Low Raman Cross Section Research Articles

Metal–Organic Frameworks–Based Surface–Enhanced Raman Scattering Substrates for Gas Sensing

Gas sensing holds great significance in environment monitoring, real–time security alerts and clinical diagnosis, which require sensing technology to distinguish various target molecules with extreme sensitivity and selectivity. Surface–enhanced Raman spectroscopy (SERS) has great potential in gas sensing for its single molecule sensitivity and fingerprint specificity. However, different from molecule sensing in solutions, SERS detection of gas often suffers from low sensitivity as gas molecules usually display a low Raman cross–section and poor affinity on traditional noble metal nanoparticle (NMNP)–based substrates. Therefore, much effort has been made to solve these problems. Fortunately, the appearance of metal–organic frameworks (MOFs) has shed new light on this direction. Due to the unique functional characteristics of MOFs, such as controllable pore size/shape, structural diversity and large specific surface area, SERS substrates based on MOFs can achieve high sensitivity, excellent selectivity and good stability. Although several reviews on MOF–based SERS substrates have been reported, few focus on gas sensing, which is a great challenge. Here, we mainly review the latest research progress on SERS substrates based on different MOFs. Sensitive and active SERS substrates can be prepared according to the unique advantages of MOFs with different metal centers. Then, we focus on composite SERS substrates based on different MOFs and NMNPs and summarize the application of composite SERS substrates in gas sensing. Finally, the future difficulties and potential possibilities of SERS substrates based on MOFs and NMNPs for gas sensing are discussed.

Intrinsic SERS Fingerprints of Aptamer-Peptide Conjugates for Direct High-Specific Profiling Abnormal Protein Levels in Cancer Patients.

Surface-enhanced Raman spectroscopy (SERS) with ultrasensitive vibrational fingerprints enables quick identification and trace detection of various kinds of molecules. But proteins usually have low Raman cross sections and are difficult to generate recognizable signals in direct SERS detection. Recently, nucleic acid-peptide conjugates are emerging with great potential in structuring, assembling, catalyzing, sensing, etc., and the coupling of aptamers further enables superior biological recognition and programmability. Here, we develop the aptamer-peptide conjugates as a new kind of SERS probe for direct high-specific profiling abnormal protein levels in cancer patients. The aptamer conjugated with glutathione (GSH) functions as both the recognition element and the SERS reporters that can simultaneously generate SERS fingerprints of both peptides and nucleic acids. This kind of biocompatible probe appears to have excellent performance in high-salt environments and realizes rapid, simple, and multisignal detection of thrombin (TB). Data-driven soft independent modeling of class analogy (DD-SIMCA) is used to distinguish SERS profiles of actual blood samples and realize the identification and classification of cancer patients. Furthermore, the effect of low-temperature storage time on blood samples is analyzed by tracking the changes of SERS profiles; the results hint that plasma samples stored under 4 °C for more than 2 days could generate false negative results due to TB hydrolysis, which has important implications for clinical sample analysis. This kind of nucleic acid-peptide conjugate provides new ideas for SERS sensing strategy in the future.

Electronic Preresonance Stimulated Raman Scattering Spectromicroscopy Using Multiple-Plate Continuum.

Stimulated Raman scattering (SRS) spectromicroscopy is a powerful technique that enables label-free detection of chemical bonds with high specificity. However, the low Raman cross section due to typical far-electronic resonance excitation seriously restricts the sensitivity and undermines its application to bio-imaging. To address this bottleneck, the electronic preresonance (EPR) SRS technique has been developed to enhance the Raman signals by shifting the excitation frequency toward the molecular absorption. A fundamental weakness of the previous demonstration is the lack of dual-wavelength tunability, making EPR-SRS only applicable to a limited number of species in the proof-of-concept experiment. Here, we demonstrate the EPR-SRS spectromicroscopy using a multiple-plate continuum (MPC) light source able to examine a single vibration mode with independently adjustable pump and Stokes wavelengths. In our experiments, the C═C vibration mode of Alexa 635 is interrogated by continuously scanning the pump-to-absorption frequency detuning throughout the entire EPR region enabled by MPC. The results exhibit 150-fold SRS signal enhancement and good agreement with the Albrecht A-term preresonance model. Signal enhancement is also observed in EPR-SRS images of the whole Drosophila brain stained with Alexa 635. With the improved sensitivity and potential to implement hyperspectral measurement, we envision that MPC-EPR-SRS spectromicroscopy can bring the Raman techniques closer to a routine in bio-imaging.

Interfacial deposition of Ag nanozyme on metal-polyphenol nanosphere for SERS detection of cellular glutathione

The low polarization and low Raman cross section characteristics of glutathione (GSH) make it challenging to directly detect GSH molecules through surface enhanced Raman scattering (SERS) technology. Development of nanostructures for indirect detection of GSH applied to the SERS platform is of great interest. Herein, silver nanoparticles (Ag NPs)/copper-polyphenol colloidal spheres (denoted as CuTA@Ag) with adjustable Ag NPs coverage are prepared by deposition of Ag NPs on the metal-polyphenol colloidal spheres via an interfacial polyphenol reduction method. The size and density of the Ag NPs deposited on the out layer can be readily adjusted by tailoring the concentrations of silver precursor. It leads to activity difference for the nanozyme and SERS characteristics. The SERS properties of the obtained CuTA@Ag are studied using oxTMB, catalytic products of nanozyme, as the probing molecules. They provide satisfactory SERS performance with a low detection limit of 10−7 M (S/N = 3) and linear determination in the 1–100 μM range for GSH. Moreover, it is further able to detect the glutathione content in cancer cells with well accurate and reproducible capability, catching the signs of rising cancer marker levels. This work proposes structurally tunable nanomaterials platform for a catalytic-based SERS assay, which is expected to utilize the high sensitivity of SERS tool for GSH detection in the cellular environment.

Novel Single-Particle Analytical Technique for Submicron Atmospheric Aerosols: Combined Use of Dark-Field Scattering and Surface-Enhanced Raman Spectroscopy.

Raman microspectrometry (RMS) is a useful single particle analysis method that can provide information on the mixing states, molecular species, and chemical functional groups of individual aerosol particles, which are difficult to determine by bulk analysis techniques. On the other hand, drawbacks, such as low Raman cross-section, spatial resolution (∼1 μm), and optical diffraction limit, make the analysis of atmospheric particles in the submicron size range difficult using conventional RMS. This study developed a new strategy to detect individual submicron-size atmospheric particles by combining dark-field (DF) microscopy and surface-enhanced Raman spectroscopy (SERS). The DF technique overcomes optical spatial diffraction limit by contrast enhancement, allowing the visualization of submicron particles. SERS facilitates spectroscopic characterization (obtaining information on molecular fingerprints and mixing states) of trace amounts of analyte by increasing the Raman scattering cross-section at the hot spot. SERS-active silver substrates sputter-coated on a Si wafer efficiently provided a clear background in the dark-field image and uniform hot spots over a large area, which were suitable for single-particle analysis. Various functional groups in individual particles and their heterogeneous mixing states were investigated, demonstrating the potential of this method to provide improved information on submicron atmospheric particles of femtogram-level masses. DF-SERS may elucidate the detailed physicochemical characteristics of individual submicron particles, providing new information on the formation mechanisms and fates of atmospheric particles.

Determination of antihypertensive drugs irbesartan and doxazosin mesylate in healthcare products and urine samples using surface-enhanced Raman scattering.

In this paper, a surface-enhanced Raman scattering (SERS) strategy was constructed for the determination of antihypertensive drugs irbesartan (IRB) and doxazosin mesylate (DOX). β-Cyclodextrin-capped silver nanoparticles (CD-AgNPs) are employed as SERS-active substrate. The introduction of β-CD with hydrophobic cavity can capture drug molecules to form host-guest complex, making the drug molecules closer to the electromagnetic enhancement field of the AgNPs, thereby enhancing the SERS signal of drug molecules with low Raman cross-section. The vibrational modes of IRB and DOX are assigned by density functional theory calculations. The linear response from 3.0 × 10-7 to 1.0 × 10-5mol L-1 for IRB and 3.0 × 10-7 to 2.0 × 10-5mol L-1 for DOX and low limits of detection (LOD) 7.5 × 10-8mol L-1 for IRB and 8.6 × 10-8mol L-1 for DOX can be achieved. Meanwhile, this SERS approach can be applicable to determine IRB and DOX in commercial drug tablets, healthcare products, and human urine samples with recoveries of 90.8-115.7% and 90.0-113.5%, respectively, with relative standard deviation (RSD) less than 4.5%. This designed SERS strategy enables for the rapid determination of IRB and DOX in drug quality monitoring and illegal additives in healthcare products as well as clinical applications.

Cu/Ag Nanoparticle-Based Surface-Enhanced Raman Scattering Substrates for Label-Free Bacterial Detection

Surface-enhanced Raman spectroscopy (SERS) is a promising analytical technique for fast and accurate disease detection due to its attractive features. However, realizing label-free direct detection is still challenging as most probes have extremely low Raman cross sections and little affinity to SERS substrates. Disappointingly, SERS spectra of most bacteria and other biological samples look similar as the differences in their molecular compositions are subtle and not detectable. Hence, the fabrication of highly enhancing plasmonic nanoparticles with excellent uniformity is demanded. Moreover, as SERS substrates are not reusable, cost-effective and simplistic fabrication methods are critical. Here, we report a facile approach to synthesizing Ag nanoparticle array on Cu-foil in less than 3 min, using only Cu-foil, silver nitrate, and hydroquinone. We employed the idea of galvanic replacement in combination with a seed-mediated particle-growth approach. The label-free bacterial detection has shown that our Cu/Ag nanoparticle substrate is superior to highly acclaimed Ag nanocubes. Creating strong second and third-generation SERS hot-spots through cooperative interaction of homo- (Ag–Ag) and heterogeneous (Ag–Cu) surfaces contributes mainly to the observed excellent enhancement. Interestingly, direct liquid bacteria sample analysis showed a 6-fold higher detection sensitivity than completely dried samples. We believe that our approach will offer remarkable advantages and change how SERS substrates are prepared and conducted in SERS-based bacterial detection.

Pushing the Limits of Surface-Enhanced Raman Spectroscopy (SERS) with Deep Learning: Identification of Multiple Species with Closely Related Molecular Structures.

Raman spectroscopy is a non-destructive and label-free molecular identification technique capable of producing highly specific spectra with various bands correlated to molecular structure. Moreover, the enhanced detection sensitivity offered by surface-enhanced Raman spectroscopy (SERS) allows analyzing mixtures of related chemical species in a relatively short measurement time. Combining SERS with deep learning algorithms allows in some cases to increase detection and classification capabilities even further. The present study evaluates the potential of applying deep learning algorithms to SERS spectroscopy to differentiate and classify different species of bile acids, a large family of molecules with low Raman cross sections and molecular structures that often differ by a single hydroxyl group. Moreover, the study of these molecules is of interest for the medical community since they have distinct pathological roles and are currently viewed as potential markers of gut microbiome imbalances. A convolutional neural network model was developed and used to classify SERS spectra from five bile acid species. The model succeeded in identifying the five analytes despite very similar molecular structures and was found to be reliable even at low analyte concentrations.

Nonenzymatic Hydrogen Peroxide Detection Using Surface-Enhanced Raman Scattering of Gold-Silver Core-Shell-Assembled Silica Nanostructures.

Hydrogen peroxide (H2O2) plays important roles in cellular signaling and in industry. Thus, the accurate detection of H2O2 is critical for its application. Unfortunately, the direct detection of H2O2 by surface-enhanced Raman spectroscopy (SERS) is not possible because of its low Raman cross section. Therefore, the detection of H2O2 via the presence of an intermediary such as 3,3,5,5-tetramethylbenzidine (TMB) has recently been developed. In this study, the peroxidase-mimicking activity of gold–silver core–shell-assembled silica nanostructures (SiO2@Au@Ag alloy NPs) in the presence of TMB was investigated using SERS for detecting H2O2. In the presence of H2O2, the SiO2@Au@Ag alloy catalyzed the conversion of TMB to oxidized TMB, which was absorbed onto the surface of the SiO2@Au@Ag alloy. The SERS characteristics of the alloy in the TMB–H2O2 mixture were investigated. The evaluation of the SERS band to determine the H2O2 level utilized the SERS intensity of oxidized TMB bands. Moreover, the optimal conditions for H2O2 detection using SiO2@Au@Ag alloy included incubating 20 µg/mL SiO2@Au@Ag alloy NPs with 0.8 mM TMB for 15 min and measuring the Raman signal at 400 µg/mL SiO2@Au@Ag alloy NPs.

Controlling Optically Driven Atomic Migration Using Crystal-Facet Control in Plasmonic Nanocavities.

Plasmonic nanoconstructs are widely exploited to confine light for applications ranging from quantum emitters to medical imaging and biosensing. However, accessing extreme near-field confinement using the surfaces of metallic nanoparticles often induces permanent structural changes from light, even at low intensities. Here, we report a robust and simple technique to exploit crystal facets and their atomic boundaries to prevent the hopping of atoms along and between facet planes. Avoiding X-ray or electron microscopy techniques that perturb these atomic restructurings, we use elastic and inelastic light scattering to resolve the influence of crystal habit. A clear increase in stability is found for {100} facets with steep inter-facet angles, compared to multiple atomic steps and shallow facet curvature on spherical nanoparticles. Avoiding atomic hopping allows Raman scattering on molecules with low Raman cross-section while circumventing effects of charging and adatom binding, even over long measurement times. These nanoconstructs allow the optical probing of dynamic reconstruction in nanoscale surface science, photocatalysis, and molecular electronics.

Volumetric Raman chemical imaging of drug delivery systems

AbstractThe ability to image drug distribution inside a several hundred micron thick polymer matrix, encapsulated by a protective coating, would greatly contribute to the understanding of the performance and shortcomings of drug delivery devices. Here, we present an experimental framework for deep volumetric Raman imaging (dVRI), where common challenges such as low Raman cross section, fluorescence, and low transparency of samples are overcome. We apply dVRI to a selection of drug delivery forms, tablets with thin protective coatings and drug‐loaded microdevices. We demonstrate three‐dimensional visualization of the different drug/polymeric materials, constituting a drug delivery device, with imaging depth of 225 μm.

Rapid and ultrasensitive surface-enhanced Raman spectroscopy detection of mercury ions with gold film supported organometallic nanobelts

Rapid, ultrasensitive and reliable detection of mercury ions (Hg2+) by surface enhanced Raman spectroscopy (SERS) is of importance, but is restricted by the extremely low Raman cross section of the Hg2+. Here, we report a facile methodology that can realize such detection based on the organometallic Cu(CH4N2S)Cl · 0.5H2O nanobelts and SERS. In the assay, Hg2+ react with the nanobelts coated on a SERS active gold nanoparticle (NP) film to form ultrafine HgS NPs in situ. Subsequently, solid HgS is SERS determined to mirror the presence of Hg2+. Importantly, such detection is rapid and ultrasensitive. Within 10 min, limit of detection (LoD) of ppt level can be realized. The high detection efficiency is attributed to the superhydrophilicity, rich micropores and ultrathin nature of the organometallic nanobelts besides the strong SERS effect of Au NP film. In addition, this detection is highly resistant to various metal ions (Cu2+, Fe3+, Bi3+, Cr3+, Na+, Ni2+, Cd2+, etc) and is highly reliable in actual water (lake and tap water). Finally, influences of some substrate parameters and detection conditions on the test results are revealed. The optimal thickness of the gold NP film is about 80 nm, and the optimal wavelength of excitation light is about 633 nm. A small amount of Cu(CH4N2S)Cl · 0.5H2O nanobelts or a large volume of Hg2+ contaminated solution contributes to low LoDs. We believe that this work provides a rapid and sensitive detection for Hg2+.

Ag nano-assemblies on Si surface via CTAB-assisted galvanic reaction for sensitive and reliable surface-enhanced Raman scattering detection

In this work, we report a quick and controllable method for fabricating Ag nanoparticles (NPs) and nano-assemblies (NAs) on silicon (Si) surface via a galvanic reaction assisted by surfactant hexadecyltrimethylammonium bromide (CTAB). Obtained Si substrates with high density Ag NAs serve as surface-enhanced Raman scattering (SERS) substrates for unlabelled molecular sensing. The addition of CTAB enables not only the electromagnetic enhancement by controllable producing Ag NAs “hotspots”, but also the signal enhancement by enriching probe molecules via hydrophobic interaction. Two concentration regimes of 1.0 × 10−8–1.0 × 10−11 M and 1.0 × 10−12–1.0 × 10−16 M have been obtained for quantitative and qualitative detection of Rhodamine 6G (R6G) in aqueous solution, respectively. As a result, for determination of R6G, the quantitative and qualitative detection limits of 1.0 × 10−11 and 1.0 × 10−16 M have been obtained, respectively, with high reproducibility showing the relative standard deviation (RSD) of ∼7.3%. Simulation has been carried out using finite-difference time-domain (FDTD) to evaluate the dependence of electric field on the size and inter-gap of Ag NPs, showing good agreement with experimental results. The high sensitivity also enables SERS characterization of non-resonant and low Raman cross-section biomolecules, for example, amino acids. Such a fabrication process is simple, fast, cheap and reproducible; and therefore, it would be helpful to produce high sensitive SERS substrates to broaden their applications in chemical and biological fields for molecular diagnostics to single-/multiple-molecule detection.

3D-Printed Peptide-Hydrogel Nanoparticle Composites for Surface-Enhanced Raman Spectroscopy Sensing

Precise control over the arrangement of plasmonic nanomaterials is critical for label-free single-molecule surface-enhanced Raman spectroscopy (SERS)-based sensing applications. SERS templates should provide high sensitivity and reproducibility and be cost-effective and easy to prepare. Additive manufacturing by extrusion-based three-dimensional (3D) printing is an emerging technique for the spatial arrangement of nanomaterials and is a method that may satisfy these SERS template requirements. In this work, we use 3D printing to produce sensitive and reproducible SERS templates using a fluorenylmethyloxycarbonyl diphenylalanine (Fmoc-FF) hydrogel loaded with silver or gold nanoparticles. The Fmoc-FF template allows the detection of low Raman cross-section molecules such as adenine at concentrations as low as 100 pM.

An atomic-defect enhanced Raman scattering (DERS) quantum probe for molecular level detection – Breaking the SERS barrier

Recently, nonplasmonic surface-enhanced Raman scattering (SERS) has gained intense interest. Compared to commonly studied noble metals, semiconductors offer more uniformity, better chemical stabilities and improved biocompatibilities, which are promising for their broader practical applications. Unfortunately, semiconductors suffer from very low enhancement efficiencies and poor sensitivities because the Raman enhancement primarily comes from charge transfer, which is a weaker mechanism compared to the plasmonic resonance of noble metals. Introducing oxygen defects has been proven to be an effective way to significantly improve the Raman activity of metal-oxide semiconductors. However, current techniques are limited to introducing surface defects, and thus the improvement is limited as a result. Herein, we demonstrate atomic-defect enhanced Raman scattering (DERS) as a new addition to the RS family. The high concentration of defects in the surface and subsurface layers of these small quantum probes improves the sensitivity of semiconductor to a detectable molecular concentration of 10−9M with a high enhancement factor of ∼1010 for the target molecule (CV). The enhancement efficiency, which is comparable to that of noble metals, is achieved by the synergistic contributions of the quantum size coupled with the excellent charge-transfer (CT) enabled by the enriched electronic states that result from the high density of defects. The nonplasmonic quantum probe also exhibits outstanding applicability for detecting biomolecules with low Raman cross-sections. In addition, the DERS probe demonstrates wavelength-independent sensing and nondestructive long-term activity, which validate the consistency of the DERS system and its universality for use in various other fields. This defect-rich nonplasmonic quantum sensor is synthesized by an ultrafast laser-induced multiphoton ionization mechanism, and the surface/subsurface defect ratio within the DERS probes can be precisely tuned by varying the laser energy.

Stimuli-responsive SERS nanoprobes for multiplexing detection

Surface-enhanced Raman scattering (SERS) is an ultrasensitive analytical tool for a variety of assays. However, its applications have been limited to sense molecules with high Raman cross-sections. Here we develop a new strategy for the SERS monitoring of species with low Raman cross-sections based on the stimuli-responsive Raman reporters (SRRRs). The SRRRs display tunable chemical structures and Raman fingerprints under the external stimulus, allowing the detection of their corresponding stimulus. A new SRRR, Bis [4,4′-(dithiophenyl azo)-1,3-benzenediamine] (DTPABDA), was reported to demonstrate multiple fingerprints and high reactivity with Cu2+ or HClO via an oxidant cyclization or cleavage reaction of azobenzene moiety, resulting in their concentration-dependent fingerprint change. The combination of DTPABDA with our reported SERS substrate (cabbage-like Au microparticles, or CLMP), SERS sensing of these two species with high sensitivity and selectivity were reported. This new sensing strategy may open a new avenue to break through the existing limitations of SERS sensors.

Photo-induced surface-enhanced Raman spectroscopy from a diphenylalanine peptide nanotube-metal nanoparticle template

UV irradiation of aligned diphenylalanine peptide nanotubes (FF-PNTs) decorated with plasmonic silver nanoparticles (Ag NPs) enables photo-induced surface-enhanced Raman spectroscopy. UV-induced charge transfer facilitates a chemical enhancement that provides up to a 10-fold increase in surface-enhanced Raman intensity and allows the detection of a wide range of small molecules and low Raman cross-section molecules at concentrations as low as 10–13 M. The aligned FF-PNT/Ag NP template further prevents photodegradation of the molecules under investigation. Our results demonstrate that FF-PNTs can be used as an alternative material to semiconductors such as titanium dioxide for photo-induced surface-enhanced Raman spectroscopy applications.

Photo-induced enhanced Raman spectroscopy for universal ultra-trace detection of explosives, pollutants and biomolecules.

Surface-enhanced Raman spectroscopy is one of the most sensitive spectroscopic techniques available, with single-molecule detection possible on a range of noble-metal substrates. It is widely used to detect molecules that have a strong Raman response at very low concentrations. Here we present photo-induced-enhanced Raman spectroscopy, where the combination of plasmonic nanoparticles with a photo-activated substrate gives rise to large signal enhancement (an order of magnitude) for a wide range of small molecules, even those with a typically low Raman cross-section. We show that the induced chemical enhancement is due to increased electron density at the noble-metal nanoparticles, and demonstrate the universality of this system with explosives, biomolecules and organic dyes, at trace levels. Our substrates are also easy to fabricate, self-cleaning and reusable.

Plasmonic microholes for SERS study of biomolecules in liquid

In this work we report on an active SERS (Surface Enhanced Raman Scattering) substrate with well-defined silver microholes for the investigation of liquid samples. The femtoliter volume confined in the holes allows to perform analysis of non-transparent aqueous solutions reducing fluorescence emission and avoiding signal absorption by surrounding liquid, which was demonstrated in the case of opaque and dye solutions. The micro-pattern based substrate was obtained by optical lithography and reactive ion etching and was selectively covered with silver nanoislands arranged in a highly homogeneous and isotropic way. Dopamine molecules and cell culture medium were used as probe analytes for SERS experiments showing that plasmonic microholes, having a very uniform enhancement, are suitable both for the detection of molecules with low Raman cross section and for the detection of biomolecules of non-transparent complex solutions. Finally, this kind of analysis requires only a tiny amount of analyte which is an important advancement for the measurements of costly or precious samples.

Optical response and SERS properties of individual large scale supracrystals made of small silver nanocrystals

There is a considerable interest in producing and understanding the optical and spectroscopic properties of ordered nanoparticle assemblies. Herein, we describe and interpret the optical absorbance and Raman properties of 5.9 nm ± 0.3 nm diameter silver nanocrystals coated with dodecanethiol and organized in highly ordered 3D superlattices of different heights. Each superlattice was studied individually, which allowed to elaborate a model based on Maxwell-Garnett theory to reproduce qualitatively the height and wavelength dependence of the absorbance. Importantly, because of their small size compared to that of traditional nanoparticles used in Surface Enhanced Raman Spectroscopy (SERS), the large 3D distribution of hot spots generated by the silver superlattices allowed to easily obtain SERS spectra of the surrounding ligands despite their intrinsic low Raman cross section. Accordingly, traces of thiophenol could be detected very easily.