Combining HT-RNAi or Compound Screens with High Content Assays
Richer Datasets Offer Higher Patho-Physiological Relevance

Ever since starting its landmark time lapse video-microscopy screen for cell division genes in C. elegans (Gönczy et al., 2000, Nature 408:331; Sönnichsen et al., 2005, Nature 434: 462), Cenix has led the industry in applying the principles of high content (HC) biology to HT-RNAi in systems from worms to human cells.

Until recently, large scale studies, whether they were screens of compound libraries or genomes, favored the use of single parameter readouts such as those enabled by conventional plate readers.  This choice reflected both the industry's widespread emphasis on maximizing analysis throughputs, and the limited availability of readout technologies allowing the long-sought combination of high throughput (HT) with high content (HC).

In fact, this limitation has begun to fade in recent years, as HT/HC readout instrumentation has shown significant progress. Beyond several emerging technologies enabling multiplexed homogeneous assays, Cenix has particularly focused its efforts on the development and HT/HC application of automated microscopy-based assays. Indeed, since this approach allows the mining of subcellular localisation data and other in situ information, it arguably offers the strongest, widest potential for rich, multi-parameter analyses. Such advanced capabilities require an optimal combination of cutting-edge microscopy hardware for fast, yet flawless image acquisition, with sofisticated computing hardware and software for HT data management, storage and automated image analysis.

The task of accurately converting complex microscopy images into a series of quantitative numeric measurements is particularly challenging and represents one of the most active areas of new technology development today. For this reason, Cenix has complemented its own strengths in high performance computing and bio-informatics by exploring a wide range of specialized third party solutions, both academic and commercial, to secure the broadest, most powerful capabilities in this area.

As a result, Cenix has partnered with Munich-based Definiens AG to integrate its Definiens XD™ image analysis technology into Cenix's HT/HC-RNAi research offerings. Based on Definiens Cognition Network Technology developed originally for satellite imagery, Definiens XD™ offers a very wide range of object-oriented analysis methods to build fully-customizable algorithms applicable to microscopy images, overcoming many limitations common to most other packages which use pixel-based paradigms.

With these tools and capabilities in place, Cenix can offer cutting edge capabilities for the development and implementation of multiplexed cell-based assays allowing multi-parameter analyses within single screening runs.

Example: Making High Content HT-RNAi Screening a Reality in Human Cells
The Cenix Oncology MultiPlex™ (O-MP1™)

 The Oncology MultiPlex-1™ (O-MP1™), monitors not only cellular proliferation, but also its key underlying processes, necrosis, apoptosis, and cell cycle progression, as shown below

The same approach is being applied to a wide range of basic and/or disease-focused processes.

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