by Keyword: Constant
Munoz-Galan, H, Molina, BG, Bertran, O, Perez-Madrigal, MM, Aleman, C, (2022). Combining rapid and sustained insulin release from conducting hydrogels for glycemic control br European Polymer Journal 181, 111670
Innovative insulin delivery systems contemplate combining multi-pharmacokinetic profiles for glycemic control. Two device configurations have been designed for the controlled release of insulin using the same chemical compounds. The first insulin delivery system, which displays a rapid release response that, in addition, is enhanced on a short time scale by electrical stimulation, consists on an insulin layer sandwiched between a conducting poly(3,4-ethylenedioxythiophene) (PEDOT) film and a poly-gamma-glutamic acid (gamma-PGA) hydrogel. The second system is constituted by gamma-PGA hydrogel loaded with insulin and PEDOT nanoparticles by in situ gelation. In this case, the insulin release, which only starts after the degradation of the hydrogel over time (i.e. on a long time scale), is slow and sustained. The combination of an on-demand and fast release profile with a sustained and slow profile, which act on different time scales, would result in a very efficient regulation of diabetes therapy in comparison to current systems, allowing to control both fast and sustained glycemic events. Considering that the two systems developed in this work are based on the same chemical components, future work will be focused on the combination of the two kinetic profiles by re-engineering a unique insulin release device using gamma-PGA, PEDOT and insulin.
JTD Keywords: Conducting polymer, Constant, Diabetes, Diabetes-mellitus, Drug-delivery, Electrodes, Electrostimulation, Glucose-responsive hydrogels, Hydrogel, Molecular dynamics, Molecular-dynamics, Nanogels, Nanoparticles, Poly(3,4-ethylenedioxythiophene), Risk
Valenti, Sofia, del Valle, Luis Javier, Romanini, Michela, Mitjana, Meritxell, Puiggalí, Jordi, Tamarit, Josep Lluís, Macovez, Roberto, (2022). Drug-Biopolymer Dispersions: Morphology- and Temperature- Dependent (Anti)Plasticizer Effect of the Drug and Component-Specific Johari–Goldstein Relaxations International Journal Of Molecular Sciences 23, 2456
Amorphous molecule-macromolecule mixtures are ubiquitous in polymer technology and are one of the most studied routes for the development of amorphous drug formulations. For these applications it is crucial to understand how the preparation method affects the properties of the mixtures. Here, we employ differential scanning calorimetry and broadband dielectric spectroscopy to investigate dispersions of a small-molecule drug (the Nordazepam anxiolytic) in biodegradable polylactide, both in the form of solvent-cast films and electrospun microfibres. We show that the dispersion of the same small-molecule compound can have opposite (plasticizing or antiplasticizing) effects on the segmental mobility of a biopolymer depending on preparation method, temperature, and polymer enantiomerism. We compare two different chiral forms of the polymer, namely, the enantiomeric pure, semicrystalline L-polymer (PLLA), and a random, fully amorphous copolymer containing both L and D monomers (PDLLA), both of which have lower glass transition temperature (Tg) than the drug. While the drug has a weak antiplasticizing effect on the films, consistent with its higher Tg, we find that it actually acts as a plasticizer for the PLLA microfibres, reducing their Tg by as much as 14 K at 30%-weight drug loading, namely, to a value that is lower than the Tg of fully amorphous films. The structural relaxation time of the samples similarly depends on chemical composition and morphology. Most mixtures displayed a single structural relaxation, as expected for homogeneous samples. In the PLLA microfibres, the presence of crystalline domains increases the structural relaxation time of the amorphous fraction, while the presence of the drug lowers the structural relaxation time of the (partially stretched) chains in the microfibres, increasing chain mobility well above that of the fully amorphous polymer matrix. Even fully amorphous homogeneous mixtures exhibit two distinct Johari–Goldstein relaxation processes, one for each chemical component. Our findings have important implications for the interpretation of the Johari–Goldstein process as well as for the physical stability and mechanical properties of microfibres with small-molecule additives.
JTD Keywords: amorphous pharmaceuticals, beta-relaxation, constant loss, crystallization, dielectric spectroscopy, dynamics, formulation morphology, glass transition, molecular mobility, nanofibers, polylactide, polymer enantiomerism, secondary relaxations, valium metabolite, viscous-liquids, Amorphous pharmaceuticals, Glass-transition, Secondary relaxations
Lozano, Helena, Millan-Solsona, Ruben, Blanco-Cabra, Nuria, Fabregas, Rene, Torrents, Eduard, Gomila, Gabriel, (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
Checa M, Millan-Solsona R, Mares AG, Pujals S, Gomila G, (2021). Fast Label-Free Nanoscale Composition Mapping of Eukaryotic Cells Via Scanning Dielectric Force Volume Microscopy and Machine Learning Small Methods 5,
Mapping the biochemical composition of eukaryotic cells without the use of exogenous labels is a long-sought objective in cell biology. Recently, it has been shown that composition maps on dry single bacterial cells with nanoscale spatial resolution can be inferred from quantitative nanoscale dielectric constant maps obtained with the scanning dielectric microscope. Here, it is shown that this approach can also be applied to the much more challenging case of fixed and dry eukaryotic cells, which are highly heterogeneous and show micrometric topographic variations. More importantly, it is demonstrated that the main bottleneck of the technique (the long computation times required to extract the nanoscale dielectric constant maps) can be shortcut by using supervised neural networks, decreasing them from weeks to seconds in a wokstation computer. This easy-to-use data-driven approach opens the door for in situ and on-the-fly label free nanoscale composition mapping of eukaryotic cells with scanning dielectric microscopy. © 2021 The Authors. Small Methods published by Wiley-VCH GmbH
JTD Keywords: label-free mapping, machine learning, nanoscale, scanning dielectric microscopy, Biochemical composition, Cells, Constant, Cytology, Data-driven approach, Dielectric forces, Dielectric materials, Eukaryotic cells, Label-free mapping, Machine learning, Mapping, Nanoscale, Nanoscale composition, Nanoscale spatial resolution, Nanotechnology, Scanning, Scanning dielectric microscopy, Supervised neural networks
Balakrishnan H, Millan-Solsona R, Checa M, Fabregas R, Fumagalli L, Gomila G, (2021). Depth mapping of metallic nanowire polymer nanocomposites by scanning dielectric microscopy Nanoscale 13, 10116-10126
Polymer nanocomposite materials based on metallic nanowires are widely investigated as transparent and flexible electrodes or as stretchable conductors and dielectrics for biosensing. Here we show that Scanning Dielectric Microscopy (SDM) can map the depth distribution of metallic nanowires within the nanocomposites in a non-destructive way. This is achieved by a quantitative analysis of sub-surface electrostatic force microscopy measurements with finite-element numerical calculations. As an application we determined the three-dimensional spatial distribution of ?50 nm diameter silver nanowires in ?100 nm-250 nm thick gelatin films. The characterization is done both under dry ambient conditions, where gelatin shows a relatively low dielectric constant, ?r ? 5, and under humid ambient conditions, where its dielectric constant increases up to ?r ? 14. The present results show that SDM can be a valuable non-destructive subsurface characterization technique for nanowire-based nanocomposite materials, which can contribute to the optimization of these materials for applications in fields such as wearable electronics, solar cell technologies or printable electronics. © The Royal Society of Chemistry.
JTD Keywords: composite, constant, electrodes, mode, nanostructures, objects, progress, subsurface, tomography, Composite materials, Dielectric materials, Electric force microscopy, Electrostatic force, Force microscopy, Low dielectric constants, Nanocomposites, Numerical calculation, Polymer nanocomposite, Printable electronics, Scanning dielectric microscopy, Silver nanowires, Solar cell technology, Stretchable conductors, Subsurface characterizations, Transparent electrodes, Wearable technology
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,
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
Checa M, Millan‐solsona R, Mares AG, Pujals S, Gomila G, (2021). Dielectric imaging of fixed hela cells by in‐liquid scanning dielectric force volume microscopy Nanomaterials 11,
Mapping the dielectric properties of cells with nanoscale spatial resolution can be an im-portant tool in nanomedicine and nanotoxicity analysis, which can complement structural and mechanical nanoscale measurements. Recently we have shown that dielectric constant maps can be obtained on dried fixed cells in air environment by means of scanning dielectric force volume mi-croscopy. Here, we demonstrate that such measurements can also be performed in the much more challenging case of fixed cells in liquid environment. Performing the measurements in liquid media contributes to preserve better the structure of the fixed cells, while also enabling accessing the local dielectric properties under fully hydrated conditions. The results shown in this work pave the way to address the nanoscale dielectric imaging of living cells, for which still further developments are required, as discussed here.
JTD Keywords: atomic force microscopy (afm), capacitance, constant, dielectric properties, electrostatic force microscopy (efm), functional microscopy, nanoscale, scanning dielectric microscopy (sdm), Atomic force microscopy (afm), Dielectric properties, Dielectrophoretic separation, Electrostatic force microscopy (efm), Functional micros-copy, Scanning dielectric microscopy (sdm), Scanning probe microscopy (spm)
Pérez, Judit, Dulay, Samuel, Mir, M., Samitier, Josep, (2018). Molecular architecture for DNA wiring Biosensors and Bioelectronics 121, 54-61
Detection of the hybridisation events is of great importance in many different biotechnology applications such as diagnosis, computing, molecular bioelectronics, and among others. However, one important drawback is the low current of some redox reporters that limits their application. This paper demonstrates the powerful features of molecular wires, in particular the case of S-[4-[2-[4-(2-Phenylethynyl)phenyl]ethynyl]phenyl] thiol molecule and the key role that play the nanometric design of the capture probe linkers to achieve an efficient couple of the DNA complementary ferrocene label with the molecular wire for an effective electron transfer in co-immobilised self-assembled monolayers (SAMs) for DNA hybridisation detection. In this article, the length of the linker capture probe was studied for electron transfer enhancement from the ferrocene-motifs of immobilised molecules towards the electrode surface to obtain higher kinetics in the presence of thiolated molecular wires. The use of the right couple of capture probe linker and molecular wire has found to be beneficial as it helps to amplify eightfold the signal obtained.
JTD Keywords: DNA hybridisation, Bioelectronics, Electron transfer rate constant, Molecular wires, Electrochemistry, Ferrocene, Biosensor
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
Gramse, G., Kasper, M., Fumagalli, L., Gomila, G., Hinterdorfer, P., Kienberger, F., (2014). Calibrated complex impedance and permittivity measurements with scanning microwave microscopy Nanotechnology 25, (14), 145703 (8)
We present a procedure for calibrated complex impedance measurements and dielectric quantification with scanning microwave microscopy. The calibration procedure works in situ directly on the substrate with the specimen of interest and does not require any specific calibration sample. In the workflow tip-sample approach curves are used to extract calibrated complex impedance values and to convert measured S11 reflection signals into sample capacitance and resistance images. The dielectric constant of thin dielectric SiO2 films were determined from the capacitance images and approach curves using appropriate electrical tip-sample models and the Îµr value extracted at f = 19.81 GHz is in good agreement with the nominal value of Îµr âˆ¼ 4. The capacitive and resistive material properties of a doped Si semiconductor sample were studied at different doping densities and tip-sample bias voltages. Following a simple serial model the capacitance-voltage spectroscopy curves are clearly related to the semiconductor depletion zone while the resistivity is rising with falling dopant density from 20 Î© to 20 kÎ©. The proposed procedure of calibrated complex impedance measurements is simple and fast and the accuracy of the results is not affected by varying stray capacitances. It works for nanoscale samples on either fully dielectric or highly conductive substrates at frequencies between 1 and 20 GHz.
JTD Keywords: Complex impedance, Dielectric constant, Nanotechnology: calibration, Resistivity, Scanning microwave microscopy
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
Fumagalli, L., Edwards, Martin Andrew, Gomila, G., (2014). Quantitative electrostatic force microscopy with sharp silicon tips Nanotechnology 25, (49), 495701 (9)
Electrostatic force microscopy (EFM) probes are typically coated in either metal (radius ~ 30 nm) or highly-doped diamond (radius ~ 100 nm). Highly-doped silicon probes, which offer a sharpened and stable tip apex (radius ~ 1–10 nm) and are usually used only in standard atomic force microscopy, have been recently shown to allow enhanced lateral resolution in quantitative EFM and its application for dielectric constant measurement. Here we present the theoretical modelling required to quantitatively interpret the electrostatic force between these sharpened tips and samples. In contrast to a sphere-capped cone geometry used to describe metal/diamond-coated tips, modelling a sharpened silicon tip requires a geometry comprised of a cone with two different angles. Theoretical results are supported by experimental measurements of metallic substrates and ~10 nm radius dielectric nanoparticles. This work is equally applicable to EFM and other electrical scanned probe techniques, where it allows quantifying electrical properties of nanomaterials and 3D nano-objects with higher resolution.
JTD Keywords: AFM, Dielectric constant, EFM, Dielectrics, Nanoparticles, Sharp tips
Artés, Juan M., Díez-Pérez, Ismael, Sanz, Fausto, Gorostiza, Pau, (2011). Direct measurement of electron transfer distance decay constants of single redox proteins by electrochemical tunneling spectroscopy ACS Nano 5, (3), 2060-2066
We present a method to measure directly and at the single-molecule level the distance decay constant that characterizes the rate of electron transfer (ET) in redox proteins. Using
an electrochemical tunneling microscope under bipotentiostatic control, we obtained current-distance spectroscopic recordings of individual redox proteins confined within a nanometric tunneling gap at a well-defined molecular orientation. The tunneling current decays exponentially, and the corresponding decay constant (β) strongly supports a two-step tunneling ET mechanism. Statistical analysis of decay constant measurements reveals differences between the reduced and oxidized states that may be relevant to the control of ET rates in enzymes and biological electron transport chains.
JTD Keywords: Long-range electron transfer (LRET), Distance decay constant, Single-molecule electrochemistry, Redox enzyme, Metalloprotein, Blue copper protein, Azurin, Electrochemical scanning tunneling microscopy and spectroscopy, Nanoelectrodes, Debye length, Electrochemical charge screening