The escalating cost of developing drugs is due, in part, to time spent assessing compounds that fail further down the drug discovery process. As such, high-content analysis (HCA) is now emerging as one of the most prominent areas in drug discovery due to its role in assessing the suitability of compounds, or targets, for extensive testing at an earlier stage in the process. The two main types of HCA instrumentation are automated fluorescence microscopy and laser-scanning cytometry. Both provide multicolored fluorescence readouts in fixed and live cells by observing fluorescently tagged markers of cellular activity, allowing researchers to screen for multiple cellular events using a single assay.
Fluorescence microscopy-based systems offer information-rich data at a high resolution, often over kinetic time points. As a result they generate vast quantities of image files (up to the terabyte level), which require analysis using complex algorithms and expensive solutions for data storage and retrieval. Many are too slow to run large primary screens, and the data too rich to interpret over large compound sets, but HCA platforms are ideally suited for secondary screening or target validation.
In contrast to imaging systems, laser-scanning technologies enable the rapid detection and quantification of multiparametric data from individual cells. One such example is the TTP LabTech ((a href="http://www.ttplabtech.com">www.ttplabtech.com) Acumen® eX3 microplate cytometer, which can monitor up to 12 fluorescent signals from objects seeded in plate densities up to 1,536 wells. The fast read times (down to 4 minutes per plate) enable the screening of up to 300,000 samples/day. In HTS mode, only information that is required is saved, reducing output files to levels that can be managed without data-storage servers. The whole-well scanning capability enables data to be collected from each cell within every well. Since cellular assays are intrinsically variable in their nature, this feature is ideal for use within a high-throughput environment to aid in the development of robust and reliable screening assays.