Multiple Readout Research Articles

Ultrafast T2 and T2* mapping using single-shot spatiotemporally encoded MRI with reduced field of view and spiral out-in-out-in trajectory.

T2 and T2* mapping are crucial components of quantitative magnetic resonance imaging, offering valuable insights into tissue characteristics and pathology. Single-shot methods can achieve ultrafast T2 or T2* mapping by acquiring multiple readout echo trains. However, the extended echo trains pose challenges, such as compromised image quality and diminished quantification accuracy. In this study, we develop a single-shot method for ultrafast T2 and T2* mapping with reduced echo train length. The proposed method is based on ultrafast single-shot spatiotemporally encoded (SPEN) MRI combined with reduced field of view (FOV) and spiral out-in-out-in (OIOI) trajectory. Specifically, a biaxial SPEN excitation scheme was employed to excite the spin signal into the spatiotemporal encoding domain. The OIOI trajectory with high acquisition efficiency was employed to acquire signals within targeted reduced FOV. Through non-Cartesian super-resolved (SR) reconstruction, 12 aliasing-free images with different echo times were obtained within 150ms. These images were subsequently fitted to generate T2 or T2* mapping simultaneously using a derived model. Accurate and co-registered T2 and T2* maps were generated, closely resembling the reference maps. Numerical simulations demonstrated substantial consistency (R2>0.99) with the ground truth values. A mean difference of 0.6% and 1.7% was observed in T2 and T2*, respectively, in in vivo rat brain experiments compared to the reference. Moreover, the proposed method successfully obtained T2 and T2* mappings of rat kidney in free-breathing mode, demonstrating its superiority over multishot methods lacking respiratory navigation. The results suggest that the proposed method can achieve ultrafast and accurate T2 and T2* mapping, potentially facilitating the application of T2 and T2* mapping in scenarios requiring high temporal resolution.

Threshold bounce — occupancy-dependent modulation of the discriminating threshold in silicon detectors

The front-end electronics of silicon detectors are typically designed to ensure optimal noise performance for the expected input charge. A combination of preamplifiers and shaper circuits result in a nontrivial response of the front-end to injected charge, and the magnitude of the response may be sizeable in readout windows subsequent to that in which the charge was initially injected. The modulation of the discriminator threshold due to the superposition of the front-end response across multiple readout windows is coined “threshold bounce”. In this paper, we report a measurement of threshold bounce using silicon modules built for the Phase-II Upgrade of the ATLAS detector at the Large Hadron Collider. These modules utilize ATLAS Binary Chips for their hit readout. The measurement was performed using a micro-focused 15 keV photon beam at the Diamond Light Source synchrotron. The effect of the choice of photon flux and discriminator threshold on the magnitude of the threshold bounce is studied. A Monte Carlo simulation which accounts for the front-end behaviour of the silicon modules is developed, and its predicted hit efficiency is found to be in good agreement with the measured hit efficiency.

A universal nucleic acid detection platform combing CRISPR/Cas12a and strand displacement amplification with multiple signal readout

Rapid and sensitive detection of nucleic acids has become crucial in various fields. However, most current nucleic acid detection methods can only be used in specific scenarios, such as RT-qPCR, which relies on fluorometer for signal readout, limiting its application at home or in the field due to its high price. In this paper, a universal nucleic acid detection platform combing CRISPR/Cas12a and strand displacement amplification (CRISPR-SDA) with multiple signal readout was established to adapt to different application scenarios. Nucleocapsid protein gene of SARS-CoV-2 (N gene) and hepatitis B virus (HBV) DNA were selected as model targets. The proposed strategy achieved the sensitivity of 53.1 fM, 0.15 pM, and 1 pM for N gene in fluorescence mode, personal glucose meter (PGM) mode and lateral flow assay (LFA) mode, respectively. It possessed the ability to differentiate single-base mismatch and the presence of salmon sperm DNA with a mass up to 105-fold of the targets did not significantly interfere with the assay signal. The general and modular design idea made CRISPR-SDA as simple as building blocks to construct nucleic acid sensing methods to meet different requirements by simply changing the SDA template and selecting suitable signal report probes, which was expected to find a breadth of applications in nucleic acids detection.

Microwave quantum diode

The fragile nature of quantum circuits is a major bottleneck to scalable quantum applications. Operating at cryogenic temperatures, quantum circuits are highly vulnerable to amplifier backaction and external noise. Non-reciprocal microwave devices such as circulators and isolators are used for this purpose. These devices have a considerable footprint in cryostats, limiting the scalability of quantum circuits. As a proof-of-concept, here we report a compact microwave diode architecture, which exploits the non-linearity of a superconducting flux qubit. At the qubit degeneracy point we experimentally demonstrate a significant difference between the power levels transmitted in opposite directions. The observations align with the proposed theoretical model. At − 99 dBm input power, and near the qubit-resonator avoided crossing region, we report the transmission rectification ratio exceeding 90% for a 50 MHz wide frequency range from 6.81 GHz to 6.86 GHz, and over 60% for the 250 MHz range from 6.67 GHz to 6.91 GHz. The presented architecture is compact, and easily scalable towards multiple readout channels, potentially opening up diverse opportunities in quantum information, microwave read-out and optomechanics.

Exploring the effects of experimental parameters and data modeling approaches on in vitro transcriptomic point-of-departure estimates

Multiple new approach methods (NAMs) are being developed to rapidly screen large numbers of chemicals to aid in hazard evaluation and risk assessments. High-throughput transcriptomics (HTTr) in human cell lines has been proposed as a first-tier screening approach for determining the types of bioactivity a chemical can cause (activation of specific targets vs. generalized cell stress) and for calculating transcriptional points of departure (tPODs) based on changes in gene expression. In the present study, we examine a range of computational methods to calculate tPODs from HTTr data, using six data sets in which MCF7 cells cultured in two different media formulations were treated with a panel of 44 chemicals for 3 different exposure durations (6, 12, 24 hr). The tPOD calculation methods use data at the level of individual genes and gene set signatures, and compare data processed using the ToxCast Pipeline 2 (tcplfit2), BMDExpress and PLIER (Pathway Level Information ExtractoR). Methods were evaluated by comparing to in vitro PODs from a validated set of high-throughput screening (HTS) assays for a set of estrogenic compounds. Key findings include: (1) for a given chemical and set of experimental conditions, tPODs calculated by different methods can vary by several orders of magnitude; (2) tPODs are at least as sensitive to computational methods as to experimental conditions; (3) in comparison to an external reference set of PODs, some methods give generally higher values, principally PLIER and BMDExpress; and (4) the tPODs from HTTr in this one cell type are mostly higher than the overall PODs from a broad battery of targeted in vitro ToxCast assays, reflecting the need to test chemicals in multiple cell types and readout technologies for in vitro hazard screening.

Multi-readout DWI with a reduced FOV for studying the coupling between diffusion and relaxation in the prostate.

To develop a DWI sequence with multiple readout echo-trains in a single shot (multi-readout DWI) over a reduced FOV, and to demonstrate its ability to achieve high data acquisition efficiency in the study of coupling between diffusion and relaxation in the human prostate. The proposed multi-readout DWI sequence plays out multiple EPI readout echo-trains after a Stejskal-Tanner diffusion preparation module. Each EPI readout echo-train corresponded to a distinct effective TE. To maintain a high spatial resolution with a relatively short echo-train for each readout, a 2D RF pulse was used to limit the FOV. Experiments were performed on the prostate of six healthy subjects to acquire a set of images with three b values (0, 500, and 1000 s/mm2 ) and three TEs (63.0, 78.8, and 94.6ms), producing three ADC maps at different TEs and three maps at different b values. Multi-readout DWI enabled a threefold acceleration without compromising the spatial resolution when compared with a conventional single-readout sequence. Images with three b values and three TEs were obtained in 3min 40 s with an adequate SNR (≥ 26.9). The ADC values (1.45 ± 0.13, 1.52 ± 0.14, and 1.58 ± 0.15 ; P < 0.01) exhibited an increasing trend as TEs increased (63.0ms, 78.8ms, and 94.6ms), whereas values (74.78 ± 13.21, 63.21 ± 7.84, and 56.61 ± 5.05 ms; P < 0.01) decreases as the b values increased (0, 500, and 1000 s/mm2 ). The multi-readout DWI sequence over a reduced FOV provides a time-efficient technique to study the coupling between diffusion and relaxation times.

Quality control testing of the HCC ASIC for the HL-LHC ATLAS ITk strip detector

The high-luminosity upgrade to the LHC requires a new silicon-strip charged-particle tracking detector for ATLAS. The HCC (Hybrid Controller Chip) is one of three new radiation-tolerant ASICs for this silicon-strip detector. As the interface to multiple binary readout ASICs, the HCC is responsible for buffering and forwarding control signals and readout requests to them as well as serializing their readout data into a 640 Mbps output. All HCCs undergo a suite of tests to verify their analog and digital functionality. The yield for the HCC exceeds the 90% target for production.

First experimental results of the spatial resolution of RSD pad arrays read out with a 16-ch board

Resistive Silicon Detectors (RSD, also known as AC-LGAD) are innovative silicon sensors, based on the LGAD technology, characterized by a continuous gain layer that spreads across the whole sensor active area. RSDs are very promising tracking detectors, thanks to the combination of the built-in signal sharing with the internal charge multiplication, which allows large signals to be seen over multiple read-out channels. This work presents the first experimental results obtained from a 3 × 4 array with 200μm pitch, coming from the RSD2 production manufactured by FBK, read out with a 16-ch digitizer. A machine learning model has been trained, with experimental data taken with a precise TCT laser setup, and then used to predict the laser shot positions, finding a spatial resolution of ∼5.5μm.

Imprinted Polydimethylsiloxane-Graphene Oxide Composite Receptor for the Biomimetic Thermal Sensing of Escherichia coli.

This work presents an imprinted polymer-based thermal biomimetic sensor for the detection of Escherichia coli. A novel and facile bacteria imprinting protocol for polydimethylsiloxane (PDMS) films was investigated, and these receptor layers were functionalized with graphene oxide (GO) in order to improve the overall sensitivity of the sensor. Upon the recognition and binding of the target to the densely imprinted polymers, a concentration-dependent measurable change in temperature was observed. The limit of detection attained for the sensor employing PDMS-GO imprints was 80 ± 10 CFU/mL, a full order lower than neat PDMS imprints (670 ± 140 CFU/mL), illustrating the beneficial effect of the dopant on the thermo-dynamical properties of the interfacial layer. A parallel benchmarking of the thermal sensor with a commercial impedance analyzer was performed in order to prove the possibility of using the developed PDMS-GO receptors with multiple readout platforms. Moreover, S. aureus, C. sakazakii and an additional E. coli strain were employed as analogue species for the assessment of the selectivity of the device. Finally, because of the potential that this biomimetic platform possesses as a low-cost, rapid, and on-site tool for monitoring E. coli contamination in food safety applications, spiked fruit juice was analyzed as a real sample. Reproducible and sensitive results fulfill the limit requirements of the applicable European microbiological regulation.

Time resolution and high-counting rate performance of plastic scintillation counter with multiple MPPC readout

We have been developing a plastic scintillation counter for the WASA detector. The performance of a plastic scintillation counter with Multi-Pixel Photon Counter (MPPC) readout has been systematically investigated for minimum ionizing particles in terms of the time resolution and the signal amplitude stability. The performance was evaluated under various incident conditions of 2.5 GeV/c proton beams and with different MPPC settings. A plastic scintillator with a size of 550×38×8mm3 was optically coupled with multiple MPPCs at each plane with a size of 38×8mm2 for detecting the scintillation photons. The observed time resolution ranges in 37–80 ps (σ) depending on the incident positions and angles for the case of three MPPCs attached to each end. We found the time resolution and the signal amplitude fairly consistent up to the counting rate of 0.2 MHz.

Dose response of visible color center radiophotoluminescence in lithium fluoride crystals irradiated with a reference 60Co gamma beam in the 1–20 Gy dose range

The visible radiophotoluminescence response of radiation-induced stable F2 and F3+ color centers in nominally pure lithium fluoride crystals, irradiated with a reference 60Co gamma beam in the 1–20 Gy dose range, was carefully investigated. After irradiation, the Stokes-shifted emission spectra of the colored crystals were measured as a function of time under continuous laser excitation at 445 nm and in stationary conditions. The F2 radiophotoluminescence intensity remains constant; the signal, spectrally integrated in a 50 nm-wide interval centered on the F2 emission peak at 670 nm, exhibited a linear dependence on the absorbed dose with a good signal-to-noise ratio, stability for multiple readout and long storage times. Combined with our previous investigations after irradiation at similar doses with low-energy protons and clinical X-ray beams, these experimental results confirm the feasibility of passive solid-state dosimeters for radiotherapy based on color center radiophotoluminescence in nominally pure lithium fluoride crystals.

Taste GPCRs and their ligands.

Taste GPCRs are expressed in taste buds on the tongue and play a key role in food choice and consumption. They are also expressed extra-orally, with various physiological roles that are currently under study. Unraveling the roles of these receptors relies on the knowledge of their ligands. Combining sensory, cell-based and computational approaches enabled the discovery of numerous agonists and several antagonists. Here we provide a short overview of taste receptor families, main recent methods for ligands discovery, and current sources of information about known ligands. The future directions that are likely to impact the taste GPCR field include focus on ligand interactions with naturally occurring polymorphisms, as well as harnessing the power of CryoEM and of multiple signaling readout techniques.

Wire-cell 3D pattern recognition techniques for neutrino event reconstruction in large LArTPCs: algorithm description and quantitative evaluation with MicroBooNE simulation

Wire-Cell is a 3D event reconstruction package for liquid argon time projection chambers. Through geometry, time, and drifted charge from multiple readout wire planes, 3D space points with associated charge are reconstructed prior to the pattern recognition stage. Pattern recognition techniques, including track trajectory and dQ/dx (ionization charge per unit length) fitting, 3D neutrino vertex fitting, track and shower separation, particle-level clustering, and particle identification are then applied on these 3D space points as well as the original 2D projection measurements. A deep neural network is developed to enhance the reconstruction of the neutrino interaction vertex. Compared to traditional algorithms, the deep neural network boosts the vertex efficiency by a relative 30% for charged-current νe interactions. This pattern recognition achieves 80–90% reconstruction efficiencies for primary leptons, after a 65.8% (72.9%) vertex efficiency for charged-current νe (νμ) interactions. Based on the resulting reconstructed particles and their kinematics, we also achieve 15-20% energy reconstruction resolutions for charged-current neutrino interactions.

Photon number resolvability of multi-pixel superconducting nanowire single photon detectors using a single flux quantum circuit

Superconducting nanowire single-photon detectors (SNSPDs) are typical switching devices capable of detecting single photons with almost 100% detection efficiency. However, they cannot determine the exact number of incident photons during a detection event. Multi-pixel SNSPDs employing multiple read-out channels can provide photon number resolvability (PNR), but they require increased cooling power and costly multi-channel electronic systems. In this work, a single-flux quantum (SFQ) circuit is employed, and PNR based on multi-pixel SNSPDs is successfully demonstrated. A multi-input magnetically coupled DC/SFQ converter (MMD2Q) circuit with a mutual inductance M is used to combine and record signals from a multi-pixel SNSPD device. The designed circuit is capable of discriminating the amplitude of the combined signals in accuracy of Φ 0/M with Φ 0 being a single magnetic flux quantum. By employing the MMD2Q circuit, the discrimination of up to 40 photons can be simulated. A 4-parallel-input MMD2Q circuit is fabricated, and a PNR of 3 is successfully demonstrated for an SNSPD array with one channel reserved for the functional verification. The results confirm that an MMD2Q circuit is an effective tool for implementing PNR with multi-pixel SNSPDs.

A Pixel Design of a Branching Ultra-Highspeed Image Sensor.

A burst image sensor named Hanabi, meaning fireworks in Japanese, includes a branching CCD and multiple CMOS readout circuits. The sensor is backside-illuminated with a light/charge guide pipe to minimize the temporal resolution by suppressing the horizontal motion of signal carriers. On the front side, the pixel has a guide gate at the center, branching to six first-branching gates, each bifurcating to second-branching gates, and finally connected to 12 () floating diffusions. The signals are either read out after an image capture operation to replay 12 to 48 consecutive images, or continuously transferred to a memory chip stacked on the front side of the sensor chip and converted to digital signals. A CCD burst image sensor enables a noiseless signal transfer from a photodiode to the in-situ storage even at very high frame rates. However, the pixel count conflicts with the frame count due to the large pixel size for the relatively large in-pixel CCD memory elements. A CMOS burst image sensor can use small trench-type capacitors for memory elements, instead of CCD channels. However, the transfer noise from a floating diffusion to the memory element increases in proportion to the square root of the frame rate. The Hanabi chip overcomes the compromise between these pros and cons.

Friend or foe? Flankers reverse the direction of orthographic neighbourhood effects

ABSTRACT Increasing the neighbourhood density of a word typically facilitates lexical decision responses and interferes in sentence reading. The Multiple Read-Out Model accounts for such variation by postulating that word responses in the lexical decision task can be made via two mechanisms – identifying the word or using the global lexical activity that it generates. Here, we asked whether adding unrelated flanking words to either side of the target would modulate the relative contribution of these two mechanisms. That is, do flankers promote the use of word identification processes that are more characteristic of sentence reading? In line with our hypothesis, in Experiment 1 flanker words increased the inhibitory influence of orthographic neighbours relative to single word presentation. In Experiment 2, flanker neighbourhood density did not affect lexical decisions to central targets. This pattern indicates that the mechanisms used to make a lexical decision can be modulated by a minimal “sentence-like” context.

A Validated Method for the Simultaneous Determination of Methamphetamine and 3,4-Methylenedioxy-N-methamphetamine in Blood-Based Liquid Chromatography-Tandem Mass Spectrometry

A liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method has been validated for the simultaneous determination of methamphetamine (MA) and 3,4-methylenedioxy-N-methamphetamine (MDMA) in the blood sample. Under the optimal experimental conditions, the concentration of MA can be determined in the range from 1 µg/L to 5000 µg/L with the method detection limit (MDL) of 0.31 µg/L. The range from 0.5 to 500 µg/L is observed for the determination of MDMA with the MDL down to 0.25 µg/L. The practical applicability of the method is performed with the recovery ranging from 85.3% to 94% for MA and from 86.9% to 95.5% for MDMA. At the different concentrations of drugs, the relative standard deviations (RSD) for both MA and MDMA are lower than 5.7%. The method was applied to analyse 1995 blood samples that had been collected from the Forensic Medicine Centre of Ho Chi Minh City. The results showed 1.75% positive with MA and 0.25% positive with MDMA. These two drugs take 10% of the total drugs positive samples. By using deuterium-labelled methamphetamine-d5 and 3,4-methylenedioxy-N-methamphetamine-d5 as the internal standards in the determination and the use of MS/MS in multiple reaction monitoring mode signal readout, the method exhibits robustness specificity and can be applied in simultaneous determination of MA and MDMA in blood with high selectivity and sensitivity.

Empirical noise performance of prototype active pixel arrays employing polycrystalline silicon thin-film transistors.

In the spirit of overcoming the signal-to-noise limitations of active matrix, flat-panel imagers (AMFPIs) which employ array circuits based on a-Si:H thin-film transistors (TFTs), an empirical investigation of the noise properties of prototype active pixel arrays based on polycrystalline silicon (poly-Si) TFTs is reported. Like a-Si:H, poly-Si supports fabrication of large area, monolithic x-ray imaging arrays and offers good radiation damage resistance, while providing electron and hole mobility orders of magnitude higher. Compared to pixel circuits typically consisting of a single addressing switch in an AMFPI array, the pixel circuit of an active pixel array includes an amplifier that magnifies the imaging signal prior to readout by external acquisition electronics. Also, while readout erases signal stored in the pixels for AMFPI arrays, active pixel arrays allow multiple nondestructive readout, which can be used to reduce noise. The prototype arrays investigated in this paper were developed to explore the effect of variation in amplifier design on noise. A pair of prototype arrays incorporating single-stage and two-stage poly-Si pixel amplifiers were examined. The arrays incorporate various amplifier designs in which dimensions of some of the three (or four) poly-Si TFTs per pixel circuit for the single-stage array, and some of the five poly-Si TFTs for the two-stage array, were varied. The arrays were operated using a recently developed electronic data acquisition system that allows variation of operational conditions such as voltages and timing of control signals. The arrays were operated in the absence of radiation in various correlated multiple sampling modes, with and without the injection of charge directly into the pixel circuits for measurements of in-pixel gain and pixel noise. Pixel noise, referred back to the input of the pixel amplifier, was compared to predictions generated by a sophisticated circuit simulation model. Across the various pixel circuit designs, the median in-pixel gain for the single-stage and two-stage arrays was measured to be ×9.3 and ×25, respectively. These gain levels were sufficient to reduce the contribution of external noise, defined as the electronic additive noise in the absence of noise contributions from circuitry in the pixel and referred back to the input of the pixel amplifier, to less than 340 e. As a result, median pixel noise results as low as ~695 e and 866 e, acquired using eight samples, were observed from the best-performing single-stage and two-stage designs, respectively. While the magnitude of pixel noise predicted by simulation was lower than the measured results, there was generally good agreement between simulation and measurement for the functional dependence of noise on operating voltages, timing, and sampling mode. The single-stage and two-stage arrays examined in this study demonstrated pixel noise well below that typically demonstrated by AMFPIs. Through proper design, it should be possible to maintain the noise levels observed in this study irrespective of the size and pitch of an active pixel array. Further reduction in pixel noise may be possible through more optimized pixel circuit design, faster readout, or improvements in fabrication.

A Stacked Back Side-Illuminated Voltage Domain Global Shutter CMOS Image Sensor with a 4.0 μm Multiple Gain Readout Pixel †.

A backside-illuminated complementary metal-oxide-semiconductor (CMOS) image sensor with 4.0 μm voltage domain global shutter (GS) pixels has been fabricated in a 45 nm/65 nm stacked CMOS process as a proof-of-concept vehicle. The pixel components for the photon-to-voltage conversion are formed on the top substrate (the first layer). Each voltage signal from the first layer pixel is stored in the sample-and-hold capacitors on the bottom substrate (the second layer) via micro-bump interconnection to achieve a voltage domain GS function. The two sets of voltage domain storage capacitor per pixel enable a multiple gain readout to realize single exposure high dynamic range (SEHDR) in the GS operation. As a result, an 80dB SEHDR GS operation without rolling shutter distortions and motion artifacts has been achieved. Additionally, less than −140dB parasitic light sensitivity, small noise floor, high sensitivity and good angular response have been achieved.

Design and Development of a Raman Lidar for Cherenkov Gamma Array Experiments

Future Cherenkov Gamma Ray (CGR) experiments will reach a sensitivity and energy resolution never obtained until now by any other high energy gamma–ray experiment. It is well known that atmospheric conditions contribute particularly in this aspect. Raman lidars can help reduce the systematic uncertainties of the molecular and aerosol components of the atmosphere so these performances can be reached. The motivation for Raman lidars and the design and development of the Montpellier Raman lidar system is described. It provides both multiple elastic and Raman readout channels and custom-made optics design. Preliminary lidar tests and signals show the actual performance of the lidar in consistency with the desired goals.