Optimising reproducibility in low quality signals without smoothing; an alternative paradigm for signal processing

Raman spectroscopy has been revolutionised in recent decades by major technological advances such as lasers, charge‐coupled detectors (CCD) and notch/edge filters. In contrast the development of signal processing algorithms has progressed at a slower pace. Spectroscopic applications increasingly focus on ‘real‐world’ applications that are not under highly controlled conditions and with more stringent limitations placed on acquisition conditions (e.g. low power for in vivo and explosives analysis). Often it is necessary to work with signals of a quality traditionally considered poor. In this study an alternative paradigm for signal processing poor quality signals is presented and rigorously assessed. Instead of estimating the background on the individual signals it is estimated on the results of a multivariate analysis. Under this paradigm prediction reproducibility is unaffected by the signal processing, unlike the traditional paradigm of correcting individual signals which induces errors that propagate through to the prediction. The paradigms were tested on a ‘real‐world’ dataset to predict the concentration of a pathologically relevant protein modification, carboxymethyl lysine (CML). Use of the new paradigm allowed signals with a signal to noise ratio (SNR) of 2.4 to give a prediction with variance just 8.7% of the mean, with the traditional paradigm giving a variance of over 140% of the mean. Significant improvement in reproducibility could even be observed with signals as good as SNR 85. The ability to obtain reproducible predictions from low quality signals allows shorter acquisition (e.g. mapping or on‐line analysis), use of low powers (in vivo diagnostics, hazardous materials analysis (HAZMAT)) or use of cheaper equipment. Copyright © 2011 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.     

An intelligent background‐correction algorithm for highly fluorescent samples in Raman spectroscopy

Fluorescent background is a major problem in recoding the Raman spectra of many samples, which swamps or obscures the Raman signals. The background should be suppressed in order to perform further qualitative or quantitative analysis of the spectra. For this purpose, an intelligent background‐correction algorithm is developed, which simulates manual background‐correction procedure intelligently. It basically consists of three aspects: (1) accurate peak position detection in the Raman spectrum by continuous wavelet transform (CWT) with the Mexican Hat wavelet as the mother wavelet; (2) peak‐width estimation by signal‐to‐noise ratio (SNR) enhancing derivative calculation based on CWT but with the Haar wavelet as the mother wavelet; and (3) background fitting using penalized least squares with binary masks. This algorithm does not require any preprocessing step for transforming the spectrum into the wavelet space and can suppress the fluorescent background of Raman spectra intelligently and validly. The algorithm is implemented in R language and available as open source software ( http://code.google.com/p/baselinewavelet ). Copyright © 2009 John Wiley & Sons, Ltd.     

Quantitative detection of captopril in tablet and blood plasma samples by the combination of surface‐enhanced Raman spectroscopy with multiplicative effects model

With p‐thiocresol as internal standard, quantitative analysis of captopril, a synthetic angiotensin converting enzyme inhibitor, was achieved by the combination of the multiplicative effects model with surface‐enhanced Raman spectroscopy (SERS). The multiplicative effects model was adopted to correct the detrimental effects caused by the heterogeneity in the physical properties of enhancing substrate (i.e. Ag nano‐particles). Experimental results showed that the calibration model built on the SERS spectra of the calibration captopril samples prepared with ultrapure water could attain quite satisfactory concentration predictions for captopril in both real‐world tablet samples and plasma samples. The recovery rates were in the range of 94.3% to 109.8%, which were in substantial agreement with the corresponding results of LC‐MS/MS. The limit of detection and limit of quantification were estimated to be 0.149 and 0.451 μM, respectively. The proposed approach has advantages of relatively low cost, simplicity, high sensitivity and good accuracy and therefore can be further developed and extended to a routine method for the quantification of captopril in complex systems. Copyright © 2015 John Wiley & Sons, Ltd.     

The characteristics of laser‐driven shock wave investigated by time‐resolved Raman spectroscopy

An accurate and simple method, Raman peak‐shift simulation, is proposed to determine the characteristics of a laser‐driven shock wave. Using the principle of the Raman peaks shifting at high pressure and the pressure distribution in the gauge layer, the profile of the Raman peak can be numerically simulated. Combined with time‐resolved Raman spectroscopy, some main characteristics of the shock wave were determined. In the experiment, polycrystalline anthracene was used as the pressure gauge. The pump–probe technique was used to obtain the time‐resolved Raman spectra of anthracene under shock loading. The velocity of the shock wave, the peak pressure and the rise time of the shock front were determined by simulating the experimental spectra numerically. The result shows that the method of Raman peak‐shift simulation is effective in obtaining the characteristics of a laser‐driven shock wave. Copyright © 2010 John Wiley & Sons, Ltd.     

Raman spectroscopy of gallium‐ and zinc‐based hydrotalcites

Insight into the unique structure of hydrotalcites (HTs) has been obtained using Raman spectroscopy. Gallium‐containing HTs of formula Zn₄ Ga₂(CO₃)(OH)₁₂ · xH₂O (2:1 ZnGa‐HT), Zn₆ Ga₂(CO₃)(OH)₁₆ · xH₂O (3:1 ZnGa‐HT) and Zn₈ Ga₂(CO₃)(OH)₁₈ · xH₂O (4:1 ZnGa‐HT) have been successfully synthesised and characterised by X‐ray diffraction (XRD) and Raman spectroscopy. The d(003) spacing varies from 7.62 Å for the 2:1 ZnGa‐HT to 7.64 Å for the 3:1 ZnGa‐HT. The 4:1 ZnGa‐HT showed a decrease in the d(003) spacing, compared to the 2:1 and 3:1 compounds. Raman spectroscopy complemented with selected infrared data has been used to characterise the synthesised gallium‐containing HTs. Raman bands observed at around 1050, 1060 and 1067 cm⁻¹ are attributed to the symmetric stretching modes of the (CO₃²⁻) units. Multiple ν₃ (CO₃²⁻) antisymmetric stretching modes are found between 1350 and 1520 cm⁻¹, confirming multiple carbonate species in the HT structure. The splitting of this mode indicates that the carbonate anion is in a perturbed state. Raman bands observed at 710 and 717 cm⁻¹ and assigned to the ν₄ (CO₃²⁻) modes support the concept of multiple carbonate species in the interlayer. Copyright © 2010 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.     

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.     

Application of portable Raman spectroscopy and benchtop spatially offset Raman spectroscopy to interrogate concealed biomaterials

In this paper, we demonstrate the ability of portable Raman spectroscopy and benchtop spatially offset Raman spectroscopy (SORS) techniques to rapidly identify real and fake ivory samples. Both techniques were able to identify exposed genuine from fake ivory samples. In contrast to conventional Raman spectroscopy, SORS was, in addition, able to identify ivory concealed by plastics, paints, varnishes and cloth. Application of the SORS technique allows the interrogation of biomaterial samples through materials in which conventional Raman spectroscopic instrumentation cannot penetrate. Copyright © 2009 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.     

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.     

Recent advances in linear and non‐linear Raman spectroscopy. Part III

Following the first two reviews on recent advances in linear and non‐linear Raman spectroscopy, the present review summarises papers mainly published in the Journal of Raman Spectroscopy during 2008. This again serves to give a brief overview of recent advances in this research field and to provide readers of this journal a quick introduction to the various sub‐fields of Raman spectroscopy. It also reflects the current research interests and trends in the Raman community. Copyright © 2009 John Wiley & Sons, Ltd.     

Recent advances in linear and non‐linear Raman spectroscopy. Part IX

This annual review is published to provide an overview of advances in the field of Raman spectroscopy as reflected in papers published each year in the Journal of Raman Spectroscopy (JRS) as well as in trends across related journals that have published papers in the broad field of Raman spectroscopy. The content is obtained from statistical data on article counts obtained from Thomson Reuters ISI Web of Science Core Collection by year and by subfield of Raman spectroscopy. Additional information is gleaned from presentations at the VIII International Conference on Advanced Vibrational Spectroscopy (ICAVS‐8) in Vienna, Austria in July 2015 and those featuring Raman scattering at SCIX 2015 organized by the Federation of Analytical Chemistry and Spectroscopy Societies (FACSS) in Providence, Rhode Island, USA, in September/October 2015. Coverage is also provided for topics from the conference ECONOS 2015 held in April in Leuven, Belgium. Finally, papers published in JRS in 2014 are highlighted and arranged by topics at the frontier of Raman spectroscopy. Taken from these various viewpoints, it is clear that Raman spectroscopy continues to be a rapidly expanding field that provides sensitive photonic information of matter at the molecular level in an ever‐widening arena of novel applications. Copyright © 2015 John Wiley & Sons, Ltd.     

Measurement and calculation of the Q‐branch spectrum of nitrogen using inverse Raman spectroscopy and cw Raman‐induced polarization spectroscopy

The techniques of inverse Raman spectroscopy, Raman‐induced polarization spectroscopy (RIPS), and optical heterodyne RIPS (OHD‐RIPS) are compared by probing the Q‐branch of the nitrogen molecule. The signal is measured employing either a photomultiplier tube (low background level–RIPS) or a photodetector (high background level–IRS and OHD‐RIPS). The measurements are performed using atmospheric mixtures of N₂ Ar with concentrations varying from 0 to 79% N₂. This strategy permits estimation of detection limits using the different techniques. Pump and probe energy levels are varied independently to study signal dependence on laser irradiance. A theoretical treatment is presented on the basis of the Raman susceptibility equations, which permits the calculation of spectra for all three techniques. Calculated Q‐branch spectra are compared with the measured spectra for the interactions of a linearly polarized probe beam with a linearly or circularly polarized pump beam. The polarizer angle in the detection path for OHD‐RIPS has a dramatic effect on the shape of the spectrum. The calculated and experimental OHD‐RIPS spectra are in good agreement over the entire range of investigated polarizer angles. Detection limits using these techniques are analyzed to suggest their applicability for measuring other species of importance in combustion and plasma systems. Copyright © 2007 John Wiley & Sons, Ltd.     

Applications of Raman spectroscopy in herbal medicine

Raman spectroscopic techniques are a group of chemical fingerprint detection methods based on molecular vibrational spectroscopy. They are compatible with aqueous solutions and are time saving, nondestructive, and highly informative. With complementary and alternative medicine (CAM) becoming increasingly popular, more people are consuming natural herbal medicines. Thus, chemical fingerprints of herbal medicines are investigated to determine the content of these products. In this study, I review the different types of Raman spectroscopic techniques used in fingerprinting herbal medicines, including dispersive Raman spectroscopy, resonance Raman spectroscopy, Fourier transform (FT)–Raman spectroscopy, surface-enhanced Raman scattering (SERS) spectroscopy, and confocal/microscopic Raman spectroscopy. Lab-grade Raman spectroscopy instruments help detect the chemical components of herbal medicines effectively and accurately without the need for complicated separation and extraction procedures. In addition, portable Raman spectroscopy instruments could be used to monitor the health and safety compliance of herbal products in the consumer market.     

Trace level detection and identification of nitro‐based explosives by surface‐enhanced Raman spectroscopy

Methods for rapid identification of explosives and their associated compounds at trace level quantities are needed for security screening applications. In this paper, we apply the surface‐enhanced Raman spectroscopy (SERS) to detect and identify traces (as low as tens of pg) of pentaerythritol tetranitrate (PETN), ethylene glycol dinitrate (EGDN), cyclotrimethylene‐trinitramine (RDX) and trinitrotoluene (TNT) using commercially available substrates (Klarite®, Renishaw diagnostics). High quality spectra were achieved within 10 s with a compact Raman spectrometer. Principal component analysis (PCA) of the data was performed to understand what factors affected the spectral variation across the samples. It was found that 76% of the spectral variation was explained by the first three PCs. Score plots for these components showed that the energetic materials can be clearly classified on the basis of SERS spectra also at trace level quantity. Our measurements further demonstrate the potential for using SERS as fast, in situ analytical tool for safety devices, with a sensitivity which competes and, in some cases, overcomes other techniques. Copyright © 2013 John Wiley & Sons, Ltd.     

Subtracted shifted Raman spectroscopy of organic dyes and lakes

Resonance Raman spectroscopy has been utilized to identify vegetal and animal dyes and lakes. These compounds have been used by artists since antiquity, and their identification has important implications in art history and conservation. The resonance condition is useful when working with real ancient objects so as to enhance the Raman scattering of chromophores with respect to the strong signal of the matrix, such as the textile or parchment over which the colorant is supported. The strong fluorescence that generally characterizes the resonance Raman spectra was eliminated by using subtracted shifted Raman spectroscopy (SSRS). A systematic study on reference organic dyes was primarily carried out to evaluate the suitability of the method and to estimate the strengths and limitations of the spectrum reconstruction process. The method was then applied to the noninvasive identification of madder on ancient dyed silk textiles such as an altar table cloth and a manutergium attributed to the Egyptian artistic textile production of the 10th–11th Century A.D. Copyright © 2009 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.     

Ultrafast Raman loss spectroscopy

This paper deals with a new form of nonlinear Raman spectroscopy called ‘ultrafast Raman loss spectroscopy (URLS)’. URLS is analogous to stimulated Raman spectroscopy (SRS) but is much more sensitive than SRS. The signals are background (noise) free unlike in coherent anti‐Stokes Raman spectroscopy (CARS) and it provides natural fluorescence rejection, which is a major problem in Raman spectroscopy. In addition, being a self‐phase matching process, the URLS experiment is much easier than CARS, which requires specific phase matching of the laser pulses. URLS is expected to be alternative if not competitive to CARS microscopy, which has become a popular technique in applications to materials, biology and medicine. Copyright © 2009 John Wiley & Sons, Ltd.     

Simple and inexpensive instrument for deep‐UV Raman spectroscopy

Deep‐UV Raman spectroscopy is a powerful way to collect chemically specific information about complex samples. The availability of inexpensive and reliable light sources in the spectral region below 250 nm has been always considered a major bottleneck problem on the way of a widespread of this powerful spectroscopic technique. We report on the efficient fourth‐harmonic generation of a low‐power microchip Nd:YAG laser operating at 946 nm. High‐quality deep‐UV Raman spectra were collected using a newly developed laser source. Copyright © 2013 John Wiley & Sons, Ltd.