Self‐Assembled SERS Substrates with Tunable Surface Plasmon Resonances

The fabrication of surface‐enhanced Raman spectroscopy (SERS) substrates that are optimized for use with specific laser wavelength–analyte combinations is addressed. In order to achieve large signal enhancement, temporal stability, and reproducibility over large substrate areas at low cost, only self‐assembly and templating processes are employed. The resulting substrates consist of arrays of gold nanospheres with controlled diameter and spacing, properties that dictate the optical response of the structure. Tunability of the extended surface plasmon resonance is observed in the range of 520–1000 nm. It is demonstrated that the enhancement factor is maximized when the surface plasmon resonance is red‐shifted with respect to the SERS instrument laser line. Despite relying on self‐organization, site‐to‐site enhancement factor variations smaller than 10% are obtained.     

Multifunctional Au‐Coated TiO2 Nanotube Arrays as Recyclable SERS Substrates for Multifold Organic Pollutants Detection

A multifunctional Au‐coated TiO₂ nanotube array is made via synthesis of a TiO₂ nanotube array through a ZnO template, followed by deposition of Au particles onto the TiO₂ surface using photocatalytic deposition and a hydrothermal method, respectively. Such arrays exhibit superior detection sensitivity with high reproducibility and stability. In addition, due to possessing stable catalytic properties, the arrays can clean themselves by photocatalytic degradation of target molecules adsorbed to the substrate under irradiation with UV light into inorganic small molecules using surface‐enhanced Raman spectroscopy (SERS) detection, so that recycling can be achieved. Finally, by detection of Rhodamine 6G (R6G) dye, herbicide 4‐chlorophenol (4‐CP), persistent organic pollutant (POP) dichlorophenoxyacetic acid (2,4‐D), and organophosphate pesticide methyl‐parathion (MP), the unique recyclable properties indicate a new route in eliminating the single‐use problem of traditional SERS substrates and show promising applications for detecting other organic pollutants.     

Supported Faceted Gold Nanoparticles with Tunable Surface Plasmon Resonance for NIR‐SERS

A novel dry plasma methodology for fabricating directly stabilized substrate‐supported gold nanoparticle (NP) ensembles for near infrared surface enhanced Raman scattering (NIR SERS) is presented. This maskless stepwise growth exploits Au‐sulfide seeds by plasma sulfidization of gold nuclei to produce highly faceted Au NPs with a multiple plasmon resonance that can be tuned from the visible to the near infrared, down to 1400 nm. The role of Au sulfidization in modifying the dynamics of Au NPs and of the corresponding plasmon resonance is discussed. The tunability of the plasmon resonance in a broad range is shown and the effectiveness as substrates for NIR SERS is demonstrated. The SERS response is investigated by using different laser sources operating both in the visible and in the NIR. SERS mapping of the SERS enhancement factor is carried out in order to evaluate their effectiveness, stability, and reproducibility as NIR SERS substrates, also in comparison with gold NPs fabricated by conventional sputtering and with the state‐of‐the‐art in the current literature.     

Surface Energy‐Controlled SERS Substrates for Molecular Concentration at Plasmonic Nanogaps

Positioning probe molecules at electromagnetic hot spots with nanometer precision is required to achieve highly sensitive and reproducible surface‐enhanced Raman spectroscopy (SERS) analysis. In this article, molecular positioning at plasmonic nanogaps is reported using a high aspect ratio (HAR) plasmonic nanopillar array with a controlled surface energy. A large‐area HAR plasmonic nanopillar array is generated using a nanolithography‐free simple process involving Ar plasma treatment applied to a smooth polymer surface and the subsequent evaporation of metal onto the polymer nanopillars. The surface energy can be precisely controlled through the selective removal of an adsorbed self‐assembled monolayer of low surface‐energy molecules prepared on the plasmonic nanopillars. This process can be used to tune the surface energy and provide a superhydrophobic surface with a water contact angle of 165.8° on the one hand or a hydrophilic surface with a water contact angle of 40.0° on the other. The highly tunable surface wettability is employed to systematically investigate the effects of the surface energy on the capillary‐force‐induced clustering among the HAR plasmonic nanopillars as well as on molecular concentration at the collapsed nanogaps present at the tops of the clustered nanopillars.     

DNA‐Directed Self‐Assembly of Core‐Satellite Plasmonic Nanostructures: A Highly Sensitive and Reproducible Near‐IR SERS Sensor

The excitation of surface plasmons in metallic nanostructures provides an opportunity to localize light at the nanoscale, well below the scale of the wavelength of the light. The high local electromagnetic field intensities generated in the vicinity of the nanostructures through this nanofocusing effect are exploited in surface enhanced Raman spectroscopy (SERS). At narrow interparticle gaps, so‐called hot‐spots, the nanofocusing effect is particularly pronounced. Hence, the engineering of substrates with a consistently high density of hot‐spots is a major challenge in the field of SERS. Here, a simple bottom‐up approach is described for the fabrication of highly SERS‐active gold core‐satellite nanostructures, using electrostatic and DNA‐directed self‐assembly. It is demonstrated that well‐defined core‐satellite gold nanostructures can be fabricated without the need for expensive direct‐write nanolithography tools such as electron‐beam lithography (EBL). Self‐assembly also provides excellent control over particle distances on the nanoscale. The as‐fabricated core‐satellite nanostructures exhibit SERS activities that are superior to commercial SERS substrates in signal intensity and reproducibility. This also highlights the potential of bottom‐up self‐assembly strategies for the fabrication of complex, well‐defined functional nanostructures with future applications well beyond the field of sensing.     

Arrays of Cone‐Shaped ZnO Nanorods Decorated with Ag Nanoparticles as 3D Surface‐Enhanced Raman Scattering Substrates for Rapid Detection of Trace Polychlorinated Biphenyls

A new, highly sensitive and uniform three‐dimensional (3D) hybrid surface‐enhanced Raman scattering (SERS) substrate has been achieved via simultaneously assembling small Ag nanoparticles (Ag‐NPs) and large Ag spheres onto the side surface and the top ends of large‐scale vertically aligned cone‐shaped ZnO nanorods (ZnO‐NRs), respectively. This 3D hybrid substrate manifests high SERS sensitivity to rhodamine and a detection limit as low as 10^?11 M to polychlorinated biphenyl (PCB) 77—a kind of persistent organic pollutants as global environmental hazard. Three kinds of inter‐Ag‐NP gaps in 3D geometry create a huge number of SERS “hot spots” that mainly contribute to the high SERS sensitivity. Moreover, the supporting chemical enhancement effect of ZnO‐NRs and the better enrichment effect ascribed to the large surface area of the substrate also help to achieve a lower detection limit. The arrays of cone‐shaped ZnO‐NRs decorated with Ag‐NPs on their side surface and large Ag spheres on the top ends have potentials in SERS‐based rapid detection of trace PCBs.     

Hierarchically Ordered Arrays of Noncircular Silicon Nanowires Featured by Holographic Lithography Toward a High‐Fidelity Sensing Platform

A novel, highly uniform and tunable hybrid plasmonic array is created via ion‐milling, catalytic wet‐etching and electron‐beam evaporation, using a holographically featured structure as a milling mask. A simple and low‐cost prism holographic lithography (HL) technique is applied to create an unprecedentedly coordinated array of elliptic gold (Au) holes, which act as the silicon (Si) etching catalyst in the reaction solution used to fabricate an elliptic silicon nanowire (SiNW) array; here, the SiNWs are arrayed hierarchically in such a way that three SiNWs are triangularly coordinated, and the triangles are arranged hexagonally. After removing the polymeric mask and metal thin film, the highly anisotropic thick Au film is deposited on the SiNW arrays. This hybrid substrate shows tunable optical properties in the near‐infrared (NIR) region from 875 nm to 1030 nm and surface‐enhanced Raman scattering (SERS) activities; these characteristics depend on the catalytic wet etching time, which changes the size of the vertical gap between the Au thick films deposited separately on the SiNWs. In addition, lateral interparticle coupling induces highly intensified SERS signals with good homogeneity. Finally, the Au‐capped elliptical SiNW arrays can be hierarchically patterned by combining prism HL and conventional photolithography, and the highly enhanced fluorescence intensity associated with both the structural effects and the plasmon resonances is investigated.     

Using SERS Tags to Image the Three‐Dimensional Structure of Complex Cell Models

Methods to image complex 3D cell cultures are limited by issues such as fluorophore photobleaching and decomposition, poor excitation light penetration, and lack of complementary techniques to verify the 3D structure. Although it remains insufficiently demonstrated, surface‐enhanced Raman scattering (SERS) imaging is a promising tool for the characterization of biological complex systems. To this aim, a controllable 3D cell culture model which spans nearly 1 cm² in surface footprint is designed. This structure is composed of fibroblasts containing SERS‐encoded nanoparticles (i.e., SERS tags), arranged in an alternating layered structure. This “sandwich” type structure allows monitoring of the SERS signals in the z‐axis and with mm dimensions in the xy‐axis. Taking advantage of correlative microscopy techniques such as electron microscopy, it is possible to corroborate nanoparticle positioning and distances in z‐depths of up to 150 µm. This study reveals a proof‐of‐concept method for detailed 3D SERS imaging of a complex, dense 3D cell culture model.     

Spatial Analysis of Metal–PLGA Hybrid Microstructures Using 3D SERS Imaging

The incorporation of gold nanoparticles in biodegradable polymeric nanostructures with controlled shape and size is of interest toward different applications in nanomedicine. Properties of the polymer such as drug loading and antibody functionalization can be combined with the plasmonic properties of gold nanoparticles, to yield advanced hybrid materials. This study presents a new way to synthesize multicompartmental microgels, fibers, or cylinders, with embedded anisotropic gold nanoparticles. Gold nanoparticles dispersed in an organic solvent can be embedded within the poly(lactic‐co‐glycolic acid) (PLGA) matrix of polymeric microstructures, when prepared via electrohydrodynamic co‐jetting. Prior functionalization of the plasmonic nanoparticles with Raman active molecules allows for imaging of the nanocomposites by surface‐enhanced Raman scattering (SERS) microscopy, thereby revealing nanoparticle distribution and photostability. These exceptionally stable hybrid materials, when used in combination with 3D SERS microscopy, offer new opportunities for bioimaging, in particular when long‐term monitoring is required.     

Nanogap‐Rich Au Nanowire SERS Sensor for Ultrasensitive Telomerase Activity Detection: Application to Gastric and Breast Cancer Tissues Diagnosis

Telomerase has attracted much attention as a universal cancer biomarker because telomerase is overexpressed in more than 85% of human cancer cells while suppressed in normal somatic cells. Since a strong association exists between telomerase activity and human cancers, the development of effective telomerase activity assay is critically important. Here, a nanogap‐rich Au nanowire (NW) surface‐enhanced Raman scattering (SERS) sensor is reported for detection of telomerase activity in various cancer cells and tissues. The nanogap‐rich Au NWs are constructed by deposition of nanoparticles on single‐crystalline Au NWs and provided highly reproducible SERS spectra. The telomeric substrate (TS) primer‐attached nanogap‐rich Au NWs can detect telomerase activity through SERS measurement after the elongation of TS primers, folding into G‐quadruplex structures, and intercalation of methylene blue. This sensor enables us to detect telomerase activity from various cancer cell lines with a detection limit of 0.2 cancer cells mL^?1. Importantly, the nanogap‐rich Au NW sensor can diagnose gastric and breast cancer tissues accurately. The nanogap‐rich Au NW sensors show strong SERS signals only in the presence of tumor tissues excised from 16 tumor‐bearing mice, while negligible signals in the presence of heated tumor tissues or normal tissues. It is anticipated that nanogap‐rich Au NW SERS sensors can be used for a universal cancer diagnosis and further biomedical applications including a diverse biomarker sensing.     

Tunable Enhancement of Raman Scattering in Graphene‐Nanoparticle Hybrids

The realization of graphene‐gold‐nanoparticle (G‐AuNP) hybrids is presented here through a versatile electrochemical approach, which allows the continuous tuning of the size and density of the particles obtainable on the graphene surface. Raman scattering from graphene, which is significantly enhanced in such hybrids, is systematically investigated as a function of the size and density of particles at the same location. In agreement with theory, it is shown that the Raman enhancement is tunable by varying predominantly the density of the nanoparticles. Furthermore, it is observed that the increase in Raman cross‐section and the strength of Raman enhancement varies as a function of the frequency of the vibrational mode, which may be correlated with the plasmonic fingerprint of the deposited AuNPs. In addition to this electromagnetic enhancement, support is found for a chemical contribution through the occurrence of charge transfer from the AuNPs onto graphene. Finally, G‐AuNP hybrids can be efficiently utilized as SERS substrates for the detection of specifically bound non‐resonant molecules, whose vibrational modes can be unambiguously identified. With the possibility to tune the degree of Raman enhancement, this is a platform to design and engineer SERS substrates to optimize the detection of trace levels of analyte molecules.     

Poly(2‐(dimethylamino)ethyl methacrylate) Brushes with Incorporated Nanoparticles as a SERS Active Sensing Layer

A simple, fast, and versatile approach to the fabrication of outstanding surface enhanced Raman spectroscopy (SERS) substrates by exploiting the optical properties of the Ag nanoparticles and functional as well as organizational characteristics of the polymer brushes is reported. First, poly(2‐(dimethylamino)ethyl methacrylate) brushes are synthesized directly on glassy carbon by self‐initiated photografting and photopolymerization and thoroughly characterized in terms of their thickness, wettability, morphology, and chemical structure by means of ellipsometry, contact angle, AFM, and XPS, respectively. Second, Ag nanoparticles are homogeneously immobilized into the brush layer, resulting in a sensor platform for the detection of organic molecules by SERS. The surface enhancement factor (SEF) as determined by the detection of Rhodamine 6G is calculated as 6 × 10⁶.     

α,ω‐Dithiol Oligo(phenylene vinylene)s for the Preparation of High‐Quality π‐Conjugated Self‐Assembled Monolayers and Nanoparticle‐ Functionalized Electrodes

While thioacetate‐terminated oligo(phenylene vinylene)s (OPVs) have been synthesized and employed in applications involving the formation of metal–molecule–metal junctions, the synthesis and application of potentially more versatile α,ω‐dithiol OPVs have not previously been described. Here, a thiomethyl‐precursor route to the synthesis of α,ω‐dithiol OPVs is reported and their ability to form well‐ordered self‐assembled monolayers (SAMs) without the addition of exogenous deprotection reagents is described. α,ω‐Dithiol OPV monolayers exhibit thicknesses consistent with molecular length and are nearly defect‐free, as assayed by electrochemical measurements. To demonstrate the ease with which SAMs containing these bifunctional OPVs can, in contrast to thioacetate functionalized OPVs, be further functionalized with materials other than gold, we have modified them in a single step with a sub‐monolayer of cadmium selenide nanocrystals (NCs). Scanning electron microscopy (SEM) and atomic force microscopy (AFM) confirm that these NC‐modified films are both smooth and uniform over the largest areas investigated (> 10 μm²) and no evidence of NC aggregation is observed. To evaluate the electrochemical response of these metal–molecule–semiconductor assemblies we have fabricated NC‐modified OPV SAMs with ferrocene‐coated NCs. Variable‐frequency alternating current voltammetry indicates that electron transfer in these assemblies is much more rapid than in analogous structures formed using simple alkane dithiols. It thus appears that α,ω‐dithiol OPVs are well suited for the formation of high‐quality conducting SAMs for the functionalization of gold and other surfaces.     

Large‐Scale Fabrication of Three‐Dimensional Surface Patterns Using Template‐Defined Electrochemical Deposition

A new strategy to achieve large‐scale, three‐dimensional (3D) micro‐ and nanostructured surface patterns through selective electrochemical growth on monolayer colloidal crystal (MCC) templates is reported. This method can effectively create large‐area (>1 cm²), 3D surface patterns with well‐defined structures in a cost‐effective and time‐saving manner (<30 min). A variety of 3D surface patterns, including semishells, Janus particles, microcups, and mushroom‐like clusters, is generated. Most importantly, our method can be used to prepare surface patterns with prescribed compositions, such as metals, metal oxides, organic materials, or composites (e.g., metal/metal oxide, metal/polymer). The 3D surface patterns produced by our method can be valuable in a wide range of applications, such as biosensing, data storage, and plasmonics. In a proof‐of‐concept study, we investigated, both experimentally and theoretically, the surface‐enhanced Raman scattering (SERS) performance of the fabricated silver 3D semishell arrays.     

Exploring How to Increase the Brightness of Surface‐Enhanced Raman Spectroscopy Nanolabels: The Effect of the Raman‐Active Molecules and of the Label Size

Due to the surface‐enhanced Raman scattering (SERS) effect, SERS labels based on noble‐metal nanoparticles loaded with Raman‐active molecules are good candidates for ultrasensitive multiplexed assays and in vitro/in vivo imaging. However, understanding how to maximize the brightness of such labels is of paramount importance for their widespread application. The effective differential Raman scattering cross‐section (dσ_R/dΩ) of SERS labels made of pegylated gold nanoparticles loaded with various Raman active molecules (Raman reporters) is studied. It is found that proper choice of the Raman reporter and of nanoparticle size can enhance the dσ_R/dΩ by several orders of magnitude. The experimental results are understood by considering the molecular cross‐section for resonant Raman scattering and the local electromagnetic enhancement factor (G_SERS) in the nearby of gold nanoparticles. These results are useful to guide the design of SERS labels with improved performances and to provide a reference for the comparison of the absolute value of the dσ_R/dΩ of SERS labels based on metal nanoparticles.     

Fabrication and Surface Functionalization of Nanoporous Gold by Electrochemical Alloying/Dealloying of Au–Zn in an Ionic Liquid,and the Self‐Assembly of L‐Cysteine Monolayers

This paper describes a totally electrochemical process for the fabrication and functionalization of high‐surface‐area, nanoporous gold films. The fabrication process involves the electrodeposition of a binary gold–zinc alloy at gold wires, followed by subsequent electrochemical dealloying of the less noble component zinc from the surface. Both the deposition and dealloying steps are conducted in a single low‐temperature bath of 40.0–60.0 mol‐% zinc chloride–1‐ethyl‐3‐methylimidazolium chloride ionic liquid at 120 °C without using any other corrosive acids or bases. The porous structure and morphology of the nanostructured gold film could be controlled by electrochemical variation of the composition of the Au–Zn surface alloy. It is demonstrated that the nanoporous gold surface can be successfully functionalized with self‐assembled monolayers of L ‐cysteine. Such functionalization greatly improves the utility of the nanoporous gold, as is demonstrated in the sensitive and selective determination of Cu(II ).     

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

The 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).     

Copper Nanoparticles Grafted on a Silicon Wafer and Their Excellent Surface‐Enhanced Raman Scattering

Copper nanoparticles grafted on a silicon wafer are fabricated by reducing copper ions with silicon–hydrogen bonds and assembling them in situ on the Si wafer. The nanoparticles, with an average size of 20 nm, grow uniformly and densely on the Si wafer, and they are used as substrates for surface‐enhanced Raman scattering. These substrates exhibit excellent enhancement in the low concentration detection (1 × 10^?9 M ) of rhodamine 6G with an enhancement factor (EF) of 2.29 × 10⁷ and a relative standard deviation (RSD) of <20%. They are also employed to detect sudan‐I dye with distinguished sensitivity and uniformity. The results are interesting and significant because Cu substrates are otherwise thought to be poor. These effects might provide new ways to think about surface‐enhanced Raman scattering based on Cu substrates.