Readout Method Research Articles

Laser-induced breakdown spectroscopy mediated amplification sensor for copper (Ⅱ) ions detection using click chemistry

New strategies for super-sensitive detection of toxic heavy-metal-ion pollutants are urgently needed. Here, we outline a simple and highly sensitive assay for copper(II) ions. The method is based on click chemistry and uses laser-induced breakdown spectroscopy (LIBS) as the readout method. Copper(I) ions formed in situ by the reduction of copper(II) ions in the presence of sodium ascorbate (AA) can catalyze the cycloaddition reaction between an alkyne and an azide (CuAAC). In the presence of copper(II) ions and AA, the AgNPs-BSA-Azide can be clicked with the BSA-Alkyne via a cycloaddition reaction to form a BSA-triazole-BSA-AgNPs sandwich conjugate based on this CuAAC&LIBS system. The intensity of the LIBS signal from the residual AgNPs-BSA-Azide in the supernatant is inversely proportional to the concentration of copper(II) ions. The sensor shows a good detection limit of 0.045 nM and a linear relationship between copper ions concentration and the LIBS signal. This click-based method will broaden the potential applications of LIBS for metal detection in drinking water and environment.

Ψ-type hybridization and CRISPR/Cas12a-based two-stage signal amplification for microRNA detection

A two-stage signal amplification strategy was designed for sensitive microRNA detection. It included nicking endonuclease free strand displacement amplification (SDA) and CRISPR/Cas12a-assisted fluorescence signal amplification. To achieve single-base specificity, a novel Ψ-type hybridization was proposed to recognize target and trigger the cyclic strand displacement amplification (CSDA) for the generation of target DNA product, which activated the trans-cleavage activity of Cas12a. In addition, an innovative fluorescence signal readout method based on mono-labeled ssDNA as reporter and tremella-like graphdiyne (GDY) as scavenger was presented, which eliminated the fluorescent background of Cas12a amplification system and led to an order of magnitude improvement in the detection limit. Combining the Ψ-type hybridization triggered CSDA and Cas12a amplification system, the fluorescence signal was linear with miR-214 concentration from 20.0 fM to 10.0 pM, and the detection limit was as low as 0.1 fM. The work provided new opportunity for miRNAs assay.

Shelving and latching spin readout in atom qubits in silicon

Singlet-triplet qubits typically require large magnetic field gradients on the order of militeslas to achieve high-fidelity electrically-controlled qubit operations. However, such large magnetic field gradients in quantum dot systems also increase charge noise and provide a relaxation pathway from the triplet to singlet qubit state, making high-fidelity readout challenging. Recently, shelving and latched readout have been employed in gate-defined quantum dots and donor-dot systems to achieve readout fidelities of 80% and 99.86%, respectively. In this paper, we theoretically examine shelving and latched singlet-triplet readout techniques for multidonor-based qubits in silicon where the large phosphorus hyperfine interaction of the order of 100 MHz gives rise to large effective magnetic field gradients (equivalent to tens of mT) but where it can change in time due to the presence of nuclear spin flips. Using numerical simulations, we show that shelving readout does not work giving a zero average visibility for mutidonor quantum dots, due to the time-varying nuclear spin polarization. To remedy this we propose adding a calibration step, in which we derive the nuclear spin polarization from a single shelving readout of a singlet state, before every qubit operation. The derived information can then be used via a feed-forward protocol to apply correct readout mapping, greatly improving the overall readout fidelity to $>99%$. We also simulate the latched readout mechanism, which is resistant to nuclear polarization changes and is thus promising for achieving high visibility readout. Here we observe a nonzero readout visibility irrespective of the nuclear spin flipping. Finally, we discuss how to optimize the readout visibility in the presence of strong hyperfine interactions and show that for both readout methods we can obtain readout fidelity $>99%$. These results demonstrate that singlet-triplet qubits based on multidonor quantum dots are a promising route for future electrically controlled qubits in silicon.

A nanopore interface for higher bandwidth DNA computing

DNA has emerged as a powerful substrate for programming information processing machines at the nanoscale. Among the DNA computing primitives used today, DNA strand displacement (DSD) is arguably the most popular, with DSD-based circuit applications ranging from disease diagnostics to molecular artificial neural networks. The outputs of DSD circuits are generally read using fluorescence spectroscopy. However, due to the spectral overlap of typical small-molecule fluorescent reporters, the number of unique outputs that can be detected in parallel is limited, requiring complex optical setups or spatial isolation of reactions to make output bandwidths scalable. Here, we present a multiplexable sequencing-free readout method that enables real-time, kinetic measurement of DSD circuit activity through highly parallel, direct detection of barcoded output strands using nanopore sensor array technology (Oxford Nanopore Technologies’ MinION device). These results increase DSD output bandwidth by an order of magnitude over what is currently feasible with fluorescence spectroscopy.

Conceptual design and science cases of a juggled interferometer for gravitational wave detection

The Juggled interferometer (JIFO) is an earth-based gravitational wave detector using repeatedly free-falling test masses. With no worries of seismic noise and suspension thermal noise, the JIFO can have much better sensitivity at lower frequencies than the current earth-based gravitational wave detectors. The data readout method of a JIFO could be challenging if one adopts the fringe-locking method. We present a phase reconstruction method in this paper by building up a complex function which has a fringe-independent signal-to-noise ratio. Considering the displacement noise budget of the Einstein Telescope (ET), we show that the juggled test masses significantly improve the sensitivity at 0.1-2.5$\,$Hz even with discontinuous data. The science cases brought with the improved sensitivity would include detecting quasi-normal modes of black holes with $10^4-10^5\,M_{\odot}$, testing Brans-Dicke theory with black-hole and neutron-star inspirals, and detecting primordial-black-hole-related gravitational waves.

Dispersive readout of a high-Q encapsulated micromechanical resonator

Encapsulated bulk mode microresonators in the megahertz range are used in commercial timekeeping and sensing applications, but their performance is limited by the current state of the art of readout methods. We demonstrate a readout using dispersive coupling between a high-Q encapsulated bulk mode micromechanical resonator and a lumped element microwave resonator that is implemented with commercially available components and standard printed circuit board fabrication methods and operates at room temperature and pressure. A frequency domain measurement of the microwave readout system yields a displacement resolution of 522 fm/Hz, which demonstrates an improvement over the state of the art of displacement measurement in bulk-mode encapsulated microresonators. This approach can readily be implemented in cryogenic measurements, allowing for future work characterizing the thermomechanical noise of encapsulated bulk mode resonators at cryogenic temperatures.

Pseudocontinuous Arterial Spin Labeling: Clinical Applications and Usefulness in Head and Neck Entities.

Simple SummaryConventional imaging methods, such as ultrasonography, computed tomography, and magnetic resonance imaging may be inadequate to accurately diagnose lesions of the head and neck because they vary widely. Recently, the arterial spin labeling technique, especially pseudocontinuous arterial spin labeling (pCASL) with the three-dimensional (3D) readout method, has been dramatically developed to improve diagnostic performance for lesion differentiation, which can show prominent blood flow characteristics. Here, we demonstrate the clinical usefulness of 3D pCASL for diagnosing various entities, including inflammatory lesions, hypervascular lesions, and neoplasms in the head and neck, for evaluating squamous cell carcinoma (SCC) treatment responses, and for predicting SCC prognosis.As functional magnetic resonance imaging, arterial spin labeling (ASL) techniques have been developed to provide quantitative tissue blood flow measurements, which can improve the performance of lesion diagnosis. ASL does not require contrast agents, thus, it can be applied to a variety of patients regardless of renal impairments and contrast agent allergic reactions. The clinical implementation of head and neck lesions is limited, although, in recent years, ASL has been increasingly utilized in brain lesions. Here, we review the development of the ASL techniques, including pseudocontinuous ASL (pCASL). We compare readout methods between three-dimensional (3D) turbo spin-echo and 2D echo planar pCASL for the clinical applications of pCASL to head and neck lesions. We demonstrate the clinical usefulness of 3D pCASL for diagnosing various entities, including inflammatory lesions, hypervascular lesions, and neoplasms; for evaluating squamous cell carcinoma (SCC) treatment responses, and for predicting SCC prognosis.

A Universal Multichannel Platform for Assembling Enzyme‐Based Boolean Logic Gates

Concatenated enzyme-based Boolean logic gates activated with 5 chemical input signals were analyzed with a smartphone photo camera. Simultaneous detection of 32 input combinations was conveniently performed using enzyme-modified fiberglass sensing spots generating fluorescence with different intensities for the 0 and 1 binary outputs. The developed technology offers an easy readout method for multi-channel logic systems.

Humidity Responsive Reflection Grating Made by Ultrafast Nanoimprinting of a Hydrogel Thin Film.

The response time of state-of-the-art humidity sensors is ≈8 s. A faster tracking of humidity change is especially required for health care devices. This research is focused on the direct nanostructuring of a humidity-sensitive polymer thin film and it is combined with an optical read-out method. The goal is to improve the response time by changing the surface-to-volume ratio of the thin film and to test a different measurement method compared to state-of-the-art sensors. Large and homogeneous nanostructured areas are fabricated by nanoimprint lithography on poly(2-hydroxyethyl methacrylate) thin films. Those thin films are made by initiated chemical vapor deposition (iCVD). To the author's knowledge, this is the first time nanoimprint lithography is applied on iCVD polymer thin films. With the imprinting process, a diffraction grating is developed in the visible wavelength regime. The optical and physicochemical behavior of the nanostructures is modeled with multi-physic simulations. After successful modeling and fabrication a first proof of concept shows that humidity dependency by using an optical detection of the first diffraction order peak is observable. The response time of the structured thin film results to be at least three times faster compared to commercialsensors.

(Digital Presentation) Stochastic Impact Electrochemistry in a Lateral-Flow Sensor Architecture

During the recent SARS-CoV-2 pandemic, lateral flow assays (LFAs) have written an indescribable story of success, as they provide means for decentralized, low-cost, and easy-to-use testing. However, LFAs in their most common form support only qualitative results and their sensitivity and limit of detection is significantly limited by the colorimetric readout method. In contrast, single-impact electrochemistry offers the possibility to quantify species beyond picomolar concentrations by recording individual species collisions with a biased microelectrode. Within this work, we investigate the integration of stochastic sensing into a LFA-architecture by combining a wax-patterned microchannel with a microelectrode array in order to detect silver nanoparticles by their oxidative dissolution. Here, we demonstrate the possibility to resolve individual nanoparticle collisions in a paper-based microchannel using a simplified reference-on-chip setup. Furthermore, we simulated a lateral-flow sensor, by flushing previously dried silver nanoparticles towards the electrode array, where the particles are subsequently detected. This proof-of-principle illustrates that single-impact electrochemistry might be a promising technique to extend the capability of LFAs. Especially, the integration of functionalized nanoparticle labels could enable the rapid and on-site detection of very dilute species with exceptional sensitivity.

A high-throughput screening assay for mutant isocitrate dehydrogenase 1 using acoustic droplet ejection mass spectrometry.

Acoustic droplet ejection mass spectrometry (ADE-MS) has recently emerged as a promising label-free, MS-based readout method for high throughput screening (HTS) campaigns in early pharmaceutical drug discovery, since it enables high-speed analysis directly from 384- or 1536-well plates. In this manuscript we describe our characterization of an ADE-MS based high sample content enzymatic assay for mutant isocitrate dehydrogenase 1 (IDH1) R132H with a strong focus on assay development. IDH1 R132H has become a very attractive therapeutic target in the field of antitumor drug discovery, and several pharmaceutical companies have attempted to develop novel small molecule inhibitors against mutant IDH1. With the development of an mIDH1 ADE-MS based HTS assay and a detailed comparison of this new readout technique to the commonly used fluorescence intensity mIDH1 assay, we demonstrated good correlation of both methods and were able to identify new potent inhibitors of mIDH1.

Integrated optical waveguide atomic force microscopy system with a differential splitter readout

There is an urgent need for high-speed atomic force microscopy (AFM) systems, and chip-AFM on an integrated optical waveguide provides a perfect solution. A differential splitter of double waveguides is introduced as a readout method of an integrated optical waveguide AFM to overcome the non-linear response of a conventional optical waveguide AFM. Results show that an optical waveguide AFM with a 190 nm width and 1 μm height nano-tip shows a good monotonic dependence on the cantilever deflection within a range of ± 0.4 μm using a differential splitter readout method.

Lymphocyte transformation test for drug allergy detection: When does it work?

BackgroundThe lymphocyte transformation test (LTT) is an in vitro test system for the detection of a sensitization in the context of allergies to drugs. Its reported sensitivity varies largely and seems to be affected by different parameters. In review articles, the average LTT performance was often calculated by combining overall mean sensitivities of various published studies, but without considering different patient characteristics or varying patient numbers per publication. ObjectiveTo investigate the impact of different patient-specific and methodological parameters on the sensitivity of the LTT based on data on the level of the individual patient extracted from single studies. MethodsWe performed an advanced literature search in PubMed and screened the identified publications according to previously defined inclusion criteria. In total, individual patient data from 721 patients were extracted from 30 studies. Random-effects meta-regression analyses were performed. ResultsThe analysis indicate that the enzyme-linked immunosorbent assay–based read-out is more sensitive compared with the classical radioactivity method (enzyme-linked immunosorbent assay: 80% vs radioactivity: 66%; P = .08). Interestingly, drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome is associated with a higher probability of a positive LTT test result compared with other investigated clinical phenotypes (“drug reaction with eosinophilia and systemic symptoms/drug-induced hypersensitivity syndrome” vs “bullous reaction”; odds ratio, 2.52; P value = .003). Our analysis also revealed an impact of the time to testing period after the occurrence of the allergic event (“< 2 weeks” vs “2 weeks-2 months”; odds ratio, 2.12; P value = .03). ConclusionThe read-out method and relevant clinical parameters affect the sensitivity of the LTT. These findings are based on a meta-analysis providing a higher level of evidence than a single study or previous reviews not considering individual patient data.

RNase H-based analysis of synthetic mRNA 5' cap incorporation.

Advances in mRNA synthesis and lipid nanoparticles technologies have helped make mRNA therapeutics and vaccines a reality. The 5′ cap structure is a crucial modification required to functionalize synthetic mRNA for efficient protein translation in vivo and evasion of cellular innate immune responses. The extent of 5′ cap incorporation is one of the critical quality attributes in mRNA manufacturing. RNA cap analysis involves multiple steps: generation of predefined short fragments from the 5′ end of the kilobase-long synthetic mRNA molecules using RNase H, a ribozyme or a DNAzyme, enrichment of the 5′ cleavage products, and LC-MS intact mass analysis. In this paper, we describe (1) a framework to design site-specific RNA cleavage using RNase H; (2) a method to fluorescently label the RNase H cleavage fragments for more accessible readout methods such as gel electrophoresis or high-throughput capillary electrophoresis; (3) a simplified method for post-RNase H purification using desthiobiotinylated oligonucleotides and streptavidin magnetic beads followed by elution using water. By providing a design framework for RNase H-based RNA 5′ cap analysis using less resource-intensive analytical methods, we hope to make RNA cap analysis more accessible to the scientific community.

Coulometric ion sensing with Li+-selective LiMn2O4 electrodes

A coulometric signal readout method, which was originally developed for solid-contact ion-selective electrodes, was investigated in this work using LiMn2O4 (LMO) as a combined ion-recognition and signal-transduction layer. The redox process of LMO, which is associated with reversible intercalation/expulsion of Li+ ions, allowed coulometric sensing of Li+ ions in aqueous solutions. On increasing the active area (mass loading) of LMO, the coulometric signal increased for a given change in Li+ ion activity. The excellent redox reversibility of LMO and its relatively low resistance were instrumental in achieving a high signal amplification together with a relatively fast response. Coating the LMO layer with a conventional Li+-selective plasticized PVC membrane was found to dramatically lower the coulometric response. Hence, the application of LMO as a combined Li+-selective electrode material and ion-to-electron transducer was found to be highly compatible with the coulometric signal readout method, especially for detecting small Li+ activity changes at high Li+ concentrations.

Radiology trainee and attending satisfaction with virtual readouts during the COVID-19 pandemic

Rationale and objectivesIn response to COVID-19, our institution implemented three virtual readout systems: a commercial HIPAA compliant web-based video conferencing platform used for screen-sharing (Starleaf), an interactive control sharing system integrated into PACS allowing simultaneous multi-user mouse control over images (Collaborate), and the telephone. Our aim was to assess overall satisfaction with and perceived effectiveness of these virtual readout methods to optimize best practices for the future. Materials and methodsAn IRB-exempt survey was electronically distributed to 64 trainees and 76 attendings at one tertiary-care institution via Survey Monkey. Questions focused on overall satisfaction, perceived effectiveness, technical difficulties, and continued future use of the three virtual readout strategies. Answers were collected with Likert scales, tick boxes, and open-ended questions. Results32/64 trainees (50%) and 32/76 attendings (42%) completed the survey. Trainees and attendings were more satisfied with screen sharing (Starleaf) and perceived it more effective than control sharing (Collaborate) or the telephone (p < 0.0001). Respondents experienced more technical difficulties with control sharing versus screen sharing (p = 0.0004) with a negative correlation between level of technical difficulties and satisfaction with screen sharing (r = −0.50, p < 0.0001) and control sharing (r = −0.38, p = 0.0006). Trainees and faculty supported a combination of in-person and virtual readouts in the future (p < 0.0001). ConclusionPlatforms mirroring in-person readouts, such as Starleaf, are preferred by both trainees and attendings over non-screen sharing platforms such as the telephone. However, technical stability determines satisfaction between similar platforms. Both trainees and attendings support incorporation of virtual readout methods in combination with traditional in-person readouts in the post-COVID-19 era.

Optically stimulated luminescence in state-of-the-art LYSO:Ce scintillators enables high spatial resolution 3D dose imaging

In this contribution, we study the optically stimulated luminescence (OSL) exhibited by commercial hbox {Lu}_{(2-x)}hbox {Y}_xhbox {SiO}_5:Ce crystals. This photon emission mechanism, complementary to scintillation, can trap a fraction of radiation energy deposited in the material and provides sufficient signal to develop a novel post-irradiation 3D dose readout. We characterize the OSL emission through spectrally and temporally resolved measurements and monitor the dose linearity response over a broad range. The measurements show that the hbox {Ce}^{3+} centers responsible for scintillation also function as recombination centers for the OSL mechanism. The capture to OSL-active traps competes with scintillation originating from the direct non-radiative energy transfer to the luminescent centers. An OSL response on the order of 100 ph/MeV is estimated. We demonstrate the imaging capabilities provided by such an OSL photon yield using a proof-of-concept optical readout method. A 0.1 hbox {mm}^3 spatial resolution for doses as low as 0.5 Gy is projected using a cubic crystal to image volumetric dose profiles. While OSL degrades the intrinsic scintillating performance by reducing the number of scintillation photons emitted following the passage of ionizing radiation, it can encode highly resolved spatial information of the interaction point of the particle. This feature combines ionizing radiation spectroscopy and 3D reusable dose imaging in a single material.

Intrinsically accurate sensing with an optomechanical accelerometer.

We demonstrate a microfabricated optomechanical accelerometer that is capable of percent-level accuracy without external calibration. To achieve this capability, we use a mechanical model of the device behavior that can be characterized by the thermal noise response along with an optical frequency comb readout method that enables high sensitivity, high bandwidth, high dynamic range, and SI-traceable displacement measurements. The resulting intrinsic accuracy was evaluated over a wide frequency range by comparing to a primary vibration calibration system and local gravity. The average agreement was found to be 2.1 % for the calibration system between 0.1 kHz and 15 kHz and better than 0.2 % for the static acceleration. This capability has the potential to replace costly external calibrations and improve the accuracy of inertial guidance systems and remotely deployed accelerometers. Due to the fundamental nature of the intrinsic accuracy approach, it could be extended to other optomechanical transducers, including force and pressure sensors.

Evidence for spin swapping in an antiferromagnet

Antiferromagnetic insulators offer strategic advantages in spintronic applications because of their negligible stray fields and ultrafast magnetic dynamics. Control of their magnetization and readout of their magnetic state are essential for these applications but remain challenging. Here we report the electrical detection of room-temperature magnetization switching in the canted antiferromagnetic insulator LaFeO3, capped with a Pt or W overlayer. The observation of a large magneto-thermovoltage with an in-plane temperature gradient suggests that the mechanism is the swapping of spin currents in the antiferromagnet. This effect provides a sensitive electrical probe of the tiny net magnetization in the insulator, which can be manipulated by a magnetic field on the order of 10 mT. Our results highlight a new material class of insulating canted antiferromagnets for spintronics and spin caloritronics and suggests a method for the electrical readout of magnetic signals in an antiferromagnetic insulator.

Deep learning based semantic segmentation and quantification for MRD biochip images

Microfluidic platforms offer prominent advantages for the early detection of cancer and monitoring the patient response to therapy. Numerous microfluidic platforms have been developed for capturing and quantifying the tumor cells integrating several readout methods. Earlier, we have developed a microfluidic platform (MRD Biochip) to capture and quantify leukemia cells. This is the first study which employs a deep learning-based segmentation to the MRD Biochip images consisting of leukemic cells, immunomagnetic beads and micropads. Implementing deep learning algorithms has two main contributions; firstly, the quantification performance of the readout method is improved for the unbalanced dataset. Secondly, unlike the previous classical computer vision-based method, it does not require any manual tuning of the parameters which resulted in a more generalized model against variations of objects in the image in terms of size, color, and noise. As a result of these benefits, the proposed system is promising for providing real time analysis for microfluidic systems. Moreover, we compare different deep learning based semantic segmentation algorithms on the image dataset which are acquired from the real patient samples using a bright-field microscopy. Without cell staining, hyper-parameter optimized, and modified U-Net semantic segmentation algorithm yields 98.7% global accuracy, 86.1% mean IoU, 92.2% mean precision, 92.2% mean recall and 92.2% mean F-1 score measure on the patient dataset. After segmentation, quantification result yields 89% average precision, 97% average recall on test images. By applying the deep learning algorithms, we are able to improve our previous results that employed conventional computer vision methods.