Raman-active Molecules Research Articles

Hybrid lipid-AuNP clusters as highly efficient SERS substrates for biomedical applications

Although Surface Enhanced Raman Scattering (SERS) is widely applied for ultrasensitive diagnostics and imaging, its potential is largely limited by the difficult preparation of SERS tags, typically metallic nanoparticles (NPs) functionalized with Raman-active molecules (RRs), whose production often involves complex synthetic approaches, low colloidal stability and poor reproducibility. Here, we introduce LipoGold Tags, a simple platform where gold NPs (AuNPs) clusters form via self-assembly on lipid vesicle. RRs embedded in the lipid bilayer experience enhanced electromagnetic field, significantly increasing their Raman signals. We modulate RRs and lipid vesicle concentrations to achieve optimal SERS enhancement and we provide robust structural characterization. We further demonstrate the versatility of LipoGold Tags by functionalizing them with biomolecular probes, including antibodies. As proof of concept, we successfully detect intracellular GM1 alterations, distinguishing healthy donors from patients with infantile GM1 gangliosidosis, showcasing LipoGold Tags as advancement in SERS probes production.

Metal-Organic Framework-Enabled Trapping of Volatile Organic Compounds into Plasmonic Nanogaps for Surface-Enhanced Raman Scattering Detection.

Utilizing electromagnetic hotspots within plasmonic nanogaps is a promising approach to create ultrasensitive surface-enhanced Raman scattering (SERS) substrates. However, it is difficult for many molecules to get positioned in such nanogaps. Metal-organic frameworks (MOFs) are commonly used to absorb and concentrate diverse molecules. Herein, we combine these two strategies by introducing MOFs into plasmon-coupled nanogaps, which has so far remained experimentally challenging. Ultrasensitive SERS substrates are fabricated through the construction of nanoparticle-on-mirror structures, where Au nanocrystals are encapsulated with a zeolitic imidazolate framework-8 (ZIF-8) shell and then coupled to a gold film. The ZIF-8 shell, as a spacer that separates the Au nanocrystal and the Au film, can be adjusted in thickness over a wide range, which allows the electric field enhancement and plasmon resonance wavelength to be varied. By trapping Raman-active molecules within the ZIF-8 shell, we show that our plasmon-coupled structures exhibit a superior SERS detection performance. A range of volatile organic compounds at the concentrations of 10-2 mg m-3 can be detected sensitively and reliably. Our study therefore offers an attractive route for synergistically combining plasmonic electric field enhancement and MOF-enabled molecular enrichment to design and create SERS substrates for ultrasensitive detection.

Exploring the interplay of LSPR and CT: Hierarchical shell thickness optimization for advanced SERS sensing using AgNW@ZIF-8 Core@Shell substrates

Synergistic surface-enhanced Raman spectroscopy (SERS) substrates, leveraging the combined strengths of electromagnetic enhancement (EM) and chemical enhancement (CM), have been extensively explored in the literature. In this study, we introduce a distinctive approach to fabricating core@shell structures, specifically employing silver nanowire @ zeolite imidazole framework-8 (AgNW@ZIF-8) as synergistic SERS substrates. Notably, these substrates offer meticulous control over shell thickness through a straightforward post-synthesis procedure. Utilizing Ag nanowires as the plasmonic core, selected for their broader localized surface plasmon resonance (LSPR) absorption range compared to nanoparticles, we encapsulate them within ZIF-8, a metal-organic framework (MOF) recognized for its proficient charge transfer (CT) properties. Our investigation encompasses the SERS performance across various Raman-active molecules, considering their diverse sizes and distinct frontier molecular orbitals (FMO) energy levels. Additionally, we systematically explore the influence of alterations in shell thickness on SERS outcomes and scrutinize the impact of probe orientation. This comprehensive study not only advances the understanding of synergistic effects intrinsic to MOFs-metal SERS substrates but also provides valuable insights for the rational design of highly sensitive substrates tailored for practical applications.

Enhanced Total Vibrational Excitation Yield in a Slow Narrow-Pulsed Hydrogen Molecular Beam.

High-efficiency excitation of a molecular beam is critical for investigating state-selected chemistry. However, achieving vibrational excitation of the entire beam for Raman-active molecules such as H2 proves extremely challenging, primarily because laser pulses are much shorter than the molecular beam. In this study, we achieve a total excitation efficiency of over 20% by employing stimulated Raman pumping (SRP) in a slow, narrow-pulsed molecular beam. Through optimizing the intensity and spot shape of the SRP lasers, we attain saturated excitation within the laser crossing region. Furthermore, by reducing the beam velocity and narrowing the beam pulse using a cold valve and a fast chopper, we significantly enhance the total excitation yield. COMSOL simulation and a newly developed model reveal that a critical velocity allows the chopper to block unexcited molecules and reserve most of the excited ones from the beam, resulting in the highest overall excitation yield. This innovative setup opens new possibilities for state-selected experiments in surface science and ion-molecule reaction dynamics, particularly involving weak transitions and pulsed lasers.

Exploring the potential of branched submicron channels-based structures in ultra-thin Ag films for SERS molecular sensing

Noble metal-based nanostructures are actively studied due to their promising prospects for fabricating efficient substrates for Surface Enhanced Raman Spectroscopy (SERS)-based molecular sensing. In this work, we report the gross potential of SERS substrates based on branched submicron channels in ultra-thin Ag films. These films were fabricated by magnetron sputtering and then annealed in high vacuum conditions to induce branched channels growth by thermal dewetting. Different sets of nominally equal samples were tested during a determined period of time, using confocal Raman spectroscopy and methylene blue (MB) as Raman-active molecule, to assess their performance for SERS in ambient aging conditions. Micro-Raman intensity mapping studies demonstrated the emergence of “hot spots” enhancing the Raman signal in the branched submicron channels. A good mass sensitivity and fast spectral acquisition were achieved using these nanostructures, observing an exceptional spectral resolution and identifying all main vibrational states of MB in a few seconds for samples with a MB surface mass density of about 2 ng/mm2. A good spectral resolution was achieved even using shorter measurement times from 1.00 to 0.05 s, suggesting the potential for fast SERS determinations. Samples showed good reproducibility in the Raman spectral response during the tested period, demonstrating the marginal impact of the aging effects on the Raman signal enhancement and ensuring a time-stable SERS performance in the short term. Our results show that the proposed nanostructures are promising candidates for the development of substrates with competitive-sensitivity, time-stability, and fast SERS response, representing a simple and attractive alternative for efficient SERS-based molecular sensing.

An amplification-free CRISPR-SERS biosensor for specific, sensitive and rapid detection of Salmonella Typhimurium in poultry

CRISPR (Clustered regularly interspaced short palindromic repeats) has been a cutting-edge biotechnology in both gene editing and biosensing due to its desirable features, such as high base resolution and set-and-forget operation. However, as a nucleic acid detection method, an DNA/RNA amplification procedure is still inevitable in CRISPR biosensors. In this study, a highly-ordered nanopore array SERS substrate, coated with silver nanoparticles, was fabricated and utilized as a platform for the specific detection of Salmonella Typhimurium (S. Typhimurium) without the time-consuming DNA amplification step. The smart sensing strategy was established by introducing an ssDNA labeled with a Raman active molecule as a signal report probe to show the changes during target identification and detection. The CRISPR-SERS biosensor was developed by combining the ultra-sensitive sensing mechanism of CRISPR technology with the SERS analytical method, aiming at detecting the invasin A gene (invA) of S. Typhimurium. The sensing materials and operation conditions were optimized to maximize the output signal and minimize the cost. The results showed that the proposed biosensor could specifically detect S. Typhimurium with a limit of detection (LOD) of 110 CFU/mL in poultry samples within 2 h. This CRISPR-SERS sensing strategy could provide an alternative way for pathogen detection in food safety monitoring.

Construction of High-Active SERS Cavities in a TiO2 Nanochannels-Based Membrane: A Selective Device for Identifying Volatile Aldehyde Biomarkers.

The accurate, sensitive, and selective on-site screening of volatile aldehyde biomarkers for lung cancer is of utmost significance for preclinical cancer diagnosis and treatment. Applying surface-enhanced Raman scattering (SERS) for gas sensing remains difficult due to the small Raman cross section of most gaseous molecules and interference from other components in exhaled breath. Using an Au asymmetrically coated TiO2 nanochannel membrane (Au/TiO2 NM) as the substrate, a ZIF-8-covered Au/TiO2 NM SERS sensing substrate is designed for the detection of exhaled volatile organic compounds (VOCs). Au/TiO2 NM provides uniformly amplified Raman signals for trace measurements in this design. Importantly, the interfacial nanocavities between Au nanoparticles (NPs) and metal-organic frameworks (MOFs) served as gaseous confinement cavities, which is the key to enhancing the capture and adsorption ability toward gaseous analytes. Both ends of the membrane are left open, allowing gas molecules to pass through. This facilitates the diffusion of gaseous molecules and efficient capture of the target analyte. Using benzaldehyde as a typical gas marker model of lung cancer, the Schiff base reaction with a Raman-active probe molecule 4-aminothiophene (4-ATP) pregrafted on Au NPs enabled trace and multicomponent detection. Moreover, the combination of machine learning (ML) and Raman spectroscopy eliminates subjective assessments of gaseous aldehyde species with the use of a single feature peak, allowing for more accurate identification. This membrane sensing device offers a promising design for the development of a desktop SERS analysis system for lung cancer point-of-care testing (POCT).

Culture-Independent Multiplexed Detection of Drug-Resistant Bacteria Using Surface-Enhanced Raman Scattering.

The rapid and accurate detection of bacteria resistance to β-lactam antibiotics is critical to inform optimal treatment and prevent overprescription of potent antibiotics. Here, we present a fast, culture-independent method for the detection of extended-spectrum β-lactamases (ESBLs) using surface-enhanced Raman scattering (SERS). The method uses Raman probes that release sulfur-based Raman active molecules in the presence of β-lactamases. The released thiol molecules can be captured by gold nanoparticles, leading to amplified Raman signals. A broad-spectrum cephalosporin probe R1G and an ESBL-specific probe R3G are designed to enable duplex detection of bacteria expressing broad-spectrum β-lactamases or ESBLs with a detection limit of 103 cfu/mL in 1 h incubation. Combined with a portable Raman microscope, our culturing-free SERS assay has reduced screening time to 1.5 h without compromising sensitivity and specificity.

Developing highly reliable SERS substrates based on Ag grown on alumina nanomeshes anodized under 1 V for efficiently sensing Raman-active molecules

We have developed silver-nanostructures grown on anodic alumina nanomesh (AAN) films to create new-type substrates for surface-enhanced Raman scattering (SERS). AAN with uniform thin sidewall of ∼ 5 nm was fabricated by anodizing Al sheets at 1 V in 6% H3PO4 solution. Subsequent AC electrochemical deposition of silver created an array of nanoparticles or nano-islands depending on growth time. The particle-island transition is non-monotonic evolution, since metal growth and dissolution compete in AC electrodeposition process. Systematic SERS study on various Ag-AAN films with trial probes of adenine solutions reveals collective contribution of electron-plasma oscillation and surface area of silver nanostructures in Raman enhancements. SERS signals are primarily contributed by surface area under excitation wavelength of 532 nm (away from plasmonic resonance). The average correlation coefficient between the SERS intensity and surface area was 0.85, indicating robust correlation. This value was reduced to 0.61 under excitation wavelength of 633 nm (closer to plasmonic resonance). Furthermore, increased Ag-deposition reduced the relative standard deviation of SERS intensities and thus improved both the uniformity and quality consistency of SERS substrates. Therefore, fabrication of SERS substrate with larger Ag surface area under similar SERS enhancement factors is suggested for high throughput in commercial sectors.

Design and Synthesis of SERS Materials for In Vivo Molecular Imaging and Biosensing.

Surface-enhanced Raman scattering (SERS) is a feasible and ultra-sensitive method for biomedical imaging and disease diagnosis. SERS is widely applied to in vivo imaging due to the development of functional nanoparticles encoded by Raman active molecules (SERS nanoprobes) and improvements in instruments. Herein, the recent developments in SERS active materials and their in vivo imaging and biosensing applications are overviewed. Various SERS substrates that have been successfully used for in vivo imaging are described. Then, the applications of SERS imaging in cancer detection and in vivo intraoperative guidance are summarized. The role of highly sensitive SERS biosensors in guiding the detection and prevention of diseases is discussed in detail. Moreover, its role in the identification and resection of microtumors and as a diagnostic and therapeutic platform is also reviewed. Finally, the progress and challenges associated with SERS active materials, equipment, and clinical translation are described. The present evidence suggests that SERS could be applied in clinical practice in the future.

Self-assembled PVP-gold nanostar films as plasmonic substrates for surface-enhanced spectroscopies: influence of the polymeric coating on the enhancement efficiency.

Colloidal nanoparticles exhibiting anisotropic morphologies are preferred in the structural design of spectroscopically active substrates due to the remarkable optical properties of this type of nano-object. In the particular case of star-like nanoparticles, their sharp tips can act as antennae for capturing and amplifying the incident light, as well as for enhancing the light emitted by nearby fluorophores or the scattering efficiency of Raman active molecules. In the current work, we aimed to implement such star-shaped nanoparticles in the fabrication of nanoparticle films and explore their use as solid plasmonic substrates for surface-enhanced optical spectroscopies. High-density, compact and robust self-assembled gold nanostar films were prepared by directly depositing them from aqueous colloidal suspension on polystyrene plates through convective self-assembly. We investigated the role of the polymeric coating, herein polyvinylpyrrolidone (PVP), in the particle assembly process, the resulting morphology and consequently, the plasmonic response of the obtained films. The efficacy of the plasmonic films as dual-mode surface-enhanced fluorescence (SEF) and surface-enhanced Raman scattering (SERS) substrates was evidenced by testing Nile Blue A (NB) and Rhodamine 800 (Rh800) molecular chromophores under visible (633 nm) versus NIR (785 nm) laser excitation. Steady-state and time-resolved fluorescence investigations highlight the fluorescence intensity and fluorescence lifetime modification effects. The experimental results were corroborated with theoretical modelling by finite-difference time-domain (FDTD) simulations. Furthermore, to prove the extended applicability of the proposed substrates in the detection of biologically relevant molecules, we tested their SERS efficiency for sensing metanephrine, a metabolite currently used for the biochemical diagnosis of neuroendocrine tumors, at concentration levels similar to other catecholamine metabolites.

Dual Biomimetic Recognition-Driven Plasmonic Nanogap-Enhanced Raman Scattering for Ultrasensitive Protein Fingerprinting and Quantitation.

Protein assays with fingerprints and high sensitivity are essential for biomedical research and applications. However, the prevailing methods mainly rely on indirect or labeled immunoassays, failing to provide fingerprint information. Herein, we report a dual biomimetic recognition-driven plasmonic nanogap-enhanced Raman scattering (DBR-PNERS) strategy for ultrasensitive protein fingerprinting and quantitation. A pair of molecularly imprinted nanoantennas were rationally engineered for specifically trapping a target protein into well-defined plasmonic nanogaps through dual-terminal recognition for ultrahigh Raman signal amplification. Meanwhile, a Raman-active small molecule was embedded into the nanoantenna as an internal standard to provide a ratiometric assay for robust quantitation. DBR-PNERS exhibited several significant merits over existing approaches, including fingerprinting, ultrahigh sensitivity, quantitation robustness, speed, sample consumption, and so on. Therefore, it can be a promising tool for a protein assay and holds a great perspective in important applications.

Coherent Raman spectroscopy on hydrogen with in-situ generation, in-situ use, and in-situ referencing of the ultrabroadband excitation.

Time-resolved spectroscopy can provide valuable insights in hydrogen chemistry, with applications ranging from fundamental physics to the use of hydrogen as a commercial fuel. This work represents the first-ever demonstration of in-situ femtosecond laser-induced filamentation to generate a compressed supercontinuum behind a thick optical window, and its in-situ use to perform femtosecond/picosecond coherent Raman spectroscopy (CRS) on molecular hydrogen (H2). The ultrabroadband coherent excitation of Raman active molecules in measurement scenarios within an enclosed space has been hindered thus far by the window material imparting temporal stretch to the pulse. We overcome this challenge and present the simultaneous single-shot detection of the rotational H2 and the non-resonant CRS spectra in a laminar H2/air diffusion flame. Implementing an in-situ referencing protocol, the non-resonant spectrum measures the spectral phase of the supercontinuum pulse and maps the efficiency of the ultrabroadband coherent excitation achieved behind the window. This approach provides a straightforward path for the implementation of ultrabroadband H2 CRS in enclosed environment such as next-generation hydrogen combustors and reforming reactors.

Strong and Elastic Membranes via Hydrogen Bonding Directed Self-Assembly of Atomically Precise Nanoclusters.

2D nanomaterials have provided an extraordinary palette of mechanical, electrical, optical, and catalytic properties. Ultrathin 2D nanomaterials are classically produced via exfoliation, delamination, deposition, or advanced synthesis methods using a handful of starting materials. Thus, there is a need to explore more generic avenues to expand the feasibility to the next generation 2D materials beyond atomic and molecular-level covalent networks. In this context, self-assembly of atomically precise noble nanoclusters can, in principle, suggest modular approaches for new generation 2D materials, provided that the ligand engineering allows symmetry breaking and directional internanoparticle interactions. Here the self-assembly of silver nanoclusters (NCs) capped with p-mercaptobenzoic acid ligands (Na4 Ag44 -pMBA30 ) into large-area freestanding membranes by trapping the NCs in a transient solvent layer at air-solvent interfaces is demonstrated. The patchy distribution of ligand bundles facilitates symmetry breaking and preferential intralayer hydrogen bondings resulting in strong and elastic membranes. The membranes with Young's modulus of 14.5 ± 0.2GPa can readily be transferred to different substrates. The assemblies allow detection of Raman active antibiotic molecules with high reproducibility without any need for substrate pretreatment.

Heralded single-photon source based on an ensemble of Raman-active molecules

Light with high mutual correlations at different frequencies can be used to create heralded single-photon sources, which may serve as the basic elements of existing quantum cryptography and quantum teleportation schemes. One of the important examples in natural systems of light with high mutual correlations is the light produced by spontaneous Raman scattering on an ensemble of molecules. In this paper, we investigate the possibility of using Raman light to create a heralded single-photon source. We show that when using Stokes scattered light for postselection of anti-Stokes scattered light, the latter may possess single-photon properties. We analyze the influence of various negative factors on the characteristics of such a heralded single-photon source, which include a time delay between Stokes and anti-Stokes photons, the finiteness of the correlation radius of an external source, and background radiation. We show that the low value of the second-order autocorrelation function of the single-photon source is preserved even when the flow of uncorrelated photons exceeds the flow of correlated photons in scattered Raman light by an order of magnitude.

Electric-Field-Induced Coherent Anti-Stokes Raman Scattering of Hydrogen Molecules in Visible Region for Sensitive Field Measurement.

Nonintrusive optical measuring of electric fields in space is crucial for various sciences and technologies. In this study, a simple and highly sensitive optical electric field measurement is demonstrated in high-pressure hydrogen by performing electric-field-induced coherent anti-Stokes Raman scattering (E-CARS) in the visible region. The minimum detectable electric field is 0.5 V/mm at atmospheric pressure. This method does not require excited or atomic species and shows a considerably higher sensitivity than those demonstrated by the commonly applied E-CARS method in the infrared region and electric-field-induced second-harmonic generation. This method can be applied to various Raman-active molecules.

Localized Dissipative Unipolar Objects under the Condition of Stimulated Raman Scattering

The possibility of the formation of dissipative unipolar soliton pulses in an amplifying medium of Raman-active molecules has been analyzed. It has been shown that the formation of such pulses is possible under the mutual compensation of Raman enhancement and irreversible losses caused by fast relaxation in the system of electron optical transitions. Since Raman enhancement is nonlinear, the threshold duration and energy of a soliton-like object being formed are determined by the parameters of the medium.

Continuously Multiplexed Ultrastrong Raman Probes by Precise Isotopic Polymer Backbone Doping for Multidimensional Information Storage and Encryption.

Raman-based super multiplexing has attracted great interest in imaging, biological analysis, identity security, and information storage. It still remains a great challenge to synthesize a large number of different Raman-active molecules to fulfill the Raman color palette. Here, we report a facile and systematic strategy to construct continuously multiplexed ultrastrong Raman probes. By precisely incorporating different ratios of 13C isotope into the backbone of poly(deca-4,6-diynedioic acid) (PDDA), we can obtain a library of PDDAs with tunable double-bond Raman frequencies and adjustable intensity ratios of two triple-bond (13C≡13C and 12C≡12C) Raman peaks, while retaining the ultrastrong Raman signals and physicochemical properties of the polymer. We also demonstrate the successful application of 13C-doped PDDAs as security inks to generate a novel 3D matrix barcode system for information encryption and high-density data storage. The isotopically doped PDDA series herein pave a new way to advance Raman-based super multiplexing for diverse applications.

SERS and Indicator Paper Sensing of Hydrogen Peroxide Using Au@Ag Nanorods.

The detection of hydrogen peroxide and the control of its concentration are important tasks in the biological and chemical sciences. In this paper, we developed a simple and quantitative method for the non-enzymatic detection of H2O2 based on the selective etching of Au@Ag nanorods with embedded Raman active molecules. The transfer of electrons between silver atoms and hydrogen peroxide enhances the oxidation reaction, and the Ag shell around the Au nanorod gradually dissolves. This leads to a change in the color of the nanoparticle colloid, a shift in LSPR, and a decrease in the SERS response from molecules embedded between the Au core and Ag shell. In our study, we compared the sensitivity of these readouts for nanoparticles with different Ag shell morphology. We found that triangle core–shell nanoparticles exhibited the highest sensitivity, with a detection limit of 10−4 M, and the SERS detection range of 1 × 10−4 to 2 × 10−2 M. In addition, a colorimetric strategy was applied to fabricate a simple indicator paper sensor for fast detection of hydrogen peroxide in liquids. In this case, the concentration of hydrogen peroxide was qualitatively determined by the change in the color of the nanoparticles deposited on the nitrocellulose membrane.

Atomically Thin TaSe2 Film as a High‐Performance Substrate for Surface‐Enhanced Raman Scattering

An atomically thin TaSe2 sample, approximately containing two to three layers of TaSe2 nanosheets with a diameter of 2.5cm is prepared here for the first time and applied on the detection of various Raman-active molecules. It achieves a limit of detection of 10-10 m for rhodamine 6G molecules. The excellent surface-enhanced Raman scattering (SERS) performance and underlying mechanism of TaSe2 are revealed using spectrum analysis and density functional theory. The large adsorption energy and the abundance of filled electrons close to the Fermi level are found to play important roles in the chemical enhancement mechanism. Moreover, the TaSe2 film enables highly sensitive detection of bilirubin in serum and urine samples, highlighting the potential of using 2D SERS substrates for applications in clinical diagnosis, for example, in the diagnosis of jaundice caused by excess bilirubin in newborn children.