Tungsten Pins Research Articles

Testing of the tungsten pin dump prototype at the JUDITH 2 testing facility

A prototype of tungsten pins beam dump was tested with high power electron beam at the JUDITH 2 facility. A maximum electron beam power of 40 kW was applied on a nominal beam spot area of 4 × 4 cm2. This corresponds to the highest achieved beam power density of 1.4 kW/cm2. Approximately 16% of the deposited energy was removed by radiation at the highest beam power values, corresponding to estimated surface temperature of ≈ 3100 K. The results of the irradiation test are presented. The further improvements of the prototype are discussed. This result provides an encouraging input for possible design of a full power beam dump for SARAF Phase II.

Effect of Various Silicone Oil And Tungsten Levels on the Stability of a Monoclonal Antibody in Nine Commercially Available Prefilled Syringes

Prefilled syringes are widely used as a primary container for therapeutic proteins because they are more convenient than glass vials. The stability of biologic molecules can be affected by different syringe materials and techniques, such as silicone oil levels and coating method, amount of tungsten remaining in the glass barrel after using a tungsten pin to create the needle hole, and end of the syringe, which can be Luer locked or pre-staked with a needle. We investigated the impact of these parameters by using a monoclonal antibody to collect the antibody's stability profile and the prefilled syringes’ functionality data. Silicone oil levels had no impact on aggregation levels, and particle counts were lowest for silicone oil–free syringes. Functionality performance was similar and did not change throughout all stability time points for all syringe configurations. The break-loose force for Ompi syringes was initially lower and increased over time to align with those of the other configurations, all of which remained well below 25 N. Tungsten contaminants and agitation stress from shipping studies did not impact quality attributes. This work can help guide the development of similar products in prefilled syringes to ensure selection of the primary container that provides adequate stability for the protein, as well as maintain the desired functionality features over the shelf life of the drug product.

Planning and delivery of intensity modulated bolus electron conformal therapy.

PurposeBolus electron conformal therapy (BECT) is a clinically useful, well‐documented, and available technology. The addition of intensity modulation (IM) to BECT reduces volumes of high dose and dose spread in the planning target volume (PTV). This paper demonstrates new techniques for a process that should be suitable for planning and delivering IM‐BECT using passive radiotherapy intensity modulation for electrons (PRIME) devices.MethodsThe IM‐BECT planning and delivery process is an addition to the BECT process that includes intensity modulator design, fabrication, and quality assurance. The intensity modulator (PRIME device) is a hexagonal matrix of small island blocks (tungsten pins of varying diameter) placed inside the patient beam‐defining collimator (cutout). Its design process determines a desirable intensity‐modulated electron beam during the planning process, then determines the island block configuration to deliver that intensity distribution (segmentation). The intensity modulator is fabricated and quality assurance performed at the factory (.decimal, LLC, Sanford, FL). Clinical quality assurance consists of measuring a fluence distribution in a plane perpendicular to the beam in a water or water‐equivalent phantom. This IM‐BECT process is described and demonstrated for two sites, postmastectomy chest wall and temple. Dose plans, intensity distributions, fabricated intensity modulators, and quality assurance results are presented.ResultsIM‐BECT plans showed improved D90‐10 over BECT plans, 6.4% versus 7.3% and 8.4% versus 11.0% for the postmastectomy chest wall and temple, respectively. Their intensity modulators utilized 61 (single diameter) and 246 (five diameters) tungsten pins, respectively. Dose comparisons for clinical quality assurance showed that for doses greater than 10%, measured agreed with calculated dose within 3% or 0.3 cm distance‐to‐agreement (DTA) for 99.9% and 100% of points, respectively.ConclusionThese results demonstrated the feasibility of translating IM‐BECT to the clinic using the techniques presented for treatment planning, intensity modulator design and fabrication, and quality assurance processes.

Fragmentation of a Monoclonal Antibody by Peroxotungstate.

Tungsten and tungsten oxide leachates found in glass pre-filled syringes were identified to initiate protein precipitation and aggregation. Here, we tested the possibility of tungsten and tungsten oxide to induce the chemical degradation of proteins via reaction with hydrogen peroxide, a possible impurity present in protein formulations, to yield peroxotungstate. A monoclonal antibody (mAb) was incubated with various concentrations of peroxotungstate and the reaction mixtures analyzed by SDS-PAGE and mass spectrometry. Exposure of a mAb to 1.07-1070ppm peroxotungstate (based on tungsten content) at temperatures of 4°C and 22°C (pH5-7) induced protein fragmentation. The extent of fragmentation increased with higher temperatures, lower pH and higher peroxotungstate concentrations. The mAb fragments were identified to contain different combinations of heavy chains (H) and light chains (L). Analogous mAb fragments were generated when the protein was exposed to H2O2 and orthotungstate at levels as low as 5ppm. In addition, extracts from tungsten pins used to manufacture glass pre-filled syringes, in combination with H2O2 caused comparable fragmentation of the mAb. Mass spectrometric identification of the fragments suggests fragment generation by oxidativedisulfide bond cleavage between the heavy and light chains, confirmed by mass spectrometry data on product formation. The mechanism of oxidative fragmentation was separately confirmed with insulin. Fragmentation of the mAb by peroxotungstate is proposed to occur through inter-chain disulfide bond oxidation to form thiosulfinate (CyS(═O)SCy) and thiosulfonate [CyS(═O)2SCy], followed by hydrolysis.

Testing of the SARAF tungsten pin beam dump

A new version of a beam dump was tested at SARAF Phase I. The beam dump consisted of a grid of tungsten pins welded to water-cool copper backing. The beam-induced heat was dissipated mainly through thermal radiation with a smaller amount via thermal conductance. Beam rastering was performed for better control of the irradiated area and beam density. A test irradiation using a 4 kW protons beam power demonstrated that the current design could readily accept average 300 W/cm2 beam power density while achieving low prompt and residual radiation levels with no blistering damage. Local melting of pins was observed at beam power density of 800 W/cm2. The results of the irradiation test are presented and analyzed and the plans for future improvements are discussed.

Zebrafish In Situ Spinal Cord Preparation for Electrophysiological Recordings from Spinal Sensory and Motor Neurons.

Zebrafish, first introduced as a developmental model, have gained popularity in many other fields. The ease of rearing large numbers of rapidly developing organisms, combined with the embryonic optical clarity, served as initial compelling attributes of this model. Over the past two decades, the success of this model has been further propelled by its amenability to large-scale mutagenesis screens and by the ease of transgenesis. More recently, gene-editing approaches have extended the power of the model. For neurodevelopmental studies, the zebrafish embryo and larva provide a model to which multiple methods can be applied. Here, we focus on methods that allow the study of an essential property of neurons, electrical excitability. Our preparation for the electrophysiological study of zebrafish spinal neurons involves the use of veterinarian suture glue to secure the preparation to a recording chamber. Alternative methods for recording from zebrafish embryos and larvae involve the attachment of the preparation to the chamber using a fine tungsten pin1,2,3,4,5. A tungsten pin is most often used to mount the preparation in a lateral orientation, although it has been used to mount larvae dorsal-side up4. The suture glue has been used to mount embryos and larvae in both orientations. Using the glue, a minimal dissection can be performed, allowing access to spinal neurons without the use of an enzymatic treatment, thereby avoiding any resultant damage. However, for larvae, it is necessary to apply a brief enzyme treatment to remove the muscle tissue surrounding the spinal cord. The methods described here have been used to study the intrinsic electrical properties of motor neurons, interneurons, and sensory neurons at several developmental stages6,7,8,9.

Sub-nanosecond time resolved light emission study for diffuse discharges in air under steep high voltage pulses

Pin-to-plane discharges in centimetre air gaps and standard conditions of pressure and temperature are generated under very high positive nanosecond scale voltage pulses. The experimental study is based on recordings of sub-nanosecond time resolved and Abel-processed light emission profiles and their complete correlation to electrical current waveforms. The effects of the voltage pulse features (amplitude between 20 and 90 kV, rise time between 2 and 5.2 ns, and time rate between 4 and 40 kV · ns−1) and the electrode configuration (gap distance between 10 and 30 mm, pin radius between 10 and 200 µm, copper, molybdenum or tungsten pin material) are described. A three time period development can be found: a glow-like structure with monotonic light profiles during the first 1.5 ns whose size depends on time voltage rate, a shell-like structure with bimodal profiles whose duration and extension in space depends on rise time, and either diffuse or multi-channel regime for the connection to the cathode plane according to gap distance. The transition of the light from monotonic to bimodal patterns reveals the relative effects and dynamics of streamer space charge and external laplacian field. A classical 2D-fluid model for streamer propagation has been used and adapted for very high and steep voltage pulses. It shows the formation of a strong space charge (streamer) very close to the pin, but also a continuity of emission between the pin and the streamer, and electric fields higher than the critical ionization field (28 kV · cm−1 in air) almost in the whole gap and very early in the discharge propagation.

Spatial Characteristics of Contact Pin-Printed Silanes and Bioconjugates on Oxidized Porous Silicon

Porous silicon (pSi) exhibits strong, visible photoluminescence (PL) at room temperature. To stabilize the pSi PL and simultaneously impart chemical functionality we oxidize pSi (ox-pSi) and then contact pin-print organically modified silanes onto the ox-pSi surface. This strategy allows rapid microarray production for numerous applications; however, spot size and chemical homogeneity across the spot are crucial factors controlling microarray spot density and utility. In this article we used a 200 μm diameter solid tungsten pin to contact pin-print 3-aminopropyltriethoxysilane (APTES-) and butyraldehydetriethoxysilane (BATES-) derived spots onto ox-pSi and then used PL and Fourier transform infrared spectroscopy (FT-IR) imaging to characterize the spot size, shape, and spatial homogeneity. The APTES-derived spots formed >30× faster and spread ∼15% further in comparison to BATES-derived spots; however, the majority of feature spreading is attributed to an oxidized, silane-free halo, which surrounds the sil...

염류용액 방전의 온도 측정에 관한 연구

In this study, electrical and spectroscopic characteristics were investigated in the pin to plate discharge of 0.9% weight per unit volume saline solution. The positive and positive- and negative-going dc pulse with 5% duty ratio were applied to tungsten pin electrode. The more amount of discharge current flew in negative discharge. The temperature, which is considered as a local value in the vicinity of vapor of discharge, was about 3,000K which is much higher than the value recommended to be controlled. It can be suggested that not only the temperature of liquid but also the local temperature of vapor is monitored to investigate damages on tissue or cells in biological application.

Characterization of Protein Aggregating Tungstates: Electrospray Mass Spectrometry Analysis of Extracts from Prefilled Syringes and from Tungsten Pins Used in the Manufacture of Syringes.

Glass prefilled syringes are increasingly becoming a container of choice for storing and administering therapeutic protein products to patients. Tungsten leaching from a PFS is known to induce protein particle formation, and the source was traced to the tungsten pins used in the manufacturing process of the syringe barrels. Study of the tungstates present in extracts from both tungsten pins used in the syringe manufacturing process and from single syringes from various suppliers was undertaken. Electrospray mass spectrometry was chosen as a technique with the sensitivity to characterize tungstates at levels (∼1 ppm of elemental tungsten) observed in single syringes. Extraction solvents were chosen to simulate the range (pH 4.0-7.0) typically used for therapeutic protein formulation. A commercial product formulation buffer was also used as an extraction solution to characterize tungstate species used for tungsten spiking studies of protein. All pin and syringe extracts from various manufacturers were similar in regards to containing stable Na/K containing lacunary polytungstate ([W11O39](7-)) species, which were the main species present in syringe extracts and are different than the metatungstate ([W12O39](6-)) species identified in commercially available sodium polytungstate and as the main species in pin extracts. These stable Na/K containing polytungstates species present in pin and syringe extracts are likely formed during the glass manufacturing process at >400 °C and may have the capability to subsequently form larger polytungstate complexes. Glass prefilled syringes are a type of container used for storing and administering biotechnology medicines to patients. The manufacturing process for the syringes may lead to very low levels of the metal tungsten being present in the syringes, and thus in the medicine stored in the syringes. The presence of tungsten in certain biotechnology medicines has been shown to cause changes to the medicine. Understanding something that can cause a medicine to change is an important part of producing safe and effective medicines for patients. The study described in this article sought to increase understanding by characterizing the form of tungsten observed in syringes from a number of vendors. Study of the tungsten present in syringes from four vendors indicates the same form of tungsten is observed regardless of the vendor. The study also found that the form of tungsten differed from that expected.

Behavior of Current Flow on Lead Zirconate Titanate Surfaces during Mechanical Impact

A new mechanical stress detection technique, based on current flow at Lead Zirconium Titanate (PZT) surfaces, is described in this paper. The current flow properties of PZT were characterized by use of a tungsten indenter. The tungsten indenter was dropped from a certain height and caused mechanical impact at the PZT-sample. The tungsten pin achieved direct contact with the upper surface of the ferroelectric specimen during the impact. This procedure allowed measurements of electrical current that flew between the PZT-surface and the tungsten pin. It was shown that ferroelectric domain switching on PZT surface and plastic deformation generates this current flow during action of loading force. The current flow disappeared in a few microseconds after removal of the loading force. The measurements were carried out using different areas of force application on the PZT surface. The mechanical stress, induced by the collision, was transmitted through the sample and generated also a measureable dipole moment. In this way it was shown that PZT exhibits high sensitivity against mechanical stress by means of electrical current flow, compared to typical dipole moment measurements. This specific material property of PZT-ceramics can be used for new mechanical stress sensor designs with higher sensitivity as normal used bulky PZT-sensors.

The spatial and temporal development of ionization waves along one dielectric tube

Atmospheric pressure plasma bullets or ionization waves have been generated in one long (Φ 2 mm × 100 mm) dielectric tube filled with He gas when a sinusoidal AC high-voltage with its fre- quencies of 9.0 kHz is applied between the tungsten pin electrodes. ICCD measurements show that the propagation of ionization waves in I, U and O tubes is anode-driven electrically, and the spatial and tem- poral development of ionization waves is strongly dependent on the He flow rate and applied voltage. Three stages are clearly observed during the propagation of ionization waves along the tube, and their propagation process is discussed based on the experimental results. The generation and propagation of ionization waves in the tube are affected by many physical processes, such as the drift motion of He + ions or excited species, the distribution of plasma potential along the dielectric tube, the surface recombination of charged species, He + -induced electron emission from the pin cathode, and so on.

Optimization of Parameters for Diameter Accuracy in Wire Electric Discharge Grinding for Micro Machining of Tungsten Rods

In this study the process of Wire Electric Discharge Grinding was carried out with a precise, flexible and corrosion resistant submerged rotary spindle which was designed, fabricated and installed in a five axis CNC Wire Electric Discharge Machining in order to produce free form surfaces on micro rods. The tungsten was taken as a work material since it is hard to machine through conventional process. Based on the literature survey the following four factors such as the spindle speed, pulse off time, peak current and wire speed are considered for obtaining high diametrical accuracy. By Taguchi parametric design the array was designed and experimental trials were taken by machining an Ø2.0mm tungsten (W) pin to Ø0.40mm under various set of parameter combinations. The S/N ratio analysis was carried out to find the optimum machining parameters and significant parameters affecting the diametrical accuracy. The analysis of variance was used to analytically verify the significant parameters. Finally it is concluded experimentally and statically that the significant parameters affecting the diameter accuracy are spindle speed and pulse off time.

First results of KALI-30 GW with 1 MV flash X-rays generation and characterization by Imaging plate

The design, development and commissioning of 1 MV pulsed electron accelerator producing Flash X-Rays is described in this paper. This pulsed power system is based on bipolar MARX generator and Blumlein followed by Explosive electron emission diode assembly. The peak pulsed power is ∼ 30 GW. The electron energies in the range of 400 keV to 1030 keV are produced and delivered to experimental load of Industrial diode. Electrons are emitted from a stainless steel ring at ground potential by explosive field emission and bombard the anode tungsten pin for flash X-rays generation. The relativistic electron beam has been simulated within the diode chamber and pattern shows the beam propagation. Imaging plates are used to characterize the source size and optimization has been reported.

Functionality of dielectrophoretically immobilized enzyme molecules

The enzyme horseradish peroxidase has been immobilized on nanoelectrode arrays by alternating current dielectrophoresis (DEP). Preservation of its enzymatic function after field application was demonstrated by oxidizing dihydrorhodamine 123 with hydrogen peroxide as co-oxidant to create its fluorescent form, rhodamine 123 (Rh123). Localization of the fluorescently labeled enzyme and its product was conducted by fluorescence microscopy. Nanoelectrodes were prepared as tungsten pins arranged in square arrays. Experimental parameters for dielectrophoretic immobilization were optimized for even enzyme distribution and for enzymatic efficiency. Enzyme activity was quantified by determination of fluorescence intensities of immobilized enzyme molecules and of Rh123 produced. These results demonstrate that DEP can be applied to immobilize enzyme molecules while retaining their activity and rendering any chemical modifications unnecessary. This introduces a novel way for the preparation of bioactive surfaces for processes such as biosensing.

Following nature's challenges

Following nature's challenges

Tungsten-Induced Denaturation and Aggregation of Epoetin Alfa During Primary Packaging as a Cause of Immunogenicity

PurposeFollowing two cases of neutralizing antibodies to epoetin alfa in an investigational clinical study, a small number of individual syringes of two drug product batches were found to contain unusually high levels of aggregation at the end of the clinical trial.MethodsWe undertook an extensive analytical approach to determine the root-cause of the increased aggregation in the affected batches.ResultsSoluble tungsten was found in the syringes, most likely derived from the pins used to manufacture the syringes. Spiking of epoetin alfa with sodium polytungstate or an extract of tungsten pins used to manufacture the syringes induced the formation of aggregates, both dimers that appeared to be covalently linked by disulphide bonds as well as higher-order aggregates. Sodium polytungstate had also a strong denaturing effect on the protein.ConclusionsWe propose tungsten-mediated unfolding and aggregation of epoetin alfa in pre-filled syringes as a potential root cause for increased immunogenicity. This finding may be more broadly applicable to this and other classes of therapeutic proteins.

Synthesis and characterization of W reinforced carbon coatings produced by Combined Magnetron Sputtering and Ion Implantation technique

W-containing carbon coatings were deposited on plain carbon steel and titanium substrates by Combined Magnetron Sputtering and Ion Implantation (CMSII) technique. A target made of fine grain graphite with cylindrical tungsten pins mounted in the area of maximum sputtering rate was used. High voltage pulses (− 30 kV, 20 μs, and 25 Hz) were superposed over the DC bias. By adjusting the processing parameters nanocomposite nc-WC 1 − x /a-C coatings with a W content from 20 to 45 at.%, with a hardness of 12–22 GPa and a friction coefficient in the range of 0.12–0.22 were produced. These coatings have a thickness of 10–13 μm, good wear resistance and a good thermal stability up to 673 K.

Striation and plasma bullet propagation in an atmospheric pressure plasma jet

An atmospheric pressure plasma jet source driven by pulsed wave of several tens of kilohertz and by sinusoidal wave was designed and characterized. A newly designed jet consists of a sharpened tungsten pin electrode covered with a cone type Teflon layer confined in a Pyrex tube. This structure provides an efficient ignition since the electric field is concentrated on the end of electrode. Using the electrical and optical characterization, the properties of plasma bullet were explored. For the Ar plasma jet driven by a pulsed wave at low duty cycles, the volume, the speed, and the luminosity of the plasma bullet became larger, and the striation behavior was observed.

Investigations on the Effects of the Tool Material, Geometry, and Tilt Angle on Friction Stir Welding of Pure Titanium

Friction stir welding (FSW) parameters, such as tool material, tool geometry, tilt angle, tool rotational speed, welding speed, and axial force play a major role in the weld quality of titanium alloys. Because of excessive erosion, tool material and geometry play the main roles in FSW of titanium alloys. Therefore, in the present work for the first time, tool material and geometry, tool tilt angle, cooling system and shielding gas effects on macrostructure, microstructure, and mechanical properties of pure titanium weld joint were investigated. Result of this research shows that Ti can be joined by the FSW, using a tool with a shoulder made of tungsten (W) and simple pin made of tungsten carbide (WC). The best conditions for welding were use of compressed air as a cooling system, tool tilt angle of 1°, and a stream of Argon as a shielding medium. Investigation on mechanical properties shows that the tensile strength and the yield strength of the welded joint in the best case could be similar to the corresponding strengths of the base metal.