Simultaneous Surface-enhanced Raman Scattering Research Articles

Biomimetic-Membrane-Protected Plasmonic Nanostructures as Dual-Modality Contrast Agents for Correlated Surface-Enhanced Raman Scattering and Photoacoustic Detection of Hidden Tumor Lesions.

Optical imaging and spectroscopic modalities are of considerable current interest for in vivo cancer detection and image-guided surgery, but the turbid or scattering nature of biomedical tissues has severely limited their abilities to detect buried or occluded tumor lesions. Here we report the development of a dual-modality plasmonic nanostructure based on colloidal gold nanostars (AuNSs) for simultaneous surface-enhanced Raman scattering (SERS) and photoacoustic (PA) detection of tumor phantoms embedded (hidden) in ex vivo animal tissues. By using red blood cell membranes as a naturally derived biomimetic coating, we show that this class of dual-modality contrast agents can provide both Raman spectroscopic and PA signals for the detection and differentiation of hidden solid tumors with greatly improved depths of tissue penetration. Compared to previous polymer-coated AuNSs, the biomimetic coatings are also able to minimize protein adsorption and cellular uptake when exposed to human plasma without compromising their SERS or PA signals. We further show that tumor-targeting peptides (such as cyclic RGD) can be noncovalently inserted for targeting the ανβ3-integrin receptors expressed on metastatic cancer cells and tracked via both SERS and PA imaging (PAI). Finally, we demonstrate image-guided resections of tumor-mimicking phantoms comprising metastatic tumor cells buried under layers of skin and fat tissues (6 mm in thickness). Specifically, PAI was used to determine the precise tumor location, while SERS spectroscopic signals were used for tumor identification and differentiation. This work opens the possibility of using these biomimetic dual-modality nanoparticles with superior signal and biological stability for intraoperative cancer detection and resection.

Simultaneous Surface-Enhanced Raman Scattering with a Kerr Gate for Fluorescence Suppression.

The combination of surface-enhanced and Kerr-gated Raman spectroscopy for the enhancement of the Raman signal and suppression of fluorescence is reported. Surface-enhanced Raman scattering (SERS)-active gold substrates were demonstrated for the expansion of the surface generality of optical Kerr-gated Raman spectroscopy, broadening its applicability to the study of analytes that show a weak Raman signal in highly fluorescent media under (pre)resonant conditions. This approach is highlighted by the well-defined spectra of rhodamine 6G, Nile red, and Nile blue. The Raman spectra of fluorescent dyes were obtained only when SERS-active substrates were used in combination with the Kerr gate. To achieve enhancement of the weaker Raman scattering, Au films with different roughnesses or Au-core-shell-isolated nanoparticles (SHINs) were used. The use of SHINs enabled measurement of fluorescent dyes on non-SERS-active, optically flat Au, Cu, and Al substrates.

Intermolecular and Electrode-Molecule Bonding in a Single Dimer Junction of Naphthalenethiol as Revealed by Surface-Enhanced Raman Scattering Combined with Transport Measurements.

Electron transport through noncovalent interaction is of fundamental and practical importance in nanomaterials and nanodevices. Recent single-molecule studies employing single-molecule junctions have revealed unique electron transport properties through noncovalent interactions, especially those through a π-π interaction. However, the relationship between the junction structure and electron transport remains elusive due to the insufficient knowledge of geometric structures. In this article, we employ surface-enhanced Raman scattering (SERS) synchronized with current-voltage (I-V) measurements to characterize the junction structure, together with the transport properties, of a single dimer and monomer junction of naphthalenethiol, the former of which was formed by the intermolecular π-π interaction. The correlation analysis of the vibrational energy and electrical conductance enables identifying the intermolecular and molecule-electrode interactions in these molecular junctions and, consequently, addressing the transport properties exclusively associated with the π-π interaction. In addition, the analysis achieved discrimination of the interaction between the NT molecule and the Au electrode of the junction, i.e., Au-π interactions through-π coupling and though-space coupling. The power density spectra support the noncovalent character at the interfaces in the molecular junctions. These results demonstrate that the simultaneous SERS and I-V technique provides a unique means for the structural and electrical investigation of noncovalent interactions.

SERS-Based Immunoassay of Myocardial Infarction Biomarkers on a Microfluidic Chip with Plasmonic Nanostripe Microcones

We developed a new plasmonic nanostripe microcone array (PNMA) substrate-integrated microfluidic chip for the simultaneous surface-enhanced Raman scattering (SERS)-based immunoassay of the creatine kinase MB isoenzyme (CK-MB) and cardiac troponin (cTnI) cardiac markers. The conventional immunoassay usually employs a microtiter plate as the solid capture plate to form the immunocomplexes. However, the two-dimensional (2D) surface of the microtiter plate limits the capture efficiency of the target antigens due to the steric hindrance effect. To address this issue, a gold film-coated microcone array with nanostripes was developed that can provide a large surface area for capture antibody conjugation and serve as a SERS-active substrate. This unique nano-microhierarchical structure showed an excellent light trapping effect and induced surface plasmon resonance to further enhance the Raman signals of the SERS nanoprobes. It significantly improved the sensitivity and applicability of SERS-based immunoassay on the microfluidic chip. With this integrated microfluidic chip, we successfully performed the simultaneous detection of CK-MB and cTnI, and the detection limit can reach 0.01 ng mL-1. It is believed that the PNMA substrate-integrated microfluidic chip would play a critical role in the rapid and sensitive diagnostics of cardiac diseases.

Rapid simultaneous SERS detection of dual myocardial biomarkers on single-track finger-pump microfluidic chip

Acute myocardial infarction (AMI) is a serious disease with high mortality that afflicts many people around the world. The main cause of death from AMI was the inaccurate early diagnosis, which resulted from the medical treatment might be a delay. Therefore, it is crucial to achieve the rapid detection of AMI. The cardiac troponin I (cTnI) level in human serum may significantly increase as the myocardial membrane ruptured, and the creatine kinase-MB (CK-MB) was also associated with the AMI recurrence and the infarct size of myocardial infarction. Both of them are regarded as important cardiac biomarkers for the early diagnosis of AMI. Therefore, we chose these two cardiac biomarkers as indicators for simultaneous detection. We proposed a single-track finger-pump microfluidic chip for simultaneous surface-enhanced Raman scattering (SERS) detection of cTnI and CK-MB. The entire detection process takes only 5 min without the cumbersome syringe pump. Meanwhile, it enables multiple reagent additions and removals of the unbonded reactants. This microfluidic sensor employed "sandwich" immunoassays based on SERS nanoprobes, AMI biomarkers, and magnetic beads. It is possible to detect two cardiac biomarkers simultaneously in a single measurement, greatly simplifying the detection process and reducing the detection time. Magnetic beads with SERS nanoprobes were separated and captured in the microchamber by a round magnet integrated into the chip. Our results showed that the detection limits of cTnI and CK-MB could reach to 0.01 ng mL−1, respectively. The limit of detections (LODs) match with the clinical threshold values for AMI biomarkers. It is believed that the proposed single-track finger-pump microfluidic chip can be used as an effective tool for determining early AMI.

Principal Component Analysis of Surface-Enhanced Raman Scattering Spectra Revealing Isomer-Dependent Electron Transport in Spiropyran Molecular Junctions: Implications for Nanoscale Molecular Electronics.

The characterization of single-molecule structures could provide significant insights into the operation mechanisms of functional devices. Structural transformation via isomerization has been extensively employed to implement device functionalities. Although single-molecule identification has recently been achieved using near-field spectroscopy, discrimination between isomeric forms remains challenging. Further, the structure–function relationship at the single-molecule scale remains unclear. Herein, we report the observation of the isomerization of spiropyran in a single-molecule junction (SMJ) using simultaneous surface-enhanced Raman scattering (SERS) and conductance measurements. SERS spectra were used to discriminate between isomers based on characteristic peaks. Moreover, conductance measurements, in conjunction with the principal component analysis of the SERS spectra, clearly showed the isomeric effect on the conductance of the SMJ.

Simultaneous Surface-Enhanced Resonant Raman and Fluorescence Spectroscopy of Monolayer MoSe2: Determination of Ultrafast Decay Rates in Nanometer Dimension.

The fact that metallic nanostructures are an excellent light receiver and transmitter connects the underlying principles of two widely applied optical processes: surface-enhanced Raman scattering (SERS) and surface-enhanced fluorescence (SEF). A comparative study of SERS and SEF can eliminate the typical unknown quantities of the system and reveal important parameters that cannot be accessed by conventional techniques. Here, we use this simultaneous SERS and SEF technique in a monolayer MoSe2 coupled plasmonic nanocavity. After optimizing the spatial and the spectral overlaps between excitonic and plasmonic resonances, the SERS and SEF enhancement factors can exceed 107 and 6000, respectively, at the same time on the same nanocube. The comparison of the SERS and SEF enhancements allows the estimation of the ultrafast total decay rate of the bright exciton in monolayer MoSe2 in the nanocavity down to tens of femtoseconds, which is otherwise hard to realize using time-resolved techniques.

Gold nanoworms: Optical properties and simultaneous SERS and fluorescence enhancement.

Fabrication of platforms for efficient Raman and fluorescence enhancement is very attractive for plasmon-based molecular sensing. For superior sensitivity, the plasmonic constituents of such platforms should be effective electromagnetic field enhancers. Furthermore, nanoparticles having plasmon peak in the spectral range of therapeutic window are superior for biomedical application. Herein, we show that worm-shaped Au nanoparticles can be used for simultaneous surface enhanced Raman scattering (SERS) and metal enhanced fluorescence (MEF). Gold nanoworms (Au-NWs) with an intense plasmon absorption in the therapeutic window were synthesized using a facile single-stepped recipe. Electron microscopy imaging revealed that Au-NWs have a non-uniform surface. Owing to their special morphology, three distinct plasmon bands were seen in the experimental spectrum. The presence of three plasmon peaks was also verified by finite element based simulations. The simulation results further show that Au-NWs can provide intense near field enhancement for multiple excitation wavelengths. As a proof of concept, we have used Au-NWs based platforms for simultaneous enhancement of fluorescence and Raman signal of rhodamine 6G (R6G) dye molecule.

Surface-Enhanced Raman Scattering in Molecular Junctions.

Surface-enhanced Raman scattering (SERS) is a surface-sensitive vibrational spectroscopy that allows Raman spectroscopy on a single molecular scale. Here, we present a review of SERS from molecular junctions, in which a single molecule or molecules are made to have contact from the top to the bottom of metal surfaces. The molecular junctions are nice platforms for SERS as well as transport measurement. Electronic characterization based on the transport measurements of molecular junctions has been extensively studied for the development of miniaturized electronic devices. Simultaneous SERS and transport measurement of the molecular junctions allow both structural (geometrical) and electronic information on the single molecule scale. The improvement of SERS measurement on molecular junctions open the door toward new nanoscience and nanotechnology in molecular electronics.

Important impact of the experimental platform on the efficient control of electronic and vibrational properties of molecular junctions

A recent work reported simultaneous surface-enhanced Raman scattering (SERS) and transport current-voltage I-V measurements in electromigrated molecular junctions based on C60. The vibrational frequencies measured there were found to be slightly but significantly shifted by the applied bias. This effect was attributed to a partial reduction of the C60 molecule. The fact that a complete redox process could not be achieved in that experiment raises the question addressed in this work on whether the experimental platform utilised (electromigrated junctions) represents the most favourable setup to achieve a(n almost) complete bias-driven reduction. The answer presented here is that (i) no matter how high the voltage is, reduction cannot exceed 50% in an experimental setup where the molecule is symmetrically coupled to the (source and drain) electrodes, (ii) reduction can be almost complete in cases of highly asymmetric molecule-electrode couplings, but in this case (iii) biases corresponding to current plateaus are required, which common junctions cannot withstand. We next discuss that, much more than in two-terminal setups, the molecular charge, orbital energies, and vibrational properties can be efficiently controlled in cases of (redox) molecules embedded in scanning tunnelling microscope (STM) junctions in electrochemical (EC) environment. The electrochemical setup turns out to provide a unique chance to control the molecular properties. The key role in the unprecedented efficiency of this control is played by the electrolyte gating, which enables a continuous change in the molecular charge by up to an entire electron (complete redox process). To exemplify, we consider EC-STM experimental transport data for the redox unit (viologen), whose essential constituent is 4,4´-bipyridine (44BPY), a molecule of special interest for the charge transport at the nanoscale.

Nanostructured surface enhanced Raman scattering sensor platform with integrated waveguide core

We present a planar waveguide based sensor capable of simultaneous surface enhanced Raman scattering (SERS)/surface plasmon resonance (SPR) sensing methodologies. The sensor consists of a nanostructured area etched into a low loss planar waveguide fabricated from silicon oxynitride. The selective deposition of the 25 nm thick gold film on the nanostructured features was applied to create the SERS/SPR active sites. In this work, we adapt the SPR approach, coupling light propagating along the slab waveguide to the nano-textured area from underneath. The shapes of the nanostructures, thickness, and morphology of the gold coating are chosen to be suitable for SERS and SPR. Effects of geometric parameters associated with the nanostructured features such as diameters, length, and pitch were investigated. Detection of Benzyl Mercaptan was accomplished using a 785 nm laser in a SERS configuration excited from the underlying waveguide core. The detection of the analyte was confirmed by normal incident SERS measurements using an InVia Raman spectrometer. The surface enhanced Raman scattering signal from the 25 nm thick Au coated nanostructures provided a maximum intensity signal of 104. Using the same device in the SPR sensing arrangement provided a wavelength shift of 25 nm and an average signal to noise ratio of 10 dB to Benzyl Mercaptan. The fabricated sensor can easily be fabricated using nano imprinting into cheap polymer substrates and would provide disposable real-world remote sensing capabilities.

Detection of effect of chemotherapeutic agents to cancer cells on gold nanoflower patterned substrate using surface-enhanced Raman scattering and cyclic voltammetry

In vitro assays have generally been carried out for cytological diagnosis and for evaluation of the cytotoxic effect of chemotherapeutic agents as an alternative to animal experiments. In this study, a method for fabrication and application of a gold nanoflower array on an ITO substrate for evaluation of the effect of chemotherapeutic agents on cancer cell behavior by the surface-enhanced Raman scattering (SERS) analysis, as well as the electrochemical detection was described. Due to the increased sensitivity provided by gold nanoflower substrates, the effect of chemotherapeutic agents at low concentration level was successfully detected based on SERS technique. This substrate was found to give enhanced Raman spectra with high surface plasmon field in the near infrared (NIR) spectral range, which minimize fluorescence interference and photo-toxicity. Cyclic voltammetry (CV) was further performed for confirmation of results obtained by SERS assay and showed increased intensity of current peaks for various concentrations at low levels. The developed Au nanoflowers modified ITO substrates developed in this study could be used as a simultaneous SERS and CV substrate to determine the effects of chemotherapeutic agents on cancer cells.

Simultaneous Raman and Fluorescence Spectroscopy of Single Conjugated Polymer Chains

Simultaneous surface enhanced Raman scattering (SERS) and fluorescence is demonstrated from single conjugated polymer chains. As resonance enhancement of SERS depends on the spectral overlap of the polymer's absorption and the incident laser, resonance Raman and fluorescence effectively probe the absorbing and emitting part of the polymer, respectively. The optical phonon energies change along the polymer chain, providing a window to spatially track excited state relaxation. Whereas a mean spatial redistribution of the excitation is witnessed by a change in vibronic fingerprint following interchromophoric energy transfer, intrachromophoric exciton self-trapping leaves the vibrations unchanged.

The electronic contribution to SERS the present experimental status

The so-called chemical contribution to surface enhanced Raman scattering (SERS) of adsorbates on cold-deposited silver films in ultrahigh vacuum (UHV) is at least three orders of magnitude. The upper limit for classical enhancement, given by SERS of H 2O, is three orders of magnitude. Simultaneous SERS and DC-resistivity measurements demonstrate that the enhanced Raman scattering originates only from adsorbed molecules interacting with itinerant electrons of Fermi energy. Silver island films in UHV show a nonclassical first layer effect of, at least, a factor of 10, which is quenched by oxygen adsorption. Submonolayer postdeposition of silver on adsorbates on smooth silver induces chemically specific and vibrationally selective Raman enhancement. Atomic scale roughness induces enhanced Raman scattering. The results are tentatively explained by an electronic enhancement mechanism based on inelastic scattering of intermediate hot electrons by adsorbate vibrations via shape resonances. Problems and ideas on the future of the SERS spectroscopy are pointed out.