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In recent years, metal-organic frameworks, in general, and zeolitic imidazolate frameworks, in special, had become popular due to their large surface area, pore homogeneity, and easy preparation and integration with plasmonic nanoparticles to produce optical sensors. Herein, we summarize the late advances in the use of these hybrid composites in the field of surface-enhanced Raman scattering and their future perspectives.

Tear analysis has become an invaluable asset in clinical research in order to identify and quantify novel biomarkers for a wide array of conditions. The present work is intended to take this area of study one step further by implementing an innovative sensing platform through which exploration of low-molecular-weight compounds is conducted outperforming traditional analytical technologies. With this aim, carefully engineered plasmonic nanoassemblies have been synergistically combined with molecular-sieving materials giving rise to size-selective samplers with SERS detection capabilities. These architectures have been then integrated onto hydrogel-based contact lenses and tested in simulated tear fluids in order to evidence their operational features. Through this approach, a prolonged analyte accumulation can be realized, thus providing a competitive advantage in those scenarios where concentration of biomarkers is typically low or minimum sample volumes are not met. Additionally, quenching of metabolic flux and analyte extraction protocols can be circumvented, hence preventing the intrinsic physical and chemical interferences stemming from these procedures. The obtained results render these sensing platforms as promising medical devices, and constitute a great opportunity in order to expand the clinical toolkit in tear analysis.

6 pags., 4 figs., Here, we present and implement a new approach for producing modular inkjet-printable surface-enhanced Raman scattering (SERS) chemosensors. These sensors, combined with a rapid large field-of-view imaging system allow for fast imaging of the chemical characteristics of a sample. The performance of these materials is illustrated by printing a pH sensor on paper and interrogating aqueous solutions at different pH values. Results show single-shot images exceeding 9 mm2 which are readily read out via SERS imaging., M.L. and N.F.v.H. acknowledge support from the Ministry of Science, Innovation, and Universities (MCIU: RTI2018-099957-J-I00 and PGC2018-096875-B-I00). N.F.v.H. acknowledges the financial support from the European Commission (ERC Advanced Grant 670949-LightNet) and the AGAUR (2017SGR1369). This work was partially funded by CEX2019-000910-S [MCIN/ AEI/10.13039/501100011033], Fundació Privada Cellex, Fundació Privada Mir-Puig, and Generalitat de Catalunya through the CERCA program. V.G. acknowledges Ministry of Science, Innovation, and Universities for financial support (FIS2017-91413-EXP and PGC2018-095777-B-C21). I.C, N.P.P., and R.A.A.P. acknowledge support by the Ministry of Science, Innovation, and Universities (PID2020-120306RB-I00 and PDC2021-121787-I00), the AGAUR (2017SGR883), and the Universitat Rovira i Virgili (2021PFR-URV-B2-02).

16 pags., 7 figs., 1 tab., Goldnanostars are among the most efficient plasmonic nano-materials for optical sensing with surface enhanced Ramans cattering. In recent years,goldnanostars have increased relevance in physics,analytical chemistry, environmental science,biology and medicine,and in particularin sensing and therapy. These colloid scan sustain ultra strong electromagnetic fields which allow their use as single particles optical enhancers;are colloidally stable and may have a marked catalytical activity. Due to their exotic shape,these colloids present characteristic optical and reactive behaviors. Here,we briefly discuss the optical properties, the synthetic routes and the analytical applications of these nanoparticles., This work is supportedby the Ministeriode Ciencia Innovacion/AEI and the European Union Next Generation /PRTR(PID2020-120306RB-I00 and PDC2021-121787-I00),the AGAUR (2017SGR883),the Universitat Rovira i Virgili (2021PFR-URV-B2-02), the Cluster of Excellence’ Advanced Imaging of Matter’of the Deutsche Forschungsgemeinschaft (DFG)– EXC 2056 – project ID390715994and the ENSEMBLE3 project(GA No. MAB/2020/14) Foundation for Polish Science-European Union (GA.No.857543)

Surface-enhanced Raman scattering (SERS) imaging is a powerful technology with unprecedent potential for ultrasensitive chemical analysis. Point-by-point scanning and often excessively long spectral acquisition-times hamper the broad exploitation of the full analytical potential of SERS. Here, we introduce large scale SERS particle screening (LSSPS), a multiplexed widefield screening approach to particle-characterization, which is 500-1000 times faster than typical confocal Raman implementations. Beyond its higher throughput, LSSPS simultaneously quantifies both the sample’s Raman and Rayleigh scattering, allowing for an unprecedented correlation of SERS activity with the particle-size and to directly quantify the fraction of SERS active particles.

Herein, we present an optimized bottom-up approach for the fabrication of homogeneous small spherical silver nanoparticles, with average diameter sizes ranging from 10 to 30 nm and the associated p...

The synthesis of a hydrogel-based soft contact lens featuring laser shielding capabilities is reported. These light-protective properties are accomplished through the integration of gold-based plasmonic nanoresonators into the lens polymer network, which provides the hydrogel with a high optical density while preserving visible light transmittance. The implementation of these hybrid materials shows great potential in the eye care setting in terms of applications. Along these lines, the ability of the Au nanocomposites to act as efficient light concentrators renders this approach a cost-effective alternative to other less absorbing formulations which may also be toxic or degradable upon light irradiation. Furthermore, the use of these hybrid lenses would provide the wearer with an all day long protection and a minimal obstruction to perform common tasks in those scenarios where high powered light sources are operated.

New SERS detection platforms are required for the quick and easy preparation of sensing devices for food, agriculture, and environmental science. For quantitative sensing, it is important that a sensing material, in addition to efficient sensing, provides extraction and concentration of the target molecules such as toxic pesticides or healthy vitamins. We design such films adopting the Liesegang rings formation process that includes the reaction–diffusion of silver nitrate and melamine followed by the precipitation of different intermediates and their reduction by light in a pectin medium. Surprisingly, we find that the presence of melamine provides an excellent substrate for the extraction of pollutants at the solid-liquid interface giving rise to a powerful but easy and fast method for the quantification of fruits’ quality. The complex silver and melamine containing films show high sensitivity even at relatively low silver concentrations.

28 pags., 14 figs. -- This article belongs to the Special Issue Exosomes in Cancers Therapy, Exosomes are emerging as one of the most intriguing cancer biomarkers in modern oncology for early cancer diagnosis, prognosis and treatment monitoring. Concurrently, several nano-plasmonic methods have been applied and developed to tackle the challenging task of enabling the rapid, sensitive, affordable analysis of exosomes. In this review, we specifically focus our attention on the application of plasmonic devices exploiting surface-enhanced Raman spectroscopy (SERS) as the optosensing technique for the structural interrogation and characterization of the heteroge-neous nature of exosomes. We summarized the current state-of-art of this field while illustrating the main strategic approaches and discuss their advantages and limitations., This research was supported by the Spanish Ministerio de Economia y Competitividad (CTQ2017-88648R and RYC-2016-20331), the Generalitat de Cataluña (2017SGR883), and the Universitat Rovira I Virgili (FR 2019-B2).

Ramon A. Alvarez-Puebla, Jian-Feng Li and Xing Yi Ling introduce the Nanoscale themed collection on advances in plasmonics and its applications.

Herein, we present a method to obtain particles composed of a segregated alloy of silver coated with gold. These particles are achieved through the controlled Ostwald ripening of small gold nanoparticles (NPs) on the surfaces of larger silver particles. The prepared segregated nanoalloyed colloids benefit from the advantages of gold and silver with none of their drawbacks. These platforms provide optical efficiencies which are superior to those of silver with the chemical resistance and biocompatibility of gold.

Plasmonic reversible gas sensors are of paramount importance for the monitoring of indoor environments. Herein, we design and engineer a plasmonic foam, with a high surface area, confined inside a capillary glass tube for the live monitoring of carbon monoxide (CO) in closed environments using surface-enhanced resonance Raman scattering. The illumination of the sensor with light during the flow of air allows the live monitoring of the concentration of atmospheric CO through surface-enhanced resonance Raman scattering. The sensor was prepared with a detection range from 10 to 40 ppm, due to health needs. The results show a sensitive, selective, reversible and robust sensor applicable to the monitoring of CO levels but also to other gas species upon appropriate functionalization.

Sensors with fast response and high sensitivity are in high demand. Metal-organic frameworks (MOFs) are controlled porous materials formed by the coordination of a metallic ion with organic linkers. These materials present many advantages such as high surface areas, large pore volumes with adjustable and homogeneous pore diameters, and easy synthetic preparation. Thanks to these intrinsic features, as well as their ability of combination with other nanostructures, MOFs have been exploited as enabling materials for sensing a broad range of analytes, from gases to small molecules and metal ions, at very low detection limits. In this chapter, we examined various types of MOFs employed in sensing applications and how the key features such as pore size and morphology, integrated with other classes of nanomaterials, determine the sensing performances and potential applications.

Direct, label-free analysis of nucleic acids via surface-enhanced Raman spectroscopy (SERS) has been continuously expanding its range of applications as an intriguing and powerful analytical tool for the structural characterization of diverse DNA structures. Still, interrogation of nucleic acid tertiary structures beyond the canonical double helix often remains challenging. In this work, we report for the first time the structural identification of DNA triplex structures. This class of nucleic acids has been attracting great interest because of their intriguing biological functions and pharmacological potential in gene therapy, and the ability for precisely engineering DNA-based functional nanomaterials. Herein, structural discrimination of the triplex structure against its duplex and tertiary strand counterparts is univocally revealed by recognizing key markers bands in the intrinsic SERS fingerprint. These vibrational features are informative of the base stacking, Hoogsteen hydrogen bonding and sugar–phosphate backbone reorganization associated with the triple helix formation. This work expands the applicability of direct SERS to nucleic acids analysis, with potential impact on fields such as sensing, biology and drug design.

This is the peer reviewed version of the following article: Martínez-Calvo, M.; Guerrini, L.; Rodríguez, J.; Álvarez Puebla, R. A.; Mascareñas, J. L. (2020), Surface-enhanced Raman Scattering Detection of Nucleic Acids exhibiting Sterically Accessible Guanines using Ruthenium-polypyridyl Reagents. J. Phys. Chem. Lett., 11: 7218–7223, which has been published in final form at https://doi.org/10.1021/acs.jpclett.0c02148. This article may be used for non-commercial purposes in accordance with ACS Terms and Conditions for Use of Self-Archived Versions Here, we report the application of surface-enhanced Raman scattering (SERS) spectroscopy as a rapid and practical tool for assessing the formation of coordinative adducts between nucleic acid guanines and ruthenium polypyridyl reagents. The technology provides a practical approach for the wash-free and quick identification of nucleic acid structures exhibiting sterically accessible guanines. This is demonstrated for the detection of a quadruplex-forming sequence present in the promoter region of the c-myc oncogene, which exhibits a nonpaired, reactive guanine at a flanking position of the G-quartets We are thankful for the financial support from the Xunta de Galicia (Centro singular de investigación de Galicia accreditation 2019-2022, ED431G 2019/03) and the European Union (European Regional Development Fund – ERDF). We also acknowledge the support given by the Spanish Grant SAF2013-41943-R and SAF2016-76689-R, the Xunta de Galicia (Grants 2015-CP082, ED431C 2017/19,), the Spanish Ministry de Economia y Competitividad (CTQ2017-88648R and RYC-2016-20331), the Generalitat de Cataluña (2017SGR883), the Universitat Rovira i Virgili (2019PFR-URV-B2-02), the Universitat Rovira i Virgili and Banco Santander (2017EXIT-08), and the European Research Council (Advanced Grant No. 340055). M.M.-C. thanks the Ministerio de Economı́a y Competitividad for the Postdoctoral fellowship (IJCI-2014-19326) and the Ministerio de Ciencia e Innovación and Ministerio de Universidades for the Distinguished Researcher contract “Beatriz Galindo” (BEAGAL18/00144). J.R. thanks Xunta de Galicia for her predoctoral fellowship SI

Supercrystals, made of ordered plasmonic nanoparticles (NPs) in close contact, turn out as efficient SERS substrates. However, the production of highly homogeneous structures implies precise control over a multitude of parameters including quality of the building blocks, solvent evaporation rate, and surface chemistry interactions. To pursue this goal, different approaches using templates to self-assembly NPs have been developed in recent years. Here, we review the most common procedures employing two different substrates, planar and patterned templates. Several approaches and strategies are described showing the optical properties of the resulted supercrystals and their behavior as SERS substrates.

SERS activity can be increased by the formation of hot spots at the interparticle junctions of plasmonic nanoparticles in very close proximity, dramatically improving the enhancement factors in comparison with isolated nanoparticles. Controlling the number and geometrical architecture of hot spots, while endowing the clusters with colloidal stability, results in feasible optical sensors, able to provide quantitative SERS responses. Here, we review the approaches proposed to date to produce colloidal stable clusters, focusing on the control of the coordination number of nanoparticle assemblies and interparticle gaps. Clusters of spherical nanoparticles of the same size and rods of the same size are described to subsequently outline core-satellite constructs of nanoparticles of different sizes. Besides, purification processes for nanoparticle clusters are revised to provide efficient production in high yields.

11 pags., 5 figs.-- Open Access funded by Creative Commons Atribution Licence 3.0, Herein, we present a fabrication approach that produces homogeneous core-satellite SERS encoded particles with minimal interparticle gaps (, This work was funded by the Spanish Ministerio de Economia y Competitividad (CTQ2017-88648R, RYC-2016-20331, and RYC2015-19107), the Generalitat de Catalunya (2017SGR883), the ˜ Universitat Rovira i Virgili (2017PFR-URV-B2-02), and the Universitat Rovira i Virgili and Banco Santander (2017EXIT-08).

Nanometric probes based on surface-enhanced Raman scattering (SERS) are promising candidates for all-optical environmental, biological and technological sensing applications with intrinsic quantitative molecular specificity. However, the effectiveness of SERS probes depends on a delicate trade-off between particle size, stability and brightness that has so far hindered their wide application in SERS imaging methodologies. In this Article, we introduce holographic Raman microscopy, which allows single-shot three-dimensional single-particle localization. We validate our approach by simultaneously performing Fourier transform Raman spectroscopy of individual SERS nanoparticles and Raman holography, using shearing interferometry to extract both the phase and the amplitude of wide-field Raman images and ultimately localize and track single SERS nanoparticles inside living cells in three dimensions. Our results represent a step towards multiplexed single-shot three-dimensional concentration mapping in many different scenarios, including live cell and tissue interrogation and complex anti-counterfeiting applications.

Detecting small variations in the levels of IL-6 is crucial for the early diagnosis of sepsis. To be useful in clinical decision-making, this requires detecting IL-6 rapidly in whole blood and with portable readers. Here we introduce immunosensors made of filter paper that use plasmonic nanoprobes to detect IL-6 rapidly in unprocessed blood with an unmodified smartphone. Key aspects of the biosensor fabrication were optimized in order to reduce the assay time without losing sensitivity. This included testing three bioconjugation routes for protein attachment to nanoprobes using gold nanoparticles covered with carboxylate or amine moieties, or polyvinylpyrrolidone (PVP), as starting materials, and using alternating layers of polyelectrolytes to bind the capture antibody to the paper substrate. Smartphone-based signal quantification was achieved with a custom-made app featuring a unique augmented reality guidance system that circumvents the need for smartphone attachments and automates all the steps involved in color quantification. The biosensors were able to detect IL-6 with a limit of detection of 0.1 pg mL(-1) and a total assay time within 17 min. They could also detect an increase in IL-6 of only 12.5 pg mL(-1) over basal levels in whole blood with 99% confidence. The high sensitivity and rapid turnaround time afforded by the optimized biosensors and the fully automated real-time densitometry app make our biosensors well suited for emergency healthcare situations such as the identification of potential sepsis cases., R. R. acknowledges financial support from FEDER/Ministerio de Ciencia, Innovacion y Universidades/Agencia Estatal de Investigacion/- Proyecto CTQ2017-82432-R (biosensor development) and Proyecto CTQ2017-92226-EXP (app development). R. R. and S. M. R. acknowledge funding from a Radix fellowship from IdISBa/Impost turisme sostenible/Govern de les Illes Balears. A. A. acknowledges a fellowship for doctoral studies from Roche (Stop fuga de cerebros program). R. A. A.-P. and N. P. P. acknowledge financial support from Spanish Ministerio de Economia y Competitividad (CTQ2017-88648R and RYC-2015-19107), the Generalitat de Cataluna (2017SGR883), the Universitat Rovira i Virgili (2018PFR-URV-B2-02), and the Universitat Rovira i Virgili and Banco Santander (2017EXIT-08).

Dual-mode optical platforms combining fluorescence (or metal-enhanced fluorescence, MEF) and surface-enhanced Raman scattering (SERS) signals into a single probe are emerging as powerful sensing analytical tools, especially in biomedical applications. SERS–fluorescence encoded particles (SFEPs) combine the unique advantages of fluorescence spectroscopy for the rapid read-out over a large area with the high-level of multiplexing and specificity of SERS. This review aims to provide a detailed summary and a critical discussion on the developments of these materials. This will start by highlighting fundamental aspects of the two techniques, then presenting their main building units and corresponding assembling designs and, finally, providing illustrative examples of potential applications.

In this manuscript, we demonstrate the applicability of a metabolic liquid biopsy for the monitoring and staging of patients with lung cancer. This method provides an unbiased detection strategy to establish a more precise correlation between CTC quantification and the actual burden of disease, therefore improving the accuracy of staging based on current imaging techniques. Also, by applying statistical analysis techniques and probabilistic models to the metabolic status and distribution of peripheral blood mononuclear cell (PBMC) populations “perturbed” by the presence of CTCs, a new category of adaptive metabolic pattern biomarker (AMPB) is described and unambiguously correlated to the different clinical stages of the patients. In fact, this strategy allows for classification of different categories of disease within a single stage (stage IV) before computed tomography (CT) and positron emission tomography (PET) scans and with lower uncertainty., Lung cancer: Blood test gauges metabolic differences to reveal disease stage A new blood test could offer accurate staging information for patients with lung cancer. Ramon Alvarez-Puebla from ICREA and Universitat Rovira i Virgili in Tarragona, Spain, and colleagues developed the test using white blood cells seeded with lung cancer cells. The researchers introduced a fluorescent analog of glucose into the samples, which allowed them to identify tumor cells on the basis of elevated sugar consumption. The team evaluated this ‘metabolic liquid biopsy’ on blood samples from a small number of healthy donors and patients with metastatic lung cancer. The assay reliably differentiated between the two groups, with no CTCs detected in the healthy controls; patients with worse outcomes had higher CTC counts; and measuring the extent to which tumor cells affected the metabolism of non-cancerous cells in the same samples correlated with disease stage accounting for a new adaptative biomarker that allows for classification of different categories of disease.

Colloidal nano- and micro-particles can introduce new properties and functionalities to existing materials and thus are a valuable building block for the construction of novel materials. This is discussed for the case of ion-selective ligands, hence molecules that can bind specifically ions of one type. First, in case ion-selective fluorescent ligands are attached to the surface of particles, these fluorophores sense the local ion concentration at the particle surface and not the bulk ion concentration. Thus, the ion-response of the ligands can be tuned by attaching them to the surface of particles. Second, in case ligands specific for particular ions are bound to the surface of particles, these ions can provide contrast and thus the particles can be imaged. This involves for example Gd-ions, which provide contrast for magnetic resonance imaging (MRI), and 111In-ions, which provide contrast for imaging of radioactivity. By attaching the ligands to the surface of particles, their physicochemical properties (as for example size and solubility) are changed, which affects their interaction with cells and, consequently, biodistribution. Attachment of ion-chelators for imaging to particles thus allows for tuning their biodistribution. Third, ion-specific ligands can be also attached to the surface of magnetic particles. In this case ions bound to the ligands can be extracted with magnetic field gradients and magnetic separation becomes possible. Therefore, magnetic particles provide a handle to the ligands, which enables the extraction of ions from solution. These examples demonstrate how the attachment of different types of colloidal particles to one existing class of molecules, ion-selective ligands, can open new fields of applications of these molecules.

Plasmonic optical biosensors for the analysis of nucleic acids have drawn a great deal of interest in nanomedicine because of their capability to overcome major limitations of conventional methods. Within this realm, surface-enhanced Raman scattering (SERS)-based sensing is progressively emerging as a powerful analytical tool beyond the basic grounds of academia to viable commercial products. SERS benefits from the synergistic combination between the intrinsic structural specificity and experimental flexibility of Raman spectroscopy, the extremely high sensitivity provided by plasmonic nanomaterials, and the tremendous advances in nanofabrication techniques and spectroscopic instrumentation. SERS application to nucleic acids analysis has been largely restricted to indirect sensing approaches, where a SERS reporter and oligonucleotide ligands are typically combined onto the nanomaterials to enable extrinsic detection of the target sequences. On the other hand, the acquisition of the intrinsic SERS vibrational fingerprint of nucleic acids (direct sensing) has traditionally suffered from major limitations. However, recent years have witnessed a burst of interest in this area, largely driven by the efforts to address key reproducibility and sensitivity issues. In this tutorial review, we summarize and discuss the most recent cutting-edge research in the field of direct SERS sensing of nucleic acids by coherently organising the diverse data reported in the literature in a structurally logical fashion.

Changes in protein expression levels and protein structure may indicate genomic mutations and may be related to some diseases. Therefore, the precise quantification and characterization of proteins can be used for disease diagnosis. Compared with several other alternative methods, surface-enhanced Raman scattering (SERS) spectroscopy is regarded as an excellent choice for the quantification and structural characterization of proteins. Herein, we review the main advance of using plasmonic nanostructures as SERS sensing platform for this purpose. Three design approaches, including direct SERS, indirect SERS, and SERS-encoded nanoparticles, are discussed in the direction of developing new precise approaches of quantification and characterization of proteins. While this Review is focused on proteins, in order to highlight concepts of SERS-based sensors also detection of other biomolecules will be discussed.

3D plasmonic colloidosomes are superior SERS sensors owing to their high sensitivity and excellent tolerance to laser misalignment. Herein, we incorporate plasmonic colloidosomes in a microfluidic channel for online SERS detection. Our method resolves the poor signal reproducibility and inter-sample contamination in the existing online SERS platforms. Our flow system offers rapid and continuous online detection of 20 samples in less than 5 min with excellent signal reproducibility. The isolated colloidosomes prevent cross-sample and channel contamination, allowing accurate quantification of samples over a concentration range of five orders of magnitude. Our system demonstrates high-resolution multiplex detection with fully preserved signal and Raman features of individual analytes in a mixture. High-throughput multi-assay analysis is performed, which highlights that our system is capable of rapid identification and quantification of a sequence of samples containing various analytes and concentrations.

Nanometric probes based on surface-enhanced Raman scattering (SERS) are promising candidates for all-optical environmental, biological and technological sensing applications with intrinsic quantitative molecular specificity. However, the effectiveness of SERS probes depends on a delicate trade-off between particle size, stability and brightness that has so far hindered their wide application in SERS imaging methodologies. In this Article, we introduce holographic Raman microscopy, which allows single-shot three-dimensional single-particle localization. We validate our approach by simultaneously performing Fourier transform Raman spectroscopy of individual SERS nanoparticles and Raman holography, using shearing interferometry to extract both the phase and the amplitude of wide-field Raman images and ultimately localize and track single SERS nanoparticles inside living cells in three dimensions. Our results represent a step towards multiplexed single-shot three-dimensional concentration mapping in many different scenarios, including live cell and tissue interrogation and complex anti-counterfeiting applications.

Changes in protein expression levels and protein structure may be related to some diseases. Thus the precise quantification and characterization of proteins is already used for the disease diagnosis. Compared with several other alternative methods, indirect surface-enhanced Raman scattering (SERS) spectroscopy, aided by the use of chemosensors with high affinity and selectivity for the target protein, is regarded as an excellent choice for the quantification and structural characterization of biopolymers. Herein, we review the main advance of using plasmonic nanostructures combined with chemosensors as SERS sensing platforms for the detection and quantification of proteins.

Newly advanced applications of surface-enhanced Raman scattering (SERS) spectroscopy (SERS) are continuously emerging as promising nanotechnological alternatives for rapid, low-cost, sensitive analysis of nucleic acids. In this chapter, we discuss the key concepts of this technique and its rationale of implementation in nucleic acid analysis, illustrating relevant and representative examples from the literature.

In this study, direct surface-enhanced Raman scattering (SERS) spectroscopy is used as an exquisite nano-optical tool for ultrasensitive structural characterisation of abasic sites in DNA. In addition, the conformational discrimination (intra- vs. extra-helical) of the nucleobase opposite to the abasic site was also achieved.

The discovery of the enhancement of Raman scattering by molecules adsorbed on nanostructured metal surfaces is a landmark in the history of spectroscopic and analytical techniques. Significant experimental and theoretical effort has been directed toward understanding the surface-enhanced Raman scattering (SERS) effect and demonstrating its potential in various types of ultrasensitive sensing applications in a wide variety of fields. In the 45 years since its discovery, SERS has blossomed into a rich area of research and technology, but additional efforts are still needed before it can be routinely used analytically and in commercial products. In this Review, prominent authors from around the world joined together to summarize the state of the art in understanding and using SERS and to predict what can be expected in the near future in terms of research, applications, and technological development. This Review is dedicated to SERS pioneer and our coauthor, the late Prof. Richard Van Duyne, whom we lost during the preparation of this article., Funding is acknowledged from the European Research Council (ERC Advanced Grant No. 787510-4DBIOSERS to L.M.L.-M., ERC Advanced Grant No. 789104-eNANO to F.J.G.A., ERC Starting Grant No. 259432-MULTIBIOPHOT to J.K., ERC Consolidator Grant No. 772108-DarkSERS); the Department of Education of the Basque Government (Grant No. IT1164-19 to J.A.); the Spanish MINECO (CTQ2017-88648-R to R.A.-P., MAT2016-77809-R to I.P.-S. and J.P.-J.); the EPSRC (EP/P034063/1 to S.B., EP/L027151/1 to J.B., EP/L014165/1 to D.G. and K.F.); IDUN-Danish National Research Foundation (DNRF122) and Villum Fonden (Grant No. 9301) to A.B.; the National Research Foundation of Korea (Grant No. 2019R1A2C3004375 to J.B.); the German Science Foundation, DFG (SFB 1278 Polytarget (Project B4) to V.D., Grant No. SCHL 594/13-1 to S.S., Germany’s Excellence Strategy (EXC 2089/1-390776260) to S.M.); the Federal Ministry of Education and Research, Germany (BMBF) (Grant InfectoGnostics 13GW0096F to D.C.-M. and J.P.); DARPA-16-35-INTERCEPT-FP-018 to L.F.; the UK BBSRC (Grant No. BB/L014823/1 to R.G.); the Department of Science and Technology (DST Nanomission Project SR/NM/NS-23/2016 to K.G.T.); the U.S. National Science Foundation (Grant No. CHE-1707859 to A.J.H., Center for Sustainable Nanotechnology CHE-1503408 (Centers for Chemical Innovation Program) to C.L.H., Center for Chemical Innovation Chemistry at the Space-Time Limit (CaSTL) CHE-1414466 to G.C.S. and R.P.V.D., Grant No. CHE-1807269 to K.A.W.); the Knut and Alice Wallenberg Foundation to M.K.; the Office of Naval Research (Grant No. N00014-18-1-2876 to N.A.K.); Royal Society of New Zealand Te Apa̅rangi to E.L.R. and B.A.; Singapore Ministry of Education, Tier 1 (RG11/18) to X.Y.L.; the Photoexcitonix Project in Hokkaido Univ., Japan, to K.M.; BioNano Health-Guard Research Center funded by the Ministry of Science and ICT (MSIT) of Korea as Global Frontier Project (Grant No. H-GUARD_2013M3A6B2078947) to J.-M.N.; NSFC of P. R. China (Grant No. 21705015 to Y.O., Grant No. 21633005 to B.R.); National Key R&D Program (2017YFA0206902) to C.X. This work was coordinated under the Maria de Maeztu Units of Excellence Program from the Spanish State Research Agency—Grant No. MDM-2017-0720.