High-throughput screening miniaturization

Mere, L., Bennett, T., Coassin, P., England, P., Hamman, B., Rink, T., Zimmerman, S., and Negulescu, P., Miniaturized FRET assays and microfluidics key components for ultra-high-throughput screening, Drug Discov. Today, 4, 363,1999. 

Pope, A.J., Haupts, U.M., Moore, K.J. Homogenous fluorescence readouts for miniaturized high-throughput screening theory and practice. Drug Discov. Today 1999, 4, 350-362. 

Stockwell, B.R., Haggarty, S.J. and Schreiber, S.L. (1999) High-throughput screening of small molecules in miniaturized mammalian cell-based assays involving post-translational modifications. Chemistry ei Biology,... 

Fig. 28 Schematic view of the Zeiss Plate Vision instrument which is state-of-the art for ultra-high throughput screening (uHTS) for drug discovery. The instrument resembles a 96-well parallel microscope the light of a excitation source (Xe-lamp or pulsed laser) is expanded to illuminate a microtiter plate. The excitation is structured into 96 channels by a mini-lens array (MLA) and focused into the well with a detection volume of < 100 nL. All 96 channels are read simultaneously by a gated, intensifed CCD. With this fast detector and the pulsed laser excitation, the instrument can be used to carry out miniaturized, 96 parallel lifetime measurements in microtiter plate format with nanosecond time resolution or time-gated detection [190]...

Even though a biochemical assay for an enzyme target might be available, development of a high-throughput screen can still pose significant challenges. First, the assay has to be miniaturized to a microtiter format (e.g., 96- or 384-well... 

Schroter, T. et al. 2008. Comparison of miniaturized time-resolved fluorescence resonance energy transfer and enzyme-coupled luciferase high-throughput screening assays to discover inhibitors of Rho-kinase II (ROCK-II). J. Biomol. Screen. 13, 17-28. 

Fig. 8.5. Miniaturized biodevices for ultra-high-throughput screening. (A) Piezo-electric ink-jet pipettor that allows pipetting down to the pico-liter scale with speeds up to 10,000 drops per second and an accuracy of 3 % [97] (B) Sample carrier containing six segments of a silicon wafer. Each segment comprises 900 reaction compartments with a maximum volume of 120 nl each [28].

Bead-Based Libraries Miniaturized High Throughput Screening... 

At the other extreme if you have no knowledge of the protein structure, no candidate ligands, and the X-ray structure is not yet known then a high throughput screening of primary large scale collections of compounds or combinatorial libraries would be screened. These techniques would use roboticized and miniaturized assays and be done to search for possible binding compounds. 

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