Towards rapid nanoscale chemical analysis using tip-enhanced Raman spectroscopy with Ag-coated dielectric tips

The influence of dielectric substrates on the Raman scattering activities of Ag overlayers has been investigated. Materials with low refractive indices, such as SiO₂, SiO_x and AlF₃, were found to provide suitable supporting platforms for Ag films to give strong surface-enhanced Raman scattering for dye molecules when illuminated at 488 nm. This finding was then extended to tip-enhanced Raman scattering (TERS). Huge enhancements of 70–80×, corresponding to net enhancements of >10⁴, were observed for brilliant cresyl blue test analyte when Ag-coated tips made from or precoated with low refractive index materials were applied. The yield of fabricated tips that significantly enhance the Raman signals was found to be close to 100%. These findings provide crucial steps towards the use of TERS as a robust technique for rapid chemical imaging with nanometer spatial resolution. Figure Silver-coated dielectric tips for tip-enhanced Raman scattering (TERS) are capable of more than 10,000-fold enhancement     

Probing Adsorption Configurations of Small Molecules on Surfaces by Single-Molecule Tip-Enhanced Raman Spectroscopy

Determining the adsorption configurations of organic molecules on surfaces, especially for relatively small molecules, is a key issue for understanding the microscopic physical and chemical processes in surface science. In this work, we have applied low-temperature ultrahigh-vacuum tip-enhanced Raman scattering (TERS) technique to distinguish the configurations of small 4,4′-bipyridine (44BPY) molecules adsorbed on the Ag(111) surface. The observed Raman spectra exhibit notable differences in the spectral features which can be assigned to three different molecular orientations, each featuring a specific fingerprint pattern based on the TERS selection rule that determines the distribution of the relative intensities of different vibrational peaks. Furthermore, such a small molecule can in turn act as a local probe to provide information on the local electric field distribution at the tip apex. Our work showcases the capability of TERS technique for obtaining information on adsorption configurations of small molecules on surfaces down to the single-molecule level, which is of fundamental importance for many applications in the fields of molecular science and surface chemistry.     

Distinguishing Enantiomers by Tip-Enhanced Raman Scattering: Chemically Modified Silver Tip with an Asymmetric Atomic Arrangement

Discrimination between enantiomers is achieved by tip-enhanced Raman scattering (TERS) using a silver tip that is chemically modified by an achiral para-mercaptopyridine (pMPY) probe molecule. Differences in the relative intensities of the pMPY spectra were monitored for three pairs of enantiomers containing hydroxy (−OH) and/or amino (−NH₂) groups. The N: or N⁺−H functionality of the pMPY-modified tip participates in hydrogen-bond interactions with a particular molecular orientation of each chiral isomer. The asymmetric arrangement of silver atoms at the apex of the tip induces an asymmetric electric field, which causes the tip to become a chiral center. Differences in the charge-transfer (CT) states of the metal-achiral probe system in conjunction with the asymmetric electric field produce different enhancements in the Raman signals of the two enantiomers. The near-field effect of the asymmetric electric field, which depends on the number of analyte functional groups capable of hydrogen-bond formation, improves the degree of discrimination.     

适用于针尖增强拉曼技术的Au针尖的研制

采用针尖增强拉曼光谱技术(TERS)研究了刻蚀电位对Au针尖刻蚀效果的影响, 初步探讨了刻蚀过程的机理. 通过监控刻蚀过程中的振荡电流-时间曲线并与扫描电镜得到的结果比较, 发现可以直接利用电流-时间曲线简单地判断刻蚀后针尖的可能形状, 而无需再借助扫描电镜进行表征. 这不但提高了实验效率, 而且还可以避免针尖在转移和电镜表征过程中可能引入的污染. 研究结果表明, 在体积比为1:1的发烟盐酸和无水乙醇的刻蚀液中, 于2.2 V的电压下, 结合电化学方法控制终点可以得到形状对称尖锐的针尖. 这种针尖不但适合于TERS研究, 而且可用作STM针尖和微纳电极并用于其它针尖增强光学技术.     

Site-Dependent TERS Study of a Porphyrin Molecule on Ag(100) at 7 K

Single-molecule tip-enhanced Raman spectroscopy (TERS) has emerged as an important technique for structural analysis at sub-molecular scale. Here in this work, we report aTERS study of an isolated free-base porphyrin molecule adsorbed on the Ag(100) surface at cryogenic temperature (∽7 K). Site-dependent TERS spectra reveal distinct local vibrational information for the chemical constituents within a single molecule. Moreover, distinct spatial features among di erent Raman peaks can be resolved from the TERS mapping images. These images are found to associate with related vibrational modes, enabling to resolve the mode associated with N-H bonds at the sub-nanometer level. This study will provide deep insights into the symmetry of adsorption con gurations and local vibrational information within a single molecule.     

Chemical Enhancement and Quenching in Single-Molecule Tip-Enhanced Raman Spectroscopy

Despite intensive research in surface enhanced Raman spectroscopy (SERS), the influence mechanism of chemical effects on Raman signals remains elusive. Here, we investigate such chemical effects through tip-enhanced Raman spectroscopy (TERS) of a single planar ZnPc molecule with varying but controlled contact environments. TERS signals are found dramatically enhanced upon making a tip–molecule point contact. A combined physico-chemical mechanism is proposed to explain such an enhancement via the generation of a ground-state charge-transfer induced vertical Raman polarizability that is further enhanced by the strong vertical plasmonic field in the nanocavity. In contrast, TERS signals from ZnPc chemisorbed flatly on substrates are found strongly quenched, which is rationalized by the Raman polarizability screening effect induced by interfacial dynamic charge transfer. Our results provide deep insights into the understanding of the chemical effects in TERS/SERS enhancement and quenching.     

Towards chemical analysis of nanostructures in biofilms II: tip-enhanced Raman spectroscopy of alginates

This study examines the feasibility of using tip-enhanced Raman spectroscopy (TERS) for label-free chemical characterization of nanostructures in biological systems. For this purpose, a well-defined model system consisting of calcium alginate fibers is studied. In a companion paper, calcium alginate fibers and their network structures were shown to be a good model for the extracellular polysaccharides of biofilms at the nanoscale. TERS analysis of biological macromolecules, such as alginates, is complicated by heterogeneity in their sequence, molecular weight, and conformations, their small Raman cross-section, and the large number of functional groups, which can chemically interact with the silver surface of the tip and cause significant band shifts. Due to these effects, Raman frequencies in TERS spectra of biopolymers do not necessarily resemble band positions in the normal Raman spectrum of the bulk material, as is the case for less complex samples (e.g., dye molecules) studied so far. Additionally, analyte decomposition due to laser heating can have a significant influence, and carbon contamination signals can sometimes even overwhelm the weak analyte signals. Based on the investigation of alginates, strategies for spectra correction, choice of appropriate reference samples, and data interpretation are presented. With this approach, characteristic frequency ranges and specific marker bands can be found for biological macromolecules that can be employed for their identification in complex environments. Figure TERS spectrum of a calcium alginate fiber bundle     

Nanoscale Chemical Imaging Using Tip‐Enhanced Raman Spectroscopy: A Critical Review

Methods for chemical analysis at the nanometer scale are crucial for understanding and characterizing nanostructures of modern materials and biological systems. Tip‐enhanced Raman spectroscopy (TERS) combines the chemical information provided by Raman spectroscopy with the signal enhancement known from surface‐enhanced Raman scattering (SERS) and the high spatial resolution of atomic force microscopy (AFM) or scanning tunneling microscopy (STM). A metallic or metallized tip is illuminated by a focused laser beam and the resulting strongly enhanced electromagnetic field at the tip apex acts as a highly confined light source for Raman spectroscopic measurements. This Review focuses on the prerequisites for the efficient coupling of light to the tip as well as the shortcomings and pitfalls that have to be considered for TERS imaging, a fascinating but still challenging way to look at the nanoworld. Finally, examples from recent publications have been selected to demonstrate the potential of this technique for chemical imaging with a spatial resolution of approximately 10 nm and sensitivity down to the single‐molecule level for applications ranging from materials sciences to life sciences.     

Effect of sample and substrate electric properties on the electric field enhancement at the apex of SPM nanotips

Finite element (FE) models were built to define the optimal experimental conditions for tip-enhanced Raman spectroscopy (TERS) of thin samples. TERS experimental conditions were mimicked by including in the FE models dielectric or metallic substrates with thin dielectric samples and by considering the wavelength dependence of the dielectric properties for the metallic materials. Electromagnetic coupling between the substrate/sample and the SPM tips led to dramatic changes of both the spatial distribution and magnitude of the scattered electric field which depended on the substrate dielectric permittivity and excitation wavelength. Raman scattering as high as 10(8) with a spatial resolution of approximately 8 nm was estimated for gold SPM tips and gold substrate when excitation is performed at 532 nm (near-resonance wavelength). For dielectric samples (approximately 4 nm thick), the enhancement of Raman scattering intensity is estimated at approximately 10(5); this does not depend significantly on the sample dielectric permittivity for dielectric samples. These results suggest that TERS experimental conditions should be estimated and optimized for every individual application considering the geometric factors and electric properties of the materials involved. Such optimizations could enlarge the range of applications for TERS to samples eliciting weaker intrinsic Raman scattering, such as biological samples.     

Signal limitations in tip-enhanced Raman scattering: the challenge to become a routine analytical technique

The fundamental parameters and limitations that determine the signal strength in tip-enhanced Raman scattering (TERS) are discussed. A semiquantitative analysis of the Raman signal expected in different experimental geometries and with different sample systems is presented, taking into account experimental parameters including Fresnel factor, numerical aperture of the illumination and collection optics, detection efficiency, and the Raman scattering cross section of the material. A top/side-on illumination geometry is essential for the study of nontransparent samples. It can yield the highest signal levels when strong tip–sample coupling using a metallic substrate provides large field enhancement. In contrast, axial/through-sample illumination is limited to transparent sample materials. Although conceptually simpler in experimental implementation and despite high numerical aperture signal collection efficiency, signals are generally weaker due to limited field enhancement. Crystalline solids with small Raman cross sections and dense molecular/biological systems with unavoidable far-field background provide the biggest challenge for TERS analysis yet at the same time hold the most exciting outstanding scientific questions TERS has the potential to answer.

Distinguishing Enantiomers by Tip‐Enhanced Raman Scattering: Chemically Modified Silver Tip with an Asymmetric Atomic Arrangement

Discrimination between enantiomers is achieved by tip‐enhanced Raman scattering (TERS) using a silver tip that is chemically modified by an achiral para‐mercaptopyridine (pMPY) probe molecule. Differences in the relative intensities of the pMPY spectra were monitored for three pairs of enantiomers containing hydroxy (?OH) and/or amino (?NH₂) groups. The N: or N⁺?H functionality of the pMPY‐modified tip participates in hydrogen‐bond interactions with a particular molecular orientation of each chiral isomer. The asymmetric arrangement of silver atoms at the apex of the tip induces an asymmetric electric field, which causes the tip to become a chiral center. Differences in the charge‐transfer (CT) states of the metal‐achiral probe system in conjunction with the asymmetric electric field produce different enhancements in the Raman signals of the two enantiomers. The near‐field effect of the asymmetric electric field, which depends on the number of analyte functional groups capable of hydrogen‐bond formation, improves the degree of discrimination.     

Tip-enhanced Raman spectroscopy for nanoscale strain characterization

Tip-enhanced Raman spectroscopy (TERS), which utilizes the strong localized optical field generated at the apex of a metallic tip when illuminated, has been shown to successfully probe the vibrational spectrum of today’s and tomorrow’s state-of-the-art silicon and next-generation semiconductor devices, such as quantum dots. Collecting and analyzing the vibrational spectrum not only aids in material identification but also provides insight into strain distributions in semiconductors. Here, the potential of TERS for nanoscale characterization of strain in silicon devices is reviewed. Emphasis will be placed on the key challenges of obtaining spectroscopic images of strain in actual strained silicon devices. Figure Figure Concept of Tip Enhanced Raman Spectroscopy (TERS), which utilizes the strong localized optical field generated at the apex of a metallic tip when illuminated. TERS has been demonstrated to successfully probe the vibrational spectrum of today’s and tomorrow’s state-of-the-art silicon and next generation semiconductor devices     

Vibrational Property of α-Borophene Determined by Tip-Enhanced Raman Spectroscopy

We report a Raman characterization of the α borophene polymorph by scanning tunneling microscopy combined with tip-enhanced Raman spectroscopy. A series of Raman peaks were discovered, which can be well related with the phonon modes calculated based on an asymmetric buckled α structure. The unusual enhancement of high-frequency Raman peaks in TERS spectra of α borophene is found and associated with its unique buckling when landed on the Ag(111) surface. Our paper demonstrates the advantages of TERS, namely high spatial resolution and selective enhancement rule, in studying the local vibrational properties of materials in nanoscale.     

Expanding generality of surface-enhanced Raman spectroscopy with borrowing SERS activity strategy

Surface-enhanced Raman scattering (SERS) was discovered three decades ago and has gone through a tortuous pathway to develop into a powerful diagnostic technique. Recently, the lack of substrate, surface and molecular generalities of SERS has been circumvented to a large extent by devising and utilizing various nanostructures by many groups including ours. This article aims to present our recent approaches of utilizing the borrowing SERS activity strategy mainly through constructing two types of nanostructures. The first nanostructure is chemically synthesized Au nanoparticles coated with ultra-thin shells (ca. one to ten atomic layers) of various transition metals, e.g., Pt, Pd, Ni and Co, respectively. Boosted by the long-range effect of the enhanced electromagnetic (EM) field generated by the highly SERS-active Au core, the originally low surface enhancement of the transition metal can be substantially improved giving total enhancement factors up to 10(4)-10(5). It allows us to obtain the Raman spectra of surface water, having small Raman cross-section, on several transition metals for the first time. To expand the surface generality of SERS, tip-enhanced Raman spectroscopy (TERS) has been employed. With TERS, a nanogap can be formed controllably between an atomically flat metal surface and the tip with an optimized shape, within which the enhanced EM field from the tip can be coupled (borrowed) effectively. Therefore, one can obtain surface Raman signals (TERS signals) from adsorbed species at Au(110), Au(111) and, more importantly, Pt(l10) surfaces. The enhancement factor achieved on these single crystal surfaces can be up to 106, especially with a very high spatial resolution down to about 14 nm. To fully accomplish the borrowing strategy from different nanostructures and to explain the experimental observations, a three-dimensional finite-difference time-domain method was used to calculate and evaluate the local EM field on the core-shell nanoparticle surfaces and the TERS tips. Finally, prospects and further developments of this valuable strategy are briefly discussed with emphasis on the emerging experimental methodologies.     

表面增强拉曼光谱:应用和发展

表面增强拉曼光谱技术(Surface-enhanced Raman spectroscopy,SERS)是一种具有超高灵敏度的指纹光谱技术,目前已广泛应用于表面科学、材料科学、生物医学、药物分析、食品安全、环境检测等领域,是一种极具潜力的痕量分析技术。 本文对SERS技术及相关的针尖增强拉曼光谱(Tip-enhanced Raman spectroscopy,TERS),壳层隔绝纳米粒子增强拉曼光谱(Shell-isolated nanoparticle-enhanced Raman spectroscopy,SHINERS)技术的发展及应用进行了综合评述,并探讨了其未来的研究热点及发展方向。     

Surface bonding on silicon surfaces as probed by tip-enhanced Raman spectroscopy

Tip-enhanced Raman spectroscopy (TERS) has been used to obtain the Raman signal of surface species on silicon single crystal surfaces without the necessity for surface enhancement by addition of Ag nanoparticles. By illuminating the hydrogen terminated silicon surface covered with a droplet of 4-vinylpyridine with UV light, a 4-ethylpyridine modified silicon surface can be easily obtained. By bringing a scanning tunneling microscope (STM) Au tip with a nanoscale tip apex to a distance of ca. 1 nm from the m...     

TERS Detection of αVβ3 Integrins in Intact Cell Membranes

Integrins are important membrane receptors that form focal adhesions with the extracellular matrix and are transmembrane signaling proteins. We demonstrate that nanoparticles functionalized with c‐RGDfC ligands bind to intact cell membranes and selectively enhance the amino acid signals of the integrin receptor when coupled with tip‐enhanced Raman scattering (TERS) detection. Controlling the plasmonic interaction between the functionalized nanoparticle and the TERS tip provides a clear Raman signal from α_Vβ₃ integrins in the cell membrane that matches the signal of the purified integrin receptor. Random aggregation of nanoparticles on the cell does not provide the same spectral information. Chemical characterization of membrane receptors in intact cellular membranes is important for understanding membrane signaling and drug targeting. These results provide a new method to investigate the chemical interactions associated with ligand binding to membrane receptors in cells.     

Chemical Imaging of RNA-Tau Amyloid Fibrils at the Nanoscale Using Tip-Enhanced Raman Spectroscopy

In the presence of cofactors, tau protein can form amyloid deposits in the brain which are implicated in many neurodegenerative disorders. Heparin, lipids, and RNA are used to recreate tau aggregates in vitro from recombinant protein. However, the mechanism of interaction of these cofactors and the interactions between cofactors and tau are poorly understood. Herein, we use tip-enhanced Raman spectroscopy (TERS) to visualize the spatial distribution of adenine, protein secondary structure, and amino acids (arginine, lysine and histidine) in single polyadenosine (polyA)-induced tau fibrils with nanoscale spatial resolution (<10–20 nm). Based on reference unenhanced and surface-enhanced Raman spectra, we show that the polyA anionic cofactor is incorporated in the fibril structure and seems to be superficial to the β-sheet core, but nonetheless enveloped within the random-coiled fuzzy coat. TERS images also prove the colocalization of positively charged arginine, lysine, and histidine amino acids and negatively charged polyA, which constitutes an important step forward to better comprehend the action of RNA cofactors in the mechanism of formation of toxic tau fibrils. TERS appears as a powerful technique for the identification of cofactors in individual tau fibrils and their mode of interaction.     

Fabrication of a Biocompatible Mica/Gold Surface for Tip-Enhanced Raman Spectroscopy

Tip-enhanced Raman spectroscopy (TERS) is a promising technique for structural studies of biological systems and biomolecules, owing to its ability to provide a chemical fingerprint with sub-diffraction-limit spatial resolution. This application of TERS has thus far been limited, due to difficulties in generating high field enhancements while maintaining biocompatibility. The high sensitivity achievable through TERS arises from the excitation of a localized surface plasmon resonance in a noble metal atomic force microscope (AFM) tip, which in combination with a metallic surface can produce huge enhancements in the local optical field. However, metals have poor biocompatibility, potentially introducing difficulties in characterizing native structure and conformation in biomolecules, whereas biocompatible surfaces have weak optical field enhancements. Herein, a novel, biocompatible, highly enhancing surface is designed and fabricated based on few-monolayer mica flakes, mechanically exfoliated on a metal surface. These surfaces allow the formation of coupled plasmon enhancements for TERS imaging, while maintaining the biocompatibility and atomic flatness of the mica surface for high resolution AFM. The capability of these substrates for TERS is confirmed numerically and experimentally. We demonstrate up to five orders of magnitude improvement in TERS signals over conventional mica surfaces, expanding the sensitivity of TERS to a wide range of non-resonant biomolecules with weak Raman cross-sections. The increase in sensitivity obtained through this approach also enables the collection of nanoscale spectra with short integration times, improving hyperspectral mapping for these applications. These mica/metal surfaces therefore have the potential to revolutionize spectromicroscopy of complex, heterogeneous biological systems such as DNA and protein complexes.     

DFT vibrational calculations of rhodamine 6G adsorbed on silver: analysis of tip-enhanced Raman spectroscopy

The tip-enhanced near-field Raman (TERS) bands of Rhodamine 6G (R6G), that we reported earlier [Chem. Phys. Lett. 2001, 335, 369.], are assigned on the basis of density-functional theory (DFT) calculations at the 6-311++G(d,p) level. The Raman and infrared intensities as well as frequencies of the vibrational modes are used for band assignments. These vibrational modes, in combination with characterization of resonant electronic transitions using time-dependent DFT calculations, predict spectral changes in resonant Raman and surface-enhanced resonant Raman scatterings of R6G. Moreover, the TERS spectra of R6G are analyzed in detail, where interactions between the tip and R6G molecules and their enhancement mechanisms are discussed. Finally, we propose a novel Raman spectroscopy technique capable of detecting molecular vibrations at sub-nanometer scale.