An apparatus for imaging a biological sample with fluorescence, the apparatus comprising: a rotatable imaging stage configured to support at least a portion of a biological sample within an imaging volume, and to rotate the at least a portion of the biological sample in two degrees of freedom; a transparent window attached to the rotatable imaging stage, having a plurality of equally spaced marks at predetermined intervals; a first camera ; a monochromatic second camera ; wherein the first and second camera are configured to take pictures of the sample at the same focal depth within the imaging volume; a partially reflective mirror , the mirror reflecting a portion of an image of the at least a portion of the biological sample to one of the cameras and the mirror transmitting a portion of the image to an optical system ; wherein the optical system is configured to present a reflected light image of the at least a portion of the biological sample to the position in space at which the focal depth of the other of the cameras is positioned; and a computer processor operatively connected with a machine-readable non-transitory medium embodying information indicative of instructions for causing the computer processor to perform an operation comprising: taking reflected light images of a biological sample on the imaging stage using the first camera, the reflected light images including the equally spaced marks; collecting fluorescence images of the biological sample using the second camera; detecting the equally spaced marks in the reflected light images or the fluorescence images; and calculating dimensions of the biological sample using the equally spaced marks in order to determine a three-dimensional position of a portion of the biological sample. a rotatable imaging stage configured to support at least a portion of a biological sample within an imaging volume, and to rotate the at least a portion of the biological sample in two degrees of freedom; a transparent window attached to the rotatable imaging stage, having a plurality of equally spaced marks at predetermined intervals; a first camera ; a monochromatic second camera ; wherein the first and second camera are configured to take pictures of the sample at the same focal depth within the imaging volume; a partially reflective mirror , the mirror reflecting a portion of an image of the at least a portion of the biological sample to one of the cameras and the mirror transmitting a portion of the image to an optical system ; wherein the optical system is configured to present a reflected light image of the at least a portion of the biological sample to the position in space at which the focal depth of the other of the cameras is positioned; and a computer processor operatively connected with a machine-readable non-transitory medium embodying information indicative of instructions for causing the computer processor to perform an operation comprising: taking reflected light images of a biological sample on the imaging stage using the first camera, the reflected light images including the equally spaced marks; collecting fluorescence images of the biological sample using the second camera; detecting the equally spaced marks in the reflected light images or the fluorescence images; and calculating dimensions of the biological sample using the equally spaced marks in order to determine a three-dimensional position of a portion of the biological sample. taking reflected light images of a biological sample on the imaging stage using the first camera, the reflected light images including the equally spaced marks; collecting fluorescence images of the biological sample using the second camera; detecting the equally spaced marks in the reflected light images or the fluorescence images; and calculating dimensions of the biological sample using the equally spaced marks in order to determine a three-dimensional position of a portion of the biological sample. <EOS>