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A new wide field-of-view confocal imaging system and its applications in drug discovery and pathology

and the techniques of fixation, embedding and staining in late 19th century,40 with continued technical development including lenses of higher numerical aperture, magnification and contrast methods, light microscopes have been important tools for the biological studies of cells and tissues, and identifying micro-organisms causing diseases.16-18 In fact, the cell theory was started based on microscopic observations. Application of CLSM started to increase rapidly in the 1990s, due to the increased availability of confocal systems thanks to advances in optics, electronics and computer technology, and newly developed fluorochromes with better matching laser lines and brighter fluorescence.41 Applications of CLSM include fluorescence detection of gene expression profiling using cDNA microarrays,42 fluorescence volume investigation and reconstruction of tissue samples,43 identification of diagnostic markers,44 and so on.

In molecular drug discovery, DNA and tissue microarrays are playing more and more important roles. The availability of multi-tumor analysis helps overcome the issues of time consumption, intensive labor, and cost in validation of multiple pathogenic markers on multiple cancer tissue specimens.38 Although the technique of TMAs provides the potential of high-throughput data acquisition, only through highly efficient imaging systems with microscopic resolution can the potential be realized.

1.3. wide field-of-view Confocal Microscopy

The wide field-of-view confocal imaging system presented in this paper is capable of confocal imaging of large area specimen in a single scan, e.g., imaging an entire standard microscope slide (1 by 3 inches in size) without tiling, while a conventional widefield light microscope or confocal microscope using microscope obj
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