Surface-enhanced Raman Scattering Hot Spots Research Articles

Single-Molecule Surface-Enhanced Raman Scattering Measurements Enabled by Plasmonic DNA Origami Nanoantennas.

Surface-enhanced Raman scattering (SERS) has the capability to detect single molecules for which high field enhancement is required. Single-molecule (SM) SERS is able to provide molecule-specific spectroscopic information about individual molecules and therefore yields more detailed chemical information than other SM detection techniques. At the same time, there is the potential to unravel information from SM measurements that remain hidden in Raman measurements of bulk material. This protocol outlines the SM SERS measurements using a DNA origami nanoantenna (DONA) in combination with atomic force microscopy (AFM) and Raman spectroscopy. A DNA origami fork structure and two gold nanoparticles are combined to form the DONAs, with a 1.2-2.0 nm gap between them. This allows an up to 1011-fold SERS signal enhancement, enabling measurements of single molecules. The protocol further demonstrates the placement of a single analyte molecule in a SERS hot spot, the process of AFM imaging, and the subsequent overlaying of Raman imaging to measure an analyte in a single DONA.

Constructing a Ring-like Self-Aggregation SERS Sensor with the Coffee Ring Effect for Ultrasensitive Detection and Photocatalytic Degradation of the Herbicides Paraquat and Diquat.

A strategy for building ring-like deposit surface-enhanced Raman scattering (SERS) sensors with the coffee ring effect through the functional modification of the silica nanoparticle surface encapsulated by free-tagged Ag nanoparticles is addressed along with their applications in the SERS-based detection and degradation of target species, including paraquat, diquat, and their free radicals. The nanogap formed by two interparticles with SERS hotspots provides a gigantic amplification signal for the Raman scattering intensity of the analyte molecule located approximately at the hotspots. The enhanced Raman spectrum signals of these target analytes were achieved through the hotspot region of the surface plasmon resonance (SPR) located on the embankment formed by self-aggregation of SiO2@Ag nanoparticles due to the coffee ring effect. Meanwhile, the intrinsic properties of Ag nanoparticles embedded onto the silica surface were applied to photocatalytically degrade the target analytes by harvesting energy from sunlight. The SERS sensor detected the analytes down to 10-9 M in the aqueous solution.

Quantitative evaluation of human carboxylesterase 1 by SERS-ELISA using a synergistic enhancement strategy based on gold nanoparticles and metal–organic framework

In this study, we synthesized gold nanoparticles (AuNPs) in situ on the surface of two-dimensional Cu-TCPP (meso-tetra(4-carboxyphenyl)porphine) metal– organic framework (MOF) nanosheets to produce AuNP@Cu-TCPP nanocomposites as surface-enhanced Raman scattering (SERS) substrates. The SERS signal was enhanced in two ways: aggregation of the AuNPs@Cu-TCPP near the SERS hotspot through the strong adsorption capacity of the MOF, and the synergistic effect between the charge-transfer enhancement of the Cu-TCPP MOF and the electromagnetic enhancement of plasmonic metal AuNPs. The SERS activity of AuNPs@Cu-TCPP was evaluated by the analysis of multiple model analytes; Rhodamine 6G (R6G) and benzidine were detected with detection limits below 10–13 and 10–12 mol·L–1, respectively. We used AuNP@Cu-TCPP as a SERS substrate combined with an enzyme-linked immuno- sorbent assay (ELISA) to detect the tumor marker carboxylesterase 1 (hCE1) in human serum. The SERS signal of benzidine at 1609 cm−1 is linearly correlated with hCE1 in the concentration range of 0.1–120 ng·mL−1. Owing to their high sensitivity and excellent SERS sensing capability, AuNPs@Cu-TCPP nanocomposites have potential applicability in the analysis of clinical samples.

Spatially Controlled Fabrication of Surface-Enhanced Raman Scattering Hot Spots through Photoinduced Dewetting of Silver Thin Films.

A well-designed narrow gap between noble metal nanostructures plays a prominent role in surface-enhanced Raman scattering (SERS) to concentrate electromagnetic fields at the local point, called a "hot spot". However, SERS-active substrate fabrication remains a substantial hurdle due to the high process cost and the difficulty of engineering efficient plasmonic hot spots at the target area. In this study, we demonstrate a simple photolithographic method for generating ultrasensitive SERS hot spots at desired positions. The solid-state dewetting of a Ag thin film (thickness of ∼10 nm) using a continuous-wave laser (∼1 MW/cm2) generates a closely packed assembly of hemispherical Ag nanoislands. Some of these nanoislands provide substantial plasmonic-field enhancement that is sufficient for single-molecule detection and plasmon-catalyzed chemical reaction. Such hot spot structures can be patterned on the substrate with a spatial resolution of better than 1 μm. In integrated analytical devices, the patterned SERS hot spots can be used as position-specific chemical-sensing elements.

A CRISPR-Cas12a integrated SERS nanoplatform with chimeric DNA/RNA hairpin guide for ultrasensitive nucleic acid detection.

Background: CRISPR-Cas12a has been integrated with nanomaterial-based optical techniques, such as surface-enhanced Raman scattering (SERS), to formulate a powerful amplification-free nucleic acid detection system. However, nanomaterials impose steric hindrance to limit the accessibility of CRISPR-Cas12a to the narrow gaps (SERS hot spots) among nanoparticles (NPs) for producing a significant change in signals after nucleic acid detection.Methods: To overcome this restriction, we specifically design chimeric DNA/RNA hairpins (displacers) that can be destabilized by activated CRISPR-Cas12a in the presence of target DNA, liberating excessive RNA that can disintegrate a core-satellite nanocluster via toehold-mediated strand displacement for orchestrating a promising “on-off” nucleic acid biosensor. The core-satellite nanocluster comprises a large gold nanoparticle (AuNP) core surrounded by small AuNPs with Raman tags via DNA hybridization as an ultrabright Raman reporter, and its disassembly leads to a drastic decrease of SERS intensity as signal readouts. We further introduce a magnetic core to the large AuNPs that can facilitate their separation from the disassembled nanostructures to suppress the background for improving detection sensitivity.Results: As a proof-of-concept study, our findings showed that the application of displacers was more effective in decreasing the SERS intensity of the system and attained a better limit of detection (LOD, 10 aM) than that by directly using activated CRISPR-Cas12a, with high selectivity and stability for nucleic acid detection. Introducing magnetic-responsive functionality to our system further improves the LOD to 1 aM.Conclusion: Our work not only offers a platform to sensitively and selectively probe nucleic acids without pre-amplification but also provides new insights into the design of the CRISPR-Cas12a/SERS integrated system to resolve the steric hindrance of nanomaterials for constructing biosensors.

Detection of Off‐Resonance Single‐Walled Carbon Nanotubes by Enormous Surface‐Enhanced Raman Scattering

AbstractThe resonant Raman spectroscopy can only detect on‐resonance single‐walled carbon nanotubes (SWNTs) within the laser resonance window. In principle, surface‐enhanced Raman scattering (SERS) spectroscopy can expand the resonance window. However, detection of off‐resonance SWNTs by SERS remains challenging due to the difficulties in locating the SWNTs exactly at the hot spots with enormous SERS enhancements. Here, polyhedral gold nanocrystals (AuNCs) are in situ prepared on SWNTs for SERS detection via a facile ultrasonic spray pyrolysis method. The fact that the edges of the AuNCs attach to the SWNTs ensures the location of SWNTs perfectly at the SERS hot spots. Consequently, the enormous SERS enhancement enables a maximum enhancement factor of (3.4 ± 0.6) × 104 for an individual SWNT, which is about two orders of magnitude higher than the maximum reported in literatures. The detection ratio of SWNTs is also dramatically increased from 33% without SERS to 76% with SERS. The existence of the polyhedral AuNCs suppresses the antenna effects of the SWNTs and allows effective enhancements of the SWNTs under various polarization conditions. The enormous enhancements also enable the detection of several new Raman bands of the SWNTs.

SERS-ELISA determination of human carboxylesterase 1 using metal-organic framework doped with gold nanoparticles as SERS substrate.

By in situ synthesis of gold nanoparticles (AuNPs) within the acid-etched (AE) MIL-101 (Cr) framework, AE-MIL-101 (Cr) nanocomposites embedded with AuNPs (AuNP/AE-MIL-101 (Cr)) were prepared as surface-enhanced Raman scattering (SERS) substrate. AuNPs are uniformly distributed and stabilized inside the metal-organic framework (MOF), thus forming more SERS hotspots. The SERS performance of AuNP/AE-MIL-101 (Cr) was evaluated using 4-mercaptophenylboronic acid (4-MPBA), 4-mercaptobenzoic acid (4-MBA), benzidine, and rhodamine 6G (R6G). The SERS substrate displays satisfying stability with very low background signal. When benzidine is used as the Raman reporter, the limit of detection (LOD) can reach 6.7 × 10-13mol·L-1, and the relative standard deviation (RSD) of the intra- and inter-batch repetitive tests is less than 5.2%. On this basis, we developed a method for the detection of human carboxylesterase 1 (hCE 1) in human serum using AuNP/AE-MIL-101 (Cr) nanocomposite as SERS substrate and enzyme-linked immunosorbent assay (ELISA) colorimetric substrate as SERS marker. This method was used to determinehCE 1 in clinical serum samples without complicated sample pretreatment, and the detection results were consistent with the data determined by ELISA. In the concentration range 0.1-120 ng·mL-1, the SERS signal intensity of benzidine at 1609cm-1 gradually decreases with the increase of hCE 1 concentration (R2= 0.9948). The average recoveries of hCE 1 in human serum are in the range 84 to 108%, with RSDs lower than 7.7%. By using AuNP/acid etching-MIL-101(Cr) metal organic framework (MOF) as SERS substrate and enzyme-linked immunosorbent assay (ELISA) colorimetric substrate as the SERS marker, a rapid and sensitive method for the determination of human carboxylesterase 1 (hCE1) in human serum samples has been developed.

A Versatile DNA Origami-Based Plasmonic Nanoantenna for Label-Free Single-Molecule Surface-Enhanced Raman Spectroscopy.

DNA origami technology allows for the precise nanoscale assembly of chemical entities that give rise to sophisticated functional materials. We have created a versatile DNA origami nanofork antenna (DONA) by assembling Au or Ag nanoparticle dimers with different gap sizes down to 1.17 nm, enabling signal enhancements in surface-enhanced Raman scattering (SERS) of up to 1011. This allows for single-molecule SERS measurements, which can even be performed with larger gap sizes to accommodate differently sized molecules, at various excitation wavelengths. A general scheme is presented to place single analyte molecules into the SERS hot spots using the DNA origami structure exploiting covalent and noncovalent coupling schemes. By using Au and Ag dimers, single-molecule SERS measurements of three dyes and cytochrome c and horseradish peroxidase proteins are demonstrated even under nonresonant excitation conditions, thus providing long photostability during time-series measurement and enabling optical monitoring of single molecules.

Polyethyleneimine mediated interaction for highly sensitive, magnetically assisted detection of tetracycline hydrochloride

Antibiotic residues in food have become the focus of attention. In this work, we report a simple self-assembly method to fabricate magnetic Fe3O4@PEI@Ag complex substrate for surface enhanced Raman scattering (SERS) detection of tetracycline hydrochloride (TC), a widely used antibiotics in breeding industry. Assembled Ag nanoparticles (AgNPs) on Fe3O4 NPs helps form more SERS hotspots by magnetic induction, which facilitate the direct aqueous detection and high sensitivity (EF = 4.0 × 106 in wet state) of the Fe3O4@PEI@Ag sensor. Polyethyleneimine (PEI) not only acts as interlayer for AgNPs assembly on Fe3O4 particles, but can also direct the interaction between TC and SERS substrate. The binding ratio between B, C, D rings of TC and PEI is calculated to be 1:4 by Ultraviolet–visible spectroscopy (UV–vis) characterization. Simulation study also confirms the multiple TC-PEI interaction mode (hydrogen, σ-π, cation-π). Fe3O4@PEI@Ag sensor also shows very high stability (signal decreases < 5% after 93 days). Fe3O4@PEI@Ag SERS sensing array could have a great potential for real-time sensitive detection of analytes. More importantly, this rational adjustment of interaction sites between substrate and analyte is expected to be a new strategy for the improvement of SERS detection sensitivity and selectivity.

Direct detection of DNA using 3D surface enhanced Raman scattering hotspot matrix.

Silver nanoparticles (AgNPs) are evaporatively self-assembled into the 3D surface enhanced Raman scattering (SERS) hotspot matrix with the assistant of glycerol to improve the spectral reproducibility in direct DNA detection. AgNPs and DNA in the glycerol-stabilized 3D SERS hotspot matrix are found to form flexible sandwich structures through electrostatic interaction where neighboring AgNPs create uniform and homogeneous localized surface plasmon resonance coupling environments for central DNA. Nearly two orders of magnitude extra SERS enhancement, more stable peak frequency and narrower peak full width at half maximum can therefore be obtained in DNA SERS spectra, which ensures highly stable and reproducible SERS signals in direct detection of both single strand DNA and double strand DNA utilizing the 3D SERS hotspot matrix. By normalizing the SERS spectra using phosphate backbone as internal standard, identification of single base variation in oligonucleotides, determination of DNA hybridization events and recognition of chemical modification on bases (hexanethiol-capped at 5' end) have been demonstrated experimentally. This proposed 3D SERS hotspot matrix opens a novel perspective in manipulating plasmonic nanoparticles to construct SERS platforms and would make the surface enhanced Raman spectroscopy a more practical and reliable tool in direct DNA detection.

Ultrasonic Modification of Ag Nanowires and Their Applications in Flexible Transparent Film Heaters and SERS Detectors.

Ultrasonic morphology modification of silver (Ag) nanowires and their applications in transparent film heaters for defogging in electric vehicles and surface-enhanced Raman scattering (SERS) detectors have been studied. With 10 min ultrasonic treatment of Ag nanowires, the electro-thermal conversion capability of Ag nanowire based transparent film heaters is efficiently improved (about 50% increase in temperature rise), which can be mainly attributed to the cross-section area reduction and the serious agglomerations of the ultrasonic modified Ag nanowire films. Furthermore, the bending or fracture caused by deformation of Ag nanowires after ultrasonic treatment provides more hot spots for SERS, and therefore lead to a significant SERS signal enhancement. This work not only greatly improves the performance of Ag nanowire based transparent film heaters and SERS detectors, but provides a new way for the functional modification of Ag nanowires.

Ordered mesoporous silver superstructures with SERS hot spots.

We have developed a method to fabricate freestanding highly ordered porous silver (Ag) superstructures by an "assembly-based nanoparticle (NP) coalescence" method. The synthesized superstructures have high-density mesopores periodically distributed over the entire structure, on which a highly enhanced electromagnetic field was observed by electron energy loss spectroscopy. Thus, the surface enhanced Raman scattering (SERS) signal of Rhodamine 6G in the ordered mesopores is 8.2 times higher compared to that in disordered porous superstructures. The results demonstrate that these freestanding mesoporous Ag superstructures are potentially good SERS substrates.

Designing surface-enhanced Raman scattering (SERS) platforms beyond hotspot engineering: emerging opportunities in analyte manipulations and hybrid materials.

Surface-enhanced Raman scattering (SERS) is a molecule-specific spectroscopic technique with diverse applications in (bio)chemistry, clinical diagnosis and toxin sensing. While hotspot engineering has expedited SERS development, it is still challenging to detect molecules with no specific affinity to plasmonic surfaces. With the aim of improving detection performances, we venture beyond hotspot engineering in this tutorial review and focus on emerging material design strategies to capture and confine analytes near SERS-active surfaces as well as various promising hybrid SERS platforms. We outline five major approaches to enhance SERS performance: (1) enlarging Raman scattering cross-sections of non-resonant molecules via chemical coupling reactions; (2) targeted chemical capturing of analytes through surface-grafted agents to localize them on plasmonic surfaces; (3) physically confining liquid analytes on non-wetting SERS-active surfaces and (4) confining gaseous analytes using porous materials over SERS hotspots; (5) synergizing conventional metal-based SERS platforms with functional materials such as graphene, semiconducting materials, and piezoelectric polymers. These approaches can be integrated with engineered hotspots as a multifaceted strategy to further boost SERS sensitivities that are unachievable using hotspot engineering alone. Finally, we highlight current challenges in this research area and suggest new research directions towards efficient SERS designs critical for real-world applications.

The effect of silica shell on the surface enhanced Raman scattering and fluorescence with Ag nanoparticles: A three-dimensional finite element method investigation

Shell-isolated nanoparticles has recently been extensively applied in surface-enhanced Raman scattering (SERS) and fluorescence (SEF) studies. In the present work, we study the SERS and SEF effect of a general model molecule placed in the middle of silica coated silver nanoparticle dimers (Ag@SiO2) for better understanding of the enhancement mechanism. The electromagnetic (EM) enhancement and fluorescence quantum yield of Ag@SiO2 dimers were simulated by using three-dimensional finite element method, and then the Raman and fluorescence enhancement factors were obtained. The influence of the size of the Ag core and the thickness of the SiO2 shell were systematically investigated and analyzed. The simulation results show that Ag@SiO2 dimers can provide the better hot spots for SERS and SEF detection when compared with bare Ag nanoparticles. It was found that the SiO2 shell can efficiently transmit the strong EM enhancement from the Ag core, and it also exhibited better fluorescence enhancement when compared to the uncoated Ag dimers. The maximum enhancement to the SERS and SEF signals as predicted by the numerical simulations are found to be around ∼109 and ∼104 with excitation wavelength of 500 nm, respectively.

Placement of Single Proteins within the SERS Hot Spots of Self-Assembled Silver Nanolenses.

This study demonstrates the bottom-up synthesis of silver nanolenses. A robust coating protocol enabled the functionalization of differently sized silver nanoparticles with DNA single strands of orthogonal sequence. Coated particles 10 nm, 20 nm, and 60 nm in diameter were self-assembled by DNA origami scaffolds to form silver nanolenses. Single molecules of the protein streptavidin were selectively placed in the gap of highest electric field enhancement. Streptavidin labelled with alkyne groups served as model analyte in surface-enhanced Raman scattering (SERS) experiments. By correlated Raman mapping and atomic force microscopy, SERS signals of the alkyne labels of a single streptavidin molecule, from a single silver nanolens, were detected. The discrete, self-similar aggregates of solid silver nanoparticles are promising for plasmonic applications.

Observing the Overgrowth of a Second Metal on Silver Cubic Seeds in Solution by Surface-Enhanced Raman Scattering.

We report the development of an isocyanide-based molecular probe for in situ characterizing the overgrowth of a second metal on silver nanocrystal seeds in solution by surface-enhanced Raman scattering (SERS). As the first demonstration, we elucidate that the vibrational frequency of 2,6-dimethylphenyl isocyanide (2,6-DMPI) can serve as a distinctive reporter for capturing the nucleation of Pt on the edges of Ag nanocubes in the aqueous solution containing a Pt precursor, ascorbic acid, and poly(vinylpyrrolidone) under ambient conditions. Our success relies on the difference in stretching frequency for the NC bond when the isocyanide group binds to the Ag and Pt atoms. Specifically, σ donation from the antibonding σ* orbital of the -NC group to the d-band of Ag would strengthen the NC bond, blue shifting the stretching frequency. In contrast, π-back-donation from the d-band of Pt to the π* antibonding orbital of the -NC group would weaken the NC bond, leading to a red shift of stretching frequency. Therefore, it is feasible to in situ characterize the outermost surface that consists of both newly deposited Pt atoms and remaining Ag atoms by following the stretching frequencies and intensities of 2,6-DMPI in real time. Because the SERS hot spots on the edges of Ag nanocubes coincide with the {110} facets preferred for the nucleation of Pt atoms, this technique is capable of resolving 27 Pt atoms being deposited on each edge of a 39 nm Ag nanocube in the original growth solution. Collectively, in situ SERS, with its consummate sensitivity to molecular structure and bonding of isocyanide-based molecular probe, could elucidate the mechanistic details involved in the seeded overgrowth of a catalytically significant metal, such as Pt, Pd, Ir, Rh, and Ru, on the surface of a Ag or Au nanocrystal seed.

Plasmonic enhancement of SERS measured on molecules in carbon nanotubes.

We isolated the plasmonic contribution to surface-enhanced Raman scattering (SERS) and found it to be much stronger than expected. Organic dyes encapsulated in single-walled carbon nanotubes are ideal probes for quantifying plasmonic enhancement in a Raman experiment. The molecules are chemically protected through the nanotube wall and spatially isolated from the metal, which prevents enhancement by chemical means and through surface roughness. The tubes carry molecules into SERS hotspots, thereby defining molecular position and making it accessible for structural characterization with atomic-force and electron microscopy. We measured a SERS enhancement factor of 106 on α-sexithiophene (6T) molecules in the gap of a plasmonic nanodimer. This is two orders of magnitude stronger than predicted by the electromagnetic enhancement theory (104). We discuss various phenomena that may explain the discrepancy (including hybridization, static and dynamic charge transfer, surface roughness, uncertainties in molecular position and orientation), but found all of them lacking in enhancement for our probe system. We suggest that plasmonic enhancement in SERS is, in fact, much stronger than currently anticipated. We discuss novel approaches for treating SERS quantum mechanically that appear promising for predicting correct enhancement factors. Our findings have important consequences on the understanding of SERS as well as for designing and optimizing plasmonic substrates.

An ordered array of hierarchical spheres for surface-enhanced Raman scattering detection of traces of pesticide

An ordered array of hierarchically-structured core-nanosphere@space-layer@shell-nanoparticles has been fabricated for surface-enhanced Raman scattering (SERS) detection. To fabricate this hierarchically-structured chip, a long-range ordered array of Au/Ag-nanospheres is first patterned in the nano-bowls on the planar surface of ordered nanoporous anodic titanium oxide template. A ultra-thin alumina middle space-layer is then conformally coated on the Au/Ag-nanospheres, and Ag-nanoparticles are finally deposited on the surface of the alumina space-layer to form an ordered array of Au/Ag-nanosphere@Al2O3-layer@Ag-nanoparticles. Finite-difference time-domain simulation shows that SERS hot spots are created between the neighboring Ag-nanoparticles. The ordered array of hierarchical nanostructures is used as the SERS-substrate for a trial detection of methyl parathion (a pesticide) in water and a limit of detection of 1 nM is reached, indicating its promising potential in rapid monitoring of organic pollutants in aquatic environment.

Metal-Catalyzed Chemical Reaction of Single Molecules Directly Probed by Vibrational Spectroscopy.

The study of heterogeneous catalytic reactions remains a major challenge because it involves a complex network of reaction steps with various intermediates. If the vibrational spectra of individual molecules could be monitored in real time, one could characterize the structures of the intermediates and the time scales of reaction steps without ensemble averaging. Surface-enhanced Raman scattering (SERS) spectroscopy does provide vibrational spectra with single-molecule sensitivity, but typical single-molecule SERS signals exhibit spatial heterogeneities and temporal fluctuations, making them difficult to be used in single-molecule kinetics studies. Here we show that SERS can monitor the single-molecule catalytic reactions in real time. The surface-immobilized reactants placed at the junctions of well-defined nanoparticle-thin film structures produce time-resolved SERS spectra with discrete, step-transitions of photoproducts. We interpret that such SERS-steps correspond to the reaction events of individual molecules occurring at the SERS hotspot. The analyses of the yield, dynamics, and the magnitude of such SERS steps, along with the associated spectral characteristics, fully support our claim. In addition, a model that is based on plasmonic field enhancement and surface photochemistry reproduces the key features of experimental observation. Overall, the result demonstrates that it is possible, under well-controlled conditions, to differentiate the chemical and physical processes contributing to the single-molecule SERS signals, and thus shows the use of single-molecule SERS as a tool for studying the metal-catalyzed organic reactions.

Agcore–Aushell bimetallic nanocomposites: Gold shell thickness dependent study for SERS enhancement

This study reports the synthesized core–shell bimetallic nanocomposites of silver and gold, respectively by varying the thickness of Au shell and studying its role in enhancing the Raman scattering of the molecule. The crystal violet (CV) was chosen as the target analyte molecule and the surface enhanced Raman scattering (SERS) enhancement of this molecule was studied as a function of Au shell thickness. The appropriate thickness of Au nanoshell, deposited on the Ag nanoparticles to obtain the maximum SERS enhancement, was identified and further increase in thickness of Au showed a decrease in intensity of the SERS signals. Among all the fabricated Ag@Au specimens ~30nm of Ag seed with 8nm of Au nanoshell showed the maximum enhancement of the SERS signals of CV. The close proximity of discontinuous Au shell acts as SERS hot spots by creating molecular level gap that accommodates the CV molecules responsible for the SERS enhancement up to the order of 1013 which is highly reproducible.