Pulsed Ion Research Articles

Enhancing the cancer metastasis diagnosis: Ultrasensitive nano sensors exploiting Cancer stem cell associated DNA methylation as a liquid biopsy marker

Cancer metastasis presents a significant clinical challenge due to its impact on patient survival rates. Early detection of metastasis is pivotal for effective intervention and improved patient outcomes. Liquid biopsy, a non-invasive diagnostic approach, holds promise for cancer detection, yet its utility in metastasis detection remains underexplored. Stable and accurate, DNA methylation reflects early tumor stages and enables molecular characterization, providing valuable longitudinal information. Despite its potential, clinical translation of DNA methylation biomarkers is limited, partially due to technology constraints and tumor heterogeneity. To enable clinical translation, an assay is needed that 1) quantifies DNA methylation, 2) integrates seamlessly into clinical workflows, and 3) ensures accuracy and sensitivity. In this study, we introduce an ultrasensitive nanosensor, Methylprobe, for DNA methylation-based liquid biopsy of metastasis. Methylprobe, synthesized via ultrashort pulsed ionization, provides signal amplification, enabling direct detection of methylated DNA in plasma. The technology is scalable and adaptable for clinical settings. The assay comprises the Methylprobe, metastasis-specific biomarkers, and a machine-learning algorithm. Tumor heterogeneity is addressed by integrating DNA-methylation signatures from distinct cancer stem cell phenotypes, enhancing assay reliability. The Methylprobe assay is validated on breast, lung, and colorectal cancer samples, demonstrating 99.8% accuracy in metastasis detection. This innovative approach offers potential as a reliable, sensitive, and accurate platform for assessing metastasis-associated DNA methylation patterns in blood plasma. Integrating Methylprobe into clinical practice could revolutionize metastasis detection, providing comprehensive insights into metastatic phenotypes and informing tailored therapeutic strategies.

Simulation of radon detection efficiency with small pulse ionization chamber based on Geant4

Radon measurement is crucial in assessing the damage to the human body caused by natural radiation. Pulsed ionization chambers are effective for real-time radon measurement and have widespread applications in other radiation techniques. However, due to practical constraints such as limited space and portability concerns, it becomes imperative to consider not only the detection efficiency but also their ease of transportation. This work utilizes the Geant4 Monte Carlo simulation toolkit to characterize the detection models of small cylindrical and flat plate-type pulsed ionization chambers, and carry out a simulation study to analyze the three crucial factors that influence detection efficiency, including the geometry of the chamber, electrode size, and operating temperature. The results indicate that the cylindrical pulse ionization chamber, with a length of 8 cm and radius of 2 cm, has the best detection efficiency and portability in terms of geometric dimensions, achieving a detection efficiency of (58 ± 4)%. Meanwhile, the flat plate pulse ionization chamber, with dimensions of 7 cm in length and 3 cm in width, achieves the best detection efficiency and portability, with a detection efficiency of (54 ± 3)%. In terms of electrode wire size, the cylindrical ionization chamber electrode wire with a length of 7 cm and a radius of 2.5 mm was optimal with a detection efficiency of (59 ± 4)%. In terms of operating temperature, the detection efficiency of the flat-plate pulsed ionization chamber was the highest at 30 °C, which was (58 ± 4)%, and that of the cylindrical pulsed ionization chamber was the highest at 20 °C, which was (63 ± 4)%. By analyzing the influencing factors of the detection efficiency of the pulsed ionization chamber, it has a certain reference value and guiding significance for the research and design of small pulsed ionization chamber detectors for radon measuring instruments.

Ultrashort Ne+ ion pulses for use in pump–probe experiments: numerical simulations

A time resolved experiment to investigate the ultrafast dynamics following an ion impact onto a solid surface requires an ultrashort ion pump pulse in combination with a properly synchronized and time resolved probe. In order to realize such an experiment, we have investigated a strategy to use femtosecond laser photoionization of atoms entrained in a pulsed supersonic jet for the production of sufficiently short ion pulses. While the generation of Arq+ ions was targeted in previous work, it has in the meantime been demonstrated that argon is not suitable due to extensive cluster formation in the supersonic expansion. Here, we therefore present numerical simulations investigating the use of neon as a precursor gas and show the feasibility of pulses containing up to ∼1000 Ne+ ions at keV energies and picosecond duration. In the process, we demonstrate that space charge broadening can be significantly reduced by detuning the flight time focusing conditions of an ion bunching system. Moreover, the results show that a controlled variation of the buncher geometry and potentials permits the generation of picosecond pulses at variable ion energy between 1 and 5 keV.

A Radio-Frequency Ion Trap System for the Multi-Reflection Time-of-Flight Mass Spectrometer at SHANS and Its Offline Commissioning

To precisely measure atomic masses and select neutron-deficient isotopes produced by fusion evaporation reactions, an MRTOF-MS (multi-reflection time-of-flight mass spectrometer) at the SHANS (Spectrometer for Heavy Atom and Nuclear Structure) is being developed. One of the key parts, an RF ion trap system with the aim to provide brilliant ion pulses with a low energy spread and narrow pulse width for ion preparation prior to injection into the MRTOF mass analyzer, has been constructed and commissioned offline successfully. The principle, construction details and test results are reported. Pulsed beams of 39K1+, 85,87Rb1+ and 133Cs1+ ions have been tested and the amplitudes and frequencies of the RF signals, DC voltages, helium gas pressure and time parameters have been scanned. The corresponding time spreads have reached 0.252 µs, 0.394 µs and 0.450 µs, respectively.

Attosecond Pulses from Ionization Injection Wakefield Accelerators

High-quality ionization injection methods for wakefield acceleration driven by lasers or charged beams (LWFA/PWFA) can be optimized so as to generate high-brightness electron beams with tuneable duration in the attosecond range. We present a model of the minimum bunch duration obtainable with low-emittance ionization injection schemes by spotting the roles of the ionization pulse duration, of the wakefield longitudinal shape and of the delay of the ionization pulse position with respect to the node of the accelerating field. The model is tested for the resonant multi-pulse ionization injection (ReMPI) scheme, showing that bunches having a length of about 300 as can be obtained with an ionization pulse having a duration of 30 fs FWHM.

Ionoacoustic monitoring of relativistic heavy ion beams

The performance of ionoacoustic detectors is investigated with respect to application of high-precision range and energy loss measurements for relativistic heavy ions. The technique is based on the generation of a pressure wave when a microsecond-pulsed relativistic ion beam is stopped in a water container. The acoustic signal from individual ion pulses is registered by a piezoelectric detector and analyzed in the time/frequency domain to identify the location of pressure wave generation. The experiments were performed at the SIS18 synchrotron at GSI Helmholtzzentrum (Darmstadt, Germany) with Xe, Pb and U ions of energies between 200 MeV/u and 1 GeV/u. We show that the signal amplitude of the acoustic pressure pulse has a linear correlation with the beam intensity within a range of at least 104 to 109 particles/spill.By determining the delay time of the primary and reflected acoustic signal in the water reservoir, the ionoacoustic technique provides information on ion ranges of 1 % accuracy. By an energy-range calibration in combination with a simulation code such as FLUKA, the range data can be used to determine the beam energy. As demonstrated, inserting targets of known thickness in front of the detector is a simple approach for measuring the energy loss of relativistic ions. The advantage of the ionoacoustic technique is the rather simple experimental setup, the huge dynamic range, the information available online by means of only a single pulse and its radiation hardness. Ionoacoustic detectors have great potential as intensity and energy monitor for short-pulsed light and heavy ion beams at existing or future high-energy ion facilities.

High-order harmonic generation, attosecond pulse, and non-sequential double ionization in the helium atom under high-intensity femtosecond laser pulses

High-order harmonic generation (HHG), attosecond pulse train (APT), isolated attosecond pulse (IAP), and non-sequential double ionization (NSDI) in the Helium atom under intense femtosecond laser pulses are computed using the time-dependent Schrodinger equation (TDSE) in one dimension (1D). By taking into account the electron–electron and electron-nucleus interactions, as well as determining the Helium atom’s ground state wave function through the imaginary time propagation (ITP) method, we are able to observe the widely recognized ‘knee structure’ in the ionization probability of the Helium atom as a function of intensity within an ionization boundary condition model. The results are in good agreement with the experimental data reported by (Walker et al (1994) Phys. Rev. Lett. 73, 1227).

Assessment of annual effective dose and health risk due to radon exposure in nurseries in the city of Poznań, Poland

The results of the scientific work presented in the World Health Organisation (WHO) report indicate that exposure to radon increases the risk of lung cancer in humans. In the past, radon concentrations of 400 Bq/m3 were considered dangerous, but today the level that poses a threat has been lowered to 100 Bq/m3. Children are particularly vulnerable to the effects of ionising radiation. In the article, the exposure of children to the effects of radon was evaluated on the basis of measurements in nurseries taken in the course of several months. A pulsed ionisation chamber with a passive diffusion sampling method was used for the measurements. The effective dose was assumed as the evaluation criterion. The research was carried out in selected rooms of two nurseries located in the city of Poznań in Poland. Similar profiles of variability in radon concentration (r = 0.88, p < 0.001) were observed in two different nurseries. The higher values of radon concentration in the rooms were found to be influenced by the low value of the wind speed. The experimental studies were supplemented with questionnaire studies, which showed that the average person's awareness of radioactivity is at a low level. The results of the effective dose level can be used to optimise future radon testing in buildings intended for various purposes.

Ion-to-Image, i2i, a Mass Spectrometry Imaging Data Analysis Platform for Continuous Ionization Techniques.

Mass spectrometry imaging (MSI) techniques generate data that reveal spatial distributions of molecules on a surface with high sensitivity and selectivity. However, processing large volumes of mass spectrometry data into useful ion images is not trivial. Furthermore, data from MSI techniques using continuous ionization sources where data are acquired in line scans require different data handling strategies compared to data collected from pulsed ionization sources where data are acquired in grids. In addition, for continuous ionization sources, the pixel dimensions are influenced by the mass spectrometer duty cycle, which, in turn, can be controlled by the automatic gain control (AGC) for each spectrum (pixel). Currently, there is a lack of data-handling software for MSI data generated with continuous ionization sources and AGC. Here, we present ion-to-image (i2i), which is a MATLAB-based application for MSI data acquired with continuous ionization sources, AGC, high resolution, and one or several scan filters. The source code and a compiled installer are available at https://github.com/LanekoffLab/i2i. The application includes both quantitative, targeted, and nontargeted data processing strategies and enables complex data sets to be processed in minutes. The i2i application has high flexibility for generating, processing, and exporting MSI data both from simple full scans and more complex scan functions interlacing MSn and SIM scan data sets, and we anticipate that it will become a valuable addition to the existing MSI software toolbox.

Effect of time-modulation bias on polysilicon gate etching

The etching characteristics were studied via time-modulation bias (bias pulsing) by varying the pulsing parameters. The etch profiles were verified using polysilicon gate structures with dense and isolated patterns. Ion energy was defined as the peak-to-peak voltage (V pp) controlled by the RF bias power. The durations of the on period and off period (off time) of bias pulsing were adjusted by the pulse frequency and duty cycle. Profile evolution was observed in the variations in V pp and off time. Increasing the ion energy induced vertical profiles of dense patterns and the tapered profiles of isolated patterns. Extending the off time of bias pulsing induced tapered profiles of dense patterns and vertical profiles of isolated patterns. These results indicated that increasing the ion energy and pulse off time simultaneously was the direction to achieve anisotropic etch profiles for both the isolated and dense patterns.

Site-specific sodiation of peptides studied by pulsed nanoelectrospray ionization

Metal ions play significant roles in biological systems. Although sodium ions play a key role in biological systems, site-specific interactions between sodium ions and protonated peptides and proteins have not been thoroughly explored. In this work, the time-dependent sodiation of protonated peptides was investigated by pulsed nanoelectrospray ionization. Mass spectra for aqueous mixtures of 5×10−6 M angiotensin II (A), bradykinin (B), and gramicidin S (G) were measured as a function of the high voltage (4000 V) pulse width (PW) with and without the application of a bias voltage (BV) to the solution. With BV = 0 V, only [B + 2H − H + Na]2+ was detected with an increase in PW from 220 μs (threshold for the signal appearance) to 1 ms. In contrast, [A + 2H − nH + nNa]2+ (n = 1–3) started to be detected with PW = 500 μs and up to n = 4 with PW = 1 ms. By the application of BV = 900 V, [B + 2H − nH + nNa]2+ with n = 0 and 1 started to be detected with PW = 40 μs. With further increase in PW up to 1 ms, [B + 2H − nH + nNa]2+ with n = 0–3 and [A + 2H − nH + nNa]2+ (n = 1–5) were detected. The observation of [B + 2H − 3H + 3Na]2+ and [A + 2H − 5H + 5Na]2+ with BV = 900 V suggests that carboxyl (−COOH), imidazole > N–H, hydroxyl (−OH) as well as amide > N–H bonds are deprotonated to form respective sodiated forms of carboxylate –COO−⋅⋅⋅⋅Na+, imidazole > N−⋅⋅⋅⋅Na+, hydroxyl –O−⋅⋅⋅⋅Na+ and amide –NC–O−⋅⋅⋅⋅Na+ bonds. Ions of G were totally suppressed by the presence of A and B in aqueous solution.

Ionization dynamics of sub-micrometer-sized clusters in intense ultrafast laser pulses

Sub-micrometer-sized targets are found in intense laser–cluster interaction experiments and laser-based material processing. Here, we investigate the internal field localization due to Mie scattering and its effect on ionization dynamics in sub-micrometer-sized clusters using Mie calculation and particle-in-cell simulations. As a result of intertwined processes of pulse propagation and ionization, sub-micrometer nanofocusing dominates at lower intensity and gives rise to an ionization hotspot at the rear of the targets while plasma shielding wins over at a higher intensity, stopping further rear side ionization. As ionization is often the precursor of other processes, understanding the ionization dynamics of ultrafast laser pulses with wavelength-sized nanostructure can be relevant for intense laser-cluster experiments and femtosecond laser micro-/nanomachining.

Dynamic Characteristics Determination of the Radiation Power Control System for the Industrial CO2 Laser Excited by а Nonself-Sustained Glow Discharge

In the article, an automatic system for radiation power control of lasers excited by а nonself-sustained glow discharge is studied using industrial lasers of the Lantan series as an example. They are designed for cutting, welding and surface modification of various materials as part of laser machines. The power of laser radiation is one of the most important parameters of a laser that determines its technological capabilities. The radiation power is controlled by changing the ionization pulses frequency of high voltage pulses with duration of 100 ns, given with a frequency of 1-5 kHz. The step response of the laser is experimentally obtained. Laser radiation is fed to a thermoelectric mirror-detector with thermo-EMF anisotropy, which measures its power. After preliminary amplification, the differential signal from the mirror-detector is recorded by a digital oscilloscope. A delay in the change in the laser radiation power relative to the control signal was established. The delay is 1487 ms that is explained by the fact that several ionization pulses are required for the initial exciting of the gas volume before the start of radiation generation. The initial section of the step response and damped oscillations are explained by the presence of a protective choke in the main discharge source connection circuit. The choke slows down the rise in current during the short circuit of discharge, allowing circuit breakers to turn off the power supply. To simulate the transient process, the step response of the oscillating circuit is used. The original signal was filtered to remove noise that does not al[1]low determining the parameters of the step response. To determine the spectrum of the step response, fast Fourier transform is carried out, frequencies introducing noise were cut out, and the inverse fast Fourier transform is performed. According to the step response obtained after filtering, the parameters of the modeling step response are determined. Based on the parameters of the step response, the laser transfer function is calculated. It makes possible to proceed to the calculation of the optimal radiation power controller, which ensures the best quality of the transient process.

Defect engineering of silicon with ion pulses from laser acceleration

Defect engineering is foundational to classical electronic device development and for emerging quantum devices. Here, we report on defect engineering of silicon with ion pulses from a laser accelerator in the laser intensity range of 1019 W cm−2 and ion flux levels of up to 1022 ions cm−2 s−1, about five orders of magnitude higher than conventional ion implanters. Low energy ions from plasma expansion of the laser-foil target are implanted near the surface and then diffuse into silicon samples locally pre-heated by high energy ions from the same laser-ion pulse. Silicon crystals exfoliate in the areas of highest energy deposition. Color centers, predominantly W and G-centers, form directly in response to ion pulses without a subsequent annealing step. We find that the linewidth of G-centers increases with high ion flux faster than the linewidth of W-centers, consistent with density functional theory calculations of their electronic structure. Intense ion pulses from a laser-accelerator drive materials far from equilibrium and enable direct local defect engineering and high flux doping of semiconductors.

GRASIAN: towards the first demonstration of gravitational quantum states of atoms with a cryogenic hydrogen beam

At very low energies, a light neutral particle above a horizontal surface can experience quantum reflection. The quantum reflection holds the particle against gravity and leads to gravitational quantum states (gqs). So far, gqs were only observed with neutrons as pioneered by Nesvizhevsky and his collaborators at ill. However, the existence of gqs is predicted also for atoms. The Grasian collaboration pursues the first observation and studies of gqs of atomic hydrogen. We propose to use atoms in order to exploit the fact that orders of magnitude larger fluxes compared to those of neutrons are available. Moreover, recently the q-Bounce collaboration, performing gqs spectroscopy with neutrons, reported a discrepancy between theoretical calculations and experiment which deserves further investigations. For this purpose, we set up a cryogenic hydrogen beam at 6 hbox {K}. We report on our preliminary results, characterizing the hydrogen beam with pulsed laser ionization diagnostics at 243 hbox {nm}.Graphical abstract

Target Density Effects on Charge Transfer of Laser-Accelerated Carbon Ions in Dense Plasma.

We report on charge state measurements of laser-accelerated carbon ions in the energy range of several MeV penetrating a dense partially ionized plasma. The plasma was generated by irradiation of a foam target with laser-induced hohlraum radiation in the soft x-ray regime. We use the tricellulose acetate (C_{9}H_{16}O_{8}) foam of 2 mg/cm^{3} density and 1mm interaction length as target material. This kind of plasma is advantageous for high-precision measurements, due to good uniformity and long lifetime compared to the ion pulse length and the interaction duration. We diagnose the plasma parameters to be T_{e}=17 eV and n_{e}=4×10^{20} cm^{-3}. We observe the average charge states passing through the plasma to be higher than those predicted by the commonly used semiempirical formula. Through solving the rate equations, we attribute the enhancement to the target density effects, which will increase the ionization rates on one hand and reduce the electron capture rates on the other hand. The underlying physics is actually the balancing of the lifetime of excited states versus the collisional frequency. In previous measurement with partially ionized plasma from gas discharge and z pinch to laser direct irradiation, no target density effects were ever demonstrated. For the first time, we are able to experimentally prove that target density effects start to play a significant role in plasma near the critical density of Nd-glass laser radiation. The finding is important for heavy ion beam driven high-energy-density physics and fast ignitions. The method provides a new approach to precisely address the beam-plasma interaction issues with high-intensity short-pulse lasers in dense plasma regimes.

Portable Iontophoresis Device for Efficient Drug Delivery.

The timely delivery of drugs to specific locations in the body is imperative to ensure the efficacy of treatment. This study introduces a portable facial device that can deliver drugs efficiently using iontophoresis. Two types of power supplies-direct current and pulse ionization supplies-were manufactured by injection molding. Electrical stimulation elements, which contained Ag metal wires, were woven into facial mask packs. The diffusion phenomenon in the skin and iontophoresis were numerically modeled. Injection molding was simulated before the device was manufactured. Analysis using rhodamine B demonstrated a remarkable increase in the moisture content of the skin and effective absorption of the drug under an applied electric field upon the application of iontophoresis. The proposed concept and design constitute a new method of achieving effective drug absorption with wearable devices.

Strong Coulomb coupling influences ion and neutral temperatures in atmospheric pressure plasmas

Molecular dynamics simulations are used to model ion and neutral temperature evolution in partially-ionized atmospheric pressure plasma at different ionization fractions. Results show that ion–ion interactions are strongly coupled at ionization fractions as low as 10−5 and that the temperature evolution is influenced by effects associated with the strong coupling. Specifically, disorder-induced heating is found to rapidly heat ions on a timescale of the ion plasma period (∼10 s ps) after an ionization pulse. This is followed by the collisional relaxation of ions and neutrals, which cools ions and heats neutrals on a longer (∼ns) timescale. Slight heating then occurs over a much longer (∼100 s ns) timescale due to ion-neutral three-body recombination. An analytic model of the temperature evolution is developed that agrees with the simulation results. A conclusion is that strong coupling effects are important in atmospheric pressure plasmas.

Development of electrostatic-induced charge detector for multiturn time-of-flight mass spectrometer.

We developed an autocorrelation function to resolve the overtaking problem in a multiturn time-of-flight mass spectrometer (TOF-MS). The function analyzes the characteristic period for one lap of each ion packet and derives a mass spectrum from a signal pulse train composed of multiturn ion packets. To detect the ion pulse train, a new nondestructive ion detector was developed and installed in the multiturn orbit of MULTUM-S II. This detector is composed of an electrostatically induced charge detector, a preamplifier, and a digitizer. The electrostatic noises are smaller than the single-ion signals owing to the accumulation of the multiturn TOF spectrum. The conventional ion detector of TOF-MS is operated after collecting the signal pulse train. The multiturn TOF spectrum was convolved with an autocorrelation function to derive the mass spectrum. The convolved mass spectrum performed a mass resolving power (MRP) of 28,200 at m/z 69 and mass accuracy of 28 ppm for the perfluorotributylamine (PFTBA) gas sample.

Synthesis of self-grown nanostructured NiO via pulse ionization for binderless psuedocapacitor electrode

In air laser irradiation was carried out onto Ni sheet with ultra-short, pulsed laser for direct synthesis of NiO thin layer. The layer consisted of 3D nanostructures with excellent porosity and enhanced surface area for the fabrication of pseudo capacitive electrodes. Mainly laser parameters such as scan speed and frequency were analyzed. It was observed that at lower scan speed, excellent surface area was achievable which during microscopy, the morphology of the structure depicted a “broccoli” like structure. The oxidized layer forms because of series of events at ultra-short duration associated with laser-material interaction in ambient conditions such as energy transfer, heating, melting, evaporation, ionization, plasma formation, rapid quenching, and oxide layer formation. The obtained oxide layer consists of 3D self-standing nanostructure with the active material directly growing on the substrate without the requirement of binder. A combined contribution of pseudo capacitance due to surface rapid, redox reactions along with ion adsorption-desorption because of EDL's presence provided remarkable performance. With this fabrication approach, NiO, a battery active material demonstrated fast charge-discharge capabilities evident from galvanostatic charge-discharge test. Owing to the idea of one step direct synthesis and green fabrication process, the performance of the electrode was remarkable. An areal capacitance of 98.682 mF cm−2 and specific capacity of 59.209 mC cm−2 was achievable at a current density of 1 mA cm−2. This work promotes the idea of green synthesis of nano morphology and one step fabrication method.