Assay development and high-throughput screening of caspases in microfluidic format

Combinatorial Chemistry & High Throughput Screening
Ge WuBill Janzen

Abstract

Caspase proteases are familiar targets in drug discovery. A common format for screening to identify caspase inhibitors employs fluorogenic or colorimetric tetra-peptide substrates in 96, 384, or 1536 -well microtiter plates. The primary motivation for increasing the number of wells per plate is to reduce the reagent cost per test and increase the throughput of HTS operations. There are significant challenges, however, to moving into or beyond the 1536-well format, such as submicroliter liquid handling, liquid evaporation, increased surface area-to-volume ratios, and the potential for artifacts and interference from small air-borne particles such as lint. Therefore, HTS scientists remain keenly interested in technologies that offer alternatives to the ever-shrinking microtiter plate well. Microfluidic assay technology represents an attractive option that, in theory, consumes only subnanoliter volumes of reagents per test. We have successfully employed a microfluidic assay technology in fluorogenic screening assays for several caspase isoforms utilizing the Caliper Technologies Labchip platform. Caspase-3 is used as a representative case to describe microfluidic assay development and initial high-throughput screening results. In...Continue Reading

Citations

Aug 18, 2009·Analytical and Bioanalytical Chemistry·Randall D ReifDimitri Pappas
Mar 3, 2010·Analytical and Bioanalytical Chemistry·Randall D ReifDimitri Pappas
Apr 12, 2011·Analytical Chemistry·Cheong Hoon KwonAli Khademhosseini
Jun 3, 2011·Analytical Chemistry·Donald WlodkowicJonathan M Cooper
Nov 22, 2007·Lab on a Chip·Nannan YeBingcheng Lin
Jan 1, 2010·Expert Opinion on Drug Discovery·Dominique PerrinAdam Shutes
Sep 20, 2007·Journal of Pharmaceutical Sciences·Jeremy GuoJames N Herron
Dec 29, 2015·Analytica Chimica Acta·Guansheng DuJaap M J den Toonder
Mar 15, 2014·Scientific Reports·Qiulin YueXin Zhang
Jun 6, 2006·Journal of Biomolecular Screening·Dominique PerrinAlexander Scheer
May 29, 2004·Assay and Drug Development Technologies·Jude DunneJavier Farinas
Aug 2, 2005·Clinical Chemistry·Michael J PugiaLloyd S Schulman

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