Multiplexed cell analysis on CellCards for drug discovery

Abstract

The desire to obtain more biologically relevant data is expanding the use of cell-based assays in drug discovery. These assays are performed and analyzed in ever more sophisticated ways (e.g. high content screening) that allow the collection of multiparametric information about cells affected by the screened compounds. The driver for these developments is the desire to increase data quality and density and reduce the use of valuable reagents and time.Here we describe an approach that adds a new dimension to the data quality/quantity mix by simultaneously analyzing several cell types in the same microplate well. The system is based on the use of encoded carriers (CellCards®) that permit the reading and analysis of cellular responses, and at the same time allow decoding and the attribution of these responses to the appropriate cell line. CellCards are rectangular particles with an expandable color barcode and a transparent section upon which cells can be grown and imaged for cellular readout. Before performing the assay, each cell line is grown on a different class of CellCards. CellCards, with attached cells, are mixed and dispensed into a microtiter plate where the assay is performed. Next the plates are imaged, decoded and the cells associated with each CellCard class are analyzed.Multiplexing cell lines allows assay controls and data normalization within each well, reducing well-to-well variability. It also allows the simultaneous interrogation of multiple targets and thus concurrent potency and selectivity screening. This may significantly reduce the time required to take a compound from primary screening into the clinic.

Microfabricated micropallets for enhancement of biomolecular techniques

“…Numerous encoding schemes and transportation techniques have been researched with interest and demand for multifunctional coding having long been identified in the literature (e.g., Braeckmans et al 2002Braeckmans et al , 2003aFinkel et al 2004;Verpoorte 2003). Many techniques and strategies exist for encoding and labeling, including beads (e.g., Fulton et al 1997;Keij and Steinkemp 1998;Kettman et al 1998;Braeckmans et al 2003a, b), quantum dots (e.g., Chan et al 2002;Gao et al 2002;Jiang et al 2005;So et al 2006) quantum dot embedded beads (e.g., Han et al 2001;Wang et al 2003), Cornell dots (e.g., Ow et al 2005), metal nanowires and nanorods (e.g., Keating and Natan 2003;Nicewarner-Peña et al 2001;Reiss et al 2002;Penn et al 2003;Walton et al 2002), glass plates (e.g., Ravkin et al 2004) and polymericbased particles (e.g., Evans et al 2003;Zhi et al 2003Zhi et al , 2005Pregibon et al 2007).…”