Fixed reference edge system for slide loading and unloading

Abstract

A fixed reference edge system is provided that guides glass slides from a slot in a slide holder onto a scanning stage and from the scanning stage into the slot in the slide holder. In one embodiment, the fixed reference edge has a first side parallel to one side of the slot in the slide holder. The system includes an assembly comprising: a push rod configured to push the slide from the slot onto the scanning stage; and a pull rod configured to pull the slide from the scanning stage into the slot in the slide holder. When the slide is pulled into the slide holder, the long edge of the slide presses against the first side of the fixed reference edge to maintain parallel orientation between the slide and the slot in the slide holder.

Description

[0001] This application is a divisional application of application number 201880070117.3, application date: November 30, 2018, invention title: Fixed reference edge system for loading and unloading wafers. Technical Field

[0002] The present invention generally relates to a digital slide scanning apparatus (e.g., for pathology), and more specifically to a fixed reference edge positioned to guide glass slides from the slide holder onto the scanning stage or from the scanning stage onto the slide holder. Background Technology

[0003] Digital pathology is an image-based information environment enabled by computer technology that allows the management of information generated from physical slides. It is partly achieved through virtual microscopy, the practice of scanning samples on physical glass slides and producing digital images that can be stored, viewed, managed, and analyzed on a computer monitor. With its ability to image the entire glass slide, digital pathology has rapidly developed and is currently considered one of the most promising avenues in diagnostic medicine for achieving even better, faster, and cheaper diagnosis, prognosis, and prediction of major diseases such as cancer.

[0004] Glass slides processed by digital slide scanning equipment are highly fragile yet valuable. Unfortunately, conventional digital slide scanners often damage glass slides when transporting them from the slide holder to the scanning stage or vice versa. Therefore, a system and method are needed to overcome these significant problems found in the conventional systems described above. Summary of the Invention

[0005] Therefore, this document describes a fixed reference edge system that guides glass slides from a slide holder onto a scanning stage and also guides glass slides from the scanning stage into the slide holder. The system includes a fixed reference edge having a first side parallel to a side of a slot in the slide holder from which the slides are unloaded. The system also includes a push / pull assembly including a push rod configured to push the glass slide directly from the slot in the slide holder onto the scanning stage, such that the long edge of the glass slide is adjacent to the first side of the fixed reference edge. The push / pull assembly further includes a pull rod configured to pull the glass slide from the scanning stage into the slot in the slide holder. When the glass slide is pulled into the slot of the slide holder, the long edge of the glass slide presses against the first side of the fixed reference edge to position the long edge of the glass slide parallel to the side of the slot of the slide holder so that it can be inserted into the slot of the slide holder without damaging the glass slide.

[0006] In one embodiment, a digital slide scanning apparatus is disclosed, comprising: a stage including a recessed slot in which a glass slide is rested during scanning; a reference edge positioned to form a long edge of the recessed slot; and an assembly configured to: push a glass slide directly from a slide holder into the recessed slot on the stage, and pull a glass slide directly from the recessed slot on the stage into the slide holder, wherein the reference edge prevents lateral rotation of the glass slide when the glass slide is pulled into the slide holder by the assembly. The reference edge may extend along the entire long edge of the glass slide when the glass slide is positioned in the recessed slot on the stage.

[0007] In one embodiment, the recessed slot includes a through-hole configured to allow illumination of the glass slide from below during scanning. The recessed slot may include at least two support surfaces on opposite sides of the through-hole, wherein the at least two support surfaces are configured to support at least two opposite edges of the glass slide when the glass slide is positioned in the recessed slot on the stage. The reference edge may be positioned on a portion of one of the at least two support surfaces.

[0008] In one embodiment, the stage further includes one or more finger grooves configured to expose one or more portions of opposite short edges of the glass slide when the slide is positioned in the recessed slot on the stage. The assembly may include a pull rod and a push rod, wherein the pull rod is configured to pull the glass slide directly from the recessed slot on the stage into the slide holder, and wherein the push rod is configured to push the glass slide directly from the slide holder into the recessed slot on the stage. The pull rod may include at least one pull finger configured to engage the short edge of the glass slide via the one or more finger grooves and to pull the glass slide directly from the recessed slot on the stage into the slide holder by sliding within the one or more finger grooves when the glass slide is positioned in the recessed slot on the stage. The at least one pull finger may be configured to lower to engage the short edge of the glass slide and raise to disengage from the short edge of the glass slide. For example, the at least one pull finger may be configured to lower and raise by rotating about the longitudinal axis of the pull rod, wherein the digital slide scanning device further includes at least one processor configured to control the rotation of the pull finger. The push rod may include at least one push finger configured to engage the short edge of the glass slide when it is in the slide holder and push the glass slide directly from the slide holder into the recessed slot on the stage. In one embodiment, the assembly further includes an opening between the push rod and the pull rod, wherein the opening is configured to allow passage of the slide holder.

[0009] The digital slide scanning apparatus may further include at least one processor configured to control at least one motor to move the assembly in two directions along a linear axis parallel to the longitudinal axis of the recessed slot on the stage and the longitudinal axis of the slot in the slide holder. The stage may further include a spring arm configured to press the long edge of the glass slide toward the reference edge to prevent lateral rotation of the glass slide. The digital slide scanning apparatus may further include at least one processor that controls the spring arm to press the long edge of the glass slide toward the reference edge to prevent lateral rotation of the glass slide as the glass slide is pulled from the stage into the slide holder.

[0010] In one embodiment, a method is disclosed, the method comprising: controlling a motor to drive an assembly to push a first glass slide directly from a slot in a slide holder onto a scanning stage of a digital slide scanning device, such that a long edge of the glass slide is positioned adjacent to one side of a reference edge on the scanning stage, wherein the side of the reference edge is parallel to one side of the slot in the slide holder; controlling the digital slide scanning device to scan the glass slide; and after scanning the glass slide, controlling the motor to drive the assembly to pull the glass slide from the scanning stage into the slot in the slide holder, wherein the side of the reference edge prevents lateral rotation of the glass slide when it is pulled into the slot in the slide holder. The method may further comprise, while the glass slide is pulled into the slot in the slide holder, controlling a spring arm on the scanning stage to press the long edge of the glass slide toward the side of the reference edge to prevent lateral rotation of the glass slide.

[0011] Other features and advantages of the invention will become more apparent to those skilled in the art after reading the following detailed description and accompanying drawings. Attached Figure Description

[0012] The structure and operation of the invention will be understood by reading the following detailed description and accompanying drawings, in which the same reference numerals refer to the same parts and wherein:

[0013] Figure 1A This is a perspective view of an example push / pull assembly of a digital wafer scanning device according to one embodiment;

[0014] Figure 1B This is a perspective view illustrating an example push / pull assembly, slide holder, and scanning stage of a digital slide scanning apparatus according to one embodiment;

[0015] Figure 2A This is a perspective view of an example scanning stage with a reference edge and a glass slide, according to one embodiment;

[0016] Figure 2B This is a perspective view of an example scanning stage with a reference edge and a glass slide, according to one embodiment;

[0017] Figure 3A This is a block diagram illustrating an example supporting processor that can be used in conjunction with the various implementations described herein;

[0018] Figure 3B This is a block diagram illustrating an example line scan camera with a single linear array according to one embodiment;

[0019] Figure 3C A block diagram illustrating an example line scan camera with three linear arrays according to one embodiment; and

[0020] Figure 3D This is a block diagram illustrating an example line scan camera with multiple linear arrays according to one embodiment. Detailed Implementation

[0021] Some embodiments disclosed herein provide a fixed reference edge to facilitate loading slides from the slide holder onto the scanning stage and unloading slides from the scanning stage into slots in the slide holder. After reading this specification, it will become apparent to those skilled in the art how the invention can be implemented in various alternative embodiments and applications. However, although various embodiments of the invention will be described herein, it should be understood that these embodiments are presented by way of example only and are not intended to be limiting. Thus, this detailed description of various alternative embodiments should not be construed as limiting the scope or breadth of the invention as set forth in the appended claims.

[0022] 1. Example push / pull assembly

[0023] Figure 1A This is a perspective view illustrating an example push / pull assembly 100 of a digital slide scanning apparatus according to one embodiment. In the illustrated embodiment, the push / pull assembly 100 includes a pull rod 110 that includes one or more pull fingers 112 extending from a surface of the pull rod 110. The push / pull assembly 100 also includes a push rod 120 that includes one or more push fingers 122 extending from a surface of the push rod 120. In the illustrated embodiment, there are two pull fingers 112 and two push fingers 122. However, in alternative embodiments, fewer pull fingers 112 and / or push fingers 122 (e.g., one) or more pull fingers 112 and / or push fingers 122 (e.g., three, four, five, etc.) may be present. Furthermore, the number of pull fingers 112 may be the same as or different from the number of push fingers 122 (e.g., fewer or more).

[0024] In one embodiment, the pull finger 112 is configured to rise so that the finger 112 does not contact the edge of the glass slide 585, and to lower so that the finger 112 contacts the edge of the glass slide 585. For example, the pull finger 112 can rotate up and down within a range of rotation about the longitudinal axis of the pull rod 110. In contrast, the push finger 122 can be fixedly positioned.

[0025] In one embodiment, one or more pull fingers 112 and one or more push fingers 122 are positioned along the same linear axis XX and spaced apart by an opening 130 between the ends of the pull fingers 112 and the push fingers 122. The width of the opening 130, orthogonal to the linear axis XX, may be at least as wide as the short edge of the glass slide 585, and the length of the opening 130 along the linear axis XX may be at least as long as the long edge of the glass slide 585. In one embodiment, the push / pull assembly 100 is substantially C-shaped and has a slide holder opening 130 configured to allow at least a portion of the slide holder 300 and the slides 585 within the slide holder 300 to be positioned between the pull fingers 112 and the push fingers 122, wherein the pull fingers 112 and the push fingers 122 are oriented within the width of the short edge of the glass slide 585 stored in the slide holder 300.

[0026] Figure 1B This is a perspective view illustrating an example push / pull assembly 100 operating within a digital slide scanning apparatus, combined with a scanning stage 200 and a slide holder 300, according to one embodiment. In the illustrated operation, a push rod 120 of the push / pull assembly 100 extends into the slide holder 300. The push / pull assembly 100 can load glass slides 585 from slots in the slide holder 300 onto the scanning stage 200, or unload glass slides 585 from the scanning stage 200 into slots in the slide holder 300.

[0027] 2. Example scanning stage

[0028] The scanning stage 200 includes a through-hole 240 to allow illumination during scanning. The through-hole has a support surface along its periphery defining a slot into which a glass slide 585 is inserted and thereby supported over the through-hole. In one embodiment, the scanning stage 200 also includes a reference edge 210 positioned on one of the support surfaces such that a first side of the reference edge 210 is parallel to one side of the slot in the slide holder 200 into which the glass slide 585 is inserted. A spring arm 220 is attached to the top surface of the scanning stage 200 and configured to press the glass slide 585 against the first side of the reference edge 210 to maintain parallel orientation between the long edge of the glass slide 585 pressed against the first side of the reference edge 210 and the side of the slot in the slide holder into which the glass slide 585 is inserted. Advantageously, this at least prevents yaw rotation (i.e., rotation about an axis orthogonal to the plane of the scanning stage 200) when unloading the glass slide 585 from the scanning stage 200 into the slide holder 300.

[0029] Figure 2AThis is a perspective view of an example scanning stage 200 having a reference edge 210 and a glass slide 585 according to one embodiment. In the illustrated embodiment, the scanning stage 200 includes a reference edge 210 positioned such that a first side is adjacent to the long edge of a glass slide 585 positioned on the scanning stage 200 for scanning. The scanning stage 200 also includes a spring arm 220 configured to press the glass slide 585 against the first side of the reference edge 210. As shown, in one embodiment, there is no contact between the spring arm 220 and the glass slide 585 when the glass slide 585 is loaded onto the scanning stage 200. For example, when the glass slide 585 is loaded onto the scanning stage 200, the processor 555 of the digital slide scanning device can control the spring arm 220 to move away from the edge 222 of the slot in which the glass slide 585 is inserted, so as to avoid contact with the glass slide 585 or at least avoid applying pressure to the glass slide 585.

[0030] In one embodiment, the scanning stage 200 includes one or more finger grooves 202 formed as recesses in the top surface of the scanning stage 200 and extending into recessed slots into which glass slides 585 are inserted for scanning. The finger grooves 202 may logically extend along the entire longitudinal length of the slots in the scanning stage 200 into which the slides 585 are inserted, but may be divided into two segments 202A and 202B by a through-hole 240 in the scanning stage 200. The finger grooves 202 are configured to receive both pulling fingers 112 and pushing fingers 122 for unloading and loading. For example, the pull finger 112 of the pull rod 110 of the push / pull assembly 100 can be lowered into the finger groove 202A to engage the first short edge of the glass slide 585 positioned on the scanning stage 200 and slide along the finger groove 202, such that the push / pull assembly 100 can completely pull the glass slide 585 out of the scanning stage 200 and into the slide holder 300. Furthermore, the push finger 122 can engage the second short edge of the glass slide 585 within the slide holder 300 opposite the first short edge to push the glass slide 585 onto the scanning stage 200 when it is loaded onto the scanning stage 200. When the glass slide 585 is pushed onto the scanning stage 200, the pusher finger 122 can slide into the finger groove 202B of the scanning stage 200 to fully push the slide 585 into the insertion slot of the scanning stage 200.

[0031] In one embodiment, the edges 212 and 222 defining the recessed slot in which the glass slide 585 is inserted may be beveled to facilitate reliable loading of the glass slide 585 from the slide holder 300 onto the scanning stage 200. For example, in the illustrated embodiment, the recessed slot in which the glass slide 585 is loaded onto the scanning stage 200 has at least three sides. One of the three sides is formed by a reference edge 210. Advantageously, all three sides of the recessed slot may be beveled, including the edge formed by the scanning stage 200 and the edge formed by the reference edge 210. Alternatively, all three sides may be non-beveled, or only some of the three sides may be beveled.

[0032] Figure 2B This is a perspective view of an example scanning stage 200 having a reference edge 210 and a glass slide 585 according to one embodiment. In the illustrated embodiment, when the glass slide 585 is unloaded from the scanning stage 200 into the slide holder 300, a spring arm 220 applies positive pressure to the long edge of the glass slide 585. For example, when the glass slide 585 is unloaded from the scanning stage 200, the processor 555 of the digital slide scanning apparatus can control the spring arm 220 to move toward the edge 222 of the slot in which the glass slide 585 is inserted, so as to contact the glass slide 585 and apply pressure thereto. The pressure applied by the spring arm 220 to one long edge of the glass slide 585 also presses the other long edge of the glass slide 585 against the reference edge 210 to prevent yaw rotation.

[0033] In the illustrated embodiment, the scanning stage 200 also includes a through-hole 240 configured to allow illumination of the glass slide 585 from below during scanning. One or more support surfaces are present along the periphery of the through-hole 240. These support surfaces are parallel to the top surface of the scanning stage 200 but recessed below it to form a recessed insertion slot for the slide 585. In one embodiment, the depth of the recessed slot may be less than the thickness of a conventional glass slide 585. In one embodiment, a spring arm 220 is similarly recessed below the top surface of the scanning stage 200 to allow contact with the edge of the glass slide 585.

[0034] 3. Example Implementation Plan

[0035] In one embodiment, a digital slide scanning apparatus includes a stage on which a glass slide is positioned for scanning. The stage includes a reference edge positioned adjacent to a long edge of the glass slide when the slide is positioned on the stage for scanning. The digital slide scanning apparatus also includes a push / pull assembly configured to push the slide directly from a slide holder onto the stage, and further configured to pull the slide directly back from the stage into the slide holder, wherein the reference edge prevents lateral rotation of the glass slide when it is pulled back into the slide holder.

[0036] In one embodiment, when the glass slide is positioned on the stage for scanning, a reference edge extends along the entire long edge of the glass slide. The stage may also include a through-hole configured to allow illumination of the glass slide during scanning, the through-hole having at least two support surfaces parallel to the surface of the scanning stage, the at least two support surfaces being configured to support at least two edges of the glass slide when it is positioned on the stage for scanning. In one embodiment, the reference edge is positioned on one of the at least two support surfaces of the through-hole.

[0037] In one embodiment, the stage further includes one or more finger grooves configured to allow access to the short edge of the glass slide when the glass slide is positioned on the stage for scanning.

[0038] In one embodiment, the push / pull assembly stage includes a push rod and a pull rod, the push rod being configured to push a slide directly from the slide holder onto the stage for scanning, and the pull rod being configured to pull a glass slide directly back from the stage into the slide holder. In one embodiment, the push rod includes at least one push finger configured to engage a short edge of the glass slide and push the glass slide directly from the slide holder onto the scanning stage. In one embodiment, the pull rod includes at least one pull finger configured to engage a glass slide and pull the glass slide directly back from the stage into the slide holder. In one embodiment, the pull rod includes at least one pull finger configured to extend into one or more finger grooves to engage a glass slide and pull the glass slide directly back from the stage into the slide holder. In one embodiment, the push / pull assembly also includes a slide holder opening between the push rod and the pull rod, the slide holder opening being configured to allow the slide holder to pass through.

[0039] In one embodiment, a method for safely loading and unloading a slide from a slide holder includes using a motor to drive a push / pull assembly to push a first glass slide directly from a first slot in the slide holder onto the scanning stage of a digital slide scanning apparatus, wherein a long edge of the first glass slide is positioned on the scanning stage adjacent to a first side of a reference edge, wherein the first side is parallel to one side of the first slot in the slide holder. The method further includes scanning the first glass slide using the digital slide scanning apparatus, and after scanning the first glass slide, using the motor to drive the push / pull assembly to pull the first glass slide from the scanning stage into the first slot in the slide holder, wherein the first side of the reference edge prevents lateral rotation of the first glass slide when it is pulled into the first slot. In one embodiment, the method further includes pressing the long edge of the first glass slide against the first side of the reference edge to prevent lateral rotation of the first glass slide when it is pulled into the first slot.

[0040] 4. Example Digital Slide Scanning Equipment

[0041] Figure 3A This is a block diagram illustrating an example processor-supporting device 550 that can be used in conjunction with the various embodiments described herein. As those skilled in the art will understand, alternative forms of device 550 may also be used. In the illustrated embodiment, device 550 is presented as a digital imaging device (also known as a digital slide scanning device, digital slide scanner, scanner, scanner system, digital imaging device, etc.), which includes: one or more processors 555; one or more memories 565; one or more motion controllers 570; one or more interface systems 575; one or more movable stages 580, each of which supports one or more glass slides 585 having one or more samples 590; one or more illumination systems 595, which illuminate the samples; one or more objectives 600, each of which defines an optical path 605 traveling along an optical axis; one or more objective positioners 630; one or more optional incident illumination systems 635 (e.g., included in a fluorescence scanner system); one or more focusing optics 610; one or more line scan cameras 615; and / or one or more area scan cameras 620, each of which defines a separate field of view 625 on the sample 590 and / or glass slide 585. Various components of the scanner system 550 are communicatively coupled via one or more communication buses 560. Although one or more of each of the various components of the scanner system 550 may be present, for the sake of simplicity of description, these components will be described in the singular unless a plural description is required to convey appropriate information.

[0042] One or more processors 555 may include, for example, a central processing unit (CPU) and a separate graphics processing unit (GPU) capable of processing instructions in parallel, or one or more processors 555 may include a multi-core processor capable of processing instructions in parallel. Additional separate processors may also be provided to control specific components or perform specific functions, such as image processing. For example, additional processors may include auxiliary processors for managing data input, auxiliary processors for performing floating-point mathematical operations, dedicated processors (e.g., digital signal processors) with an architecture suitable for rapidly executing signal processing algorithms, slave processors (e.g., back-end processors) subordinate to the main processor, and additional processors for controlling the line scan camera 615, stage 580, objective lens 225, and / or display (not shown). Such additional processors may be separate discrete processors or may be integrated with processor 555. One or more processors 555 may be configured to control the motors driving the push / pull assembly 100, and are also configured to control the movement of the scanning stage 200 and the slide holder 300, thereby controlling the overall workflow of the digital imaging apparatus and loading the glass slide 585 from the slide holder 300 onto the stage 200 and unloading the glass slide 585 from the stage 200 into the slide holder 300.

[0043] Memory 565 provides storage for data and instructions of a program executable by processor 555. Memory 565 may include one or more volatile and / or non-volatile computer-readable storage media for storing data and instructions, including, for example, random access memory, read-only memory, hard disk drive, removable storage device drive, etc. Processor 555 is configured to execute instructions stored in memory 565 and communicate with various components of scanner system 550 via communication bus 560 to implement the overall functionality of scanner system 550.

[0044] One or more communication buses 560 may include communication buses 560 configured to transmit analog electrical signals, and may also include communication buses 560 configured to transmit digital data. Therefore, communication from the processor 555, motion controller 570, and / or interface system 575 via one or more communication buses 560 may include both electrical signals and digital data. The processor 555, motion controller 570, and / or interface system 575 may also be configured to communicate with one or more of the various elements of the scanning system 550 via a wireless communication link.

[0045] The motion control system 570 is configured to precisely control and coordinate the XYZ movement of the stage 580 and objective lens 600 (e.g., via objective lens positioner 630). The motion control system 570 is also configured to control the movement of any other moving parts in the scanner system 550. For example, in a fluorescence scanner embodiment, the motion control system 570 is configured to coordinate the movement of filters, etc., in the incident illumination system 635.

[0046] Interface system 575 allows scanner system 550 to interface with other systems and human operators. For example, interface system 575 may include a user interface for providing information directly to the operator and / or allowing direct input from the operator. Interface system 575 is also configured to facilitate communication and data transfer between scanner system 550 and one or more external devices directly connected to it (e.g., printers, removable storage media, etc.) or external devices (such as image server systems, operator stations, user stations, and management server systems) connected to scanner system 550 via a network (not shown).

[0047] Illumination system 595 is configured to illuminate a portion of sample 590. Illumination system 595 may include, for example, a light source and illumination optics. The light source may be a variable intensity halogen light source having a concave mirror to maximize light output and a KG-1 filter to suppress heat. The light source may also be any type of arc lamp, laser, or other light source. In one embodiment, illumination system 595 illuminates sample 590 in transmission mode, such that line scan camera 615 and / or area scan camera 620 sense the optical energy transmitted through sample 590. Optionally or additionally, illumination system 595 may be configured to illuminate sample 590 in reflection mode, such that line scan camera 615 and / or area scan camera 620 sense the optical energy reflected from sample 590. In general, illumination system 595 is configured to be suitable for probing microscope sample 590 in any known mode of optical microscopy.

[0048] In one embodiment, the scanner system 550 optionally includes an epi-illumination system 635 to optimize the scanner system 550 for fluorescence scanning. Fluorescence scanning is the scanning of a sample 590 comprising fluorescent molecules, which are photon-sensitive molecules that absorb light (excitement) at a specific wavelength. These photon-sensitive molecules also emit light (emission) at higher wavelengths. Because this photoluminescence phenomenon is very inefficient, the amount of emitted light is typically very low. This low amount of emitted light typically hinders conventional techniques (e.g., transmission-mode microscopy) used for scanning and digitizing the sample 590. Advantageously, in an optional fluorescence scanner system embodiment of the scanner system 550, a line scan camera 615 comprising multiple linear sensor arrays (e.g., a time-delay integration (TDI) line scan camera) is used to increase the light sensitivity of the line scan camera by exposing the same region of the sample 590 to each of the multiple linear sensor arrays of the line scan camera 615. This is particularly useful when scanning weakly fluorescent samples with low-emission light.

[0049] Therefore, in the fluorescence scanner system implementation, the line scan camera 615 is preferably a monochrome TDI line scan camera. Advantageously, monochrome images are desirable in fluorescence microscopy because they provide a more accurate representation of the actual signals from the various channels present on the sample. As those skilled in the art will understand, the fluorescent sample 590 can be labeled with a variety of fluorescent dyes that emit light at different wavelengths, these wavelengths also referred to as “channels”.

[0050] Furthermore, since the low-end and high-end signal levels of various fluorescent samples exhibit a broad spectrum of wavelengths to be sensed by the line scan camera 615, it is desirable that the low-end and high-end signal levels sensed by the line scan camera 615 be similarly broad. Therefore, in the fluorescence scanner embodiment, the line scan camera 615 used in the fluorescence scanning system 550 is a monochrome 10-bit 64-line array TDI line scan camera. It should be noted that various bit depths of the line scan camera 615 can be employed for use with the fluorescence scanner embodiment of the scanning system 550.

[0051] The movable stage 580 is configured to perform precise XY-axis movement under the control of processor 555 or motion controller 570. The movable stage can also be configured to move along the Z-axis under the control of processor 555 or motion controller 570. The movable stage is configured to position the sample at a desired location during image data acquisition by line scan camera 615 and / or area scan camera. The movable stage is also configured to accelerate the sample 590 to a substantially constant speed in the scanning direction and then maintain that substantially constant speed during image data acquisition by line scan camera 615. In one embodiment, the scanner system 550 may employ a high-precision and tightly coordinated XY grid to aid in positioning the sample 590 on the movable stage 580. In one embodiment, the movable stage 580 is a linear motor-based XY stage employing high-precision encoders on both the X and Y axes. For example, very precise nano-encoders may be used on the axis in the scanning direction and on the axis in a direction perpendicular to the scanning direction and in the same plane as the scanning direction. The stage is also configured to support a glass slide 585 on which the sample 590 is placed.

[0052] Sample 590 can be anything that can be examined by optical microscopy. For example, glass microscope slides 585 are frequently used as observation substrates for samples including tissues and cells, chromosomes, DNA, proteins, blood, bone marrow, urine, bacteria, droplets, biopsy material, or any other type of dead or living, stained or unstained, labeled or unlabeled biological material or substance. Sample 590 can also be an array of any type of DNA or DNA-related material (such as cDNA, RNA, or proteins) deposited on any type of slide or other substrate, including any and all samples commonly referred to as microarrays. Sample 590 can be a microtiter plate, such as a 96-well plate. Other examples of sample 590 include integrated circuit boards, electrophoresis records, petri dishes, membranes, semiconductor materials, forensic materials, and machined parts.

[0053] Objective lens 600 is mounted on objective lens positioner 630. In one embodiment, the objective lens positioner may employ a very precise linear motor to move objective lens 600 along the optical axis defined by objective lens 600. For example, the linear motor of objective lens positioner 630 may include a 50-nanometer encoder. The relative positions of stage 580 and objective lens 600 on the XYZ axes are coordinated and controlled in a closed-loop manner using motion controller 570 under the control of processor 555, which employs memory 565 to store information and instructions, including computer-executable programming steps for the entire operation of scanning system 550.

[0054] In one embodiment, objective 600 is a plan apochromatic (“APO”) infinity-corrected objective with a numerical aperture corresponding to the desired highest spatial resolution, wherein objective 600 is suitable for transmission-mode illumination microscopy, reflection-mode illumination microscopy, and / or incident-illumination-mode fluorescence microscopy (e.g., Olympus 40X, 0.75NA or 20X, 0.75NA). Advantageously, objective 600 is capable of correcting chromatic aberration and spherical aberration. Since objective 600 is infinity-corrected, focusing optics 610 can be positioned above objective 600 in optical path 605, where the light beam passing through objective is collimated. Focusing optics 610 focuses the light signal captured by objective 600 onto the light-response elements of line scan camera 615 and / or area scan camera 620 and may include optical components (such as filters, magnifier-converter lenses, etc.). Objective 600, combined with focusing optics 610, provides total magnification for scanning system 550. In one embodiment, the focusing optics 610 may include a barrel lens and an optional 2X magnification converter. Advantageously, the 2X magnification converter allows the native 20X objective lens 600 to scan the sample 590 at a 40X magnification.

[0055] The line scan camera 615 includes at least one linear array of image elements (“pixels”). The line scan camera can be monochrome or color. A color line scan camera typically has at least three linear arrays, while a monochrome line scan camera can have a single linear array or multiple linear arrays. Any type of singular or complex linear array can also be used, whether packaged as part of the camera or custom-integrated into an imaging electronics module. For example, a 3-linear-array (“red-green-blue” or “RGB”) color line scan camera or a 96-linear-array monochrome TDI can also be used. TDI line scan cameras typically provide a significantly better SNR in the output signal by summing intensity data from previously imaged areas of the sample, resulting in a signal-to-noise ratio (SNR) that is proportional to the square root of the number of integration stages. TDI line scan cameras include multiple linear arrays. For example, a TDI line scan camera can have 24, 32, 48, 64, 96, or even more linear arrays. The scanner system 550 also supports linear arrays manufactured in various formats, including some with 512 pixels, some with 1,024 pixels, and others with up to 4,096 pixels. Similarly, linear arrays with various pixel sizes can also be used in the scanner system 550. A key requirement for selecting any type of line scan camera 615 is that the movement of the stage 580 can be synchronized with the line rate of the line scan camera 615, so that the stage 580 can be in motion relative to the line scan camera 615 during digital image capture of the sample 590.

[0056] Image data generated by the line scan camera 615 is stored in a portion of memory 565 and processed by processor 555 to generate a continuous digital image of at least a portion of sample 590. The continuous digital image may be further processed by processor 555, and the processed continuous digital image may also be stored in memory 565.

[0057] In embodiments having two or more line scan cameras 615, at least one of the line scan cameras 615 may be configured to function as a focus sensor, operating in combination with at least one of the line scan cameras 615 configured to function as an imaging sensor. The focus sensor may be logically positioned on the same optical axis as the imaging sensor, or the focus sensor may be logically positioned before or after the imaging sensor relative to the scanning direction of the scanner system 550. In one embodiment where at least one line scan camera 615 functions as a focus sensor, image data generated by the focus sensor is stored in a portion of memory 565 and processed by one or more processors 555 to generate focus information, thereby allowing the scanner system 550 to adjust the relative distance between the sample 590 and the objective lens 600 to maintain focus on the sample during scanning. Alternatively, in one embodiment, at least one line scan camera 615 used as a focus sensor may be oriented such that each of the plurality of individual pixels of the focus sensor is positioned at a different logical height along the optical path 605.

[0058] In operation, various components of the scanner system 550 and the programmed modules stored in the memory 565 enable the automatic scanning and digitization of a sample 590 positioned on a glass slide 585. The glass slide 585 is securely placed on a movable stage 580 of the scanner system 550 to scan the sample 590. Under the control of the processor 555, the movable stage 580 accelerates the sample 590 to a substantially constant speed for sensing by the line scan camera 615, wherein the speed of the stage is synchronized with the line rate of the line scan camera 615. After scanning an image data strip, the movable stage 580 decelerates and brings the sample 590 to a substantially complete stop. The movable stage 580 then moves orthogonally to the scanning direction to position the sample 590 for scanning subsequent image data strips (e.g., adjacent strips). Additional strips are then scanned until the entire portion or the entire sample 590 has been scanned.

[0059] For example, during a digital scan of sample 590, consecutive digital images of sample 590 are acquired as multiple consecutive fields of view, which are combined together to form image stripes. Multiple adjacent image stripes are similarly combined to form a portion of or the entire sample 590 as a consecutive digital image. Scanning of sample 590 may include acquiring vertical or horizontal image stripes. Scanning of sample 590 may be top-down, bottom-up, or both (bidirectional), and may begin at any point on the sample. Alternatively, scanning of sample 590 may be left-to-right, right-to-left, or both (bidirectional), and may begin at any point on the sample. Additionally, image stripes need not be acquired in an adjacent or consecutive manner. Furthermore, the resulting image of sample 590 may be an image of the entire sample 590 or only a portion of sample 590.

[0060] In one embodiment, computer-executable instructions (e.g., programmed modules or other software) are stored in memory 565 and, when executed, enable scanning system 550 to perform the various functions described herein. In this specification, the term "computer-readable storage medium" is used to refer to any medium used to store computer-executable instructions and provide them to scanning system 550 for execution by processor 555. Examples of such media include memory 565 and any removable or external storage medium (not shown) that is directly or indirectly communicatively coupled (e.g., via a network) to scanning system 550.

[0061] Figure 3B A line scan camera with a single linear array 640 is shown, which can be implemented as a charge-coupled device (“CCD”) array. The single linear array 640 includes a plurality of individual pixels 645. In the illustrated embodiment, the single linear array 640 has 4,096 pixels. In alternative embodiments, the linear array 640 may have more or fewer pixels. For example, common formats for linear arrays include 512, 1,024, and 4,096 pixels. The pixels 645 are arranged linearly to define a field of view 625 of the linear array 640. The size of the field of view varies depending on the magnification of the scanner system 550.

[0062] Figure 3C A line scan camera with three linear arrays is shown, each of which can be implemented as a CCD array. The three linear arrays are combined to form a color array 650. In one embodiment, each individual linear array in the color array 650 detects a different color intensity (e.g., red, green, or blue). Color image data from each individual linear array in the color array 650 are combined to form a single field of view 625 of color image data.

[0063] Figure 3D A line scan camera with multiple linear arrays is shown, each of which can be implemented as a CCD array. The multiple linear arrays are combined to form a TDI array 655. Advantageously, the TDI line scan camera can provide a significantly better SNR in its output signal by increasing the SNR proportional to the square root of the number of linear arrays (also called integral stages) by summing intensity data from previously imaged regions of a sample. TDI line scan cameras can include even more linear arrays. For example, common formats for TDI line scan cameras include 24, 32, 48, 64, 96, 120, and even more linear arrays.

[0064] The above description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the invention. Various modifications to these embodiments will be apparent to those skilled in the art, and the general principles described herein can be applied to other embodiments without departing from the spirit or scope of the invention. Therefore, it should be understood that the description and drawings presented herein represent currently preferred embodiments of the invention, and thus represent the subject matter broadly contemplated by the invention. It should also be understood that the scope of the invention fully covers other embodiments that may become apparent to those skilled in the art, and the scope of the invention is accordingly not limited.

Claims

1. A digital wafer scanning device, the digital wafer scanning device comprising: The stage includes a recessed slot in which a glass slide rests during scanning; a reference edge positioned to form a long edge of the recessed slot parallel to the direction of glass slide extension or retraction; and a spring arm configured to press the long edge of the glass slide toward the reference edge. A push / pull assembly configured to push a glass slide out of the slide holder into a recessed slot on the stage, and to pull a glass slide from the recessed slot on the stage into the slide holder; and At least one hardware processor is configured to control a spring arm to press the long edge of the glass slide against a reference edge when the glass slide is pulled from a recessed slot on the stage into the slide holder. As the glass slide is pushed out of the slot in the slide holder, the spring arm on the stage is controlled to move away from the glass slide to avoid contact with it.

2. The digital slide scanning apparatus of claim 1, wherein when the glass slide is positioned in the recessed slot on the stage, the reference edge extends along the entire length of the long edge of the glass slide.

3. The digital slide scanning apparatus of claim 1, wherein the recessed slot includes a through-hole configured to allow illumination of the glass slide from below during scanning.

4. The digital slide scanning apparatus of claim 3, wherein the recessed slot includes at least two support surfaces on opposite sides of the through-hole, and wherein the at least two support surfaces are configured to support at least two opposite edges of the glass slide when the glass slide is positioned in the recessed slot on the stage.

5. The digital slide scanning apparatus of claim 4, wherein the reference edge is positioned on a portion of one of the at least two support surfaces.

6. The digital slide scanning apparatus of claim 1, wherein the stage further comprises one or more finger grooves configured to expose one or more portions of opposite short edges of the glass slide when the glass slide is positioned in the recessed slot on the stage.

7. The digital slide scanning apparatus of claim 6, wherein the push / pull assembly includes a pull rod and a push rod, wherein the push rod is configured to push a glass slide from the slide holder into the recessed slot on the stage, and wherein the pull rod is configured to pull a glass slide from the recessed slot on the stage into the slide holder.

8. The digital slide scanning apparatus of claim 7, wherein the pull rod includes at least one pull finger, the at least one pull finger being configured to engage a short edge of the glass slide via the one or more finger grooves and to pull the glass slide from the recessed slot on the stage into the slide holder by sliding within the one or more finger grooves when the glass slide is positioned in the recessed slot on the stage.

9. The digital slide scanning apparatus of claim 8, wherein the at least one pull finger is configured to lower to engage the short edge of the glass slide and raise to disengage from the short edge of the glass slide.

10. The digital wafer scanning apparatus of claim 9, wherein the at least one pull finger is configured to lower and raise by rotating about the longitudinal axis of the pull rod, and the at least one processor is configured to control the rotation of the pull finger.

11. The digital slide scanning apparatus of claim 7, wherein the push rod includes at least one push finger configured to engage a short edge of the glass slide when the glass slide is in the slide holder and push the glass slide from the slide holder into the recessed slot on the stage.

12. The digital slide scanning apparatus of claim 11, wherein the at least one push finger is fixedly positioned.

13. The digital wafer scanning apparatus of claim 7, wherein the push / pull assembly further includes an opening between the push rod and the pull rod, and wherein the opening is configured to allow the wafer carrier to pass through.

14. The digital slide scanning apparatus of claim 13, wherein the push rod includes at least one pushing finger, the pull rod includes at least one pulling finger, and wherein the opening is located between the at least one pushing finger and the at least one pulling finger.

15. The digital slide scanning apparatus of claim 14, wherein at least one pushing finger and at least one pulling finger are positioned along the linear axis of the opening.

16. The digital wafer scanning apparatus according to claim 1, wherein the push / pull assembly is formed in a C-shape.

17. The digital slide scanning apparatus of claim 1, wherein, The at least one processor is configured to control at least one motor to move the push / pull assembly in two directions along a linear axis parallel to the longitudinal axis of the recessed slot on the stage and the longitudinal axis of the slot in the slide holder.

18. A method for loading and unloading a wafer, comprising: A motor is controlled to drive a push / pull assembly to push a glass slide from a slot in a slide holder onto a scanning stage of a digital slide scanning device, thereby positioning one long edge of the glass slide near one side of a reference edge on the scanning stage, wherein said side of the reference edge is parallel to one side of the glass slide push-out or pull-out direction. Scan glass slides; After scanning the glass slide, the push / pull assembly is driven to pull the glass slide from the scanning stage into the slot of the slide holder; and... As the glass slide is pulled into the slot of the slide holder, a spring arm on the stage is controlled to press one long edge of the glass slide toward one side of the reference edge.

19. The method of claim 18, further comprising, when the glass slide is pushed out of the slot in the slide holder, controlling the spring arm on the scanning stage to move away from the glass slide to avoid contact with the glass slide.

Images