Activationless Electron Transfer of Redox-DNA in Electrochemical Nanogaps.

Our recent discovery of decreased reorganization energy in electrode-tethered redox-DNA systems prompts inquiries into the origin of this phenomenon and suggests its potential use to lower the activation energy of electrochemical reactions. Here, we show that the confinement of the DNA chain in a nanogap amplifies this effect to an extent to which it nearly abolishes the intrinsic activation energy of electron transfer. Employing electrochemical atomic force microscopy (AFM-SECM), we create sub-10 nm nanogaps between a planar electrode surface bearing end-anchored ferrocenylated DNA chains and an incoming microelectrode tip. The redox cycling of the DNA's ferrocenyl (Fc) moiety between the surface and the tip generates a measurable current at the scale of ∼10 molecules. Our experimental findings are rigorously interpreted through theoretical modeling and original molecular dynamics simulations (Q-Biol code). Several intriguing findings emerge from our investigation: (i) The electron transport resulting from DNA dynamics is many times faster than predicted by simple diffusion considerations. (ii) The current in the nanogap is solely governed by the electron transfer rate at the electrodes. (iii) This rate rapidly saturates as overpotentials applied to the nanogap electrodes increase, implying near-complete suppression of the reorganization energy for the oxidation/reduction of the Fc heads within confined DNA. Furthermore, evidence is presented that this may constitute a general, previously unforeseen, behavior of redox polymer chains in electrochemical nanogaps.

Ballistic Brownian Motion of Nanoconfined DNA.

Theoretical treatments of polymer dynamics in liquid generally start with the basic assumption that motion at the smallest scale is heavily overdamped; therefore, inertia can be neglected. We report on the Brownian motion of tethered DNA under nanoconfinement, which was analyzed by molecular dynamics simulation and nanoelectrochemistry-based single-electron shuttle experiments. Our results show a transition into the ballistic Brownian motion regime for short DNA in sub-5 nm gaps, with quality coefficients as high as 2 for double-stranded DNA, an effect mainly attributed to a drastic increase in stiffness. The possibility for DNA to enter the underdamped regime could have profound implications on our understanding of the energetics of biomolecular engines such as the replication machinery, which operates in nanocavities that are a few nanometers wide.

Single-Cell Electrochemical Aptasensor Array.

Despite several demonstrations of electrochemical devices with limits of detection (LOD) of 1 cell/mL, the implementation of single-cell bioelectrochemical sensor arrays has remained elusive due to the challenges of scaling up. In this study, we show that the recently introduced nanopillar array technology combined with redox-labeled aptamers targeting epithelial cell adhesion molecule (EpCAM) is perfectly suited for such implementation. Combining nanopillar arrays with microwells determined for single cell trapping directly on the sensor surface, single target cells are successfully detected and analyzed. This first implementation of a single-cell electrochemical aptasensor array, based on Brownian-fluctuating redox species, opens new opportunities for large-scale implementation and statistical analysis of early cancer diagnosis and cancer therapy in clinical settings.

Electrochemical Shot Noise of a Redox Monolayer.

Redox monolayers are the base for a wide variety of devices including high-frequency molecular diodes or biomolecular sensors. We introduce a formalism to describe the electrochemical shot noise of such a monolayer, confirmed experimentally at room temperature in liquid. The proposed method, carried out at equilibrium, avoids parasitic capacitance, increases the sensitivity, and allows us to obtain quantitative information such as the electronic coupling (or standard electron transfer rates), its dispersion, and the number of molecules. Unlike in solid-state physics, the homogeneity in energy levels and transfer rates in the monolayer yields a Lorentzian spectrum. This first step for shot noise studies in molecular electrochemical systems opens perspectives for quantum transport studies in a liquid environment at room temperature as well as highly sensitive measurements for bioelectrochemical sensors.

Electrochemical response of surface-attached redox DNA governed by low activation energy electron transfer kinetics.

The mechanism responsible for electron transport within layers of redox DNA anchored to electrodes has been extensively studied over the last twenty years, but remains controversial. Herein, we thoroughly study the electrochemical behavior of a series of short, model, ferrocene (Fc) end-labeled dT oligonucleotides, terminally attached to gold electrodes, using high scan rate cyclic voltammetry complemented by molecular dynamics simulations. We evidence that the electrochemical response of both single-stranded and duplexed oligonucleotides is controlled by the electron transfer kinetics at the electrode, obeying Marcus theory, but with reorganization energies considerably lowered by the attachment of the ferrocene to the electrode via the DNA chain. This so far unreported effect, that we attribute to a slower relaxation of water around Fc, uniquely shapes the electrochemical response of Fc-DNA strands and, being markedly dissimilar for single-stranded and duplexed DNA, contributes to the signaling mechanism of E-DNA sensors.

Nanoscale electrochemical charge transfer kinetics investigated by electrochemical scanning microwave microscopy.

We show how microwave microscopy can be used to probe local charge transfer reactions with unprecedented sensitivity, visualizing surface reactions with only a few hundred molecules involved. While microwaves are too fast under classical conditions to interact and sense electrochemical processes, this is different at the nanoscale, where our heterodyne microwave sensing method allows for highly sensitive local cyclic voltammetry (LCV) and local electrochemical impedance spectroscopy (LEIS). LCV and LEIS allow for precise measurement of the localized charge transfer kinetics, as illustrated in this study for a ferrocene self-assembled monolayer immersed in an electrolyte. The theoretical analysis presented here enables a consistent mapping of the faradaic kinetics and the parasitic contributions (nonfaradaic) to be spectrally resolved and subtracted. In particular, this methodology reveals an undistorted assessment of accessible redox site density of states associated with faradaic capacitance, fractional surface coverage and electron transfer kinetics at the nanoscale. The developed methodology opens a new perspective on comprehending electrochemical reactivity at the nanoscale.

Prevalence and Main Clinical Characteristics of Fully Vaccinated Patients Admitted to Hospital for Delta Variant COVID-19.

Objectives: The Delta variant of the novel beta coronavirus responsible for the current coronavirus pandemic (COVID-19) spread across Europe during the summer of 2021. Little is known of vaccine efficacy on this variant. Our aim was to study the prevalence and clinical characteristics of fully vaccinated subjects admitted to hospital for Delta variant COVID-19. Methods: We identified patients admitted to Cannes hospital for Delta-variant-related Covid-19 infection from July to September 2021. Their main demographic parameters, inflammatory markers, and clinical characteristics were recorded. Differences between fully vaccinated subjects and unvaccinated or incompletely vaccinated individuals were analyzed. Results: We included 126 patients (57% male, mean age 64 years, mean delay since symptoms onset 7.8 days). Among admitted patients, 94 (75%) were not vaccinated, 11 (8%) incompletely so and 21 (17%) were fully vaccinated. Fully vaccinated patients were older (77 vs. 61 vs. 62 years, p = 0.003), with fewer days since symptoms onset (5.9 vs. 8.0 vs. 9.3 days, p = 0.035) than unvaccinated or incompletely vaccinated patients, respectively. Severe pneumonia was less frequent among completely vaccinated subjects (67 vs. 84 vs. 100%, p = 0.038), while rates of transfer to the ICU, mechanical ventilation or death did not differ. Thirteen fully vaccinated patients underwent a thoracic CT scan, revealing involvement of lung parenchyma in four of them. Discussion: Prevalence of hospitalization for Delta-variant COVID-19 in fully vaccinated subjects was low and, despite their age and comorbid conditions, these patients had a high rate of favorable outcome.

Attoampere Nanoelectrochemistry.

Electrochemical microscopy techniques have extended the understanding of surface chemistry to the micrometer and even sub-micrometer level. However, fundamental questions related to charge transport at the solid-electrolyte interface, such as catalytic reactions or operation of individual ion channels, require improved spatial resolutions down to the nanoscale. A prerequisite for single-molecule electrochemical sensitivity is the reliable detection of a few electrons per second, that is, currents in the atto-Ampere (10-18 A) range, 1000 times below today's electrochemical microscopes. This work reports local cyclic voltammetry (CV) measurements at the solid-liquid interface on ferrocene self-assembled monolayer (SAM) with sub-atto-Ampere sensitivity and simultaneous spatial resolution < 80 nm. Such sensitivity is obtained through measurements of the charging of the local faradaic interface capacitance at GHz frequencies. Nanometer-scale details of different molecular organizations with a 19% packing density difference are resolved, with an extremely small dispersion of the molecular electrical properties. This is predicted previously based on weak electrostatic interactions between neighboring redox molecules in a SAM configuration. These results open new perspectives for nano-electrochemistry like the study of quantum mechanical resonance in complex molecules and a wide range of applications from electrochemical catalysis to biophysics.

Multi-user volumetric 360° display based on retro-reflective transparent surfaces.

We present in details the development of a 360° volumetric display based on the use of a transparent projection surface. The optical scheme derives from the Pepper's ghost configuration, known as holographic display. Our optical system requires high angular diffusion efficiency and an innovative transparent retro-reflective surface has been developed for that purpose. This surface is made of sparse cube corner distribution and we give some elements of its design and characterization. We describe also the optical design of the 360° display and gave the feedback of its presentation to the public during a symposium.

Noise suppression beyond the thermal limit with nanotransistor biosensors.

Transistor biosensors are mass-fabrication-compatible devices of interest for point of care diagnosis as well as molecular interaction studies. While the actual transistor gates in processors reach the sub-10 nm range for optimum integration and power consumption, studies on design rules for the signal-to-noise ratio (S/N) optimization in transistor-based biosensors have been so far restricted to 1 µm2 device gate area, a range where the discrete nature of the defects can be neglected. In this study, which combines experiments and theoretical analysis at both numerical and analytical levels, we extend such investigation to the nanometer range and highlight the effect of doping type as well as the noise suppression opportunities offered at this scale. In particular, we show that, when a single trap is active near the conductive channel, the noise can be suppressed even beyond the thermal limit by monitoring the trap occupancy probability in an approach analog to the stochastic resonance effect used in biological systems.

Insulin resistance causes inflammation in adipose tissue.

Obesity is a major risk factor for insulin resistance and type 2 diabetes. In adipose tissue, obesity-mediated insulin resistance correlates with the accumulation of proinflammatory macrophages and inflammation. However, the causal relationship of these events is unclear. Here, we report that obesity-induced insulin resistance in mice precedes macrophage accumulation and inflammation in adipose tissue. Using a mouse model that combines genetically induced, adipose-specific insulin resistance (mTORC2-knockout) and diet-induced obesity, we found that insulin resistance causes local accumulation of proinflammatory macrophages. Mechanistically, insulin resistance in adipocytes results in production of the chemokine monocyte chemoattractant protein 1 (MCP1), which recruits monocytes and activates proinflammatory macrophages. Finally, insulin resistance (high homeostatic model assessment of insulin resistance [HOMA-IR]) correlated with reduced insulin/mTORC2 signaling and elevated MCP1 production in visceral adipose tissue from obese human subjects. Our findings suggest that insulin resistance in adipose tissue leads to inflammation rather than vice versa.

Electrochemical Imaging of Dense Molecular Nanoarrays.

The aim of the present work is to explore the combination of atomic force electrochemical microscopy, operated in molecule touching mode (Mt/AFM-SECM), and of dense nanodot arrays, for designing an electrochemically addressable molecular nanoarray platform. A high density nanoarray of single grained gold nanodots (∼15 nm-diameter nanoparticles, 100 nm pitch) is decorated by a model molecular system, consisting of ferrocene (Fc) labeled polyethylene glycol (PEG) disulfide chains. We show that the high resolution of Mt/AFM-SECM enables the electrochemical interrogation of several hundreds of individual nanodots in a single image acquisition. As a result, the statistical dispersion of the nanodot molecular occupancy by Fc-PEG chains can be reliably quantified, evidencing that as little as a few tens of copies of redox-labeled macromolecules immobilized on individual nanodots can be detected. The electrochemical reactivity of individual nanodots can also be reliably sampled over a large population of nanodots. We evidence that the heterogeneous rate constant characterizing the electron transfer between the nanodots and the Fc heads displays some quantifiable variability but that the electron transfer remains in any case in the quasi-reversible regime. Overall, we demonstrate that Mt/AFM-SECM enables high throughput reading of dense nanoarrays, with a sensitivity and a read-out speed considerably higher than previously reported for scanning electrochemical microscopy (SECM) imaging of molecular microarrays.

High speed e-beam lithography for gold nanoarray fabrication and use in nanotechnology.

E-beam lithography has been used for reliable and versatile fabrication of sub-15 nm single-crystal gold nanoarrays and led to convincing applications in nanotechnology. However, so far this technique was either too slow for centimeter to wafer-scale writing or fast enough with the so-called dot on the fly (DOTF) technique but not optimized for sub-15 nm dots dimension. This prevents use of this technology for some applications and characterization techniques. Here, we show that the DOTF technique can be used without degradation in dots dimension. In addition, we propose two other techniques. The first one is an advanced conventional technique that goes five times faster than the conventional one. The second one relies on sequences defined before writing which enable versatility in e-beam patterns compared to the DOTF technique with same writing speed. By comparing the four different techniques, we evidence the limiting parameters for the writing speed. Wafer-scale fabrication of such arrays with 50 nm pitch allowed XPS analysis of a ferrocenylalkyl thiol self-assembled monolayer coated gold nanoarray.

Quantitative impedance characterization of sub-10 nm scale capacitors and tunnel junctions with an interferometric scanning microwave microscope.

We present a method to characterize sub-10 nm capacitors and tunnel junctions by interferometric scanning microwave microscopy (iSMM) at 7.8 GHz. At such device scaling, the small water meniscus surrounding the iSMM tip should be reduced by proper tip tuning. Quantitative impedance characterization of attofarad range capacitors is achieved using an 'on-chip' calibration kit facing thousands of nanodevices. Nanoscale capacitors and tunnel barriers were detected through variations in the amplitude and phase of the reflected microwave signal, respectively. This study promises quantitative impedance characterization of a wide range of emerging functional nanoscale devices.

Structural, magnetic and optical properties of an Fe(III) dimer bridged by the meridional planar divergent N,N'-bis(salicyl)hydrazide and its photo- and electro-chemistry in solution.

{Fe(III)Cl(DMF)(2)}(2)(L) where L is N,N'-bis(salicyl)hydrazide has been synthesized as red crystals and characterized using single-crystal diffraction, infrared and UV-vis spectroscopies, and its magnetic properties studied. The dimeric unit in the structure is formed through the two meridional sets of divergent O, N, O coordinating atoms of the hexacoordinated and quadruply charged ligand. With the presence of the inversion symmetry the Fe atoms are strictly planar with the ligand. The magnetic exchange interaction is found to be antiferromagnetic with a J = -5.98(3) cm(-1) through the rare Fe-N-N-Fe pathway. Irradiation of the FeCl(3)/H(4)L red DMF solution in the visible region of the spectrum resulted in its complete discoloration and from which the unknown colorless salt [Fe(II)(DMF)(6)][Fe(II)Cl(4)] and the neutral ligand have been identified by single crystal diffraction. The UV-visible spectra of FeCl(3), H(4)L and their mixture in DMF solution indicate that the iron complex is the absorbing species and the presence of the free ligand in the irradiated solution suggests that the ligand is potentially acting as a catalyst to the photoreduction of Fe(III) to Fe(II), while electrochemistry points to a mixed-valent (Fe(II)-Fe(III)) intermediate in the process.

Temporal factors in violence related injuries--An 11 year trend analysis of violence-related injuries from a Swiss Emergency Department.

BACKGROUND: Injury from interpersonal violence is a major social and medical problem in the industrialized world. Little is known about the trends in prevalence and injury pattern or about the demographic characteristics of the patients involved. METHODS: In this retrospective analysis, we screened the database of the Emergency Department of a large university hospital for all patients who were admitted for injuries due to interpersonal violence over an 11 year period. For all patients identified, we gathered data on age, country of origin, quality of injury, and hospitalization or outpatient management. A trend analysis was performed using Kendall's tau-b correlation coefficients for regression analysis. RESULTS: The overall number of patients admitted to our Emergency Department remained stable over the study period. Non-Swiss nationals were overrepresented in comparison to the demographics of the region where the study was conducted. There was a trend toward a more severe pattern of injury, such as an increase in the number of severe head injuries. CONCLUSIONS: Although the overall number of patients remained stable over the study period, there was an alarming trend toward a more severe pattern of injury, expressed by an increase in severe head traumas.

Conductance statistics from a large array of sub-10 nm molecular junctions.

Devices made of few molecules constitute the miniaturization limit that both inorganic and organic-based electronics aspire to reach. However, integration of millions of molecular junctions with less than 100 molecules each has been a long technological challenge requiring well controlled nanometric electrodes. Here we report molecular junctions fabricated on a large array of sub-10 nm single crystal Au nanodots electrodes, a new approach that allows us to measure the conductance of up to a million of junctions in a single conducting atomic force microscope (C-AFM) image. We observe two peaks of conductance for alkylthiol molecules. Tunneling decay constant (ß) for alkanethiols, is in the same range as previous studies. Energy position of molecular orbitals, obtained by transient voltage spectroscopy, varies from peak to peak, in correlation with conductance values.

Large array of sub-10-nm single-grain Au nanodots for use in nanotechnology.

A uniform array of single-grain Au nanodots, as small as 5-8 nm, can be formed on silicon using e-beam lithography. The as-fabricated nanodots are amorphous, and thermal annealing converts them to pure Au single crystals covered with a thin SiO(2) layer. These findings are based on physical measurements, such as atomic force microscopy (AFM), atomic-resolution scanning transmission electron microscopy, and chemical techniques using energy dispersive X-ray spectroscopy. A self-assembled organic monolayer is grafted on the nanodots and characterized chemically with nanometric lateral resolution. The extended uniform array of nanodots is used as a new test-bed for molecular electronic devices.

Referral practice among Swiss and non-Swiss walk-in patients in an urban surgical emergency department.

AIM: To assess the relationship between nationality, gender and age and use of health services among patients visiting an urban university hospital emergency department (ED). INTRODUCTION: ED crowding is an increasingly significant national and international problem. Overcrowding has many potential detrimental effects, including frustration for patients and ED personnel and greater risk of poor outcomes. This is partially caused by the growing numbers of visits by so called "walk-in patients" with minor problems. METHODS: From May 1, 2007 to May 31, 2008, sociodemographic information was collected prospectively from 6955 male and 4303 female patients at Inselspital, University Hospital Bern, Switzerland, who had requested our emergency services for non-urgent problems. A stratified sample of 1173 patients was taken for further analysis of referral by a general practitioner (GP) and having a GP at all. RESULTS: In all, 26% of visits were by foreign nationals. Only 57% of these were registered with a GP, compared to 83% of Swiss nationals (p <0.0001). Swiss patients referred themselves to us in 87%, compared to 97% self-referrals among foreigners (p <0.0001). Between 7:00 pm and 7:00 am, our ED was significantly more often visited by non-Swiss patients (p <0.0001). Foreign patients were significantly younger than Swiss patients (median age 45, range 1-98 years versus age 35, range 2-89 years, p <0.0001). CONCLUSION: Nationality is associated with greater use of ED services for non-urgent problems. Several explanations are conceivable for this. Clinical and policy efforts must address barriers to GP care, since in the long term the GP provides better and more cost-effective care for patients with minor complaints.