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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.

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).

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.

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).

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).

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.

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.

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.

As medicine continues to advance our understanding of and knowledge about the complex and multifactorial nature of cancer, new major technological challenges have emerged in the design of analytical methods capable of characterizing and assessing the dynamic heterogeneity of cancer for diagnosis, prognosis and monitoring, as required by precision medicine. With this aim, novel nanotechnological approaches have been pursued and developed for overcoming intrinsic and current limitations of conventional methods in terms of rapidity, sensitivity, multiplicity, non-invasive procedures and cost. Eminently, a special focus has been put on their implementation in liquid biopsy analysis. Among optical nanosensors, those based on surface-enhanced Raman scattering (SERS) have been attracting tremendous attention due to the combination of the intrinsic prerogatives of the technique (e.g., sensitivity and structural specificity) and the high degree of refinement in nano-manufacturing, which translate into reliable and robust real-life applications. In this review, we categorize the diverse strategic approaches of SERS biosensors for targeting different classes of tumor biomarkers (cells, nucleic acids and proteins) by illustrating key recent research works. We will also discuss the current limitations and future research challenges to be addressed to improve the competitiveness of SERS over other methodologies in cancer medicine.

8 pags., 5 figs., 1 tab., Herein we illustrate an effective protocol to boost the optical enhancing properties of gold nanostars. By coating single nanostars with a mesoporous silica layer of the appropriate size (yolk capsules), to localize them under optical microscopy, it is possible to enumerate single particles and design SERS quantitative methods with minute amounts of metallic particles., N. P.-P., L. G., and M. A. C.-D. thank the MINECO-Spain (CTM2014-58481R, CTM2017-84050R, CTQ2017-88648R and RYC-2015-19107), Xunta de Galicia (Centro Singular de Investigacion de Galicia, Acc. 2016-19 and EM2014/035), Generalitat de Cataluña (2017SGR883), URV (2017PFRURV_B2-02), URV and Banco Santander (2017EXIT-08) and the European Union (ERDF). This project has received funding from the European Union’s Horizon 2020 research and innovation program under the MarieSkłodowska-Curie grant agreement No. 713679 and from the Universitat Rovira i Virgili. X. X. acknowledges the Lee Family Scholarship.

Surface-enhanced Raman scattering (SERS) is a molecular-specific spectroscopic technique that provides up to 1010-fold enhancement of signature Raman fingerprints using nanometer-scale 0D to 2D platforms. Over the past decades, 3D SERS platforms with additional plasmonic materials in the z-axis have been fabricated at sub-micrometer to centimeter scale, achieving higher hotspot density in all x, y, and z spatial directions and higher tolerance to laser misalignment. Moreover, the flexibility to construct platforms in arbitrary sizes and 3D shapes creates attractive applications besides traditional SERS sensing. In this Account, we introduce our library of substrate-based and substrate-less 3D plasmonic platforms, with an emphasis on their non-sensing applications as microlaboratories and data storage labels. We aim to provide a scientific synopsis on these high-potential yet currently overlooked applications of SERS and ignite new scientific discoveries and technology development in 3D SERS platforms to tackle real-world issues. One highlight of our substrate-based SERS platforms is multilayered platforms built from micrometer-thick assemblies of plasmonic particles, which can achieve up to 1011 enhancement factor. As an alternative, constructing 3D hotspots on non-plasmonic supports significantly reduces waste of plasmonic materials while allowing high flexibility in structural design. We then introduce our emerging substrate-less plasmonic capsules including liquid marbles and colloidosomes, which we further incorporate the latter within an aerosol to form centimeter-scale SERS-active plasmonic cloud, the world's largest 3D SERS platform to date. We then discuss the various emerging applications arising only from these 3D platforms, in the fields of sensing, microreactions, and data storage. An important novel sensing application is the stand-off detection of airborne analytes that are several meters away, made feasible with aerosolized plasmonic clouds. We also describe plasmonic capsules as excellent miniature lab-in-droplets that can simultaneously provide in situ monitoring at the molecular level during reaction, owing to their ultrasensitive 3D plasmonic shells. We highlight the emergence of 3D SERS-based data storage platforms with 10-100-fold higher storage density than 2D platforms, featuring a new approach in the development of level 3 security (L3S) anti-counterfeiting labels. Ultimately, we recognize that 3D SERS research can only be developed further when its sensing capabilities are concurrently strengthened. With this vision, we foresee the creation of highly applicable 3D SERS platforms that excel in both sensing and non-sensing areas, providing modern solutions in the ongoing Fourth Industrial Revolution. Ministry of Education (MOE) Accepted version This work was funded by Singapore Ministry of Education, Tier 1 (RG11/18) and Tier 2 (MOE2016-T2-1-043) grants, and Max Planck Institute-Nanyang Technological University Joint Lab, the Spanish Ministerio de Economia y Competitividad (CTQ2017-88648R and RYC-2015-19107), the Generalitat de Cataluña (2017SGR883), the Universitat Rovira i Virgili (2017PFR-URV-B2-02), and the Universitat Rovira i Virgili and Banco Santander (2017EXIT-08).

Cancer heterogeneity increasingly requires ultrasensitive techniques that allow early diagnosis for personalized treatment. In addition, they should preferably be non-invasive tools that do not damage surrounding tissues or contribute to body toxicity. In this context, liquid biopsy of biological samples such as urine, blood, or saliva represents an ideal approximation of what is happening in real time in the affected tissues. Plasmonic nanoparticles are emerging as an alternative or complement to current diagnostic techniques, being able to detect and quantify novel biomarkers such as specific peptides and proteins, microRNA, circulating tumor DNA and cells, and exosomes. Here, we review the latest ideas focusing on the use of plasmonic nanoparticles in coded and label-free surface-enhanced Raman scattering (SERS) spectroscopy. Moreover, surface plasmon resonance (SPR) spectroscopy, colorimetric assays, dynamic light scattering (DLS) spectroscopy, mass spectrometry or total internal reflection fluorescence (TIRF) microscopy among others are briefly examined in order to highlight the potential and versatility of plasmonics.

In this work, we report novel methods to produce SERS encoded nanoparticles (SEPs). Either as single nanoparticles (NPs) or as more complex core-satellites structures. Single NPs are produced in an easy and fast one-pot approach which, are further use as building blocks to produce the core–satellite SEPs. The presented protocols are very versatile allowing the NPs SERS codification with an extensive variety of Raman codes. Moreover, this protocol can be applied to different NPs materials and shapes. Furthermore, the core–satellite SEPs are designed to exhibit minimal interparticle distances (

Due to the high surface: volume ratio and the extraordinary properties arising from the nanoscale (optical, electric, magnetic, etc.), nanoparticles (NPs) are excellent candidates for multiple applications. In this context, nanoscience is opening a wide range of modern technologies in biological and biomedical fields, among others. However, one of the main drawbacks that still delays its fast evolution and effectiveness is related to the behavior of nanomaterials in the presence of biological fluids. Unfortunately, biological fluids are characterized by high ionic strengths which usually induce NP aggregation. Besides this problem, the high content in biomacromolecules—such as lipids, sugars, nucleic acids and, especially, proteins—also affects NP stability and its viability for some applications due to, for example, the formation of the protein corona around the NPs. Here, we will review the most common strategies to achieve stable NPs dispersions in high ionic strength fluids and, also, antifouling strategies to avoid the protein adsorption.

Highly nonlinear optical processes require high intensities, typically achieved with ultrashort laser pulses, and hence, they were first observed with the advent of picosecond laser technology. An alternative approach for reaching the required field intensities is offered by localized optical resonances in tailored plasmonic nanostructures, enabling the enhancement of a multitude of nonlinear phenomena. However, so far, plasmon-enhanced high-order nonlinear effects have been restricted to experiments involving short-pulsed and ultrafast laser sources. Here, we demonstrate localized three-photon photoemission from chemically synthesized plasmonic gold nanostars under continuous-wave illumination at sub-MWcm−2 incident intensities. Intensity- and polarization-dependent measurements confirm the nonlinearity of the photoemission process and agree with quantum mechanical calculations of the electron yield from nanostar tips with features smaller than 5 nm, which facilitate local intensity enhancement factors exceeding 1000. Our results open up new avenues for the design of accessible nanoscale coherent electron sources, with potential applications in microscopy, spectroscopy, sensing, and signal processing. Photoemission from nanostructures has raised considerable interest in recent years. The authors propose a low-budget scheme for multiphoton photemission with a continuous-wave laser that may inspire design of accessible nanoscale coherent electron sources.

DOI: 10.1021/acsnano.5b07966 As more biological activities of ribonucleic acids continue to emerge, the development of efficient analytical tools for RNA identification and characterization is necessary to acquire an in-depth understanding of their functions and chemical properties. Herein, we demonstrate the capacity of label-free direct surface-enhanced Raman scattering (SERS) analysis to access highly specific structural information on RNAs at the ultrasensitive level. This includes the recognition of distinctive vibrational features of RNAs organized into a variety of conformations (micro-, fully complementary duplex-, small interfering- A nd short hairpin-RNAs) or characterized by subtle chemical differences (single-base variances, nucleobase modifications and backbone composition). This method represents a key advance in the ribonucleic acid analysis and will have a direct impact in a wide range of different fields, including medical diagnosis, drug design, and biotechnology, by enabling the rapid, high-throughput, simple, and low-cost identification and classification of structurally similar RNAs.

We report a very effective synthetic approach to achieve the in situ growth, directly at the surface of single walled carbon nanotubes, of shape controlled anatase TiO 2 nanocrystals, either as nanorods or nanospheres, by simply tuning the ratio between reactants. Remarkably, the obtained SWCNTs/TiO 2 heterostructures result dispersible in organic solvents, leading to optically clear dispersions. The photocatalytic activity of the SWCNTs/TiO 2 heterostructures, compared with bare TiO 2 nanorods or nanospheres demonstrates a significant enhancement. In particular, SWCNTs/TiO 2 heterostructures demonstrates an enhancement of reaction rate up to 3 times with respect to the commercially available standard TiO 2 powder (TiO 2 P25) under UV light and up to 2 times under visible light.

11] and encouraged by the need of optimization of the self-assembly process that may allow the design of large-scale supercrystals with high optical activity for SERS detection, we report on a straightforward approach to obtain long-range plas-monic supercrystals made of standing core-shell gold-silver nanorods (Au@AgNRs), stabilized with gemini surfactants, by controlling the drop casting conditions. Au@AgNRs (length = 71

// Ana Fernandez-Carrascal 1, * , Manuel Garcia-Algar 1, * , Moritz Nazarenus 1 , Alicia Torres-Nunez 1 , Luca Guerrini 1 , Neus Feliu 2, 3 , Wolfgang J. Parak 3 , Eduardo Garcia-Rico 4 and Ramon A. Alvarez-Puebla 1, 5 1 Department of Physical Chemistry and EMaS, Universitat Rovira i Virgili, Tarragona, Spain 2 Karolinska Institutet, Stockholm, Sweden 3 Philipps-Universitat Marburg, Fachbereich Physik, Marburg, Germany 4 Department of Medical Oncology, Hospital Universitario HM Torrelodones, Torrelodones, Madrid, Spain 5 ICREA, Barcelona, Spain * These authors have contributed equally to this work Correspondence to: Eduardo Garcia-Rico, email: egarcia@hmhospitales.com Ramon A. Alvarez-Puebla, email: ramon.alvarez@urv.cat Keywords: circulating tumor cells, breast cancer, optical sensing, glucose uptake, hyperoxia Received: January 31, 2017 Accepted: June 05, 2017 Published: June 16, 2017 ABSTRACT Quantification of circulating tumor cells (CTCs) in blood samples from cancer patients is a non-invasive approach to monitoring the status of the disease. Most of the methods proposed in the recent years are phenomenological and rely on the use of antibodies labelled with fluorophores, magnetic particles, or immobilized on surfaces to capture the CTCs. Herein, we designed and optimized a method that employs a glucose analogue labelled with a fluorophore which takes advantage of the different metabolic pathways of cancer cells to discern them from normal ones. Notably, we demonstrate that fluorescence signal in tumor cells can be greatly maximized by applying hyperoxia conditions without damaging the cells. These results are demonstrated by means of confocal fluorescence and flow-cytometry measurements in peripheral blood mononuclear cells (PBMC) extracted after Ficoll of human blood samples and spiked with a known concentration of MCF-7 tumor cells.

Early diagnosis, monitoring and treatment selection of cancer represent major challenges in medicine. The definition of the complex clinical and molecular landscape of cancer requires the combination of multiple techniques and the investigation of multiple targets. As a result, diagnosis is normally lengthy, expensive and, in many cases, cannot be performed recursively. In recent years, optical biosensors, especially those based on the unique properties of plasmonic nanostructures, have emerged as one of the most exciting tools in nanomedicine, capable of overcoming key limitations of classical techniques. In this review, we specifically focus our attention on the latest advances in optical biosensors exploiting surface-enhanced Raman scattering encoded particles for the characterization of tumor single cells (molecular biology) and tissues (immunohistochemistry and guided surgery), as well as their application in guided surgery or even in bioimaging of living organisms.

The design and use of materials in the nanoscale size range for addressing medical and health-related issues continues to receive increasing interest. Research in nanomedicine spans a multitude of areas, including drug delivery, vaccine development, antibacterial, diagnosis and imaging tools, wearable devices, implants, high-throughput screening platforms, etc. using biological, nonbiological, biomimetic, or hybrid materials. Many of these developments are starting to be translated into viable clinical products. Here, we provide an overview of recent developments in nanomedicine and highlight the current challenges and upcoming opportunities for the field and translation to the clinic., This work was supported by the Deutscher Akademischer Austauschdienst (DAAD to Philipps Universität Marburg and Zhejiang University, Hangzhou), the Chinesisch Deutsches Zentrum für Wissenschaftsförderung (“CDZ” to Z.G. and W.J.P.), and the Chinese Academy of Science (CAS). Part of this work was supported by the National Natural Science Foundation (51390481, 81227902, 81625011), National Basic Research Program (2014CB931900) of China (to Y.S.), by the European Commission grant Futurenanoneeds (to V.P. and W.J.P.), by the Spanish Ministerio de Economia y Competitividad (CTQ2011-23167 and CTQ2014-59808R to R.A.A.P.), the Generalitat of Catalunya (2014-SGR-612 to R.A.A.P.), the Deutsche Forschungsgemeinschaft (DFG) (AL552/8-1 to R.T.), the Swiss National Science Foundation (NRP62 to P.H.), the Claude & Julianna Foundation (grant to P.H.), the National Science Foundation (NSF) grants CHE-1306928 (to R.P.) and ECS-0601345; CBET 0933384; CBET 0932823; and CBET 1036672 (to N.A.K.), Canadian Institute of Health Research (grant to W.C.W.C.), and Natural Sciences and Engineering Research Council of Canada (grant to W.C.W.C.). S.A. and B.P. acknowledge a fellowship from the Alexander von Humboldt Foundation. N.F. acknowledges the Lars Hiertas Minne Foundation. M.C. acknowledges Ikerbasque for a Research Fellow position. X.C. acknowledges the Intramural Research Program (IRP), National Institute of Biomedical Imaging and Bioengineering (NIBIB), National Institutes of Health (NIH). B.Z.T. acknowledges the Innovation and Technology Commission of Hong Kong (ITC-CNERC14SC01). The Pancreatic Cancer research of A.E.N. and H.M. was funded by the U.S. National Cancer Institute, NIH grant # U01CA198846. A.E. acknowledges Junta de Andalucía (Spain) for a Talentia Postdoc Fellowship, co-financed by the European Union's Seventh Framework Programme, grant agreement no 267226. A.G.S. acknowledges support by BOF (UGent) and FWO (Research Foundation Flanders). Part of this work was supported by the National Natural Science Foundation of China.

An optofluidic device for cell discrimination with two independent interrogation regions is presented. Pumping light coupling to the device and cells’ fluorescence extraction from the two interrogation zones is accomplished employing optical fibers embedded in said optofluidic chip. To test the reliability of this device AU-565 cells -expressing EpCAM and HER2 receptors- and RAMOS cells were mixed in a controlled manner, confined inside an hydrodynamic focused flow in the microfluidic chip and detected individually to be later discriminated as positive (signal re- ception from fluorescently labeled antibodies from the AU-565 cells) or negative events (RAMOS cells). A correlation analysis is performed over the two intensity versus time signals obtained at each of the two interrogation zones. A post-processing analysis permits a peak-to-peak pairing between the two output signals, being the detected peaks at each channel events related to the passing of a single cell through an interrogation region. Said method reduces the influence of noise on the overall data and allows to better discern actual cells’ characteristic intensity bursts from noise without the need of digitally aided signal processing.

International audience; Raspberry-like nano-objects made of large plasmonic satellites (>10 nm) covering a central dielectric particle have many potential applications as photonic materials, superlenses and (bio-) sensors, but their synthesis remains challenging. Herein, we show how to build stable and robust raspberry-like nano-systems with close-packed satellites, by combining monodisperse silica particles (80 or 100 nm diameter) and oppositely charged noble metal nanoparticles (Au or Ag) with well-defined sizes (10-50 nm). The spectral characteristics of their associated plasmonic resonances (wavelength, linewidth, extinction cross-section) and the electromagnetic coupling between satellites were observed using the spatial modulation spectroscopy technique and interpreted through a numerical model. The composite nano-objects exhibit numerous hot spots at satellite junctions, resulting in excellent surface-enhanced Raman scattering (SERS) performance. The SERS efficiency of the raspberry-like clusters is highly dependent on their structure.

10 pags., 7 figs., Current understanding of the mechanisms underlying noncovalent interactions between native DNA and nanoparticles, as well as their impact on the double-helix structure, is far from providing a comprehensive view. It is known that these interactions are largely defined by the physicochemical properties of the metal/liquid interface, in particular by the nanoparticle surface charge. Remarkably, while DNA unzipping upon binding with cationic nanoparticles is reported, the exact determinants of this structural perturbation remain unclear. Herein, plasmon-based spectroscopies (surface-enhanced Raman scattering (SERS) and surface-plasmon resonance (SPR) and theoretical simulations are combined to directly investigate the role of the cooperative binding of cationic nanoparticles with different surface charges on the structural integrity of a large variety of DNAs. The intrinsic nature of the SERS effect unlocks the possibility of selectively examining the impact of nanoparticle clustering on the duplex structure over a wide degree of colloidal aggregation and without the need of external intercalating dyes or strand labeling. This extensive work provides new fundamental insights into the interaction between nucleic acids and nanoparticles, addressing key questions regarding the role played by multiple variables such as the nanoparticle surface charge, the DNA-mediated cluster size and geometry, and nucleic acids' length, composition, and conformational properties., Ministerio de Economia y Competitividad. Grant Number: CTQ2014‐59808R European Research Council. Grant Number: 2014 623527 Generalitat de Catalunya. Grant Number: 2014‐SGR‐480

NOTICE: This is the peer reviewed version of the following article: Elena Pazos, Manuel García-Algar, Cristina Penas, Moritz Nazarenus, Arnau Torruella, Nicolas Pazos-Perez, Luca Guerrini, M. Eugenio Vázquez, Eduardo Garcia-Rio*, José L. Macareñas* and Ramon A. Alvarez-Puebla* (2016), SERS Surface Selection Rules for the Proteomic Liquid Biopsy in Real Samples: Efficient Detection of the Oncoprotein cMYC. J. Am. Chem. Soc., 138, 14206-14209 [DOI: 10.1021/jacs.6b08957]. This article may be used for non-commercial purposes in accordance with ACS Publications Terms and Conditions for self-archiving Blood-based biomarkers (liquid biopsy) offer extremely valuable tools for the noninvasive diagnosis and monitoring of tumors. The protein c-MYC, a transcription factor that has been shown to be deregulated in up to 70% of human cancers, can be used as a robust proteomic signature for cancer. Herein, we developed a rapid, highly specific, and sensitive surface-enhanced Raman scattering (SERS) assay for the quantification of c-MYC in real blood samples. The sensing scheme relies on the use of specifically designed hybrid plasmonic materials and their bioderivatization with a selective peptidic receptor modified with a SERS transducer. Peptide/c-MYC recognition events translate into measurable alterations of the SERS spectra associated with a molecular reorientation of the transducer, in agreement with the surface selection rules. The efficiency of the sensor is demonstrated in cellular lines, healthy donors and a cancer patient This work was funded by Marie Curie Actions (FP7/2007-2013, TECNIOspring no. 600388 and PrioSERS FP72014-623527), the European Research Council (Advanced Grant No. 340055), the Spanish MINECO (CTQ2014-59808R, SAF2013-41943-R, CTQ2015-70698-R, CTQ2013-49317-EXP and the orfeo-cinqa network), the Generalitat of Catalonia (2014-SGR-480, AGAUR 2014 052 and AGAUR 2014 054), the Xunta de Galicia (GRC2013-041), and Medcom Advance S.A. SI

Ultrasensitive direct SERS analysis offers a powerful analytical tool for the structural characterization and classification of nucleic acids. However, acquisition of reliable spectral fingerprints of such complex biomolecules poses important challenges. In recent years, many efforts have been devoted to overcome these limitations, mainly implementing silver colloids as plasmonic substrates. However, a reliable cross-comparison of results reported in the recent literature is extremely hard to achieve, mostly due to the broad set of different surface properties of the plasmonic nanoparticles. Herein, we perform a thorough investigation of the role played by the metal/liquid interface composition of silver colloids in the direct label-free SERS analysis of DNA. Target molecules of increasing complexity, from short homopolymeric strands to long genomic duplexes, were used as probes. We demonstrate how apparently subtle changes in the colloidal surface chemistry can dramatically modify the affinity and the final SERS spectral profile of DNA. This has significant implications for the future design of new analytical strategies for the detection of DNA using SERS without labels.

Iodide ions have been used as an additive to fabricate homogeneous gold spheres with a la carte dimensions, ranging from the nano- (50 nm) to the microscale (ca. 1 μm). Due to the high uniformity and surface functionalization of the produced materials, they undergo spontaneous assembly into organized superlattices upon solvent drying. Thus, optical properties of the particles including localized surface plasmon resonances and surface enhanced Raman scattering (SERS) response, both in solution and organized into superlattices, are also reported. © 2012 American Chemical Society., This work was funded by the Spanish Ministerio de Ciencia e Innovacion (CTQ2011-23167) and by the German science foundation within SFB 840, TP B5.

In this tutorial review, we provide an overview of the recent research toward surface functionalization of plasmonic nanoparticles for the generation of advanced optical sensors that make possible the analysis of various moieties by means of surface enhanced Raman scattering (SERS). Such moieties include atomic ions, low affinity target molecules, inorganic anions, biometabolites, pathogen markers and/or other analytes of interest even under very demanding circumstances such as those related to real life samples. We expect this review to be of interest to researchers in a broad diversity of fields that can take advantage of the unprecedented sensitivity of this type of molecular spectroscopy, in a wide variety of analytical and bioanalytical problems.