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high-throughput screening (hts) | bmg labtech

high-throughput screening (hts) | bmg labtech

A tool for running millions of biological or chemical tests in a short time is high-throughput screening. It is mainly used in drug discovery processes to identify biologically relevant compounds. Following you will learn what high throughput screening is, what is required to run high-throughput tests and which assays are primarily used.

High-throughput screening (HTS) is a drug discovery process that allows automated testing of large numbers of chemical and/or biological compounds for a specific biological target. High-throughput screening methods are extensively used in the pharmaceutical industry, leveraging robotics and automation to quickly test the biological or biochemical activity of a large number of molecules, usually drugs. They accelerate target analysis, as large scale compound libraries can quickly be screened in a cost effective way. HTS is a useful tool for assessing for instance pharmacological targets, pharmacologically profiling agonists and antagonists for receptors (such as GPCRs) and enzymes.

The primary goal of HTS is to identify through compound library screenings, candidates that affect the target in the desired way, so called hits or leads. This is usually achieved employing liquid handling devices, robotics, plate readers as detectors and dedicated software for instrumentation control and data processing.

Importantly, high-throughput screening processes do not usually identify drugs, as several properties that are critical to the development of a new drug cannot be assessed by compound library screening. For instance HTS cannot evaluate toxicity and bioavailability. The primary role of high-throughput screening assays is instead to identify leads and provide suggestions for their optimization. The results of HTS assays provide hence the starting point for further steps in the drug discovery pipeline like drug design, and for understanding the interaction or role of a particular biochemical process.

In recent times, HTS was largely enabled by the modern advances in robotics, liquid handling, plate reader detection as well as high-speed computers. Nevertheless, to run effectively, high-throughput screening still requires a highly specialized and expensive screening facility that not every lab can afford. As an alternative to setting up ones own facility, institutions with limited budgets usually access HTS services provided by third party provides such as Contract Research Organisations (CRO) or, mainly in an academic environment, core facilities.

Samples are usually of cellular or biochemical nature, depending on the assay to be run. High-throughput screening necessitates that samples are prepared in an arrayed format. The key platform or sample carrier used is therefore the microplate. Typical formats include 384-, 1536-, or 3456-well plates. The nature of the sample and of the detection assay may affect the choice of the microplate format and its colour. Screening facilities usually keep their compound library collections stored in so called stock plates. Stock plates are not directly used in experiments. Instead, when needed, compounds from a stock plate are copied to an assay plate through a pipetting station.

Automation is an important element in HTS as conversion of a benchtop to an automated high-throughput screening assay enforces specific constraints affecting the practical assay design. Ideally, a HTS assay is performed in a single well, with a low amount of reagents (miniaturization), and minimal or no further manipulation than injection of the sample/compound to be tested. Accordingly, the choice of the optimal detection mode and assay has to be subordinated to automation issues.For more information on the identification of false positives in screening attempts please see AN 359: Identification of false positives in a HTRF screen for small molecule inhibitors of PD-1/PD-L1.

Establishing a stringent assay and an effective quality control method are major issues when setting up an automated screen. The clearer the distinction between negative and positive controls, the higher the possibility to obtain high-quality data with a neglectable number of false negative but especially false positive results.

The scope of a robotic platform is to autonomously manage multiple plates simultaneously, significantly speeding up data acquisition. Robotic platforms for high-throughput screenings range from simple automated liquid handling machines to multidimensional workstations performing multiple functions. This is usually achieved with the support of one or more mechanical arms. Typically, a robotic system manages microplates from station to station for several steps such as reagent addition, mixing, incubation, and detection.

In high-throughput screenings data acquisition is usually performed by an optical measurement, quantifying the amount of light produced by the sample. Different readouts such as fluorescent or luminescent detection, colourimetry, or light scatter (turbidity) are available. Common detection modes include fluorescence intensity and polarization, FRET, time-resolved fluorescence (e.g.: HTRF, LANCE, etc), luminescence (e.g.: NanoBRET), and AlphaScreen.

Depending on the biological question to be answered, data quality as well as cost-effectiveness, different light-based detection readouts may be chosen. Specialized instrumentation, like multi-mode microplate readers, can sequentially perform different experiments or apply different detection protocols on the wells. The output thereof is a grid of numeric values.

To better understand what are the microplate reader requirements of screening facilities, read here Mark Wigglesworths full interview. Mark is Director of High-Throughput Screening at AstraZeneca in the UK and has integrated a PHERAstar FSX in AstraZeneca's screening facility.

We found that the improvements in the new PHERAstar FSX outperformed our historic experiences and the other readers in our trial. The reader has fitted well into our assay development and screening groups, where it has been used frequently for a variety of technologies.

A HTS-dedicated plate reader can measure hundreds of plates in a single day, generating a considerable amount of data points. Consequently, data management is a critical point in automated high-throughput screening, given the large number of compounds tested, the variety of chemical libraries and the necessity to correlate and compare results from different screening campaigns. Dedicated data analysis and management platforms (e.g.: Genedata) intertwine data originated from different screening campaigns with compound structures, as well as performed assays to each other, facilitating the extraction of detailed information from different perspectives.

Compound library screenings have to be usually measured as fast as possible, in very small volumes (a few L) and produce robust results. Besides the ease of use and flexibility to perform different assays, this requires a very sensitive and precise instrumentation. Watch Cline Legros from Servier, France, commenting on her experience with the PHERAstar platform.

Although one of the most targeted group of receptors in drug screening are G-Protein Coupled Receptors (GPCRs), not every benchtop assay can be converted to an automated HTS, especially when using living cells. Application Note 287 describes how for the first time NanoBRET was successfully used to monitor ligand-GPCRs binding in living cells.

An important issue in HTS is miniaturisation. Samples have to be as small as possible in order to save costs, but still deliver reliable results. The sensitivity of the microplate reader and its ability to reliably measure samples in high-density plate formats is consequently of great importance. In Application Note 229, DiscovereX PathHunter reporter cell lines were measured with the PHERAstar FS in both 1536- and 3456-well plates. The reader was able to detect signal coming from as few as 1,000 cells in a 1,536- and 250 cells in a 3,456-well plate. Similarly, Application Note 260 shows how an AlphaLISA assay was miniaturized down to 2 L per sample in a 1536-well plate and detected on the PHERAstar FS.

In drug screening, speed is as important as miniaturization. Application Note 295 shows how the PHERAstar FSX equipped with the TRF excitation laser, is able to detect HTRF assays in 1536-well plates on the fly in only 36 seconds, still delivering a Z` value > 0.8.

The Pivot Park Screening Centre in Oss, the Netherlands, relies on the PHERAstar FSX for effective hit discovery. In our customer success story Improving hit discovery efficiency at Europes leading screening centre, their CTO, Steven van Helden discusses innovation in drug discovery and the future of screening technology.

In the post Choosing the best microplate reader, Mark Wigglesworth, Director High Throughput Screening at AstraZeneca UK discusses the microplate reader requirements needed to keep up with AZs screening necessities and why AZ chose the PHERAstar FSX.

Searching for novel kinase inhibitors with the PHERAstar FSX plate reader at BIENTA laboratory in Kyiv, Ukraine. The HTS group screened more than 600,000 compounds in kinase assays using ATP depletion assay, measuring luminescence in a coupled luciferase reaction.

PHERAstar plate readers are routinely used in the laboratory as they provide an accurate signal, high throughput and sensitivity, as well as stable temperature control required for luminescent kinase assays.

3733 | jbl professional loudspeakers

3733 | jbl professional loudspeakers

For critical sound reproduction in cinemas utilizing a solid screen. The 3733 uses the 4739 LF for increased low frequency output. The M/HF utilizes Dual Dissimilar Arraying technology to shape the coverage pattern for the optimal use. In addition the horn design improves the frequency response and lowers distortion at higher output. The 2415-XP high frequency drivers represent JBLs latest HF compression driver, designed to achieve higher output with lower harmonic distortion.

reducing blue light on your pc screen | hp tech takes

reducing blue light on your pc screen | hp tech takes

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dg900 high resolution arbitrary waveform generators with sifi ii technology | rigol

dg900 high resolution arbitrary waveform generators with sifi ii technology | rigol

To get started using your instruments over the bus download UltraSigma instrument communication software or for older instruments or customized installations review the How to Guide: Using VISA and drivers to communicate with instruments

Ultra Station-adv Full advanced version of UltraStation wave generation software for DG1000Z, DG4000, DG5000 Series generators as well as DS1000Z and DS2000A "-S" embedded generators. This is a software upgrade license.

9350 | jbl professional loudspeakers

9350 | jbl professional loudspeakers

The 9350 packs a sonic punch, and delivers extraordinary coverage through its advanced engineering, including three patent-pending technologies. Each loudspeaker generates a sculpted side or rear pattern, adjusted with the flick of a switch. With a passive crossover network, waveguide technologies, and line array techniques, coverage can be adjusted to fit a theatre's unique environment. The 9350 further enhances coverage by configurable vertical and horizontal coverage angles based on whether the surround is located on the rear or side wall location. The result? Premium performance and left/right balance overall, an accomplishment unheard of in cinema. It means the sonic sweet spot just got a whole lot bigger, and that sculpted, impactful sound now comes from all sides. Ultimately, the audience becomes immersed in an audio experience like none other. Rely on the 9350, the ideal complement to front screen loudspeakers, for superior sonic character and dynamics - everywhere.

The 2520 Quick Mount Surround Bracket is a new loudspeaker accessory which should be used for wall mounting applications when installing 9300 Series Surrounds. Specific models include: 9300, 9310, 9320, and 9350. The 2520 bracket is not recommended for ceiling mount applications

ease screen recorder- v3.6017

ease screen recorder- v3.6017

Ease Screen Recorder

the action priority matrix - time management tools from

the action priority matrix - time management tools from

By choosing activities intelligently, we can make the very most of our time and opportunities. However, by choosing badly, we can bog ourselves down in time-depleting, low-yield projects that stop us moving forward.

This is where an "Action Priority Matrix" can be useful. These simple diagrams help you choose the activities you should prioritize and the ones you should avoid, if you want to make the most of your time and opportunities.

This is useful, because we rarely have time to complete all of the tasks and projects on our wish lists. When we use the matrix to choose activities intelligently, we can spend more of our time on the high-value activities that keep us moving forwards.

Use common sense to interpret the lines that separate the four quadrants. After all, there's only a small difference between a 4.9-impact activity defined as a "thankless task" and a 5.1-impact task defined as a "major project."

The approach we describe above explains how you can use the Action Priority Matrix as an informal or personal way of prioritizing tasks. However, you can use this approach on a larger scale by using, for example, "financial return" as the scale on the vertical axis, and "person months" on the horizontal axis.

Alternatively, you could substitute "feasibility" for "effort" on the horizontal axis to prioritize projects based on your ability to implement them. (This variant is sometimes known as the "Impact/Feasibility Matrix.")

Also see our article on Eisenhower's Urgent/Important Principle this is a similar tool that you can use to manage your priorities, and it is particularly useful for bringing "firefighting" under control.

The Action Priority Matrix is a simple tool that helps you choose which activities to prioritize , and which activities to delegate or eliminate. This helps you make best use of the opportunities available to you.

To use the matrix, make a list of your ongoing activities and goals. Score each task on impact and effort, using a 0 to 10 scale. Next, plot your activities on the matrix, and then prioritize, delegate, or drop activities appropriately.

This site teaches you the skills you need for a happy and successful career; and this is just one of many tools and resources that you'll find here at Mind Tools. Subscribe to our free newsletter, or join the Mind Tools Club and really supercharge your career!

gpr | radiodetection

gpr | radiodetection

GPR (Ground Penetrating Radar) systems enableoperators to detect underground utilities, particularly non-conductive pipes andducts, using high-frequency Radar. When locating underground utilities, GPR can be a valuable complement to electromagnetic cable and pipe locators.

Radiodetection's LMX100 and LMX200innovative GPR systems both use ultra-wide band 250MHz, specifically chosen for effective utility locating. Our GPR products featureinternal GPS and high resolution touch screens. For connectivity and ease of reporting, both offer on-board Wi-Fi and a USB port. Additionally, the LMX200allows users to create depth slices and review their locate path on screen while on site, and selectively enhance shallow/small, medium depth/size, or deep/large targets using the proprietary DynaQ technology.

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