PubMed Health⌕ Search

PubMed · 10841599

Implementing multilevel dynamic scheduling for a highly flexible 5-rail high throughput screening system.

Abstract

As automation solves the bottleneck involved in drug screening, new bottlenecks present themselves. Some of these bottlenecks include sample management, hit picking and confirmation, and reagents lost as a result of incomplete runs. To keep up with the demands of a large HTS department, scientists spend a disproportionate amount of time simply feeding these systems with samples and reagents. Automating the sample management functions directly on the screening systems would solve this problem. With the use of online data analysis, an integrated sample store permits automated hit picking and confirmation. In addition to these issues, other bottlenecks are often caused by instrument malfunctions. A single lost run can now mean a loss of hundreds of plates and the reagents associated with their testing. A system was designed to include four assaying systems that are fed by an automated online sample repository system. Redundancy between the assaying systems allows for an extra level of error handling in case of a malfunction. The control of such a system requires a sophisticated scheduler/controller software package capable of coordinating the interaction between multiple systems and reacting to changes in the robotic environment in realtime. This paper discusses the design of the system as well as the requirements and selection of an appropriate scheduler/controller package.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

M N Feiglin, S Skwish, M Laab, A Heppel. 2000. Implementing multilevel dynamic scheduling for a highly flexible 5-rail high throughput screening system.. https://doi.org/10.1177/108705710000500108

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

Synthesis and biological activity of PTEN-resistant analogues of phosphatidylinositol 3,4,5-trisphosphate.

The activation of phosphatidylinositol 3-kinase (PI 3-K) and subsequent production of PtdIns(3,4,5)P3 launches a signal transduction cascade that impinges on a plethora of downstream effects on cell physiology. Control of PI 3-K and PtdIns(3,4,5)P3 levels is an important therapeutic target in treatments for allergy, inflammation, cardiovascular, and malignant human diseases. We designed metabolically stabilized, that is, phosphatase resistant, analogues of PtdIns(3,4,5)P3 as probes for long-lived potential agonists or potential antagonists for cellular events mediated by PtdIns(3,4,5)P3. In particular, two types of analogues were prepared containing phosphomimetics that would be selectively resistant to the lipid 3-phosphatase PTEN. The total asymmetric synthesis of the 3-phosphorothioate-PtdIns(3,4,5)P3 and 3-methylenephosphonate-PtdIns(3,4,5)P3 analogues is described. These two analogues showed differential binding to PtdIns(3,4,5)P3 binding modules, and both were potential long-lived activators that mimicked insulin action in sodium transport in A6 cells.

Drug Evaluation, Preclinical↗

A microfluidics-based mobility shift assay to discover new tyrosine phosphatase inhibitors.

Protein tyrosine phosphatases (PTPs) play key roles in regulating tyrosine phosphorylation levels in cells. Since the discovery of PTP1B as a major drug target for diabetes and obesity, PTPs have emerged as a new and promising class of signaling targets for drug development in a variety of therapeutic areas. The routine use of generic substrate 6,8-difluoro-4-methylumbelliferyl phosphate (DiFMUP) in our hands led to the discovery of very similar and often not very selective molecules. Therefore, to increase the chances to discover novel chemical scaffolds, a side-by-side comparison between the DiFMUP assay and a chip-based mobility shift assay with a specific phosphopeptide was performed, on 1 PTP, using a focused set of compounds. Assay robustness and sensitivity were comparable for both the DiFMUP and mobility shift assays. The off-chip mobility shift assay required a longer development time because of identification, synthesis, and characterization of a specific peptide, and its cost per point was higher. However, although most potent scaffolds found with the DiFMUP assay were confirmed in the mobility shift format, the off-chip mobility shift assay led to the identification of previously unidentified chemical scaffolds with improved druglike properties.

Drug Evaluation, Preclinical↗