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7 pags., 6 figs., -- Open Access funded by Creative Commons Atribution Licence 4.0, The design of achromatic optical components requires materials with high transparency and low dispersion. We show that although metals are highly opaque, densely packed arrays of metallic nanoparticles can be more transparent to infrared radiation than dielectrics such as germanium, even when the arrays are over 75% metal by volume. Such arrays form effective dielectrics that are virtually dispersion-free over ultra-broadband ranges of wavelengths from microns up to millimeters or more. Furthermore, the local refractive indices may be tuned by altering the size, shape, and spacing of the nanoparticles, allowing the design of gradient-index lenses that guide and focus light on the microscale. The electric field is also strongly concentrated in the gaps between the metallic nanoparticles, and the simultaneous focusing and squeezing of the electric field produces strong ‘doubly-enhanced’ hotspots which could boost measurements made using infrared spectroscopy and other non-linear processes over a broad range of frequencies., S.J.P. would like to acknowledge his studentship from the Centre for Doctoral Training on Theory and Simulation of Materials at Imperial College London funded by EPSRC Grant No. EP/L015579/1. R.A.A.-P., N.P.-P., L.G., and M.A.C.-D. thank the MINECO-Spain (CTM2014-58481R, CTM2017-84050R, CTQ2017-88648R, RYC-2015-19107 and RYC2016-20331), Xunta de Galicia (Centro Singular de Investigacion de Galicia, Acc. 2016-19 and EM2014/035), Generalitat de Cataluña (2017SGR883), URV (2017PFR-URV_B2-02), URV and Banco Santander (2017EXIT-08) and European Union (ERDF). X.X. acknowledges the Lee Family Scholarship. S.A.M. and R.V.C. acknowledge the EPSRC Mathematical Fundamentals of Metamaterials programme grant (EP/L024926/1) and the US Air Force Office of Scientific Research/EOARD (FA9550-17-1-0300). S.A.M. additionally acknowledges the Lee-Lucas Chair in Physics and DFG Cluster of Excellence Nanoinitiative Munich, and the Bavarian “Solar Technologies Go Hybrid” (SolTech) programme. R.V.C. thanks the Leverhulme Trust for their support. V.G. acknowledges the Consejo Superior de Investigaciones Cientficas (INTRAMURALES 201750I039).

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.

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.

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

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.

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 combination of molecular sensors and plasmonic materials is emerging as one of the most promising approaches for ultrasensitive SERS-based detection of metal ions in complex fluids. However, only a very small fraction of the large pool of potential chemosensors described in classical analytical chemistry has been successfully implemented into viable SERS platforms for metal ion determination. This is due to the molecular restrictions that require the chemosensor to adhere onto the plasmonic surface while retaining the capability to undergo large structural alterations upon metal ion binding. In this work, we demonstrate that the structural and functional plasticity of DNA for interacting with small aromatic molecules can be exploited to this end. DNA coating of silver nanoparticles modulates the interaction of the commercially available alizarin red S (ARS) chemosensor with the nanomaterial, translating its recognition capabilities from bulk solution onto the plasmonic surface, while simultaneously directing the particle assembling into highly efficient SERS clusters. The sensing approach was successfully applied to the multiplex, quantitative determination of Al(III) and Fe(III) in tap water in the subppb level.

Point mutations in Ras oncogenes are routinely screened for diagnostics and treatment of tumors (especially in colorectal cancer). Here, we develop an optical approach based on direct SERS coupled with chemometrics for the study of the specific conformations that single-point mutations impose on a relatively large fragment of the K-Ras gene (141 nucleobases). Results obtained offer the unambiguous classification of different mutations providing a potentially useful insight for diagnostics and treatment of cancer in a sensitive, fast, direct and inexpensive manner.

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.

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.

There is great interest in developing complex, 3D plasmonic materials with unusual structural properties. This can be achieved via template-assisted approaches exploiting scaffold elements to engineer unique plasmonic substrates, which would be otherwise impossible to synthesize. Herein, we present a novel, simple, and low-cost template-assisted method for producing interconnected 3-D silver microstructures by utilizing vermiculite, a well-known silicate, as both in-situ reductant and template for silver growth. The silicate network of the vermiculite can be easily removed by dissolution with hydrofluoric acid, which, simultaneously, leads to the formation of a magnesium fluoride skeleton supporting a plasmonically active silver film. Optical, morphological, and chemical properties of the materials were extensively investigated, revealing, for example, that hybrid silver microstructures can be exploited as valuable SERS substrates over a broad spectral range of excitation wavelengths.

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.

Recognition of chemical modifications in canonical nucleobases of nucleic acids is of key importance since such modified variants act as different genetic encoders, introducing variability in the biological information contained in DNA. Herein, we demonstrate the feasibility of direct SERS in combination with chemometrics and microfluidics for the identification and relative quantification of 4 different cytosine modifications in both single- and double-stranded DNA. The minute amount of DNA required per measurement, in the sub-nanogram regime, removes the necessity of pre-amplification or enrichment steps (which are also potential sources of artificial DNA damages). These findings show great potentials for the development of fast, low-cost and high-throughput screening analytical devices capable of detecting known and unknown modifications in nucleic acids (DNA and RNA) opening new windows of activity in several fields such as biology, medicine and forensic sciences.

The universal one-pot and up-scalable synthesis of SERS encoded nanoparticles relies on the controlled co-absorption of mercaptoundecanoic acid (MUA) and the Raman code on the metallic surfaces of the nanoparticles. In contrast to most of the reported procedures which typically involve complex steps, the present method has demonstrated to be an easy and fast one-pot approach for the production of SERS-encoded nanoparticles. This versatile strategy allows for the SERS codification of particles with every molecule with affinity toward the metal surface, independently of its chemical nature, as exemplified here in the fabrication of 3 different encoded particles using the same standard procedure. In addition to the easiness of preparation, scalability to the liter regime, stability in aqueous solutions including PBS and chemical diversity, our SERS-encoded particles show considerably higher optical efficiency than those fabricated by using PEG or PVP polymers.

Seed-mediated methods employing cetyltrimethylammonium bromide (CTAB) as a surfactant, and silver salts as additives, are the most common synthetic strategies for high-yield productions of quality Au nanorods. However, the mechanism of these reactions is not yet fully understood and, importantly, significant lab-to-lab reproducibility issues still affect these protocols. In this study, the direct correlation between the hidden content of iodide impurities in CTAB reagents, which can drastically differ from different suppliers or batches, and the optimal concentration of silver required to maximize the nanorods yield is demonstrated. As a result, high-quality nanorods are obtained at different iodide contents. These results are interpreted based on the different concentrations of CTAB and cetyltrimethylammonium iodide (CTAI) complexes with Ag+ and Au+ metal ions in the growth solution, and their different binding affinity and reduction potential on distinct crystallographic planes. Notably, the exhaustive conversion of CTAI-Au+ to CTAI-Ag+ appears to be the key condition for maximizing the nanorod yield.

Silicon nanoparticles are unique materials with applications in a variety of fields, from electronics to catalysis and biomedical uses. Despite technological advancements in nanofabrication, the development of a simple and inexpensive route for the synthesis of homogeneous silicon nanoparticles remains highly challenging. Herein, we describe a new, simple and inexpensive colloidal synthetic method for the preparation, under normal pressure and mild temperature conditions, of relatively homogeneous spherical silicon nanoparticles of either ca. 4 or 6 nm diameter. The key features of this method are the selection of a eutectic salt mixture as a solvent, the identification of appropriate silicon alkoxide precursors, and the unconventional use of alkali earth metals as shape-controlling agents.

There are numerous reports about particle–cell interaction studies in the literature. Many of those are performed in two-dimensional cell cultures. While the interpretation of such studies seems trivial at first sight, in fact for quantitative analysis some basic physical and physicochemical bases need to be considered. This starts with the dispersion of the particles, for which gravity, Brownian motion, and interparticle interactions need to be considered. The respective strength of these interactions determines whether the particles will sediment, are dispersed, or are agglomerated. This in turn largely influences their interaction with cells. While in the case of well-dispersed particles only a fraction of them will come into contact with cells in a two-dimensional culture, (agglomeration-induced) sedimentation drives the particles toward the cell surface, resulting in enhanced uptake.

Chemical speciation of heavy metals has become extremely important in environmental and analytical research because of the strong dependence that toxicity, environmental mobility, persistence and bioavailability of these pollutants have on their specific chemical forms. Novel nano-optical-based detection strategies, capable of overcoming the intrinsic limitations of well-established analytic methods for the quantification of total metal ion content, have been reported, but the speciation of different chemical forms has not yet been achieved. Here, we report the first example of a SERS-based sensor for chemical speciation of toxic metal ions in water at trace levels. Specifically, the inorganic Hg(2+) and the more toxicologically relevant methylmercury (CH₃Hg(+)) are selected as analytical targets. The sensing platform consists of a self-assembled monolayer of 4-mercaptopyridine (MPY) on highly SERS-active and robust hybrid plasmonic materials formed by a dense layer of interacting gold nanoparticles anchored onto polystyrene microbeads. The co-ordination of Hg(2+) and CH₃Hg(+) to the nitrogen atom of the MPY ring yields characteristic changes in the vibrational SERS spectra of the organic chemoreceptor that can be qualitatively and quantitatively correlated to the presence of the two different mercury forms.

An optical sensor was developed for the quantitative determination of intracellular nitric oxide. The sensor consists of plasmonic nanoprobes that have a coating of mesoporous silica and an inner gold island film functionalized with a chemoreceptor for NO.

We report a procedure to prepare highly monodisperse copper telluride nanocubes, nanoplates, and nanorods. The procedure is based on the reaction of a copper salt with trioctylphosphine telluride in the presence of lithium bis(trimethylsilyl)amide and oleylamine. CuTe nanocrystals display a strong near-infrared optical absorption associated with localized surface plasmon resonances. We exploit this plasmon resonance for the design of surface-enhanced Raman scattering sensors for unconventional optical probes. Furthermore, we also report here our preliminary analysis of the use of CuTe nanocrystals as cytotoxic and photothermal agents.

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.

DOI: 10.1038/s41598-017-04033-9 https://www.nature.com/articles/s41598-017-04033-9 Filiació URV: SI Metastatic cancer patients require a continuous monitoring during the sequential treatment cycles to carefully evaluate their disease evolution. Repetition of biopsies is very invasive and not always feasible. Herein, we design and demonstrate a 3D-flow focusing microfluidic device, where all optics are integrated into the chip, for the fluorescence quantification of CTCs in real samples. To test the chip performance, two cell membrane targets, the epithelial cell adhesion molecule, EpCAM, and the receptor tyrosine-protein kinase, HER2, are selected. The efficiency of the platform is demonstrated on cell lines and in a variety of healthy donors and metastatic-breast cancer patients.

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.

Design of ultrasensitive DNA sensors based on the unique physical properties of plasmonic nanostructures has become one of the most exciting areas in nanomedicine. However, despite the vast number of proposed applications, the determination of the base composition in nucleic acids, a fundamental parameter in genomic analyses and taxonomic classification, is still restricted to time-consuming and poorly sensitive conventional methods. Herein, we demonstrate the possibility of determining the base composition in single- and double-stranded DNA by using a simple, low-cost, high-throughput, and label-free surface-enhanced Raman scattering (SERS) method in combination with cationic nanoparticles.

Recently, plasmonic-based biosensing has experienced an unprecedented level of attention, with a particular focus on the nucleic acid detection, offering efficient solutions to engineer simple, fast, highly sensitive sensing platforms while overcoming important limitations of PCR and microarray techniques. In the broad field of plasmonics, surface-enhanced Raman scattering (SERS) spectroscopy has arisen as a powerful analytical tool for detection and structural characterization of biomolecules. Today applications of SERS to nucleic acid analysis largely rely on indirect strategies, which have been demonstrated very effective for pure sensing purposes but completely dismiss the exquisite structural information provided by the direct acquisition of the biomolecular vibrational fingerprint. Contrarily, direct label-free SERS of nucleic acid shows an outstanding potential in terms of chemical-specific information which, however, remained largely unexpressed mainly because of the inherent poor spectral reproducibility and/or limited sensitivity. To address these limitations, we developed a fast and affordable high-throughput screening direct SERS method for gaining detailed genomic information on nucleic acids (DNA and RNA) and for the characterization and quantitative recognition of DNA interactions with exogenous agents. The simple strategy relies on the electrostatic adhesion of DNA/RNA onto positively-charged silver colloids that promotes the nanoparticle aggregation into stable clusters yielding intense and reproducible SERS spectra at picogram level (i.e. the analysis can be performed without the necessity of amplification steps thus providing realistic direct information of the nucleic acid in its native state). We anticipate this method to gain a vast impact and set of applications in different fields, including medical diagnostics, genomic screening, drug discovery, forensic science and even molecular electronics.

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.

Microdroplets have been used as reactors for the fabrication of agarose beads with high uniformity in shape and size, and densely loaded with silver ions, which were subsequently reduced into nanoparticles using hydrazine. The resulting nanocomposite beads not only display a high plasmonic activity, but can also trap/concentrate analytes, which can be identified by means of surface-enhanced Raman scattering (SERS) spectroscopy. The size of the beads is such that it allows the detection of a single bead under a conventional optical microscope, which is very useful to reduce the amount of material required for SERS detection.

Gold nanostars are multibranched nanoparticles with sharp tips, which display extremely interesting plasmonic properties but require optimization. We present a systematic investigation of the influence of different parameters on the size, morphology, and monodispersity of Au nanostars obtained via seeded growth in concentrated solutions of poly(vinylpyrrolidone) in N,N-dimethylformamide. Controlled prereduction of Au(3+) to Au(+) was found to influence monodispersity (narrower plasmon bands), while the [HAuCl(4)]/[seed] molar ratio significantly affects the morphology and tip plasmon resonance frequency. We also varied the size of the seeds (2-30 nm) and found a clear influence on the final nanostar dimensions as well as on the number of spikes, while synthesis temperature notably affects the morphology of the particles, with more rounded morphologies formed above 60 °C. This rounding effect allowed us to confirm the importance of sharp tips on the optical enhancing behavior of these nanoparticles in surface-enhanced raman scattering (SERS). Additionally, the sensitivity toward changes in the local refractive index was found to increase for larger nanostars, though lower figure of merit (FOM) values were obtained because of the larger polydispersity.

Development of multifunctional drug delivery vehicles with therapeutic and imaging capabilities as well as in situ methods of monitoring of intracellular processes will greatly benefit from a simple method of preparation of plasmonic Au structures with nanometer scale gaps between sharp metallic elements where the so-called SERS hot spots can be formed. Here the synthesis of gold lace capsules with average diameters ca. 100 nm made of a network of metallic branches 3-5 nm wide and separated by 1-3 nm gaps is reported. Biocompatible amphiphilic polyurethanes (PUs) were used as template for these particles. The unusual topology of the produced gold lace shells somewhat reminiscent of Fabergé eggs is likely to reflect the network of hydrophobic and hydrophilic domains of PU globules. The gold lace develops from initial open weblike structures by gradual enveloping the PU template. The diameter of gold lace shell is determined by the size of PUs in water and can be adjusted by the molecular mass of PUs. The close proximity between branches makes them excellent supports for surface-enhanced Raman spectroscopy (SERS), which was demonstrated using 1-naphthalenethiol upon excitation with photons with different wavelengths. The loading and releasing of pyrene as a model of hydrophobic drugs and the use of SERS to monitor it were demonstrated.

This article provides an overview of recent research on the synthesis and surface-plasmon-related properties of noble metal nanoplates. The first part is dedicated to summarizing the most relevant wet-chemical and physical synthetic protocols that have been used to obtain Au and Ag nanotriangles/ nanoplates in high yield, with a discussion of the formation mechanisms proposed by the different authors. Finally, we present a description of the characteristic optical properties of nanoparticles with this particular morphology, in relation with the possibility of exciting different surface plasmon modes and concentrating high electromagnetic fields at certain areas, which is important for applications in surface-enhanced Raman scattering (SERS).

We describe the design and fabrication of composite agarose gels, highly loaded with silver nanoparticles. Because the gel can collapse upon drying and recover when rehydrated, it can be foreseen as an excellent mechanical molecular trap that additionally gives rise to dynamic hot spots as the network volume decreases and the silver particles get close to each other, thereby generating the high electromagnetic fields that are needed for ultradetection. Additionally, as silver nanoparticles are physically trapped inside the polymer network, analytes can be washed out by dialysis when immersed in a washing solution, so that recycling can be achieved. Finally, the use of SERS for ultradetection of dichlorodiphenyl-trichloroethane (DDT) is reported for the first time, demonstrating the ability of this novel nanocomposite material to reversibly sequester nonconventional SERS analytes.

Thiol-modified poly(ethylene glycol) (mPEG-SH) has been used to replace standard capping agents from the surfaces of gold nanoparticles with different sizes and shapes. Upon PEG stabilization, the nanoparticles can be transferred into ethanol, where silica can be directly grown on the particle surfaces through the standard Stober process. The obtained silica shells are uniform and homogeneous, and the method allows a high degree of control over shell thickness for any particle size and shape. Additionally, Raman-active molecules can be readily incorporated within the composite nanoparticles during silica growth so that SERS/SERRS-encoded nanoparticles can be fabricated containing a variety of tags, thereby envisaging multiplexing capability.

Surface-enhanced Raman scattering (SERS) is a powerful analytical technique for ultrasensitive chemical and biochemical analysis. Among common substrates for SERS, the most important are colloidal nanocrystal suspensions of gold, silver, and their alloys, which are produced by a variety of physical and chemical reduction methods. In a colloidal suspension, the closer interaction between the adsorbent and adsorbate allows the analyte to be naturally retained on the colloid’s surface. These mixed systems may later be studied directly by bulk SERS or cast and air-dried onto an appropriate substrate (glass or silicon wafers) and analyzed by microspectroscopic SERS. The main disadvantage of this method is the low stability of colloidal suspensions; physical (i.e., shape and size) and chemical (i.e., surface charge) properties often vary within days of preparation. Thus, in order to extend the shelf life of the colloidal suspensions, the addition of stabilizers to prevent aggregation and flocculation by increasing the electrostatic potential around the nanoparticles was reported. However, while this process stabilizes the particles, it hinders the interaction between the adsorbent and adsorbate, thus decreasing the SERS output. In recent years, many attempts have been made to deposit optically active nanoparticles on polymer microbeads in order to produce composite materials suitable for SERS. Unfortunately, such materials tend to have low nanoparticle loading and weak SERS because of limited nanoparticle accessibility in the polymer matrix. Recently, Kinoshita et al. established the extraordinary capability of poly(ethylene glycol) (PEG) to selectively retain Au. In the present paper, this property was exploited to produce a gold nanoparticle

Nanoalloys are clusters formed of two or more metallic elements and are of interest for applications in catalysis, spectroscopy, photonics, electronics, and magnetism. The hybridization of the individual plasmonic absorptions of different alloyed metals allows for plasmon tunability and a better coupling of plasmon-excitation line, giving rise to significant increases in the enhancement factor for surface-enhanced Raman scattering (SERS) spectroscopy. Here we report simple fabrication procedures for the preparation of Ag/Au nanoalloys on Si/SiOx substrates, with tunable plasmon resonances. The mechanism and kinetic of the nanoalloy formation and its optical properties were studied by SEM, XPS, SPR, and SERS.

In this work, we have devised and fabricated a magnetic + optical, bifunctional colloidal system that combines flexible handling and efficient SERS analytical capabilities. This system comprises silica-coated magnetic γ-Fe2O3 (maghemite) cores, coated with a dense monolayer of gold nanorods presenting long-term optical stability and a high density of hot spots per area unit. The magnetic functionality allows for the use of a small number of capsules that can be later concentrated under a magnetic field for SERS analysis thereby increasing the detection limits.

This paper describes morphological and optical changes induced by seed-mediated growth of gold nanorods in the presence of iodide ions. Addition of small amounts of iodide to the growth solution results in the growth of nanoparticles with dumbbell-like structure, meaning that gold salt reduction takes place preferentially at the rod tips. However, when excess iodide is added, homogeneous rod growth is observed, and therefore the original shape is retained. By controlling the experimental conditions, the position of the longitudinal plasmon band of grown nanorods can be shifted up to as much as 250 nm. These optical effects were also simulated by means of the boundary element method (BEM), achieving an excellent agreement with the experimental spectra. X-ray photoelectron spectroscopy (XPS) and surface enhanced Raman spectroscopy (SERS) analysis of the gold nanorods before and after iodide addition revealed the presence of AuI and AgI at the particles surface. A growth mechanism is proposed on the basis of preferential iodide adsorption at the tips {111} facets, leading to the formation of AgI, followed by reduction of gold salt precursor due to a decrease in the surface redox potential.