Abstract: A method for operating a scanning microscope system. The optimal number of required through-focus scans, that is required to predict the position of a focal plane of the objective with respect to the object to produce the image with minimized blur, is not pre-determined but rather defined iteratively in real-time, contemporaneously with conducting the sample scanning operation itself.

Abstract: System and method for correcting a topography of an object being imaged by a multi-array microscope system. The object is forced to conform to a surface of the substrate supporting the object with a suction force and the topography of the chosen object surface is determined. The supporting substrate is bent with the use of force applied to the substrate with at least one actuator such as to reduce the deviations of the determined topography of the object's surface from a pre-determined reference surface by transferring the changes in the curvature of the supporting substrate to the object. In particular, the chosen surface of the object can be substantially flattened for ease of simultaneous imaging of this surface with multiple objectives of the multi-array microscope.

Abstract: A method for object preparation for imaging with an array microscope system without scanning. Artifact-free image is formed based on scanning-free imaging of an object array formed from spatially-separated portions of the initially spatially-continuous object that are arranged, in the object plane of the array microscope, in a pattern associated with an array of individual objectives of the array microscope. The size of an individual portion of the object does not exceed the size of a FOV of the individual objective defined in the object plane.

Abstract: Method and system of interferometrically measuring, in reflection, a non-spherical surface with two diffracted beams (of different diffraction orders) formed by a diffractive element positioned transversely to the axis of a common-path interferometer. The first diffracted beam substantially maintains the wavefront of a beam incident onto the diffractive element, while the second diffracted beam has a wavefront profile corresponding to the profile of the measured surface. The first diffracted beam may be reflected by the surface in a cat's eye configuration, while the second diffracted beam is reflected by the surface in a confocal configuration. The surface being measured can be modified to substantially balance radiant powers of the first and second diffracted beams upon reflection off the surface.

Abstract: Method and system of interferometrically measuring, in reflection, a non-spherical surface with two diffracted beams (of different diffraction orders) formed by a diffractive element positioned transversely to the axis of a common-path interferometer. The first diffracted beam substantially maintains the wavefront of a beam incident onto the diffractive element, while the second diffracted beam has a wavefront profile corresponding to the profile of the measured surface. The first diffracted beam may be reflected by the surface in a cat's eye configuration, while the second diffracted beam is reflected by the surface in a confocal configuration. The surface being measured can be modified to substantially balance radiant powers of the first and second diffracted beams upon reflection off the surface.

Abstract: Two-dimensional scanning array microscope system, which has fields of view of individual objectives overlapping at the object, produces a composite image of the object that is devoid of optical distortions caused by such overlapping. Method for processing imaging data with the system includes precise identification of detector pixels corresponding to different portions of multiple image swaths projected on the detector by the system during the scan of the object, and, based on such identification, allocating or assigning of detector pixels that receive light from the object through more than one objective to only one of objectives, thereby correcting imaging data received in real time to remove a portion of data corresponding to image overlaps.

Abstract: System and method for identification of foreign object debris, FOD, in a sample, based on comparison of edge features identified in images of the sample takes at a reference point in time and at a later time (when FOD may be already present). The rate of success of identification of the FOD is increased by compensation for relative movement between the imaging camera and the sample, which may include not only processing the sample's image by eroding of imaging data but also preceding spatial widening of edge features that may be indicative of FOD.

Abstract: Two-dimensional scanning array microscope system, which has fields of view of individual objectives overlapping at the object, produces a composite image of the object that is devoid of optical distortions caused by such overlapping. Method for processing imaging data with the system includes precise identification of detector pixels corresponding to different portions of multiple image swaths projected on the detector by the system during the scan of the object, and, based on such identification, allocating or assigning of detector pixels that receive light from the object through more than one objective to only one of objectives, thereby correcting imaging data received in real time to remove a portion of data corresponding to image overlaps.

Abstract: System and method for correcting a topography of an object being imaged by a multi-array microscope system. The object is forced to conform to a surface of the substrate supporting the object with a suction force and the topography of the chosen object surface is determined. The supporting substrate is bent with the use of force applied to the substrate with at least one actuator such as to reduce the deviations of the determined topography of the object's surface from a pre-determined reference surface by transferring the changes in the curvature of the supporting substrate to the object. In particular, the chosen surface of the object can be substantially flattened for ease of simultaneous imaging of this surface with multiple objective of the multi-array microscope.

Abstract: A microscope array with staggered rows of magnifying imaging systems is used to scan a biological tissue sample in a single linear pass to produce an image and corresponding optical-density data. A conventional computerized algorithm is used to identify, isolate and produce segmented images of nuclei contained in the image. The OD values corresponding to nuclear chromatin are used to identify numerical patterns known to have statistical significance in relation to the health condition of the biological tissue. These patterns are analyzed to detect pre-neoplastic changes in histologically normal-appearing tissue that suggest a risk for the development of a pre-malignant and a potentially malignant lesion. This information is then converted to a visually perceptible form incorporated into the image of the tissue sample and is displayed for qualitative analysis by a pathologist.

Abstract: An imaging apparatus consists of multiple miniaturized microscopes arranged into an array capable of simultaneously imaging respective portions of an object. A continuous linear translation approach is followed to scan the object and generate multiple image swaths of the object. In order to improve the quality of the composite image produced by concatenation of the image swaths, the performance of each microscope is normalized to the same base reference for each relevant optical-system property. Correction factors are developed through calibration to equalize the spectral response measured at each detector, to similarly balance the gains and offsets of the detector/light-source combinations associated with the various objectives, to correct for geometric misalignments between microscopes, and to correct optical and chromatic aberrations in each objective.

Abstract: In a scanning microscope, slides are fed automatically from a magazine to the imaging system. Each slide is labeled in some fashion with information for selecting the appropriate modality of operation of the scanner for that slide and the modality is implemented automatically. The information is preferably tied to and defined by a laboratory information system (LIS). For example, the instructions may regard the type of microscopy (i.e., trans- or epi-illumination), multi-spectral imaging with particular spectral bands combined with a particular set of z-positions, alternative filters, settings for the numerical aperture of the condenser, alternative detector operation for different resolutions, and alternative post-scan analyses of the data, as deemed optimal for the scan. The label may also contain the slide's identity, a pathologist's name, desired post-scan handling protocol, etc. The preferred array microscope to carry out the invention is also described.

Abstract: An array microscope scans a slide in rapid sequence at different wavelengths to record multiple spectral images of the sample. Full spatial resolution of the image sensor is realized at each color because pixels are not shared between spectral bands. The object and detector are placed at conjugate distances selected to produce substantially equal magnification with minimum chromatic aberration at all wavelengths to ensure registration of all images. Spectral analysis is carried out by combining the images captured at each wavelength. The greater-than-RGB spectral resolution provided by the combination of images enables the isolation and display of the effects produced by the contemporaneous use of more than two stains on a tissue for improved pathological analysis.

Abstract: A liquid lens includes a segmented electrode that allows the simultaneous application of different potentials across the lens's meniscus to obtain a predetermined aberration correction condition and to adjust focal length as necessary to conform to the topography of the object being scanned. The lens also includes a gas plenum interfacing with one of the liquids of the lens to allow for volume changes in the lens cell due to temperature variations. This combination of features produces a liquid-lens cell capable of maintaining substantially constant transverse magnification and diffraction-limited image quality over a useful range of focal length. As such, the lens is particularly suitable for incorporation in an array of micro-objectives used in a scanning microscope.

Abstract: A microscope array for simultaneously imaging multiple objects. A preferred embodiment of a method according to the invention includes arranging the objects into an array, providing a microscope array having a plurality of imaging elements with respective fields of view arranged into a corresponding array such that the imaging elements are optically aligned respectively with the objects, and simultaneously imaging the objects with the microscope array to produce respective images of the objects. The invention also provides for scanning while imaging, and for stepping and repeating the imaging process.

Abstract: A single-axis illumination system for a multiple-axis imaging system, particularly an array microscope. A single-axis illumination system is used to trans-illuminate an object viewed with an array of imaging elements having multiple respective axes. The numerical apertures of the imaging elements are preferably matched to the numerical aperture of the illumination system. For Kohler illumination, the light source is placed effectively at the front focal plane of the illumination system. For critical illumination, the light source is effectively imaged onto the object plane of the imaging system. For dark field illumination, an annular light source is effectively provided. For phase contrast microscopy, an annular phase mask is placed effectively at the back focal plane of the objective lens of the imaging system and a corresponding annular amplitude mask is provided effectively at the light source.

Abstract: An equalization system for a multi-axis imaging system. A plurality of light detectors are arranged in a detector array and a plurality of light sources corresponding to detectors in the detector array are arranged in a source array so that light radiated from a point on the object illuminated by a given source is detected by a corresponding detector. A signal conditioning system is provided for receiving output signals from the plurality of detectors. An equalizer system, adapted to interact with said signal conditioning system, is provided for equalizing the output values for given amounts of optical power illuminating the respective fields of view of the imaging elements.

Abstract: A liquid lens includes a segmented electrode that allows the simultaneous application of different potentials across the lens's meniscus to obtain a predetermined aberration correction condition and to adjust focal length as necessary to conform to the topography of the object being scanned. The lens also includes a gas plenum interfacing with one of the liquids of the lens to allow for volume changes in the lens cell due to temperature variations. This combination of features produces a liquid-lens cell capable of maintaining substantially constant transverse magnification and diffraction-limited image quality over a useful range of focal length. As such, the lens is particularly suitable for incorporation in an array of micro-objectives used in a scanning microscope.

Abstract: A multiple-axis imaging system having optical elements whose optimal image positions can be individually adjusted, comprising a plurality of optical array elements having respective optical axes and being individually disposed with respect to one another to image respective sections of an object; and a plurality of image position shifting devices corresponding to respective optical elements for separately establishing the image positions for a plurality of the optical array elements. The multi-axis imaging system preferably comprises a miniaturized microscope array. The shifting devices may comprise wavelength filters or optical-path-length-altering elements, such as a plane parallel plates. The devices may also comprise a pair of wedges that adjustably overlap one another, the wedges having apexes that point in opposite directions and respective corresponding planar surfaces that are parallel to one another.

Abstract: An imaging apparatus consists of multiple miniaturized microscopes arranged into an array capable of simultaneously imaging respective portions of an object. A continuous linear translation approach is followed to scan the object and generate multiple image swaths of the object. In order to improve the quality of the composite image produced by concatenation of the image swaths, the performance of each microscope is normalized to the same base reference for each relevant optical-system property. Correction factors are developed through calibration to equalize the spectral response measured at each detector, to similarly balance the gains and offsets of the detector/light-source combinations associated with the various objectives, to correct for geometric misalignments between microscopes, and to correct optical and chromatic aberrations in each objective.