Development of RADFET detector for personal dosimeter system for European astronauts

Radiation environment in space is very complex, with varying contributions from photons, electrons, protons, and heavy ions. There is a need to measure radiation dose received by the astronauts onboard International Space Station (ISS), and the European Space Agency (ESA) has been supporting a collaborative research project aimed at development of a personal dosimeter for European astronauts at ISS. The development of the personal dosimeter system is in the final phase, with the launch expected in the second half of 2015. The system is called “European Crew Personal Active Dosimeter (EuCPAD)” and consists of a base unit and several mobile units. Base unit is stationery and houses system electronics, Tissue Equivalent Proportional Counter (TEPC), and charging slots for mobile units. Mobile units are worn by the astronauts during their daily activities and consist of four dosimetric modules: thin silicon diode, thick silicon diode, Direct Ion Storage (DIS) dosimeter, and Radiation Sensing Field Effect Transistor (RADFET). We describe the EuCPAD system and our efforts in development of the RADFET module for the EuCPAD mobile unit.Third International Conferenceon Radiation and Applications in Various Fields of Research, RAD 2015, June8-12, 2015, Budva, Montenegr

Sensitivity of standard and stacked RADFET dosimeters

Radiation Sensing Field Effect Transistors (RADFETs), also known as MOSFET dosimeters, are discrete p-channel MOSFETs with the gate oxide engineered for increased radiation sensitivity. RADFETs are small, require very little or no power during operation, read-out is simple and non-destructive, and their electronic signal is suitable for integration with the electronics systems. For these reasons RADFETs have found applications in quality assurance of radiotherapy, dose monitoring in high energy physics laboratories, accidental personal dosimetry, and space. Lower dose applications, such as e.g. occupational personal dosimetry and radiology, are currently out of reach owing to inherent sensitivity limits of the standard RADFET technology. Tyndall National Institute has been involved in RADFET research and development, fabrication, and commercialisation for several decades and has acquired significant experience in the technology and applications. This paper presents Tyndall recent efforts in RADFET manufacturing and characterisation for different applications and discusses possible approaches towards increased sensitivity of the technology, including standard and stacked RADFETs.Fourth International Conferenceon Radiation and Applications in Various Fields of Research, RAD 2016, May 23-27, 2016, Niš, Serbi

An improved RADFET-based module with an extended dose range of 1 kGy TID based on COTS parts

An improved RADFET based module dosemeter has been developed by Varadis (a spin out company of Tyndall National Institute in Cork, Ireland) with serial number RM-VT01-A. The module is based on commercially available, commercial-off-the-shelf (COTS) parts and represents an updated version of its predecessor RM-VT01 with an upper dose limit of 10Gy (1 kRad) also based on COTS parts. The RM-VT01-A module was tested to a total dose of 1kGy (100 kRad) in Co60 field at Vinča Institute of Nuclear Sciences, Belgrade, Serbia. The improved module circuit was specifically designed to address the challenge of withstanding 1 kGy (100 kRad) received dose. The primary goal of this poster is to present the improvements in the circuit design and working principle. For this purpose, eleven modules were tested, 8 powered and 3 unpowered during irradiation. The module electronics accommodates both irradiation “sense” and readout “single-current-point” mode, outputting the RADFET threshold voltage (VT) as a dosimetric information, directly proportional to the absorbed dose. The output voltage of the module was measured with a simple benchtop voltmeter to demonstrate module operation simplicity and easy system integrability. The experimental data results showed excellent agreement with the dosimetry system used at the Vinca irradiation facility, and calibration data of the VT01 RadFET part.ELICSIR Project Symposium; January 25-27, 2023, Niš, Serbi

Atypical antipsychotic clozapine binds fibrinogen and affects fibrin formation

Clozapine is an atypical antipsychotic used for the treatment of schizophrenia. The prescribed target daily doses may reach 900 mg. Literature studies report a connection between clozapine usage and thrombosis development. Our in vitro study aimed to provide insight into molecular bases of this observation, investigating clozapine binding to fibrinogen, the main plasma protein involved in hemostasis. Fibrinogen/clozapine interaction was confirmed by protein fluorescence quenching, with an affinity constant of 1.7 × 105 M−1. Direct interactions did not affect the structure of fibrinogen, nor fibrinogen melting temperature. Clozapine binding affected fibrin formation by reducing coagulation speed and thickness of fibrin fibers suggesting that in the presence of clozapine, fibrinogen may acquire thrombogenic characteristics. Although no difference in fibrin gel porosity was detected, other factors present in the blood may act synergistically with altered fibrin formation to modify fibrin clot, thus increasing the risk for development of thrombosis in patients on clozapine treatment. ORAC and HORAC assays showed that clozapine reduced free radical-induced oxidation of fibrinogen. All observed effects of clozapine on fibrinogen are dose-dependent, with the effect on fibrin formation being more pronounced.This is the peer-reviewed version of the article: Gligorijević, N.; Vasović, T.; Lević, S. M.; Miljević, Č.; Nedić, O.; Nikolić, M. Atypical Antipsychotic Clozapine Binds Fibrinogen and Affects Fibrin Formation. International Journal of Biological Macromolecules 2020, 154, 142–149. [https://doi.org/10.1016/j.ijbiomac.2020.03.119

Antipsychotic clozapine binds catalase and preserves its activity in oxidative environment

Oxidative stress undoubtedly accompanies mental disorders, and the pleiotropic effects of atypical antipsychotics, recommended drugs in the treatment of psychosis, are not clarified at the molecular level. Catalase is one of the key enzymes of the primary antioxidant protection system. This work studied the binding of second-generation antipsychotic drug Clozapine to commercial bovine liver catalase. Using various spectroscopic methods under simulated physiological conditions, we found moderate binding affinity of clozapine for catalase (Ka ~ 2x105 M-1), the binding influenced the secondary and tertiary structure of protein (according to UV-VIS and CD spectroscopy) and it managed to slightly increase its thermal stability. In AAPH induced oxidation experiments, we found that clozapine efficiently protects catalase from free-radicals oxidation and preserves its activity. Clozapine affects catalase activity in dose dependant manner, having no significant effect at lower concentrations but significantly inhibiting enzyme at saturating concentrations. In conclusion, our results indicate that the effect of direct binding of clozapine to catalase can be both beneficial and harmful and that this effect is dose dependent.The Biochemistry Global Summit, 25th IUBMB Congress, 46th FEBS Congress, 15th PABMB Congress, July 9-14, 2022, Lisbon, Portuga

Comprehensive characterisation of Tyndall National Institute RADFETs for commercial applications in various fields

Radiation Sensing Field Effect Transistors (RADFETs), also known as MOSFET dosimeters or pMOS dosimeters, have found applications in space, high-energy physics laboratories, and radiotherapy clinics. The RADFET is a discrete p-channel MOSFET with a thick gate oxide (typically from 100 nm to over 1 µm), optimised for radiation sensitivity. Radiation induces charges in the gate oxide, which cause the shift of the threshold voltage proportional to the radiation dose. The main good features of the RADFET are small size, simple/immediate/non-destructive read-out, electronic signal, and small cost when produced in volume. The main shortcoming is limited sensitivity, which precludes the use of standard RADFET designs in applications requiring minimum detectable dose lower than approx. 1 cGy. Tyndall National Institute has been developing RADFETs for almost three decades. The technology has recently been transferred to a start-up company Varadis. We present results of electrical and radiation characterisation steps done on Varadis commercial RADFET products. We discuss critical issues in relation to the optimum use of RADFETs and possible methods for lowering the minimum detectable dose.RAP 2019 : International conference on radiation applications; Proceedings book; September 16-19, 2019, Belgrad

Mean field approximation for noisy delay coupled excitable neurons

Mean field approximation of a large collection of FitzHugh-Nagumo excitable neurons with noise and all-to-all coupling with explicit time-delays, modelled by $N\gg 1$ stochastic delay-differential equations is derived. The resulting approximation contains only two deterministic delay-differential equations but provides excellent predictions concerning the stability and bifurcations of the averaged global variables of the exact large system.Comment: 15 pages, 3 figure

Atypical antipsychotic clozapine binds fibrinogen and affects fibrin formation

Clozapine is an atypical antipsychotic used for the treatment of schizophrenia. Prescribed daily doses of clozapine may reach over 900 mg/day. Some studies reported a connection between clozapine usage and the development of thrombosis. Our in vitro study aimed to provide insight into molecular bases of this observation, investigating clozapine binding to isolated fibrinogen, the main protein involved in hemostasis. Fibrinogen/clozapine interaction was confirmed by protein fluorescence quenching, with affinity constant calculated to be 1.7 9 105 M1 and the number of binding sites more than one. Direct interactions do not affect the structure of fibrinogen, as determined by UV-VIS spectrometry and Fourier-transform infrared spectroscopy, nor fibrinogen melting temperature, examined by fluorescence spectroscopy. However, clozapine binding affected fibrin formation, by reducing coagulation speed and thickness of fibrin fibers. This behavior suggests that in the presence of clozapine, fibrinogen may acquire thrombogenic characteristics. Although no difference in fibrin gel porosity was detected, other factors present in the blood may act synergistically with altered fibrin formation to modify fibrin clot, thus increasing the risk for development of thrombosis in individuals on clozapine treatment. By ORAC and HORAC antioxidant assays, we found that clozapine efficiently protects fibrinogen from free-radicals oxidation. Since the effect of clozapine on fibrin formation is dose-dependent, it seems that the dosage of the medication could be the main factor that determines if clozapine will have a more positive or negative effect on fibrinogen and coagulation process in vivo

A Metal Oxide Semiconductor ionizing radiation detector architecture with increased voltage sensitivity

A Metal Oxide Semiconductor (MOS) ionizing radiation detector architecture which senses trapped charge in the dielectric due to incident ionizing radiation is presented. The detector architecture increases output voltage signal as a function of trapped charge in the sensing dielectric in comparison with state of the art MOSFET (RADFET) technology. Numerical simulations were employed to help develop the device concept. It is shown that an improved voltage sensitivity is possible due to a reduction in the sensing capacitance which, unlike RADFET technology, is decoupled from the dielectric capacitance. An initial prototype of the detector has been fabricated in the silicon fabrication facility of Tyndall National Institute and irradiation experiments have been performed which confirm the improved voltage sensitivity versus commercial RADFET detectors. It is envisaged that further sensitivity increases may be possible by integrating dielectrics other than silicon dioxide.X JUBILEE International Conference on Radiation in Various Fields of Research : RAD 2022 (Spring Edition) : book of abstracts; June 13-17, 2022; Herceg Novi, Montenegr

Supplementary data for the article: Šunderić, M.; Vasović, T.; Milčić, M.; Miljević, Č.; Nedić, O.; Nikolić, M. R.; Gligorijević, N. Antipsychotic Clozapine Binding to Alpha-2-Macroglobulin Protects Interacting Partners against Oxidation and Preserves the Anti-Proteinase Activity of the Protein. International Journal of Biological Macromolecules 2021, 183, 502–512. https://doi.org/10.1016/j.ijbiomac.2021.04.155.

Supplementary material for: [https://doi.org/10.1016/j.ijbiomac.2021.04.155]Related to published version: [https://cherry.chem.bg.ac.rs/handle/123456789/4538