Forum 03/04/2004

“Automated Optical Microscopy of Subcellular Dynamics & Signaling”

Jeffrey Price – Bioengineering Dept, UCSD, Q3DM Inc.

Optical microscopy is an important tool for analyzing subcellular distributions of molecules and understanding molecular-functional relationships. But microscopy information gathering has been largely manually driven. Automating microscopy may yield tremendous increases in the efficiency of microscope-based discoveries. I will summarize some of the autofocus, image segmentation and software engineering advances that yielded the Q3DM high throughput microscope (now owned by Beckman Coulter). With the microscope fully automated, continuing challenges are largely oriented around image and data analysis techniques that remove the tedium of analyzing as many as millions of cells per slide or microtiter plate. Automated high throughput/high-resolution microscopy creates a potentially overwhelming number of cellular and subcellular measurements. Cellular heterogeneity adds complexity, can hinder screen significance and complicate drug discovery assay design. Dynamic data-driven mining creates defined subpopulations without physical sorting to facilitate rapid design and testing of new subcellular assays. Cell cycle phases, metabolic states and subcellular localization of molecules are examples where subpopulation assays may enable more productive screening. Powerful dynamic data mining tools enable efficient use of the large amount of information produced by automated microscopy.

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