Raman Probe Research Articles

Photoinduced Enhanced Raman Probe for Use in Highly Specific and Sensitive Imaging for Tyrosine Dimerization in Inflammatory Cells.

A background-free photoinduced enhanced Raman (PIER) probe for highly sensitive detection of tyrosine dimerization process due to oxidative reaction in inflammatory cells is presented. The PIER probe could monitor oxidative reaction in real time by producing time-resolved spectral with discrete changes in Raman intensity. To the best of our knowledge, this is the first report on C≡C probes with PIER and vastly improved Raman activity. These results will contribute to the cutting edge of development of stable and highly sensitive chemical imaging technology.

Enhancement of the Au/ZnO-NA Plasmonic SERS Signal Using Principal Component Analysis as a Machine Learning Approach

In this work, we modeled a novel approach to enhance surface-enhanced Raman scattering (SERS) signals using principal component analysis (PCA) as a machine learning approach. Zinc oxide nanoarrays (ZnO-NAs) were synthesized using a hydrothermal method followed by zinc oxide nucleation on ITO glass substrates via an oxidation furnace at 500 °C. The surface morphology was improved by short rapid thermal annealing (S-RTA) after deposition of a gold layer via a thermal evaporator to avoid chemical contamination of the sensing surface, which is a suitable plasmonic platform for the generation of “hot spots” for SERS enhancement with fewer defects. The proposed Au/ZnO-NA SERS sensor exhibited an enhancement factor (EF) of 1.15 × 10 7 via the R6G Raman probe and excellent uniformity over the entire surface. The PCA algorithm was used to extract useful features and information from the SERS signal. The algorithm was implemented with MATLAB software (R2019a) by the multivariable analytical tool to find an enhanced signal (~3 times higher) with high uniformity, which has great potential and is applicable to a wide range of probe molecules suitable in medical, safety, and environmental applications.

Optimized amplitude modulation in femtosecond stimulated Raman microscopy.

In femtosecond stimulated Raman microscopy, two laser pulses (Raman pump and probe) interact at the focus of a scanning microscope. To retrieve the Raman signature of the sample, an amplitude modulation of the pump pulses is necessary. Here, different methods to achieve this modulation are presented and compared.

Imaging the invisible-Bioorthogonal Raman probes for imaging of cells and tissues.

A revolutionary avenue for vibrational imaging with super-multiplexing capability can be seen in the recent development of Raman-active bioortogonal tags or labels. These tags and isotopic labels represent groups of chemically inert and small modifications, which can be introduced to any biomolecule of interest and then supplied to single cells or entire organisms. Recent developments in the field of spontaneous Raman spectroscopy and stimulated Raman spectroscopy in combination with targeted imaging of biomolecules within living systems are the main focus of this review. After having introduced common strategies for bioorthogonal labeling, we present applications thereof for profiling of resistance patterns in bacterial cells, investigations of pharmaceutical drug-cell interactions in eukaryotic cells and cancer diagnosis in whole tissue samples. Ultimately, this approach proves to be a flexible and robust tool for in vivo imaging on several length scales and provides comparable information as fluorescence-based imaging without the need of bulky fluorescent tags.

Plasmon resonance excitation enhances Raman emission and amplifies the molecular vibration on Au (1 1 1) film

The enhancement of Raman scattering by localized plasmonic resonances has boosted spectroscopic analysis down to the single-molecule level. Here, the simultaneous measurement of the surface plasmon resonance and surface-enhanced Raman scattering on a flat Au surface is demonstrated. The results emphasize that, under the conditions of plasmon resonance, the electromagnetic field is enhanced, permitting the readout of the surface-enhanced Raman scattering signal.Peaks at different frequencies characterized the spectra of the molecules selected as Raman probes. In the first approach, we explained our findings referring to classical optomechanics. Because the plasmon lifetime and the molecular vibrational have the same magnitude and the molecular dephasing is not expected phenomenon, we fostered the hypothesis that a stronger coupling occurs. In fact, the coupling rate between the monolayer and the plasmon is enhanced with an order of gv0=0.12MHz, which is wider than the laser linewidth and leads to coherent amplification of molecular motion.In conclusion, the possibility to run the SERS in the Kretschmann configuration with flat gold substrates opens endless possibilities in nanophotonics for fundamental investigations and their applications.

Fabrication of Au nanoparticles embedded holey g-C3N4 as SERS substrates for sensitive and reliable detection

Holey g-C3N4 (H-C3N4) with in situ grown Au nanoparticles (Au@H-C3N4) was synthesized to produce high performance and ultrasensitive SERS active substrates. The H-C3N4 with the porous structure provided the support for embedding enough Au NPs, which avoided the aggregation of Au NPs on the surface of H-C3N4. The results showed that crystal violet as a Raman probe showed a detection level of 2.7 × 10−9 M with an enhancement factor of 6.8 × 105. Au@H-C3N4 was used successfully to detect the residues of prohibited additives, melamine and sodium thiocyanate, from milk samples, which displayed a good linear range from 1 × 10−4 to 5 × 10−7 M (R2 = 0.986) and 1 × 10−3 to 5 × 10−6 M (R2 = 0.971), respectively. In this study, Au@H-C3N4 SERS substrates with high sensitivity have high potential as SERS platform for trace detection.

Surface reaction strategy for Raman probing trace cadmium ion

Prevalent contamination of water by cadmium ion (Cd2+) brings environmental risk, which threatening to human health including renal dysfunction, reduced lung capacity, and some cancers. It calls for rapid, sensitive and selective protocol to analyze Cd2+ on field. In this work, specific Raman probe is rationally designed by gold nanoparticles (AuNPs) functionalized with tripeptide glutathione (GSH) and Rhodamine 6G (R6G) (denoted as R6G/GSH/AuNPs), which is explored for indirectly determining trace Cd2+ in river water. Based on chelating interaction between GSH and Cd2+ to form tetrahedral Cd(SG)4, which trends easy detachment from R6G/GSH/AuNPs. With increasing Cd2+ concentration, the Raman probe without protection of GSH happens due aggregation and Raman signal of R6G increases correspondingly. The R6G/GSH/AuNPs-based Raman detection of Cd2+ in river water shows rapidness, excellent sensitivity, selectivity and good repeatability. Limit of detection of 10 ppb with a widely linear range of 0.5–20 ppm could be achieved. It could be perspective that such Raman probe could be extended to be used for on-site monitoring trace Cd2+ in river water system.

Roughened silver microtubes for reproducible and quantitative SERS using a template-assisted electrosynthesis approach

The synthesis and application of silver microtube substrates for quantification by surface enhanced Raman spectroscopy (SERS) is presented in this work. The roughened silver microtubes were prepared by template assisted electrosynthesis method. Using rhodamine 6G as a Raman probe molecule, the silver microtubes were tested for SERS determination, demonstrating a high performance for quantitative analysis with high precision and low data dispersion (%RSD < 3), which is the limiting step in quantitative SERS. This performance can be explained by obtaining a single silver microtube substrate highly homogeneous in SERS activity in the whole surface and with high reproducibility between different synthesis batches.

Self-assembling of metallic Rh over DNA as nano-chains: An effective organosol for catalysis and SERS studies

Rarely explored materials in organic medium for catalytic applications are one of the promising methods for high rate conversion and selectivity to achieve monodispersity. In this present work, for the first time, we have prepared Rh NPs in organic medium (as organosol) using microwave heating condition. The process results a colloidal solution that is stable for more than five months while keeping at low temperature in refrigerator. The self-assembled Rh-DNA as organosol was formed in two different morphologies such as nano-chains and nano-beads simply by varying the metal ions to DNA molar concentration as Rh-DNA (0.0035 M) and Rh-DNA (0.007 M), respectively. Interestingly, here, DNA was used as a scaffold which has manifold advantages over other commonly used scaffolds by providing its aromatic base pairs, negative phosphate groups and hydroxyl groups to stabilize Rh3+ metal ions. This colloidal solution can readily be dispersed in many organic solvents (protic and aprotic) which is an added advantage compared to aquasol where dispersion to other organic solvents is a problem for catalytic applications. The as prepared two set of Rh-DNA (0.0035 and 0.007 M) were applied for catalytic nitro compound reduction and Surface Enhanced Raman Scattering (SERS) studies. The synthesized two sets of Rh-DNA organosol was highly capable of reducing four different nitro compounds and comparatively, Rh-DNA (0.0035 M) showed better catalytic activity than other one. The enhancement factor (EF) values was calculated at different concentrations ranging from 10−3 M to 10−6 M and the obtained highest EF value is 2.89 × 106 for Rh-DNA (0.0035 M) while using methylene blue (MB) as a Raman probe molecule. This method of synthesis is too simple and gives highly stable solution of Rh-DNA that can be successfully utilized in multidisciplinary applications particularly in medicinal and energy related fields in near future.

A SERS quenching method for the sensitive determination of insulin.

In this work, we utilise the disulphide bond structure of insulin and a new benzothiazole Raman probe for the detection of human insulin using surface-enhanced Raman spectroscopy (SERS). The disulphide bond structure of the insulin was reduced to generate free sulfhydryl terminal groups. When reacted with benzothiazole-functionalised gold nanoparticles, the reduced protein desorbs the Raman probe and causes its Raman signal intensity to quench. Using this approach, insulin was quantified in the concentration range of 1 × 10-14 -1 × 10-8 M by SERS quenching. The limit of quantification of insulin by the SERS quenching method was found to be 1 × 10-14 M (0.01 pM or 58 pg/L), which satisfies the requirements for monitoring its blood concentration in patients. Because many proteins and peptides have disulphide bonds in their molecular structures, the new SERS quenching method has a strong potential for the rapid determination of ultralow concentrations of proteins in formulations and biological fluids.

Continuous Manufacturing of a Polymer Stabilized Emulsion Monitored with Process Analytical Technology.

Moving from batch to continuous manufacturing (CM) requires implementation of process analytical technology (PAT), as it is crucial to monitor and control these processes. CM of semi-solids has been demonstrated but implementation of a broader range of PAT tools with in- or on-line process interfacing at the end of the CM line has not been demonstrated. The goal of this work was to continuously manufacture creams and to investigate whether in- and on-line measurement of viscosity, changes in the concentration of active pharmaceutical ingredient (API), and pH could be used to support optimization of a model cream product. Additionally, the torque of the mixers was assessed for determination of the physical properties of the cream. Two Raman probes with different probe optics were compared for characterization of the API concentration. The API concentration, amount of neutralizer, and mixing speed of the CM line were systematically varied. Both the PhAT probe with a larger sampling volume and immersion Raman probe with a smaller sampling volume could detect the step changes in the API concentration. The torque from the mixer was compared with the viscosity measurements, but the torque signal could not be correlated with the viscosity due to the dynamic nature of the polymer conformation and the time-dependency of this property. Adjustment of pH of the cream could be monitored with the current installation. The investigated PAT tools could be implemented into a continuous line and, further, be used to support the optimization of a model cream composition and related process parameters.

Stealth modified bottom up SERS substrates for label-free therapeutic drug monitoring of doxorubicin in blood serum

Herein, we report the simple and inexpensive approach for the large-scale fabrication of uniform bottom-up Surface Enhanced Raman Spectroscopy (SERS) substrate. SERS substrate was fabricated by controlled sputtering of 10 nm thick gold film on self-assembled silica nanoparticles (SiNPs) of ~120 nm on glass substrates. The SERS detection has been firstly demonstrated using Rhodamine B as a Raman probe molecule with a detection limit of 10−10 M on Au sputtered SiNPs (i.e., Au@SiNPs). The experimental Raman enhancement from 0 to 6 was achieved on Au@SiNPs due to the generation of multiple SERS hotspot. To combat blood serum fouling, the zwitterionic modification of l-cysteine was done on Au@SiNPs substrates which lowered blood serum fouling by 48%. Our SERS-based sensor demonstrated high reproducibility for the detection of Doxorubicin in undiluted blood serum with a limit of detection of 20 nM, which greatly exceeded the detection range of available methodologies. We envision that the translation of this SERS substrate for the detection of chemo-drugs like Doxorubicin will assist clinicians in making rapid and/or early decisions in patients undergoing sustained chemotherapy to lower its side-effects or to incorporate other treatment methodologies as an option for Personalized treatment.

Tailoring carbon for single molecule detection – Broad spectrum 3D quantum sensor

Current single-molecule SERS sensing is mostly done by plasmonic materials like Gold and Silver due to higher enhancement efficiency. However, plasmonic materials suffer from inherent disadvantages, including inconsistent spectral signature and non-biocompatibility. Researchers are actively searching for a replacement with superior biocompatibility and a uniform spectral signature. Quantum scale Graphene-based SERS signifies a newfound frontier in this regard, owing to high surface area and tunable optical and electronic properties. The use of GQD as a SERS sensor is still critically impeded by low enhancement factor as well as inferior sensitivity due to wavelength-dependent fluorescence property. In this work, we introduce a 3-D Graphene Oxide Quantum sensor (GOQS) with an unmatched enhancement of 1014, enabling ultra-sensitive detection with a limit of detection down to single molecule sensitivity. With 3-D architecture, the interference of the inherent fluorescence of GQD is eliminated, thereby achieving a relatively high enhancement factor on par with plasmonic materials. The high enhancement factor is a combined effect of quantum confinement, edge effects, and charge transfer through molecular adsorption. The single molecule sensitivity (10 −15 M) was experimentally verified using a Raman Probe molecule (CV, R6 G) with excellent repeatability. As a distinct confirmation of single molecule sensitivity of GOQS, we have detected two Raman probe molecules (CV, R6 G) simultaneously, thereby systematically computing the probability of detecting at 10 -15 M level. The ability to detect and distinguish Raman probe molecules simultaneously down to femtomolar level is the lowest limit of detection reported in a non-plasmonic sensor thus far. GOQS was demonstrated for the detecting of disease biomarkers and using Tryptophan. An environmental contaminant Bisphenol-A was detected at a concentration of 10−15 M, corresponding to 2000 ppb. The experimental results indicate a new paradigm towards the activation of quantum scale graphene as a broad-spectrum SERS sensor for numerous ultra-trace analysis.

Surface plasmons and SERS application of Au nanodisk array and Au thin film composite structure

A composite structure of an Au nanodisk array and an Au film is designed to excite local surface plasmons and propagating surface plasmons and generate strong resonance coupling. The finite difference time domain method was used to study the surface plasmons effect of the structure. The composite substrate of an Au disk array with a 760-nm period and a 130-nm diameter was prepared via electron beam lithography. The SERS characteristics of the substrate were studied using rhodamine 6G (R6G) as a Raman probe molecule. The Raman intensity of R6G on the substrate reached values as high as 82.9% of the first measurement intensity, after the SERS substrate had been exposed to the atmosphere for 30 days. The results show that the proposed substrate yields good uniformity, reproducibility, and stability, thereby providing an effective and feasible scheme for the detection of molecules.

Tetracationic Bis-Triarylborane 1,3-Butadiyne as a Combined Fluorimetric and Raman Probe for Simultaneous and Selective Sensing of Various DNA, RNA, and Proteins.

A bis‐triarylborane tetracation (4‐Ar2B‐3,5‐Me2C6H2)‐C≡C−C≡C‐(3,5‐Me2C6H2‐4‐BAr2 [Ar=(2,6‐Me2‐4‐NMe3‐C6H2)+] (24+) shows distinctly different behaviour in its fluorimetric response than that of our recently published bis‐triarylborane 5‐(4‐Ar2B‐3,5‐Me2C6H2)‐2,2′‐(C4H2S)2–5′‐(3,5‐Me2C6H2‐4‐BAr2) (34+). Single‐crystal X‐ray diffraction data on the neutral bis‐triarylborane precursor 2 N confirm its rod‐like dumbbell structure, which is shown to be important for DNA/RNA targeting and also for BSA protein binding. Fluorimetric titrations with DNA/RNA/BSA revealed the very strong affinity of 24+ and indicated the importance of the properties of the linker connecting the two triarylboranes. Using the butadiyne rather than a bithiophene linker resulted in an opposite emission effect (quenching vs. enhancement), and 24+ bound to BSA 100 times stronger than 34+. Moreover, 24+ interacted strongly with ss‐RNA, and circular dichroism (CD) results suggest ss‐RNA chain‐wrapping around the rod‐like bis‐triarylborane dumbbell structure like a thread around a spindle, a very unusual mode of binding of ss‐RNA with small molecules. Furthermore, 24+ yielded strong Raman/SERS signals, allowing DNA or protein detection at ca. 10 nm concentrations. The above observations, combined with low cytotoxicity, efficient human cell uptake and organelle‐selective accumulation make such compounds intriguing novel lead structures for bio‐oriented, dual fluorescence/Raman‐based applications.

In Situ Gas Monitoring by Fiber-Coupled Raman Spectrometry for H₂-Risk Management in Nuclear Containment During a Severe Nuclear Accident

During a severe nuclear accident leading up to core melting, molten corium–concrete interaction (MCCI) and core-coolant water reaction both release large amounts of hydrogen (H2) gas in the containment atmosphere. According to the Shapiro–Moffette ternary diagram and depending on local partial pressures of H2, air, and water vapor, deflagration/detonation may occur with potential deleterious impact over equipment and structures. CO and CO2 are also of interest, as revealing gases for MCCI. Pressurized Water Reactors (PWRs) of French Nuclear Power Plants (NPPs) are equipped with passive autocatalytic recombiners (PARs), partly mitigating the H2 risk. However, the H2-risk management strategy may be significantly improved by performing in situ monitoring of H2, O2, N2, H2O, CO, and CO2 partial pressures at several locations inside the containment, to account for potential local combustion risk. Raman spectrometry (RS) involves only one laser and spectrometer equipped with a 2-D charge-coupled device (CDD). Raman probes are chemically selective and may be radiation-hardened. Custom-made fiber-coupled Raman probes, linked with a readout unit, were qualified in a climatic chamber, a flame-propagation tube, a 60Co irradiation cell, a 3-D shaking table, a steam jet and the MISTRA facility (1/10 reduced-scale containment mock-up dedicated to thermo-hydraulic tests).

A Multi-Core Fibre Photonic Lantern-Based Spectrograph for Raman Spectroscopy

We report on the development of a compact (volume $\approx$ 100\:cm$^3$), multimode diffraction-limited Raman spectrograph and probe designed to be compact as possible. The spectrograph uses `off the shelf' optics, a custom 3D-printed two-part housing and harnesses a multi-core fibre (MCF) photonic lantern (multimode to few-mode converter), which slices a large 40~\textmu m multimode input into a near-diffraction-limited 6~\textmu m aperture. Our unique design utilises the hexagonal geometry of our MCF, permitting high multimode collection efficiency with near-diffraction-limited performance in a compact design. Our approach does not require a complex reformatter or mask and thus preserves spectral information and throughput when forming the entrance slit of the spectrograph. We demonstrate the technology over the interval 800~nm to 940~nm (200~cm$^{-1}$ to 2000~cm$^{-1}$) with a resolution of 0.3\:nm (4\:cm$^{-1}$), but other spectral regions and resolutions from the UV to the near infrared are also possible. We demonstrate the performance of our system by recording the Raman spectra of several compounds, including the pharmaceuticals paracetamol and ibuprofen.

Time-Resolved Impulsive Stimulated Raman Spectroscopy with Synchronized Triple Mode-Locked Lasers.

A complete understanding of a photochemical reaction dynamics begins with real-time measurements of both electronic and vibrational structures of photoexcited molecules. Time-resolved impulsive stimulated Raman spectroscopy (TR-ISRS) with femtosecond actinic pump, Raman pump, and Raman probe pulses is one of the incisive techniques enabling one to investigate the structural changes of photoexcited molecules. Herein, we demonstrate that such femtosecond TR-ISRS is feasible with synchronized triple mode-locked lasers without using any time-delay devices. Taking advantage of precise control of the three repetition rates independently, we could achieve automatic scanning of two delay times between the three pulses, which makes both rapid data acquisition and wide dynamic range measurement of the fifth-order TR-ISRS signal achievable. We thus anticipate that the present triple mode-locked laser-based TR-ISRS technique will be of critical use for long-term monitoring of photochemical reaction dynamics in condensed phases and biological systems.

Impact of Automation in Pharmaceutical Industry on Roles and Responsibilities of Quality Assurance: A Review

Automation is the use of different control technologies in sectors with minimal or decreased human interference to operate a range of procedures. Automation has made its way to the pharmaceutical industries in the recent past. Automation has been implemented in production, packaging, labeling, and warehousing departments. Production of personalized medicines has become a reality after implementing automated machines. The R and D sector has also been affected by incorporating the latest technologies. The conventional functions of Quality Assurance (QA) department were limited to preparing standard operating procedures (SOPs), carrying out audits, qualification, and validation of equipment and processes. This review focuses on the implementation of automated technologies in pharmaceutical industries and the impact it has had on the pharmaceutical quality assurance department. This article covers topics such as the Raman probe and the different ways it has been made use of in the pharmaceutical industries. The conventional role played by the QA department has also been enlisted while also mentioning how they change with the implementation of automated technologies.

Investigations on the origin of strain variation in the zinc-blende phase along the depth of GaP/Si(1 1 1) using spatially resolved polarized and wavelength dependent Raman spectroscopy

The surface and micro structure variations in the technologically important GaP/Si hetero-structures are investigated by the spatially resolved polarized Raman spectroscopy. The hetero-structures probed from two different directions 〈1 1 1〉 and <11¯0> reveal the presence of strain distributed zinc-blende (ZB) GaP phases and the dominance of wurtzite (WZ) phase near the GaP-Si interface. The azimuthal dependence of the optical phonon intensity of nucleating layer endorses the dominance of WZ phase at the interface. The study illustrates that spatially resolved polarized Raman probe, across the hetero-junction is extremely useful for distinguishing the WZ and ZB stacks. It can positively be utilized for the integration of crystal phase quantum structures of III-V semiconductors on the Si and Ge substrates, without any physical damage to the structures.