Abstract: A biological tissue sample is scanned in a single 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: 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: 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: 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: An epi-illumination system for an array microscope. For Kohler illumination, illumination light sources are placed, actually or virtually, at the pupils of respective individual microscope elements of an array microscope. In one Kohler illumination embodiment, the light source is a point source comprising the tip of an optical fiber placed on the optical axis at the pupil of its corresponding microscope element. In another Kohler illumination embodiment, the illumination light is provided by a reflective boundary placed on the optical axis of a corresponding microscope element. For critical illumination the light sources are placed at locations conjugate with their respective object planes so as to image the light sources thereon.

Abstract: A single-axis optical system is introduced in the imaging channel of an array microscope in order to relay the image of the sample object onto a detector placed apart from the array. Because of the relatively large size of the single-axis system, sufficient space is available to provide simultaneous epi-illumination to all objectives in the array with a single lateral source directed toward the sample object by a beam splitter positioned along the imaging train. As a result of this configuration, conjugate aperture-stop positions are provided that can be used to place optical elements in the system to affect the properties of the illumination and/or the imaging wavefronts.

Abstract: A multi-axis imaging system and method wherein a plurality of optical elements are arranged to produce in image space thereof respective images of respective regions in object space thereof, and a plurality of image sensing elements corresponding to respective optical elements are disposed in image space of the image sensing elements to capture images of the respective regions. At least one baffle is positioned along an optical pathway of at least one of the optical elements to block light from outside the field of view of the one of the optical elements from reaching a corresponding image sensing element.

Abstract: A multi-spectral miniature microscope objective imaging system for a miniature microscope array includes one or more illuminating light sources for illuminating an object with light including multiple spectral bands, a multi-spectral imaging miniature microscope objective for imaging the object, and one or more detectors for detecting a images corresponding to each of the multiple bands separated from other wavelengths of the light.

Abstract: A multi-axis projection imaging system. Such a system includes a plurality of objectives defining respective object fields of view and corresponding image fields of view. An object is adapted for controllably illuminating the object fields of view with light that varies spatially in one or more selected characteristics, for creating respective images within the image fields of view.

Abstract: A method and system for limiting the amount of image data to be captured by a scanning imaging array. A low-resolution preliminary image of an object is acquired. Data from the preliminary image is used to identify features of interest in the object or to perform other image analyses that do not require a high-resolution image. Thereafter a scanning imaging array may be used to acquire a high-resolution image of only limited areas of the object including the features of interest or of only limited object characteristics. In one embodiment, the preliminary image is acquired using a separate, linear scanning array extending laterally with respect to the scan direction of the scanning imaging array. In another embodiment, an under sampled portion of the imaging elements of the scanning imaging array, or detectors thereof, is used to pre-scan the object to produce the low-resolution preliminary image.

Abstract: A miniature microscope objective for a miniature microscope array (MMA) includes preferably at least three or four lenses including from object to image a first positive lens, a second positive lens and a third negative lens. The objective has a numerical aperture (NA) that provides diffraction limited performance, and is preferably between 0.4 and 0.9 for the four lens design. The magnification of the objective is below approximately the outer diameter (OD) divided by the field of view (FOV), and is preferably between approximately 1 and 12, and is further preferably greater than 4. The ratio of magnification (M) to numerical aperture (NA) for the objective thereby has a magnitude that is less than substantially 30.

Abstract: A microscope stage providing improved optical performance. A carriage for supporting an object has a transparent portion for receiving the object and permitting trans-illumination thereof. A base supports the carriage, at least a portion of the base comprising a transparent material to permit illumination of the specimen there through. Bearings disposed between the base and the carriage support the carriage on the base and permit relative movement thereof. The base has a dovetail cross sectional shape with bearings between the top of the carriage and the base and between the sidewalls of the carriage and the base. A cover is coupled to the carriage so as to transfer force thereto without imparting a significant movement thereto. A mechanism connected to the cover for moving the carriage relative to the base is disposed at a position offset from the axis of lateral symmetry of the carriage and base.

Abstract: An imaging system with an integrated source and detector array. 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 in an epi-illumination system so that light radiated from a point on the object illuminated by a given source is detected by a corresponding detector. An optical system is disposed with respect to the source array and the detector array so as to illuminate an object with light from the source array and image the object on the detector array. Ordinarily, the sources and detectors are coplanar and, preferably, are fabricated or at least mounted on the same substrate. One or more sources in the source array may have a corresponding plurality of detectors, and one or more detectors in the detector array may have a corresponding plurality of sources.

Abstract: An imaging system with an integrated source and detector array. A plurality of light detectors are arranged in an array and a corresponding plurality of light sources are arranged in an array in an epi-illumination system so that light radiated from a point on the object illuminated by a given source is detected by a corresponding detector. An optical system is disposed so as to illuminate an object with light from the source array and image the object on the detector array. Ordinarily, the sources and detectors are coplanar and, preferably, are fabricated or at least mounted on the same substrate. In one embodiment the Airy pattern of the point response of the optical system encompasses both a detector and corresponding light sources. In another embodiment, the optical pathway is split by a diffractive element to produce conjugate points corresponding to light sources and their respective detectors. In a further embodiment, the pathway is split by a Wollaston prism.

Abstract: A miniature microscope objective includes at least three or four miniature lenses including from object to image at least a first positive lens, a second positive lens, and a third lens. The numerical aperture (NA) is greater than 0.4 and no more than approximately 0.9. The magnification variation ?M/M over red, green and blue wavelengths spanning 165 nm or more is less than 0.3% to 1.5%, an image size variation is less than a sampling distance, at least one lens has an aspheric departure, and the miniature objective includes at least one diffractive surface.

Abstract: A slide loading mechanism utilizes compressed air as the transport medium to move the slides from a magazine to the stage of a microscope. The stage is provided with a carriage moving horizontally along a direct path between the stage and the magazine. A conveyor coupled to the carriage includes a tongue suitable for positioning under the slide of interest in the magazine when the carriage is at one end of its travel path, so that the slide may be picked up for translation to the stage of the microscope. When the carriage is moved to the opposite end of its travel path, the tongue is completely removed from the magazine, which may be freely moved vertically by an elevator to align another slide for processing.

Abstract: A multiple-axis imaging system having individually-adjustable optical elements and a method for individually adjusting optical elements of the system. The system comprises a plurality of optical 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 individually-operable positioning devices corresponding to respective optical elements for positioning the optical elements with respect to their respective optical axes. The positioning devices are specifically adapted to adjust the axial position, lateral position and angular orientation of the optical elements with respect to their respective optical axes. The system is particularly adapted for use as a microscope array, and the positioning devices may be micro-actuators.

Abstract: An array of microscopes and a method of imaging an object with the array of microscopes. The array includes a plurality of optical elements being individually disposed with respect to a corresponding image plane and configured to image respective sections of an object, and includes a plurality of image sensors corresponding to respective optical elements and configured to capture corresponding representations of the respective sections of the object. The method includes imaging respective sections of an object with a plurality of optical elements and capturing corresponding representations of sections of the object from a plurality of image sensors.

Abstract: A multi-spectral miniature microscope objective imaging system for a miniature microscope array includes one or more illuminating light sources for illuminating an object with light including multiple spectral bands, a multi-spectral imaging miniature microscope objective for imaging the object, and one or more detectors for detecting a images corresponding to each of the multiple bands separated from other wavelengths of the light.