scholarly journals Solid form characterisation in the pharma industry using high throughput automated screening, manual investigation and process

2002 ◽  
Vol 58 (s1) ◽  
pp. c8-c8
Author(s):  
P. Higginson ◽  
R. Docherty ◽  
R. Storey
Keyword(s):  
High Throughput ◽  
Automated Screening ◽  
Solid Form

scholarly journals A versatile automated high-throughput drug screening platform for zebrafish embryos

2020 ◽  
Author(s):  
Alexandra Lubin ◽  
Jason Otterstrom ◽  
Yvette Hoade ◽  
Ivana Bjedov ◽  
Eleanor Stead ◽  
...  
Keyword(s):  
High Throughput ◽  
Drug Screening ◽  
Imaging System ◽  
Cell Types ◽  
Wide Range ◽  
Stem And Progenitor Cells ◽  
Multiple Cell ◽  
Flexible Imaging ◽  
Automated Screening ◽  
Screening Platform

AbstractZebrafish provide a unique opportunity for drug screening in living animals, with the fast developing, transparent embryos allowing for relatively high throughput, microscopy-based screens. However, the limited availability of rapid, flexible imaging and analysis platforms has limited the use of zebrafish in drug screens. We have developed a easy-to-use, customisable automated screening procedure suitable for high-throughput phenotype-based screens of live zebrafish. We utilised the WiScan®Hermes High Content Imaging System to rapidly acquire brightfield and fluorescent images of embryos, and the WiSoft®Athena Zebrafish Application for analysis, which harnesses an Artificial Intelligence-driven algorithm to automatically detect fish in brightfield images, identify anatomical structures, partition the animal into regions, and exclusively select the desired side-oriented fish. Our initial validation combined structural analysis with fluorescence images to enumerate GFP-tagged haematopoietic stem and progenitor cells in the tails of embryos, which correlated with manual counts. We further validated this system to assess the effects of genetic mutations and x-ray irradiation in high content using a wide range of assays. Further, we performed simultaneous analysis of multiple cell types using dual fluorophores in high throughput. In summary, we demonstrate a broadly applicable and rapidly customisable platform for high content screening in zebrafish.

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 Automated screening ofC. elegansneurodegeneration mutants enabled by microfluidics and image analysis algorithms

2018 ◽  
Vol 10 (9) ◽  
pp. 539-548 ◽  
Author(s):  
Ivan de Carlos Cáceres ◽  
Daniel A. Porto ◽  
Ivan Gallotta ◽  
Pamela Santonicola ◽  
Josue Rodríguez-Cordero ◽  
...  
Keyword(s):  
Image Analysis ◽  
Spinal Muscular Atrophy ◽  
High Throughput ◽  
Muscular Atrophy ◽  
High Throughput Screen ◽  
C Elegans ◽  
Genetic Mechanisms ◽  
Automated Screening

A fully automated high-throughput screen usingC. elegansto investigate genetic mechanisms affecting spinal muscular atrophy (SMA).

scholarly journals Optimized and Automated Protocols for High-Throughput Screening of Amylosucrase Libraries

2007 ◽  
Vol 12 (5) ◽  
pp. 715-723 ◽  
Author(s):  
Stéphane Emond ◽  
Gabrielle Potocki-Véronèse ◽  
Philippe Mondon ◽  
Khalil Bouayadi ◽  
Hakim Kharrat ◽  
...  
Keyword(s):  
Organic Solvents ◽  
High Throughput ◽  
High Throughput Screening ◽  
General Procedure ◽  
Random Mutagenesis ◽  
Culture Conditions ◽  
Screening Assay ◽  
High Production Rate ◽  
Automated Screening

This article describes the design and validation of a general procedure for the high-throughput isolation of amylosucrase variants displaying higher thermostability or increased resistance to organic solvents. This procedure consists of 2 successive steps: an in vivo selection that eliminates inactive variants followed by automated screening of active variants to isolate mutants displaying enhanced features. The authors chose an Escherichia coli expression vector, allowing a high production rate of the recombinant enzyme in miniaturized culture conditions. The screening assay was validated by minimizing variability for various parameters of the protocol, especially bacterial growth and protein production in cultures in 96-well microplates. Recombinant amylosucrase production was normalized by decreasing the coefficient of variance from 27% to 12.5%. Selective screening conditions were defined to select variants displaying higher thermostability or increased resistance to organic solvents. A first-generation amylosucrase variant library, constructed by random mutagenesis, was subjected to this procedure, yielding a mutant displaying a 25-fold increased stability at 50 °C compared to the parental wild-type enzyme. ( Journal of Biomolecular Screening 2007:715-723)

scholarly journals Optimization of a Luminescence-Based High-Throughput Screening Assay for Detecting Apyrase Activity

2016 ◽  
Vol 22 (1) ◽  
pp. 94-101 ◽  
Author(s):  
John R. Veloria ◽  
Ashwini K. Devkota ◽  
Eun Jeong Cho ◽  
Kevin N. Dalby
Keyword(s):  
High Throughput ◽  
Herbicide Resistance ◽  
High Throughput Screening ◽  
Detection System ◽  
Cost Effective ◽  
Adenosine Monophosphate ◽  
Adenosine Diphosphate ◽  
Screening Assay ◽  
High Throughput Screening Assay ◽  
Automated Screening

Apyrase is a calcium-activated enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to adenosine diphosphate (ADP), adenosine monophosphate (AMP), and Pi. It is currently used in studies involving cancer and platelet aggregation in humans, as well as herbicide resistance in plants. Inhibitors of apyrase are being investigated for their use to suppress tumors and combat herbicide resistance. Only a few inhibitors of apyrase have been reported, many of which were identified through automated screening using a 96-well plate format and colorimetric phosphate detection. However, these screens have had limitations, including large volumes, inconsistent reproducibility, high incidence of false hits, and lack of higher-throughput compatibility. A luciferin/luciferase-based detection system has been reported to examine potential inhibitors of apyrase; however, these reactions were performed in tubes with the assay completion in seconds, which necessitate the development of a high-throughput screening (HTS)–compatible format for screening. Therefore, a more cost-effective biochemical assay that improved the limitations of the previous assay formats using a commercially available luminescence-based detection system was developed. This new robust mix-and-read platform incorporates a low-volume luminescence-based protocol, formatted for use in 384-well microplates. This new format provides a simple and cost-effective method to screen for apyrase inhibitors and will facilitate larger HTS efforts to identify potent inhibitors of apyrase.

Protein formulation through automated screening of pH and buffer conditions, using the Robotein® high throughput facility

2021 ◽  
Author(s):  
Ruth Kellner ◽  
Romain Malempré ◽  
Julie Vandenameele ◽  
Alain Brans ◽  
Anne-Françoise Hennen ◽  
...  
Keyword(s):  
High Throughput ◽  
Protein Formulation ◽  
Automated Screening

scholarly journals Methods for High-Throughput Drug Combination Screening and Synergy Scoring

2016 ◽  
Author(s):  
Liye He ◽  
Evgeny Kulesskiy ◽  
Jani Saarela ◽  
Laura Turunen ◽  
Krister Wennerberg ◽  
...  
Keyword(s):  
Cancer Cells ◽  
High Throughput ◽  
Drug Combination ◽  
High Throughput Screening ◽  
Treatment Options ◽  
Drug Combinations ◽  
Molecular Medicine ◽  
Targeted Drugs ◽  
Functional Profiling ◽  
Automated Screening

AbstractGene products or pathways that are aberrantly activated in cancer but not in normal tissue hold great promises for being effective and safe anticancer therapeutic targets. Many targeted drugs have entered clinical trials but so far showed limited efficacy mostly due to variability in treatment responses and often rapidly emerging resistance. Towards more effective treatment options, we will critically need multi-targeted drugs or drug combinations, which selectively inhibit the cancer cells and block distinct escape mechanisms for the cells to become resistant. Functional profiling of drug combinations requires careful experimental design and robust data analysis approaches. At the Institute for Molecular Medicine Finland (FIMM), we have developed an experimental-computational pipeline for high-throughput screening of drug combination effects in cancer cells. The integration of automated screening techniques with advanced synergy scoring tools allows for efficient and reliable detection of synergistic drug interactions within a specific window of concentrations, hence accelerating the identification of potential drug combinations for further confirmatory studies.

scholarly journals Common features of antibacterial compounds: an analysis of 10000 compounds library

2015 ◽  
Vol 61 (6) ◽  
pp. 785-790 ◽  
Author(s):  
M.S. Veselov ◽  
P.V. Sergiev ◽  
I.A. Osterman ◽  
D.A. Skvortsov ◽  
A.Ya. Golovina ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibacterial Activity ◽  
Organic Compounds ◽  
High Throughput ◽  
High Throughput Screening ◽  
Chemical Space ◽  
Molecular Target ◽  
Antibacterial Compounds ◽  
Common Features ◽  
Automated Screening

Antibacterial compounds are one of the essential classes of clinically important drugs. High throughput screening allowed revealing potential antibiotics active towards any molecular target in bacterial cell. We used a library of 9820 organic compounds with highly diversified structures to screen for antibacterial activity. As the result of automated screening, 103 compounds were found to possess antibacterial activity against Escherichia coli. The properties of these compounds were compared with those of initial library. Non-linear Kohonen mapping was used to analyze the differences between non-active molecules from initial library, identified antibacterial hits and compounds with reported antibacterial activity. It was found that identified antibacterial compounds are located in the separated area of chemical space. It can be therefore suggested that these molecules belong to novel classes of antibacterial compounds and could be studied further.

Exploring the crystal form landscape

2020 ◽  
pp. 78-135
Author(s):  
Joel Bernstein
Keyword(s):  
High Throughput ◽  
Crystal Form ◽  
Time Frame ◽  
Theoretical Background ◽  
Experimental Techniques ◽  
Crystallization Conditions ◽  
Kinetic Crystallization ◽  
Solid Form ◽  
Evolving Models

Chapter 3 deals with the theoretical background, the strategies, and the experimental techniques for exploring the crystal for landscape. The various and evolving models for aggregation and nucleation are discussed, followed by the description of thermodynamic (i.e., approximately equilibrium) and kinetic crystallization conditions, followed by the use of thermodynamic information obtained in Chapter 2 for designing crystallization strategies. The various aspects of solid form screens—design, composition, time frame, variables to consider, application of high throughput methods—are discussed, followed by a description of the screen on the specific example of axitinib. The chapter closes with discussions of concomitant polymorphs and disappearing polymorphs.

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