Tip‐enhanced Raman spectroscopy – an interlaboratory reproducibility and comparison study

Since its first experimental realization, tip‐enhanced Raman spectroscopy (TERS) has emerged as a potentially powerful nanochemical analysis tool. However, questions about the comparability and reproducibility of TERS data have emerged. This interlaboratory comparison study addresses these issues by bringing together different TERS groups to perform TERS measurements on nominally identical samples. Based on the spectra obtained, the absolute and relative peak positions, number of bands, peak intensity ratios, and comparability to reference Raman and surface‐enhanced Raman spectroscopy (SERS) data are discussed. Our general findings are that all research groups obtained similar spectral patterns, irrespective of the setup or tip that was used. The TERS (and SERS) spectra consistently showed fewer bands than the conventional Raman spectrum. When comparing these three methods, the spectral pattern match and substance identification is readily possible. Absolute and relative peak positions of the three major signals of thiophenol scattered by 19 and 9 cm⁻¹, respectively, which can probably be attributed to different spectrometer calibrations. However, within the same group (but between different tips), the signals only scattered by 3 cm⁻¹ on average. This study demonstrated the suitability of TERS as an analytical tool and brings TERS a big step forward to becoming a routine technique. Copyright © 2014 John Wiley & Sons, Ltd.     

Electrochemical fabrication of silver tips for tip‐enhanced Raman spectroscopy assisted by a machine vision system

Both tip‐enhanced Raman spectroscopy and scanning tunneling microscopy require the use of sharp tips. Electrochemical etching appears to be the most widely used method for preparing tips. To address the over‐etching problem associated with the silver tips by either using voltage or current as a feedback, we developed here an optical method‐based machine vision to achieve a quick cutoff of the circuit once the tip forms. It is a fully automated method with a response time of about 40 ms and is tolerated with any existing electrochemical etching method. We can significantly decrease the time of over‐etching of the silver tip when short rectangular pulses with a duty cycle of 28.6% were used. The mean radius of curvature was ca. 58 nm, as measured from over 50 tips. The capacities of silver tips for high‐resolution scanning tunneling microscopy imaging and high‐sensitivity tip‐enhanced Raman studies have been demonstrated. Copyright © 2016 John Wiley & Sons, Ltd.     

Deep‐UV tip‐enhanced Raman scattering

We report for the first time the tip‐enhancement of resonance Raman scattering using deep ultraviolet (DUV) excitation wavelength. The tip‐enhancement was successfully demonstrated with an aluminum‐coated silicon tip that acts as a plasmonic material in DUV wavelengths. Both the crystal violet and adenine molecules, which were used as test samples, show electronic resonance at the 266‐nm excitation used in the experiments. With results demonstrated here, molecular analysis and imaging with nanoscale spatial resolution in DUV resonance Raman spectroscopy can be realized using the tip‐enhancement effect. Copyright © 2009 John Wiley & Sons, Ltd.     

Highly reproducible tip‐enhanced Raman scattering using an oxidized and metallized silicon cantilever tip as a tool for everyone

We have successfully improved the reproducibility of tip‐enhancement effect on metallized silicon cantilever tips for characterization of carbon nanotubes. Plasmon resonance tuning relative to an excitation wavelength is crucial for efficient tip‐enhancement, which is accomplished by thermal oxidization and subsequent metallization of commercial silicon tips. Because of the change of the refractive index of the tip from silicon to silicon dioxide, the plasmon resonance of the silver‐coated tip is blue‐shifted showing an enormous enhancement at 532 nm excitation. Highly reproducible tips exhibit an enhancement factor of >100 with a 100% yield. Because the tips are fabricated from commercially available silicon cantilever tips in a simple and robust way, our approach provides an important step of ‘tip‐enhanced Raman spectroscopy for everyone’. Copyright © 2012 John Wiley & Sons, Ltd.     

Enhancement of lattice defect signatures in graphene and ultrathin graphite using tip‐enhanced Raman spectroscopy

Understanding the role of defects in graphene is the key to tailoring the properties of graphene and promoting the development of graphene‐based devices. Defects can affect the electronic properties of a device while also offering a means by which to functionalize the local properties. Using tip‐enhanced Raman spectroscopy (TERS), heightened defect sensitivity was demonstrated on graphene edges, folds, and overlapping regions. Measurements confirm that TERS can provide simultaneous structural and spectral information on a localized scale, hence offering defect characterization on a scale that is not obtainable using conventional Raman spectroscopy. This study observed preferential enhancement of the D band signal on multilayered graphene and ultrathin graphite; in addition, other key defect signatures were also enhanced and detected. We present our findings in relation to theoretical predictions of graphene defect signatures and an analysis of the sensitivity of TERS in measuring two‐dimensional structures. Copyright © 2013 John Wiley & Sons, Ltd.     

Nano‐imaging through tip‐enhanced Raman spectroscopy: Stepping beyond the classical limits

The spatial resolution in optical imaging is restricted by so‐called diffraction limit, which prevents it to be better than about half of the wavelength of the probing light. Tip‐enhanced Raman spectroscopy (TERS), which is based on the SPP‐induced plasmonic enhancement and confinement of light near a metallic nanostructure, can however, overcome this barrier and produce optical images far beyond the diffraction limit. Here in this article, the basic phenomenon involved in TERS is reviewed, and the high spatial resolution achieved in optical imaging through this technique is discussed. Further, it is shown that when TERS is combined with some other physical phenomena, the spatial resolution can be dramatically improved. Particularly, by including tip‐applied extremely localized pressure in TERS process, it has been demonstrated that a spatial resolution as high as 4 nm could be achieved.     

Characterizing unusual metal substrates for gap‐mode tip‐enhanced Raman spectroscopy

In this article, the electromagnetic (EM) field in gap‐mode tip‐enhanced Raman spectroscopy (TERS) is investigated theoretically and experimentally for a range of commonly used and unusual metal and nonmetal substrates. By approaching a metal tip to a substrate, both form a coupled system that confines the EM field created at the tip apex. The influence of the substrate onto the EM field enhancement is observed in a top‐illumination gap‐mode TERS setup for different metal substrates. These include Au, the most commonly used substrate, and also a wide range of rarely or previously unused TERS substrates (Cu, Ag, Al, Pd, Pt, Ni, Ti, Mo, W, stainless steel, Al₂O₃, SiO₂). Self‐assembled monolayers of thiols and brilliant cresyl blue thin film samples are investigated experimentally on nine metal substrates, all showing considerable TERS enhancement. With finite difference time domain and finite element simulations used, the article provides a good estimate of the EM field enhancement for a wide range of substrates for users to estimate how well a substrate of choice will perform in a gap‐mode TERS experiment. The reduction in EM field strength |E²| compared with Au is less than an order of magnitude for many metals (Calculations: Cu 92%, Ag 81%, Ni 53%). This article experimentally shows that a wide variety of conductive substrates can be used, when one is willing to trade a fraction of the EM field enhancement. TERS was seen on all metal substrates including stainless steel, yet quantification was not always possible. These qualitative results were complemented with intensities from calculations. The wider variety of substrates will increase the applicability of TERS and evolve it one step further towards use in standard analytics. Copyright © 2012 John Wiley & Sons, Ltd.     

Surface‐enhanced Raman spectroscopy for trace‐level detection of explosives

The detection of explosives and their associated compounds for security screening is an active area of research and a wide variety of detection methods are involved in this very challenging area. Surface‐enhanced Raman scattering (SERS) spectroscopy is one of the most sensitive tools for the detection of molecules adsorbed on nano‐scale roughened metal surface. Moreover, SERS combines high sensitivity with the observation of vibrational spectra of species, giving complete information on the molecular structure of material under study. In this paper, SERS was applied to the detection of very small quantities of explosives adsorbed on industrially made substrates. The spectra were acquired with a compact Raman spectrometer. Usually, a high signal‐to‐noise (S/N) spectrum, suitable for identification of explosive molecules down to few hundreds of picograms, was achieved within 30 s. Our measurements suggest that it is possible to exploit SERS using a practical detection instrument for routine analysis. Copyright © 2010 John Wiley & Sons, Ltd.     

Gold‐coated zinc oxide nanowire‐based substrate for surface‐enhanced Raman spectroscopy

Zinc oxide nanowires with two distinct morphologies were synthesized on silicon substrates using a simple thermal evaporation and vapor transport method in an oxidizing environment. The as‐synthesized nanowires were coated with gold to allow excitation of surface plasmons over a broad frequency range. SERS studies with near‐IR excitation at 785 nm showed significant enhancement (average enhancement > 10⁶) with excellent reproducibility to detect monolayer concentrations of 4‐methylbenzenethiol (4‐MBT) and 1,2‐benzendithiol (1,2‐BDT) probe molecules. The Raman enhancement showed a strong dependence on the gold film thickness, and the peak enhancement was observed for a ∼40‐nm‐thick film. The Raman enhancement was stronger for randomly oriented nanowires compared to aligned ones suggesting the importance of contributions from the junctions of nanowires. Copyright © 2009 John Wiley & Sons, Ltd.     

In‐situ Raman spectroscopy of current‐carrying graphene microbridge

In‐situ Raman spectroscopy was performed on chemical vapor deposited graphene microbridge (3 μm × 80 μm) under electrical current density up to 2.58 × 10⁸ A/cm² in ambient conditions. We found that both the G and the G′ peak of the Raman spectra do not restore back to the initial values at zero current, but to slightly higher values after switching off the current through the microbridge. The up‐shift of the G peak and the G′ peak, after switching off the electrical current, is believed to be due to p‐doping by oxygen adsorption, which is confirmed by scanning photoemission microscopy. Both C–O and C=O bond components in the C1s spectra from the microbridge were found to be significantly increased after high electrical current density was flown. The C=O bond is likely the main source of the p‐doping according to our density functional theory calculation of the electronic structure. Copyright © 2014 John Wiley & Sons, Ltd.     

Understanding tip‐enhanced Raman spectra of biological molecules: a combined Raman,SERS and TERS study

Although conventional Raman, surface‐enhanced Raman (SERS) and tip‐enhanced Raman spectroscopy (TERS) have been known for a long time, a direct, thorough comparison of these three methods has never been carried out. In this paper, spectra that were obtained by conventional Raman, SERS (on gold and silver substrates) and TERS (in ‘gap mode’ with silver tips and gold substrates) are compared to learn from their differences and similarities. Because the investigation of biological samples by TERS has recently become a hot topic, this work focuses on biologically relevant substances. Starting from the TER spectra of bovine serum albumin as an example for a protein, the dipeptides Phe–Phe and Tyr–Tyr and the tripeptide Tyr–Tyr–Tyr were investigated. The major findings were as follows. (1) We show that the widely used assumption that spectral bands do not shift when comparing SER, TER and conventional Raman spectra (except due to binding to the metal surface in SERS or TERS) is valid. However, band intensity ratios can differ significantly between these three methods. (2) Marker bands can be assigned, which should allow one to identify and localize proteins in complex biological environments in future investigations. From our results, general guidelines for the interpretation of TER spectra are proposed. Copyright © 2012 John Wiley & Sons, Ltd.     

Ultraviolet tip‐enhanced nanoscale Raman imaging

We have constructed an ultraviolet (UV)‐apertureless near‐field scanning optical microscope‐Raman spectroscopy system by using an aluminum tip for the simultaneous measurement of topography and Raman scattering of nanomaterials with high spatial resolution. The topography, Rayleigh scattering image, and tip‐enhanced Raman scattering image of the carbon nanotube film showed that a spatial resolution of around 19 nm was achieved. This spatial resolution of UV‐Raman mapping image exceeds that of previous approaches, which have several hundred nanometers of spatial resolution. Copyright © 2012 John Wiley & Sons, Ltd.     

Multianalyte immunoassay based on surface‐enhanced Raman spectroscopy

In this paper, two immunoassay methods based on SERS are developed for multiplex analysis, both of which stemmed from the concept of forming a sandwich structure ‘capture antibody substrate/antigen/Raman‐reporter‐labeled immuno‐nanoparticles’. They are two‐molecule labeled one‐nanoparticle and one‐molecule labeled two‐nanoparticle methods. In both the methods, two different antibodies covalently bound to a solid substrate can specifically capture two different antigens from a sample. The captured antigens in turn bind selectively to their corresponding antibodies immobilized on Raman‐reporter‐labeled nanoparticles. Multianalyte immunoassay is successfully demonstrated by the detection of characteristic Raman bands of the probe molecules only when the antigen and antibody are matched. Copyright © 2007 John Wiley & Sons, Ltd.     

Experimental and statistical analysis methods for peptide detection using surface‐enhanced Raman spectroscopy

Surface‐enhanced Raman spectroscopy (SERS) has the potential to make a significant impact in biology research due to its ability to provide information orthogonal to that obtained by traditional techniques such as mass spectrometry (MS). While SERS has been well studied for its use in chemical applications, detailed investigations with biological molecules are less common. In addition, a clear understanding of how methodology and molecular characteristics impact the intensity, the number of peaks, and the signal‐to‐noise of SERS spectra is largely missing. By varying the concentration and order of addition of the SERS‐enhancer salt (LiCl) with colloidal silver, we were able to evaluate the impact of these variables on peptide spectra using a quantitative measure of spectra quality based on the number of peaks and peak intensity. The LiCl concentration and order of addition that produced the best SERS spectra were applied to a panel of synthetic peptides with a range of charges and isoelectric points (pIs) where the pI was directly correlated with higher spectral quality. Those peptides with moderate to high pIs and spectra quality scores were differentiated from each other using the improved method and a hierarchical clustering algorithm. In addition, the same method and algorithm was applied to a set of highly similar phosphorylated peptides, and it was possible to successfully classify the majority of peptides on the basis of species‐specific peak differences. Copyright © 2008 John Wiley & Sons, Ltd.     

Non‐invasive depth profiling by space and time‐resolved Raman spectroscopy

Time‐resolved Raman spectroscopy, spatially offset Raman spectroscopy and time‐resolved spatially offset Raman spectroscopy (TR‐SORS) have proven their capability for the non‐invasive profiling of deep layers of a sample. Recent studies have indicated that TR‐SORS exhibits an enhanced selectivity toward the deep layers of a sample. However, the enhanced depth profiling efficiency of TR‐SORS, in comparison with time‐resolved Raman spectroscopy and spatially offset Raman spectroscopy, is yet to be assessed and explained in accordance to the synergistic effects of spatial and temporal resolutions. This study provides a critical investigation of the depth profiling efficiency of the three deep Raman techniques. The study compares the efficiency of the various deep Raman spectroscopy techniques for the stand‐off detection of explosive precursors hidden in highly fluorescing packaging. The study explains for the first time the synergistic effects of spatial and temporal resolutions in the deep Raman techniques and their impact on the acquired spectral data. Copyright © 2013 John Wiley & Sons, Ltd.     

Plasmon‐enhanced Raman scattering by suspended carbon nanotubes

We report plasmon‐enhanced Raman scattering of the order of 10³ by a metallic carbon nanotube partially suspended inside a near‐field cavity. The tube is part of a small bundle, and is interfaced with an Au nanodisc dimer using a recently developed assembly scheme based on dielectrophoretic deposition. Spatially resolved Raman measurements with two excitation wavelengths and two orthogonal polarizations confirm that the enhancement arises from a 65 nm long suspended tube segment. We show that the orientation of the tube inside the cavity can be as effective for generating enhancement as placing the nanotube precisely in a plasmonic hotspot. Position and shape of the G‐peak show that the suspended part of the tube is free of strain and doped with a Fermi energy shift ≤40 meV. (© 2014 WILEY‐VCH Verlag GmbH &Co. KGaA, Weinheim)     

Silica‐overcoated substrates for detection of proteins by surface‐enhanced Raman spectroscopy

Ag film over nanosphere (AgFON) substrates for surface‐enhanced Raman spectroscopy (SERS) are shown to be ineffective for the detection of proteins in phosphate buffer solution (PBS) because of the decomposition of the substrate resulting in a total loss of SERS activity. However, modification of these substrates with SiO₂ overlayers overcomes this problem. The SiO₂ overlayers are produced by filtered arc deposition (FAD) and are characterised by atomic force microscopy (AFM). Their porosity is examined using Raman spectroscopy and the detection of cytochrome c and bovine serum albumin in PBS is successfully demonstrated. These findings show promise for the detection of proteins in biologically relevant conditions using Ag‐based SERS substrates. Copyright © 2008 John Wiley & Sons, Ltd.     

Exploring the origin of tip‐enhanced Raman scattering; preparation of efficient TERS probes with high yield

Tip‐enhanced Raman scattering (TERS) spectroscopy is a promising technique for nanoscale chemical analysis. However, there are several challenges preventing widespread application of this technology, including reproducible fabrication of efficient TERS probes. These problems reflect a lack of clear understanding of the origins of, and the parameters influencing TERS. It is believed that the coating characteristics at the apex of the tip have a major effect on the near‐field optical enhancement and thus the TERS activity of a metalized probe. Here we show that the aspect ratio of the tip can play a significant role in the efficiency of TERS probes. We argue that the electrostatic field arising from the lightning‐rod effect has a substantial role in the observed TERS effect. This argument is supported by ‘edge‐enhanced Raman scattering’ which is shown for a noble metal film. Furthermore, it is reported that an associated tip‐surface‐enhanced Raman scattering effect can be achieved by using a TERS‐inactive metalized probe on a surface‐enhanced Raman spectroscopy‐inactive roughened surface. This observation can be explained by an interparticle enhancement of the electromagnetic field. Copyright © 2011 John Wiley & Sons, Ltd.     

Detection of melamine in liquid milk using surface‐enhanced Raman scattering spectroscopy

Melamine, a nitrogen‐rich chemical, has recently caused enormous economic losses to the food industry due to the cases of milk products adulterated by melamine. This has led to an urgent need of rapid and reliable methods for detection of melamine in food. In this study, surface‐enhanced Raman scattering (SERS) spectroscopy was used to detect melamine in liquid milk. The sample preparation with liquid milk is very easy; it has to be only diluted with double‐distilled water followed by centrifugation. By using a silver colloid, at least a 10⁵‐fold enhancement of the Raman signal was achieved for the measurement of melamine. The limit of detection by this method was 0.01 µg ml⁻¹ for melamine standard samples. Based on the intensity of the Raman vibrational bands normalised to that of the band at 928 cm⁻¹ (CH₂), an external standard method was employed for quantitative analysis. The linear regression square (R²) of the curve was 0.9998; the limit of quantitation using this approach was 0.5 µg ml⁻¹ of melamine in liquid milk; the relative standard deviation was ≤10%; and recoveries were from 93 to 109%. The test results for SERS were very precise and as good as those obtained by liquid chromatography/tandem mass spectrometry. The method was simple, fast(only needs about 3 min), cost effective, and sensitive for the detection of melamine in liquid milk samples. Therefore, it is more suitable for the field detection of melamine in liquid milk. Copyright © 2010 John Wiley & Sons, Ltd.     

Tip‐based plasmonics: squeezing light with metallic nanoprobes

Nanofabricated metallic tips are at the core of important research in single‐molecule imaging, near‐field scanning optical microscopy, tip‐enhanced Raman spectroscopy, as well as potential commercial applications such as heat‐assisted magnetic recording. While challenging to fabricate, much progress has been made towards the reliable production of extremely sharp (10 nm) metallic probes. In this review, the various factors that go into the design of metallic tips, their fabrication, packaging and system integration, characterization, passivation, and eventual use are discussed. Fabrication challenges, implementation issues, optical excitation schemes, and various current and emerging applications are also discussed. For the rapidly emerging fields of plasmonics and nanophotonics, the use of sharp metallic tips has generated significant scientific progress and will play an integral role well into the future.