Patent Description:
The present invention generally relates to a digital slide scanning apparatus, and more particularly, to a scanning stage with a fixed reference edge and a movable opposing edge that are used to secure a slide (e.g., glass slide) to a support surface of the scanning stage of the digital slide scanning apparatus (e.g., for digital pathology).

Digital pathology is an image-based information environment which is enabled by computer technology that allows for the management of information generated from a physical slide. Digital pathology is enabled in part by virtual microscopy, which is the practice of scanning a specimen on a physical glass slide and creating a digital slide image that can be stored, viewed, managed, and analyzed on a computer monitor. With the capability of imaging an entire glass slide, the field of digital pathology has exploded and is currently regarded as one of the most promising avenues of diagnostic medicine in order to achieve even better, faster, and cheaper diagnosis, prognosis, and prediction of important diseases, such as cancer.

Glass slides that are scanned by a digital slide scanning apparatus must remain stationary, relative to the stage, during scanning to generate high quality digital image data. Additionally, when a glass slide is unloaded from the scanning stage into a slide rack, the orientation of the edges of a glass slide must be tightly controlled, to avoid damaging the glass slide. <CIT> discloses a slide handler instrument that automatically transfers glass microscope slides from a cassette or magazine to a motorized microscope stage and then returns the slide back into the second cassette. The instrument system has a slide cassette indexer, an XY-stage, and a slide exchange arm. These components are connected together and integrated into one unitary modular instrument that can be moved from one microscope to another. <CIT> discloses a microscope slide stage for holding a plurality of slides in a plane for sequential viewing by any slide viewer, the stage including a plurality of slide slots have associated with each slot a slidable wedging clamp for securing slides on the stage. The slide stage is particularly suitable for use with computerized slide mapping and analyzing devices. Conventional digital slide scanners employ costly solutions to ensure high quality digital image data and avoid damaging glass slides during processing. Therefore, what is needed is a system and method that overcomes these significant problems found in the conventional systems described above.

Accordingly, an opposing edges system is described herein that both secures a glass slide during scanning and guides a glass slide being unloaded from the scanning stage into a slide rack by pushing and/or pulling the slide off the support surface. In an embodiment, the system includes a fixed reference edge that has a surface facing a first edge (e.g., first long edge) of the glass slide. The system also includes a movable opposing edge that has a surface facing a second edge (e.g., second long edge) of the glass slide. The movable opposing edge is controlled by a processor of the digital scanning apparatus. When a glass slide is loaded onto the stage, the movable opposing edge is controlled by the processor to engage the opposing edge surface with the second edge of the glass slide. The processor further controls the movable opposing edge to press the first edge of the glass slide against the reference edge surface, and thereby secure the glass slide for scanning.

The processor also controls the movable opposing edge to press the first edge of the glass slide against the reference edge surface when the glass slide is being unloaded from the scanning stage into the slide rack by pushing and/or pulling the slide off the support surface. Advantageously, the reference edge surface is parallel to a side of the slide rack slot into which the glass slide will be inserted. The system also includes a push/pull assembly that includes a pull bar that is configured to pull the glass slide from the scanning stage into the slot of the slide rack while the first long edge of the glass slide is simultaneously being pressed against the reference edge surface.

Specifically, the present disclosure relates to digital slide scanning apparatuses and corresponding methods according to the appended claims.

Other features and advantages of the present invention will become more readily apparent to those of ordinary skill in the art after reviewing the following detailed description and accompanying drawings.

The structure and operation of the present invention will be understood from a review of the following detailed description and the accompanying drawings in which like reference numerals refer to like parts and in which:.

An opposing-edges system is disclosed herein for the scanning and processing of glass slides by a digital slide scanning apparatus. In an embodiment, the system comprises a fixed reference edge and a movable opposing edge (e.g., a spring arm) that are positioned on opposite sides of a support surface of a scanning stage upon which a glass slide is positioned for scanning. The movable opposing edge is controlled to move toward the fixed reference edge and engage the glass slide to secure the glass slide to the scanning stage during scanning. The glass slide remains secured between the movable opposing edge and the fixed edge when the glass slide is unloaded from the stage to a slide rack of the digital slide scanning apparatus, and a push/pull assembly pulls the slide from the scanning stage into the slide rack. In an embodiment, the fixed reference edge is parallel to and/or aligned with a side of the slide rack in which the glass slide is being inserted.

After reading this description it will become apparent to one skilled in the art how to implement the invention in various alternative embodiments and alternative applications. However, although various embodiments of the present invention will be described herein, it is understood that these embodiments are presented by way of example only, and not limitation. As such, this detailed description of various alternative embodiments should not be construed to limit the scope of the present invention as set forth in the appended claims.

<FIG> is a perspective view diagram illustrating an example scanning stage with a glass slide positioned between a reference edge and an opposing edge during loading onto the stage <NUM>, according to an embodiment. In the illustrated embodiment, the scanning stage <NUM> has a reference edge no positioned with a surface that is facing a first long edge of the adjacent glass slide <NUM> positioned on the stage <NUM> for scanning. The scanning stage <NUM> also includes a movable opposing edge <NUM> having a surface facing a second long edge of the glass slide <NUM> positioned on the stage <NUM> for scanning. The movable opposing edge <NUM> is configured to move toward the reference edge <NUM> or away from the reference edge <NUM>, for example, under the control of a processor of the digital slide scanning apparatus. The scanning stage <NUM> also includes one or more pull finger grooves <NUM> to facilitate unloading of the glass slide <NUM> from the scanning stage <NUM> and into a slide rack <NUM> (e.g., illustrated in <FIG> and <FIG>, according to an embodiment).

Embodiments will be primarily described herein as sandwiching a glass slide between the reference edge <NUM> and the movable opposing edge <NUM> along the glass slide's long edge. However, in an alternative embodiment, the glass slide could be sandwiched between the reference edge <NUM> and the movable opposing edge <NUM> along the glass side's short edge. Furthermore, there is no requirement that the slides be glass slides. Slides, other than glass slides, can be loaded, unloaded, and supported on the stage <NUM> in the same manner as described herein with respect to glass slides.

In the illustrated embodiment, in <FIG>, the surface of the movable opposing edge <NUM> is not in contact with the glass slide <NUM>. In an embodiment, the processor of the digital slide scanning apparatus controls the movable opposing edge <NUM> to not make contact with the glass slide <NUM> during loading of the glass slide <NUM> from the slide rack <NUM> onto the scanning stage <NUM>.

In the illustrated embodiment, the movable opposing edge <NUM> comprises a spring arm that is moved by a rotary bearing <NUM> in conjunction with a linear spring <NUM>. However, it should be understood that other commercial off-the-shelf components may be used to move the movable opposing edge <NUM>. In addition, any means, other than a spring arm, may be used to implement the movable opposing edge <NUM>, as long as the movable opposing edge <NUM> can be moved between a position in which at least a portion of the movable opposing edge <NUM> contacts and applies pressure to the glass slide <NUM> and a position in which the movable opposing edge <NUM> does not contact or apply pressure to the glass slide <NUM>. In an embodiment, the movable opposing edge <NUM> and the mechanism that moves the movable opposing edge <NUM> are implemented so as to enable a processor to control the movable opposing edge <NUM> to apply at least two different amounts of pressure when in contact with the glass slide <NUM> (e.g., a first amount of pressure for scanning, and a second amount of pressure for unloading).

<FIG> is a perspective view diagram illustrating the scanning stage <NUM> with the glass slide <NUM> positioned between the reference edge <NUM> and the opposing edge <NUM> during scanning, according to an embodiment. In contrast to <FIG>, in <FIG>, the surface of the movable opposing edge <NUM> is in contact with the glass slide <NUM>. As mentioned above, the processor of the digital slide scanning apparatus may be configured to control the movable opposing edge <NUM> to move at least an end surface of the movable opposing edge <NUM> toward the reference edge <NUM>, from a position that does not contact the glass slide <NUM> (e.g., illustrated in <FIG>) to a position that does contact the glass slide <NUM> (e.g., illustrated in <FIG>). The movable opposing edge <NUM> is configured to engage the second long edge of the glass slide <NUM> with an end surface of the movable opposing edge <NUM> that faces the glass slide <NUM>. Specifically, the end surface of the movable opposing edge <NUM> imparts lateral pressure to the glass slide <NUM> to press the first long edge of the glass slide <NUM> against the surface of the reference edge <NUM> that is facing the glass slide <NUM>. This secures the glass slide <NUM> to the surface of the stage <NUM>, between the reference edge <NUM> and the pressing end surface of the movable opposing edge <NUM>, during scanning.

<FIG> is a perspective view diagram illustrating the scanning stage <NUM> with the glass slide <NUM> positioned between the reference edge <NUM> and the opposing edge <NUM> during unloading from the stage <NUM>, according to an embodiment. As illustrated, the end surface of the movable opposing edge <NUM> is in contact with the glass slide <NUM>. The movable opposing edge <NUM> is configured to impart lateral pressure to press the first long edge of the glass slide <NUM> against the facing surface of the fixed reference edge <NUM> while the glass slide <NUM> is being unloaded from the slide stage <NUM>. The facing surface of the fixed reference edge <NUM> may be positioned parallel to and aligned with a side of the slide rack <NUM> into which the glass slide <NUM> is being inserted.

In an embodiment, the amount of pressure applied to the glass slide <NUM> by the movable opposing edge <NUM> during unloading is less than the amount of pressure applied to the glass slide <NUM> by the movable opposing edge <NUM> during scanning. For example, the processor of the digital slide scanning apparatus may control the movable opposing edge <NUM> to apply less pressure from the end surface to the glass slide <NUM> during unloading, and control the movable opposing edge <NUM> to apply more pressure from the end surface to the glass slide <NUM> during scanning.

<FIG> is a perspective view diagram illustrating the scanning stage <NUM> with no glass slide <NUM> and the reference edge <NUM> removed to illustrate the underlying structure, according to an embodiment. As illustrated, the stage <NUM> comprises a through hole <NUM> in the surface upon which the glass slide <NUM> rests, such that the glass slide <NUM> can be illuminated from below (e.g., by illumination system <NUM>). In the illustrated embodiment, the through hole <NUM> also separates the pull finger groove(s) <NUM> into two sections 130A and 130B on opposite sides of the through hole <NUM>. Each pull finger groove in one section 130A/130B is aligned, in a line across the through hole, with a corresponding pull finger groove in the other section 130B/130A.

As illustrated, the through hole <NUM> is surrounded on two or more sides by a slide support surface <NUM> of the stage <NUM>, upon which the glass slide <NUM> rests. In the illustrated embodiment, the pull finger grooves <NUM> are provided within the slide support surface <NUM> on both short sides of the through hole <NUM>. The slide support surface <NUM> may be recessed into the scanning stage <NUM>. In an embodiment, the depth of this slide recess may be sized such that, when a glass slide <NUM> rests on the slide support surface <NUM>, the top surface of the glass slide <NUM> is substantially flush with the top surface of the scanning stage <NUM>. Alternatively, the depth of the slide recess may be sized such that, when a glass slide <NUM> rests on the slide support surfaces <NUM>, the top surface of the glass slide is slightly below the top surface of the scanning stage <NUM>. As another alternative, the depth of the slide recess may be sized such that, when a glass slide <NUM> rests on the slide support surfaces <NUM>, the top surface of the glass slide is slightly above the top surface of the scanning stage <NUM>.

In an embodiment, the stage <NUM> comprises a reference edge groove <NUM> into which the reference edge is fitted and secured (e.g., via one or more screws). The reference edge groove <NUM> is formed such that the reference edge <NUM> is positioned on a support surface on one side of the through hole <NUM> (e.g., a long side), such that a first side of the reference edge <NUM> is parallel to and aligned with a side of the slot in the slide rack <NUM> into which the glass slide <NUM> is unloaded or inserted. The movable opposing edge <NUM> is attached to a top surface of the stage <NUM> on an opposite side of the through hole <NUM> than the reference edge <NUM>. The movable opposing edge <NUM> is configured to impart lateral pressure to the glass slide <NUM> to press the glass slide <NUM> against the first side of the reference edge <NUM> in order to maintain a parallel orientation between the long edge of the glass slide <NUM>, that is pressed against the first side of the reference edge <NUM>, and the side of the slot in the slide rack <NUM> into which the glass slide is unloaded or inserted.

<FIG> and <FIG> are perspective view diagrams illustrating an example push/pull assembly <NUM>, slide rack <NUM>, and scanning stage <NUM> of a digital slide scanning apparatus, according to an embodiment. In the illustrated embodiment, the push/pull assembly <NUM> is shown comprising a push bar <NUM> extending into the slide rack <NUM>. The illustrated push/pull assembly <NUM> also comprises a pull bar <NUM> with an open end comprising one or more pull fingers <NUM>. Pull finger(s) <NUM> are configured to move within corresponding pull finger groove(s) <NUM> in the stage <NUM>.

In an embodiment, the processor of the digital slide scanning apparatus controls the push/pull assembly <NUM> to load a glass slide <NUM> from the slide rack <NUM> onto the scanning stage <NUM>, and unload the glass slide <NUM> from the scanning stage <NUM> into the slide rack <NUM>. Specifically, the push bar <NUM> and pull fingers <NUM> work in combination to push a glass slide <NUM>, to be scanned, out from the slide rack <NUM> and onto the slide support surface <NUM> of the scanning stage <NUM>. After the glass slide <NUM> is scanned, the push bar <NUM> and pull fingers <NUM> work in combination to push the glass slide <NUM> off the slide support surface <NUM> of the scanning stage <NUM> and into a slot in the slide rack <NUM> that is aligned with and in the same plane as the slide recess in the scanning stage <NUM>. <FIG> illustrates the push/pull assembly <NUM> when a glass slide <NUM> is entirely supported on the scanning stage <NUM>, whereas <FIG> illustrates the push/pull assembly <NUM> when the glass slide <NUM> is partially supported on the scanning stage <NUM> and partially within a slot of the slide rack <NUM> (e.g., during loading or unloading of the glass slide <NUM>).

<FIG> is a block diagram illustrating an example glass slide <NUM>, positioned between the reference edge <NUM> and the movable opposing edge <NUM>, according to an embodiment. In the illustrated embodiment, the facing surfaces of both the fixed reference edge <NUM> and the movable opposing edge <NUM>, that face the glass slide <NUM>, are configured at an angle. Specifically, the top of both facing surfaces contact a top portion of the glass slide <NUM>, and, from the top to bottom, gradually recede away from the side surfaces of the glass slide <NUM>, such that the bottom of both facing surfaces do not contact or are recessed away from a bottom portion of the glass slide <NUM>. In other words, at a top of the glass slide <NUM>, the facing surfaces of the fixed reference edge <NUM> and the movable opposing edge <NUM> contact the glass slide <NUM>, whereas, at the bottom of the glass slide <NUM>, there is a gap 300A between the facing surface of the fixed reference edge <NUM> and the glass slide <NUM> and a gap 300B between the facing surface of the movable opposing edge <NUM> and the glass slide <NUM>. This orientation of the angled facing surfaces imparts downward pressure on the glass slide <NUM> to secure the glass slide <NUM> to the slide support surface <NUM> of the scanning stage <NUM> when the opposing edge <NUM> laterally presses the glass slide <NUM> into the reference edge <NUM>.

In an embodiment, a digital slide scanning apparatus includes a stage comprising a surface upon which a glass slide is positioned during scanning, the glass slide having a first long edge and a second long edge and a first short edge and a second short edge. The scanning apparatus also includes a reference edge attached to the stage and positioned adjacent to the first long edge of the glass slide when the slide is positioned for scanning. At least a portion of the reference edge extends above the surface upon which the glass slide is positioned during scanning. The scanning device also includes an opposing edge attached to the stage and positioned proximal to the second long edge of the glass slide. Similarly to the reference edge, at least a portion of the opposing edge extends above the surface upon which the glass slide is positioned during scanning. The opposing edge is also configured to move toward the reference edge and away from the reference edge. The scanning apparatus also includes a processor configured to control the movable opposing edge, such that, prior to scanning of the glass slide, the processor controls the opposing edge to move toward the reference edge and engage the second long edge of the glass slide to press the first long edge of the glass slide against the reference edge.

In an embodiment, a surface of the reference edge facing the glass slide is angled such that a lower portion of the reference edge surface facing the glass slide is recessed away from the glass slide. Similarly, in an embodiment, a surface of the opposing edge facing the glass slide is angled such that a lower portion of the opposing edge surface facing the glass slide is recessed away from the glass slide. When the angled opposing edge surface presses the glass slide against the angled reference edge surface, the combined angled surfaces provide downward pressure and secure the slide to a surface of the stage.

In an embodiment, the opposing edge comprises a spring arm that pivots above the surface of the stage upon which the glass slide is positioned, the spring arm operatively connected to a linear spring configured to actuate the spring arm and press a surface of the opposing edge against the second long edge of the glass slide. In an embodiment, the processor is configured to control operation of the linear spring and thereby control movement of the opposing edge. In an embodiment, the processor controls the opposing edge to move the opposing edge away from the reference edge during loading of a glass slide from the slide rack onto the scanning stage. In an embodiment, the processor controls the opposing edge to maintain contact between a surface of the opposing edge and the glass slide and a surface of the reference edge and the glass slide during scanning of the glass slide.

In an embodiment, a method comprises positioning a glass slide on a surface of a scanning stage, the glass slide comprising a first long edge, a second long edge, a first short edge, and a second short edge, wherein the first long edge of the glass slide is adjacent a reference edge. The method also comprises controlling an opposing edge to engage the second long edge of the glass slide, and controlling the opposing edge to press the first long edge of the glass slide against the reference edge. The method also comprises maintaining contact between the opposing edge and the second long edge of the glass slide and the first long edge of the glass slide and the reference edge during scanning of the glass slide. In an embodiment, the method also includes controlling the opposing edge to press the first long edge against the reference edge, while controlling a push/pull assembly to unload the glass slide from the stage into a slide rack.

<FIG> is a block diagram illustrating an example processor-enabled device <NUM> that may be used in connection with various embodiments described herein. Alternative forms of the device <NUM> may also be used as will be understood by the skilled artisan. In the illustrated embodiment, the device <NUM> is presented as a digital imaging device (also referred to herein as a scanner system, a scanning system, a scanning apparatus, a digital scanning apparatus, a digital slide scanning apparatus, etc.) that comprises one or more processors <NUM>, one or more memories <NUM>, one or more motion controllers <NUM>, one or more interface systems <NUM>, one or more movable stages <NUM> that each support one or more glass slides <NUM> with one or more samples <NUM>, one or more illumination systems <NUM> that illuminate the sample, one or more objective lenses <NUM> that each define an optical path <NUM> that travels along an optical axis, one or more objective lens positioners <NUM>, one or more optional epi-illumination systems <NUM> (e.g., included in a fluorescence scanner system), one or more focusing optics <NUM>, one or more line scan cameras <NUM> and/or one or more additional cameras <NUM> (e.g., a line scan camera or an area scan camera), each of which define a separate field of view <NUM> on the sample <NUM> and/or glass slide <NUM>. The various elements of the scanner system <NUM> are communicatively coupled via one or more communication busses <NUM>. Although there may be one or more of each of the various elements of the scanner system <NUM>, for the sake of simplicity, these elements will be described herein in the singular except when needed to be described in the plural to convey the appropriate information.

The one or more processors <NUM> may include, for example, a central processing unit (CPU) and a separate graphics processing unit (GPU) capable of processing instructions in parallel, or the one or more processors <NUM> may include a multicore processor capable of processing instructions in parallel. Additional separate processors may also be provided to control particular components or perform particular functions, such as image processing. For example, additional processors may include an auxiliary processor to manage data input, an auxiliary processor to perform floating point mathematical operations, a special-purpose processor having an architecture suitable for fast execution of signal-processing algorithms (e.g., digital-signal processor), a slave processor subordinate to the main processor (e.g., back-end processor), an additional processor for controlling the line scan camera <NUM>, the stage <NUM>, the objective lens <NUM>, and/or a display (not shown). Such additional processors may be separate discrete processors or may be integrated with the processor <NUM>.

The memory <NUM> provides storage of data and instructions for programs that can be executed by the processor <NUM>. The memory <NUM> may include one or more volatile and/or non-volatile computer-readable storage mediums that store the data and instructions, including, for example, a random access memory, a read only memory, a hard disk drive, a removable storage drive, and/or the like. The processor <NUM> is configured to execute instructions that are stored in the memory <NUM> and communicate via communication bus <NUM> with the various elements of the scanner system <NUM> to carry out the overall function of the scanner system <NUM>.

The one or more communication busses <NUM> may include a communication bus <NUM> that is configured to convey analog electrical signals, and may include a communication bus <NUM> that is configured to convey digital data. Accordingly, communications from the processor <NUM>, the motion controller <NUM>, and/or the interface system <NUM>, via the one or more communication busses <NUM>, may include both electrical signals and digital data. The processor <NUM>, the motion controller <NUM>, and/or the interface system <NUM> may also be configured to communicate with one or more of the various elements of the scanning system <NUM> via a wireless communication link.

The motion control system <NUM> is configured to precisely control and coordinate X, Y, and/or Z movement of the stage <NUM> (e.g., within an X-Y plane) and/or the objective lens <NUM> (e.g., along a Z axis orthogonal to the X-Y plane, via the objective lens positioner <NUM>). The motion control system <NUM> is also configured to control movement of any other moving part in the scanner system <NUM>. For example, in a fluorescence scanner embodiment, the motion control system <NUM> is configured to coordinate movement of optical filters and the like in the epi-illumination system <NUM>.

The interface system <NUM> allows the scanner system <NUM> to interface with other systems and human operators. For example, the interface system <NUM> may include a user interface to provide information directly to an operator and/or to allow direct input from an operator. The interface system <NUM> is also configured to facilitate communication and data transfer between the scanning system <NUM> and one or more external devices that are directly connected (e.g., a printer, removable storage medium) or external devices such as an image server system, an operator station, a user station, and an administrative server system that are connected to the scanner system <NUM> via a network (not shown).

The illumination system <NUM> is configured to illuminate a portion of the sample <NUM>. The illumination system may include, for example, a light source and illumination optics. The light source may comprise a variable intensity halogen light source with a concave reflective mirror to maximize light output and a KG-<NUM> filter to suppress heat. The light source could also comprise any type of arc-lamp, laser, or other source of light. In an embodiment, the illumination system <NUM> illuminates the sample <NUM> in transmission mode such that the line scan camera <NUM> and/or camera <NUM> sense optical energy that is transmitted through the sample <NUM>. Alternatively, or in combination, the illumination system <NUM> may also be configured to illuminate the sample <NUM> in reflection mode such that the line scan camera <NUM> and/or camera <NUM> sense optical energy that is reflected from the sample <NUM>. The illumination system <NUM> may be configured to be suitable for interrogation of the microscopic sample <NUM> in any known mode of optical microscopy.

In an embodiment, the scanner system <NUM> optionally includes an epi-illumination system <NUM> to optimize the scanner system <NUM> for fluorescence scanning. Fluorescence scanning is the scanning of samples <NUM> that include fluorescence molecules, which are photon-sensitive molecules that can absorb light at a specific wavelength (excitation). These photon-sensitive molecules also emit light at a higher wavelength (emission). Because the efficiency of this photoluminescence phenomenon is very low, the amount of emitted light is often very low. This low amount of emitted light typically frustrates conventional techniques for scanning and digitizing the sample <NUM> (e.g., transmission mode microscopy). Advantageously, in an optional fluorescence scanner system embodiment of the scanner system <NUM>, use of a line scan camera <NUM> that includes multiple linear sensor arrays (e.g., a time delay integration ("TDI") line scan camera) increases the sensitivity to light of the line scan camera by exposing the same area of the sample <NUM> to each of the multiple linear sensor arrays of the line scan camera <NUM>. This is particularly useful when scanning faint fluorescence samples with low emitted light.

Accordingly, in a fluorescence scanner system embodiment, the line scan camera <NUM> is preferably a monochrome TDI line scan camera. Advantageously, monochrome images are ideal in fluorescence microscopy because they provide a more accurate representation of the actual signals from the various channels present on the sample. As will be understood by those skilled in the art, a fluorescence sample <NUM> can be labeled with multiple florescence dyes that emit light at different wavelengths, which are also referred to as "channels.

Furthermore, because the low and high end signal levels of various fluorescence samples present a wide spectrum of wavelengths for the line scan camera <NUM> to sense, it is desirable for the low and high end signal levels that the line scan camera <NUM> can sense to be similarly wide. Accordingly, in a fluorescence scanner embodiment, a line scan camera <NUM> used in the fluorescence scanning system <NUM> is a monochrome <NUM>-bit <NUM>-linear-array TDI line scan camera. It should be noted that a variety of bit depths for the line scan camera <NUM> can be employed for use with a fluorescence scanner embodiment of the scanning system <NUM>.

The movable stage <NUM> is configured for precise X-Y movement under control of the processor <NUM> or the motion controller <NUM>. The movable stage may also be configured for Z movement under control of the processor <NUM> or the motion controller <NUM>. The movable stage is configured to position the sample in a desired location during image data capture by the line scan camera <NUM> and/or the area scan camera. The movable stage is also configured to accelerate the sample <NUM> in a scanning direction to a substantially constant velocity, and then maintain the substantially constant velocity during image data capture by the line scan camera <NUM>. In an embodiment, the scanner system <NUM> may employ a high-precision and tightly coordinated X-Y grid to aid in the location of the sample <NUM> on the movable stage <NUM>. In an embodiment, the movable stage <NUM> is a linear-motor-based X-Y stage with high-precision encoders employed on both the X and the Y axis. For example, very precise nanometer encoders can be used on the axis in the scanning direction and on the axis that is in the direction perpendicular to the scanning direction and on the same plane as the scanning direction. The stage is also configured to support the glass slide <NUM> upon which the sample <NUM> is disposed.

The sample <NUM> can be anything that may be interrogated by optical microscopy. For example, a glass microscope slide <NUM> is frequently used as a viewing substrate for specimens that include tissues and cells, chromosomes, DNA, protein, blood, bone marrow, urine, bacteria, beads, biopsy materials, or any other type of biological material or substance that is either dead or alive, stained or unstained, labeled or unlabeled. The sample <NUM> may also be an array of any type of DNA or DNA-related material such as cDNA or RNA or protein that is deposited on any type of slide or other substrate, including any and all samples commonly known as a microarrays. The sample <NUM> may be a microtiter plate (e.g., a <NUM>-well plate). Other examples of the sample <NUM> include integrated circuit boards, electrophoresis records, petri dishes, film, semiconductor materials, forensic materials, or machined parts.

Objective lens <NUM> is mounted on the objective positioner <NUM>, which, in an embodiment, employs a very precise linear motor to move the objective lens <NUM> along the optical axis defined by the objective lens <NUM>. For example, the linear motor of the objective lens positioner <NUM> may include a <NUM> nanometer encoder. The relative positions of the stage <NUM> and the objective lens <NUM> in X, Y, and/or Z axes are coordinated and controlled in a closed-loop manner using motion controller <NUM> under the control of the processor <NUM> that employs memory <NUM> for storing information and instructions, including the computer-executable programmed steps for overall scanning system <NUM> operation.

In an embodiment, the objective lens <NUM> is a plan apochromatic ("APO") infinity corrected objective with a numerical aperture corresponding to the highest spatial resolution desirable, where the objective lens <NUM> is suitable for transmission-mode illumination microscopy, reflection-mode illumination microscopy, and/or epi-illumination-mode fluorescence microscopy (e.g., an Olympus 40X, <NUM>. 75NA or 20X, <NUM> NA). Advantageously, objective lens <NUM> is capable of correcting for chromatic and spherical aberrations. Because objective lens <NUM> is infinity corrected, focusing optics <NUM> can be placed in the optical path <NUM> above the objective lens <NUM> where the light beam passing through the objective lens <NUM> becomes a collimated light beam. The focusing optics <NUM> focus the optical signal captured by the objective lens <NUM> onto the light-responsive elements of the line scan camera <NUM> and/or the area scan camera <NUM> and may include optical components such as filters, magnification changer lenses, and/or the like. The objective lens <NUM>, combined with the focusing optics <NUM>, provides the total magnification for the scanning system <NUM>. In an embodiment, the focusing optics <NUM> may contain a tube lens and an optional 2X magnification changer. Advantageously, the 2X magnification changer allows a native 20X objective lens <NUM> to scan the sample <NUM> at 40X magnification.

The line scan camera <NUM> comprises at least one linear array of picture elements ("pixels"). The line scan camera may be monochrome or color. Color line scan cameras typically have at least three linear arrays, while monochrome line scan cameras may have a single linear array or plural linear arrays. Any type of singular or plural linear array, whether packaged as part of a camera or custom-integrated into an imaging electronic module, can also be used. For example, a <NUM> linear array ("red-green-blue" or "RGB") color line scan camera or a <NUM> linear array monochrome TDI may also be used. TDI line scan cameras typically provide a substantially better signal-to-noise ratio ("SNR") in the output signal by summing intensity data from previously imaged regions of a specimen, yielding an increase in the SNR that is in proportion to the square-root of the number of integration stages. TDI line scan cameras comprise multiple linear arrays. For example, TDI line scan cameras are available with <NUM>, <NUM>, <NUM>, <NUM>, <NUM>, or even more linear arrays. The scanner system <NUM> also supports linear arrays that are manufactured in a variety of formats including some with <NUM> pixels, some with <NUM> pixels, and others having as many as <NUM> pixels. Similarly, linear arrays with a variety of pixel sizes can also be used in the scanner system <NUM>. The salient requirement for the selection of any type of line scan camera <NUM> is that the motion of the stage <NUM> can be synchronized with the line rate of the line scan camera <NUM>, so that the stage <NUM> can be in motion with respect to the line scan camera <NUM> during the digital image capture of the sample <NUM>.

The image data generated by the line scan camera <NUM> is stored in a portion of the memory <NUM> and processed by the processor <NUM> to generate a contiguous digital image of at least a portion of the sample <NUM>. The contiguous digital image can be further processed by the processor <NUM> and the revised contiguous digital image can also be stored in the memory <NUM>.

In an embodiment with two or more line scan cameras <NUM>, at least one of the line scan cameras <NUM> can be configured to function as a focusing sensor that operates in combination with at least one of the other line scan cameras <NUM> that is configured to function as an imaging sensor. The focusing sensor can be logically positioned on the same optical axis as the imaging sensor or the focusing sensor may be logically positioned before or after the imaging sensor with respect to the scanning direction of the scanner system <NUM>. In such an embodiment with at least one line scan camera <NUM> functioning as a focusing sensor, the image data generated by the focusing sensor is stored in a portion of the memory <NUM> and processed by the one or more processors <NUM> to generate focus information, to allow the scanner system <NUM> to adjust the relative distance between the sample <NUM> and the objective lens <NUM> to maintain focus on the sample during scanning. Additionally, in an embodiment, the at least one line scan camera <NUM> functioning as a focusing sensor may be oriented such that each of a plurality of individual pixels of the focusing sensor is positioned at a different logical height along the optical path <NUM>.

In operation, the various components of the scanner system <NUM> and the programmed modules stored in memory <NUM> enable automatic scanning and digitizing of the sample <NUM>, which is disposed on a glass slide <NUM>. The glass slide <NUM> is securely placed on the movable stage <NUM> of the scanner system <NUM> for scanning the sample <NUM>. Under control of the processor <NUM>, the movable stage <NUM> accelerates the sample <NUM> to a substantially constant velocity for sensing by the line scan camera <NUM>, where the speed of the stage is synchronized with the line rate of the line scan camera <NUM>. After scanning a stripe of image data, the movable stage <NUM> decelerates and brings the sample <NUM> to a substantially complete stop. The movable stage <NUM> then moves orthogonal to the scanning direction to position the sample <NUM> for scanning of a subsequent stripe of image data (e.g., an adjacent stripe). Additional stripes are subsequently scanned until an entire portion of the sample <NUM> or the entire sample <NUM> is scanned.

For example, during digital scanning of the sample <NUM>, a contiguous digital image of the sample <NUM> is acquired as a plurality of contiguous fields of view that are combined together to form an image stripe. A plurality of adjacent image stripes are similarly combined together to form a contiguous digital image of a portion or the entire sample <NUM>. The scanning of the sample <NUM> may include acquiring vertical image stripes or horizontal image stripes. The scanning of the sample <NUM> may be either top-to-bottom, bottom-to-top, or both (bi-directional), and may start at any point on the sample. Alternatively, the scanning of the sample <NUM> may be either left-to-right, right-to-left, or both (bi-directional), and may start at any point on the sample. Additionally, it is not necessary that image stripes be acquired in an adjacent or contiguous manner. Furthermore, the resulting image of the sample <NUM> may be an image of the entire sample <NUM> or only a portion of the sample <NUM>.

In an embodiment, computer-executable instructions (e.g., programmed modules and software) are stored in the memory <NUM> and, when executed, enable the scanning system <NUM> to perform the various functions described herein. In this description, the term "computer-readable storage medium" is used to refer to any media used to store and provide computer-executable instructions to the scanning system <NUM> for execution by the processor <NUM>. Examples of these media include memory <NUM> and any removable or external storage medium (not shown) communicatively coupled with the scanning system <NUM> either directly or indirectly, for example via a network (not shown).

<FIG> illustrates a line scan camera having a single linear array <NUM>, which may be implemented as a charge coupled device (CCD) array. The single linear array <NUM> comprises a plurality of individual pixels <NUM>. In the illustrated embodiment, the single linear array <NUM> has <NUM> pixels. In alternative embodiments, linear array <NUM> may have more or fewer pixels. For example, common formats of linear arrays include <NUM>, <NUM>, and <NUM> pixels. The pixels <NUM> are arranged in a linear fashion to define a field of view <NUM> for the linear array <NUM>. The size of the field of view <NUM> varies in accordance with the magnification of the scanner system <NUM>.

<FIG> illustrates a line scan camera having three linear arrays, each of which may be implemented as a CCD array. The three linear arrays combine to form a color array <NUM>. In an embodiment, each individual linear array in the color array <NUM> detects a different color intensity, for example, red, green, or blue. The color image data from each individual linear array in the color array <NUM> is combined to form a single field of view <NUM> of color image data.

Claim 1:
A digital slide scanning apparatus (<NUM>) comprising:
a stage (<NUM>) comprising a support surface (<NUM>) configured to support a slide (<NUM>) during scanning, the slide having a first side surface and a second side surface opposite the first side surface;
a reference edge (<NUM>) attached to the stage, wherein a facing side surface of the reference edge extends above the support surface, such that, when a slide is on the support surface, the facing side surface of the reference edge faces the first side surface of the slide;
a movable opposing edge (<NUM>) attached to the stage, wherein a facing side surface of the movable opposing edge extends above the support surface, such that, when a slide is on the support surface, the facing side surface of the movable opposing edge faces the second side surface of the slide, and wherein the movable opposing edge (<NUM>) is configured to move toward the reference edge (<NUM>) and away from the reference edge (<NUM>); and
at least one processor configured to,
when a slide (<NUM>) is being loaded from a slot in a slide rack, comprising a plurality of slots configured to hold slides, onto the support surface of the stage (<NUM>), control the movable opposing edge (<NUM>) to remain away from the second side surface of the slide, so as not to apply any pressure from the movable opposing edge (<NUM>) to the second side surface of the slide,
when the slide (<NUM>) is being scanned, control the movable opposing edge to contact the second side surface of the slide, so as to apply a first amount of pressure from the movable opposing edge (<NUM>) to the second side surface of the slide, and,
when the slide is being unloaded from the support surface of the stage (<NUM>) into a slot in the slide rack by pushing and/or pulling the slide (<NUM>) off the support surface (<NUM>), controlling the movable opposing edge (<NUM>) to contact the second side surface of the slide, so as to apply a second amount of pressure, less than the first amount of pressure, from the movable opposing edge (<NUM>) to the second side surface of the slide while the slide (<NUM>) is being pushed and/or pulled off the support surface (<NUM>).