2014, Ziemak, Steven, Kirshenbaum, K., Saha, S.R., Hu, R., Reid, J.-Ph., Gordon, R., Taillefer, L., Evtushinsky, D., Thirupathaiah, S., Büchner, B., Borisenko, S.V., Ignatov, A., Kolchmeyer, D., Blumberg, G., Paglione, J.

Thermal conductivity, point contact spectroscopy, angle-resolved photoemission and Raman spectroscopy measurements were performed on BaFe1.9Pt0.1As2 single crystals obtained from the same synthesis batch in order to investigate the superconducting energy gap structure using multiple techniques. Low temperature thermal conductivity was measured in the superconducting state as a function of temperature and magnetic field, revealing an absence of quasiparticle excitations in the $T\to 0$ limit up to 15 T applied magnetic fields. Point-contact Andreev reflection spectroscopy measurements were performed as a function of temperature using the needle-anvil technique, yielding features in the conductance spectra at both 2.5 meV and 7.0 meV scales consistent with a multi-gap scenario. Angle-resolved photoemission spectroscopy probed the electronic band structure above and below the superconducting transition temperature of Tc = 23 K, revealing an isotropic gap of magnitude $\sim 3$ meV on both electron and hole pockets. Finally, Raman spectroscopy was used to probe quasiparticle excitations in multiple channels, showing a threshold energy scale of 3 meV below Tc. Overall, we find strong evidence for an isotropic gap structure with no nodes or deep minima in this system, with a 3 meV magnitude gap consistently observed and a second, larger gap suggested by point-contact spectroscopy measurements. We discuss the implications that the combination of these results reveal about the superconducting order parameter in the BaFe2−xPtxAs2 doping system and how this relates to similar substituted iron pnictides.

2019, Mondol, Abdullah S., Töpfer, Natalie, Rüger, Jan, Neugebauer, Ute, Popp, Jürgen, Schie, Iwan W.

Raman spectroscopy has been widely used in clinical and molecular biological studies, providing high chemical specificity without the necessity of labels and with little-to-no sample preparation. However, currently performed Raman-based studies of eukaryotic cells are still very laborious and time-consuming, resulting in a low number of sampled cells and questionable statistical validations. Furthermore, the approach requires a trained specialist to perform and analyze the experiments, rendering the method less attractive for most laboratories. In this work, we present a new high-content analysis Raman spectroscopy (HCA-RS) platform that overcomes the current challenges of conventional Raman spectroscopy implementations. HCA-RS allows sampling of a large number of cells under different physiological conditions without any user interaction. The performance of the approach is successfully demonstrated by the development of a Raman-based cell viability assay, i.e., the effect of doxorubicin concentration on monocytic THP-1 cells. A statistical model, principal component analysis combined with support vector machine (PCA-SVM), was found to successfully predict the percentage of viable cells in a mixed population and is in good agreement to results obtained by a standard cell viability assay. This study demonstrates the potential of Raman spectroscopy as a standard high-throughput tool for clinical and biological applications.

2019, Frosch, Timea, Wyrwich, Elisabeth, Yan, Di, Domes, Christian, Domes, Robert, Popp, Jürgen, Frosch, Torsten

The fight against counterfeit pharmaceuticals is a global issue of utmost importance, as failed medication results in millions of deaths every year. Particularly affected are antimalarial tablets. A very important issue is the identification of substandard tablets that do not contain the nominal amounts of the active pharmaceutical ingredient (API), and the differentiation between genuine products and products without any active ingredient or with a false active ingredient. This work presents a novel approach based on fiber-array based Raman hyperspectral imaging to qualify and quantify the antimalarial APIs lumefantrine and artemether directly and non-invasively in a tablet in a time-efficient way. The investigations were carried out with the antimalarial tablet Riamet® and self-made model tablets, which were used as examples of counterfeits and substandard. Partial least-squares regression modeling and density functional theory calculations were carried out for quantification of lumefantrine and artemether and for spectral band assignment. The most prominent differentiating vibrational signatures of the APIs were presented.

2010, Chursanova, M.V., Dzhagan, V.M., Yukhymchuk, V.O., Lytvyn, O.S., Valakh, M.Y., Khodasevich, I.A., Lehmann, D., Zahn, D.R.T., Waurisch, C., Hickey, S.G.

Nanostructured silver films have been prepared by thermal deposition on silicon, and their properties as SERS substrates investigated. The optimal conditions of the post-growth annealing of the substrates were established. Atomic force microscopy study revealed that the silver films with relatively dense and homogeneous arrays of 60-80-nm high pyramidal nanoislands are the most efficient for SERS of both organic dye and inorganic nanoparticles analytes. The noticeable enhancement of the Raman signal from colloidal nanoparticles with the help of silver island films is reported for the first time. © 2009 The Author(s).

2017, Cordero, Eliana, Korinth, Florian, Stiebing, Clara, Krafft, Christoph, Schie, Iwan W., Popp, Jürgen

Raman spectroscopy provides label-free biochemical information from tissue samples without complicated sample preparation. The clinical capability of Raman spectroscopy has been demonstrated in a wide range of in vitro and in vivo applications. However, a challenge for in vivo applications is the simultaneous excitation of auto-fluorescence in the majority of tissues of interest, such as liver, bladder, brain, and others. Raman bands are then superimposed on a fluorescence background, which can be several orders of magnitude larger than the Raman signal. To eliminate the disturbing fluorescence background, several approaches are available. Among instrumentational methods shifted excitation Raman difference spectroscopy (SERDS) has been widely applied and studied. Similarly, computational techniques, for instance extended multiplicative scatter correction (EMSC), have also been employed to remove undesired background contributions. Here, we present a theoretical and experimental evaluation and comparison of fluorescence background removal approaches for Raman spectra based on SERDS and EMSC.

2019, Mondol, Abdullah S., Patel, Milind D., Rüger, Jan, Stiebing, Clara, Kleiber, Andreas, Henkel, Thomas, Popp, Jürgen, Schie, Iwan W.

Pollen studies play a critical role in various fields of science. In the last couple of decades, replacement of manual identification of pollen by image-based methods using pollen morphological features was a great leap forward, but challenges for pollen with similar morphology remain, and additional approaches are required. Spectroscopy approaches for identification of pollen, such as Raman spectroscopy has potential benefits over traditional methods, due to the investigation of the intrinsic molecular composition of a sample. However, current Raman-based characterization of pollen is complex and time-consuming, resulting in low throughput and limiting the statistical significance of the acquired data. Previously demonstrated high-throughput screening Raman spectroscopy (HTS-RS) eliminates the complexity as well as human interaction by incorporation full automation of the data acquisition process. Here, we present a customization of HTS-RS for pollen identification, enabling sampling of a large number of pollen in comparison to other state-of-the-art Raman pollen investigations. We show that using Raman spectra we are able to provide a preliminary estimation of pollen types based on growth habits using hierarchical cluster analysis (HCA) as well as good taxonomy of 37 different Pollen using principal component analysis-support vector machine (PCA-SVM) with good accuracy even for the pollen specimens sharing similar morphological features. Our results suggest that HTS-RS platform meets the demands for automated pollen detection making it an alternative method for research concerning pollen.

2019, Frosch, Timea, Wyrwich, Elisabeth, Yan, Di, Popp, Jürgen, Frosch, Torsten

The particle shape, size and distribution of active pharmaceutical ingredients (API) are relevant quality indicators of pharmaceutical tablets due to their high impact on the manufacturing process. Furthermore, the bioavailability of the APIs from the dosage form depends largely on these characteristics. Routinely, particle size and shape are only analyzed in the powder form, without regard to the effect of the formulation procedure on the particle characteristics. The monitoring of these parameters improves the understanding of the process; therefore, higher quality and better control over the biopharmaceutical profile can be ensured. A new fiber-array-based Raman hyperspectral imaging technique is presented for direct simultaneous in-situ monitoring of three different active pharmaceutical ingredients- acetylsalicylic acid, acetaminophen and caffeine- in analgesic tablets. This novel method enables a chemically selective, noninvasive assessment of the distribution of the active ingredients down to 1 µm spatial resolution. The occurrence of spherical and needle-like particles, as well as agglomerations and the respective particle size ranges, were rapidly determined for two commercially available analgesic tablet types. Subtle differences were observed in comparison between these two tablets. Higher amounts of acetaminophen were visible, more needle-shaped and bigger acetylsalicylic acid particles, and a higher incidence of bigger agglomerations were found in one of the analgesic tablets.

2020, Korinth, Florian, Schmälzlin, Elmar, Stiebing, Clara, Urrutia, Tanya, Micheva, Genoveva, Sandin, Christer, Müller, André, Maiwald, Martin, Sumpf, Bernd, Krafft, Christoph, Tränkle, Günther, Roth, Martin M, Popp, Jürgen

Wide field Raman imaging using the integral field spectroscopy approach was used as a fast, one shot imaging method for the simultaneous collection of all spectra composing a Raman image. For the suppression of autofluorescence and background signals such as room light, shifted excitation Raman difference spectroscopy (SERDS) was applied to remove background artifacts in Raman spectra. To reduce acquisition times in wide field SERDS imaging, we adapted the nod and shuffle technique from astrophysics and implemented it into a wide field SERDS imaging setup. In our adapted version, the nod corresponds to the change in excitation wavelength, whereas the shuffle corresponds to the shifting of charges up and down on a Charge-Coupled Device (CCD) chip synchronous to the change in excitation wavelength. We coupled this improved wide field SERDS imaging setup to diode lasers with 784.4/785.5 and 457.7/458.9 nm excitation and applied it to samples such as paracetamol and aspirin tablets, polystyrene and polymethyl methacrylate beads, as well as pork meat using multiple accumulations with acquisition times in the range of 50 to 200 ms. The results tackle two main challenges of SERDS imaging: gradual photobleaching changes the autofluorescence background, and multiple readouts of CCD detector prolong the acquisition time.

2014, Schmälzlin, E., Moralejo, B., Rutowska, M., Monreal-Ibero, A., Sandin, C., Tarcea, N., Popp, J., Roth, M.M.

Until now, spatially resolved Raman Spectroscopy has required to scan a sample under investigation in a time-consuming step-by-step procedure. Here, we present a technique that allows the capture of an entire Raman image with only one single exposure. The Raman scattering arising from the sample was collected with a fiber-coupled high-performance astronomy spectrograph. The probe head consisting of an array of 20 × 20 multimode fibers was linked to the camera port of a microscope. To demonstrate the high potential of this new concept, Raman images of reference samples were recorded. Entire chemical maps were received without the need for a scanning procedure.

2014, Huang, Y., Fang, Y., Zhang, Z., Zhu, L., Sun, M.

Due to its amazing ability to manipulate light at the nanoscale, plasmonics has become one of the most interesting topics in the field of light-matter interaction. As a promising application of plasmonics, surface-enhanced Raman scattering (SERS) has been widely used in scientific investigations and material analysis. The large enhanced Raman signals are mainly caused by the extremely enhanced electromagnetic field that results from localized surface plasmon polaritons. Recently, a novel SERS technology called remote SERS has been reported, combining both localized surface plasmon polaritons and propagating surface plasmon polaritons (PSPPs, or called plasmonic waveguide), which may be found in prominent applications in special circumstances compared to traditional local SERS. In this article, we review the mechanism of remote SERS and its development since it was first reported in 2009. Various remote metal systems based on plasmonic waveguides, such as nanoparticle-nanowire systems, single nanowire systems, crossed nanowire systems and nanowire dimer systems, are introduced, and recent novel applications, such as sensors, plasmon-driven surface-catalyzed reactions and Raman optical activity, are also presented. Furthermore, studies of remote SERS in dielectric and organic systems based on dielectric waveguides remind us that this useful technology has additional, tremendous application prospects that have not been realized in metal systems.