Noninvasive detection of concealed liquid explosives using Raman spectroscopy

We present a Raman spectroscopic method for the noninvasive detection of liquid explosives within bottles, and other packaging, of substantially higher sensitivity and wider applicability than that currently available via conventional Raman spectroscopy. The approach uses a modification of the spatially offset Raman spectroscopy (SORS) concept, which permits the interrogation of a wide range of containers, including transparent, colored, and diffusely scattering plastic and glass beverage, medicine, and cosmetic bottles, with no change in experimental geometry. The enhanced sensitivity is achieved by the technique's inherent ability to effectively suppress fluorescence and Raman contributions originating from the wall of the container. The application is demonstrated on the noninvasive detection of hydrogen peroxide solution, a critical component of a number of liquid explosives. In contrast to conventional Raman spectroscopy, the modified SORS concept enables the detection of concealed hydrogen peroxide solution in all the studied cases.     

Superficial‐Layer‐Enhanced Raman Scattering (SLERS) for Depth Detection of Noncontact Molecules

Although the strength of Raman signals can be increased by many orders of magnitude on noble metal nanoparticles, this enhancement is confined to an extremely short distance from the Raman‐active surface. The key to the development of Raman spectroscopy for applications in diagnosis and detection of cancer and inflammatory diseases, and in pharmacology, relies on the capability of detecting analytes that are noninteractive with Raman‐active surfaces. Here, a new Raman enhancement system is constructed, superficial‐layer‐enhanced Raman scattering (SLERS), by covering elongated tetrahexahedral gold nanoparticle arrays with a superficial perovskite (CH₃NH₃PbBr₃) film. Plasmonic decay is depressed along the vertical direction away from the noble metal surface and the penetration depth is increased in the perovskite media. The vertical penetration of SLERS is verified by the spatial distribution of the analytes via Raman imaging in layer‐scanning mode.     

Chitosan-coated anisotropic silver nanoparticles as a SERS substrate for single-molecule detection

Surface-enhanced Raman spectroscopy (SERS) is a technique that has become widely used for identifying and providing structural information about molecular species in low concentration. There is an ongoing interest in finding optimum particle size, shape and spatial distribution for optimizing the SERS substrates and pushing the sensitivity toward the single-molecule detection limit. This work reports the design of a novel, biocompatible SERS substrate based on small clusters of anisotropic silver nanoparticles embedded in a film of chitosan biopolymer. The SERS efficiency of the biocompatible film is assessed by employing Raman imaging and spectroscopy of adenine, a significant biological molecule. By combining atomic force microscopy with SERS imaging we find that the chitosan matrix enables the formation of small clusters of silver nanoparticles, with junctions and gaps that greatly enhance the Raman intensities of the adsorbed molecules. The study demonstrates that chitosan-coated anisotropic silver nanoparticle clusters are sensitive enough to be implemented as effective plasmonic substrates for SERS detection of nonresonant analytes at the single-molecule level.     

Multicomponent blood analysis by near-infrared Raman spectroscopy

We demonstrate the use of Raman spectroscopy to measure the concentration of many important constituents (analytes) in serum and whole blood samples at physiological concentration in vitro across a multipatient data set. A near-infrared (830-nm) diode laser generates Raman spectra that contain superpositions of Raman signals from different analytes. Calibrations for glucose, cholesterol, urea, and other analytes are developed by use of partial least-squares cross validation. We predict six analytes in serum with significant accuracy in a 66-patient data set, using 60-s spectra. The calibrations are shown to be fairly robust against system drift over the span of seven weeks. In whole blood, a preliminary analysis yields accurate predictions of some of the same analytes and also hematocrit. The results hold promise for potential medical applications.     

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

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

Butterfly-wing hierarchical metallic glassy nanostructure for surface enhanced Raman scattering

Nano Research - The surface-enhanced Raman spectroscopy (SERS) is a technique for the detection of analytes on the surface with an ultrahigh sensitivity down to the atomic-scale, yet the...     

Bio-imaging, detection and analysis by using nanostructures as SERS substrates

Surface-enhanced Raman scattering (SERS) is a phenomenon that occurs on nanoscale-roughed metallic surface. The magnitude of the Raman scattering signal can be greatly enhanced when the scatterer is placed in the very close vicinity of the surface, which enables this phenomenon to be a highly sensitive analytical technique. SERS inherits the general strongpoint of conventional Raman spectroscopy and overcomes the inherently small cross section problem of a Raman scattering. It is a sensitive and nondestructive spectroscopic method for biological samples, and can be exploited either for the delivery of molecular structural information or for the detection of trace levels of analytes. Therefore, SERS has long been regarded as a powerful tool in biomedical research. Metallic nanostructure plays a key role in all the biomedical applications of SERS because the enhanced Raman signal can only be obtained on the surface of a finely divided substrate. This review focuses on progress made in the use of SERS as an analytical technique in bio-imaging, analysis and detection. Recent progress in the fabrication of SERS active nanostructures is also highlighted.     

Semi-automated detection of trace explosives in fingerprints on strongly interfering surfaces with Raman chemical imaging

We have previously demonstrated the use of wide-field Raman chemical imaging (RCI) to detect and identify the presence of trace explosives in contaminated fingerprints. In this current work we demonstrate the detection of trace explosives in contaminated fingerprints on strongly Raman scattering surfaces such as plastics and painted metals using an automated background subtraction routine. We demonstrate the use of partial least squares subtraction to minimize the interfering surface spectral signatures, allowing the detection and identification of explosive materials in the corrected Raman images. The resulting analyses are then visually superimposed on the corresponding bright field images to physically locate traces of explosives. Additionally, we attempt to address the question of whether a complete RCI of a fingerprint is required for trace explosive detection or whether a simple non-imaging Raman spectrum is sufficient. This investigation further demonstrates the ability to nondestructively identify explosives on fingerprints present on commonly found surfaces such that the fingerprint remains intact for further biometric analysis.     

Trace explosive detection in aqueous samples by solid-phase extraction ion mobility spectrometry (SPE-IMS)

Law enforcement agencies use ion mobility spectrometers for the detection of explosives, drugs of abuse, and chemical warfare agents. Ion mobility spectrometry (IMS) has the advantages of short analysis times, detections in the parts per billion concentrations, and high sensitivity. On-site environmental analysis of explosives or explosive residues in water is possible with ion mobility spectrometers. Unfortunately, the direct analysis of low levels of explosives in water is difficult. Extraction provides a method for pre-concentrating the analytes and removing interferents. Coupling solid-phase extraction (SPE) with IMS is useful for the identification of trace amounts of explosives in water. Commercially available SPE disks were used. After extraction, the sample disk is inserted into the ion mobility spectrometer, where the analytes are thermally desorbed from the disk. Concentrations as low as one part per trillion were detected with a Barringer Ionscan 350. An external computer and acquisition software (LabVIEW, National Instruments) were used to collect data. SIMPLISMA (SIMPLe-to-use-Interactive Self-modeling Mixture Analysis) was applied to the data to resolve features that vary with respect to time.     

Remote Raman spectroscopy for planetary exploration: a review

In this review, we discuss the current state of standoff Raman spectroscopy as it applies to remote planetary applications, including standoff instrumentation, the technique's ability to identify biologically and geologically important analytes, and the feasibility to make standoff Raman measurements under various planetary conditions. This is not intended to be an exhaustive review of standoff Raman and many excellent papers are not mentioned. Rather it is intended to give the reader a quick review of the types of standoff Raman systems that are being developed and that might be suitable for astrospectroscopy, a look at specific analytes that are of interest for planetary applications, planetary measurement opportunities and challenges that need to be solved, and a brief discussion of the feasibility of making surface and plume planetary Raman measurements from an orbiting spacecraft.     

Effect of oxidation on surface-enhanced Raman scattering activity of silver nanoparticles: a quantitative correlation

We quantitatively studied, using X-ray photoelectron spectroscopy (XPS), oxidation of substrate-immobilized silver nanoparticles (Ag NPs) in a wide range of conditions, including exposure to ambient air and controlled ozone environment under UV irradiation, and we correlated the degree of silver oxidation with surface-enhanced Raman scattering (SERS) enhancement factors (EFs). The SERS activity of pristine and oxidized Ag NPs was assessed by use of trans-1,2-bis(4-pyridyl)ethylene (BPE) and sodium thiocynate as model analytes at the excitation wavelength of 532 nm. Our study showed that the exposure of Ag NPs to parts per million (ppm) level concentrations of ozone led to the formation of Ag(2)O and orders of magnitude reduction in SERS EFs. Such an adverse effect was also notable upon exposure of Ag NPs under ambient conditions where ozone existed at parts per billion (ppb) level. The correlated XPS and SERS studies suggested that formation of just a submonolayer of Ag(2)O was sufficient to decrease markedly the SERS EF of Ag NPs. In addition, studies of changes in plasmon absorption bands pointed to the chemical enhancement as a major reason for deterioration of SERS signals when substrates were pre-exposed to ambient air, and to a combination of changes in chemical and electromagnetic enhancements in the case of substrate pre-exposure to elevated ozone concentrations. Finally, we also found UV irradiation and ozone had a synergistic effect on silver oxidation and thus a detrimental effect on SERS enhancement of Ag NPs and that such oxidation effects were analyte-dependent, as a result of inherent differences in chemical enhancements and molecular binding affinities for various analytes.     

Molecular imaging with SERS-active nanoparticles

Raman spectroscopy has been explored for various biomedical applications (e.g., cancer diagnosis) because it can provide detailed information on the chemical composition of cells and tissues. For imaging applications, several variations of Raman spectroscopy have been developed to enhance its sensitivity. To date, a wide variety of molecular targets and biological events have been investigated using surface-enhanced Raman scattering (SERS)-active nanoparticles. The superb multiplexing capability of SERS-based Raman imaging, already successfully demonstrated in live animals, can be extremely powerful in future research where different agents can be attached to different Raman tags to enable the simultaneous interrogation of multiple biological events. Over the last several years, molecular imaging with SERS-active nanoparticles has advanced significantly and many pivotal proof-of-principle experiments have been successfully carried out. It is expected that SERS-based imaging will continue to be a dynamic research field over the next decade.     

Probing the effect of molecular orientation on the intensity of chemical enhancement using graphene-enhanced Raman spectroscopy

A rational approach to investigate the effect of molecular orientation on the intensity of chemical enhancement using graphene-enhanced Raman spectroscopy (GERS) is developed. A planar molecule, copper phthalocyanine (CuPc), is used as probe molecule. Annealing allows the CuPc molecule in a Langmuir-Blodgett film to change orientation from upstanding to lying down. The UV-visible absorption spectra prove the change of the molecular orientation, as well as the variation of the interaction between the CuPc molecule and graphene. The Raman spectra of the molecule in the two different orientations are compared and analyzed. The results show that chemical enhancement is highly sensitive to the molecular orientation. The different molecular orientations induce different magnitudes of the interaction between the molecule and graphene. The stronger the interaction, the more the Raman signal is enhanced. Furthermore, the sensitivity of GERS to molecular orientation is promising to determine the orientation of the molecule on graphene. Based on this molecular orientation sensitive Raman enhancement, quantitative calculation of the magnitude of the chemical enhancement is implemented for a series of Pc derivatives. It shows that the magnitude of the chemical enhancement can be used to evaluate the degree of interaction between the molecules and graphene. Moreover, an understanding of the chemical enhancement in GERS is promoted and the effect of molecular orientation on the intensity of chemical enhancement is explained.     

Airborne chemistry coupled to Raman spectroscopy

In this paper, the use of airborne chemistry (acoustically levitated drops) in combination with Raman spectroscopy is explored. We report herein the first Raman studies of crystallization processes in levitated drops and the first demonstration of surface-enhanced Raman scattering (SERS) detection in this medium. Crystallization studies on the model compounds benzamide and indomethacin resulted in the formation of two crystal modifications for each compound, suggesting that this methodology may be useful for investigation of polymorphs. SERS detection resulted in a signal enhancement of 27 000 for benzoic acid and 11 000 for rhodamine 6-G. The preliminary results presented here clearly indicate that several important applications of the combination between Raman spectroscopy and acoustic drop levitation can be expected in the future.     

Carbon nanotube-tipped endoscope for in situ intracellular surface-enhanced Raman spectroscopy

Gold nanoparticle-decorated carbon nanotubes (CNTs) are used to study intracellular environments in situ using surface-enhanced Raman spectroscopy (SERS). CNTs are decorated with gold nanoparticles and assembled onto the tips of pulled glass capillaries to form a SERS-enabled endoscope. The sub-micrometer size and high mechanical strength of the endoscope make it possible to penetrate the cell membrane for intracellular probing and remain positioned inside during lengthy SERS measurements without causing damage to the cell. Using the SERS-enabled endoscope, DNA and other biomolecules are detected in situ within the nucleus of a single human cervical carcinoma cell in a minimally invasive manner. The SERS-enabled endoscopes exhibit high selectivity and sensitivity for detecting trace amounts of analytes (≈1 pM) in biofluid environments, highlighting their capabilities as label-free, biological sensors for real-time in situ cellular diagnostics, biological detection, and pharmaceutical research.     

Dependence of signal on depth in transmission Raman spectroscopy

Recently, transmission Raman spectroscopy has been shown to be a valuable tool in the volumetric quantification of pharmaceutical formulations. In this work a Monte Carlo simulation and experimental study are performed to elucidate the dependence of the Raman signal on depth from the viewpoint of probing pharmaceutical tablets and powders in this experimental configuration. The transmission Raman signal is shown to exhibit a moderate bias toward the center of the tablets and this can be considerably reduced by using a recently developed Raman signal-enhancing concept, the "photon diode." The enhancing element not only reduces the bias but also increases the overall Raman signal intensity and consequently improves the signal-to-noise ratio of the measured spectrum. Overall, its implementation with appropriately chosen reflectivity results in a more uniform volumetric sampling across the half of the tablet where the photon diode is used (or across the tablet's entire depth if two photon diodes are used on each side of tablet) and enhanced overall sensitivity. These findings are substantiated experimentally on a segmented tablet by inserting a poly(ethelyne terephthalate) (PET) film doped with TiO(2) at different depths and monitoring its contribution to the overall transmission Raman signal from the segmented tablet. The numerical simulations also indicate considerable sensitivity of the overall Raman signal to the absorption of the sample, which is in line with large migration distances traversed by photons in these measurements. The presence of sample absorption was shown numerically to reduce the signal enhancement effect while the overall depth-dependence profile remained broadly unchanged. The absorption was also shown to produce a depth profile with the photon diode similar to that without it, although with a reduced absolute intensity of Raman signals and diminished enhancement effect.     

Spectral tuning of localised surface plasmon-polariton resonance in metallic nano-crescents

The utilisation of plasmonic effects in metallic nanostructures is gaining importance for applications in molecular sensing. Of special interest is the local field enhancement effect, which enables surface-enhanced Raman scattering and significantly boosts the sensitivity of the Raman technique. For in vivo biological research, the ability to excite the resonance of localised surface plasmon-polaritons within the biological window is often desired. A new nanostructure called the nano-crescent is introduced and exhibits strong plasmonic activities within the biological window using a novel intra-particle plasmonic coupling scheme.     

Surface enhanced coherent anti-stokes Raman scattering on nanostructured gold surfaces

Coherent anti-Stokes Raman spectroscopy (CARS) is a well-known tool in multiphoton imaging and nonlinear spectroscopy. In this work we combine CARS with plasmonic surface enhancement on reproducible nanostructured surfaces. We demonstrate strong correlation between plasmon resonances and surface-enhanced CARS (SECARS) intensities on our nanostructured surfaces and show that an enhancement of ～10(5) can be obtained over standard CARS. Furthermore, we find SECARS to be >10(3) times more sensitive than surface-enhanced Raman Spectroscopy (SERS). We also demonstrate SECARS imaging of molecular monolayers. Our work paves the way for reliable single molecule Raman spectroscopy and fast molecular imaging on plasmonic surfaces.     

Multiplexed microfluidic surface-enhanced Raman spectroscopy

Over the past few decades, surface-enhanced Raman spectroscopy (SERS) has garnered respect as an analytical technique with significant chemical and biological applications. SERS is important for the life sciences because it can provide trace level detection, a high level of structural information, and enhanced chemical detection. However, creating and successfully implementing a sensitive, reproducible, and robust SERS active substrate continues to be a challenging task. Herein, we report a novel method for SERS that is based upon using multiplexed microfluidics (MMFs) in a polydimethylsiloxane platform to perform parallel, high throughput, and sensitive detection/identification of single or various analytes under easily manipulated conditions. A facile passive pumping method is used to deliver Ag colloids and analytes into the channels where SERS measurements are done under nondestructive flowing conditions. With this approach, SERS signal reproducibility is found to be better than 7%. Utilizing a very high numerical aperture microscope objective with a confocal-based Raman spectrometer, high sensitivity is achieved. Moreover, the long working distance of this objective coupled with an appreciable channel depth obviates normal alignment issues expected with translational multiplexing. Rapid evaluation of the effects of anion activators and the type of colloid employed on SERS performance are used to demonstrate the efficiency and applicability of the MMF approach. SERS spectra of various pesticides were also obtained. Calibration curves of crystal violet (non-resonant enhanced) and Mitoxantrone (resonant enhanced) were generated, and the major SERS bands of these analytes were observable down to concentrations in the low nM and sub-pM ranges, respectively. While conventional random morphology colloids were used in most of these studies, unique cubic nanoparticles of silver were synthesized with different sizes and studied using visible wavelength optical extinction spectrometry, scanning electron microscopy, and the MMF-SERS approach.