Introduction to the Journal of Raman Spectroscopy Emerging Investigators Special Issue

The vibrancy of any scientific field, to a large extent, is reflected in the outstanding contributions of its early career stage investigators. The intent of this Journal of Raman Spectroscopy Emerging Investigators Special Issue is to highlight the ongoing development and applications of Raman methodology that this diverse cohort of invited younger investigators is making to address scientific questions across a wide range of disciplines. Although the use and reliance on Raman spectroscopic signatures by Emerging Investigators is reflected in the ongoing increase of Raman-related publications per year,1 the intent of this Journal of Raman Spectroscopy effort was to primarily focus this Emerging Investigators in Raman Spectroscopy Special Issue on early career stage participants at the 27th International Conference on Raman Spectroscopy (ICORS) that took place in Long Beach, CA, in August 2022. This was the most recent ICORS meeting. Here, we interpreted Emerging Investigators to mean early carrier scientists at the Assistant or very recent Associate Professor level in academic settings, or those who are about to launch their independent research careers. This Special Issue includes 14 invited contributions from emerging investigators from around the world. The research topics covered by these contributions reflect areas where Raman activity is currently making its strongest impact. The articles in this special issue can be grouped into four broad categories: bioanalytical (normal) Raman, SERS analytical and bioanalytical studies, coherent Raman scattering, and Raman of two-dimensional materials, and are summarized as follows. Raman spectroscopy is of course a well-established analytical technique due to its ability to provide highly specific Raman fingerprints for purposes of identifying molecular components in simple and complex samples. Contributions from the laboratories of M. Hedegaard (University of Southern Denmark, Denmark),2 D. Kurouski (Texas A&M, USA),3 and L. Tadeese (MIT, USA),4 all describe experimental investigations where (normal) Raman measurements are used to address bioanalytical questions and, consistent with other current research trends, employ broadly define machine learning and multivariate classification methods for providing quantitative analytical information. Hedegaard et al.2 show that a SVM analysis of the spent culture media of stem cells can establish the pluripotency of these cells. These results suggest Raman can be a highly effective technique for monitoring and controlling the growth of stem cells, which are recognized crucial components of future treatment options for serious and chronic diseases. Rodriguez and Kurouski3 demonstrate that by exploiting the noninvasive, nondestructive, quantitative character of normal Raman spectroscopy, coupled with multivariate data analysis approaches, the amounts of carbohydrates, gluten, carotenoids, and fats in baked foods can be determined. Such applications in the food industry are intended to foster better human health outcomes. In a proof of concept study, antibody coated magnetic Dynabeads exhibit a unique normal Raman signature that can be used to indicate foodborne pathogens and replace immunofluorescent probes when combined with a prior species specific separation step as described in Tadeese et al.4 While the above bioanalytical papers employ visible excitation and normal spontaneous Raman spectroscopy, the largest topical group of Special Issue contributions are in the area of analytical papers that exploit the well-established phenomenon of surface enhanced Raman spectroscopy (SERS) especially in novel bioanalytical applications. The Sharma lab (University of Tennessee, USA)5 demonstrates that SERS provides highly specific and sensitive detection and differentiation of the vital neurotransmitter dopamine and its metabolites when combined with machine learning algorithms. These compounds are central to proper brain function and are recognized as indicators of neurological disorders and some diseases. As shown in this work, the enhancement due to the plasmonic effects of Au nanoparticles allows determinations at physiologically relevant concentrations in biological fluids. N. Choi et al.6 (University of Duisburg-Essen, Germany) report on the development of an optimized SERRS (surface-enhanced resonance Raman scattering)-based lateral flow assay strip to improve the detection sensitivity of beta-hCG, a pregnancy diagnostic biomarker. For this purpose, Au nanostars act as the highly sensitive SERS nanotag combined with the electronically and plasmonically enhanced 785 nm excited NIR dyes. In another biological SERS study, Voronine and co-workers (University of South Florida, USA)7 provide one of first examples of biosensing based on aluminum (Al) plasmonics. A methodology was established for successfully acquiring SERS images of the intact cell membranes of ovarian cancer cells on roughened Al substrates. Despite the relatively small enhancement factor (~30), Al was selected as an alternative to Au and Ag due to the cost, poor repeatability, and toxicity of these noble metal substrates. In another example of the use of SERS for a bioanalytical application Profant et al.8 (Charles University, Czech Republic) explore how SERS can be valuable in developing an optical method for the detection and analysis of thiram, a widely known fungicide. SERS measurements of solid state and several solution samples of thiram, coupled with DFT calculations, were carried out to learn about the molecular details of thiram conformations and surface interactions to maximize the potential for SERS to be used for sensitive detection of this analyte. The contribution from the lab of Pietro Strobbia9 (University of Cincinnati, USA) also addresses SERS detection of environmental contaminants but employs a very different approach based on rationally designed aptamers for homogeneous SERS detection. These workers demonstrate a design procedure centered on a well-characterized aptamer sequence for ATP binding and then transfer the knowledge gained to develop an aptamer for estradiol, a common water contaminant. These homogenous sensors allow for in situ analysis and continuous monitoring which are highly valuable for environmental analysis in the field. A more general spectroscopic investigation of SERS is given by the Gawinkowski (Institute of Physical Chemistry Polish Academy of Sciences, Poland) group10 who report on a constructed, integrated microscope system equipped with a range of Raman excitation wavelengths for studying the properties of plasmonically active nanostructured surfaces via SERS that can have applications in various fields. In particular, SERS excitation profiles and SERS directionality defocused hyperspectral imaging of a model dye on Au nanorods, have been obtained and analyzed. These observations of SERS signal heterogeneity and directionality are intended to be used for developing new SERS substrates with improved detection limits as well as revealing the effects of plasmonic nanostructure on the electronic and geometric structure of adsorbates. Coherent Raman spectroscopies can offer significant advantages over spontaneous Raman observations for some applications, as has been well established since the commercial accessibility of high-powered lasers in the visible. This has been especially true for imaging where rapid, real-time, label-free chemically specific targeting can be highly beneficial for biomedical applications. Zhang (Purdue, University, USA)11 has reviewed recent achievements in Raman imaging using coherent anti-Stokes Raman scattering (CARS) and stimulated Raman scattering (SRS) to study the quantity, distribution, composition, and dynamics of lipid droplets which are ubiquitous organelles found in most mammalian cells and play a pivotal role in various cellular functions. Hyper-spectral CARS and SRS imaging in both cells and living organisms are discussed. Furthermore, SRS results are presented describing how lipid droplet mobility may be controlled with photo-switchable dyes. In a technically related contribution to this Special Issue, the Kieu (University of Arizona, USA) group12 has developed a numerical simulation technique for maximizing the performance of spectral focusing, a widely used current experimental technique for accomplishing rapid coherent Raman imaging. Their approach is demonstrated for a fiber laser system. The developed simulation tool accommodates optical pulses of arbitrary shape and is available in user-friendly, open-source software package that is applicable to high resolution Raman spectral acquisitions in the fingerprint and CH region. The final contribution in the CRS area is the work by V. Kumar et al. (University of Duisburg-Essen, Germany)13 providing the first demonstration of heterodyne-detected CARS-ROA (Raman optical activity) of chiral molecules in an achiral solvent. The most significant advantage heterodyne-detected CARS-ROA offers relative to ROA is the reduction of signal acquisition time from several hours to several minutes due to the high ratio of the chiral Raman signal compared to the achiral CARS background. Experimental measures demonstrate the ability to rapidly distinguish the R- and S-atropisomers of MOM-BINOL, an important synthetic precursor to a variety of chiral organo-catalysts. These results represent the first step toward exploiting the speed of coherent ROA for the purpose of kinetically monitoring reaction dynamics. The final grouping of papers to this Special Issue reflects a newer materials research area of Raman scattering especially active in the past decade; the use of spontaneous Raman for the structural characterization of materials with reduced dimensionality for the purpose of understanding the unique properties of these ultrathin films. The Xi Ling laboratory (Boston University, USA) contribution14 demonstrates how the Raman spectra of transition metal dichalcogenides (TMDCs) such as few-layer stacked MoS2 can be used to determine the layered architecture of these complex structures. Central to this work is a machine learning-assisted low-frequency Raman based methodology, informed by DFT results, that can characterize the twist angle of these thin layered samples. More specifically, this combined experimental and theoretical methodology finds that the low frequency modes are mainly influenced by nearest and second nearest layer effects and thus results in an improved model for understanding the interlayer breathing modes of stacked few-layer MoS2. Extension to other 2D materials systems can be readily achieved. The other contribution in the 2D materials area is an experimental study of the TMDC WS2 thin films.15 Tischler's group (Bar-Ilan University, Israel) exploits the phenomenon known as interference enhanced Raman Scattering (IERS) resulting from the constructive interferences of spontaneous Raman signals generated by layered materials that are deposited on various metal dielectric coated substrates relative to Si/SiO2. The observed IERS spectra and corresponding enhancement factors derived from these interference effects determine structural and defect information in these few-layered 2D materials as demonstrated by the Raman results of several layer WS2 on Au and Al coatings.