SERS substrate realizes highly sensitive detection of uric acid at a level of 50 nM in pretreatment-free urine. Currently, this portable, flexible, simple, fast and cost-effective SERS substrate has great potential for early screening and clinical diagnosis of diseases in different biofluids.

Construction of Ag nanowire@Au nanoparticle nano nests with densely stacked small gaps for actively trapping molecules to realize diversity SERS detection.

Highly sensitive surface-enhanced Raman spectroscopy (SERS) sensing not only depends on an active substrate with high density of hot spots, but also depends more on whether the molecules can effectively enter the hot spot region. In this paper, a new SERS detection method based on the nano nest model is developed to autonomously capture molecules into hot spots. The nano nest is composed of silver nanowires modified with gold nanoparticles (Ag NW@Au NPs), which not only form high density hot spots between particles or particles-wires, but also have a coupled electromagnetic field enhancement effect. The SERS detection method based nano nest actively traps molecules through the capillary stage, and makes the molecules move toward densely stacked small gaps (hot spots) by capillary action. The above method has been used to detect different kinds of molecules, such as pesticide residues, adenosine triphosphate in culture medium, and antibiotic residues in aquatic products. In addition, an in situ SERS monitoring of allergic reactions was also performed using nano nests with the feature of actively trapping molecules into the hot spots. This nano nest will be able to perform a direct monitoring of biochemical reactions, and more importantly, it can provide a new scheme for SERS detection.

Insight into ultrasensitive and high-stability flocculation-enhanced Raman spectroscopy for the in situ noninvasive probing of cupping effect substances.

The aggregation of nanoparticles is the key factor to form hot spots for the flocculation-enhanced Raman spectroscopy (FLERS) method. However, the structure of flocculation is still not clear. It is therefore necessary to explore and analyze the aggregation process of nanoparticles more carefully, so as to realize a better application of FLERS. Here, we report the application of in situ liquid cell transmission electron microscopy (TEM) combined with an in situ high-speed camera to analyze the particle behaviors. The results showed that flocculation can exist stably and the gap between the nanoparticles in the flocculation always remained at 7-9 nm, which ensured the high stability and sensitivity of the FLERS method. We successfully applied FLERS to the in situ noninvasive probing of cupping effect substances. The results indicated the scientific principle behind the traditional Chinese medicine method to some extent, which thus provides a new and effective method for the in situ dynamic monitoring of biological systems.

Elucidation of leak-resistance DNA hybridization chain reaction with universality and extensibility.

Hybridization chain reaction (HCR) was a significant discovery for the development of nanoscale materials and devices. One key challenge for HCR is the vulnerability to background leakage in the absence of the initiator. Here, we systematically analyze the sources of leakage and refine leak-resistant rule by using molecular thermodynamics and dynamics, biochemical and biophysical methods. Transient melting of DNA hairpin is revealed to be the underlying cause of leakage and that this can be mitigated through careful consideration of the sequence thermodynamics. The transition threshold of the energy barrier is proposed as a testing benchmark of leak-resistance DNA hairpins. The universal design of DNA hairpins is illustrated by the analysis of hsa-miR-21-5p as biomarker when used in conjunction with surface-enhanced Raman spectroscopy. We further extend the strategy for specific signal amplification of miRNA homologs. Significantly, it possibly provides a practical route to improve the accuracy of DNA self-assembly for signal amplification, and that could facilitate the development of sensors for the sensitive detection of interest molecules in biotechnology and clinical medicine.

General Surface-Enhanced Raman Spectroscopy Method for Actively Capturing Target Molecules in Small Gaps.

Over the past decade, many efforts have been devoted to designing and fabricating substrates for surface-enhanced Raman spectroscopy (SERS) with abundant hot spots to improve the sensitivity of detection. However, there have been many difficulties involved in causing molecules to enter hot spots actively or effectively. Here, we report a general SERS method for actively capturing target molecules in small gaps (hot spots) by constructing a nanocapillary pumping model. The ubiquity of hot spots and the inevitability of molecules entering them lights up all the hot spots and makes them effective. This general method can realize the highly sensitive detection of different types of molecules, including organic pollutants, drugs, poisons, toxins, pesticide residues, dyes, antibiotics, amino acids, antitumor drugs, explosives, and plasticizers. Additionally, in the dynamic detection process, an efficient and stable signal can be maintained for 1-2 min, which increases the practicality and operability of this method. Moreover, a dynamic detection process like this corresponds to the processes of material transformation in some organisms, so the method can be used to monitor transformation processes such as the death of a single cell caused by photothermal stimulation. Our method provides a novel pathway for generating hot spots that actively attract target molecules, and it can achieve general ultratrace detection of diverse substances and be applied to the study of cell behaviors in biological systems.

Construction of Optimal SERS Hotspots Based on Capturing the Spike Receptor-Binding Domain (RBD) of SARS-CoV-2 for Highly Sensitive and Specific Detection by a Fish Model.

It is highly challenging to construct the best SERS hotspots for the detection of proteins by surface-enhanced Raman spectroscopy (SERS). Using its own characteristics to construct hotspots can achieve the effect of sensitivity and specificity. In this study, we built a fishing mode device to detect the receptor-binding domain (RBD) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at low concentrations in different detection environments and obtained a sensitive SERS signal response. Based on the spatial resolution of proteins and their protein-specific recognition functions, SERS hotspots were constructed using aptamers and small molecules that can specifically bind to RBD and cooperate with Au nanoparticles (NPs) to detect RBD in the environment using SERS signals of beacon molecules. Therefore, two kinds of AuNPs modified with aptamers and small molecules were used in the fishing mode device, which can specifically recognize and bind RBD to form a stable hotspot to achieve high sensitivity and specificity for RBD detection. The fishing mode device can detect the presence of RBD at concentrations as low as 0.625 ng/mL and can produce a good SERS signal response within 15 min. Meanwhile, we can detect an RBD of 0.625 ng/mL in the mixed solution with various proteins, and the concentration of RBD in the complex environment of urine and blood can be as low as 1.25 ng/mL. This provides a research basis for SERS in practical applications for protein detection work.

Cys-functionalized AuNP substrates for improved sensing of the marine toxin STX by dynamic surface-enhanced Raman spectroscopy.

Saxitoxin (STX) as one of the most harmful and typical paralytic shellfish toxins, is posing a serious threat to environmental and human health, thus it is essential to develop a sensitive and reliable analytical method for STX detection. Herein, we proposed a strategy for rapid and sensitive detection of STX with surface-enhanced Raman spectroscopy (SERS), by employing cysteine modified gold nanoparticles (Cys-AuNPs) as SERS probe to capture STX molecules through electrostatic interactions and multiple hydrogen bonds between Cys and STX molecules. Moreover, the XPS and zeta potential results indicated that Cys could bond to AuNPs through Au-S bonds and the addition of STX could induce the efficient aggregation of Cys-AuNPs owing to the presence of electrostatic interactions and multiple hydrogen bonds between Cys and STX molecules. Furthermore, considering the high sensitivity and stability of the dynamic surface-enhanced Raman spectroscopy (D-SERS) strategy with the formation of a 3D hotspot matrix, the highly sensitive detection of STX was realized to a level of 1 × 10-7 M by using the D-SERS strategy. Consequently, Cys-AuNPs as high affinity substrates can provide high sensitivity for the detection of STX through the D-SERS strategy. Graphical abstract.

Assembling PVP-Au NPs as portable chip for sensitive detection of cyanide with surface-enhanced Raman spectroscopy.

Cyanide (C≡N) can lead to blood, cardiovascular system, and nervous system disorders owing to the acute and chronic toxicity; thus, aiming at the group or individual poisoning incidents, it is necessary to develop the sensitive and credible method for rapid on-site detection of poisons cyanide. Surface-enhanced Raman spectroscopy (SERS) with the advantages of providing fingerprint information of target molecules and single-molecules sensitivity has been widely used in on-site analysis; however, the SERS measurements always suffer from the problem of the stability of substrates. Here, the polyvinylpyrrolidone (PVP)-stabilized Au NPs (PVP-Au NPs) have been assembled through the simple, convenient evaporation-induced strategy with the large-scale hotspots substrates. The presence of PVP can not only facilitate the assembly of Au NPs but also prevent the corrosion of CN- towards the Au NPs with the formation of [Au (CN)2]-1, providing high stable and reproducible SERS signals. Moreover, the PVP-Au NPs have been assembled on the Si wafer to fabricate the portable SERS chip for rapid on-site detection of CN- with an RSD of 5.8% and limitation of 100 ppb. Furthermore, by coupling a portable Raman spectrometer, the SERS spectra of CN- spiked into different specimens to simulate the poison samples have been collected and analyzed on SERS chips with the recovery of 89-103% and RSD not higher than 11.3%. Consequently, the fabricated SERS chip with assembled PVP-Au NPs can provide sensitive and credible detection for CN- in different specimens, and then would satisfy the rapid on-site evaluation of CN- in poisoning incidents with the portable Raman spectrometer. Graphical Abstract.

Highly sensitive detection of an antidiabetic drug as illegal additives in health products using solvent microextraction combined with surface-enhanced Raman spectroscopy.

A rapid and accurate method for the sensitive detection of illegal drug additives including atenolol (ATN), metformin hydrochloride (MET), and phenformin hydrochloride (PHE) in health products using solvent microextraction (SME) combined with surface-enhanced Raman spectroscopy (SERS) was developed. Various illegal drug additives in different health products were separated via microextraction and then detected in situ using a portable Raman spectrometer with Ag colloids acting as SERS-active substrates. The effects of experimental parameters on the detection sensitivity and producibility were evaluated, and the applications of illegal additives spiked into samples were systematically investigated with SME-SERS. It was demonstrated that the mixture of CH3OH and CHCl3 (v/v = 1 : 4) as the extractant was suitable for the rapid microextraction separation of illegal drug additives and also induced the distribution of the Ag colloids (2 M) on the CHCl3 surface. More importantly, CH3OH can carry the drug molecules to enter into the inter-particles of the Ag colloids in this process, and then significantly improve the detection sensitivity of illegal drug additives. Furthermore, the high-throughput and real-time detection of illegal drug additives spiked into health products with SME-SERS in multi-well 96 plates were achieved with the level of 0.1 µg mg-1. The results reveal that this rapid and convenient method could be used for the effective separation and sensitive detection of illegal additives in complex specimen.

Metal coordination-functionalized Au-Ag bimetal SERS nanoprobe for sensitive detection of glutathione.

We demonstrated a surface-enhanced Raman spectroscopy (SERS) nanoprobe, neocuproine-Cu (Nc-CuII)-functionalized Au-Ag "nanobowls" (Au-Ag NBs/Nc-CuII), for detection of glutathione (GSH). Detection was accomplished with alternation of SERS spectra from Nc-CuII into Nc-CuI resulting from the reaction of GSH with Nc-CuII on Au-Ag NBs. This nanoprobe exhibited high selectivity and sensitivity (µM) towards GSH.

High-affinity Fe3O4/Au probe with synergetic effect of surface plasmon resonance and charge transfer enabling improved SERS sensing of dopamine in biofluids.

Development of analytical methods allowing sensitive detection of neurotransmitters in various biofluids is vital. However, limitations of these methods include interference of impurities and stringent requirements concerning sample purity. In the current work, we developed a strategy for the rapid and sensitive analysis of dopamine (DA) in various biofluids with a smart surface-enhanced Raman spectroscopy (SERS) probe composed of magnetite Fe3O4 and Au nanoparticles (Fe3O4/Au NPs). Besides the simple and quick separation of DA from the specimen, Fe3O4 not only enabled a specific chemical interaction with DA molecules, but also acted as a SERS substrate capable of electromagnetically enhancing the Raman signal of DA. Therefore, the Fe3O4/Au NP composite with its coexisting electric-field effect and charger transfer (CT) enhancement was found to be beneficial for capturing the target molecules in biological environments and then enhancing the DA sensitivity. To understand the strong binding interaction between Fe3O4/Au and DA, X-ray photoelectron spectroscopy (XPS) was carried out, specifically to illuminate the chemical adsorption or possible CT complex. Moreover, a rapid purification strategy for further separating DA from serum was developed, and thus a high nanometer-level sensitivity was achieved. In addition, the feasibility of using Fe3O4/Au combined with the developed purification method was also verified using various tissue homogenates spiked with DA molecules. Such a nanocomposite can offer the possibility of efficiently separating DA from the complex specimen and then providing the sensitive detection of DA for various tissues. Accordingly, the smart SERS Fe3O4/Au nanocomposite probe, with its advantages of simple pre-treatment and synergetic enhanced mechanisms, shows great promise for the rapid and sensitive detection of DA in complicated specimens.

Functionalized acupuncture needle as a SERS-active platform for rapid and sensitive determination of adenosine triphosphate.

The development of sensitive and rapid methods for analysis and detection of small molecules is highly desirable for medical diagnostics and therapeutics. We report an acupuncture needle functionalized with gold nanoparticles (Au NPs) and a macrocyclic amine (MA) Raman tag as the platform to realize the sensitive detection of adenosine triphosphate (ATP) by surface-enhanced Raman spectroscopy (SERS). The assembled Au NPs with abundant hot spots on the surface of the needle avoids the aggregation of Au NPs and results in a good signal response. Moreover, there is strong combination between ATP and MA through electrostatic adsorption, hydrogen-bonding interactions, and π-π stacking, and as a consequence, this functionalized needle can be used as a SERS platform for detection of ATP (25 nM) through a decrease of the Raman signal of MA resulting from the high chemical affinity of ATP for MA. Specially, the Au NP/MA-functionalized needle is conveniently used to monitor ATP (100 nM) added to serum, and demonstrates great promise in the study and detection of ATP in a complex sample, laying the foundation for SERS applications in complex acupuncture specimens with fast response and simple operation. Graphical abstract.

Amphiphilic Functionalized Acupuncture Needle as SERS Sensor for In Situ Multiphase Detection.

Surface enhanced Raman spectroscopy (SERS) is a powerful spectroscopic technique with unique vibrational fingerprints, making it an ideal candidate for in situ multiphase detection. However, it is a great challenge to determine how to guide the SERS sensor to target molecules of interest in multiphase heterogeneous samples with minimal disturbance. Here, we present a portable ultrasensitive and highly repeatable SERS sensor for in situ multiphase detection. The sensor is composed of commercial Ag acupuncture needle and PVP-Au nanoparticles (Au NPs). The PVP on the Au NPs can adsorb and induce the Au NPs into a highly uniform array on the surface of the Ag needle because of its adhesiveness and steric nature. The Au NPs-Ag Needle system (Au-AgN) holds a huge SERS effect, which is enabled by the multiple plasmonic couplings from particle-film and interparticle. The PVP, as the amphiphilic polymer, promotes the target molecules to adsorb on surface of the Au-AgN whether in the oil phase or in the water phase. In this work, the Au-AgN sensor was directly inserted into the multiphase system with the laser in situ detection, and SERS detection at different spots of the Au-AgN sensor provided Raman signal of targets molecule in the different phase. In situ multiphase detection can minimize the disturbance of sampling and provide more accurate information. The facile fabrication and amphiphilic functionalization make Au-AgN sensor as generalized SERS detection platform for on-site testing of aqueous samples, organic samples, even the multiphase heterogeneous samples.