Boronic acid-functionalized plasmonic interfaces enable ultrasensitive molecular recognition and biosensing in plasmonic nanocavities, yet their photochemical stability under hot-carrier excitation remains poorly understood. Here, we elucidate the plasmonic nanocavity-induced degradation pathway of self-assembled monolayers (SAMs) of 4-mercaptophenylboronic acid (4-MPBA) on Au(111) using hyperspectral tip-enhanced Raman spectroscopy (TERS). In situ TERS measurements visualize a stepwise plasmon-driven degradation process at the solid-air interface. Plasmonic excitation initiates deboronation and intermolecular cross-linking within the monolayer, followed by progressive oxidation at the sulfur center and eventual C-S bond cleavage. Complementary electrospray ionization mass spectrometry and X-ray photoelectron spectroscopy identify the final degradation products as oxidized sulfur species, consistent with the TERS spectral signatures. Temperature-programmed desorption mass spectrometry rules out thermal heating as the primary driving force, while density functional theory calculations support plasmon-mediated molecular activation via direct excitation or hot-electron transfer. Together, these results reveal a previously unrecognized degradation pathway of 4-MPBA SAMs on Au(111) that can be directly visualized within a plasmonic nanocavity, providing molecular-level insight into plasmon-driven interfacial chemistry and guiding the design of more stable boronic acid-based plasmonic biosensors.

Antimony selenide (Sb2Se3) has emerged as one of the promising alternative p-type absorbers for thin-film photovoltaics due to its earth abundance, favourable band gap, and high absorption coefficient. However, its practical efficiency remains still limited by crystallographic anisotropy and intrinsically low carrier density, motivating the search for effective doping strategies. Copper (Cu) has recently been introduced as a dopant in Sb2Se3, yet the nanoscale details of its incorporation and distribution at relatively high concentrations (3-5%) remain unclear. Here, we employ conductive atomic force microscopy (C-AFM) in combination with AFM topography to directly compare undoped and Cu-doped Sb2Se3 thin films prepared by radio-frequency magnetron sputtering. Correlated current and morphology mapping reveal an approximately two-order-of-magnitude increase in conductivity upon Cu doping, with a relatively homogeneous distribution across grains in device-relevant thick films. Characterization of thinner films can provide details also on other nanosized features, like localized conductivity hotspots and potential percolative shunts at grain boundaries. Such nanoscale insights are essential for a comprehensive understanding of this dopant behavior and, at the same time, highlight a novel C-AFM-based approach to study doping effects in semiconductor thin films.

Strain is a proven technique for modifying the bandgap and enhancing carrier mobility in 2D materials. Most current strain engineering techniques rely on the post-growth transfer of these atomically thin materials from growth substrates to target surfaces, limiting their integration into nanoelectronics. Here, we present a new approach where strain in 2D materials is already introduced directly during their growth on grayscale-patterned topographies instead of flat surfaces. Both strain levels and orientations are deterministically engineered by controlling grayscale surface contour lengths through thermal expansion mismatches in nanostructured stacks, where the conformally grown and firmly attached 2D material is forced to match the underlying morphology change during cooling. With this method, we experimentally demonstrate precise control of localized tensile strain from 0 to 0.5% in grown MoS2 monolayer along both uni- and multiaxial directions, while higher strain levels are shown to be theoretically possible. This strain-engineered growth of 2D material films directly on the target substrates is a generic and adaptable approach to various combinations of grayscale-thin-film/substrates and eliminates all the transfer-related limitations of previous approaches, thus paving the way for integrating strained 2D materials into next-generation nanoelectronics.

Heterogeneous catalysts underpin much of the modern chemical industry, yet their rational design for enhanced activity, selectivity, and sustainability remains a formidable challenge due to the intrinsic structural and chemical heterogeneity of catalytic surfaces. Conventional ensemble-averaged characterization techniques often fail to capture the nanoscale complexity that governs catalytic function. Over the past two decades, tip-enhanced Raman spectroscopy (TERS) has emerged as a powerful nanoanalytical technique, offering single-molecule sensitivity and spatial resolution down to the Ångström scale. In this Review, we present TERS as a versatile, nondestructive, and label-free approach for probing heterogeneous catalytic reactions with nanometer-scale chemical specificity in air, liquid, and electrochemical environments. We first introduce the fundamental principles and instrumental implementations that underpin reliable TERS measurements. We then provide a comprehensive and critical assessment of reported ex situ, in situ, and emerging operando TERS studies across a wide range of catalytic systems, highlighting key mechanistic insights uniquely accessible by this technique. Finally, we discuss the technical challenges and methodological requirements for advancing operando TERS toward realistic reaction conditions, and outline promising directions for future research. By integrating practical considerations with conceptual advances, this Review aims to serve as a comprehensive guide for researchers seeking to apply TERS to nanoscale chemical analysis in heterogeneous catalysis.

Mechanistic insights into the molecular-level dynamics of nitroarene hydrogenation on Pt remain limited, largely because most prior studies rely on ex situ, ensemble-averaged measurements, or simulations considered in isolation. Here, we address this gap and demonstrate a novel methodology combining in situ tip-enhanced Raman spectroscopy (TERS) with density functional theory (DFT) modeling to track, at a well-defined single plasmonic junction, the hydrogenation of chloronitrothiophenol (CNTP) on atomically flat Pt(111). In situ TERS captures the dynamic transformation of CNTP → chloroaminothiophenol (CATP) under ambient H2 exposure with a characteristic time scale of ∼6 s. Complementary DFT modeling maps the reaction energetics, revealing novel mechanistic insights: CNTP desorption is rapid initially (barrier 0.61 eV) but slows down once the Pt(111) surface is at about half-coverage; molecular bending on the half-covered Pt(111) surface is barrierless and exergonic; the first hydrogen addition to CNTP is facile (barrier 0.26 eV), while the second hydrogen addition is kinetically most demanding (barrier 0.83 eV), yielding a time scale of seconds that matches experimental results and identifies the rate-determining step. These findings advance molecular-level understanding of nitroarene hydrogenation on Pt(111) and demonstrate in situ TERS integrated with first-principles DFT modeling as a powerful platform for operando mechanistic studies of heterogeneous catalytic processes at the nanoscale.

Mapping the spatial distribution of valley polarization at the nanoscale is essential for understanding the influence of local inhomogeneities to the performance of transition metal dichalcogenide (TMD) valleytronic devices but remains challenging due to the spatial resolution limits of conventional optical techniques. Herein, we introduce tip-enhanced circularly polarized photoluminescence (TECPPL) imaging, enabling the simultaneous mapping of exciton emission intensity and valley polarization. We investigate a monolayer (1L) MoS2/WS2 heterojunction (HJ) and observe pronounced near-field (NF) photoluminescence (PL) enhancement under both σ+σ+ and σ+σ- polarization configurations. A NF circular polarization degree (Pc) of 0.67 is achieved, representing a 4-fold increase over the far-field (FF) measurement. The high local signal enhancement enables direct visualization of spatial variations in both the PL intensity and Pc with a spatial resolution of ∼20 nm. Our results establish TECPPL as a powerful nanospectroscopic tool and offer new insights into the spatially resolved valleytronic behavior of TMD heterostructures.

The on-surface condensation of boronic acids is a key step in fabricating functional interfaces with tailored properties; yet, a clear understanding of the molecular structural transformations involved remains a significant challenge. Here, we directly monitor the condensation reaction in a self-assembled monolayer of 4-mercaptophenylboronic acid (MPBA) on Au(111) using tip-enhanced Raman spectroscopy (TERS). The structural evolution in the MPBA adlayer is tracked via the emergence of new peaks, blue shifts, and intensity changes in characteristic Raman bands. Hyperspectral TERS imaging provides comprehensive insight into molecular transformations, including B-O-B bond formation, increased molecular constraints, and an evolution in molecular orientation. Furthermore, density functional theory simulations confirm that the boroxine trimer is the primary product of the on-surface condensation reaction. This study provides significant insights into on-surface boronic acid condensation chemistry for the rational design of functionalized surfaces with targeted chemical properties.

CrSBr, a layered van der Waals material with intrinsic air stability and layer-dependent magnetic and electronic properties, has emerged as a promising 2D semiconductor. However, nanoscale insight into its thicknessdependent structural and electronic behavior remains limited. In this study, we employ hyperspectral tipenhanced Raman spectroscopy (TERS) imaging to investigate the vibrational and electronic properties of exfoliated CrSBr nanoflakes. Both confocal Raman and TERS measurements reveal a systematic enhancement of the A2g Raman mode relative to the A3g mode in thinner flakes. The I (A2g)/I (A3g) intensity ratio decreases consistently with increasing flake thickness, reflecting underlying changes in the electronic band structure. Hyperspectral TERS mapping confirms this trend at the single-flake level and suggests a resonance Raman enhancement influenced by electron-phonon coupling near the band edge. Our results establish the I (A2g)/I (A3g) ratio as a sensitive spectroscopic marker for thickness-dependent band structure evolution in CrSBr. More broadly, this work highlights hyperspectral TERS as a powerful tool for probing local structure-property relationships in emerging low-dimensional materials.

Nanoplastics pose growing environmental and health risks, yet their label-free, nondestructive detection and characterization, especially at the single-particle level, remain challenging. Here, we deploy AFM-based tip-enhanced Raman spectroscopy (AFM-TERS) to chemically characterize individual polystyrene (PS) nanoplastic particles via hyperspectral imaging under ambient conditions. TERS spectra from nanoparticles as small as 32 nm establish reliable single-particle sensitivity beyond the optical diffraction limit. Furthermore, hyperspectral TERS maps reveal pronounced intraparticle heterogeneity, reflected spatially as varying red-/blue-shifts of PS marker bands with broad frequency distributions, without any systematic dependence on particle size. Correlative AFM phase imaging exposes nanoscale variations in local stiffness indicating strain heterogeneity as the origin of the spectral shifts. These results demonstrate that AFM-TERS enables single-particle mapping of intraparticle heterogeneity in nanoplastics. This offers new possibilities to identify nanoplastics with molecular specificity and monitor chemical transformations at the single-particle level within complex biological and environmental matrices.

Bacterial extracellular vesicles (EVs) are nanosized vesicles released by both Gram-negative and Gram-positive bacteria, playing critical roles in microbial communication, host-pathogen interactions, and immune modulation. Despite their significance in research and clinical applications, conventional isolation methods, such as ultracentrifugation (UC), are often slow, labor-intensive, and susceptible to contamination. In this study, we evaluated a novel portable microstructured electrochemical device (PMED) designed for rapid and selective bacterial EV isolation directly from biological samples. Using immunoaffinity-based capture and voltage-triggered release, the device-isolated EVs from Gram-negative Escherichia coli (E. coli), Gram-positive Lactobacillus fermentum (Lb. fermentum) culture supernatants and from urine samples spiked with E. coli , showing superior purity compared to UC. Characterization through nanoparticle tracking analysis (NTA), dynamic light scattering (DLS), and Western blot confirms enhanced selectivity and reduced contaminants. Functional assays demonstrated that device-isolated Lb. fermentum EVs selectively activated Toll-like receptor 4 (TLR4) without triggering TLR2, unlike UC-isolated EVs, suggesting a more refined immunomodulatory effect. These findings highlight the device's translational potential for EV-based diagnostics, particularly for noninvasive urinary tract infection detection, and its broader applications in studying bacterial communication and immune regulation.

Tip-enhanced Raman spectroscopy (TERS) was invented almost 25 years ago and was quickly recognized as one of the few nano-optical techniques that confine light at the nanoscale to explore light-matter interactions at the nanoscale. Even several years after its invention, the spatial resolution in TERS studies is not only somewhat controversial, especially for AFM-based TERS measurements of samples at room temperature, but also not reported in the literature in a consistent, generally accepted fashion. This Mini-Review discusses the current situation and how spatial resolution in TERS is reported in different ways that yield different values because no standard method is defined. More importantly, the spatial resolution in TERS is influenced by various experimental conditions and other factors in a comprehensive fashion, which have often been ignored. We consider all possible factors that affect spatial resolution in TERS and provide guidelines on how to determine and report spatial resolution.

Thermochromic vanadium dioxide (VO2) thin films, known for their reversible metal-insulator transition (MIT) near 68 °C, are promising candidates for energy-efficient applications such as smart window coatings. However, optimizing their structural and interfacial properties to enhance thermochromic performance remains a significant challenge. Traditional characterization techniques such as X-ray diffraction and transmission electron microscopy face inherent limitations in simultaneously providing detailed chemical information and nanoscale spatial resolution─capabilities that are essential for resolving localized structural heterogeneity and interfacial phenomena. This study employs hyperspectral tip-enhanced Raman spectroscopy (TERS) imaging to address these limitations and investigate the nanoscale structure of pristine VO2 and VO2/TiO2 thin films. TERS imaging revealed nanoscale regions of lattice deformations and nanocrystallites with different orientations in VO2 thin films, resulting in a high density of grain boundaries that elevate the MIT temperature. In VO2/TiO2 bilayers, TERS detected coexisting anatase and brookite phases in the TiO2 layer, with tensile strain in the brookite phase and the VO2/TiO2 interface characterized by localized intermixing and strain. These novel insights underscore the polycrystalline nature of the thin films grown with pulsed layer deposition technique and highlight the critical role of nanoscale structural and interfacial properties in determining thermochromic performance of VO2-based thin films. Furthermore, this study demonstrates the effectiveness of TERS as a robust nanoanalytical tool for advancing the design of VO2-based smart coatings and functional materials.

Tip-enhanced Raman spectroscopy (TERS) has established itself as a powerful tool in nanoscale chemical analysis, providing unprecedented spatial resolution with high molecular sensitivity and chemical specificity. TERS employs localized surface plasmon resonance at the apex of a sharp scanning probe microscopy tip to overcome the diffraction limit inherent in conventional Raman spectroscopy, achieving spatial resolutions down to the nanometer scale. In this article, we highlight major advancements in TERS over the past five years from our laboratory at ETH Zurich in the following key areas: heterogeneous catalysis, photovoltaic materials, biological membranes, and on-surface molecular assembly. Our recent studies demonstrate the unique capabilities of TERS for in situmonitoring of catalytic reactions, nanoscale mapping of phase behavior in biomembranes, and precise characterization of photovoltaic interfaces. Through these applications, we highlight the potential of TERS for addressing critical challenges across the chemical, biological, and materials sciences. This review serves as a guide for researchers aiming to harness TERS for label-free, non-destructive nanoanalysis to advance understanding of complex molecular materials and processes through ultrahigh sensitivity, specificity, and spatial resolution.

Efficient H2 activation under mild conditions is crucial for achieving energy-efficient catalytic hydrogenation but remains a major challenge. Here, we demonstrate nanoscale visualization of plasmon-enhanced H2 activation on the Pt(111) surface at room temperature under visible light by employing a combination of tip-enhanced Raman spectroscopy (TERS), density functional theory, finite element method (FEM), and quantum mechanical modeling. Time-dependent in situ TERS successfully tracked H2 activation via reductive desorption, while hyperspectral imaging revealed a 20% increase in H2 activation in 180–300 nm regions around the TERS near-field. Plasmonic heating was excluded as the origin of the enhanced H2 activation based on both experimental spectroscopic evidence and FEM simulations. Instead, first-principles quantum calculations demonstrated that hot electrons generated in the TERS near-field can drive H2 dissociation at the top, bridge, and fcc sites on the Pt(111) surface via indirect hot electron transfer mechanism. Importantly, we demonstrate that the activated hydrogen atoms on Pt(111) surface can propagate beyond the plasmonic near-field through a “crowd effect”. This fundamental study provides direct experimental evidence and mechanistic insights into plasmon-enhanced H2 activation and propagation on the Pt(111) surface, offering a new route for energy-efficient catalytic hydrogenation.

Gaining mechanistic understanding of oxygen activation on metal surfaces is a topical area of research in surface science. However, direct investigation of on-surface oxidation processes at the nanoscale and the empirical validation of oxygen activation pathways remain challenging for the conventional analytical tools. In this study, we applied tip-enhanced Raman spectroscopy (TERS) to gain mechanistic insights into oxygen activation on bulk Au(111) surface. Specifically, oxidation of 4-aminothiophenol (4-ATP) to 4-nitrothiophenol (4-NTP) on Au(111) surface was investigated using hyperspectral TERS imaging. Nanoscale TERS images revealed a markedly higher oxidation efficiency in disordered 4-ATP adlayers compared to the ordered adlayers signifying that the oxidation of 4-ATP molecules proceeds via interaction with the on-surface oxidative species. These results were further validated via direct oxidation of the 4-ATP adlayers with H2O2 solution. Finally, TERS measurements of oxidized 4-ATP adlayers in the presence of H2O18 provided the first empirical evidence for the generation of oxidative species on bulk Au(111) surface via water-mediated activation of molecular oxygen. This study expands our mechanistic understanding of oxidation chemistry on bulk Au surface by elucidating the oxygen activation pathway.

In this study, we investigate the impact of deuteration on the formation of phase-separated domains in supported lipid monolayers using hyperspectral Tip-Enhanced Raman Spectroscopy (TERS) imaging. The intricate organization of biological membranes plays a crucial role in cellular functions. Various factors that influence domain formation have been identified in previous studies such as lipid tail length and cholesterol concentration. Deuterium labeling of lipids has proven useful for probing cellular structures and dynamics, but its impact on lipid phase separation remains underexplored. By examining 1:1 mixed monolayers of dipalmitoylphosphatidylcholine (DPPC) and deuterated DPPC on Au(111) surfaces, we reveal partial segregation of domains rich in deuterated and nondeuterated lipids. This study addresses a gap in knowledge by examining the impact of deuteration on lipid tail behavior, offering new insights into how even subtle structural modifications can influence phase behavior. Furthermore, it demonstrates that TERS can be a powerful, nondestructive, and label-free nanoanalytical tool for analyzing lipid membranes and advance the field of membrane biophysics.

In transferred twisted bilayer (tBL) two-dimensional transition-metal dichalcogenides (TMDs), large strain in the nanowrinkles can induce strong deforming potential, resulting in strong localized excitonic behavior. Probing localized interlayer exciton behavior challenges the spatial resolution and sensitivity of conventional analytical tools. Herein, we have applied tip-enhanced photoluminescence (TEPL) nanoscopy for investigation of nanowrinkles in tBL MoS2. The localization of interlayer and intralayer excitons at the nanowrinkles was clearly revealed in the hyperspectral TEPL image of tBL MoS2. Using high-resolution TEPL data, the excitonic potential at the nanowrinkles was experimentally determined to be 8.6 +/- 1.9 meV. Furthermore, the TEPL experimental results were corroborated by numerical simulations based on the exciton diffusion theory. The novel insights into the excitonic behavior of nanowrinkles in t2L MoS2 obtained in this work deepen our understanding of the optoelectronic behavior in t2L TMD materials.

Interfacial regions play a key role in determining the overall power conversion efficiency of thin film solar cells. However, the nanoscale investigation of thin film interfaces using conventional analytical tools is challenging due to a lack of required sensitivity and spatial resolution. Here, we surmount these obstacles using tip-enhanced Raman spectroscopy (TERS) and apply it to investigate the absorber (Sb2Se3) and buffer (CdS) layers interface in a Sb2Se3-based thin film solar cell. Hyperspectral TERS imaging with 10 nm spatial resolution reveals that the investigated interface between the absorber and buffer layers is far from uniform, as TERS analysis detects an intermixing of chemical compounds instead of a sharp demarcation between the CdS and Sb2Se3 layers. Intriguingly, this interface, comprising both Sb2Se3 and CdS compounds, exhibits an unexpectedly large thickness of 295 ± 70 nm attributable to the roughness of the Sb2Se3 layer. Furthermore, TERS measurements provide compelling evidence of CdS penetration into the Sb2Se3 layer, likely resulting from unwanted reactions on the absorber surface during chemical bath deposition. Notably, the coexistence of ZnO, which serves as the uppermost conducting layer, and CdS within the Sb2Se3-rich region has been experimentally confirmed for the first time. This study underscores TERS as a promising nanoscale technique to investigate thin film inorganic solar cell interfaces, offering novel insights into intricate interface structures and compound intermixing.

Field-effect transistors (FETs) based on two-dimensional materials (2DMs) with atomically thin channels have emerged as a promising platform for beyond-silicon electronics. However, low carrier mobility in 2DM transistors driven by phonon scattering, remains a critical challenge. To address this issue, we propose the controlled introduction of localized biaxial tensile strain as an effective mean to inhibit electron-phonon scattering in 2DM. Strain is achieved by conformally adhering the 2DM via van-der-Waals forces to a dielectric layer previously nanoengineered with a gray-tone topography. Our results show that a monolayer MoS2 FETs under tensile strain achieves an 8-fold increase in on-state current reaching mobilities of 185 cm2/Vs at room temperature, in good agreement with theoretical calculations. The present work on nanotopographic grayscale surface engineering and the use of high-quality dielectric materials has the potential to find application in the nanofabrication of photonic and nanoelectronic devices.