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.     

Non-lithographic SERS substrates: tailoring surface chemistry for Au nanoparticle cluster assembly

Near‐field plasmonic coupling and local field enhancement in metal nanoarchitectures, such as arrangements of nanoparticle clusters, have application in many technologies from medical diagnostics, solar cells, to sensors. Although nanoparticle‐based cluster assemblies have exhibited signal enhancements in surface‐enhanced Raman scattering (SERS) sensors, it is challenging to achieve high reproducibility in SERS response using low‐cost fabrication methods. Here an innovative method is developed for fabricating self‐organized clusters of metal nanoparticles on diblock copolymer thin films as SERS‐active structures. Monodisperse, colloidal gold nanoparticles are attached via a crosslinking reaction on self‐organized chemically functionalized poly(methyl methacrylate) domains on polystyrene‐block‐poly(methyl methacrylate) templates. Thereby nanoparticle clusters with sub‐10‐nanometer interparticle spacing are achieved. Varying the molar concentration of functional chemical groups and crosslinking agent during the assembly process is found to affect the agglomeration of Au nanoparticles into clusters. Samples with a high surface coverage of nanoparticle cluster assemblies yield relative enhancement factors on the order of 10⁹ while simultaneously producing uniform signal enhancements in point‐to‐point measurements across each sample. High enhancement factors are associated with the narrow gap between nanoparticles assembled in clusters in full‐wave electromagnetic simulations. Reusability for small‐molecule detection is also demonstrated. Thus it is shown that the combination of high signal enhancement and reproducibility is achievable using a completely non‐lithographic fabrication process, thereby producing SERS substrates having high performance at low cost.     

Hot-spot engineering in polygonal nanofinger assemblies for surface enhanced Raman spectroscopy

Multiparticle assemblies of nanoscale structures are the fundamental building blocks for powerful plasmonic devices. Here we show the controlled formation of polygonal metal nanostructure assemblies, including digon, trigon, tetragon, pentagon, and hexagon arrays, which were formed on top of predefined flexible polymer pillars that undergo self-coalescence, analogous to finger closing, with the aid of microcapillary forces. This hybrid approach of combining top-down fabrication with self-assembly enables the formation of complex nanoplasmonic structures with sub-nanometer gaps between gold nanoparticles. On comparison of the polygon-shaped assemblies, the symmetry dependence of the nanoplasmonic structures was determined for application to surface enhanced Raman spectroscopy (SERS), with the pentagonal assembly having the largest Raman enhancement for the tested molecules. Electromagnetic simulations of the polygonal structures were performed to visualize the field enhancements of the hot spots so as to guide the rational design of optimal SERS structures.     

Diverse bio-sensing and therapeutic applications of plasmon enhanced nanostructures

Substantial advancements have been observed over the years in the research and development of Localized Surface Plasmon Resonance (LSPR). A variety of current and future applications involving anisotropic plasmonic nanoparticles include biosensors, photothermal therapies, photocatalysis, and various other fields. Amongst various other applications, plasmonic enhancements are deployed in Surface Enhanced Raman Spectroscopy (SERS) mediated bio-sensing, absorption spectroscopy based analyte quantification, and fluorescence spectroscopy-based biomolecular detection up to femtomolar level and even on the level of single molecules. LSPR based healthcare diagnostics and therapeutics have grown much faster than expected, with an increased number of published original research articles and reviews. Despite the extensive literature available, a comprehensive review with a focused emphasis on recent advances in the field of plasmonic particle anisotropy, plasmonic nanostructure, plasmonic coupling mediated enhanced LSPR intensity and their diverse applications in biosensing is needed. This article focuses on LSPR properties of anisotropic nanostructures like spherical gold nanoparticles (AuNP), gold nanorod (AuNR), gold nanostar (AuNs), gold nanorattles (AuNRT), gold nanoholes (AuNH), dimeric nanostructures and their role in plasmonic enhancements for targeted biosensing and therapeutic research. The contemporary state of the art biosensing development around SERS has also been discussed. A detailed literature analysis of recent development in micro-surgery, photothermal tumor killing, biosensor development for detection up to single molecule level, high-efficiency drug delivery are covered in this article. Furthermore, recent and advanced technologies including Spatially Offset Raman Spectroscopy (SORS), Surface Enhanced Resonance Raman Spectroscopy (SERRS), and Surface Enhanced Spatially Offset Raman Spectroscopy (SESORS) are presented citing their importance in biosensing. We complement this review article with relevant theoretical frameworks to understand finer nuances within the literature that is discussed.     

A Flexible Caterpillar‐Like Gold Nanoparticle Assemblies with Ultrasmall Nanogaps for Enhanced Dual‐Modal Imaging and Photothermal Therapy

Gold nanoparticle (AuNP) assemblies (GNAs) have attracted attention since enhanced coupling plasmonic resonance (CPR) emerged in the nanogap between coupling AuNPs. For one dimensional GNAs (1D‐GNAs), most CPR from the nanogaps could be easily activated by electromagnetic waves and generate drastically enhanced CPR because the nanogaps between coupling AuNPs are linearly distributed in the 1D‐GNAs. The reported studies focus on the synthesis of 1D‐GNAs and fundamental exploration of CPR. There are still problems which impede further applications in nanomedicine, such as big size (>500 nm), poor water solubility, and/or poor stability. In this study, a kind of 1D flexible caterpillar‐like GNAs (CL‐GNAs) with ultrasmall nanogaps, good water solubility, and good stability is developed. The CL‐GNAs have a flexible structure that can randomly move to change their morphology, which is rarely reported. Numerous ultrasmall nanogaps (<1 nm) are linearly distributed along the structure of CL‐GNAs and generate enhanced CPR. The toxicity assessments in vitro and vivo respectively demonstrate that CL‐GNAs have a low cytotoxicity and good biocompatibility. The CL‐GNAs can be used as an efficient photothermal agent for photothermal therapy, a probe for Raman imaging and photothermal imaging.     

Monitoring Early‐Stage Nanoparticle Assembly in Microdroplets by Optical Spectroscopy and SERS

Microfluidic microdroplets have increasingly found application in biomolecular sensing as well as nanomaterials growth. More recently the synthesis of plasmonic nanostructures in microdroplets has led to surface‐enhanced Raman spectroscopy (SERS)‐based sensing applications. However, the study of nanoassembly in microdroplets has previously been hindered by the lack of on‐chip characterization tools, particularly at early timescales. Enabled by a refractive index matching microdroplet formulation, dark‐field spectroscopy is exploited to directly track the formation of nanometer‐spaced gold nanoparticle assemblies in microdroplets. Measurements in flow provide millisecond time resolution through the assembly process, allowing identification of a regime where dimer formation dominates the dark‐field scattering and SERS. Furthurmore, it is shown that small numbers of nanoparticles can be isolated in microdroplets, paving the way for simple high‐yield assembly, isolation, and sorting of few nanoparticle structures.     

Design of Magnetic‐Plasmonic Nanoparticle Assemblies via Interface Engineering of Plasmonic Shells for Targeted Cancer Cell Imaging and Separation

Magnetic‐plasmonic nanoparticles have received considerable attention for widespread applications. These nanoparticles (NPs) exhibiting surface‐enhanced Raman scattering (SERS) activities are developed due to their potential in bio‐sensing applicable in non‐destructive and sensitive analysis with target‐specific separation. However, it is challenging to synthesize these NPs that simultaneously exhibit low remanence, maximized magnetic content, plasmonic coverage with abundant hotspots, and structural uniformity. Here, a method that involves the conjugation of a magnetic template with gold seeds via chemical binding and seed‐mediated growth is proposed, with the objective of obtaining plasmonic nanostructures with abundant hotspots on a magnetic template. To obtain a clean surface for directly functionalizing ligands and enhancing the Raman intensity, an additional growth step of gold (Au) and/or silver (Ag) atoms is proposed after modifying the Raman molecules on the as‐prepared magnetic‐plasmonic nanoparticles. Importantly, one‐sided silver growth occurred in an environment where gold facets are blocked by Raman molecules; otherwise, the gold growth is layer‐by‐layer. Moreover, simultaneous reduction by gold and silver ions allowed for the formation of a uniform bimetallic layer. The enhancement factor of the nanoparticles with a bimetallic layer is approximately 10⁷. The SERS probes functionalized cyclic peptides are employed for targeted cancer‐cell imaging and separation.     

Wafer‐Scale Double‐Layer Stacked Au/Al2O3@Au Nanosphere Structure with Tunable Nanospacing for Surface‐Enhanced Raman Scattering

Fabricating perfect plasmonic nanostructures has been a major challenge in surface enhanced Raman scattering (SERS) research. Here, a double‐layer stacked Au/Al₂O₃@Au nanosphere structures is designed on the silicon wafer to bring high density, high intensity “hot spots” effect. A simply reproducible high‐throughput approach is shown to fabricate feasibly this plasmonic nanostructures by rapid thermal annealing (RTA) and atomic layer deposition process (ALD). The double‐layer stacked Au nanospheres construct a three‐dimensional plasmonic nanostructure with tunable nanospacing and high‐density nanojunctions between adjacent Au nanospheres by ultrathin Al₂O₃ isolation layer, producing highly strong plasmonic coupling so that the electromagnetic near‐field is greatly enhanced to obtain a highly uniform increase of SERS with an enhancement factor (EF) of over 10⁷. Both heterogeneous nanosphere group (Au/Al₂O₃@Ag) and pyramid‐shaped arrays structure substrate can help to increase the SERS signals further, with a EF of nearly 10⁹. These wafer‐scale, high density homo/hetero‐metal‐nanosphere arrays with tunable nanojunction between adjacent shell‐isolated nanospheres have significant implications for ultrasensitive Raman detection, molecular electronics, and nanophotonics.     

Photonic Crystal Hydrogel Enhanced Plasmonic Staining for Multiplexed Protein Analysis

Plasmonic nanoparticles are commonly used as optical transducers in sensing applications. The optical signals resulting from the interaction of analytes and plamsonic nanoparticles are influenced by surrounding physical structures where the nanoparticles are located. This paper proposes inverse opal photonic crystal hydrogel as 3D structure to improve Raman signals from plasmonic staining. By hybridization of the plasmonic nanoparticles and photonic crystal, surface‐enhanced Raman spectroscopy (SERS) analysis of multiplexed protein is realized. It benefits the Raman analysis by providing high‐density “hot spots” in 3D and extra enhancement of local electromagnetic field at the band edge of PhC with periodic refractive index distribution. The strong interaction of light and the hybrid 3D nanostructure offers new insights into plasmonic nanoparticle applications and biosensor design.     

Hybrid Structures for Surface‐Enhanced Raman Scattering: DNA Origami/Gold Nanoparticle Dimer/Graphene

A combination of three innovative materials within one hybrid structure to explore the synergistic interaction of their individual properties is presented. The unique electronic, mechanical, and thermal properties of graphene are combined with the plasmonic properties of gold nanoparticle (AuNP) dimers, which are assembled using DNA origami nanostructures. This novel hybrid structure is characterized by means of correlated atomic force microscopy and surface‐enhanced Raman scattering (SERS). It is demonstrated that strong interactions between graphene and AuNPs result in superior SERS performance of the hybrid structure compared to their individual components. This is particularly evident in efficient fluorescence quenching, reduced background, and a decrease of the photobleaching rate up to one order of magnitude. The versatility of DNA origami structures to serve as interface for complex and precise arrangements of nanoparticles and other functional entities provides the basis to further exploit the potential of the here presented DNA origami–AuNP dimer–graphene hybrid structures.     

Self‐Assembled Large Au Nanoparticle Arrays with Regular Hot Spots for SERS

The cost‐effective self‐assembly of 80 nm Au nanoparticles (NPs) into large‐domain, hexagonally close‐packed arrays for high‐sensitivity and high‐fidelity surface‐enhanced Raman spectroscopy (SERS) is demonstrated. These arrays exhibit specific optical resonances due to strong interparticle coupling, which are well reproduced by finite‐difference time‐domain (FDTD) simulations. The gaps between NPs form a regular lattice of hot spots that enable a large amplification of both photoluminescence and Raman signals. At smaller wavelengths the hot spots are extended away from the minimum‐gap positions, which allows SERS of larger analytes that do not fit into small gaps. Using CdSe quantum dots (QDs) a 3–5 times larger photoluminescence enhancement than previously reported is experimentally demonstrated and an unambiguous estimate of the electromagnetic SERS enhancement factor of ≈10⁴ is obtained by direct scanning electron microscopy imaging of QDs responsible for the Raman signal. Much stronger enhancement of ≈10⁸ is obtained at larger wavelengths for benzenethiol molecules penetrating the NP gaps.     

Site‐Specific SERS Assay for Survivin Protein Dimer: From Ensemble Experiments to Correlative Single‐Particle Imaging

An assay for Survivin, a small dimeric protein which functions as modulator of apoptosis and cell division and serves as a promising diagnostic biomarker for different types of cancer, is presented. The assay is based on switching on surface‐enhanced Raman scattering (SERS) upon incubation of the Survivin protein dimer with Raman reporter‐labeled gold nanoparticles (AuNP). Site‐specificity is achieved by complexation of nickel‐chelated N‐nitrilo‐triacetic acid (Ni‐NTA) anchors on the particle surface by multiple histidines (His₆‐tag) attached to each C‐terminus of the centrosymmetric protein dimer. Correlative single‐particle analysis using light sheet laser microscopy enables the simultaneous observation of both elastic and inelastic light scattering from the same sample volume. Thereby, the SERS‐inactive AuNP‐protein monomers can be directly discriminated from the SERS‐active AuNP‐protein dimers/oligomers. This information, i.e. the percentage of SERS‐active AuNP in colloidal suspension, is not accessible from conventional SERS experiments due to ensemble averaging. The presented correlative single‐particle approach paves the way for quantitative site‐specific SERS assays in which site‐specific protein recognition by small chemical and in particular supramolecular ligands can be tested.     

Plasmonic coupling interference (PCI) nanoprobes for nucleic acid detection

A label-free approach using plasmonic coupling interference (PCI) nanoprobes for nucleic acid detection using surface-enhanced Raman scattering (SERS) is described. To induce a strong plasmonic coupling effect, a nanonetwork of silver nanoparticles with the Raman label located between adjacent nanoparticles is assembled by Raman-labeled DNA-locked nucleic acid (LNA) duplexes. The PCI method then utilizes specific nucleic acid sequences of interest as competitor elements for the Raman-labeled DNA strands to interfere the formation of nanonetworks in a competitive binding process. As a result, the plasmonic coupling effect induced through the formation of the nanonetworks is significantly diminished, resulting in a reduced SERS signal. The potential of the PCI technique for biomedical applications is illustrated by detecting single-nucleotide polymorphism (SNP) and microRNA sequences involved in breast cancers. The results of this study could lead to the development of nucleic acid diagnostic tools for biomedical diagnostics and biosensing applications using SERS detection.     

Large‐Area 3D Hierarchical Superstructures Assembled from Colloidal Nanoparticles

Assembling nanosized building blocks into macroscopic 3D complex structures is challenging. Here, nanosized metal and semiconductor building blocks with a variety of sizes and shapes (spheres, stars, and rods) are successfully assembled into a broad range of hierarchical (nanometer to micrometer) assemblies of functional materials in centimeter size using butterfly wings as templates. This is achieved by the introduction of steric hindrance to the assembly process, which compensates for attraction from the environmentally sensitive hydrogen bonds and prevents the aggregation of nanosized building blocks. Of these materials, Au nanostar assemblies show a superior enhancement in surface‐enhanced Raman scattering (SERS) performance (rhodamine 6G, 1506 cm^?1) under 532, 633, and 780 nm excitation—this is 3.1–4.4, 3.6–3.9, and 2.9–47.3 folds surpassing Au nanosphere assemblies and commercial SERS substrates (Q‐SERS), respectively. This method provides a versatile route for the assembly of various nanosized building blocks into different 3D superstructures and for the construction of hybrid nanomaterials and nanocomposites.     

High Surface‐Enhanced Raman Scattering Performance of Individual Gold Nanoflowers and Their Application in Live Cell Imaging

Molecular imaging techniques based on surface‐enhanced Raman scattering (SERS) face a lack of reproducibility and reliability, thus hampering its practical application. Flower‐like gold nanoparticles have strong SERS enhancement performance due to having plenty of hot‐spots on their surfaces, and this enhancement is not dependent on the aggregation of the particles. These features make this kind of particle an ideal SERS substrate to improve the reproducibility in SERS imaging. Here, the SERS properties of individual flower‐like gold nanoparticles are systematically investigated. The measurements reveal that the enhancement of a single gold nanoparticle is independent of the polarization of the excitation laser with an enhancement factor as high as 10⁸. After capping with Raman signal molecules and folic acid, the gold nanoflowers show strong Raman signal in the living cells, excellent targeting properties, and a high signal‐to‐noise ratio for SERS imaging.     

Hot Spot Engineering in Hierarchical Plasmonic Nanostructures

The controllable nanogap structures offer an effective way to obtain strong and tunable localized surface plasmon resonance (LSPR). A novel hierarchical plasmonic nanostructure (HPN) is created by incorporating a rotating coordinate system into colloidal lithography. In this nanostructure, the hot spot density is increased drastically by the long-range ordered morphology with discrete metal islands filled in the structural units. Based on the Volmer–Weber growth theory, the precise HPN growth model is established, which guides the hot spot engineering for improved LSPR tunability and strong field enhancement. The hot spot engineering strategy is examined by the application of HPNs as the surface-enhanced Raman spectroscopy (SERS) substrate. It is universally suitable for various SERS characterization excited at different wavelengths. Based on the HPN and hot spot engineering strategy, single-molecule level detection and long-range mapping can be realized simultaneously. In that sense, it offers a great platform and guides the future design for various LSPR applications like surface-enhanced spectra, biosensing, and photocatalysis.     

Combined Visible Plasmons of Ag Nanoparticles and Infrared Plasmons of Graphene Nanoribbons for High-Performance Surface-Enhanced Raman and Infrared Spectroscopies

Ag nanoparticles (NPs) modified graphene nanoribbons (GNRs) are proposed to function as the high-performance shared substrates for surface-enhanced Raman and infrared absorption spectroscopy (SERS and SEIRAS). This is realized by modulating the localized plasmonic resonances of Ag NPs in visible region and GNRs in mid-infrared region simultaneously, so as to selectively employ each resonance to acquire SERS and SEIRAS on a single substrate. As a proof of concept, shared substrates are prepared by fabricating GNRs on a Fabry–Pérot like cavity, followed by depositing a thin Ag film with annealing treatment to achieve Ag NPs. Complementary Raman and infrared active vibrational modes of rhodamine 6G molecules can be extracted from the SERS and SEIRAS spectra. By optimizing the dimension of Ag NPs, SERS enhancement factors at the order of 10⁵ can be achieved, which are comparable with or even larger than that of the reported shared substrates. Meanwhile, various polyethylene oxide vibrational modes can be recognized with maximum SEIRAS amplification up to 170 times, which is one order larger than that of the reported graphene plasmonic infrared sensors. Such plasmonic nanosensor with excellent SERS and SEIRAS performance exhibits promising potential for biosensing applications on an integrated lab-on-a-chip strategy.     

M‐shaped Grating by Nanoimprinting: A Replicable,Large‐Area,Highly Active Plasmonic Surface‐Enhanced Raman Scattering Substrate with Nanogaps

Plasmonic nanostructures separated by nanogaps enable strong electromagnetic‐field confinement on the nanoscale for enhancing light‐matter interactions, which are in great demand in many applications such as surface‐enhanced Raman scattering (SERS). A simple M‐shaped nanograting with narrow V‐shaped grooves is proposed. Both theoretical and experimental studies reveal that the electromagnetic field on the surface of the M grating can be pronouncedly enhanced over that of a grating without such grooves, due to field localization in the nanogaps formed by the narrow V grooves. A technique based on room‐temperature nanoimprinting lithography and anisotropic reactive‐ion etching is developed to fabricate this device, which is cost‐effective, reliable, and suitable for fabricating large‐area nanostructures. As a demonstration of the potential application of this device, the M grating is used as a SERS substrate for probing Rhodamine 6G molecules. Experimentally, an average SERS enhancement factor as high as 5×10⁸ has been achieved, which verifies the greatly enhanced light–matter interaction on the surface of the M grating over that of traditional SERS surfaces.     

Magnetic Plasmon Networks Programmed by Molecular Self‐Assembly

Nanoscale manipulation of magnetic fields has been a long‐term pursuit in plasmonics and metamaterials, as it can enable a range of appealing optical properties, such as high‐sensitivity circular dichroism, directional scattering, and low‐refractive‐index materials. Inspired by the natural magnetism of aromatic molecules, the cyclic ring cluster of plasmonic nanoparticles (NPs) has been suggested as a promising architecture with induced unnatural magnetism, especially at visible frequencies. However, it remains challenging to assemble plasmonic NPs into complex networks exhibiting strong visible magnetism. Here, a DNA‐origami‐based strategy is introduced to realize molecular self‐assembly of NPs forming complex magnetic architectures, exhibiting emergent properties including anti‐ferromagnetism, purely magnetic‐based Fano resonances, and magnetic surface plasmon polaritons. The basic building block, a gold NP (AuNP) ring consisting of six AuNP seeds, is arranged on a DNA origami frame with nanometer precision. The subsequent hierarchical assembly of the AuNP rings leads to the formation of higher‐order networks of clusters and polymeric chains. Strong emergent plasmonic properties are induced by in situ growth of silver upon the AuNP seeds. This work may facilitate the development of a tunable and scalable DNA‐based strategy for the assembly of optical magnetic circuitry, as well as plasmonic metamaterials with high fidelity.     

Plasmonic Nanoassemblies: Tentacles Beat Satellites for Boosting Broadband NIR Plasmon Coupling Providing a Novel Candidate for SERS and Photothermal Therapy

Optical theranostic applications demand near‐infrared (NIR) localized surface plasmon resonance (LSPR) and maximized electric field at nanosurfaces and nanojunctions, aiding diagnosis via Raman or optoacoustic imaging, and photothermal‐based therapies. To this end, multiple permutations and combinations of plasmonic nanostructures and molecular “glues” or linkers are employed to obtain nanoassemblies, such as nanobranches and core–satellite morphologies. An advanced nanoassembly morphology comprising multiple linear tentacles anchored onto a spherical core is reported here. Importantly, this core‐multi‐tentacle‐nanoassembly (CMT) benefits from numerous plasmonic interactions between multiple 5 nm gold nanoparticles (NPs) forming each tentacle as well as tentacle to core (15 nm) coupling. This results in an intense LSPR across the “biological optical window” of 650?1100 nm. It is shown that the combined interactions are responsible for the broadband LSPR and the intense electric field, otherwise not achievable with core–satellite morphologies. Further the sub 80 nm CMTs boosted NIR‐surface‐enhanced Raman scattering (SERS), with detection of SERS labels at 47 × 10^‐9 m , as well as lower toxicity to noncancerous cell lines (human fibroblast Wi38) than observed for cancerous cell lines (human breast cancer MCF7), presents itself as an attractive candidate for use as biomedical theranostics agents.