scholarly journals Accelerating High-Throughput Screening for Structural Materials with Production Management Methods

Materials ◽  
2018 ◽  
Vol 11 (8) ◽  
pp. 1330 ◽  
Author(s):  
Alexander Bader ◽  
Finn Meiners ◽  
Kirsten Tracht
Keyword(s):  
High Throughput ◽  
Material Flow ◽  
High Throughput Screening ◽  
Production Management ◽  
Waiting Times ◽  
Complex Structure ◽  
New Drugs ◽  
Order Processing ◽  
Speed Up ◽  
Process Trial

High-throughput screenings are widely accepted for pharmaceutical developments for new substances and the development of new drugs with required characteristics by evolutionary studies. Current research projects transfer this principle of high-throughput testing to the development of metallic materials. In addition to new generating and testing methods, these types of high-throughput systems need a logistical control and handling method to reduce throughput time to get test results faster. Instead of the direct material flow found in classical high-throughput screenings, these systems have a very complex structure of material flow. The result is a highly dynamic system that includes short-term changes such as rerun stations, partial tests, and temporarily paced sequences between working systems. This paper presents a framework that divides the actions for system acceleration into three main sections. First, methods for special applications in high-throughput systems are designed or adapted to speed up the generation, treatment, and testing processes. Second, methods are needed to process trial plans and to control test orders, which can efficiently reduce waiting times. The third part of the framework describes procedures for handling samples. This reduces non-productive times and reduces order processing in individual lots.

High-throughput screening in the diagnostics industry

2002 ◽  
Vol 30 (4) ◽  
pp. 794-797 ◽  
Author(s):  
S. Wilson ◽  
S. Howell
Keyword(s):  
Product Development ◽  
High Throughput ◽  
High Throughput Screening ◽  
Rapid Identification ◽  
Target Antigen ◽  
Cycle Times ◽  
Development Cycle ◽  
Speed Up ◽  
Product Development Cycle ◽  
Automated Screening

The diagnostics industry is constantly under pressure to bring innovation quicker to market and so the impetus to speed up product-development cycle times becomes greater. There are a number of steps in the product-development cycle where the application of high-throughput screening can help. In the case of lateral-flow immunodiagnostics the selection of antibody reagents is paramount. In particular, rapid identification of antibody pairs that are able to ‘sandwich’ around the target antigen is required. One screen that has been applied successfully is the use of surface plasmon resonance biosensors like Biacore®. Using such a system one can evaluate over 400 antibody pairings in under 5 days. Conventional approaches to screen this number of antibody pairs would take many months. Other automated screening systems like DELFIA® can be used in processing the vast amount of tests required for clinical trials. In addition, the use of robotics to automate routine product testing can be used to shorten the product-development cycle.

scholarly journals A Homogeneous, High-Throughput Fluorescence Anisotropy-Based DNA Supercoiling Assay

2010 ◽  
Vol 15 (9) ◽  
pp. 1088-1098 ◽  
Author(s):  
Adam Shapiro ◽  
Haris Jahic ◽  
Swati Prasad ◽  
David Ehmann ◽  
Jason Thresher ◽  
...  
Keyword(s):  
High Throughput ◽  
Fluorescence Anisotropy ◽  
High Throughput Screening ◽  
Topoisomerase I ◽  
Dna Supercoiling ◽  
New Drugs ◽  
E Coli ◽  
Cellular Processes ◽  
The Difference ◽  
Cellular Replication

The degree of supercoiling of DNA is vital for cellular processes, such as replication and transcription. DNA topology is controlled by the action of DNA topoisomerase enzymes. Topoisomerases, because of their importance in cellular replication, are the targets of several anticancer and antibacterial drugs. In the search for new drugs targeting topoisomerases, a biochemical assay compatible with automated high-throughput screening (HTS) would be valuable. Gel electrophoresis is the standard method for measuring changes in the extent of supercoiling of plasmid DNA when acted upon by topoisomerases, but this is a low-throughput and laborious method. A medium-throughput method was described previously that quantitatively distinguishes relaxed and supercoiled plasmids by the difference in their abilities to form triplex structures with an immobilized oligonucleotide. In this article, the authors describe a homogeneous supercoiling assay based on triplex formation in which the oligonucleotide strand is labeled with a fluorescent dye and the readout is fluorescence anisotropy. The new assay requires no immobilization, filtration, or plate washing steps and is therefore well suited to HTS for inhibitors of topoisomerases. The utility of this assay is demonstrated with relaxation of supercoiled plasmid by Escherichia coli topoisomerase I, supercoiling of relaxed plasmid by E. coli DNA gyrase, and inhibition of gyrase by fluoroquinolones and nalidixic acid.

scholarly journals Development of a High-Throughput Scintillation Proximity Assay for the Identification of C-Domain Translational Initiation Factor 2 Inhibitors

2002 ◽  
Vol 7 (6) ◽  
pp. 541-546 ◽  
Author(s):  
Sonia Delle Fratte ◽  
Chiara Piubelli ◽  
Enrico Domenici
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Ribosomal Subunit ◽  
New Drugs ◽  
Initiation Factor ◽  
Translational Initiation ◽  
Scintillation Proximity Assay ◽  
Initiation Factor 2 ◽  
Subsequent Capture ◽  
Translational Initiation Factor

Translational initiation factor 2 (IF2) is the largest of the 3 factors required for translation initiation in prokaryotes and has been shown to be essential in Escherichia coli. It stimulates the binding of fMet-tRNAfMet to the 30S ribosomal subunit in the presence of GTP. The selectivity is achieved through specific recognition of the tRNAfMet blocked α-amino group. IF2 is composed of 3 structural domains: N-domain, whose function is not known; G-domain, which contains the GTP/GDP binding site and the GTPase catalytic center; and C-domain, which recognizes and binds fMet-tRNAfMet. Its activity is strictly bacteria specific and highly conserved among prokaryotes. So far, antibiotics targeting IF2 function are not known, and this makes it an ideal target for new drugs with mechanisms of resistance not yet developed. A few assays have been developed in the past, which allow the detection of IF2 activity either directly or indirectly. In both instances, the assays are based on radioactive detection and do not allow for high throughput because of the need for separation or solvent extraction steps. The authors describe a novel biochemical assay for IF2 that exploits the molecular recognition of fMet-tRNAfMet by the C-domain. The assay is based on the incubation of biotinyl-IF2 with fMet-tRNAfMet and the subsequent capture of the radiolabeled complex by streptavidin-coated beads, exploiting the scintillation proximity assay (SPA) technology. The assay has been designed in an automatable, homogeneous, miniaturized fashion suitable for high-throughput screening and is rapid, sensitive, and robust to dimethyl sulfoxide (DMSO) up to 10% v/v. The assay, used to screen a limited chemical collection of about 5000 compounds and a subset of compounds originated by a 2-D substructural search, has shown to be able to detect potential IF2 inhibitors.

scholarly journals Nano-biofilm Arrays as a Novel Universal Platform for Microscale Microbial Culture and High-Throughput Downstream Applications

2019 ◽  
Vol 26 (14) ◽  
pp. 2529-2535 ◽  
Author(s):  
Anand Srinivasan ◽  
Anand K. Ramasubramanian ◽  
José L. Lopez-Ribot
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Antimicrobial Agents ◽  
Microarray Platform ◽  
New Drugs ◽  
Microbial Culture ◽  
Phenotypic Properties ◽  
Microbial Biofilms ◽  
Antibiotic Drug

Biofilms are the predominant mode of microbial growth and it is now fully accepted that a majority of infections in humans are associated with a biofilm etiology. Biofilms are defined as attached and structured microbial communities surrounded by a protective exopolymeric matrix. Importantly, sessile microorganisms growing within a biofilm are highly resistant to antimicrobial agents. Thus, there is an urgent need to develop new and improved anti-biofilm therapies. Unfortunately, most of the current techniques for in-vitro biofilm formation are not compatible with high throughput screening techniques that can speed up discovery of new drugs with anti-biofilm activity. To try to overcome this major impediment, our group has developed a novel technique consisting of micro-scale culture of microbial biofilms on a microarray platform. Using this technique, hundreds to thousands of microbial biofilms, each with a volume of approximately 30-50 nanolitres, can be simultaneously formed on a standard microscope slide. Despite more than three orders of magnitude of miniaturization over conventional biofilms, these nanobiofilms display similar growth, structural and phenotypic properties, including antibiotic drug resistance. These nanobiofilm chips are amenable to automation, drastically reducing assay volume and costs. This technique platform allows for true high-throughput screening in search for new anti-biofilm drugs.

High Throughput Screening for Drug Discovery and Virus Detection

2021 ◽  
Vol 24 ◽  
Author(s):  
Adetola Okea ◽  
Deniz Sahin ◽  
Xin Chen ◽  
Ying Shang
Keyword(s):  
Drug Discovery ◽  
High Throughput ◽  
High Throughput Screening ◽  
Virus Detection ◽  
Flow Time ◽  
New Drugs ◽  
Mixed Integer ◽  
General Process ◽  
Screening Systems

Background: High throughput screening systems are automated labs for the analysis of many biochemical substances in the drug discovery and virus detection process. This paper was motivated by the problem of automating testing for viruses and new drugs using high throughput screening systems. The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the turn of 2019-2020 presented extradentary challenges to public health. Existing approaches to test viruses and new drugs do not use optimal schedules and are not efficient. Objective: The scheduling of activities performed by various resources in a high throughput screening system affects its efficiency, throughput, operations cost, and quality of screening. This study aims to minimize the total screening (flow) time and ensure the consistency and quality of screening. Methods: This paper develops innovative mixed integer models that efficiently compute optimal schedules for screening many microplates to identify new drugs and determine whether samples contain viruses. The methods integrate job-shop and cyclic scheduling. Experiments are conducted for a drug discovery process of screening an enzymatic assay and a general process of detecting SARS-CoV-2. Results: The method developed in this article can reduce screening time by as much as 91.67%. Conclusion: The optimal schedules for high throughput screening systems greatly reduce the total flow time and can be computed efficiently to help discover new drugs and detect viruses.

scholarly journals Homogeneous Time-Resolved Fluorescence Quenching Assay (LANCE) for Caspase-3

2002 ◽  
Vol 7 (3) ◽  
pp. 223-231 ◽  
Author(s):  
Jarkko Karvinen ◽  
Pertti Hurskainen ◽  
Sujatha Gopalakrishnan ◽  
David Burns ◽  
Usha Warrior ◽  
...  
Keyword(s):  
Fluorescence Quenching ◽  
High Throughput ◽  
High Throughput Screening ◽  
Caspase 3 ◽  
New Drugs ◽  
Time Resolved Fluorescence ◽  
Time Resolved ◽  
Viral Proteases ◽  
Modern Drug ◽  
Quenching Assay

In addition to kinases and G protein—coupled receptors, proteases are one of the main targets in modern drug discovery. Caspases and viral proteases, for instance, are potential targets for new drugs. To satisfy the current need for fast and sensitive high-throughput screening for inhibitors, new homogeneous protease assays are needed. We used a caspase-3 assay as a model to develop a homogeneous time-resolved fluorescence quenching assay technology. The assay utilizes a peptide labeled with both a luminescent europium chelate and a quencher. Cleavage of the peptide by caspase-3 separates the quencher from the chelate and thus recovers europium fluorescence. The sensitivity of the assay was 1 pg/μl for active caspase-3 and 200 pM for the substrate. We evaluated the assay for high-throughput usage by screening 9600 small-molecule compounds. We also evaluated this format for absorption/distribution/metabolism/excretion assays with cell lysates. Additionally, the assay was compared to a commercial fluorescence caspase-3 assay.

scholarly journals AMIDE v2: High-Throughput Screening Based on AutoDock-GPU and Improved Workflow Leading to Better Performance and Reliability

2021 ◽  
Vol 22 (14) ◽  
pp. 7489
Author(s):  
Pierre Darme ◽  
Manuel Dauchez ◽  
Arnaud Renard ◽  
Laurence Voutquenne-Nazabadioko ◽  
Dominique Aubert ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
High Performance ◽  
Graphics Processing Unit ◽  
Target Identification ◽  
Computation Time ◽  
Processing Unit ◽  
Biological Target ◽  
Speed Up ◽  
Graphics Processing

Molecular docking is widely used in computed drug discovery and biological target identification, but getting fast results can be tedious and often requires supercomputing solutions. AMIDE stands for AutoMated Inverse Docking Engine. It was initially developed in 2014 to perform inverse docking on High Performance Computing. AMIDE version 2 brings substantial speed-up improvement by using AutoDock-GPU and by pulling a total revision of programming workflow, leading to better performances, easier use, bug corrections, parallelization improvements and PC/HPC compatibility. In addition to inverse docking, AMIDE is now an optimized tool capable of high throughput inverse screening. For instance, AMIDE version 2 allows acceleration of the docking up to 12.4 times for 100 runs of AutoDock compared to version 1, without significant changes in docking poses. The reverse docking of a ligand on 87 proteins takes only 23 min on 1 GPU (Graphics Processing Unit), while version 1 required 300 cores to reach the same execution time. Moreover, we have shown an exponential acceleration of the computation time as a function of the number of GPUs used, allowing a significant reduction of the duration of the inverse docking process on large datasets.

scholarly journals High-throughput screening of new drugs targeting lung CSCs

2018 ◽  
Vol 29 ◽  
pp. viii668
Author(s):  
H.A. Amado Labrador ◽  
E. Jantus-Lewintre ◽  
S. Calabuig Fariñas ◽  
C. Aguilar-Gallardo ◽  
J. Murga ◽  
...  
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
New Drugs

scholarly journals Design and Implementation of High Throughput Screening Assays for Drug Discoveries

2021 ◽  
Author(s):  
Fawzi Faisal Bokhari ◽  
Ashwag Albukhari
Keyword(s):  
High Throughput ◽  
High Throughput Screening ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Correlation Spectroscopy ◽  
Screening Methods ◽  
Distribution Analysis ◽  
Time Resolved ◽  
Speed Up ◽  
Pharmaceutical Industries

The process of drug discovery is challenging and a costly affair. It takes about 12 to 15 years and costs over $1 billion dollars to develop a new drug and introduce the finished product in the market. With the increase in diseases, virus spread, and patients, it has become essential to invent new medicines. Consequently, today researchers are becoming interested in inventing new medicines faster by adopting higher throughput screening methods. One avenue of approach to discovering drugs faster is the High-Throughput Screening (HTS) method, which has gained a lot of attention in the previous few years. Today, High-Throughput Screening (HTS) has become a standard method for discovering drugs in various pharmaceutical industries. This review focuses on the advancement of technologies in High-Throughput Screening (HTS) methods, namely fluorescence resonance energy transfer (FRET), biochemical assay, fluorescence polarization (FP), homogeneous time resolved fluorescence (HTRF), Fluorescence correlation spectroscopy (FCS), Fluorescence intensity distribution analysis (FIDA), Nuclear magnetic resonance (NMR), and research advances in three major technology areas including miniaturization, automation and robotics, and artificial intelligence, which promises to help speed up the discovery of medicines and its development process.

scholarly journals Detection of Drug-Induced Torsades de Pointes Arrhythmia Mechanisms Using hiPSC-CM Syncytial Monolayers in a High-Throughput Screening Voltage Sensitive Dye Assay

2019 ◽  
Vol 173 (2) ◽  
pp. 402-415 ◽  
Author(s):  
Andre Monteiro da Rocha ◽  
Jeffery Creech ◽  
Ethan Thonn ◽  
Sergey Mironov ◽  
Todd J Herron
Keyword(s):  
Action Potential ◽  
High Throughput ◽  
Action Potential Duration ◽  
High Throughput Screening ◽  
Torsades De Pointes ◽  
New Drugs ◽  
Cell Type ◽  
Screening Assay ◽  
Drug Induced ◽  
Voltage Sensitive Dye

Abstract We validated 3 distinct hiPSC-CM cell lines—each of different purity and a voltage sensitive dye (VSD)-based high-throughput proarrhythmia screening assay as a noncore site in the recently completed CiPA Myocyte Phase II Validation Study. Blinded validation was performed using 12 drugs linked to low, intermediate, or high risk for causing Torsades de Pointes (TdP). Commercially sourced hiPSC-CMs were obtained either from Cellular Dynamics International (CDI, Madison, Wisconsin, iCell Cardiomyoyctes2) or Takara Bio (CLS, Cellartis Cardiomyocytes). A third hiPSC-CM cell line (MCH, Michigan) was generated in house. Each cell type had distinct baseline electrophysiological function (spontaneous beat rate, action potential duration, and conduction velocity) and drug responsiveness. Use of VSD and optical mapping enabled the detection of conduction slowing of sodium channel blockers (quinidine, disopyramide, and mexiletine) and drug-induced TdP-like activation patterns (rotors) for some high- and intermediate-risk compounds. Low-risk compounds did not induce rotors in any cell type tested. These results further validate the utility of hiPSC-CMs for predictive proarrhythmia screening and the utility of VSD technology to detect drug-induced APD prolongation, arrhythmias (rotors), and conduction slowing. Importantly, results indicate that different ratios of cardiomyocytes and noncardiomyocytes have important impact on drug response that may be considered during risk assessment of new drugs. Finally, we present the first blinded CiPA hiPSC-CM validation results to simultaneously detect drug-induced conduction slowing, action potential duration prolongation, action potential triangulation, and drug-induced rotors in a proarrhythmia assay.

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