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Here, we investigate the correlation between the heat generated by gold nanoparticles, in particular nanospheres and nanobipyramids, and their plasmonic response manifested by the presence of Localized Surface Plasmon Resonances (LSPRs). Using a tunable laser and a thermal camera, we measure the temperature increase induced by colloidal nanoparticles in an aqueous solution as a function of the excitation wavelength in the optical regime. We demonstrate that the photothermal performances of the nanoparticles are strongly related not only to their plasmonic properties but also to the size and shape of the nanoparticles. The contribution of the longitudinal and transversal modes in gold nanobipyramids is also analyzed in terms of heat generation. These results will guide us to design appropriate nanoparticles to act as efficient heat nanosources.

The sensitive and accurate detection of tumor cells is essential for successful cancer therapy and improving cancer survival rates. However, current tumor cell detection technologies have some limitations for clinical applications due to their complexity, low specificity, and high cost. Herein, we describe the design of a terahertz anti-resonance hollow core fiber (THz AR-HCF) biosensor that can be used for tumor cell detection. Through simulation and experimental comparisons, the low-loss property of the THz AR-HCF was verified, and the most suitable fiber out of multiple THz AR-HCFs was selected for biosensing applications. By measuring different cell numbers and different types of tumor cells, a good linear relationship between THz transmittance and the numbers of cells between 10 and 10 6 was found. Meanwhile, different types of tumor cells can be distinguished by comparing THz transmission spectra, indicating that the biosensor has high sensitivity and specificity for tumor cell detection. The biosensor only required a small amount of sample (as low as 100 μL), and it enables label-free and nondestructive quantitative detection. Our flow cytometry results showed that the cell viability was as high as 98.5 ± 0.26% after the whole assay process, and there was no statistically significant difference compared with the negative control. This study demonstrates that the proposed THz AR-HCF biosensor has great potential for the highly sensitive, label-free, and nondestructive detection of circulating tumor cells in clinical samples.

Interleukin 6 (IL-6) is pleiotropic cytokine with pathological pro-inflammatory effects in various acute, chronic and infectious diseases. It is involved in a variety of biological processes including immune regulation, hematopoiesis, tissue repair, inflammation, oncogenesis, metabolic control, and sleep. Due to its important role as a biomarker of many types of diseases, its detection in small amounts and with high selectivity is of particular importance in medical and biological fields. Laboratory methods including enzyme-linked immunoassays (ELISAs) and chemiluminescent immunoassays (CLIAs) are the most common conventional methods for IL-6 detection. However, these techniques suffer from the complexity of the method, the expensiveness, and the time-consuming process of obtaining the results. In recent years, too many attempts have been conducted to provide simple, rapid, economical, and user-friendly analytical approaches to monitor IL-6. In this regard, biosensors are considered desirable tools for IL-6 detection because of their special features such as high sensitivity, rapid detection time, ease of use, and ease of miniaturization. In this review, current progresses in different types of optical biosensors as the most favorable types of biosensors for the detection of IL-6 are discussed, evaluated, and compared.

Exosomal microRNA (miRNA) is a promising non-invasive biomarker for liquid biopsies. Herein, we fabricated a terahertz (THz) metamaterial biosensor that comprises an array of gold (Au) discs surrounded by annular grooves for exosomal miRNA assays based on duplex-specific nuclease (DSN)-triggered rolling circle amplification (RCA). In this strategy, the target miRNA is captured by a probe P0 immobilized on magnetic beads (MBs); it then repeatedly releases a primer P1 under the action of DSN, which acts as a highly specific initiator of the subsequent RCA step utilizing biotin-dUTP. After target recycling and nucleic acid amplification, the biotinylated amplification products were captured by the streptavidin (SA)-functionalized THz metamaterials, and further conjugated to SA-modified AuNPs that permit formation of a trimeric complex of SA-biotinylated RCA products-AuNP. The complex population scales with the starting concentration of the target miR-21, resulting in a red shift of the resonance peak of the THz metamaterials. This biosensor can lead to highly specific and sensitive detection with one-base mismatch discrimination and a limit of detection (LOD) down to 84 aM. Significant distinctions are seen in the frequency shifts for exosomal miR-21 quantitation in clinical plasma samples between pancreatic cancer patients and healthy controls. The frequency shifts of the THz metamaterials are consistent versus the reverse transcription-polymerase chain reaction (RT-PCR) results, illustrating the applicability and accuracy of our assay in real clinical samples., (Copyright © 2021 Elsevier B.V. All rights reserved.)

We study the interaction between one aptamer and its analyte (the MnSOD protein) by the combination of surface-enhanced Raman scattering and multivariate statistical analysis. We observe the aptamer structure and its evolution during the interaction under different experimental conditions (in air or in buffer). Through the spectral treatment by principal component analysis of a large set of SERS data, we were able to probe the aptamer conformations and orientations relative to the surface assuming that the in-plane nucleoside modes are selectively enhanced. We demonstrate that the aptamer orientation and thus its flexibility rely strongly on the presence of a spacer of 15 thymines and on the experimental conditions with the aptamer lying on the surface in air and standing in the buffer. We reveal for the first time that the interaction with MnSOD induces a large loss of flexibility and freezes the aptamer structure in a single conformation.

Terahertz (THz) spectroscopy has drawn great interest for the functional and conformational investigations of nucleic acids, but its intrinsic sensitivity hinders potential bio-sensing applications. Here, a novel THz biosensor was developed for detecting microRNA (miRNA) samples based on metamaterials coupled with nanoparticles and strand displacement amplification (SDA). In this method, the SDA reaction amplifies the target miRNA and generates copious yields of secondary DNA molecules (Trigger DNA), which are subsequently conjugated to metallic nanoparticles that form nanoparticle-Trigger DNA complexes. These complexes produce remarkable frequency shifts of metamaterials when linked to a large refractive index metallic nanoparticle like Au. The dependence of the metamaterial resonance on the nanoparticle diameter and metal type was investigated experimentally and theoretically. Under optimal conditions, the THz metamaterial biosensor presents good detection sensitivity with a limit of detection of 14.54 aM and exhibits a linear response for miRNA-21 at a concentration range from 1 fM to 10 pM. By measuring the miRNA-21 in spiked clinical serum samples, the sample recoveries were determined to be in the range between 90.92% and 107.01%. These findings demonstrate that the novel THz biosensor offers the capability for highly sensitive miRNA detection, with noteworthy potential applications in nucleic acid analysis and cancer diagnosis., (Copyright © 2020 Elsevier B.V. All rights reserved.)

In this work, we bring back a rapid way to conceive doxorubicin (DOX) hybrid gold nanoparticles, in which DOX and Au(iii) ions were complexed with a hydrochloride-lactose-modified chitosan, named CTL and dicarboxylic acid-terminated polyethylene-glycol (PEG), leading to hybrid polymer-sugar-metal nanoparticles (DOX-AuGSs). All formulations were assessed by spectroscopic techniques (Raman and UV-Vis) and transmission electron microscopy (TEM). To estimate the therapeutic effect of DOX-AuGSs in liver cancer, murine HepG2 cells were used to induce a hepatic carcinoma model in nude mice. The survival time of the tumor-bearing mice, body weight and tumor volume were measured and recorded. The cytokines were used to detect the serum inflammatory factors, and the blood cell analyzer was used to determine the blood cell content of different groups of nude mice. The outcomes demonstrate that DOX-AuGCs significantly suppressed the tumor growth derived from human HepG2 injection and reduce the tumor index without affecting the body weight of mice. Moreover, DOX-AuGCs significantly reduced the serum levels of cytokines IL-6, TNF-α and IL-12 P70. Finally, a histological analysis of the heart tissue sections indicated that DOX-AuGCs significantly reduce the chronic myocardial toxicity of DOX during the period of treatment., Competing Interests: There are no conflicts of interest., (This journal is © The Royal Society of Chemistry.)

Herein, we report a new approach to rapidly actuate the plasmonic characteristics of thin gold films perforated with nanohole arrays that are coupled with arrays of gold nanoparticles. The near-field interaction between the localized and propagating surface plasmon modes supported by the structure was actively modulated by changing the distance between the nanoholes and nanoparticles and varying the refractive index symmetry of the structure. This approach was applied by using a thin responsive hydrogel cushion, which swelled and collapsed by a temperature stimulus. The detailed experimental study of the changes and interplay of localized and propagating surface plasmons was complemented by numerical simulations. We demonstrate that the interrogation and excitation of the optical resonance to these modes allow the label-free SPR observation of the binding of biomolecules, and is applicable for in situ SERS studies of low molecular weight molecules attached in the gap between the nanoholes and nanoparticles.

Our understanding of the fate and distribution of micro- and nano- plastics in the marine environment is limited by the intrinsic difficulties of the techniques currently used for the detection, quantification, and chemical identification of small particles in liquid (light scattering, vibrational spectroscopies, and optical and electron microscopies). Here we introduce Raman Tweezers (RTs), namely optical tweezers combined with Raman spectroscopy, as an analytical tool for the study of micro- and nanoplastics in seawater. We show optical trapping and chemical identification of sub-20 μm plastics, down to the 50 nm range. Analysis at the single particle level allows us to unambiguously discriminate plastics from organic matter and mineral sediments, overcoming the capacities of standard Raman spectroscopy in liquid, intrinsically limited to ensemble measurements. Being a microscopy technique, RTs also permits one to assess the size and shapes of particles (beads, fragments, and fibers), with spatial resolution only limited by diffraction. Applications are shown on both model particles and naturally aged environmental samples, made of common plastic pollutants, including polyethylene, polypropylene, nylon, and polystyrene, also in the presence of a thin eco-corona. Coupled to suitable extraction and concentration protocols, RTs have the potential to strongly impact future research on micro and nanoplastics environmental pollution, and enable the understanding of the fragmentation processes on a multiscale level of aged polymers.

Co-amorphous drugs have shown significant potential in improving the stability and bioavailability compared with single neat amorphous drugs. Here, we explored the molecular interactions of cimetidine, naproxen, indomethacin and their binary co-amorphous mixtures via Raman and terahertz (THz) spectroscopy. We used quench-cooled method to prepare the neat amorphous drugs and their binary co-amorphous mixtures and tested their thermodynamic properties through differential scanning calorimetry (DSC). Then, we found that the stability of co-amorphous drugs was stronger than their neat amorphous components. Furthermore, Raman spectroscopy was used to characterize the vibrational modes between different co-amorphous drugs. Generally, we found that the stability of co-amorphous drugs was better than their neat amorphous components for these samples we tested. Meanwhile, we complemented the detection of THz spectroscopy and found that crystalline and amorphous drugs could be better distinguished., Competing Interests: The authors declare that there are no conflicts of interest related to this article.

Colistin is recognized as the last therapeutic option for multidrug-resistant Gram-negative bacteria infection. In addition, bacterial resistance to colistin could be transmitted between different species through plasmid-mediated mcr-1 gene transfer. Therefore, rapid screening of colistin-resistant isolates will play a key role in controlling the spread of resistance and improving patient outcomes. We developed a rapid method for the detection of colistin-resistance in Escherichia coli, Acinetobacter baumannii, and Pseudomonas aeruginosa bacteria based on Raman spectroscopy and hierarchical cluster analysis. Bacteria were incubated with and without colistin using CAMHB as the liquid culture medium. They were then centrifuged and dried on a glass slide. Five Raman spectra of each of the samples were recorded and analyzed by the hierarchical cluster analysis method to determine whether the bacteria were resistant. To evaluate this method, 123 clinical bacterial isolates (42 isolates of E. coli, 41 isolates of A. baumannii and 40 isolates of P. aeruginosa) were tested. The detection sensitivity and specificity were 90.9% and 91.1%, respectively, compared with the reference broth microdilution method. The screening is easy to perform and can be completed in 1.5 h, suggesting that it holds great potential to be an initial screening method in countries and areas where colistin becomes the last resort antibiotic.

The study of protein interactions with gold nanoparticles (GNP) is a key step prior to any biomedical application. These interactions depend on many GNP parameters such as size, surface charge, chemistry, and shape. In this work, we propose to use a sensitive technique named scattering correlation spectroscopy or SCS to study protein interactions with GNP. SCS allowed the investigation of the GNP hydrodynamic radius with a very high sensitivity before and after interaction with proteins. No labeling is needed. As a proof-of-concept, two of the most used morphologies of GNP-based nanovectors have been used within this work: spherical-shaped GNP (GNS) and branched-shaped GNP (GNU). The measurement of several parameters such as the number of proteins binding to one GNP, the binding affinity and the cooperativeness of binding for three different plasma proteins on the GNP surface was carried out. While GNS showed an increase in the hydrodynamic radius, indicating that each kind of protein binds on the GNS in a specific orientation, GNU showed different orientations of proteins due to their multi-oriented surfaces (tips) with a higher surface to volume area. Quantitative data based on the Hill model were extracted to obtain the affinity of the proteins to both GNS and GNU surfaces. Data variations can be understood in terms of the electrostatic properties of the proteins, which interact differently with the negatively charged GNP surfaces.

Terahertz (THz) metamaterial-based reflection spectroscopy is proposed for label-free sensing of living cells by a self-referenced method. When sensing the living Madin-Darby canine kidney cell monolayer and phosphate buffered saline solution, self-referenced signals showed significant differences in peak intensity because of inherent discrepancy in the imaginary part of their complex refractive indices, as confirmed by 3D-FDTD simulations. The resonance peak intensity was unaffected by cell monolayer thickness variation, demonstrating feasibility for sensing various cells. Simulations and experiments showed that saponin-induced changes in cell permeability could be monitored in real-time. The self-referenced signal was linearly dependent on the adherent cell density, illustrating a label-free in situ THz metamaterial-based cell sensor., Competing Interests: The authors declare that there are no conflicts of interest related to this article.

Simple, rapid, and efficient cell viability assays play a fundamental role in much of biomedical research, including cell toxicology investigations and antitumor drug screening. Here, we demonstrate for the first time a rapid and label-free cell viability assay using THz spectroscopy in combination with a new optical clearing agent (OCA) and microfluidic technology. This strategy uses a considerably less absorptive OCA to replace the highly absorptive water molecules around the living cells and thus to decrease the background signal interference. Three low-viscosity oils were screened as potential OCA candidates, among which fluorinated oil was selected because of its lower absorption and lowest cytotoxicity. After the liquid medium was replaced with fluorinated oil in a microfluidic chip, an obvious THz spectral difference was observed between the fluorinated oils with and without living cells. This change in THz response was preliminarily attributed to the distinguishable signals between the cells and the fluorinated oil. In addition, we applied this method to cell viability assays of human breast cancer cells (MDA-MB-231) after treatment with different antitumor drugs. The results indicated that THz spectroscopy with the aid of the proposed water-replacement strategy presented excellent quantification of cell viability with the advantages of a rapid, label-free, nondestructive microassay, which offers significant potential to developing a convenient and practical cell analysis platform.

Galectins (Gal) are a family of glycan-binding proteins characterized by their affinity for β-galactosides. Galectin-1 (Gal-1), a dimeric lectin with two galactoside-binding sites, regulates cancer progression and immune responses. Coordination chemistry has been engaged to develop versatile multivalent neoglycoconjugates for binding Gal-1. In this study we report a fast and original method to synthesize hybrid gold nanoparticles in which a hydrochloride lactose-modified chitosan, named CTL, is mixed with dicarboxylic acid-terminated polyethylene glycol (PEG), leading to shell-like hybrid polymer-sugar-metal nanoparticles (CTL-PEG-AuNPs). The aim of this paper is to preliminarily study the interaction of the CTL-PEG-AuNPs with a target protein, namely, Gal-1, under specific conditions. The molecular interaction has been measured by Transmission Electron Microscopy (TEM), UV-vis, and Raman Spectroscopy on a large range of Gal-1 concentrations (from 0 to 10 -12 M). We observed that the interaction was strongly dependent on the Gal-1 concentration at the surface of the gold nanoparticles.

The facile preparation of arrays of plasmonic nanoparticles over a square centimeter surface area is reported. The developed method relies on tailored laser interference lithography (LIL) that is combined with dry etching and it offers means for the rapid fabrication of periodic arrays of metallic nanostructures with well controlled morphology. Adjusting the parameters of the LIL process allows for the preparation of arrays of nanoparticles with a diameter below hundred nanometers independently of their lattice spacing. Gold nanoparticle arrays were precisely engineered to support localized surface plasmon resonance (LSPR) with different damping at desired wavelengths in the visible and near infrared part of the spectrum. The applicability of these substrates for surface enhanced Raman scattering is demonstrated where cost-effective, uniform and reproducible substrates are of paramount importance. The role of deviations in the spectral position and the width of the LSPR band affected by slight variations of plasmonic nanostructures is discussed.

Optical forces are used to aggregate plasmonic nanoparticles and create SERS-active hot spots in liquid. When biomolecules are added to the nanoparticles, high sensitivity SERS detection can be accomplished. Here, we pursue studies on Bovine Serum Albumin (BSA) detection, investigating the BSA-nanorod aggregations in a range from 100 µM to 50 nM by combining light scattering, plasmon resonance and SERS, and correlating the SERS signal with the concentration. Experimental data are fitted with a simple model describing the optical aggregation process. We show that BSA-nanorod complexes can be optically printed on non-functionalized glass surfaces, designing custom patterns stable with time. Furthermore, we demonstrate that this methodology can be used to detect catalase and hemoglobin, two Raman resonant biomolecules, at concentrations of 10 nM and 1 pM, respectively, i.e., well beyond the limit of detection of BSA. Finally, we show that nanorods functionalized with specific aptamers can be used to capture and detect Ochratoxin A, a fungal toxin found in food commodities and wine. This experiment represents the first step towards the addition of molecular specificity to this novel biosensor strategy., Competing Interests: The authors declare no conflict of interest.

The trace detection of toxic compounds in complex matrices is a major concern, in particular when it comes to mycotoxins in food. We developed a highly sensitive and specific SERS sensor for the detection of ochratoxin A using a simple rough gold film as a substrate. When adding the analyte, we observed spectral variations related to the interaction of the analyte with the specific aptamer used as a bioreceptor. Using a partial least squares regression method, our sensor is able to detect concentrations down to the picomolar range, which is much lower than the minimum legal concentration allowed in food products. Moreover, we demonstrate the accurate detection of the analyte in a wide concentration range from the picomolar up to the micromolar level. The detection was validated with negative detection tests using deoxynivalenol and bovine serum albumin.

Here, we present a surface-enhanced Raman spectroscopy (SERS) nanosensor for environmental pollutants detection. This study was conducted on three polycyclic aromatic hydrocarbons (PAHs): benzo[a]pyrene (BaP), fluoranthene (FL), and naphthalene (NAP). SERS substrates were chemically functionalized using 4-dodecyl benzenediazonium-tetrafluoroborate and SERS analyses were conducted to detect the pollutants alone and in mixtures. Compounds were first measured in water-methanol (9:1 volume ratio) samples. Investigation on solutions containing concentrations ranging from 10 -6 g L -1 to 10 -3 g L -1 provided data to plot calibration curves and to determine the performance of the sensor. The calculated limit of detection (LOD) was 0.026 mg L -1 (10 -7 mol L -1 ) for BaP, 0.064 mg L -1 (3.2 × 10 -7 mol L -1 ) for FL, and 3.94 mg L -1 (3.1 × 10 -5 mol L -1 ) for NAP, respectively. The correlation between the calculated LOD values and the octanol-water partition coefficient (K ow ) of the investigated PAHs suggests that the developed nanosensor is particularly suitable for detecting highly non-polar PAH compounds. Measurements conducted on a mixture of the three analytes (i) demonstrated the ability of the developed technology to detect and identify the three analytes in the mixture; (ii) provided the exact quantitation of pollutants in a mixture. Moreover, we optimized the surface regeneration step for the nanosensor., Competing Interests: The authors declare no conflict of interest.

Spleen Tyrosine Kinase (Syk) plays a crucial role in immune cell signalling and its altered expression or activation are involved in several cancers. Syk activity relies on its phosphorylation status and its multiple phosphorylation sites predict several Syk conformations. In this report, we characterized Syk structural changes according to its phosphorylation/activation status by Surface Enhanced Raman Spectroscopy (SERS). Unphosphorylated/inactive and phosphorylated/active Syk forms were produced into two expression systems with different phosphorylation capability. Syk forms were then analysed by SERS that was carried out in liquid condition on a lithographically designed gold nanocylinders array. Our study demonstrated that SERS signatures of the two Syk forms were drastically distinct, indicating structural modifications related to their phosphorylation status. By comparison with the atomic structure of the unphosphorylated Syk, the SERS peak assignments of the phosphorylated Syk nearest gold nanostructures revealed a differential interaction with the gold surface. We finally described a model for Syk conformational variations according to its phosphorylation status. In conclusion, SERS is an efficient technical approach for studying in vitro protein conformational changes and might be a powerful tool to determine protein functions in tumour cells.

Herein we investigate the structure/function relationships of fucoidans from Ascophyllum nodosum to analyze their pro-angiogenic effect and cellular uptake in native and glycosaminoglycan-free (GAG-free) human endothelial cells (HUVECs). Fucoidans are marine sulfated polysaccharides, which act as glycosaminoglycans mimetics. We hypothesized that the size and sulfation rate of fucoidans influence their ability to induce pro-angiogenic processes independently of GAGs. We collected two fractions of fucoidans, Low and Medium Molecular Weight Fucoidan (LMWF and MMWF, respectively) by size exclusion chromatography and characterized their composition (sulfate, fucose and uronic acid) by colorimetric measurement and Raman and FT-IR spectroscopy. The high affinities of fractionated fucoidans to heparin binding proteins were confirmed by Surface Plasmon Resonance. We evidenced that LMWF has a higher pro-angiogenic (2D-angiogenesis on Matrigel) and pro-migratory (Boyden chamber) potential on HUVECs, compared to MMWF. Interestingly, in a GAG-free HUVECs model, LMWF kept a pro-angiogenic potential. Finally, to evaluate the association of LMWF-induced biological effects and its cellular uptake, we analyzed by confocal microscopy the GAGs involvement in the internalization of a fluorescent LMWF. The fluorescent LMWF was mainly internalized through HUVEC clathrin-dependent endocytosis in which GAGs were partially involved. In conclusion, a better characterization of the relationships between the fucoidan structure and its pro-angiogenic potential in GAG-free endothelial cells was required to identify an adapted fucoidan to enhance vascular repair in ischemia., Competing Interests: The authors declare no conflict of interest.

The two-step nucleation model for crystal nuclei formation explains several experimental and theoretical results better than the classical nucleation theory. We report here direct visualization of the two-step nucleation model for organic molecular crystallization. Evaporative crystallization from a solution of a dibenzoylmethane boron complex that displays mechanofluorochromism, a fluorescence color change induced by mechanical perturbation, was probed by fluorescence change. The dependence of fluorescence change on dispersion concentration of the complex in a polymer matrix was also investigated. We detected transitional emission from the amorphous cluster state prior to crystallization. This is the first demonstration of the two-step nucleation model based on fluorescence color changes.

In this article we show that linear nanoantennas can be used as shared substrates for surface-enhanced Raman and infrared spectroscopy (SERS and SEIRS, respectively). This is done by engineering the plasmonic properties of the nanoantennas, so to make them resonant in both the visible (transversal resonance) and the infrared (longitudinal resonance), and by rotating the excitation field polarization to selectively take advantage of each resonance and achieve SERS and SEIRS on the same nanoantennas. As a proof of concept, we have fabricated gold nanoantennas by electron beam lithography on calcium difluoride (1-2 μm long, 60 nm wide, 60 nm high) that exhibit a transverse plasmonic resonance in the visible (640 nm) and a particularly strong longitudinal dipolar resonance in the infrared (tunable in the 1280-3100 cm(-1) energy range as a function of the length). SERS and SEIRS detection of methylene blue molecules adsorbed on the nanoantenna's surface is accomplished, with signal enhancement factors of 5×10(2) for SERS (electromagnetic enhancement) and up to 10(5) for SEIRS. Notably, we find that the field enhancement provided by the transverse resonance is sufficient to achieve SERS from single nanoantennas. Furthermore, we show that by properly tuning the nanoantenna length the signals of a multitude of vibrational modes can be enhanced with SEIRS. This simple concept of plasmonic nanosensor is highly suitable for integration on lab-on-a-chip schemes for label-free chemical and biomolecular identification with optimized performances.

Subsurface hydrothermal degradation of yttria stabilized tetragonal zirconia polycrystals (3Y-TZP) is presented. Evaluation of low temperature degradation (LTD) phase transformation induced by aging in 3Y-TZP is experimentally studied by Raman confocal microspectroscopy. A non-linear distribution of monoclinic volume fraction is determined in depth by using different pinhole sizes. A theoretical simulation is proposed based on the convolution of the excitation intensity profile and the Beer-Lambert law (optical properties of zirconia) to compare between experiment and theory. The calculated theoretical degradation curves matche closely to the experimental ones. Surface transformation (V0) and transformation factor in depth (T) are obtained by comparing simulation and experience for each sample with nondestructive optical sectioning.

The paper outlines the optimization of plasmonic nanostructures in order to improve their sensing properties such as their sensitivity and their ease of manipulation. The key point in this study is the optimization of the localized surface plasmon resonance (LSPR) properties essential to the sensor characteristics, and more especially for surface-enhanced Raman scattering (SERS). Two aspects were considered in order to optimize the sensing performance: apolar plasmonic nanostructures for non polarization dependent detection and improvements of SERS sensitivity by using a molecular adhesion layer between gold nanostructures and glass. Both issues could be generalized to all plasmon-resonance-based sensing applications.