Readout Technology Research Articles

超分辨近场结构光盘的传统以及差分读出方法研究

超分辨近场结构光盘的传统以及差分读出方法研究

Thermally Denatured BSA, a Surrogate Additive to Replace BSA in Buffers for High-Throughput Screening

The use of thermally denatured bovine serum albumin (tdBSA) as an additive in high-throughput screening (HTS) buffers has been studied with the aim of finding a surrogate to native albumin devoid of its inconveniences, in particular its compound masking effect. The presence of aggregates in the thermally denatured material did not have any negative impact on common readout technologies used in HTS such as fluorescence intensity (FLINT), fluorescence polarization, time-resolved fluorescence resonance energy transfer (TR-FRET) and luminescence. tdBSA rendered the same beneficial effects as native albumin in several assays or even improved its performance due to the lack of specific binding properties. Although tdBSA still binds compounds nonspecifically as any other protein does, it mitigates the compound masking effect observed with native albumin and can be postulated as a convenient surrogate to BSA for HTS purposes.

Affinity-based screening techniques: their impact and benefit to increase the number of high quality leads

Importance of the field: The generation of new chemical leads as a starting point for drug development is a critical step in pharmaceutical drug discovery. High-throughput screening and the attached processes have rapidly evolved over the past few years to become one of the main sources for new leads by testing large compound libraries for activity against a target of interest in biochemical in vitro tests using the recombinant protein or cell-based assays. Very recently, the traditional functional assay read-out technologies are being complemented by biophysical methods which directly measure the physical interaction (affinity) between a low molecular weight compound and a target protein. These technologies are receiving increasing attention and application for affinity screening and increasingly complement and augment the more classical activity screens. Today, such biophysical techniques are applied in hit identification as well as later stages such as hit validation, optimization and lead optimization phase.Areas covered in this review: This review focuses on the principle and application of selected affinity-based screening technologies, especially those which increasingly have been used in different phases of the lead finding process over the past few years. Furthermore, we highlight how throughput, robustness and information content of the discussed methods guide and determine their impact in lead finding and how to make the best use of them.What the reader will gain: The reader will gain an insight into the very broad spectrum of biophysical affinity screening methods and its high potential to support the generation of new leads. As a consequence, the reader will be able to judge which affinity method is of advantage at a certain lead discovery phase.Take home message: Biophysical methods are very powerful tools to identify new hits and/or validate/optimize a hit to a lead. Those technologies often offer novel ways of screening complementing available classical screening technologies. An integrated, holistic approach using the combination of functional read-out technologies with different biophysical methods enables a project team to efficiently promote and progress the most promising chemotypes.

Readout ASIC With SOI Technology for X-Ray CCDs

We developed an analog front-end application specific integrated circuit (ASIC) with a fully depleted (FD) silicon-on-insulator (SOI) technology for readout of X-ray CCDs. The ASIC contains seven readout channels, each of which is equipped with the correlated double sampling circuit followed by an amplitude-to-pulse width conversion circuit. We combined the ASIC with an X-ray CCD for performance evaluation tests. We succeeded in processing analog signals from the CCD and confirmed an X-ray imaging and photon-counting capabilities by irradiating a radioisotope <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">55</sup> Fe. The energy resolution is 305 eV at 5.9 keV (full-width at half maximum) and the readout noise is 53.7 μV for power consumption of 33 mW per chip. The ASIC proves that the FD-SOI process can be a practically usable option for front-end applications.

Quality control and single nucleotide resolution analysis of methylated DNA immunoprecipitation products

DNA methylation patterns are altered in many diseases, and their analysis has become of great interest. Methylated DNA immunoprecipitation (MeDIP) is a simple method to enrich the methylated fraction of the genome. However, it has been difficult to assess the quality and the detailed methylation patterns of the immunoprecipitated DNA. Here we present a simple method for the analysis of the immunoprecipitated DNA at single nucleotide resolution by bisulfite treatment and pyrosequencing of genomic regions. The presented method can be used as an initial quality measure prior to genome-wide read-out technologies such as microarrays and second-generation sequencing.

New optical technology for low mass intelligent trigger and readout

New optical devices offer the potential for reductions in mass, power, and cost of data paths for on-board trigger and readout of tracking detectors. We give examples of optical modulators, MEMS beam steering devices, and optical coupling. We also present results on radiation hardness of materials as well as different approaches to using optics in triggering.

Impact of new technologies for cellular screening along the drug value chain

High-information screening formats, using more physiologically relevant cellular models and readout approaches, are slowly replacing traditional, target-orientated approaches in drug discovery programs. With improved access to primary cells, as well as label-free, non-intrusive methods of compound interrogation (such as automated electrophysiology), high-thoughput screening facilities have to adapt to more complex assay scenarios. The implementation of novel cellular systems, readout technologies and data management in a drug discovery company are essential to improve the current falling productivity evident in recent years throughout the pharmaceutical industry.

Development of high resolution Micro-Pattern Gas Detectors with wide readout pads

A Micro Pattern Gas Detector (MPGD) requires 200 μm wide anode readout pads to achieve ∼ 40 μm resolution. With the development of the new charge dispersion readout concept for MPGDs with a resistive anode, comparable resolution can be achieved with order of magnitude wider pads. We present here an overview and present status of the charge dispersion MPGD readout technology. The development of MPGDs with a resistive anode may permit experiments with large area high resolution tracking requirements to consider using MPGDs which would have been otherwise prohibitive due to excessive readout channel count.

Advances in Computed Radiography: Dual-Side Readout

Computed radiography is the generic term given to the class of digital radiographic detectors that use photostimulable storage phosphors (PSPs) to absorb incident x-ray energy with the subsequent storage of proportional charge at localized energy traps and subsequent laser-moderated photostimulated luminescence (PSL) to measure and convert the trapped energy into a corresponding digital image. Recent advances in computed radiographic (CR) detector and readout technology have been the introduction of dual-side readout methods, structured PSP detectors, and parallel readout methods [ 1 Cowen A.R. Davies A.G. Kengylics S.M. Advances in computed radiography systems and their physical imaging characteristics. Clin Radiol. 2007; 62: 1132-1141 Abstract Full Text Full Text PDF PubMed Scopus (45) Google Scholar ]. This technical note reviews the characteristics and benefits of dual-side readout methods for CR imaging, which were first introduced with prototype digital mammographic cassette-based systems in about 2001 and subsequently with clinical radiographic systems from 2004 to the present.

Sensing mechanism of room temperature CO 2 sensors based on primary amino groups

This work reports measurements to elucidate the reaction mechanisms of sensitive materials containing primary amino groups with CO 2. The sensing mechanism is based on their ability to perform reversible acid–base reactions. The effect discussed for most of the previously used sensing layers concerns the formation of bicarbonate species, which requires H 2O as well as an increased temperature. By using work function readout technology an operation at room temperature of the sensing layers is enabled providing satisfying sensor responses in terms of SNR ( signal noise ratio) and response time. In contrast to the previously investigated higher operation temperature, the response resulting from a room temperature measurement appears to be dominated by the reversible formation of carbamate, which does not require the presence of water. The presence of carbamate is considered to be the reason of the improved sensing performance of this sensing material at room temperature with work function readout. To confirm this hypothesis, DRIFT-MIR, Raman, XPS and NMR spectroscopy were employed to investigate the formation of species after manufacturing of the sensitive layers. Besides the formation of bicarbonate, the results show a strong indication for carbamate formation.

Novel trends in high-throughput screening

High-throughput screening (HTS) is a well-established process for lead discovery in Pharma and Biotech companies and is now also being used for basic and applied research in academia. It comprises the screening of large chemical libraries for activity against biological targets via the use of automation, miniaturized assays and large-scale data analysis. Since its first advent in the early to mid 1990s, the field of HTS has seen not only a continuous change in technology and processes, but also an adaptation to various needs in lead discovery. HTS has now evolved into a mature discipline that is a crucial source of chemical starting points for drug discovery. Whereas in previous years much emphasis has been put on a steady increase in screening capacity ('quantitative increase') via automation and miniaturization, the past years have seen a much greater emphasis on content and quality ('qualitative increase'). Today, many experts in the field see HTS at a crossroad with the need to decide on either higher throughput/more experimentation or a greater focus on assays of greater physiological relevance, both of which may lead to higher productivity in pharmaceutical R&D. In this paper, we describe the development of HTS over the past decade and point out our own ideas for future directions of HTS in biomedical research. We predict that the trend toward further miniaturization will slow down with the balanced implementation of 384 well, 1536 well, and 384 low volume well plates. Furthermore, we envisage that there will be much more emphasis on rigorous assay and chemical characterization, particularly considering that novel and more difficult target classes will be pursued. In recent years we have witnessed a clear trend in the drug discovery community toward rigorous hit validation by the use of orthogonal readout technologies, label free and biophysical methodologies. We also see a trend toward a more flexible use of the various screening approaches in lead discovery, that is, the use of both full deck compound screening as well as the use of focused screening and iterative screening approaches. Moreover, we expect greater usage of target identification strategies downstream of phenotypic screening and the more effective implementation of affinity selection technologies as a result of advances in chemical diversity methodologies. We predict that, ultimately, each hit finding strategy will be much more project-related, tailor-made, and better integrated into the broader drug discovery efforts.

Charge collection efficiencies of planar silicon detectors after reactor neutron and proton doses up to [formula omitted

The planned luminosity upgrade of the large hadron collider at CERN (Super-LHC) will provide a challenging environment for the tracking and vertexing detector systems. The innermost devices at a radius about 4 cm from the interaction region will have to be able to withstand a combined charged and neutron hadron dose in the order of 10 16 1 MeV neutron equivalent particles ( n eq ) per square centimeter over the anticipated 5 year lifespan of the SLHC experiments. Planar, segmented silicon detectors with n-strip readout are one of the many radiation tolerant technologies under consideration for use for the Super-LHC tracking detectors in either pixel or strip geometries. This paper details charge collection efficiency measurements made with silicon sensors that have been irradiated to doses as high as 1.5 × 10 16 n eq cm - 2 with reactor neutrons and as high as 1.6 × 10 16 n eq cm - 2 with 26 MeV protons and 24 GeV protons. In this study, n + segmented strip readout in either n-bulk (n-in-n) or p-bulk (n-in-p) substrates are considered. Both diode configurations were processed in substrates grown with float zone (FZ) and magnetic Czochralski (MCz) techniques. For the fluences studied, all the n + strip readout technologies are still viable assuming that adequate bias voltage and cooling can be supplied and low noise, low threshold readout electronics can be designed.

Nano-engineered ultra-high-gain microchannel plates

Highly localized and very fast electron amplification of microchannel plates (MCPs) enables a large number of high-resolution and high-sensitivity detection technologies, which provide spatial and/or temporal information for each detected photon/electron/ion/neutron. Although there has been significant progress in photocathode and readout technologies the MCPs themselves have not evolved much from the technology developed several decades ago. Substantial increases in the gain of existing MCP technology have been accomplished by utilizing state-of-the-art processes developed for nano-engineered structures. The gain of treated MCPs with aspect ratio of 40:1 is reproducibly measured to reach unprecedented values of 2×10 5. This gain enhancement is shown to be stable during MCP operation. In addition, the initial experiments indicate improved stability of gain as a function of extracted charge and MCP storage conditions. We also present results from a fully independent thin-film process for manufacturing non-lead glass MCPs using engineered thin films for both the resistive and emissive layers. These substrate-independent MCPs show high gain, less gain degradation with extracted charge, and greater pore-to-pore and plate-to-plate uniformity than has been possible with conventional lead glass structures.

A Fluorescence Lifetime-Based Assay for Protease Inhibitor Profiling on Human Kallikrein 7

Fluorescence lifetime is an intrinsic parameter describing the fluorescence process. Changes in the fluorophore's physicochemical environment can lead to changes in the fluorescence lifetime. When used as the readout in biological assays, it is thought to deliver superior results to conventional optical readouts. Hence it has the potential to replace readout technologies currently established in drug discovery such as absorption, luminescence or fluorescence intensity. Here we report the development of an activity assay for human kallikrein 7, a serine protease involved in skin diseases. As a probe, we have selected a blue-fluorescent acridone dye, featuring a remarkably long lifetime that can be quenched by either of the 2 natural amino acids, tyrosine and tryptophan. Incorporating this probe and 1 of the quenching amino acids on either side of the scissile bond of the substrate peptide enables us to monitor the enzymatic activity by quantifying the increase in the fluorescence lifetime signal. A systematic investigation of substrate structures has led to a homogenous, microplate-based, compound profiling assay that yields inhibitory constants down into the single-digit nanomolar range. This type of assay has now been added to our standard portfolio of screening techniques, and is routinely used for compound profiling.

Typetesting of physical characteristics of digital mammography systems for screening within the Flemish breast cancer screening programme

To investigate compliance with the acceptance criteria of the European guidelines for quality assurance in breast cancer screening, a typetesting programme of the physical characteristics of digital mammography systems based on direct readout (DR) technology or computed radiography (CR) was organised and executed within the Flemish breast cancer screening programme. While in general image quality/dose characteristics of flat panel DR systems passed the acceptance criteria more easily than CR systems, the slit-scanning direct photon counting system included in present study was outstanding in combining a very low dose with a good image quality. The data obtained up to now indicate the necessity of retuning the AEC for DR systems according to constant contrast to noise ratio (CNR) over the whole range of PMMA thicknesses (20–70 mm) to improve image quality in imaging breasts of large thickness at the cost of higher doses. For the two CR systems which passed the typetesting procedure dose levels do not allow a similar improvement of CNR for thick objects for these systems. The obtained results highlight the importance of the use of high Z target/filter combinations in X-ray generating systems for imaging thick objects to meet the image quality/dose criteria. With respect to image display aspects high-quality 3-megapixel LCD monitors succeeded also in the typetesting procedure in addition to 5-megapixel monitors. However, as zooming and scrolling are necessary for 3-megapixel monitors to get the full resolution capabilities of the image capture system, 5-megapixel monitors are preferred in a busy screening environment.

Digital radiography detectors – A technical overview: Part 1

During the last two decades screen-film (SF) systems have been replaced by digital X-ray systems. The advent of digital technologies brought a number of digital solutions based on different detector and readout technologies. Improvements in technology allowed the development of new digital technologies for projection radiography such as computed radiography (CR) and digital radiography (DR). The large number of scientific papers concerning digital X-ray systems that have been published over the last 25 years indicates the relevance of these technologies in healthcare. There are important differences among different detector technologies that may affect system performance and image quality for diagnostic purposes. Radiographers are expected to have an effective understanding of digital X-ray technologies and a high level of knowledge and awareness concerning the capabilities of these systems. Patient safety and reliable diagnostic information are intrinsically linked to these factors. In this review article – which is the first of two parts – a global overview of the digital radiography systems (both CR and DR) currently available for clinical practice is provided.

Fluxonic cellular automata

We propose a quantum cellular automata composed of nanostructured mesoscopic superconducting squares, where the logic states are defined by two trapped vortices in a 2×2 blind hole matrix. We present the functioning logic gate based on this fluxonic cellular automata, where the logic operations are verified through theoretical simulations within the Ginzburg-Landau formalism. The input signals are defined using the vortex interaction with current loops placed on top of the two diagonal blind holes of the input cell. The readout technology may be chosen from a large variety of modern vortex imaging methods, transport, and local density of states measurements.

Calibration model of a dual gain flat panel detector for 2D and 3D x‐ray imaging

The continuing research and further development in flat panel detector technology have led to its integration into more and more medical x-ray systems for two-dimensional (2D) and three-dimensional (3D) imaging, such as fixed or mobile C arms. Besides the obvious advantages of flat panel detectors, like the slim design and the resulting optimum accessibility to the patient, their success is primarily a product of the image quality that can be achieved. The benefits in the physical and performance-related features as opposed to conventional image intensifier systems, (e.g., distortion-free reproduction of imaging information or almost linear signal response over a large dynamic range) can be fully exploited, however, only if the raw detector images are correctly calibrated and postprocessed. Previous procedures for processing raw data contain idealizations that, in the real world, lead to artifacts or losses in image quality. Thus, for example, temperature dependencies or changes in beam geometry, as can occur with mobile C arm systems, have not been taken into account up to this time. Additionally, adverse characteristics such as image lag or aging effects have to be compensated to attain the best possible image quality. In this article a procedure is presented that takes into account the important dependencies of the individual pixel sensitivity of flat panel detectors used in 2D or 3D imaging and simultaneously minimizes the work required for an extensive recalibration. It is suitable for conventional detectors with only one gain mode as well as for the detectors specially developed for 3D imaging with dual gain read-out technology.

Advances in Digital Radiography: Physical Principles and System Overview

During the past two decades, digital radiography has supplanted screen-film radiography in many radiology departments. Today, manufacturers provide a variety of digital imaging solutions based on various detector and readout technologies. Digital detectors allow implementation of a fully digital picture archiving and communication system, in which images are stored digitally and are available anytime. Image distribution in hospitals can now be achieved electronically by means of web-based technology with no risk of losing images. Other advantages of digital radiography include higher patient throughput, increased dose efficiency, and the greater dynamic range of digital detectors with possible reduction of radiation exposure to the patient. The future of radiography will be digital, and it behooves radiologists to be familiar with the technical principles, image quality criteria, and radiation exposure issues associated with the various digital radiography systems that are currently available.

Simultaneous PET/MR will replace PET/CT as the molecular multimodality imaging platform of choice

Suggestions for topics suitable for these Point/Counterpoint debates should be addressed to Colin G. Orton, Professor Emeritus, Wayne State University, Detroit: ortonc@comcast.net. Persons participating in Point/Counterpoint discussions are selected for their knowledge and communicative skill. Their positions for or against a proposition may or may not reflect their personal opinions or the positions of their employers.