A modular, fully integrated ultra-high-throughput screening system based on confocal fluorescence analysis techniques.
The rapid increase in size of compound libraries, as well as new targets emerging from the Human Genome Project, require progress in ultra-high-throughput screening (uHTS) systems. In a joint effort with scientists and engineers from the biotech and the pharmaceutical industry, a modular, fully integrated system for miniaturized uHTS was developed. The goal was to achieve high data quality in small assay volumes (1-4 microL) combined with reliable and unattended operation. Two new confocal fluorescence readers have been designed. One of the instruments is a 4-channel confocal fluorescence reader, measuring with 4 objectives in parallel. The fluorescence readout is based on single-molecule detection methods, allowing high sensitivity at low tracer concentrations and delivering an information-rich output. The other instrument is a confocal fluorescence imaging reader, where the images are analyzed in terms of generic patterns and quantified in units of intensity per pixel. Both readers are spanning the application range from assays with isolated targets in homogenous solution or membrane vesicle-based assays (4-channel reader) to cell-based assays (imaging reader). Results from a comprehensive test on these assay types demonstrate the high quality and robustness of this screening system.
Jäger
Stefan
S
Evotec OAI/Evotec Technologies, Hamburg, Germany. stefan.jaeger@evotecoai.com
Garbow
Norbert
N
Kirsch
Achim
A
Preckel
Hartwig
H
Gandenberger
Frank U
FU
Herrenknecht
Kurt
K
Rüdiger
Martin
M
Hutchinson
Jonathan P
JP
Bingham
Ryan P
RP
Ramon
Fernando
F
Bardera
Ana
A
Martin
Julio
J
D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016923:Cell Death; D002460:Cell Line; D002470:Cell Survival; D003201:Computers; D004340:Drug Contamination; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation* / Q000379:methods*; D005453:Fluorescence; D006801:Humans; D020128:Inhibitory Concentration 50; D008024:Ligands; D018613:Microscopy, Confocal; D010455:Peptides / Q000032:analysis; D011506:Proteins / Q000032:analysis; D012270:Ribosomes / Q000187:drug effects; D012680:Sensitivity and Specificity; D020298:U937 Cells
D000900:Anti-Bacterial Agents; D008024:Ligands; D010455:Peptides; D011506:Proteins