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Rational DOE-protocols for 96-well plates
Umeå University, Faculty of Science and Technology, Department of Chemistry.
Umeå University, Faculty of Science and Technology, Department of Chemistry.
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2006 (English)In: Chemometrics and Intelligent Laboratory Systems, ISSN 0169-7439, E-ISSN 1873-3239, Vol. 83, no 1, 66-74 p.Article in journal (Refereed) Published
Abstract [en]

The use of 96-well plates for chemical and biological applications has rapidly increased as new applicable domains have been discovered and new laboratory instruments developed. There are 96, 384, 1536, etc. plates customized for diverse applications such as biological assays, sample preparation, solid-phase extraction and crystallization. Multi-pipettes as well as automated pipette systems accelerate the preparation of plates resulting in even faster evaluation systems. A bottleneck in the use of multi-unit plates is method development and optimization. By applying rational experimental design, the optimization could be made more efficient and less time-consuming. Unfortunately, the workload related to manual preparation of multi-unit plates according to an experimental design is often considered overwhelming. The present study introduces a new approach for experimental design in 96-well plates that minimizes the manual workload without compromising the quality of the experimental design. This approach is scalable to larger rectangular formats such as 384- and 1536-well plates. The optimal combinations will be delineated and applied experimentally to a reporter-gene assay.

Place, publisher, year, edition, pages
Amsterdam: Elsevier , 2006. Vol. 83, no 1, 66-74 p.
Keyword [en]
DOE, 96-well technology, RED-MUP, Assay optimisation
URN: urn:nbn:se:umu:diva-4945DOI: 10.1016/j.chemolab.2006.01.005OAI: diva2:144246
Available from: 2006-02-07 Created: 2006-02-07 Last updated: 2013-02-28Bibliographically approved
In thesis
1. Experimental Designs at the Crossroads of Drug Discovery
Open this publication in new window or tab >>Experimental Designs at the Crossroads of Drug Discovery
2006 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

New techniques and approaches for organic synthesis, purification and biological testing are enabling pharmaceutical industries to produce and test increasing numbers of compounds every year. Surprisingly, this has not led to more new drugs reaching the market, prompting two questions – why is there not a better correlation between their efforts and output, and can it be improved? One possible way to make the drug discovery process more efficient is to ensure, at an early stage, that the tested compounds are diverse, representative and of high quality. In addition the biological evaluation systems have to be relevant and reliable. The diversity of the tested compounds could be ensured and the reliability of the biological assays improved by using Design Of Experiments (DOE) more frequently and effectively. However, DOE currently offers insufficient options for these purposes, so there is a need for new, tailor-made DOE strategies. The aim of the work underlying this thesis was to develop and evaluate DOE approaches for diverse compound selection and efficient assay optimisation. This resulted in the publication of two new DOE strategies; D-optimal Onion Design (DOOD) and Rectangular Experimental Designs for Multi-Unit Platforms (RED-MUP), both of which are extensions to established experimental designs.

D-Optimal Onion Design (DOOD) is an extension to D-optimal design. The set of possible objects that could be selected is divided into layers and D-optimal selection is applied to each layer. DOOD enables model-based, but not model-dependent, selections in discrete spaces to be made, since the selections are not only based on the D-optimality criterion, but are also biased by the experimenter’s prior knowledge and specific needs. Hence, DOOD selections provide controlled diversity.

Assay development and optimisation can be a major bottleneck restricting the progress of a project. Although DOE is a recognised tool for optimising experimental systems, there has been widespread unwillingness to use it for assay optimisation, mostly because of the difficulties involved in performing experiments according to designs in 96-, 384- and 1536- well formats. The RED-MUP framework combines classical experimental designs orthogonally onto rectangular experimental platforms, which facilitates the execution of DOE on these platforms and hence provides an efficient tool for assay optimisation.

In combination, these two strategies can help uncovering the crossroads between biology and chemistry in drug discovery as well as lead to higher information content in the data received from biological evaluations, providing essential information for well-grounded decisions as to the future of the project. These two strategies can also help researchers identify the best routes to take at the crossroads linking biological and chemical elements of drug discovery programs.

Place, publisher, year, edition, pages
Umeå: Kemi, 2006. 80 p.
Chemometrics, Design of experiments, Experimental design, Multivariate data-analysis, D-optimal design, 96-well technology, Drug discovery, Assay optimisation, QSAR
National Category
Organic Chemistry
urn:nbn:se:umu:diva-693 (URN)91-7264-032-4 (ISBN)
Public defence
2006-03-04, KB3B1, KBC, Umeå Universitet, Umeå, 10:00
Available from: 2006-02-07 Created: 2006-02-07 Last updated: 2011-03-09Bibliographically approved

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