Dual Readout Research Articles

First demonstration of a combined light and charge pixel readout on the anode plane of a LArTPC

The novel SoLAr concept aims to extend sensitivities of liquid-argon neutrino detectors down to the MeV scale for next-generation detectors. SoLAr plans to accomplish this with a liquid-argon time projection chamber that employs an anode plane with dual charge and light readout, which enables precision matching of light and charge signals for data acquisition and reconstruction purposes. We present the results of a first demonstration of the SoLAr detector concept with a small-scale prototype detector integrating a pixel-based charge readout and silicon photomultipliers on a shared printed circuit board. We discuss the design of the prototype, and its operation and performance, highlighting the capability of such a detector design.

Scintillation light in SBND: simulation, reconstruction, and expected performance of the photon detection system

SBND is the near detector of the Short-Baseline Neutrino program at Fermilab. Its location near to the Booster Neutrino Beam source and relatively large mass will allow the study of neutrino interactions on argon with unprecedented statistics. This paper describes the expected performance of the SBND photon detection system, using a simulated sample of beam neutrinos and cosmogenic particles. Its design is a dual readout concept combining a system of 120 photomultiplier tubes, used for triggering, with a system of 192 X-ARAPUCA devices, located behind the anode wire planes. Furthermore, covering the cathode plane with highly-reflective panels coated with a wavelength-shifting compound recovers part of the light emitted towards the cathode, where no optical detectors exist. We show how this new design provides a high light yield and a more uniform detection efficiency, an excellent timing resolution and an independent 3D-position reconstruction using only the scintillation light. Finally, the whole reconstruction chain is applied to recover the temporal structure of the beam spill, which is resolved with a resolution on the order of nanoseconds.

Measurement of scintillation from proportional electron multiplication in liquid xenon using a needle

Charge amplification in liquids could provide single-phase xenon time projection chambers with background discrimination and fiducialisation capabilities similar to those found in dual-phase detectors. Although efforts to achieve the high electric field required for charge amplification and proportional scintillation in liquid xenon have been previously reported, their application to large-scale detectors remains elusive. This work presents a new approach to this challenge, where — instead of the thin-wire approach of previous studies — a needle-like high-voltage electrode is employed to demonstrate proportional charge amplification and secondary scintillation production in liquid xenon. This is an important milestone towards the development of an electrode structure that could be utilised in a large-scale, single-phase time projection chamber with dual read-out.

Portable detection of Salmonella in food of animal origin via Cas12a-RAA combined with an LFS/PGM dual-signaling readout biosensor.

Ahighly specific and sensitive rapid two-signal assay was developedfor the detection of Salmonella typhimurium in foods of animal origin. TheinvA gene of Salmonella was usedas the biorecognition element and recombinase-assisted amplification (RAA) technology for signal amplification. By utilizing the specific recognition and efficient trans-cleavage activity of CRISPR/Cas12a, point-of-care testing (POCT) for S. typhimurium was achieved via lateral flow strips (LFS) and personal glucometer (PGM) biosensors as dual signal readout systems, with sensitivities of 33CFU/mL and 20CFU/mL, respectively. Users can select the appropriate test system on the basis of specific application requirements: LFSs are ideal for rapid onsite screening, whereas glucometer biosensors offer precise quantitative determination. This approach simplifies the use of large instruments and overcomes site constraints, demonstrating good accuracy and applicability in animal-derived samples, with significant potential for the detection of other pathogens and for use in restricted environments.

Light-induced reversible switching of generation and extinction of an organic radical anion.

Radicals play a crucial role across various domains, ranging from serving as catalysts in chemical reactions to materials for spintronic applications. Currently, a major challenge for the chemists is the development of the next generation of organic radicals controllable by photons. To tackle this challenge, here we introduce a dyad system that combines a dimethyldihydropyrene (DHP) photochromic unit with a naphthalene diimide (NDI) moiety. This system forms a stable organic NDI-based radical-anion upon exposure to light in a solvent containing a small amount of an amine that acts as an electron donor. The radical anion formation has also been demonstrated with a chemical reductant. The photoisomerization of this photochromic system converts it into a less-conjugated and less-electron-rich form, affecting the generation of the radical as well as its stability. Consequently, light-induced isomerization effectively quenches the radical. Thus, the formation and existence of the radical can be adjusted by manipulating the photoisomerization of the photochromic unit under diverse light sources. Additionally, the system exhibits significant differences in emission in the radical and the closed-shell state, thereby offering a dual readout of the state of the molecule.

Rapid, sensitive, and visual detection of swine Japanese encephalitis virus with a one-pot RPA-CRISPR/EsCas13d-based dual readout portable platform

Japanese encephalitis (JE), a mosquito-borne zoonotic disease caused by the Japanese encephalitis virus (JEV), poses a serious threat to global public health. The low viremia levels typical in JEV infections make RNA detection challenging, necessitating early and rapid diagnostic methods for effective control and prevention. This study introduces a novel one-pot detection method that combines recombinant enzyme polymerase isothermal amplification (RPA) with CRISPR/EsCas13d targeting, providing visual fluorescence and lateral flow assay (LFA) results. Our portable one-pot RPA-EsCas13d platform can detect as few as two copies of JEV nucleic acid within 1 h, without cross-reactivity with other pathogens. Validation against clinical samples showed 100 % concordance with real-time PCR results, underscoring the method's simplicity, sensitivity, and specificity. This efficacy confirms the platform's suitability as a novel point-of-care testing (POCT) solution for detecting and monitoring the JE virus in clinical and vector samples, especially valuable in remote and resource-limited settings.

Dual-mode electrochemical/colorimetric capillary-driven microfluidic device for simultaneous determination of Δ⁹-tetrahydrocannabinol and cannabidiol in cannabis flower

Cannabis flower is well-known for its high levels of cannabidiol (CBD). However, the medical-grade cannabis flowers must meet strict standards to guarantee high CBD content and minimal to no contamination of Δ⁹-tetrahydrocannabinol (Δ⁹-THC). Given their similar redox potentials as determined by electrochemical detection, a dual readout approach becomes essential for accurately measuring the individual concentrations of Δ⁹-THC. In this work, we developed a capillary-driven microfluidic device that integrated electrochemical and colorimetric detections. The device was made from low-cost, transparent hydrophilic PET film and double-sided adhesive film with a pump-free delivery function. Once the sample solution was loaded, analysis of total Δ⁹-THC and CBD was conducted using an electrochemical technique, with a limit of detection (LOD) of 0.26 μg/mL and linear ranges of 0 – 120 μg/mL for both total Δ⁹-THC and CBD. Simultaneously, the sample solution autonomously flowed to the colorimetric zone within the transparent hydrophilic PET film, with corresponding LOD and linear ranges of 0.44 μg/mL and 0–120 μg/mL specifically for CBD. The method involved subtracting the CBD concentration obtained by colorimetry from the total Δ⁹-THC and CBD concentration obtained by electrochemical detection. Therefore, the proposed device, with its excellent analytical performance and advantageous features of affordability, simplicity, and fully portable light-controlled box, offers a practical alternative for quality control in the assessment of Δ⁹-THC and CBD levels in cannabis flowers.

Unimolecular Cucurbit[7]uril‐Based Indicator Displacement Assay with Dual Signal‐Readout for the Detection of Drugs

Point‐of‐care diagnostics relies on optical and electrochemical sensors to develop devices that are both compact and cost‐effective. Therefore, the search for new design principles for chemosensors that enable multiple signal outputs is a particularly interesting concept. In this work, we present an unimolecular chemosensor based on cucurbit[7]uril that combines two signal readouts ‐ namely fluorescent and electrochemical signals ‐ in a single chemosensor design. This is achieved by utilizing the tunable fluorescence and the electrochemical properties of the reporter molecule, which depend on whether or not it is engulfed by the cucurbit[7]uril cavity. By setting up an assay using the dual readout chemosensor, illicit drug formulations containing pancuronium bromide or nicotine can be detected at low micromolar concentrations (0 – 100 μM). This assay is compatible with standard fluorescence plate readers and electrochemical devices, including commercially available screen‐printed electrodes (SPEs). Overall, the chemosensor presented in this study represents a significant advance in the development of cucurbit[7]uril chemosensors, characterized by multimodal detection capabilities. It uniquely combines traditional optical and electrochemical detection methods in a single molecular design.

Insight into the synthesis and mechanism of oxacalix[4]arene based nanohybrids for dual readout sensing and removal of Hg2+ ions

Mercury contamination has been a major concern for decades and its removal from environment and natural waterbodies are of highest priority. Inspired by the fact to detect trace amount of mercury and consequently removal of the same, here we present a silver nanoparticle based affordable, rapid and sensitive probe for inspecting the mercury levels on various waterbodies and soil samples with exceptional sensitivity (12 nM). This study reports the design, synthesis and characterization of novel disulfonic acid functionalized oxacalix[4]arene appended silver nanoparticles (DSOC@AgNPs). Driven by the distinct color change phenomena of DSOC@AgNPs upon interaction with Hg2+ ions, we have fabricated a paper strip-based ready-to-use detection kit for rapid detection of mercury ions up to sub-nanomolar concentration. Moreover, DSOC@AgNPs modified screen-printed carbon electrodes (SPCE) have been developed and utilized as a rapid detection kit for mercury in environmental samples. DSOC@AgNPs encapsulated ZIF-8 nanohybrid (DSOC@AgNPs-ZIF) have been employed for the removal of Hg2+ ions from mercury contaminated wastewater with a removal efficiency of 95%. Incidentally, this is the first report for the removal of Hg2+ ions (CH3Hg+ and Hg2+ species) using oxacalixarene-stabilized AgNPs. Further, the surface-modified Rh6G-DSOC@AgNPs reveal its bio-imaging potentiality for mercury detection in living systems and also exhibited dose-dependent cytotoxicity against MCF-7 cells, with an IC50 value of 354.62 μM.

Optical storage and encryption via efficient reversible luminescence modulation based on copper-doped borate glass

Transparent glass is a promising candidate for optical storage media due to its large capacity and high stability advantages. Previously reported optical storage glass systems meet various problems, such as high manufacturing costs, low security levels, etc. Herein, a kind of copper-contained borate glass was designed and fabricated, emitting tunable broadband upon various ultraviolet light excitations. By alternating 360 nm laser (10.7 W/cm2) irradiation for 15 s and thermal treatment at 400 ℃ for 2 h, the emission intensity of the glass can be reversibly regulated, which is associated with the variation of oxidation states of the copper element. Relying on their efficient reversible luminescence modulation behaviors, the potential application of this glass as an optical storage and encryption media is developed, exhibiting the high performances of repeatable writing and erasing, dual mode readout, high-level safety, and good writing resolution for the Cu-doped borate glass.

Ag-modified CuO cavity arrays as a SERS-electrochemical dual signal platform for thiram detection

Rapid and sensitive determination of pesticide residues in fruits and vegetables is critical for human health and ecosystems. This paper used an Ag-modified CuO sphere-cavity array (CuO@Ag) electrode as a thiram SERS/electrochemical dual readout detection platform. Numerous Raman “hotspots” generated by uniformly distributed silver nanoparticles, charge transfer at the CuO@Ag interface, and the formation of Ag-thiram complexes contribute to the significant enhancement of this SERS substrate, which results in excellent SERS performance with an enhancement factor up to 1.42 × 106. When using SERS as the readout technique, the linear range of the substrate for thiram detection was 0.05–20 nM with a detection limit (LOD) of up to 0.0067 nM. Meanwhile, a correlation between the value of change in current density and thiram concentration was established due to the formation of stable complexes of thiram with Cu2+ generated at specific potentials. The linear range of electrochemical detection was 0.05–20.0 μM, and the detection limit was 0.0167 μM. The newly devised dual-readout sensor offers notable sensitivity and stability. The two signal readout methods complement each other in terms of linear range and detection limit, making it a convenient tool for assessing thiram residue levels in agro-food. At the same time, the combination of commercially available portable equipment makes on-site monitoring possible.

Synergistic synthesis of gold nanoflowers as upconversion near-infrared nanoprobe energy acceptor and recognition unit for improved hydrogen sulfide sensing

A highly sensitive and selective upconversion near-infrared (NIR) fluorescence and colorimetric dual readout hydrogen sulfide (H2S) nanoprobe was constructed based on the excellent NIR fluorescence emission performance of upconversion nanomaterials (UCNPs), the specific recognition effect of synergistically synthesized gold nanoflowers (trypsin-stabled AuNFs (Try-AuNFs)) and the effective NIR fluorescence quenching capability. In this assay, the sensing strategy included three processes. First of all, the synthesized UCNPs can emit 803 nm NIR fluorescence when they were excited by 980 nm excitation light. Secondly, as a result of the principle of fluorescence resonance energy transfer (FRET), Try-AuNFs can effectively quench the NIR fluorescence of UCNPs at 803 nm, which can effectively improve the signal-to-background ratio of nanoprobes, thereby improving the sensitivity of the probes. Thirdly, in the presence of H2S, the Try protective layer on the surface of Try-AuNFs was specifically penetrated, which will subsequently cleave Try-AuNFs via the strong S–Au bond. As such, the NIR fluorescence of UCNPs will be restored, achieving high selectivity and sensitivity detection of H2S. Under optimized conditions, the linear response range of H2S was 0.1–300 μM, and the detection limit was 53 nM. It is worth noting that the Try on the surface of Try-AuNFs via the synergistic effect can increase the steric hindrance of the probe, and this can effectively prevent the interaction between the probe with biothiols (cysteine (Cys), homocysteine (Hcy)) and other natural amino acids (non-thiol-containing) with resultant in the high selectivity regarding the detection of H2S in human serum, which is unlikely to be achieved by AuNFs synthesized by the gold seed method (Se-AuNFs). This work not only provided a new type of UCNPs fluorescence quencher and recognition unit, but also exemplified that the use of the physical properties (steric hindrance) of protein ligands on the surface of nanoflowers can improve the specificity of the probe. This will provide new ideas for the design of other nanoprobes.

Development of particle flow algorithms based on Neural Network techniques for the IDEA calorimeter at future colliders

IDEA (Innovative Detector for an Electron-positron Accelerator) is an innovative general-purpose detector concept, designed to study electron-positron collisions at future e+e− circular colliders. The detector will be equipped with a dual read-out calorimeter able to measure separately the hadronic component and the electromagnetic component of the showers initiated by the impinging hadrons. Particle flow algorithms (PFAs) have become the paradigm of detector design for the high energy frontier and this work focuses on a project to build a particle flow algorithm for the IDEA detector using Machine Learning (ML) techniques. ML is used for particle reconstruction and identification profiting of the high granularity of the fiber-based dual-readout calorimeter. Neural Networks (NN) are built for electron reconstruction inside the calorimeter. The performance of several NN architectures is shown, with particular attention to the layer setup and the activation function choices. The performance is evaluated on the energy resolution function of the reconstructed particles. The algorithm is trained using both parallel CPUs and GPU, and the time performance and the memory usage of the two approaches are systematically compared.

A rapid and ultra-sensitive dual readout platform for Klebsiella pneumoniae detection based on RPA-CRISPR/Cas12a.

The bacterium Klebsiella pneumoniae (Kp) was the primary pathogen of hospital-acquired infection, but the current detection method could not rapidly and conveniently identify Kp. Recombinase polymerase amplification (RPA) was a fast and convenient isothermal amplification technology, and the clustered regularly interspaced short palindromic repeats (CRISPR) system could rapidly amplify the signal of RPA and improve its limit of detection (LOD). In this study, we designed three pairs of RPA primers for the rcsA gene of Kp, amplified the RPA signal through single-strand DNA reporter cleavage by CRISPR/Cas12a, and finally analyzed the cleavage signal using fluorescence detection (FD) and lateral flow test strips (LFTS). Our results indicated that the RPA-CRISPR/Cas12a platform could specifically identify Kp from eleven common clinical pathogens. The LOD of FD and LFTS were 1 fg/μL and 10 fg/μL, respectively. In clinical sample testing, the RPA-CRISPR/Cas12a platform was consistent with the culture method and qPCR method, and its sensitivity and specificity were 100% (16/16) and 100% (9/9), respectively. With the advantages of detection speed, simplicity, and accuracy, the RPA-CRISPR/Cas12a platform was expected to be a convenient tool for the early clinical detection of Kp.

Lateral flow strip assay of a gene segment in the COVID-19 virus with combined dual readout mode and preliminary multisite hybrid chain reaction amplification.

The past and present scenario of COVID-19 has revealed the necessity of simple point-of-care tests. When combined with the great advantages of amplification, lateral flow assay nucleic acid analysis represents a more sensitive molecular diagnostic technique compared to universal protein analysis. Room temperature operation, an enzyme-free nature, and in situ elongation make hybrid chain reaction amplification (HCR) a good candidate for amplified combined lateral flow assays (LFAs). Since dual modes of detection can not only satisfy different application scenarios, but also reduce the false-negative rate, in this paper, visual and fluorescent detection based on labelling with colloidal gold nanoparticles and fluorescence labelling were incorporated into a HCR integrated with a LFA. The detection assay was finished in 30 minutes. The linear relationship between the signal and the concentration of the characteristic segment in the COVID-19 ORF gene was demonstrated. The obtained detection limits of as low as 10 fM (6.02 × 103 copies per mL) and 1 fM (6.02 × 102 copies per mL), respectively, were comparable with those in the literature. The multi-site HCR amplification integrated with LFA of a 1053 bp nucleic acid chain was also preliminarily studied, and tri-site amplification was found to exhibit higher signal intensity than single-site amplification. This study provides a promising strategy for simple, sensitive, and wide-ranging detection of pathogenic bacteria.

Homogeneous electroanalysis coupled with colorimetry dual-mode sensing of silver ion in water based on target-inhibited peroxidase activity of Pt@ZIF-8 nanozyme

Electrochemical sensing is the commonly used method for the detection of heavy metal silver ion (Ag+), while the conventional electrochemical sensors generally require the existence of electrode modifications and even electrodeposition step coupled with a single-mode readout. Herein, by preparing ZIF-8 organometallic frame load with platinum nanoparticles (Pt@ZIF-8) as nanozyme and o-phenylenediamine (OPD) as colorless substance, taking advantage of the superior peroxidase activity of Pt@ZIF-8 that can catalyze the oxidation of OPD to product electroactive/yellow 2,3-diaminophenazinc and the target-inhibited effect towards nanozyme activity from Ag+, a homogeneous electroanalysis coupled with colorimetry (HEA-CM) dual-mode sensing platform was designed for the first time to detect Ag+. Furthermore, the colorimetric images were converted on a smartphone to digital signals for the quantitative analysis. The designed strategy could offer multiple advantages such as electrodeposition-free, modification-free and dual channel readout. After investigating the sensing mechanism and experimental parameters, the analytical performance of the designed strategy was evaluated, obtaining extremely low detection limit (0.034 nM), reliable recovery rate (99.61 %-101.6 %) and wide linearity. This work offered an effective method for the simple, sensitive, rapid, accurate and multiplexed determination of Ag+, and also opened a new pathway for the detection of other heavy metals based on HEA-CM dual-mode strategy.

An accurate and sensitive sensor based on the internal filtration effect for the detection of alkaline phosphatase and ascorbic acid by the Fenton reaction and dual readout signal

Ascorbic acid (AA) and alkaline phosphatase (ALP) in human serum are indispensable substances in the process of biological metabolism, and their abnormal contents are strongly associated with a range of diseases. Therefore, it is meaningful to develop a simple, accurate and sensitive assay for the detection of AA and ALP. Up-conversion nanoparticles (UCNPs) have some unique characteristics, especially, the potential for background-free excitation by the near-infrared region (NIR) significantly improves the limits of detection (LODs). Moreover, sensors based on the inner filter effect (IFE) do not require covalent linkage between receptors and fluorophores or surface modification, thus the probe fabrication is simple and flexible UCNP-based. Therefore, a simple, selective, sensitive, and flexible sensing system for the detection of AA and ALP is proposed by combining the IFE and the cyclic signal amplification strategy. Under ideal circumstances, the LODs of ALP through the colorimetric and fluorescence method were 0.192 U/L and 0.013 U/L. The established sensing platform was applied to assessing ALP activity in human serum, and the detection results are close to those of commercially available kits, indicating its immense potential as an effective and convenient tool for monitoring ALP activity in clinical settings.

Colorimetric and photothermal dual readout biosensor for flap endonuclease 1 based on target-prevented gold nanoparticles aggregation

A colorimetric and photothermal dual readout biosensor for Flap endonuclease 1 (FEN1) quantification was developed on the basis of target-prevented gold nanoparticles (AuNPs) aggregation. The exposed 5′-flap of double-flap DNA substrate modified on SAMBs was firstly cleaved by FEN1. Large amount of cleaved 5′-flap remained in the supernatant after simple magnetic separation, which can adsorb on the surface of AuNPs and effectively prevent the dispersed AuNPs from aggregation under high ionic concentration, accompanied with the color changing of the system, which can be recognized by nake eyes easily. The absorption intensity at 528 nm shows a good linear relationship with the increasing FEN1 concentration from 5.0 × 10-3 to 3.1 × 10-2 U μL-1 with a LOD of 1.6 × 10-3 U μL-1 (S/N = 3). Given the aggregated AuNPs have higher photothermal effect than that of the dispersed AuNPs, the target-prevented AuNPs aggregation avoids a sharp increase of temperature for the system under the laser radiation. The temperature change is linearly correlated with the FEN1 concentration in the range of 3.1 × 10-3–6.1 × 10-2 U μL-1 with a LOD of 1.1 × 10-3 U μL-1. The whole detection process can be completed within 1 h. The proposed system had been applied to detect FEN1 concentration in serum samples with satisfied results, which can be applied in resource-limited area easily and quickly.

Rapid, sensitive, and visual detection of Clonorchis sinensis with an RPA-CRISPR/Cas12a-based dual readout portable platform

Clonorchis sinensis is a food-borne parasite that parasitizes the liver and bile ducts of humans and many animals. This parasite exerts a high burden due to diverse hepatobiliary morbidities (e.g., cholangitis, cholecystitis, cholelithiasis, and cholangiocarcinoma), and an effective detection strategy is urgently needed. CRISPR/Cas12a exhibits nonspecific trans-cleavage activity upon binding to its specific target and has been widely used for nucleic acid detection. In this study, an RPA-CRISPR/Cas12a-based dual readout portable detection platform was established, which shows high sensitivity (one copy/μl) and specificity (no cross-reactivity with common pathogens) by rapid preamplification and combines lateral flow strips and visual fluorescence for visualization of results by the naked eye within 1 h. Moreover, 50 human fecal swabs and 50 fish flesh samples were detected by this platform and nested PCR. The CRISPR/Cas12a-based dual readout portable platform showed 10.0 % (5/50) C. sinensis-positive samples in human fecal swabs and 28.0 % (14/50) in fish flesh, which was consistent with the results of nested PCR. The results demonstrate that our portable platform has the advantages of stability, sensitivity, accuracy, and low equipment requirements. Furthermore, we provide novel point-of-care testing (POCT) for clinical use in remote rural and resource-constrained areas.

Cell-free transcription-translation system: a dual read-out assay to characterize riboswitch function.

Cell-free protein synthesis assays have become a valuable tool to understand transcriptional and translational processes. Here, we established a fluorescence-based coupled in vitro transcription-translation assay as a read-out system to simultaneously quantify mRNA and protein levels. We utilized the well-established quantification of the expression of shifted green fluorescent protein (sGFP) as a read-out of protein levels. In addition, we determined mRNA quantities using a fluorogenic Mango-(IV) RNA aptamer that becomes fluorescent upon binding to the fluorophore thiazole orange (TO). We utilized a Mango-(IV) RNA aptamer system comprising four subsequent Mango-(IV) RNA aptamer elements with improved sensitivity by building Mango arrays. The design of this reporter assay resulted in a sensitive read-out with a high signal-to-noise ratio, allowing us to monitor transcription and translation time courses in cell-free assays with continuous monitoring of fluorescence changes as well as snapshots of the reaction. Furthermore, we applied this dual read-out assay to investigate the function of thiamine-sensing riboswitches thiM and thiC from Escherichia coliand the adenine-sensing riboswitch ASW from Vibrio vulnificusand pbuE from Bacillus subtilis, which represent transcriptional and translational on- and off-riboswitches, respectively. This approach enabled a microplate-based application, a valuable addition to the toolbox for high-throughput screening of riboswitch function.