Jarek Wosik

Design Maps for the Hyperthermic Treatment of Tumors with Superparamagnetic Nanoparticles

A plethora of magnetic nanoparticles has been developed and investigated under different alternating magnetic fields (AMF) for the hyperthermic treatment of malignant tissues. Yet, clinical applications of magnetic hyperthermia are sporadic, mostly due to the low energy conversion efficiency of the metallic nanoparticles and the high tissue concentrations required. Here, we study the hyperthermic performance of commercially available formulations of superparamagnetic iron oxide nanoparticles (SPIOs), with core diameter of 5, 7 and 14 nm, in terms of absolute temperature increase ΔT and specific absorption rate (SAR). These nanoparticles are operated under a broad range of AMF conditions, with frequency f varying between 0.2 and 30 MHz; field strength H ranging from 4 to 10 kA m−1; and concentration cMNP varying from 0.02 to 3.5 mg ml−1. At high frequency field (∼30 MHz), non specific heating dominates and ΔT correlates with the electrical conductivity of the medium. At low frequency field (<1 MHz), non specific heating is negligible and the relaxation of the SPIO within the AMF is the sole energy source. We show that the ΔT of the medium grows linearly with cMNP, whereas the SARMNP of the magnetic nanoparticles is independent of cMNP and varies linearly with f and H2. Using a computational model for heat transport in a biological tissue, the minimum requirements for local hyperthermia (Ttissue >42°C) and thermal ablation (Ttissue >50°C) are derived in terms of cMNP, operating AMF conditions and blood perfusion. The resulting maps can be used to rationally design hyperthermic treatments and identifying the proper route of administration – systemic versus intratumor injection – depending on the magnetic and biodistribution properties of the nanoparticles.

Parallel and orthogonal E-field alignment of single-walled carbon nanotubes by ac dielectrophoresis.

We designed planar electrodes, for dielectrophoretic manipulation of single-walled carbon nanotubes (SWNTs), built as metal-oxide-semiconductor nanogap capacitors with common substrate and oxide thicknesses of 17 and 150 nm. Such design generates high electric fields (10(9) V m(-1)) and also the fringing field is curved due to the conducting substrate, unlike fields generated by conventionally used planar electrodes. Scanning electron microscopy images showed SWNTs aligned parallel and perpendicular to the electrodes. Raman spectroscopic mapping was used to produce separate images of the metallic (m-SWNT) and semiconducting (s-SWNT) nanotube density distributions. As expected, parallel alignment of the m-SWNTs with the E-field was found; however, also a perpendicular alignment of s-SWNTs was observed. Such orthogonal alignment of s-SWNTs is a rare observation and has not been experimentally reported before in detail with Raman images. Due to the unique electrode design, we were able to obtain substantial separation of m-SWNTs and s-SWNTs. Numerical modeling of the electric field factor of the dielectrophoresis force was done, and it matched perfectly with the experimental results. The orthogonal alignment of s-SWNTs results from comparable values of parallel and perpendicular polarizability to the nanotube axis.

Reduction of electrode polarization capacitance in low-frequency impedance spectroscopy by using mesh electrodes

Dielectric measurements of biological samples are obscured by electrode polarization, which at low frequencies dominates over the actual sample response. Reduction of this artifact is especially necessary in studying interactions of electric field with biological systems in the α-dispersion range. We developed a method to reduce the influence of electrode polarization by employing mesh instead of solid electrodes as sensing probes, thereby reducing the area of the double layer. The design decreases the electrode-electrolyte contact area by almost 40% while keeping the bulk sample capacitance the same. Interrogation electric fields away from the electrode surface and sensitivity are unaffected. Electrodes were microfabricated (600μm×50μm, spacing of 100μm) with and without mesh holes 7.5μm×7.5μm in size. Simulations of electric field performed using Comsol Multiphysics showed non-uniformity of the electric field within less than 1.5μm from the electrode surface, which encompasses the double layer region, but at greater distance the solid and mesh electrodes gave the same results. Mesh electrodes reduced capacitance measurements for water and KCl solutions of different concentrations at low frequencies (<10kHz), while higher frequency capacitance remained the same for both electrode types, confirming our hypothesis that this design leaves the electric field mainly unaffected. Impedance measurements at low frequencies for water and mice heart mitochondrial suspension were lower for mesh than for solid electrodes. Comsol simulations confirmed these results by showing that mesh electrodes have a greater charge density than solid electrodes, which affects conductance. These electrodes are being used for mitochondrial membrane potential studies.

Cluster ion beam smoothing of SiC and YBCO surfaces

Abstract Optimization of the surface topography, especially in high-temperature superconductor (HTS) and silicon carbide is crucial for device processing. Surface smoothing in these materials was investigated using gas cluster ion beams (GCIB) capable of delivering cluster ions of ≥2000 Ar atoms with energies of up to 30 kV. Examination of the surface topography after cluster ion irradiation was done using cross-sectional transmission electron microscopy (TEM) and atomic force microscopy (AFM). The results indicate that typical as-deposited YBCO films on MgO substrates have an average roughness of the order of 40 nm and interpeak distance between 300 and 600 nm. Application of GCIB to the surface planarization reduces the roughness to only 10 nm. Also, power handling and microwave surface resistance of the YBCO film and its relationship to surface smoothness are reported. Similar observations using bulk SiC are discussed.

Perfusion in rat brain at 7 T with arterial spin labeling using FAIR-TrueFISP and QUIPSS.

Measurement of perfusion in longitudinal studies allows for the assessment of tissue integrity and the detection of subtle pathologies. In this work, the feasibility of measuring brain perfusion in rats with high spatial resolution using arterial spin labeling is reported. A flow-sensitive alternating recovery sequence, coupled with a balanced gradient fast imaging with steady-state precession readout section was used to minimize ghosting and geometric distortions, while achieving high signal-to-noise ratio. The quantitative imaging of perfusion using a single subtraction method was implemented to address the effects of variable transit delays between the labeling of spins and their arrival at the imaging slice. Studies in six rats at 7 T showed good perfusion contrast with minimal geometric distortion. The measured blood flow values of 152.5+/-6.3 ml/100 g per minute in gray matter and 72.3+/-14.0 ml/100 g per minute in white matter are in good agreement with previously reported values based on autoradiography, considered to be the gold standard.

Influence of columnar defects on surface resistance of YBa2Cu3Ox superconducting thin films; nonlinear effects

We report on measurements of surface resistance (Rs) of YBa2Cu3Ox thin films irradiated with 0.9 GeV Pb ions. Measurements of Rs versus microwave-frequency (rf) magnetic field and temperature were carried out using a dielectric resonator technique. At low temperatures, no significant difference was observed between surface resistance of irradiated and nonirradiated films. However, at higher temperatures the irradiated films exhibited not only higher Rs but also a nonlinear dependence of Rs on rf magnetic field. A simple model for microwave losses in thin superconducting films induced by columnar defects is proposed. Using this model, the observed changes in Rs have been attributed to additional losses and/or heating effects in the insulator-superconductor boundary between an amorphous core of the columnar defects (several nanometers in diameter) and the surrounding superconducting material.

Mitochondrial membrane studies using impedance spectroscopy with parallel pH monitoring.

A biological microelectromechanical system (BioMEMS) device was designed to study complementary mitochondrial parameters important in mitochondrial dysfunction studies. Mitochondrial dysfunction has been linked to many diseases, including diabetes, obesity, heart failure and aging, as these organelles play a critical role in energy generation, cell signaling and apoptosis. The synthesis of ATP is driven by the electrical potential across the inner mitochondrial membrane and by the pH difference due to proton flux across it. We have developed a tool to study the ionic activity of the mitochondria in parallel with dielectric measurements (impedance spectroscopy) to gain a better understanding of the properties of the mitochondrial membrane. This BioMEMS chip includes: 1) electrodes for impedance studies of mitochondria designed as two- and four-probe structures for optimized operation over a wide frequency range and 2) ion-sensitive field effect transistors for proton studies of the electron transport chain and for possible monitoring other ions such as sodium, potassium and calcium. We have used uncouplers to depolarize the mitochondrial membrane and disrupt the ionic balance. Dielectric spectroscopy responded with a corresponding increase in impedance values pointing at changes in mitochondrial membrane potential. An electrical model was used to describe mitochondrial sample’s complex impedance frequency dependencies and the contribution of the membrane to overall impedance changes. The results prove that dielectric spectroscopy can be used as a tool for membrane potential studies. It can be concluded that studies of the electrochemical parameters associated with mitochondrial bioenergetics may render significant information on various abnormalities attributable to these organelles.

A method to measure specific absorption rate of nanoparticles in colloidal suspension using different configurations of radio-frequency fields.

We report a method for characterization of the efficiency of radio-frequency (rf) heating of nanoparticles (NPs) suspended in an aqueous medium. Measurements were carried out for water suspended 5 nm superparamagnetic iron-oxide NPs with 30 nm dextran matrix for three different configurations of rf electric and magnetic fields. A 30 MHz high-Q resonator was designed to measure samples placed inside a parallel plate capacitor and solenoid coil with or without an rf electric field shield. All components of rf losses were analyzed and rf electric and magnetic field induced heating of NPs and the dispersion medium was determined and discussed.

Microwave properties of single-walled carbon nanotubes films below percolation threshold

A film residue obtained by evaporating surfactant-stabilized single-walled carbon nanotube (SWNT) suspension was characterized at 12 GHz using a scanning-sample dielectric resonator technique. Resonant frequency and quality factor changes were measured and cavity perturbation method was used to calculate the SWNT complex permittivity. The effective permittivity of the SWNT was determined as (3516-j316.5), which provided an average dielectric constant and conductivity for a single SWNT to be 8.1×105 and 8.4×106 S/m, respectively. Microwave induced losses originated only from the electric field, not from the magnetic field, thus indicating an absence of direct electrical contact between nanotubes and a below percolation-limit configuration.

Protein adsorption enhanced radio-frequency heating of silica nanoparticles

Measurements of specific-absorption-rate (SAR) of silica 30, 50, and 100 nm nanoparticles (NP) suspended in water were carried out at 30 MHz in 7 kV/m radio-frequency (rf) electric field. Size dependent, NP-suspension interface related heating of silica NP was observed. To investigate a possible mechanism of heating, bovine serum albumin was adsorbed on the surface of silica NPs in suspension. It resulted in significant enhancement of SAR when compared to bare silica NPs. A calorimetric and rf loss model was used to calculate effective conductivity of silica NP with/without adsorbed albumin as a function of silica size and albumin concentration.