A compact scintillator-based detector with collimator and shielding for dose monitoring in boron neutron capture therapy.

Boron neutron capture therapy exploits 10B(n,α)7Li reactions for targeted tumor destruction. In this work, we aimed at developing a dose monitoring system based on the detection of 478 keV gamma rays emitted by the reactions, which is very challenging due to the severe background present. We investigated a compact gamma-ray detector with a pinhole collimator and shielding housing. Experimental nuclear reactor measurements involved varying boron concentrations and artificial shifts of the sources. The system successfully resolved the 478 keV photopeak and detected 1 cm lateral displacements, confirming its suitability for precise boron dose monitoring.

A Frequency-Switching Inductive Power Transfer System for Wireless, Miniaturised and Large-Scale Neural Interfaces.

Three-coil inductive power transfer is the state-of-the-art solution to power multiple miniaturised neural implants. However, the maximum delivered power is limited by the efficiency of the powering link and safety constrains. Here we propose a frequency-switching inductive link, where the passive resonator normally used in a three-coil link is replaced by an active resonator. It receives power from the external transmitter via a two-coil inductive link at the low frequency of 13.56 MHz. Then, it switches the operating frequency to the higher frequency of 433.92 MHz through a dedicated circuitry. Last, it transmits power to 1024 miniaturised implants via a three-coil inductive link using an array of 37 focusing resonators for a brain coverage of 163.84 mm 2. Our simulations reported a power transfer efficiency of 0.013 % and a maximum power delivered to the load of 1970 µW under safety-constrains, which are respectively two orders of magnitude and more than six decades higher compared to an equivalent passive three-coil link. The frequency-switching inductive system is a scalable and highly versatile solution for wireless, miniaturised and large-scale neural interfaces.

First experimental demonstration of real-time neutron capture discrimination in helium and carbon ion therapy.

This work provides the first experimental proof of an increased neutron capture photon signal following the introduction of boron to a PMMA phantom during helium and carbon ion therapies in Neutron Capture Enhanced Particle Therapy (NCEPT). NCEPT leverages [Formula: see text]B neutron capture, leading to the emission of detectable 478 keV photons. Experiments were performed at the Heavy Ion Medical Accelerator in Chiba, Japan, with two Poly(methyl methacrylate) (PMMA) targets, one bearing a boron insert. The BeNEdiCTE gamma-ray detector measured an increase in the 478 keV signal of 45 ± 7% and 26 ± 2% for carbon and helium ion irradiation, respectively. Our Geant4 Monte Carlo simulation model, developed to investigate photon origins, found less than 30% of detected photons originated from the insert, while boron in the detector's circuit boards contributed over 65%. Further, the model investigated detector sensitivity, establishing its capability to record a 10% increase in 478 keV photon detection at a target [Formula: see text]B concentration of 500 ppm using spectral windowing alone, and 25% when combined with temporal windowing. The linear response extended to concentrations up to 20,000 ppm. The increase in the signal in all evaluated cases confirm the potential of the proposed detector design for neutron capture quantification in NCEPT.

Potentialities of CdZnTe Quasi-Hemispherical Detectors for Hard X-ray Spectroscopy of Kaonic Atoms at the DAΦNE Collider.

Kaonic atom X-ray spectroscopy is a consolidated technique for investigations on the physics of strong kaon-nucleus/nucleon interaction. Several experiments have been conducted regarding the measurement of soft X-ray emission (<20 keV) from light kaonic atoms (hydrogen, deuterium, and helium). Currently, there have been new research activities within the framework of the SIDDHARTA-2 experiment and EXCALIBUR proposal focusing on performing precise and accurate measurements of hard X-rays (>20 keV) from intermediate kaonic atoms (carbon, aluminum, and sulfur). In this context, we investigated cadmium-zinc-telluride (CdZnTe or CZT) detectors, which have recently demonstrated high-resolution capabilities for hard X-ray and gamma-ray detection. A demonstrator prototype based on a new cadmium-zinc-telluride quasi-hemispherical detector and custom digital pulse processing electronics was developed. The detector covered a detection area of 1 cm2 with a single readout channel and interesting room-temperature performance with energy resolution of 4.4% (2.6 keV), 3% (3.7 keV), and 1.4% (9.3 keV) FWHM at 59.5, 122.1, and 662 keV, respectively. The results from X-ray measurements at the DAΦNE collider at the INFN National Laboratories of Frascati (Italy) are also presented with particular attention to the effects and rejection of electromagnetic and hadronic background.

Prompt-gamma fall-off estimation with C-ion irradiation at clinical energies, using a knife-edge slit camera: A Monte Carlo study.

PURPOSE: In-vivo range verification has been a hot topic in particle therapy since two decades. Many efforts have been done for proton therapy, while fewer studies were conducted considering a beam of carbon ions. In the present work, a simulation study was performed to show whether it is possible to measure the prompt-gamma fall-off inside the high neutron background typical of carbon-ion irradiation, using a knife-edge slit camera. In addition to this, we wanted to estimate the uncertainty in retrieving the particle range in the case of a pencil beam of C-ions at clinically relevant energy of 150 MeVu. METHODS: For these purposes, the Monte Carlo code FLUKA was adopted for simulations and three different analytical methods were implemented to get the accuracy in the range retrieval of the simulated set-up. RESULTS: The analysis of simulation data has brought to the promising and desired precision of about 4 mm in the determination of the dose profile fall-off in case of a spill irradiation, for which all the three cited methods were coherent in their predictions. CONCLUSIONS: The Prompt Gamma Imaging technique should be further studied as a tool to reduce range uncertainties affecting carbon ion radiation therapy.

A Pipe-Embeddable Impedance Sensor for Monitoring Water Leaks in Distribution Networks: Design and Validation.

Water leakage is one of main problems of distribution infrastructures, reaching unacceptable peaks of 50% of water lost in old networks in several countries. In order to address this challenge, we present an impedance sensor able to detect small water leaks (below 1 L of released volume). The combination of real-time sensing and such a sensitivity allows for early warning and fast response. It relies on a set of robust longitudinal electrodes applied on the external surface of the pipe. The presence of water in the surrounding medium alters its impedance in a detectable way. We report detailed numerical simulations for the optimization of electrode geometry and sensing frequency (2 MHz), as well as the successful experimental proof in the laboratory of this approach for a pipe length of 45 cm. Moreover, we experimentally tested the dependence of the detected signal on the leak volume, temperature, and morphology of the soil. Finally, differential sensing is proposed and validated as a solution to reject drifts and spurious impedance variations due to environmental effects.

Contactless Sensing of Water Properties for Smart Monitoring of Pipelines.

A key milestone for the pervasive diffusion of wireless sensing nodes for smart monitoring of water quality and quantity in distribution networks is the simplification of the installation of sensors. To address this aspect, we demonstrate how two basic contactless sensors, such as piezoelectric transducers and strip electrodes (in a longitudinal interdigitated configuration to sense impedance inside and outside of the pipe with potential for impedimetric leak detection), can be easily clamped on plastic pipes to enable the measurement of multiple parameters without contact with the fluid and, thus, preserving the integrity of the pipe. Here we report the measurement of water flow rate (up to 24 m3/s) and temperature with ultrasounds and of the pipe filling fraction (capacitance at 1 MHz with ~cm3 resolution) and ionic conductivity (resistance at 20 MHz from 700 to 1400 µS/cm) by means of impedance. The equivalent impedance model of the sensor is discussed in detail. Numerical finite-element simulations, carried out to optimize the sensing parameters such as the sensing frequency, confirm the lumped models and are matched by experimental results. In fact, a 6 m long, 30 L demonstration hydraulic loop was built to validate the sensors in realistic conditions (water speed of 1 m/s) monitoring a pipe segment of 0.45 m length and 90 mm diameter (one of the largest ever reported in the literature). Tradeoffs in sensors accuracy, deployment, and fabrication, for instance, adopting single-sided flexible PCBs as electrodes protected by Kapton on the external side and experimentally validated, are discussed as well.

Detection and discrimination of neutron capture events for NCEPT dose quantification.

Neutron Capture Enhanced Particle Therapy (NCEPT) boosts the effectiveness of particle therapy by capturing thermal neutrons produced by beam-target nuclear interactions in and around the treatment site, using tumour-specific [Formula: see text]B or [Formula: see text]Gd-based neutron capture agents. Neutron captures release high-LET secondary particles together with gamma photons with energies of 478 keV or one of several energies up to 7.94 MeV, for [Formula: see text]B and [Formula: see text]Gd, respectively. A key requirement for NCEPT's translation is the development of in vivo dosimetry techniques which can measure both the direct ion dose and the dose due to neutron capture. In this work, we report signatures which can be used to discriminate between photons resulting from neutron capture and those originating from other processes. A Geant4 Monte Carlo simulation study into timing and energy thresholds for discrimination of prompt gamma photons resulting from thermal neutron capture during NCEPT was conducted. Three simulated [Formula: see text] mm[Formula: see text] cubic PMMA targets were irradiated by [Formula: see text]He or [Formula: see text]C ion beams with a spread out Bragg peak (SOBP) depth range of 60 mm; one target is homogeneous while the others include [Formula: see text] mm[Formula: see text] neutron capture inserts (NCIs) of pure [Formula: see text]B or [Formula: see text]Gd located at the distal edge of the SOBP. The arrival times of photons and neutrons entering a simulated [Formula: see text] mm[Formula: see text] ideal detector were recorded. A temporal mask of 50-60 ns was found to be optimal for maximising the discrimination of the photons resulting from the neutron capture by boron and gadolinium. A range of candidate detector and thermal neutron shielding materials were simulated, and detections meeting the proposed acceptance criteria (i.e. falling within the target energy window and arriving 60 ns post beam-off) were classified as true or false positives, depending on their origin. The ratio of true/false positives ([Formula: see text]) was calculated; for targets with [Formula: see text]B and [Formula: see text]Gd NCIs, the detector materials which resulted in the highest [Formula: see text] were cadmium-shielded CdTe and boron-shielded LSO, respectively. The optimal irradiation period for both carbon and helium ions was 1 µs for the [Formula: see text]B NCI and 1 ms for the [Formula: see text]Gd NCI.

Handheld Magnetic-Compliant Gamma-Ray Spectrometer for Environmental Monitoring and Scrap Metal Screening.

Spotting radioactive material in waste is of paramount importance for environment protection. This is particularly challenging when orphan sources are hidden in scrap metal that shields their activity from the traditional detectors in the portals scanning incoming trucks. In order to address this issue, we present a wireless and compact SiPM-based gamma spectrometer compatible with strong magnetic fields (0.1 T) to be installed in the bore of the lifting electromagnets to scan reduced volumes of metal and thus achieve higher sensitivity. The microcontroller-based instrument provides 11% energy resolution (at 662 keV), an energy range from 60 keV to 1.5 MeV, a max. count rate of 30 kcps, a weight <1 kg, and a power consumption <1 W. The results of its extensive characterization in the laboratory and its validation in the field, including operation in a scrap yard as well as on a drone, are reported.

Miniaturized USB-powered multi-channel module for gamma spectroscopy and imaging.

LAILA is a miniaturized eight-channel electronic readout system for compact γ-ray detectors, combining high-resolution spectroscopy capability with position sensitivity. Compactness is achieved by the combination of a novel CMOS front-end ASIC (Application-Specific Integrated Circuit) for analog processing of a large signal current from Silicon PhotoMultiplier (SiPM) solid-state photodetectors, with a microcontroller-based data acquisition system. The adoption of automatic gain regulation in the gated-integrator stage of the ASIC offers an 84 dB dynamic range, combining single-photon sensitivity with an extended input photon energy range (20 keV-4 MeV, using 30 µm-cell SiPMs). Using this module with properly merged 144 SiPM pixels coupled to a 3 in.-thick lanthanum bromide scintillation crystal, a 3% energy resolution at 662 keV and 1 cm spatial resolution in the estimation of the interaction coordinates are experimentally demonstrated in this work.

Challenges for Microelectronics in Non-Invasive Medical Diagnostics.

Microelectronics is emerging, sometimes with changing fortunes, as a key enabling technology in diagnostics. This paper reviews some recent results and technical challenges which still need to be addressed in terms of the design of CMOS analog application specific integrated circuits (ASICs) and their integration in the surrounding systems, in order to consolidate this technological paradigm. Open issues are discussed from two, apparently distant but complementary, points of view: micro-analytical devices, combining microfluidics with affinity bio-sensing, and gamma cameras for simultaneous multi-modal imaging, namely scintigraphy and magnetic resonance imaging (MRI). The role of integrated circuits is central in both application domains. In portable analytical platforms, ASICs offer miniaturization and tackle the noise/power dissipation trade-off. The integration of CMOS chips with microfluidics poses multiple open technological issues. In multi-modal imaging, now that the compatibility of the acquisition chains (thousands of Silicon Photo-Multipliers channels) of gamma detectors with Tesla-level magnetic fields has been demonstrated, other development directions, enabled by microelectronics, can be envisioned in particular for single-photon emission tomography (SPECT): a faster and simplified operation, for instance, to allow transportable applications (bed-side) and hardware pre-processing that reduces the number of output signals and the image reconstruction time.

A Self-Powered Wireless Water Quality Sensing Network Enabling Smart Monitoring of Biological and Chemical Stability in Supply Systems.

A smart, safe, and efficient management of water is fundamental for both developed and developing countries. Several wireless sensor networks have been proposed for real-time monitoring of drinking water quantity and quality, both in the environment and in pipelines. However, surface fouling significantly affects the long-term reliability of pipes and sensors installed in-line. To address this relevant issue, we presented a multi-parameter sensing node embedding a miniaturized slime monitor able to estimate the micrometric thickness and type of slime. The measurement of thin deposits in pipes is descriptive of water biological and chemical stability and enables early warning functions, predictive maintenance, and more efficient management processes. After the description of the sensing node, the related electronics, and the data processing strategies, we presented the results of a two-month validation in the field of a three-node pilot network. Furthermore, self-powering by means of direct energy harvesting from the water flowing through the sensing node was also demonstrated. The robustness and low cost of this solution enable its upscaling to larger monitoring networks, paving the way to water monitoring with unprecedented spatio-temporal resolution.

Development of clinical simultaneous SPECT/MRI.

There is increasing clinical use of combined positron emission tomography and MRI, but to date there has been no clinical system developed capable of simultaneous single-photon emission computed tomography (SPECT) and MRI. There has been development of preclinical systems, but there are several challenges faced by researchers who are developing a clinical prototype including the need for the system to be compact and stationary with MRI-compatible components. The limited work in this area is described with specific reference to the Integrated SPECT/MRI for Enhanced stratification in Radio-chemo Therapy (INSERT) project, which is at an advanced stage of developing a clinical prototype. Issues of SPECT/MRI compatibility are outlined and the clinical appeal of such a system is discussed, especially in the management of brain tumour treatment.

Miniaturized Impedance Flow Cytometer: Design Rules and Integrated Readout.

A dual-channel credit-card-sized impedance cell counter featuring a throughput of 2000 cell/s and detection of single yeast cells (5 µm) with a signal-to-noise ratio of 20 dB is presented. Its compactness is achieved by a CMOS ASIC combining a lock-in impedance demodulator with an oversampling 20-bit ΣΔ ADC and real-time peak detection embedded in field-programmable gate array. The module is coupled to a dielectrophoretic cell-sorting microfluidic device, offering compact and label-free electrical readout that replaces the need for a fluorescence microscope and, thus, is suitable for point-of-care diagnostics. The independent role of each dimension of the planar sensing microelectrodes is demonstrated, with simulations and experiments, along with its relevant effect on the spectrum of thin channels, deriving useful design guidelines.

Differential Electrochemical Conductance Imaging at the Nanoscale.

Electron transfer in proteins is essential in crucial biological processes. Although the fundamental aspects of biological electron transfer are well characterized, currently there are no experimental tools to determine the atomic-scale electronic pathways in redox proteins, and thus to fully understand their outstanding efficiency and environmental adaptability. This knowledge is also required to design and optimize biomolecular electronic devices. In order to measure the local conductance of an electrode surface immersed in an electrolyte, this study builds upon the current-potential spectroscopic capacity of electrochemical scanning tunneling microscopy, by adding an alternating current modulation technique. With this setup, spatially resolved, differential electrochemical conductance images under bipotentiostatic control are recorded. Differential electrochemical conductance imaging allows visualizing the reversible oxidation of an iron electrode in borate buffer and individual azurin proteins immobilized on atomically flat gold surfaces. In particular, this method reveals submolecular regions with high conductance within the protein. The direct observation of nanoscale conduction pathways in redox proteins and complexes enables important advances in biochemistry and bionanotechnology.

Unscrambling light-automatically undoing strong mixing between modes.

Propagation of light beams through scattering or multimode systems may lead to the randomization of the spatial coherence of the light. Although information is not lost, its recovery requires a coherent interferometric reconstruction of the original signals, which have been scrambled into the modes of the scattering system. Here we show that we can automatically unscramble optical beams that have been arbitrarily mixed in a multimode waveguide, undoing the scattering and mixing between the spatial modes through a mesh of silicon photonics tuneable beam splitters. Transparent light detectors integrated in a photonic chip are used to directly monitor the evolution of each mode along the mesh, allowing sequential tuning and adaptive individual feedback control of each beam splitter. The entire mesh self-configures automatically through a progressive tuning algorithm and resets itself after significantly perturbing the mixing, without turning off the beams. We demonstrate information recovery by the simultaneous unscrambling, sorting and tracking of four mixed modes, with residual cross-talk of -20 dB between the beams. Circuit partitioning assisted by transparent detectors enables scalability to meshes with a higher port count and to a higher number of modes without a proportionate increase in the control complexity. The principle of self-configuring and self-resetting in optical systems should be applicable in a wide range of optical applications.

Light-induced dipole moment modulation in diarylethenes: a fundamental study.

The dipole moment of photochromic diarylethenes is determined in solution for both the coloured and uncoloured forms by measuring the capacitance of a capacitor filled with a photochromic solution as a dielectric material. Diarylethenes with different substituents are investigated and the modulation of the dipole moment is related to their chemical structures. We determine a modulation of the dipole moment up to 4 Debye. We discuss the model used to obtain the dipole moment from the capacitance measurements and we compare the experimental results with the outcomes from DFT calculations. The results highlight the importance of conformational effects in the description of the dipole moment of diarylethenes.

High-bandwidth detection of short DNA in nanopipettes.

Glass or quartz nanopipettes have found increasing use as tools for studying the biophysical properties of DNA and proteins, and as sensor devices. The ease of fabrication, favourable wetting properties and low capacitance are some of the inherent advantages, for example compared to more conventional, silicon-based nanopore chips. Recently, we have demonstrated high-bandwidth detection of double-stranded (ds) DNA with microsecond time resolution in nanopipettes, using custom-designed electronics. The electronics design has now been refined to include more sophisticated control features, such as integrated bias reversal and other features. Here, we exploit these capabilities and probe the translocation of short dsDNA in the 100 bp range, in different electrolytes. Single-stranded (ss) DNA of similar length are in use as capture probes, so label-free detection of their ds counterparts could therefore be of relevance in disease diagnostics.

High-speed detection of DNA translocation in nanopipettes.

We present a high-speed electrical detection scheme based on a custom-designed CMOS amplifier which allows the analysis of DNA translocation in glass nanopipettes on a microsecond timescale. Translocation of different DNA lengths in KCl electrolyte provides a scaling factor of the DNA translocation time equal to p = 1.22, which is different from values observed previously with nanopipettes in LiCl electrolyte or with nanopores. Based on a theoretical model involving electrophoresis, hydrodynamics and surface friction, we show that the experimentally observed range of p-values may be the result of, or at least be affected by DNA adsorption and friction between the DNA and the substrate surface.

Single-Molecule Studies of Unlabeled Full-Length p53 Protein Binding to DNA.

p53 is an antitumor protein that plays an important role in apoptosis, preserving genomic stability and preventing angiogenesis, and it has been implicated in a large number of human cancers. For this reason it is an interesting target for both fundamental studies, such as the mechanism of interaction with DNA, and applications in biosensing. Here, we report a comprehensive study of label-free, full length p53 (flp53) and its interaction with engineered double-stranded DNA in vitro, at the single-molecule level, using atomic force microscopy (AFM) imaging and solid-state nanopore sensing. AFM data show that dimeric and tetrameric p53 bind to the DNA in a sequence-specific manner, confirming previously reported relative binding affinities. The statistical significance is tested using both the Grubbs test and stochastic simulations. For the first time, ultralow noise solid-state nanopore sensors are employed for the successful differentiation between bare DNA and p53/DNA complexes. Furthermore, translocation statistics reflect the binding affinities of different DNA sequences, in accordance with AFM data. Our results thus highlight the potential of solid-state nanopore sensors for single-molecule biosensing, especially when labeling is either not possible or at least not a viable option.