by Keyword: polarization

Eills, J, Azagra, M, Gómez-Cabeza, D, Tayler, MCD, Marco-Rius, I, (2024). Polarization losses from the nonadiabatic passage of hyperpolarized solutions through metallic components Journal Of Magnetic Resonance Open 18, 100144

From complex -mixture analysis to in vivo molecular imaging, applications of liquid -state nuclear spin hyperpolarization have expanded widely over recent years. In most cases, hyperpolarized solutions are generated and transported from the polarization instrument to the measurement device. The sample hyperpolarization usually survives this transport, since the changes in magnetic fields that are external to the sample are typically adiabatic (slow) with respect to the internal nuclear spin dynamics. The passage of polarized samples through weakly magnetic components such as stainless steel syringe needles and ferrules is not always adiabatic, can lead to near -complete destruction of the magnetization. To avoid this effect becoming "folklore"in field of hyperpolarized NMR, we present a systematic investigation to highlight the problem and investigate possible solutions. Experiments were carried out on: (i) dissolution-DNP-polarized [1-13C]pyruvate with detection at 1.4 T, and (ii) 1.5 -T -polarized H2O with NMR detection at 2.5 mu T. We show that the degree adiabaticity of solutions passing through metal parts is intrinsically unpredictable, likely depending on factors such as solution flow rate, degree of remanent ferromagnetism in the metal, and nuclear spin However, the magnetization destruction effects can be suppressed by application of an external field order of 0.1-10 mT.

JTD Keywords: Benchtop nmr, Hyperpolarization, Low-field mri, Non-adiabatic, Para-hydrogen, Spin relaxation

Barskiy, DA, Blanchard, JW, Budker, D, Stern, Q, Eills, J, Elliott, SJ, Picazo-Frutos, R, Garcon, A, Jannin, S, Koptyug, IV, (2023). Possible Applications of Dissolution Dynamic Nuclear Polarization in Conjunction with Zero- to Ultralow-Field Nuclear Magnetic Resonance Applied Magnetic Resonance 54, 1221-1240

The combination of a powerful and broadly applicable nuclear hyperpolarization technique with emerging (near-)zero-field modalities offers novel opportunities in a broad range of nuclear magnetic resonance spectroscopy and imaging applications, including biomedical diagnostics, monitoring catalytic reactions within metal reactors and many others. These are discussed along with a roadmap for future developments.

JTD Keywords: Couplings, Hyperpolarization, Nmr, Parahydrogen, Phase, Radicals, Time

Yeste, J, Azagra, M, Ortega, MA, Portela, A, Matajsz, G, Herrero-Gómez, A, Kim, Y, Sriram, R, Kurhanewicz, J, Vigneron, DB, Marco-Rius, I, (2023). Parallel detection of chemical reactions in a microfluidic platform using hyperpolarized nuclear magnetic resonance Lab On A Chip 23, 4950-4958

The sensitivity of NMR may be enhanced by more than four orders of magnitude via dissolution dynamic nuclear polarization (dDNP), potentially allowing real-time, in situ analysis of chemical reactions. However, there has been no widespread use of the technique for this application and the major limitation has been the low experimental throughput caused by the time-consuming polarization build-up process at cryogenic temperatures and fast decay of the hyper-intense signal post dissolution. To overcome this limitation, we have developed a microfluidic device compatible with dDNP-MR spectroscopic imaging methods for detection of reactants and products in chemical reactions in which up to 8 reactions can be measured simultaneously using a single dDNP sample. Multiple MR spectroscopic data sets can be generated under the same exact conditions of hyperpolarized solute polarization, concentration, pH, and temperature. A proof-of-concept for the technology is demonstrated by identifying the reactants in the decarboxylation of pyruvate via hydrogen peroxide (e.g. 2-hydroperoxy-2-hydroxypropanoate, peroxymonocarbonate and CO2). dDNP-MR allows tracing of fast chemical reactions that would be barely detectable at thermal equilibrium by MR. We envisage that dDNP-MR spectroscopic imaging combined with microfluidics will provide a new high-throughput method for dDNP enhanced MR analysis of multiple components in chemical reactions and for non-destructive in situ metabolic analysis of hyperpolarized substrates in biological samples for laboratory and preclinical research.

JTD Keywords: injections, nmr, pyruvate, Polarization

Eills, J, Picazo-Frutos, R, Burueva, DB, Kovtunova, LM, Azagra, M, Marco-Rius, I, Budker, D, Koptyug, IV, (2023). Combined homogeneous and heterogeneous hydrogenation to yield catalyst-free solutions of parahydrogen-hyperpolarized [1-13C]succinate Chemical Communications 59, 9509-9512

We show that catalyst-free aqueous solutions of hyperpolarized [1-13C]succinate can be produced using parahydrogen-induced polarization (PHIP) and a combination of homogeneous and heterogeneous catalytic hydrogenation reactions. We generate hyperpolarized [1-13C]fumarate via PHIP using para-enriched hydrogen gas with a homogeneous ruthenium catalyst, and subsequently remove the toxic catalyst and reaction side products via a purification procedure. Following this, we perform a second hydrogenation reaction using normal hydrogen gas to convert the fumarate into succinate using a solid Pd/Al2O3 catalyst. This inexpensive polarization protocol has a turnover time of a few minutes, and represents a major advance for in vivo applications of [1-13C]succinate as a hyperpolarized contrast agent.

JTD Keywords: acid, c-13, conversion, fumarate, in-vivo, metabolism, order, Induced polarization

Chuchkova, L, Bodenstedt, S, Picazo-Frutos, R, Eills, J, Tretiak, O, Hu, YA, Barskiy, DA, de Santis, J, Tayler, MCD, Budker, D, Sheberstov, KF, (2023). Magnetometer-Detected Nuclear Magnetic Resonance of Photochemically Hyperpolarized Molecules Journal Of Physical Chemistry Letters 14, 6814-6822

Photochemically induced dynamic nuclear polarization (photo-CIDNP) enables nuclear spin ordering by irradiating samples with light. Polarized spins are conventionally detected via high-field chemical-shift-resolved NMR (above 0.1 T). In this Letter, we demonstrate in situ low-field photo-CIDNP measurements using a magnetically shielded fast-field-cycling NMR setup detecting Larmor precession via atomic magnetometers. For solutions comprising mM concentrations of the photochemically polarized molecules, hyperpolarized 1H magnetization is detected by pulse-acquired NMR spectroscopy. The observed NMR line widths are about 5 times narrower than normally anticipated in high-field NMR and are systematically affected by light irradiation during the acquisition period, reflecting a reduction of the transverse relaxation time constant, T2*, on the order of 10%. Magnetometer-detected photo-CIDNP spectroscopy enables straightforward observation of spin-chemistry processes in the ambient field range from a few nT to tens of mT. Potential applications of this measuring modality are discussed.

JTD Keywords: field-dependence, mechanism, nmr, parahydrogen, photo-cidnp, polarization, quinone, spin-hyperpolarization, Radical-pair

Eills, J, Budker, D, Cavagnero, S, Chekmenev, EY, Elliott, SJ, Jannin, S, Lesage, A, Matysik, J, Meersmann, T, Prisner, T, Reimer, JA, Yang, HM, Koptyug, IV, (2023). Spin Hyperpolarization in Modern Magnetic Resonance Chemical Reviews 123, 1417-1551

Magnetic resonance techniques are successfully utilized in a broad range of scientific disciplines and in various practical applications, with medical magnetic resonance imaging being the most widely known example. Currently, both fundamental and applied magnetic resonance are enjoying a major boost owing to the rapidly developing field of spin hyperpolarization. Hyperpolarization techniques are able to enhance signal intensities in magnetic resonance by several orders of magnitude, and thus to largely overcome its major disadvantage of relatively low sensitivity. This provides new impetus for existing applications of magnetic resonance and opens the gates to exciting new possibilities. In this review, we provide a unified picture of the many methods and techniques that fall under the umbrella term "hyperpolarization" but are currently seldom perceived as integral parts of the same field. Specifically, before delving into the individual techniques, we provide a detailed analysis of the underlying principles of spin hyperpolarization. We attempt to uncover and classify the origins of hyperpolarization, to establish its sources and the specific mechanisms that enable the flow of polarization from a source to the target spins. We then give a more detailed analysis of individual hyperpolarization techniques: the mechanisms by which they work, fundamental and technical requirements, characteristic applications, unresolved issues, and possible future directions. We are seeing a continuous growth of activity in the field of spin hyperpolarization, and we expect the field to flourish as new and improved hyperpolarization techniques are implemented. Some key areas for development are in prolonging polarization lifetimes, making hyperpolarization techniques more generally applicable to chemical/biological systems, reducing the technical and equipment requirements, and creating more efficient excitation and detection schemes. We hope this review will facilitate the sharing of knowledge between subfields within the broad topic of hyperpolarization, to help overcome existing challenges in magnetic resonance and enable novel applications.

JTD Keywords: electron-paramagnetic-resonance, high-resolution nmr, hydrogen-induced polarization, level anti-crossings, long-lived states, parahydrogen-induced polarization, photosynthetic reaction-center, reversible exchange catalysis, solid-state nmr, Dynamic-nuclear-polarization

Mouloudakis, K, Bodenstedt, S, Azagra, M, Mitchell, MW, Marco-Rius, I, Tayler, MCD, (2023). Real-Time Polarimetry of Hyperpolarized 13C Nuclear Spins Using an Atomic Magnetometer Journal Of Physical Chemistry Letters , 1192-1197

We introduce a method for nondestructive quantification of nuclear spin polarization, of relevance to hyperpolarized spin tracers widely used in magnetic resonance from spectroscopy to in vivo imaging. In a bias field of around 30 nT we use a high-sensitivity miniaturized 87Rb-vapor magnetometer to measure the field generated by the sample, as it is driven by a windowed dynamical decoupling pulse sequence that both maximizes the nuclear spin lifetime and modulates the polarization for easy detection. We demonstrate the procedure applied to a 0.08 M hyperpolarized [1-13C]-pyruvate solution produced by dissolution dynamic nuclear polarization, measuring polarization repeatedly during natural decay at Earth's field. Application to real-time and continuous quality monitoring of hyperpolarized substances is discussed.

JTD Keywords: performance, polarization, Atomic magnetometers, Bias field, High sensitivity, Hyperpolarized, In-vivo imaging, Magnetic resonance, Magnetic-resonance, Magnetic-resonance,polarizatio, Magnetic-resonance,polarization,performanc, Magnetometers, Non destructive, Nuclear spins, Nuclear-spin polarization, Performance, Polarization, Rb vapors, Real- time, Spin dynamics, Spin polarization

Lolo, FN, Walani, N, Seemann, E, Zalvidea, D, Pavón, DM, Cojoc, G, Zamai, M, de Lesegno, CV, de Benito, FM, Sánchez-Alvarez, M, Uriarte, JJ, Echarri, A, Jiménez-Carretero, D, Escolano, JC, Sánchez, SA, Caiolfa, VR, Navajas, D, Trepat, X, Guck, J, Lamaze, C, Roca-Cusachs, P, Kessels, MM, Qualmann, B, Arroyo, M, Del Pozo, MA, (2023). Caveolin-1 dolines form a distinct and rapid caveolae-independent mechanoadaptation system Nature Cell Biology 25, 120-133

In response to different types and intensities of mechanical force, cells modulate their physical properties and adapt their plasma membrane (PM). Caveolae are PM nano-invaginations that contribute to mechanoadaptation, buffering tension changes. However, whether core caveolar proteins contribute to PM tension accommodation independently from the caveolar assembly is unknown. Here we provide experimental and computational evidence supporting that caveolin-1 confers deformability and mechanoprotection independently from caveolae, through modulation of PM curvature. Freeze-fracture electron microscopy reveals that caveolin-1 stabilizes non-caveolar invaginations-dolines-capable of responding to low-medium mechanical forces, impacting downstream mechanotransduction and conferring mechanoprotection to cells devoid of caveolae. Upon cavin-1/PTRF binding, doline size is restricted and membrane buffering is limited to relatively high forces, capable of flattening caveolae. Thus, caveolae and dolines constitute two distinct albeit complementary components of a buffering system that allows cells to adapt efficiently to a broad range of mechanical stimuli.© 2022. The Author(s).

JTD Keywords: cavin, cell-migration, cholesterol, extracellular-matrix, nanoscale organization, particle-size, polarization, size distribution, tension, Plasma-membrane

Romero, D, Calvo, M, Le Rolle, V, Behar, N, Mabo, P, Hernandez, A, (2022). Multivariate ensemble classification for the prediction of symptoms in patients with Brugada syndrome Medical & Biological Engineering & Computing 60, 81-94

Identification of asymptomatic patients at higher risk for suffering cardiac events remains controversial and challenging in Brugada syndrome (BS). In this work, we proposed an ECG-based classifier to predict BS-related symptoms, by merging the most predictive electrophysiological features derived from the ventricular depolarization and repolarization periods, along with autonomic-related markers. The initial feature space included local and dynamic ECG markers, assessed during a physical exercise test performed in 110 BS patients (25 symptomatic). Morphological, temporal and spatial properties quantifying the ECG dynamic response to exercise and recovery were considered. Our model was obtained by proposing a two-stage feature selection process that combined a resampled-based regularization approach with a wrapper model assessment for balancing, simplicity and performance. For the classification step, an ensemble was constructed by several logistic regression base classifiers, whose outputs were fused using a performance-based weighted average. The most relevant predictors corresponded to the repolarization interval, followed by two autonomic markers and two other makers of depolarization dynamics. Our classifier allowed for the identification of novel symptom-related markers from autonomic and dynamic ECG responses during exercise testing, suggesting the need for multifactorial risk stratification approaches in order to predict future cardiac events in asymptomatic BS patients.

JTD Keywords: brugada syndrome, depolarization disorders, ensemble classifier, heart-rate recovery, Acute myocardial-ischemia, Autonomics, Brugada syndrome, Brugadum syndrome, Cardiac death, Depolarization, Depolarization disorder, Depolarization disorders, Dynamic ecg, Electrocardiography, Electrophysiology, Ensemble classifier, Ensemble-classifier, Events, Exercise, Forecasting, Heart, Heart-rate, Heart-rate recovery, Prognosis, Qrs, Quantification, Recovery, Repolarization, Sudden cardiac death

Sans, J, Arnau, M, Sanz, V, Turon, P, Alemán, C, (2022). Polarized Hydroxyapatite: New Insights and Future Perspectives Through Systematic Electrical Characterization at the Interface Advanced Materials Interfaces 9, 2101631

Lozano, H, Millan-Solsona, R, Blanco-Cabra, N, Fabregas, R, Torrents, E, Gomila, G, (2021). Electrical properties of outer membrane extensions from Shewanella oneidensis MR-1 Nanoscale 13, 18754-18762

Outer membrane extensions from the metal-reducing bacterium Shewanella oneidensis MR-1 show an insulating behavior in dry air environment as measured by scanning dielectric microscopy.

JTD Keywords: constant, dielectric polarization, microbial nanowires, nanoscale, transport, Air environment, Bacteria, Bacterial cells, Bacterial nanowires, Dry air, Metal-reducing bacteria, Outer membrane, Phase-minerals, Proteins, Shewanella oneidensis mr-1, Solid phasis, Solid-phase, Space division multiple access, Tubulars

Di Muzio, M, Millan-Solsona, R, Dols-Perez, A, Borrell, JH, Fumagalli, L, Gomila, G, (2021). Dielectric properties and lamellarity of single liposomes measured by in-liquid scanning dielectric microscopy Journal Of Nanobiotechnology 19, 167

Liposomes are widely used as drug delivery carriers and as cell model systems. Here, we measure the dielectric properties of individual liposomes adsorbed on a metal electrode by in-liquid scanning dielectric microscopy in force detection mode. From the measurements the lamellarity of the liposomes, the separation between the lamellae and the specific capacitance of the lipid bilayer can be obtained. As application we considered the case of non-extruded DOPC liposomes with radii in the range ~ 100–800 nm. Uni-, bi- and tri-lamellar liposomes have been identified, with the largest population corresponding to bi-lamellar liposomes. The interlamellar separation in the bi-lamellar liposomes is found to be below ~ 10 nm in most instances. The specific capacitance of the DOPC lipid bilayer is found to be ~ 0.75 µF/cm2 in excellent agreement with the value determined on solid supported planar lipid bilayers. The lamellarity of the DOPC liposomes shows the usual correlation with the liposome's size. No correlation is found, instead, with the shape of the adsorbed liposomes. The proposed approach offers a powerful label-free and non-invasive method to determine the lamellarity and dielectric properties of single liposomes. [Figure not available: see fulltext.].

JTD Keywords: constant, force, lamellarity, liposomes, membrane capacitance, model, nanoscale, scanning dielectric microscopy, Lamellarity, Liposomes, Membrane capacitance, Nanoscale, Polarization properties, Scanning dielectric microscopy

Sans, J, Arnau, M, Estrany, F, Turon, P, Aleman, C, (2021). Regulating the Superficial Vacancies and OH− Orientations on Polarized Hydroxyapatite Electrocatalysts Advanced Materials Interfaces 8, 2100163

Smart designs of hydroxyapatite (HAp) materials with customized electrical properties are drawing increasing attention for their wide range of potential applications. Such enhanced electrical properties directly arise from the number and orientation of OH groups in the HAp lattice. Although different polarization treatments have been proposed to enhance the final conductivity by generating vacancies at high temperatures and imposing specific OH orientations through electric voltages, no direct measurement showing the evolution that OH groups undergo has been described yet. In this article, the first direct empirical observation that allows the characterization of both the generation of vacancies and the polarization of OH groups is reported. The mechanisms behind the electrical enhancement are elucidated allowing to distinguish between charge accumulation at the crystal grains, which is due to the formed vacancies, and charge accumulation in the boundaries of particles. In addition, a linear dependence between the number of vacancies and the superficial charge is observed. Therefore, it is demonstrated that the charge accumulation at the micrometric grain boundaries has a great impact on the catalytic properties of the thermally stimulated polarized HAp. These results will be used for further optimization of the catalyst properties. − − − −

JTD Keywords: electrocatalysts, hydroxyl orientation, thermally stimulated polarization, vacancies, Charge delocalization, Electrocatalysts, Hydroxyl orientation, Thermally stimulated polarization, Vacancies

Sans, J, Sanz, V, del Valle, LJ, Puiggali, J, Turon, P, Aleman, C, (2021). Optimization of permanently polarized hydroxyapatite catalyst. Implications for the electrophotosynthesis of amino acids by nitrogen and carbon fixation Journal Of Catalysis 397, 98-107

The enhanced catalytic activity of permanently polarized hydroxyapatite, which is achieved using a thermally stimulated polarization process, largely depends on both the experimental conditions used to prepare crystalline hydroxyapatite from its calcium and phosphate precursors and the polarization process parameters. A mineral similar to brushite, which is an apatitic phase that can evolve to hydroxyapatite, is found at the surface of highly crystalline hydroxyapatite. It appears after chemical precipitation and hydrothermal treatment performed at 150 degrees C for 24 h followed by a sinterization at 1000 degrees C and a polarization treatment by applying a voltage of 500 Vat high temperature. Both the high crystallinity and the presence of brushite-like phase on the electrophotocatalyst affect the nitrogen and carbon fixation under mild reaction conditions (95 degrees C and 6 bar) and the synthesis of glycine and alanine from a simple gas mixture containing N-2, CO2, CH4 and H2O. Thus, the Gly/Ala ratio can be customized by controlling the presence of brushite on the surface of the catalyst, enabling to develop new strategies to regulate the production of amino acids by nitrogen and carbon fixation. (C) 2021 Elsevier Inc. All rights reserved.

JTD Keywords: Amino acids, Brushite, Carbon, Carbon dioxide fixation, Catalyst activity, Catalytic apatites, Chemical precipitation, Crystalline hydroxyapatite, Crystallinity, Decomposition, Enhanced catalytic activity, Experimental conditions, Heterogeneous catalysis, High crystallinity, Hydrothermal synthesis, Hydrothermal treatments, Hydroxyapatite, Lactic-acid, Mild reaction conditions, Molecular nitrogen fixation, Nitrogen, Nitrogen fixation, Phosphate, Polarization, Precipitation (chemical), Process parameters, Thermally stimulated polarization

Santos-Pata, Diogo, Zucca, Riccardo, López-Carral, Héctor, Verschure, P., (2019). Modulating grid cell scale and intrinsic frequencies via slow high-threshold conductances: A simplified model Neural Networks 119, 66-73

Grid cells in the medial entorhinal cortex (MEC) have known spatial periodic firing fields which provide a metric for the representation of self-location and path planning. The hexagonal tessellation pattern of grid cells scales up progressively along the MEC’s layer II dorsal-to-ventral axis. This scaling gradient has been hypothesized to originate either from inter-population synaptic dynamics as postulated by attractor networks, or from projected theta frequency waves to different axis levels, as in oscillatory models. Alternatively, cellular dynamics and specifically slow high-threshold conductances have been proposed to have an impact on the grid cell scale. To test the hypothesis that intrinsic hyperpolarization-activated cation currents account for both the scaled gradient and the oscillatory frequencies observed along the dorsal-to-ventral axis, we have modeled and analyzed data from a population of grid cells simulated with spiking neurons interacting through low-dimensional attractor dynamics. We observed that the intrinsic neuronal membrane properties of simulated cells were sufficient to induce an increase in grid scale and potentiate differences in the membrane potential oscillatory frequency. Overall, our results suggest that the after-spike dynamics of cation currents may play a major role in determining the grid cells’ scale and that oscillatory frequencies are a consequence of intrinsic cellular properties that are specific to different levels of the dorsal-to-ventral axis in the MEC layer II.

JTD Keywords: Grid cells, Entorhinal, Hyperpolarization, Navigation, Space

de Goede, M., Dijkstra, M., Obregón, R., Ramón-Azcón, J., Martínez, Elena, Padilla, L., Mitjans, F., Garcia-Blanco, S. M., (2019). Al2O3 microring resonators for the detection of a cancer biomarker in undiluted urine Optics Express 27, (13), 18508-18521

Concentrations down to 3 nM of the rhS100A4 protein, associated with human tumor development, have been detected in undiluted urine using an integrated sensor based on microring resonators in the emerging Al2O3 photonic platform. The fabricated microrings were designed for operation in the C-band (λ = 1565 nm) and exhibited a high-quality factor in air of 3.2 × 105. The bulk refractive index sensitivity of the devices was ~100 nm/RIU (for TM polarization) with a limit of detection of ~10−6 RIU. A surface functionalization protocol was developed to allow for the selective binding of the monoclonal antibodies designed to capture the target biomarker to the surface of the Al2O3 microrings. The detection of rhS100A4 proteins at clinically relevant concentrations in urine is a big milestone towards the use of biosensors for the screening and early diagnosis of different cancers. Biosensors based on this microring technology can lead to portable, multiplexed and easy-to-use point of care devices.

JTD Keywords: Distributed feedback lasers, Effective refractive index, Laser coupling, Polarization maintaining fibers, Refractive index, Scanning electron microscopy

Aragonès, Albert C., Medina, Ernesto, Ferrer-Huerta, Miriam, Gimeno, Nuria, Teixidó, Meritxell, Palma, Julio L., Tao, Nongjian, Ugalde, Jesus M., Giralt, Ernest, Díez-Pérez, Ismael, Mujica, Vladimiro, (2017). Measuring the spin-polarization power of a single chiral molecule Small 13, (2), 1602519

The electronic spin filtering capability of a single chiral helical peptide is measured. A ferromagnetic electrode source is employed to inject spin-polarized electrons in an asymmetric single-molecule junction bridging an α-helical peptide sequence of known chirality. The conductance comparison between both isomers allows the direct determination of the polarization power of an individual chiral molecule.

JTD Keywords: Alpha-helical peptides, Chiral transport, Single-molecule wires, Spin-polarization power, Spin-polarized transmission

Cuervo, A., Dans, P. D., Carrascosa, J. L., Orozco, M., Gomila, G., Fumagalli, L., (2014). Direct measurement of the dielectric polarization properties of DNA Proceedings of the National Academy of Sciences of the United States of America 111, (35), E3624-E3630

The electric polarizability of DNA, represented by the dielectric constant, is a key intrinsic property that modulates DNA interaction with effector proteins. Surprisingly, it has so far remained unknown owing to the lack of experimental tools able to access it. Here, we experimentally resolved it by detecting the ultraweak polarization forces of DNA inside single T7 bacteriophages particles using electrostatic force microscopy. In contrast to the common assumption of low-polarizable behavior like proteins (εr ~ 2–4), we found that the DNA dielectric constant is ~ 8, considerably higher than the value of ~ 3 found for capsid proteins. State-of-the-art molecular dynamic simulations confirm the experimental findings, which result in sensibly decreased DNA interaction free energy than normally predicted by Poisson–Boltzmann methods. Our findings reveal a property at the basis of DNA structure and functions that is needed for realistic theoretical descriptions, and illustrate the synergetic power of scanning probe microscopy and theoretical computation techniques.

JTD Keywords: Atomic force microscopy, Atomistic simulations, DNA packaging, DNA-ligand binding, Poisson-Boltzmann equation, capsid protein, DNA, double stranded DNA, amino acid composition, article, atomic force microscopy, bacteriophage, bacteriophage T7, dielectric constant, dipole, DNA binding, DNA packaging, DNA structure, electron microscopy, ligand binding, nonhuman, polarization, priority journal, protein analysis, protein DNA interaction, scanning probe microscopy, static electricity, virion, virus capsid, virus particle, atomic force microscopy, atomistic simulations, DNA packaging, DNA-ligand binding, Poisson-Boltzmann equation, Bacteriophage T7, Capsid, Cations, Dielectric Spectroscopy, DNA, DNA, Viral, DNA-Binding Proteins, Electrochemical Techniques, Ligands, Microscopy, Atomic Force, Models, Chemical, Nuclear Proteins

Gomila, G., Gramse, G., Fumagalli, L., (2014). Finite-size effects and analytical modeling of electrostatic force microscopy applied to dielectric films Nanotechnology 25, (25), 255702 (11)

A numerical analysis of the polarization force between a sharp conducting probe and a dielectric film of finite lateral dimensions on a metallic substrate is presented with the double objective of (i) determining the conditions under which the film can be approximated by a laterally infinite film and (ii) proposing an analytical model valid in this limit. We show that, for a given dielectric film, the critical diameter above which the film can be modeled as laterally infinite depends not only on the probe geometry, as expected, but mainly on the film thickness. In particular, for films with intermediate to large thicknesses (>100 nm), the critical diameter is nearly independent from the probe geometry and essentially depends on the film thickness and dielectric constant following a relatively simple phenomenological expression. For films that can be considered as laterally infinite, we propose a generalized analytical model valid in the thin-ultrathin limit (<20-50 nm) that reproduces the numerical calculations and the experimental data. Present results provide a general framework under which accurate quantification of electrostatic force microscopy measurements on dielectric films on metallic substrates can be achieved.

JTD Keywords: Dielectric constant, Dielectric films, Electrostatic force microscopy, Quantification, Analytical models, Electric force microscopy, Electrostatic force, Film thickness, Permittivity, Probes, Substrates, Ultrathin films, Accurate quantifications, Electrostatic force microscopy, Finite size effect, Lateral dimension, Metallic substrate, Numerical calculation, Polarization forces, Quantification, Dielectric films

Gramse, G., Gomila, G., Fumagalli, L., (2012). Quantifying the dielectric constant of thick insulators by electrostatic force microscopy: effects of the microscopic parts of the probe Nanotechnology 23, (20), 205703

We present a systematic analysis of the effects that the microscopic parts of electrostatic force microscopy probes (the cone and cantilever) have on the electrostatic interaction between the tip apex and thick insulating substrates (thickness>100mum). We discuss how these effects can influence the measurement and quantification of the local dielectric constant of the substrates. We propose and experimentally validate a general methodology that takes into account the influence of the cone and the cantilever, thus enabling us to obtain very accurate values of the dielectric constants of thick insulators.

JTD Keywords: Polarization, Samples

Correa, R., Laciar, E., Arini, P., Jané, R., (2010). Analysis of QRS loop in the Vectorcardiogram of patients with Chagas' disease Engineering in Medicine and Biology Society (EMBC) 32nd Annual International Conference of the IEEE , IEEE (Buenos Aires, Argentina) , 2561-2564

In the present work, we have studied the QRS loop in the Vectorcardiogram (VCG) of 95 chronic chagasic patients classified in different groups (I, II and III) according to their degree of myocardial damage. For comparison, the VCGs of 11 healthy subjects used as control group (Group O) were also examined. The QRS loop was obtained for each patient from the XYZ orthogonal leads of their High-Resolution Electrocardiogram (HRECG) records. In order to analyze the variations of QRS loop in each detected beat, it has been proposed in this study the following vectorcardiographic parameters a) Maximum magnitude of the cardiac depolarization vector, b) Volume, c) Area of QRS loop, d) Ratio between the Area and Perimeter, e) Ratio between the major and minor axes of the QRS loop and f) QRS loop Energy. It has been found that one or more indexes exhibited statistical differences (p<0.05) between groups 0-II, O-III, I-II, I-III and II-III. We concluded that the proposed method could be use as complementary diagnosis technique to evaluate the degree of myocardial damage in chronic chagasic patients.

JTD Keywords: Practical, Experimental/ bioelectric phenomena, Diseases, Electrocardiography, Medical signal, Processing/ QRS loop, Vectorcardiogram, Cardiac depolarization vector, Myocardial damage, Chagas disease, Complementary diagnosis technique, High-resolution electrocardiogram

Gramse, G., Casuso, I., Toset, J., Fumagalli, L., Gomila, G., (2009). Quantitative dielectric constant measurement of thin films by DC electrostatic force microscopy Nanotechnology 20, (39), 395702

A simple method to measure the static dielectric constant of thin films with nanometric spatial resolution is presented. The dielectric constant is extracted from DC electrostatic force measurements with the use of an accurate analytical model. The method is validated here on thin silicon dioxide films (8 nm thick, dielectric constant approximately 4) and purple membrane monolayers (6 nm thick, dielectric constant approximately 2), providing results in excellent agreement with those recently obtained by nanoscale capacitance microscopy using a current-sensing approach. The main advantage of the force detection approach resides in its simplicity and direct application on any commercial atomic force microscope with no need of additional sophisticated electronics, thus being easily available to researchers in materials science, biophysics and semiconductor technology.

JTD Keywords: Roscopy, Membrane, Tip, Polarizability, Polarization, Resolution, Nanotubes, Charge

Castellarnau, Marc, Errachid, Abdelhamid, Madrid, Cristina, Juárez, Antonio, Samitier, Josep, (2006). Dielectrophoresis as a tool to characterize and differentiate isogenic mutants of Escherichia coli Biophysical Journal , 91, (10), 3937-3945

In this study we report on an experimental method based on dielectrophoretic analysis to identify changes in four Escherichia coli isogenic strains that differed exclusively in one mutant allele. The dielectrophoretic properties of wild-type cells were compared to those of hns, hha, and hha hns mutant derivatives. The hns and hha genes code respectively for the global regulators Hha and H-NS. The Hha and H-NS proteins modulate gene expression in Escherichia coli and other Gram negative bacteria. Mutations in either hha or hns genes result in a pleiotropic phenotype. A two-shell prolate ellipsoidal model has been used to fit the experimental data, obtained from dielectrophoresis measurements, and to study the differences in the dielectric properties of the bacterial strains. The experimental results show that the mutant genotype can be predicted from the dielectrophoretic analysis of the corresponding cultures, opening the way to the development of microdevices for specific identification. Therefore, this study shows that dielectrophoresis can be a valuable tool to study bacterial populations which, although apparently homogeneous, may present phenotypic variability.

JTD Keywords: H-NS, Dielectric behaviour, Hemolysin genes, Cells, Separation, Expression, Proteins, HHA, Electrorotation, Polarization