Abstract
Functional cell-based assays have gained increasing importance for microplate-based high throughput screening (HTS). The use of high-density microplates, most prominently 1536-well plates, and miniaturized assay formats allow screening of comprehensive compound collections with more than 1 million compounds at ultra-high throughput, i.e. in excess of 100,000 samples per day. uHTS operations with numerous campaigns per year should generally support this throughput at all different steps of the process, including the underlying compound logistics, the (automated) testing of the corporate compound collection in the bioassay, and the subsequent follow-up studies for hit confirmation and characterization. A growing number of reports document the general feasibility of cell-based uHTS in microliter volumes. In addition, full automation with integrated robotic systems allows the realization of also complex assay protocols with multiple liquid handling and signal detection steps. For this review, cell-based assays are categorized based on the kinetics of the cellular response to be quantified in the test and the readout method employed. Thus, assays measuring fast cellular responses with high temporal resolution, e.g., receptor mediated calcium signals or changes in membrane potential, are at one end of this spectrum, while tests quantifying cellular transcriptional responses mark the opposite end. Trends for cell-based uHTS assays developed at Bayer-Schering Pharma are, first, to incorporate assay integral reference signals allowing the experimental differentiation of target hits from non-specifically acting compounds, and second, to make use of kinetic, real-time readouts providing additional information on the mode-of-action of test compounds.
Keywords: Ultra-High Throughput Screening, cell-based assays, high-density microplates, bioassay, kinetic
Combinatorial Chemistry & High Throughput Screening
Title: Functional Cell-Based Assays in Microliter Volumes for Ultra-High Throughput Screening
Volume: 11 Issue: 7
Author(s): Frank Wunder, Bernd Kalthof, Thomas Muller and Jorg Huser
Affiliation:
Keywords: Ultra-High Throughput Screening, cell-based assays, high-density microplates, bioassay, kinetic
Abstract: Functional cell-based assays have gained increasing importance for microplate-based high throughput screening (HTS). The use of high-density microplates, most prominently 1536-well plates, and miniaturized assay formats allow screening of comprehensive compound collections with more than 1 million compounds at ultra-high throughput, i.e. in excess of 100,000 samples per day. uHTS operations with numerous campaigns per year should generally support this throughput at all different steps of the process, including the underlying compound logistics, the (automated) testing of the corporate compound collection in the bioassay, and the subsequent follow-up studies for hit confirmation and characterization. A growing number of reports document the general feasibility of cell-based uHTS in microliter volumes. In addition, full automation with integrated robotic systems allows the realization of also complex assay protocols with multiple liquid handling and signal detection steps. For this review, cell-based assays are categorized based on the kinetics of the cellular response to be quantified in the test and the readout method employed. Thus, assays measuring fast cellular responses with high temporal resolution, e.g., receptor mediated calcium signals or changes in membrane potential, are at one end of this spectrum, while tests quantifying cellular transcriptional responses mark the opposite end. Trends for cell-based uHTS assays developed at Bayer-Schering Pharma are, first, to incorporate assay integral reference signals allowing the experimental differentiation of target hits from non-specifically acting compounds, and second, to make use of kinetic, real-time readouts providing additional information on the mode-of-action of test compounds.
Export Options
About this article
Cite this article as:
Wunder Frank, Kalthof Bernd, Muller Thomas and Huser Jorg, Functional Cell-Based Assays in Microliter Volumes for Ultra-High Throughput Screening, Combinatorial Chemistry & High Throughput Screening 2008; 11 (7) . https://dx.doi.org/10.2174/138620708785204054
DOI https://dx.doi.org/10.2174/138620708785204054 |
Print ISSN 1386-2073 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5402 |
Call for Papers in Thematic Issues
Artificial Intelligence Methods for Biomedical, Biochemical and Bioinformatics Problems
Recently, a large number of technologies based on artificial intelligence have been developed and applied to solve a diverse range of problems in the areas of biomedical, biochemical and bioinformatics problems. By utilizing powerful computing resources and massive amounts of data, methods based on artificial intelligence can significantly improve the ...read more
Eco-friendly Agents for Biological Control of Pathogenic Diseases
The discovery of an alternative biological approach to disease management includes work on medicinal products derived from natural sources as a starting point for the development of eco-friendly agents for these diseases and the injuries they cause, as well as reducing human contact with hazardous chemicals and their residues. We ...read more
Emerging trends in diseases mechanisms, noble drug targets and therapeutic strategies: focus on immunological and inflammatory disorders
Recently infectious and inflammatory diseases have been a key concern worldwide due to tremendous morbidity and mortality world Wide. Recent, nCOVID-9 pandemic is a good example for the emerging infectious disease outbreak. The world is facing many emerging and re-emerging diseases out breaks at present however, there is huge lack ...read more
Exploring Spectral Graph Theory in Combinatorial Chemistry
Scope of the Thematic Issue: Combinatorial chemistry involves the synthesis and analysis of a large number of diverse compounds simultaneously. Traditional methods rely on brute force experimentation, which can be time-consuming and resource-intensive. Spectral Graph Theory, a branch of mathematics dealing with the properties of graphs in relation to the ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
Related Articles
-
Benzothiazole Derivatives: Novel Inhibitors of Methylglyoxal Mediated Glycation of Proteins In Vitro
Medicinal Chemistry Paclitaxel Formulations: Challenges and Novel Delivery Options
Current Drug Delivery A Review on Deep Learning Architecture and Methods for MRI Brain Tumour Segmentation
Current Medical Imaging Microwave-Assisted Synthesis of Imido-Substituted 2-Chloro-1,4-naphthoquinone Derivatives and their Cytotoxic Activities on Three Human Prostate Cancer Cell Lines
Letters in Drug Design & Discovery The Association Between the Chronic Use of Non-Steroidal Anti- Inflammatory Drugs and Oxidative and Inflammatory Markers in the Elderly
Inflammation & Allergy - Drug Targets (Discontinued) Translational Gap in Glioma Research
Anti-Cancer Agents in Medicinal Chemistry Plant Proteinases and Inhibitors: An Overview of Biological Function and Pharmacological Activity
Current Protein & Peptide Science Magnetic and Gold-Coated Magnetic Iron Oxide Nanoparticles as Detection Tools: Preparation, Characterization, and Biosensing Applications
Current Nanoscience Synthesis, Cytotoxic Evaluation, Docking and QSAR Study of N-(4-Oxo- 2-(4-((5-Aryl-1,3,4-Thiadiazol-2-yl)Amino)Phenyl)Thiazolidin-3-yl) Benzamides as Antitubulin Agents
Current Topics in Medicinal Chemistry Bile Acids and Derivatives, Their Nuclear Receptors FXR, PXR and Ligands: Role in Health and Disease and Their Therapeutic Potential
Anti-Cancer Agents in Medicinal Chemistry Preparation and Optimization of Moxifloxacin Microspheres for Colon Targeted Delivery Using Quality by Design Approach: In Vitro and In Vivo Study
Current Drug Delivery Novel Conjugated Unsaturated Ketones with Submicromolar Potencies Towards some Leukemic and Colon Cancer Cells
Medicinal Chemistry A panoramic view of chronic liver diseases and natural remedies reported in Traditional Persian Medicine
Current Pharmaceutical Design Natural Products and their (Semi-)Synthetic Forms in the Treatment of Migraine: History and Current Status
Current Medicinal Chemistry The Use of Proteomics to Study Infectious Diseases
Infectious Disorders - Drug Targets Small Molecule Fluorescent Probes for the Detection of Amyloid Self-Assembly In Vitro and In Vivo
Current Protein & Peptide Science Screening for Infectious Diseases During Pregnancy: Which Test and Which Situation
Current Women`s Health Reviews Design and Synthesis of 2-(Arylmethylideneamino) Isoindolines as New Potential Analgesic and Anti-Inflammatory Agents: A Molecular Hybridization Approach
Current Pharmaceutical Design Meet Our Editorial Board Member
Current Gene Therapy Tolfenamic Acid Prevents Amyloid β-induced Olfactory Bulb Dysfunction In Vivo
Current Alzheimer Research