We propose to develop a next-generation, highly flexible optical system for use in a whole- slide scanner to rapidly generate virtual slides in pathology and cytology. The primary use of this optical system is to enable ultra-rapid and accurate imaging of tissue, frozen-tissue, tissue-microarray (TMA), and cytology glass slides for clinical and research purposes. This optical system will allow scanning a microscope slide in a single sweep at a minimum numerical aperture of NA = 0.65, covering the entire width and length of a glass slide with 0.23-fm sampling. The optical system is based on an array of miniature microscopes. Each microscope in the array includes a variable-optical-power, liquid-lens element. The liquid-lens elements are controlled electrically and permit the individual focusing of each miniature microscope during scanning of tissue and cell specimens. As a result, the array microscope can rapidly and continually reconfigure itself during imaging to produce the most accurate, high-quality images of histology and cytology specimens. The long-term goal is to image slide-borne specimens in less than 60 seconds at 0.23-fm sampling (i.e., equivalent to a 40X magnification). The proposed liquid lenses are designed to rapidly adjust focus or to enable extended-depth-of-field imaging relevant for cytology slides. The Phase I project emphasizes development of a novel liquid-lens element and assembly of a liquid-lens array microscope prototype. The evaluation of the prototype emphasizes image quality as a function of focus at multiple depths achieved with the liquid lens. Image quality will be measured in terms of resolution and distortion. In Phase II, we plan to complete development of a modular, "industrial" version of the liquid lens array-microscope instrument including 120 miniature microscopes. Liquid-lens technology, combined with DMetrix's ultra-rapid, automated array-microscope technology, represents a key development in advancing diagnostic and prognostic tissue-based digital-pathology analysis. The result of this combination will be a less costly, fast and highly accurate microscopic imaging device. This device will generate high-resolution digital images for use in telemedicine, reduced turnaround-time healthcare, drug development, and computer-aided diagnosis
