Nano-atomic scale hydrophobic/philic confinement of peptides on mineral surfaces by cross-correlated SPM and quantum mechanical DFT analysis.

The fundamental knowledge of the interaction between biomolecules and mineral surfaces is of utmost importance to drive new technological advancements, particularly for condensation, aggregation, catalysis and exchange of biomolecules. The mineral surface can be used in several fields and applications, for instance in biotechnology, environmental science and remediation, soil science, agro-food and related technology. This kind of knowledge may also provide several suggestions and have implications also for the prebiotic chemistry field, namely the study of the abiotic physicochemical steps that could have led to the 'creation' of the first known living organism. Nowadays, this kind of information at the micro and nanometric scale can be explored with several experimental and theoretical techniques and, among them, atomic force microscopy (AFM)-related methods and density functional theory (DFT) are particularly suited to investigate adsorption processes at single molecule level. In the present work, the specific interaction at the atomic scale between a small peptide (di-glycine) and the (001) surface of clinochlore, a mineral presenting alternately stacked talc-like layers (hydrophilic) and brucite-like sheets (hydrophobic), was characterized by means of a cross-correlated approach combining AFM and DFT simulations. The experiments evidenced the preferential adsorption of di-glycine onto the hydrophobic brucite-like sheet of the mineral, with the observed molecules organized as dot-like (single-molecules), agglomerates, filament-like and network structures by the surface, whereas only very few peptides were imaged onto the hydrophilic talc-like layer. From the theoretical analysis, the most stable conformation of the di-glycine peptide adsorbed on the mineral surface was calculated, and the binding energy analysis of the specific interaction of the molecule, depending on the local chemistry of the substrate, provided fundamental information to interpret end explain the experimental evidence. LAY DESCRIPTION: The present work aims at extending the knowledge of the biomolecules/minerals interaction world. The fundamental knowledge of the interaction between biomolecules and mineral surfaces is of utmost importance to drive the development of new technological advancements, particularly for condensation, aggregation, catalysis and exchange of biomolecules. The mineral surface can be used as substrate in several fields and applications, for instance in biotechnology, environmental science and remediation, soil science, agro-food and related technology. This kind of research may also provide several suggestions and have implications also for the prebiotic chemistry field, namely the study of the abiotic physicochemical steps that could have led to the "creation" of the first known living organism. Nowadays, this kind of research at the micro and nanometric scale can be performed with several experimental techniques and, among them, scanning probe microscopy-related methods are particularly suited to investigate surface adsorption processes at single molecule level. In the present work, the focus is on the specific interaction at the atomic scale between a small peptide (di-glycine) and the surface of clinochlore (a diffuse clay mineral). Clinochlore is a mineral belonging to the phyllosilicate, formed by alternately stacked hydrophilic talc-like layers [chemical formula Mg3 Si4 O10 (OH)2 ] and hydrophobic brucite-like sheets [magnesium hydroxide, Mg(OH)2 ]. Since these two kind of layered structures are held together by weak (van der Waals) forces, the mineral can be easily cleaved along the [001] crystallographic direction (the stacking direction) and the resulting (001) clinochlore surface may presents at the nanoscale some remainders of one layer (brucite-like or talc-like) on the other. This means that this mineral exposes to the environment two different type of surfaces, one hydrophilic and one hydrophobic, which can selectively interact with (adsorb) different type of molecules at the nanoscale. Clinochlore is also one of the 420 mineral species that were likely present on Earth at the time of life's origins, thus it could have played a fundamental role in prebiotic chemistry. In this study, the interaction between di-glycine and clinochlore was characterized by means of both atomic force microscopy (AFM) at the nanometric scale and density functional theory (DFT) simulations, correlating the results of the two methods (cross-correlation approach). The experiments evidenced the preferential adsorption of di-glycine onto the hydrophobic brucite-like sheet of the mineral, with the observed molecules organized as dot-like (single-molecules) structures, agglomerates, filaments and networks by the surface, whereas only very few peptides were imaged onto the hydrophilic talc-like layer. From the theoretical analysis, the most stable conformation of the di-glycine adsorbed on the mineral surface was calculated, and the binding energy analysis of the specific interaction of the molecule, depending on the local chemistry of the substrate, provided fundamental information to interpret end explain the experimental evidence.

Factors affecting safe and healthy diet in older adults in Italy: results of a preliminary study performed in a community-dwelling sample.

OBJECTIVE: To investigate, through a questionnaire, older adults' demographic and socio-economic characteristics, knowledge, attitudes and practices in terms of food safety and healthy diet; and to develop dietary and hygiene indices able to represent participants' nutritional and food safety behaviour, exploring their association with demographic and socio-economic factors. DESIGN: One-year cross-sectional study. SETTING: Gemelli Teaching Hospital (Rome, Italy). PARTICIPANTS: People aged ≥65 years, Italian speaking, accessing the Centre of Ageing Medicine. RESULTS: Mean age of the sample was 74 (sd 7·7) years. Subjective perception of a safe diet was high: 64·2 % of respondents believed they have a balanced diet. Interviewees got informed about proper nutrition mainly from television, magazines, newspapers, Internet (29·9 %) and from health professionals (34·8 %) such as dietitians, whereas 15·4 % from general practitioners. Regarding food safety, 33·8 % of participants reported to consume expired food, even more than once per month; between 80 and 90 % of participants reported to follow food safety practices during preparation and cooking, even though 49·3 % defrosted food at room temperature. Calculated dietary and hygiene indices showed that the elderly participants were far from having optimal nutritional and food safety behaviours. CONCLUSIONS: These results suggest it is necessary to increase the awareness of older adults in the matter of healthy diet and food safety. Specific and targeted educational interventions for the elderly and their caregivers could improve the adoption of recommended food safety practices and safe nutritional behaviours among older adults.

Targeted next-generation sequencing of circulating-tumor DNA for tracking minimal residual disease in localized colon cancer.

BACKGROUND: A high percentage of patients diagnosed with localized colon cancer (CC) will relapse after curative treatment. Although pathological staging currently guides our treatment decisions, there are no biomarkers determining minimal residual disease (MRD) and patients are at risk of being undertreated or even overtreated with chemotherapy in this setting. Circulating-tumor DNA (ctDNA) can to be a useful tool to better detect risk of relapse. PATIENTS AND METHODS: One hundred and fifty patients diagnosed with localized CC were prospectively enrolled in our study. Tumor tissue from those patients was sequenced by a custom-targeted next-generation sequencing (NGS) panel to characterize somatic mutations. A minimum variant allele frequency (VAF) of 5% was applied for variant filtering. Orthogonal droplet digital PCR (ddPCR) validation was carried out. We selected known variants with higher VAF to track ctDNA in the plasma samples by ddPCR. RESULTS: NGS found known pathological mutations in 132 (88%) primary tumors. ddPCR showed high concordance with NGS (r = 0.77) for VAF in primary tumors. Detection of ctDNA after surgery and in serial plasma samples during follow-up were associated with poorer disease-free survival (DFS) [hazard ratio (HR), 17.56; log-rank P = 0.0014 and HR, 11.33; log-rank P = 0.0001, respectively]. Tracking at least two variants in plasma increased the ability to identify MRD to 87.5%. ctDNA was the only significantly independent predictor of DFS in multivariable analysis. In patients treated with adjuvant chemotherapy, presence of ctDNA after therapy was associated with early relapse (HR 10.02; log-rank P < 0.0001). Detection of ctDNA at follow-up preceded radiological recurrence with a median lead time of 11.5 months. CONCLUSIONS: Plasma postoperative ctDNA detected MRD and identified patients at high risk of relapse in localized CC. Mutation tracking with more than one variant in serial plasma samples improved our accuracy in predicting MRD.

In vitro effects of fluoride-based and desensitizing toothpastes on dentine permeability.

This study aims to evaluate the effectiveness in reducing dentine permeability of three different toothpastes comparing with a sodium fluoride one. Dentine permeability was measured by a fluid filtration system. Dentin discs were randomized in four experimental groups and treated with different commercial toothpastes, as it follows. Group A: Sensodyne® Rapid, with strontium acetate; group B: Elmex Sensitive ProfessionalTM, with arginine and 450 ppm monofluoro-phosphate; group C: Colgate Total Advanced®, with 1450 ppm NaF; group D: AZ Pro-Expert®, with 1100 ppm SnF2. After brushing specimens of each groups were assigned to two subgroups and: 1) stored in artificial saliva (2 h) and treated with 6% citric acid for 1 min; 2) stored in artificial saliva for 24 h. SEM analysis was performed to investigate dentinal tubules occlusion of acid treated and stored in artificial saliva samples. Dentin permeability proved affected by dentifrice treatments. The toothpastes specifically formulated for hypersensitivity showed significant effects concerning decrease of dentine permeability. SEM observations demonstrated the presence of dentifrice particles on dentin surface and inside dentin tubules. Stannous fluoride treated samples exhibited the greater tubules occlusion.

Active Aging and Elderly's Quality of Life: Comparing the Impact on Literature of Projects Funded by the European Union and USA.

BACKGROUND: The objective of this research is to verify whether European projects on Active Aging (AA) and Elderly Quality of Life (Qol) funded by the Seventh Framework Programme (FP7) produce an impact on literature similar to projects funded by the National Health Institute (NHI) of the United States on international literature using well-known bibliometric indicators. This effort may be useful in developing standardized and replicable procedures. METHODS: Fifteen randomly selected projects on AA and Elderly Qol concluded in August 2017 and funded by FP7 were compared to similar projects funded by the US NHI with reference to papers published (Scopus and Scholar), papers published in Q1 journals, and the number of citations of the papers linked to the projects. RESULTS: In all the indicators considered, the European projects showed no difference with the US NHI projects. CONCLUSIONS: The EU-funded AA and Qol Elderly projects have an impact on scientific literature comparable to projects funded in the United States by the NHI Agency.Our results are consistent with the data on general medical research, which indicates that, European research remains at a high level of competitiveness.In this experimental study, our methodology appeared to be convincing and reliable and it could be applied to the extent of the impact of more extensive research areas.Our research did not evaluate the relationship between funding required by research and scientific productivity.

Risk for Depression, Burnout and Low Quality of Life Among Personnel of a University Hospital in Italy is a Consequence of the Impact One Economic Crisis in the Welfare System?

BACKGROUND: Research literature suggests that burnout, depression, and a low mental quality of life (QOL) are common among health care workers. Economic crisis might have increased the burden of burnout, depression and low QOL in health care workers. OBJECTIVES: To identify depression risk, burnout levels, and quality of life in a sample of workers of an Italian university hospital. METHOD: Cross sectional study with comparison with two community surveys database results (n = 2000 and 1500, respectively). Overall, 522 workers accepted to take part in the study, representing a 78% response rate (out of 669 individuals). RESULTS: The frequency of positivity at the screener for Major Depressive Disorder among health care workers was more than double than that in the standardized community sample (33.3% vs 14.1%, p<0.0001). All professionals, except the administrative staff and technicians (i.e. those who do not have contact with patients), showed a statistically higher frequency of positivity for depressive episodes compared to the controls. Among the medical staff, the highest risk was found in the surgeon units, while the lowest one was in the laboratories. Surgeons also were those most exposed to high risk of burnout, as measured by the Maslach Burnout Inventory. CONCLUSION: Since burnout is linked to patient safety and quality of patient care, and contribute to medical errors, dedicated interventions aimed at reducing poor mental health and low quality of life in medical staff are indicated.

Equivalence of pure propane and propane TE gases for microdosimetric measurements.

A tissue-equivalent proportional counter (TEPC) simulates micrometric volumes of tissue if the energy deposited in the counter cavity is the same as that in the tissue volume. Nevertheless, a TEPC measures only the ionisations created in the gas, which are later converted into imparted energy. Therefore, the equivalence of the simulated diameter (Dρ) in two gases should be based on the equality of the mean number of ions pairs in the gas rather than on the imparted energy. Propane-based tissue-equivalent gas is the most commonly used gas mixture at present, but it has the drawback that its composition may change with time. From this point of view, the use of pure propane offers practical advantages: higher gas gain and longer stability. In this work, microdosimetric measurements performed with pure propane, at site sizes 0.05 mg cm(-2) ≤ Dρ ≤ 0.3 mg cm(-2), demonstrate that the response of a propane-filled detector in gamma and in neutron fields is almost the same if an appropriate gas density is used.

Nanodosimetric descriptors of the radiation quality of carbon ions.

In view of the emerging interest of carbon ions in radiotherapy and of the strong correlation between the track structure and the radiobiological effectiveness of ionising radiations, the track-structure properties of (12)C-ions were studied at particle energies close to the Bragg peak. To perform the investigations, ionisation-cluster-size distributions for nanometre-sized target volumes were measured with the track-nanodosimeter installed at the TANDEM-ALPI accelerator complex at LNL, and calculated using a dedicated Monte Carlo simulation code. The resulting cluster-size distributions are used to derive particular descriptors of particle track structure. Here, the main emphasis is laid on the mean ionisation-cluster size M1 and the cumulative probability Fk of measuring cluster sizes ν ≥ k. From the radiobiological point of view, Fk is of particular interest because an increasing k corresponds to an increase of damages of higher complexity. In addition, Fk saturates with increasing radiation quality like radiobiological cross sections as a function of linear energy transfer. Results will be presented and discussed for (12)C-ions at 96 and 240 MeV.

Nanodosimetric track structure in homogeneous extended beams.

Physical aspects of particle track structure are important in determining the induction of clustered damage in relevant subcellular structures like the DNA and higher-order genomic structures. The direct measurement of track-structure properties of ionising radiation is feasible today by counting the number of ionisations produced inside a small gas volume. In particular, the so-called track-nanodosimeter, installed at the TANDEM-ALPI accelerator complex of LNL, measures ionisation cluster-size distributions in a simulated subcellular structure of dimensions 20 nm, corresponding approximately to the diameter of the chromatin fibre. The target volume is irradiated by pencil beams of primary particles passing at specified impact parameter. To directly relate these measured track-structure data to radiobiological measurements performed in broad homogeneous particle beams, these data can be integrated over the impact parameter. This procedure was successfully applied to 240 MeV carbon ions and compared with Monte Carlo simulations for extended fields.

EuTEPC: measurements in gamma and neutron fields.

The EuTEPC (European TEPC) is a novel spherical tissue-equivalent gas-proportional single-wire counter that has been designed and constructed at the National Laboratories of Legnaro of Italian Nuclear Physics Institute in collaboration with the University of Padova, the DLR (German Aerospace Centre) and Austrian Institute of Technology. Its peculiarity is the spherical A-150 cathode wall which is sub-divided in nine sectors. Each sector is properly and differently biased, in order to obtain a uniform electric field along the anode wire, for reaching a good isotropic response and energy resolution. The counter components can be easily replaced and reassembled including the anode wire. The counter could be used as a monitor area inside the International Space Station. This paper describes first microdosimetric measurements in (60)Co, (137)Cs and (241)Am-Be(α,n) gamma and neutron fields performed with the EuTEPC filled with pure propane gas. Measurements have been performed simulating sites sizes, ranging from 0.05 up to 0.25 mg cm(-2) in pure propane, which correspond from 0.7 up to 3.3 µm equivalent site sizes in propane-TE gas. Comparisons with some literature spectra are presented.

Lineal energy calibration of a spherical TEPC.

Tissue-equivalent proportional counters (TEPCs) do not always allow built-in calibration alpha-particle sources, and the lineal energy calibration of these counters must be performed with an external radiation able to penetrate the detector walls. The irradiation field can be used for calibration if a particular marker point of known lineal energy is identified in the measured spectrum. This point is often identified with the proton edge, which corresponds to the maximum energy deposited by protons in the given volume. If the proton edge cannot be identified precisely in the measured spectrum, a gamma source can be used instead, identifying the maximum lineal energy due to electrons (e-edge). The technique was already described and applied for cylindrical TEPCs, allowing a calibration with an overall uncertainty smaller than 5 % (Conte et al. Lineal energy calibration of mini tissue equivalent gas-proportional counters (TEPC). AIP Conf. Proc. 1530, 171-178 (2013)). In the present work, this study was repeated for spherical detectors. First a marker point was identified in the microdosimetric spectrum of a (137)Cs gamma source, then a precise value of lineal energy was assigned to it. Gas pressures were varied to simulate diameters from 0.5 and 3 µm at density 1 g cm(-3). A simple power equation is given for allowing calibration of TEPCs filled with C3H8-TE gas at different pressures, using an external (137)Cs gamma source.

Influence of the physical data to calibrate TEPCs.

Tissue-equivalent proportional counters (TEPCs) measure distributions of ionisations, produced in the gas cavity by the radiation field which are afterwards converted into distributions of energy imparted by applying a calibration factor. To calibrate the pulse-height spectra, first, a marker point must be identified in the measured spectrum. Then, an accurate value of lineal energy must be assigned to this marker. A common marker that is often used for calibration is the so-called proton-edge (p-edge). It is a distinctive feature of a proton or neutron spectrum which corresponds to the maximum amount of energy that a proton can deposit in the active volume of the detector. A precise method to identify the marker point was applied to identify the p-edge with an uncertainty below 1 %. To evaluate the final uncertainty of the calibration, the uncertainty of the energy value assigned to the p-edge must also be considered. This value can be evaluated using different energy-range tables. This study investigates how the choice of different input databases for calibration purposes influences the calibration. The effect of three different frequently used sets of input data was analysed for pure propane gas and for propane-TE gas mixture.

Future development of biologically relevant dosimetry.

Proton and ion beams are radiotherapy modalities of increasing importance and interest. Because of the different biological dose response of these radiations as compared with high-energy photon beams, the current approach of treatment prescription is based on the product of the absorbed dose to water and a biological weighting factor, but this is found to be insufficient for providing a generic method to quantify the biological outcome of radiation. It is therefore suggested to define new dosimetric quantities that allow a transparent separation of the physical processes from the biological ones. Given the complexity of the initiation and occurrence of biological processes on various time and length scales, and given that neither microdosimetry nor nanodosimetry on their own can fully describe the biological effects as a function of the distribution of energy deposition or ionization, a multiscale approach is needed to lay the foundation for the aforementioned new physical quantities relating track structure to relative biological effectiveness in proton and ion beam therapy. This article reviews the state-of-the-art microdosimetry, nanodosimetry, track structure simulations, quantification of reactive species, reference radiobiological data, cross-section data and multiscale models of biological response in the context of realizing the new quantities. It also introduces the European metrology project, Biologically Weighted Quantities in Radiotherapy, which aims to investigate the feasibility of establishing a multiscale model as the basis of the new quantities. A tentative generic expression of how the weighting of physical quantities at different length scales could be carried out is presented.

Microdosimetric measurements in the thermal neutron irradiation facility of LENA reactor.

A twin TEPC with electric-field guard tubes has been constructed to be used to characterize the BNCT field of the irradiation facility of LENA reactor. One of the two mini TEPC was doped with 50ppm of (10)B in order to simulate the BNC events occurring in BNCT. By properly processing the two microdosimetric spectra, the gamma, neutron and BNC spectral components can be derived with good precision (~6%). However, direct measurements of (10)B in some doped plastic samples, which were used for constructing the cathode walls, point out the scarce accuracy of the nominal (10)B concentration value. The influence of the Boral(®) door, which closes the irradiation channel, has been measured. The gamma dose increases significantly (+51%) when the Boral(®) door is closed. The crypt-cell-regeneration weighting function has been used to measure the quality, namely the RBEµ value, of the radiation field in different conditions. The measured RBEµ values are only partially consistent with the RBE values of other BNCT facilities.

TEPC gas gain measurements in propane.

Knowledge of the gas gain is important to optimise the design and the operating characteristics of tissue-equivalent proportional counters (TEPCs), especially for simulated sites smaller than 1 µm. TEPC area monitors of the order of centimetres must operate at very low gas pressure to simulate micrometric volumes, consequently the Townsend theory cannot be applied: effects related to the presence of an electric-field gradient become important and must be considered. A detailed description of the electron avalanche formation is complex, but in most practical cases an analytical formula can be used. The so-called gradient-field model includes three characteristic constants of the counting gas, which were already experimentally determined for propane-tissue equivalent (TE) and dimethyl ether (DME) gases. The aim of this work is to measure the gas-dependent parameters for propane gas. Preliminary results obtained with a spherical TEPC are presented.

Track structure of carbon ions: measurements and simulations.

The likelihood of radiation to produce clustered damages in irradiated biological tissue and the reparability of such damages are closely related to the stochastics of localised ionising interactions within small volumes of nanometre sizes, determined by the particle track structure. Track structure investigations in nanometre-sized volumes have been subject of research for several decades, mainly by means of Monte Carlo simulations. Today, the 'track-nanodosimeter', installed at the TANDEM-ALPI accelerator complex of LNL, is a measuring device able to count the electrons produced in a 20-nm equivalent sensitive site (De Nardo et al. A detector for track-nanodosimetry. Nucl. Instrum. Methods. Phys. Res. A 484: , 312-326 (2002)). It allows studying track structure properties both in the near neighbourhood of a primary particle trajectory and separately in the penumbra region. An extended study for different ionising particles of medical interest has been recently performed with the track-nanodosimeter (Conte et al. Track structure of light ions: experiments and simulations. New J. Phys. 14: , 093010, (2012)). Here, new experimental data and results of Monte Carlo simulations for 240- and 96-MeV (12)C-ions are presented and discussed.

Monte Carlo tools to supplement experimental microdosimetric spectra.

Tissue-equivalent proportional counters (TEPCs) are widely used in experimental microdosimetry for characterising the radiation quality in radiation protection and radiation therapy environments. Generally, TEPCs are filled with tissue-equivalent gas mixtures, at low gas pressure, to simulate tissue site sizes similar to the cell nucleus (1 or 2 µm). The TEPC response using Monte Carlo (MC) codes can be applied to supplement experimental measurements. Most of general-purpose MC codes currently available recourse to the condensed-history approach to model the electron transport and do not transport low-energy electrons (<1 keV), which can lead to systematic errors, especially in thin layers and in gas-condensed medium interfaces. In this work, a comparison between experimental microdosimetric spectra of (60)Co and (137)Cs radiation at different simulated sizes (from 1.0 to 3.0 µm) in pure propane versus simulated spectra obtained with two general-purpose codes FLUKA and PENELOPE, which include a detailed simulation of electron-photon transport in arbitrary materials, including gases, is presented.

Trauma- and stressor related disorders in the tuareg refugees of a cAMP in burkina faso.

BACKGROUND: Post-traumatic stress disorder (PTSD) is reported to be common among refugees. We set out to explore risk of Trauma- and Stress-or-Related Disorders and the associated burden of psychological distress in a refugee camp of Malian Refugees in Burkina Faso. METHODS: One out of five persons living in the camp was selected randomly and interviewed using the French version of the Short Screening Scale for PTSD and the validated K6 scale to measure psychiatric morbidity. RESULTS: Around 60% of the interviewed sample (N=408) met the criteria for Trauma- and Stress-or-Related Disorders and also reported severe mental distress on K6 scores. Women aged 40 and over were found to be at higher risk of Trauma- and Stress-or-Related Disorders whereas young people (39 or younger) scored higher on K6 ratings. Around 83% of the surveyed subjects had a family member killed in the war, 91% a relative in the war, more than 80% had a family member suffering from physical injuries, and 90% reported problems with food and housing. The frequency of these life events was not surprisingly higher in persons with Trauma- and Stress-or-Related Disorders, with the death of a family member and severe problems with food being specifically related to them. CONCLUSION: These results point to important psychological suffering in a population that is often ignored by the media and international political authorities. Immediate steps are required to provide urgent legal and humanitarian protection to those who are forced to flee their homes and cross international borders because of disasters.

SPM nanolithography of hydroxy-silicates.

Bio-nanopatterning of surfaces is becoming a crucial technique with applications ranging from molecular and cell biology to medicine. Scanning probe microscopy (SPM) is one of the most useful tools for nanopatterning of flat surfaces. However, these patterns are usually built on homogeneous surfaces and require chemical functionalization to ensure specific affinity. Layered magnesium-aluminum hydroxide-silicates have already shown unique self-assembly properties on DNA molecules, due to their peculiar crystal chemistry based on alternating positive and negative crystal layers. However, patterns on these surfaces tend to be randomly organized. Here we show etching and oxidation at the nanometer scale of magnesium-aluminum hydroxide-silicates using the same SPM probe for the creation of organized nanopatterns. In particular, it is possible to produce three-dimensional structures in a reproducible way, with a depth resolution of 0.4 nm, lateral resolution of tens of nm, and a speed of about 10 µm s(-1). We report, as an example, the construction of an atomically flat charged pattern, designed to guide DNA deposition along predetermined directions without the need of any chemical functionalization of the surface.

Note: radiofrequency scanning probe microscopy using vertically oriented cantilevers.

We present a simple method, based on the modification of a widespread atomic force microscope, that allows the simultaneous acquisition of the sample topography and RF spectra at the nanoscale minimizing the parasitic capacitance of the cantilever. We used a microcantilever set with its long axis perpendicular to the specimen surface and connected to a vector network analyzer (RF range 100 kHz-8.5 GHz) to measure RF impedance signal variations at the cantilever apex-sample interface. The RF impedance signal was found highly sensitive to very short probe-to-sample distances (<50 nm) and to material properties at the interface.