An imaging and diagnostic system and method for focal scanning of a specimen using optical projection tomographic microscopy and computer generation of three-dimensional images is disclosed. One embodiment includes a light source and an imaging system having an adjustable focal position, which acquires a plurality of digital 2D projection images of biological tissue placed within a specimen tube that translates and rotates past an optical lens in a helical pattern. A computer captures the images and generates a 3D composite image. Also disclosed is a system and method for preparing a specimen for optical microscopy. One embodiment includes fixing, staining, and/or optically clearing biological tissue within a microfluidic specimen chamber prior to placement in a specimen tube.