RBIO-06. MECHANISM OF ACTION AND ASSOCIATED EFFECTS OF TUMOR TREATING FIELDS (TTFIELDS) ON LIVING CELLS USING SIMULATIONS

Following FDA approval, TTFields treatment has become a commonly used modality for treating patients with Glioblastoma (GBM) and Mesothelioma. From the early 2000’s, extensive research has been performed in in-vitro systems for studying the effects of TTFields on living cells. These studies have shown that multiple cellular functions are affected by TTFields. However, the physical mechanism by which the fields exert effects on cells are not well understood. We propose an analytical model for predicting the geometric and electrical parameters enabling amplification of the electric field in the living cells. This amplification favors the emergence of local heating, dielectrophoretic (DEP) force, or electrostatic pressure at TTFields frequencies. This model is supported by simulations of cells in different configurations. Computational studies were performed with Comsol Multiphysics software. Cell models were constituted of cytoplasm, membrane and extracellular matrix. A field of 1V/cm was generated at different frequencies between 10kHz and 1GHz. Maximal field amplification of X20 of the applied field (@200 kHz) was observed in a model of confluent cells with 5nm intercellular distance. Such field amplification could create electrostatic pressure on the membrane potentially leading to its deformation and to stress on the cytoskeleton. Analytical calculations show the field gradient could result in DEP forces of ~10pN on the membrane. Such force could potentially disrupt the membrane or junctions. Results show that a 10nm pore in membrane would lead to a 450 times amplification in the pore’s vicinity, potentially resulting in forces of between 0.1pN and 100pN on intracellular structures. Those forces are sufficient for disrupting microtubules. Specific Absorption Rates of up to 106 W/kg were observed in the vicinity of the pore, suggesting that strong thermal effects may also explain the effect of TTFields on cells. Our generic analytical model predicts the conditions for field amplification at TTFields frequencies.

A Liquid Metal Encapsulation for Analyzing Porous Nanomaterials by Atom Probe Tomography

Analyzing porous (nano)materials via atom probe tomography has been notoriously difficult. Voids and pores act as concentrators of the electrostatic pressure, which results in premature specimen failure, and the electrostatic field distribution near voids leads to aberrations that are difficult to predict. In this study, we propose a new encapsulating method for porous samples using a low melting point Bi–In–Sn alloy, known as Field's metal. As a model material, we used porous iron made by direct-hydrogen reduction of single-crystalline wüstite. The complete encapsulation was performed using in situ heating on the stage of a scanning electron microscope. No visible corrosion nor dissolution of the sample occurred. Subsequently, specimens were shaped by focused ion-beam milling under cryogenic conditions at −190°C. The proposed approach is versatile and can be applied to provide good quality atom probe datasets from micro/nanoporous materials.

Critically Charged Superfluid 4He Surface in Inhomogeneous Electric Fields

We have studied the spatial distribution of charges trapped at the surface of superfluid helium in the inhomogeneous electric field of a metallic tip close to the liquid surface. The electrostatic pressure of the charges generates a deformation of the liquid surface, leading to a “hillock” (called “Taylor cone”) or “dimple”, depending on whether the tip is placed above or below the surface. We use finite element simulations for calculating the surface profile and the corresponding charge density in the vicinity of the tip. Typical electric fields E are in the range of a few kV/cm, the maximum equilibrium surface deformations have a height on the order of (but somewhat smaller than) the capillary length of liquid 4He (0.5 mm), and the maximum number density of elementary charges in a hillock or dimple, limited by an electrohydrodynamic instability, is some 1013 m−2. These results can be used to determine the charge density at a liquid helium surface from the measured surface profile. They also imply that inhomogeneous electric fields at a bulk helium surface do not allow one to increase the electron density substantially beyond the limit for a homogeneous field, and are therefore not feasible for reaching a density regime where surface state electrons are expected to show deviations from the classical behavior. Some alternative solutions are discussed.

Tunable graphene phononic crystal

In the field of phononics, periodic patterning controls vibrations and thereby the flow of heat and sound in matter. Bandgaps arising in such phononic crystals realize low-dissipation vibrational modes and enable applications towards mechanical qubits, efficient waveguides, and state-of-the-art sensing. Here, we combine phononics and two-dimensional materials and explore the possibility of manipulating phononic crystals via applied mechanical pressure. To this end, we fabricate the thinnest possible phononic crystal from monolayer graphene and simulate its vibrational properties. We find a bandgap in the MHz regime, within which we localize a defect mode with a small effective mass of 0.72 ag = 0.002 mphysical. Finally, we take advantage of graphene’s flexibility and mechanically tune a finite size phononic crystal. Under electrostatic pressure up to 30 kPa, we observe an upshift in frequency of the entire phononic system by more than 350%. At the same time, the defect mode stays within the bandgap and remains localized, suggesting a high-quality, dynamically tunable mechanical system.

Thermodynamic processes in dusty plasma

Here, we propose a thermodynamic model for dusty plasma, where the dust is confined in a small volume within a large plasma background by external fields. In this model, the parameters of dust, e.g. Helmholtz energy, pressure, entropy and enthalpy, etc. can be calculated for given dust density and temperature. The model is solved analytically in the mean field (gaseous) limit and various processes associated with the gaseous phase of dust, e.g. adiabatic/isothermal/constant internal energy expansion/compression, specific heat, free expansion within the plasma background, and the dispersion of novel acoustic waves are studied. Some predictions of the model, e.g. electrostatic pressure of the dust and the isothermal equation of state, have been earlier verified in experiments and numerical simulations. The model is compared with an earlier thermodynamic model of dusty plasma proposed by Hamaguchi and Farouki.

An Analysis of the Aerodynamic Response of an Electroactive Membrane

Dielectric elastomer membranes are a category of electroactive polymers composed of a thin elastomer film sandwiched between two compliant electrodes. An electrostatic pressure is created when there is an externally applied voltage on the electrodes which creates compression in the thickness direction and extension in the in-plane direction. This outlines a variation of the tension in the membrane that can be used to change its dynamic behavior. In this study, a specimen of an electroactive membrane, VHB 4910 is considered to observe the aerodynamic characteristics under external flow of air. Both experimental and numerical analyses are performed to predict the fluid-structure interaction behavior of the specimen for different angles of attack. A vibration testing arrangement is used to estimate the resonance frequencies and the mode shapes which are validated by the finite element results. From the study, the coefficient of lift is found to increase with the angle of attack up to a critical value. Similarly, the coefficient of drag increases with the angle of attack. Both lift and drag coefficients decrease with the Reynolds number. The magnitudes of the natural frequencies decrease as the applied voltages rise. The natural frequencies and mode shapes of the membrane can be tuned by changing the pretension, the pressure, and/or the voltage.

Sensorless Force Control Interface for DEAP Stack-Actuators

Transducers based on dielectric electroactive polymers (DEAP) offer an attractive balance of work density and electromechanical efficiency. For example in automation and haptic applications, especially multilayer transducers are used to scale up their absolute deformation and force. Depending on the application different transducer controls have to be realized to match the specifications of the particular application. However, analogous to conventional electromechanical drive systems an inner sensor-less force control can be realized for DEAP transducers, too. For this force control the nonlinear relations between voltage and electrostatic pressure as well as the electromechanical coupling have to be considered. The resulting open-loop force control can be used for superimposed motion controls, such as position, vibration and impedance controls. Therefore, within this contribution the authors propose a model-based feedforward force control based on an overall model of the transducer that does not require any force measurement. Finally, the derived open-loop force control interface is experimentally validated using in-house developed DEAP stack-transducers and driving power electronics.