Mixing in standard 384-well plates is different from mixing in 96-well formats. The aspect ratio of a typical well, the balance of surface tension and mass of the fluids, and the scale of diffusion all add to the increased difficulty in mixing fluids in higher-density plates. Here we examine two methods to measure mixing and some common techniques for mixing in 384-well plates. While conventional shaking can suffice, alternative methods can accelerate and improve the efficiency of mixing in 384-well plates.
[Show abstract][Hide abstract] ABSTRACT: An ATPG for resistive bridging faults is proposed that combines the advantages of section-based generation and interval-based simulation. In contrast to the solutions introduced so far, it can handle arbitrary non-feedback bridges between two nodes, including ones detectable at higher resistance and undetectable at lower resistance, and faults requiring more than one vector for detection.
Current and Defect Based Testing, 2004. DBT 2004. Proceedings. 2004 IEEE International Workshop on; 05/2004
[Show abstract][Hide abstract] ABSTRACT: An efficient and versatile Compound Management operation is essential for the success of all downstream processes in high-throughput screening (HTS) and small molecule lead development. Staff, equipment, and processes need to be not only reliable, but remain flexible and prepared to incorporate paradigm changes. In the present report, we describe a system and associated processes which enable handling of compounds for both screening and follow-up purposes at the NIH Chemical Genomics Center (NCGC), a recently-established HTS and probe development center within the Molecular Libraries Initiative of the NIH Roadmap. Our screening process, termed quantitative HTS (qHTS), involves assaying the complete compound library, currently containing >200,000 members, at a series of dilutions to construct a full concentration-response profile. As such, Compound Management at the NCGC has been uniquely tasked to prepare, store, register, and track a vertically-developed plate dilution series (i.e., inter-plate titrations) in the 384-well format. These are compressed into a series of 1,536-well plates and are registered to track all subsequent plate storage. Here, we present details on the selection of equipment to enable automated, reliable and parallel compound manipulation in 384- and 1,536-well formats, protocols for preparation of inter-plate dilution series for qHTS, as well as qHTS-specific processes and issues.
Journal of the Association for Laboratory Automation 04/2008; 13(2):79-89. DOI:10.1016/j.jala.2007.12.004 · 1.50 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Rapid mixing in microplates is still an underappreciated challenge in screening assay development, particularly with the use of noncontact nanoliter liquid handlers. In high-content/throughput screening (HC/TS), fast and efficient mixing between compounds and cell culture medium is even more critical as biological kinetics dictates speed of mixing, usually within a few minutes. Moreover, mixing in HC/TS should be gentle enough to avoid any negative disruption in cell layer. Here the authors introduce a method to accurately quantify drop diffusion into a microplate well, independently of buffer, liquid handler, or dispensing protocol. This method was used to determine the effect of various mixing methods on the diffusion of a nanoliter drop of pure DMSO in aqueous buffer in 384-well plates. Rapid plate shaking and additional buffer addition were shown to be the most efficient and effective mixing methods for HC/TS. However, efficient mixing by plate shaking is limited by assay volume. Bulk addition shows fast and efficient mixing, without negative effects on cells. Moreover, this simple, fast, and inexpensive method can be easily adapted on any platform.
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