Single-particle Surface-enhanced Raman Scattering Research Articles

Accurate Quantification and Imaging of Cellular Uptake Using Single-Particle Surface-Enhanced Raman Scattering.

Understanding the uptake, distribution, and stability of gold nanoparticles (NPs) in cells is of fundamental importance in nanoparticle sensors and therapeutic development. Single nanoparticle imaging with surface-enhanced Raman spectroscopy (SERS) measurements in cells is complicated by aggregation-dependent SERS signals, particle inhomogeneity, and limited single-particle brightness. In this work, we assess the single-particle SERS signals of various gold nanoparticle shapes and the role of silica encapsulation on SERS signals to develop a quantitative probe for single-particle level Raman imaging in living cells. We observe that silica-encapsulated gap-enhanced Raman tags (GERTs) provide an optimized probe that can be quantifiable per voxel in SERS maps of cells. This approach is validated by single-particle inductively coupled mass spectrometry (spICP-MS) measurements of NPs in cell lysate post-imaging. spICP-MS also provides a means of measuring the tag stability. This analytical approach can be used not only to quantitatively assess nanoparticle uptake on the cellular level (as in previous digital SERS methods) but also to reliably image the subcellular distribution and to assess the stability of NPs in cells.

Branched Aluminum Nanocrystals with Internal Hot Spots: Synthesis and Single-Particle Surface-Enhanced Raman Scattering.

Owing to their unique and sustainable surface plasmonic properties, Al nanocrystals have attracted increasing attention for plasmonic-enhanced applications, including single-particle surface-enhanced Raman scattering (SERS). However, whether Al nanocrystals can achieve single-particle SERS is still unknown, mainly due to the synthetic difficulty of Al nanocrystals with internal gaps. Herein, we report a regrowth method for the synthesis of Al nanohexapods with tunable and uniform internal gaps for single-particle SERS with an enhancement factor of up to 1.79 × 108. The uniform branches of the Al nanohexapods can be systematically tuned regarding their dimensions, terminated facets, and internal gaps. The Al nanohexapods generate hot spots concentrated in the internal gaps due to the strong plasmonic coupling between the branches. A single-particle SERS measurement of Al nanohexapods shows strong Raman signals with maximum enhancement factors comparable to that of Au counterparts. The large enhancement factor indicates that Al nanohexapods are good candidates for single-particle SERS.

Shape-Preserving Transformation of Electrodeposited Macroporous Microparticles for Single-Particle SERS Applications

Microparticles composed of bicontinuous and ordered macropores are important in many applications. However, rational integration of ordered macropores into a single crystalline microparticle remains a challenge. Here, we report a method to prepare three-dimensionally ordered macroporous (3DOM) Ag7O8NO3 micropyramids via selectively cementing the colloidal crystal templates via an electrochemical method and their shape-preserving transformation into 3DOM Ag micropryamids formed by Ag nanoparticles via a chemical reduction process. The interconnected macropores facilitated the transportation and enrichment of the analyte molecules into the 3DOM Ag micropyramids. The dense Ag nanoparticles on the skeletons of the 3DOM Ag micropyramids provided strong electromagnetic fields. Taken together, a 3DOM Ag micropyramid as a kind of single-particle surface-enhanced Raman scattering (SERS) sensing substrate demonstrated high SERS sensitivity and outstanding SERS signal reproducibility. We explored the application of 3DOM Ag micropyramids in SERS detection of biomolecules (e.g., adenosine, adenine, hemoglobin bovine, and lysozyme) and proved their potentials in distinguishing exosomes from tumor and non-tumor cells. The method can be extended to prepared 3DOM structures of other materials with promising applications in sensing, separation, and catalytic fields.

Gap-enhanced gold nanodumbbells with single-particle surface-enhanced Raman scattering sensitivity.

Gap-enhanced Raman tags (GERTs) have been widely used for surface-enhanced Raman scattering (SERS) imaging due to their excellent SERS performances. Here, we reported a synthetic strategy for novel gap-enhanced dumbbell-like nanoparticles with anisotropic shell coatings. Controlled shell growth at the tips of gold nanorods was achieved by using cetyltrimethylammonium bromide (CTAB) as a capping agent. A mechanism related to the shape-directing effects of CTAB was proposed to explain the findings. Optimized gap-enhanced gold dumbbells exhibited highly enhanced SERS responses compared to rod cores, with an enhancement ratio of 101.5. We further demonstrated that gap-enhanced AuNDs exhibited single-particle SERS sensitivity with an acquisition time as fast as 0.1 s per spectrum, showing great potential for high-speed SERS imaging.

Three-dimensional nanoframes with dual rims as nanoprobes for biosensing

Three-dimensional (3D) nanoframe structures are very appealing because their inner voids and ridges interact efficiently with light and analytes, allowing for effective optical-based sensing. However, the realization of complex nanoframe architecture with high yield is challenging because the systematic design of such a complicated nanostructure lacks an appropriate synthesis protocol. Here, we show the synthesis method for complex 3D nanoframes wherein two-dimensional (2D) dual-rim nanostructures are engraved on each facet of octahedral nanoframes. The synthetic scheme proceeds through multiple executable on-demand steps. With Au octahedral nanoparticles as a sacrificial template, sequential processes of edge-selective Pt deposition and inner Au etching lead to Pt octahedral mono-rim nanoframes. Then, adlayers of Au are grown on Pt skeletons via the Frank-van der Merwe mode, forming sharp and well-developed edges. Next, Pt selective deposition on both the inner and outer boundaries leads to tunable geometric patterning on Au. Finally, after the selective etching of Au, Pt octahedral dual-rim nanoframes with highly homogeneous size and shape are achieved. In order to endow plasmonic features, Au is coated around Pt frames while retaining their geometric shape. The resultant plasmonic dual-rim engraved nanoframes possess strong light entrapping capability verified by single-particle surface-enhanced Raman scattering (SERS) and show the potential of nanoprobes for biosensing through SERS-based immunoassay.

Enormous Enhancement in Single-Particle Surface-Enhanced Raman Scattering with Size-Controllable Au Double Nanorings

Enormous Enhancement in Single-Particle Surface-Enhanced Raman Scattering with Size-Controllable Au Double Nanorings

Ring-in-a-Triangle Nanoframes: Integrating with Intra- and Interhotspots for Highly Amplified Near-Field Focusing.

The development of a stepwise synthetic strategy for Au ring-in-a-triangle nanoframes with a high degree of structural solidity is essential to the advancement of highly amplified near-field focusing. This strategy leads to the formation of an inscribed nanoring in a triangular metal frame with stability to withstand elevated temperatures and an oxidizing environment, which is critical for successful single-particle surface-enhanced Raman scattering (SERS). The existence of inscribed nanorings plays an important role in enhancing the so-called "lightning rod effect," whereby the electromagnetic near-field enhancement occurs on the highly curved curvature of a metallic interface. We evaluated the corresponding single-particle SERS as a function of the thickness of the rims and then constructed two-dimensional (2D) bulk SERS substrates, wherein an ensemble of hotspots exists. The synergic contribution from both inter- and intrahotspots allowed the outstanding linearity of the calibration curve and the lowest limit of detection, ∼10-18 M for the analyte concentration.

Au Nanorings with Intertwined Triple Rings.

We designed complex Au nanorings with intertwined triple rings (ANITs) in a single entity to amplify the efficacy of near-field focusing. Such a complex and unprecedented morphology at the nanoscale was realized through on-demand multistepwise reactions. Triangular nanoprisms were first sculpted into circular nanorings, followed by a series of chemical etching and deposition reactions eventually leading to ANITs wherein thin metal bridges hold the structure together without any linker molecules. In the multistepwise reaction, the well-faceted growth pattern of Au, which induces the growth of two distinctive flat facets in a lateral direction, is important to evolve the morphology from single to multiple nanorings. Although our synthesis proceeds through multiple steps in one batch without purification steps, it shows a remarkably high yield (>∼90%) at the final stage. The obtained high degree of homogeneity (in both shape and size) of the resulting ANITs allowed us to systematically investigate the corresponding localized surface plasmon resonance (LSPR) coupling with varying nanoring arrangements and observe their single-particle surface enhanced Raman scattering (SERS). Surprisingly, individual ANITs exhibited an enormously large enhancement factor (∼109), which confirms their superior near-field focusing relative to other reported nanoparticles.

Toward Vibrational Tomography of Citrate on Dynamically Changing Individual Silver Nanoparticles

This study explored changes in binding modes of the most common ligand, citrate on silver nanoparticles (AgNPs) using single-particle surface-enhanced Raman scattering (SP-SERS). Single AgNPs of 50 ± 10 nm diameter anchored on clean glass slides were monitored using time-dependent SP-SERS with 632.8 nm excitation at 1.3 μW incident (0.5 μW absorbed) power per nanoparticle. We observed several distinct spectra of citrate during time-dependent SP-SERS. Analysis of 1400 spectra showed the existence of two major groups termed as favorable (F) and probable (P) spectra based on their likelihood of appearance and intensities. These distinct spectra corresponded to a multitude of binding modes, structures, and variants of photocatalyzed products of citrate on the surface of dynamically changing AgNPs. Density functional theory (DFT) simulations were performed to model the structures and binding modes of citrate on an Ag(111) surface, and corresponding Raman spectra were computed and compared with distinct spectral types. Experiments performed with deuterated (2,2,4,4-d4) citrate-capped AgNPs provided additional evidence to understand the shifts in vibrational features obtained in SP-SERS of citrate-capped AgNPs. These systematic analyses of time-dependent SP-SERS spectra may be used for the reconstruction and vibrational tomography (VT) of ligands at the single-particle level. The proposed VT approach is similar to sectioning an object through a multitude of orientations and reconstructing its three-dimensional structure, although the structures reconstructed here are molecular orientations.

Synthesis and Single-Particle Surface-Enhanced Raman Scattering Study of Plasmonic Tripod Nanoframes with Y-Shaped Hot-Zones.

Herein, plasmonic metal tripod nanoframes with three-fold symmetry were synthesized in a high yield (∼83%), and their electric field distribution and single-particle surface-enhanced Raman scattering (SERS) were studied. We realized such complex frame morphology by synthesizing analogous tripod nanoframes through multiple transformations. The precise control of the Au growth pattern led to uniform tripod nanoframes embedded with circle or line-shaped hot spots. The linear-shaped nanogaps ("Y"-shaped hot-zone) of the frame structures can strongly and efficiently confine the electric field, allowing for strong SERS signals. Coupled with a high synthetic yield of the targeted frame structure, strong and uniform SERS signals were obtained inside the nanoframe gaps. Remarkably, quite reproducible SERS signals were obtained with these structures-the SERS enhancement factors with an average value of 7.9 × 107 with a distribution of enhancement factors from 2.2 × 107 to 2.2 × 108 for 45 measured individual particles.

Rapid ultrasensitive monitoring the single-particle surface-enhanced Raman scattering (SERS) using a dark-field microspectroscopy assisted system

The observation of single-particle surface-enhanced Raman scattering (SERS) has generated considerable interest both in the nanomaterials filed and in the single-particle spectroscopy community. It is a challenge to realize rapid, facile, and high throughput SERS at single nanoparticle level. Here, without the complex experimental device and difficult experimental operations, a general single-particle SERS technique has been achieved by using dark-field-assisted surface-enhanced Raman spectroscopy (DFSERS). This advanced method provides in-situ characterization of the chemical reaction performance at single gold nanorod.

Size-controllable and uniform gold bumpy nanocubes for single-particle-level surface-enhanced Raman scattering sensitivity.

Gold nanocubes modified to form roughened structures, namely, gold bumpy nanocubes (Au BNCs), with very strong and uniform single-particle surface-enhanced Raman scattering (SERS) intensity were developed. The Au BNCs were synthesized by controlled regrowth, competing with 4-aminothiophenol during gold nanocube growth. Under controlled conditions, Au BNCs of various sizes were successfully generated while maintaining a cubic outline. As the bumpy surfaces of the Au BNCs increased the number of hot spots on a single cubic nanoparticle, these nanoparticles exhibited 15-times stronger SERS than normal cubic nanoparticles. We expect that this unique nanostructure will be applicable in versatile fields as an ultrasensitive SERS nanoprobe or nanoantenna owing to its cubic outline and high uniformity, as well as the ease of particle size adjustment.

Facile One-Pot Synthesis of Nanodot-Decorated Gold-Silver Alloy Nanoboxes for Single-Particle Surface-Enhanced Raman Scattering Activity.

Surface-enhanced Raman scattering (SERS) is an important, highly sensitive technique for chemical and biological analysis, which is critically dependent upon high-performance metallic substrates. Anisotropic gold (Au)-silver (Ag) alloy nanoboxes are attractive SERS substrates because of the greatly enhanced Raman signals from the strong electromagnetic fields on the sharp corners. Yet, the routine approach of Au-Ag alloy nanobox synthesis is still challenging because of the complicated procedures and use of biologically/environmentally unfriendly reagents. To facilitate the usage of Au-Ag alloy nanoboxes for broad SERS applications, we propose a facile green strategy to synthesize Au-Ag alloy nanoboxes with superior single-particle SERS sensitivity. Our novel straightforward strategy involves HAuCl4 and AgNO3 reduction by ascorbic acid, which is achieved in an aqueous one-pot reaction at ambient temperature. Significantly, the surfaces of the prepared Au-Ag alloy nanoboxes are judiciously designed to introduce nanodots, generating numerous "hot spots" for high Raman signal enhancement as indicated by rigorous numerical simulations. By combining scanning electron microscopy and Raman mapping images, we demonstrate the application of Au-Ag alloy nanoboxes for single-particle sensing SERS activity. The as-prepared Au-Ag alloy nanoboxes are expected to facilitate their further applications in quantitative and ultrasensitive SERS detection.

Temperature‐Induced Stacking to Create Cu2O Concave Sphere for Light Trapping Capable of Ultrasensitive Single‐Particle Surface‐Enhanced Raman Scattering

AbstractThe fabrication of bowl or concave particles with “asymmetric centers” has drawn considerable attentions, in which multiple scattering occurs inside the particles and the ability of light scattering is distinctly enhanced. However, the limited variety of templates, the uncontrollable dimensions such as the size of concavity and the complex growth process have posed serious limitations to the reproducible construction of concave particles with desired geometries and their light‐trapping properties. Herein, a “temperature‐induced stacking” strategy is proposed to create controllable concavity Cu2O spheres for the first time. Different sizes of F68 micelles can be formed through aggregation under different reaction temperatures, which can serve as soft template to tailor concave geometries of Cu2O spheres. The as‐prepared Cu2O concave sphere (CS) can serve as single‐particle (SP) surface‐enhanced Raman scattering (SERS) substrate for highly repeatable and consistent Raman spectra. The unique cavity of Cu2O CS entraps light effectively, which also enhances the scattering length owing to multiple light scattering. Combined with slightly increased surface area and charge‐transfer process, Cu2O CS exhibits remarkable single‐particle SERS performance, with an ultralow low detection limit (2 × 10−8 mol L−1) and metal comparable enhancement factor (2.8 × 105).

Anomalous spectral correlations between SERS enhancement and far-field optical responses in roughened Au mesoparticles

Depending on the experimental conditions and plasmonic systems, the correlations between near-field surface enhanced Raman scattering (SERS) behaviors and far-field optical responses have sometimes been accepted directly, or argued, or explored. In this work, we have numerically demonstrated the anomalous spectral correlations between the near- and far-field properties for roughened Au mesoparticles. As a counterexample, it is witnessed that the dipole extinction peak of the mesoparticles may mislead us in seeking favorable SERS performance. The simple Rayleigh scattering spectra can also be misguided in the presence of dark modes. For roughened mesoparticles with a moderate size here, the huge near-field enhancement is a synergistic result of the overall dark quadrupole mode and the substructural bonding dipole coupling. The conclusions demonstrated here would be of general interest to the field of plasmonics, especially the optimization of single-particle SERS substrates.

Facile synthesis of hydrangea flower-like hierarchical gold nanostructures with tunable surface topographies for single-particle surface-enhanced Raman scattering.

The physicochemical properties of noble metal nanocrystals depend strongly on their size and shape, and it is becoming clear that the design and facile synthesis of particular nanostructures with tailored shape and size is especially important. Herein a novel class of hydrangea flower-like hierarchical gold nanostructures with tunable surface topographies and optical properties are prepared for the first time by a facile, one-pot, seedless synthesis using ascorbic acid (AA) to reduce hydrogen tetrachloroaurate (HAuCl4) in the presence of (1-hexadecyl)trimethylammonium chloride (CTAC). The morphologies of the synthesized gold nanoflowers are controlled and fine-tuned by varying the synthetic conditions such as the concentration of reagents and the growth temperature. Due to their unique hierarchical three-dimensional (3D) structures with rich hot spots, these gold nanoflowers exhibit an efficient performance in single-particle surface-enhanced Raman scattering (SERS). The work stands out as an interesting approach for anisotropic particle synthesis and morphological control, and the proposed novel, hierarchical gold nanoflowers have a number of exciting potential applications in SERS-based sensors.

Precision synthesis: designing hot spots over hot spots via selective gold deposition on silver octahedra edges.

A major challenge in plasmonic hot spot fabrication is to efficiently increase the hot spot volumes on single metal nanoparticles to generate stronger signals in plasmon-enhanced applications. Here, the synthesis of designer nanoparticles, where plasmonic-active Au nanodots are selectively deposited onto the edge/tip hot spot regions of Ag nanoparticles, is demonstrated using a two-step seed-mediated precision synthesis approach. Such a "hot spots over hot spots" strategy leads to an efficient enhancement of the plasmonic hot spot volumes on single Ag nanoparticles. Through cathodoluminescence hyperspectral imaging of these selective edge gold-deposited Ag octahedron (SEGSO), the increase in the areas and emission intensities of hot spots on Ag octahedra are directly visualized after Au deposition. Single-particle surface-enhanced Raman scattering (SERS) measurements demonstrate 10-fold and 3-fold larger SERS enhancement factors of the SEGSO as compared to pure Ag octahedra and non-selective gold-deposited Ag octahedra (NSEGSO), respectively. The experimental results corroborate well with theoretical simulations, where the local electromagnetic field enhancement of our SEGSO particles is 15-fold and 1.3-fold stronger than pure Ag octahedra and facet-deposited particles, respectively. The growth mechanisms of such designer nanoparticles are also discussed together with a demonstration of the versatility of this synthetic protocol.

Graphene oxide and shape-controlled silver nanoparticle hybrids for ultrasensitive single-particle surface-enhanced Raman scattering (SERS) sensing

Graphene oxide (GO) is an emerging material for surface-enhanced Raman scattering (SERS) due to its strong chemical enhancement. Studying the SERS performance of plasmonic nanoparticle/GO hybrid materials at the single particle level is crucial for direct probing of the chemical effect of GO on plasmonic nanoparticles. In this work, we integrate GO and shape-controlled Ag nanoparticles to create hybrid nanomaterials, and the chemical enhancement arising from GO is investigated using single-particle SERS measurements. Ag nanoparticle@GO hybrid nanostructures are prepared by assembling Ag nanoparticles, including spheres, cubes and octahedra with GO sheets. The SERS behaviors of the hybrid nanostructures are characterized, and 2-3 times enhanced SERS intensities are detected from the Ag nanoparticle@GO hybrid nanostructures as compared to pure Ag nanoparticles. Furthermore, we probe the mechanism of SERS enhancement in the hybrid nanostructures by changing the surface coverage of GO on Ag octahedra, by using reduced GO in place of GO as well as by using probe molecules of different electronegativities. This hybrid system is an excellent candidate for single-particle SERS sensors. Sub-nanomolar levels of aromatic molecules are detected using a single Ag/GO hybrid nanomaterial. This as-prepared GO and shape-controlled Ag nanoparticle hybrid is capable of serving as a high performance SERS platform, providing new opportunities for efficient chemical and biological sensing applications.

Optical Properties of Noncontinuous Gold Shell Engineered on Silica Mesosphere

The optical properties of individual noncontinuous shells with different gold coverage are investigated by the single-particle dark field scattering measurements and single-particle surface-enhanced Raman scattering (SERS) measurements at different excitation wavelengths. By controlling the growth of gold seeds, multi-metallic nanogaps/crevices with different optical responses are assembled on silica mesospheres forming noncontinuous shells that can be confirmed through the transmission electron microscope images. We find the surface plasmon resonance of single shell red-shifts from 510 to 680 nm with the increase of gold coverage. At the excitation of 532 and 785 nm, the best enhancements about 2.0 × 105 and 1.1 × 107 are obtained on spheres with ∼60 and 83 % gold coverage, respectively. The weak polarization-dependent SERS indicates that the enhancement is from the multi-gaps on single noncontinuous shell. This optical tunable and SERS active noncontinuous gold shell can be applied in biosensing, ultra trace detection, and molecule analysis needing multi-wavelengths excitation.

Hollow Gold−Silver Double-Shell Nanospheres:  Structure, Optical Absorption, and Surface-Enhanced Raman Scattering

Hollow gold−silver double-shell nanospheres (AuAgHNSs) have been synthesized and their structural, optical, and single-particle surface-enhanced Raman scattering (SERS) properties characterized. The structure of these AuAgHNSs have been determined by transmission electron microscopy (TEM), revealing a uniform silver outer shell of approximately 3 nm deposited by seed-mediated growth on 28 ± 6.2 nm hollow gold nanospheres (AuHNSs). Their plasmon resonance combines the energies of both the silver and the gold shells, broadening the absorption profile, while their overall structure maintains a spherical shape. This property is useful for SERS and other applications that require small, spherical nanostructures and broad, tunable absorption. The mechanism of silver growth on AuHNSs and gold NPs is proposed as silver island formation before complete encapsulation. SERS studies of mercaptobenzoic acid (MBA) before and after silver deposition show a 4−5-fold enhancement over AuHNSs with little change in signal co...