Magnetic-Plasmonic Nanocomposites as Versatile Substrates for Surface-enhanced Raman Scattering (SERS) Spectroscopy.

Surface-enhanced Raman scattering (SERS) spectroscopy, a highly sensitive technique for detecting trace-level analytes, relies on plasmonic substrates. The choice of substrate, its morphology, and the excitation wavelength are crucial in SERS applications. To address advanced SERS requirements, the design and use of efficient nanocomposite substrates have become increasingly important. Notably, magnetic-plasmonic (MP) nanocomposites, which combine magnetic and plasmonic properties within a single particle system, stand out as promising nanoarchitectures with versatile applications in nanomedicine and SERS spectroscopy. In this review, we present an overview of MP nanocomposite fabrication methods, explore surface functionalization strategies, and evaluate their use in SERS. Our focus is on how different nanocomposite designs, magnetic and plasmonic properties, and surface modifications can significantly influence their SERS-related characteristics, thereby affecting their performance in specific applications such as separation, environmental monitoring, and biological applications. Reviewing recent studies highlights the multifaceted nature of these materials, which have great potential to transform SERS applications across a range of fields, from medical diagnostics to environmental monitoring. Finally, we discuss the prospects of MP nanocomposites, anticipating favorable developments that will make substantial contributions to various scientific and technological areas.

Composite nanoparticle-metal-organic frameworks for SERS sensing.

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

Yolk-Shell Nanostars@Metal Organic Frameworks as Molecular Sieves for Optical Sensing and Catalysis.

Hybrid composites between nanoparticles and metal organic frameworks (MOFs) have been described as optimal materials for a wide range of applications in optical sensing, drug delivery, pollutant removal or catalysis. These materials are usually core-shell single- or multi-nanoparticles, restricting the inorganic surface available for reaction. Here, we develop a method for the preparation of yolk-shells consisting in a plasmonic gold nanostar coated with MOF. This configuration shows more colloidal stability, can sieve different molecules based on their size or charge, seems to show some interesting synergy with gold for their application in photocatalysis and present strong optical activity to be used as SERS sensors.

Widefield SERS for High-Throughput Nanoparticle Screening.

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 to directly quantify the fraction of SERS-active particles which allows for an unprecedented correlation of SERS activity with particle size. .

Three-Dimensional Surface-Enhanced Raman Scattering Platforms: Large-Scale Plasmonic Hotspots for New Applications in Sensing, Microreaction, and Data Storage.

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.

Cancer Diagnosis through SERS and Other Related Techniques.

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.

Multiplex SERS Chemosensing of Metal Ions via DNA-Mediated Recognition.

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.

Erratum: Corrigendum: Plasmonic nanosensors with inverse sensitivity by means of enzyme-guided crystal growth.

Nature Materials 11, 604-607 (2012); published online 27 May 2012; corrected after print 15 December 2017. In the version of this Letter originally published, the x and y values of the data points in Fig. 2c were incorrect. The original and corrected versions are shown below. The authors have also made some changes to the Supplementary Information: Fig.

Addendum: Plasmonic nanosensors with inverse sensitivity by means of enzyme-guided crystal growth.

This corrects the article DOI: 10.1038/nmat3337.

Corrigendum: Plasmonic nanosensors with inverse sensitivity by means of enzyme-guided crystal growth.

This corrects the article DOI: 10.1038/nmat3337.

Spontaneous Formation of Cold-Welded Plasmonic Nanoassemblies with Refracted Shapes for Intense Raman Scattering.

Nanostructures with concave shapes made from continuous segments of plasmonic metals are known to dramatically enhance Raman scattering. Their synthesis in solutions is hindered, however, by their thermodynamic instability due to large surface area and high curvature of refracted geometries with nanoscale dimensions. Herein, we show that nanostructures with concave geometries can spontaneously form via self-organization of gold nanoparticles (NPs) at the air-water interface. The weakly bound surface ligands on the particle surface make possible their spontaneous accumulation and self-assembly at the air-water interface, forming monoparticulate films. Upon heating to 80 °C, the NPs further assemble into concave nanostructures where NPs are cold-welded to each other. Furthermore, the nanoassemblies effectively adsorb molecular analytes during their migration from the bulk solution to the surface where they can be probed by laser spectroscopies. We demonstrate that these films with local concentration of analytes increased by orders of magnitude and favorable plasmonic shapes can be exploited for surface-enhanced Raman scattering for high-sensitivity analysis of aliphatic molecules.

Surface-enhanced Raman spectroscopy (SERS) characterisation of abasic sites in DNA duplexes.

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.

Direct surface-enhanced Raman scattering (SERS) spectroscopy of nucleic acids: from fundamental studies to real-life applications.

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

Aqueous Stable Gold Nanostar/ZIF-8 Nanocomposites for Light-Triggered Release of Active Cargo Inside Living Cells.

A plasmonic core-shell gold nanostar/zeolitic-imidazolate-framework-8 (ZIF-8) nanocomposite was developed for the thermoplasmonic-driven release of encapsulated active molecules inside living cells. The nanocomposites were loaded, as a proof of concept, with bisbenzimide molecules as functional cargo and wrapped with an amphiphilic polymer that prevents ZIF-8 degradation and bisbenzimide leaking in aqueous media or inside living cells. The demonstrated molecule-release mechanism relies on the use of near-IR light coupled to the plasmonic absorption of the core gold nanostars, which creates local temperature gradients and thus, bisbenzimide thermodiffusion. Confocal microscopy and surface-enhanced Raman spectroscopy (SERS) were used to demonstrate bisbenzimide loading/leaking and near-IR-triggered cargo release inside cells, thereby leading to DNA staining.

Silver-Assisted Synthesis of Gold Nanorods: the Relation between Silver Additive and Iodide Impurities.

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.

Quantitative Particle-Cell Interaction: Some Basic Physicochemical Pitfalls.

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.

Conformational SERS Classification of K-Ras Point Mutations for Cancer Diagnostics.

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.

Online Flowing Colloidosomes for Sequential Multi-analyte High-Throughput SERS Analysis.

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

Surface-Enhanced Raman Scattering Surface Selection Rules for the Proteomic Liquid Biopsy in Real Samples: Efficient Detection of the Oncoprotein c-MYC.

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.