Simultaneous quantification of Young's modulus and dispersion forces with nanoscale spatial resolution.

Many advances in polymers and layered materials rely on a precise understanding of the local interactions between adjacent molecular or atomic layers. Quantifying dispersion forces at the nanoscale is particularly challenging with existing methods often time consuming, destructive, relying on surface averaging or requiring bespoke equipment. Here, we present a non-invasive method able to quantify the local mechanical and dispersion properties of a given sample with nanometer lateral precision. The method, based on atomic force microscopy (AFM), uses the frequency shift of a vibrating AFM cantilever in combination with established contact mechanics models to simultaneously derive the Hamaker constant and the effective Young's modulus at a given sample location. The derived Hamaker constant and Young's modulus represent an average over a small (typically <100) number of molecules or atoms. The oscillation amplitude of the vibrating AFM probe is used to select the length-scale of the features to analyse, with small vibrations able to resolve the contribution of sub-nanometric defects and large ones exploring effectively homogeneous areas. The accuracy of the method is validated on a range of 2D materials in air and water as well as on polymer thin films. We also provide the first experimental measurements of the Hamaker constant of HBN, MoT2, WSe2and polymer films, verifying theoretical predictions and computer simulations. The simplicity and robustness of the method, implemented with a commercial AFM, may support a broad range of technological applications in the growing field of polymers and nanostructured materials where a fine control of the van der Waals interactions is crucial to tune their properties.

Quantitative Detection of Biological Nanovesicles in Drops of Saliva Using Microcantilevers.

Extracellular nanovesicles (EVs) are lipid-based vesicles secreted by cells and are present in all bodily fluids. They play a central role in communication between distant cells and have been proposed as potential indicators for the early detection of a wide range of diseases, including different types of cancer. However, reliable quantification of a specific subpopulation of EVs remains challenging. The process is typically lengthy and costly and requires purification of relatively large quantities of biopsy samples. Here, we show that microcantilevers operated with sufficiently small vibration amplitudes can successfully quantify a specific subpopulation of EVs directly from a drop (0.1 mL) of unprocessed saliva in less than 20 min. Being a complex fluid, saliva is highly non-Newtonian, normally precluding mechanical sensing. With a combination of standard rheology and microrheology, we demonstrate that the non-Newtonian properties are scale-dependent, enabling microcantilever measurements with a sensitivity identical to that in pure water when operating at the nanoscale. We also address the problem of unwanted sensor biofouling by using a zwitterionic coating, allowing efficient quantification of EVs at concentrations down to 0.1 µg/mL, based on immunorecognition of the EVs' surface proteins. We benchmark the technique on model EVs and illustrate its potential by quantifying populations of natural EVs commonly present in human saliva. The method effectively bypasses the difficulty of targeted detection in non-Newtonian fluids and could be used for various applications, from the detection of EVs and viruses in bodily fluids to the detection of molecular clusters or nanoparticles in other complex fluids.

Real-time tracking of ionic nano-domains under shear flow.

The behaviour of ions at solid-liquid interfaces underpins countless phenomena, from the conduction of nervous impulses to charge transfer in solar cells. In most cases, ions do not operate as isolated entities, but in conjunction with neighbouring ions and the surrounding solution. In aqueous solutions, recent studies suggest the existence of group dynamics through water-mediated clusters but results allowing direct tracking of ionic domains with atomic precision are scarce. Here, we use high-speed atomic force microscopy to track the evolution of Rb+, K+, Na+ and Ca2+ nano-domains containing 20 to 120 ions adsorbed at the surface of mica in aqueous solution. The interface is exposed to a shear flow able to influence the lateral motion of single ions and clusters. The results show that, when in groups, metal ions tend to move with a relatively slow dynamics, as can be expected from a correlated group motion, with an average residence timescale of ~ 1-2 s for individual ions at a given atomic site. The average group velocity of the clusters depends on the ions' charge density and can be explained by the ion's hydration state. The lateral shear flow of the fluid is insufficient to desorb ions, but indirectly influences the diffusion dynamics by acting on ions in close vicinity to the surface. The results provide insights into the dynamics of ion clusters when adsorbed onto an immersed solid under shear flow.

Impact of water on the lubricating properties of hexadecane at the nanoscale.

Fluid lubricants are routinely used to reduce friction in a wide range of applications, from car engines to machinery and hard-disk drives. However, their efficiency can be significantly influenced by the ambient conditions they are exposed to, in particular humidity. Our understanding of the molecular mechanisms responsible for the well-documented impact of water on lubrication remains limited, hindering the improvement of tribological formulations. Here, we use Atomic Force Microscopy (AFM) and shear force spectroscopy to investigate the structural and dynamical behaviour of a model lubricant, hexadecane, confined between an AFM probe and a hydrophilic mica surface at different temperatures and humidities. We show that both the nanoscale structure and the tribological behaviour of the system are dominated by the nucleation of water nanodroplets at the interface. The process is favoured at higher temperature and can be explained with classical nucleation theory whereby the droplets become stable when larger than 20 nm to 50 nm size, depending on the ambient conditions. Below this threshold, a molecularly thin film of water molecules coats the surface uniformly. Highly localised shear measurements demonstrate a detrimental impact of the nanodroplets on shear with a twofold increase in the lubricated friction force. However, this can be mitigated by the adjunction of an amphiphilic additive, here oleic acid.

Lubricated friction around nanodefects.

The lubrication properties of nanoconfined liquids underpin countless natural and industrial processes. However, our current understanding of lubricated friction is still limited, especially for nonideal interfaces exhibiting nanoscale chemical and topographical defects. Here, we use atomic force microscopy to explore the equilibrium and dynamical behavior of a model lubricant, squalane, confined between a diamond tip and graphite in the vicinity of an atomic step. We combine high-resolution imaging of the interface with highly localized shear measurements at different velocities and temperatures to derive a quantitative picture of the lubricated friction around surface defects. We show that defects tend to promote local molecular order and increase friction forces by reducing the number of stable molecular configurations in their immediate vicinity. The effect is general, can propagate over hundreds of nanometers, and can be quantitatively described by a semiempirical model that bridges the molecular details and mesoscale observations.

Vitamin K Concentration and Cognitive Status in Elderly Patients on Anticoagulant Therapy: A Pilot Study.

OBJECTIVES: Recent studies have suggested that vitamin K may exert significant effects on the central nervous system. The present study investigates the relationship between vitamin K plasmatic levels and cognitive functions in elderly patients on oral anticoagulant therapy (OAT). DESIGN: At the Thrombosis Centre of Haematology, "Sapienza" University of Rome, 85 patients on OAT, aged between 75 and 92, were randomly enrolled in the study. Patients were on OAT with vitamin K antagonists (VKAs). Vitamin K1 concentrations were determined using standardized High-Performance Liquid Chromatography (HPLC). Cognitive functions were assessed using the Milan Overall Dementia Assessment (MODA). RESULTS: MODA scores are positively correlated to vitamin K1 concentration. Patients with vitamin K1 below 0.100 µg/L and between 0.100 and 0.400 µg/L and between 0.100 and 0.400 µg/L and between 0.100 and 0.400 p < 0.001). Even long-term OAT (>10 years) does not affect MODA scores. Education seems to exert a greater role on the cognitive status in comparison with aging. CONCLUSIONS: The study shows a positive association between vitamin K1 concentration and cognitive status in elderly patients (≥75 years) on OAT. The relationship between vitamin K1 concentration and MODA scores is described by a linear model. Cognitive status is not influenced by the duration of OAT but by the years of education.

Correction to: Plasma Vitamin K1 Levels in Italian Patients Receiving Oral Anticoagulant Therapy for Mechanical Heart Prosthesis: A Case-Control Study.

Throughout the manuscript the units of plasma vitamin K1 concentration which previously read.

Lubricating properties of single metal ions at interfaces.

The behaviour of ionic solutions confined in nanoscale gaps is central to countless processes, from biomolecular function to electrochemistry, energy storage and lubrication. However, no clear link exists between the molecular-level behaviour of the liquid and macroscopic observations. The problem mainly comes from the difficulty to interrogate a small number of liquid molecules. Here, we use atomic force microscopy to investigate the viscoelastic behaviour of pure water and ionic solutions down to the single ion level. The results show a glassy-like behaviour for pure water, with single metal ions acting as lubricants by reducing the elasticity of the nano-confined solution and the magnitude of the hydrodynamic friction. At small ionic concentration (<20 mM) the results can be quantitatively explained by the ions moving via a thermally-activated process resisted by the ion's hydration water (Prandtl-Tomlinson model). The model breaks down at higher salt concentrations due to ion-ion interaction effects that can no longer be neglected. The correlations are confirmed by direct sub-nanometre imaging of the interface at equilibrium. The results provide a molecular-level basis for explaining the tribological properties of aqueous solutions and suggest that ion-ion interactions create mesoscale effects that prevent a direct link between nanoscale and macroscopic measurements.

Direct observation of the dynamics of single metal ions at the interface with solids in aqueous solutions.

The dynamics of ions adsorbed at the surface of immersed charged solids plays a central role in countless natural and industrial processes such as crystal growth, heterogeneous catalysis, electrochemistry, or biological function. Electrokinetic measurements typically distinguish between a so-called Stern layer of ions and water molecules directly adsorbed on to the solid's surface, and a diffuse layer of ions further away from the surface. Dynamics within the Stern layer remain poorly understood, largely owing to a lack of in-situ atomic-level insights. Here we follow the dynamics of single Rb+ and H3O+ ions at the surface of mica in water using high-resolution atomic force microscopy with 25 ms resolution. Our results suggest that single hydrated Rb+ions reside τ1 = 104 ± 5 ms at a given location, but this is dependent on the hydration state of the surface which evolves on a slower timescale of τ2 = 610 ± 30 ms depending on H3O+ adsorption. Increasing the liquid's temperature from 5 °C to 65 °C predictably decreases the apparent glassiness of the interfacial water, but no clear effect on the ions' dynamics was observed, indicating a diffusion-dominated process. These timescales are remarkably slow for individual monovalent ions and could have important implications for interfacial processes in electrolytes.

Sub-nanometer Resolution Imaging with Amplitude-modulation Atomic Force Microscopy in Liquid.

Atomic force microscopy (AFM) has become a well-established technique for nanoscale imaging of samples in air and in liquid. Recent studies have shown that when operated in amplitude-modulation (tapping) mode, atomic or molecular-level resolution images can be achieved over a wide range of soft and hard samples in liquid. In these situations, small oscillation amplitudes (SAM-AFM) enhance the resolution by exploiting the solvated liquid at the surface of the sample. Although the technique has been successfully applied across fields as diverse as materials science, biology and biophysics and surface chemistry, obtaining high-resolution images in liquid can still remain challenging for novice users. This is partly due to the large number of variables to control and optimize such as the choice of cantilever, the sample preparation, and the correct manipulation of the imaging parameters. Here, we present a protocol for achieving high-resolution images of hard and soft samples in fluid using SAM-AFM on a commercial instrument. Our goal is to provide a step-by-step practical guide to achieving high-resolution images, including the cleaning and preparation of the apparatus and the sample, the choice of cantilever and optimization of the imaging parameters. For each step, we explain the scientific rationale behind our choices to facilitate the adaptation of the methodology to every user's specific system.

Plasma Vitamin K1 Levels in Italian Patients Receiving Oral Anticoagulant Therapy for Mechanical Heart Prosthesis: A Case-Control Study.

BACKGROUND: Oral anticoagulant therapy (OAT) with a vitamin K antagonist (VKA) is the choice of treatment for preventing thromboembolism in patients with mechanical heart valve prosthesis (MHP). The percentage of time in the therapeutic range (TTR%) expresses the OAT quality. We planned a case-control study in order to determine vitamin K1 plasmatic concentrations in MHP patients and to correlate these with TTR%. MATERIALS AND METHODS: Of 756 MHP patients receiving OAT, 125 patients (61 younger than 65 years, and 64 older than 65 years) and 120 healthy blood donors, matched for sex and age, were enrolled in the study. All subjects completed a living questionnaire regarding diet, and underwent blood collection. Vegetable and fruit intake was categorized as optimal or suboptimal, and the high-performance liquid chromatography method was used to determine vitamin K1 levels. RESULTS: Neither the patients nor controls had been taking vitamin supplements prior to the start of the study. The median vitamin K1 level was 290 pg/mL in 72 controls with optimal intake, and 274 pg/mL in 48 controls with suboptimal intake, while the median vitamin K1 level in MHP patients with optimal intake was 409 pg/mL, significantly higher (p < 0.001) than the 133.5 pg/mL in patients with suboptimal intake. Vitamin K1 concentration in MHP patients appears to be linked to an age-related threshold: in patients younger than 65 years of age, the median vitamin K1 level was 431 pg/mL, significantly higher (p < 0.05) than the 290 pg/mL in patients older than 65 years of age. No clear relation was found between vitamin K1 levels and TTR% (Pearson = 0.14). However, patients with vitamin K1 >160 pg/mL showed a TTR% >60 %. Among patients younger than 65 years, subjects with vitamin K1 >160 pg/mL showed a median TTR of 66 %, this being significantly higher (p < 0.001) than the 46 % level shown by patients with vitamin K1 <160 pg/mL. CONCLUSIONS: Vitamin K1 concentrations in MHP patients seem to be related to both diet and age.