阅读说明：本技术 用于载片装载和卸载的固定的基准边缘系统 (Fixed reference edge system for slide loading and unloading ) 是由 N.纽伯格 于 2018-11-30 设计创作，主要内容包括：提供了一种固定的基准边缘系统,所述固定的基准边缘系统将玻璃载片从载片架的插槽导引到扫描载物台上并且将所述玻璃载片从所述扫描载物台导引到所述载片架的所述插槽中。在一个实施方案中,所述固定的基准边缘具有与所述载片架的所述插槽的一侧平行的第一侧。所述系统包括总成,所述总成包括：推杆,所述推杆被配置为将所述载片从所述插槽推动到所述扫描载物台上；以及拉杆,所述拉杆被配置为将所述载片从所述扫描载物台拉动到所述载片架的所述插槽中。当所述载片被拉动到所述载片架中时,所述载片的长边缘压靠在所述固定的基准边缘的所述第一侧上,以维持所述载片与所述载片架的所述插槽之间的平行定向。(A fixed reference edge system is provided that guides a glass slide from a slot of a slide rack onto a scanning stage and guides the glass slide from the scanning stage into the slot of the slide rack. In one embodiment, the fixed reference edge has a first side parallel to a side of the slot of the slide holder. The system includes an assembly, the assembly including: a push bar 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 of the slide holder. When the slide is pulled into the slide holder, a long edge of the slide presses against the first side of the fixed reference edge to maintain a parallel orientation between the slide and the slot of the slide holder.)

1. A digital slide scanning apparatus, the digital slide scanning apparatus comprising:

an object stage, the object stage comprising: a recessed slot in which a glass slide rests during scanning; and a reference edge positioned to form a long edge of the recessed socket; and

an assembly configured to

Pushing the glass slide directly out of the slide holder into the recessed slot on the stage, an

Pulling a glass slide from the recessed slot on the stage directly into the slide holder,

wherein the reference edge prevents yaw rotation of the glass slide as the glass slide is pulled into the slide holder by the assembly.

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

3. The digital slide scanning device 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 device 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 opposing edges of a glass slide when the glass slide is positioned in the recessed slot on the stage.

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

7. The digital slide scanning device of claim 6, wherein the assembly comprises a pull rod and a push rod, wherein the pull rod is configured to pull a 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 out of the slide holder into the recessed slot on the stage.

8. The digital slide scanning device of claim 7, wherein the drawbar includes at least one pull finger configured to engage a short edge of a glass slide via the one or more finger grooves and to pull the glass slide from the recessed slot on the stage directly 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 device of claim 8, wherein the at least one pull finger is configured to be lowered to engage the short edge of the glass slide and raised to disengage the short edge of the glass slide.

10. The digital slide scanning device of claim 9, wherein the at least one pull finger is configured to be lowered and raised by rotating about a longitudinal axis of the pull rod, and wherein the digital slide scanning device further comprises at least one processor configured to control the rotation of the pull finger.

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

12. The digital slide scanning device of claim 7, wherein the assembly further comprises an opening between the push rod and the pull rod, and wherein the opening is configured to allow the slide holder to pass through.

13. The digital slide scanning device of claim 12, further comprising at least one processor configured to control at least one motor to move the assembly in two directions along a linear axis parallel to a longitudinal axis of the recessed slot on the stage and a longitudinal axis of a slot in the slide holder.

14. The digital slide scanning device of claim 1, wherein the stage further comprises a spring arm configured to press a long edge of a glass slide toward the reference edge to prevent the yaw rotation of the glass slide.

15. The digital slide scanning apparatus of claim 14, further comprising at least one processor that controls the spring arm to press the long edge of the glass slide toward the reference edge to prevent the yaw rotation of the glass slide as the glass slide is pulled from the stage into the slide holder.

16. A method, the method comprising:

controlling a motor to drive an assembly to push a first glass slide directly from a slot of a slide rack onto a scanning stage of a digital slide scanning device so as to position a long edge of the glass slide 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 of the slide rack;

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 of the slide holder, wherein the side of the reference edge prevents yaw rotation of the glass slide when the glass slide is pulled into the slot of the slide holder.

17. The method of claim 16, further comprising 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 the yaw rotation of the glass slide as the glass slide is pulled into the slot of the slide holder.

Technical Field

The present invention relates generally to a digital slide scanning device (e.g., for pathology), and more particularly to a fixed reference edge positioned to guide the loading and unloading of glass slides from and to a slide rack onto and into a scanning stage.

Background

Digital pathology is an image-based information environment implemented by computer technology that allows management of information generated from physical slides. Digital pathology is accomplished in part by virtual microscopy, a practice of scanning a sample on a physical glass slide and producing a digital slide image that can be stored, viewed, managed, and analyzed on a computer monitor. By the ability to image whole glass slides, the field of digital pathology has developed dramatically and is currently considered one of the most promising approaches in diagnostic medicine to achieve even better, faster and cheaper diagnosis, prognosis and prediction of significant diseases (such as cancer).

Glass slides processed by digital slide scanning devices are very fragile but expensive. Unfortunately, conventional digital slide scanners tend to damage the glass slide as it is transported from the slide rack to the scanning stage or from the scanning stage to the slide rack. Accordingly, there is a need for a system and method that overcomes these significant problems found in the conventional systems described above.

Disclosure of Invention

Thus, described herein is a fixed reference edge system that guides the loading of glass slides from a slide rack onto a scanning stage and also guides the unloading of glass slides from the scanning stage into the slide rack. The system includes a fixed reference edge having a first side parallel to a side of a slot of the slide rack from which the slide is unloaded. The system also includes a push/pull assembly including a push rod configured to push the glass slide out of the slot of the slide holder directly onto the scanning stage such that a 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 of 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 for insertion into the slot of the slide holder without damaging the glass slide.

In one embodiment, a digital slide scanning apparatus is disclosed, comprising: an object stage comprising a recessed slot within which a glass slide rests during scanning; and a reference edge positioned to form a long edge of the recessed socket; and an assembly configured to: pushing a glass slide directly out of a slide rack into the recessed slot on the stage, and pulling a glass slide directly into the slide rack from the recessed slot on the stage, wherein the reference edge prevents yaw rotation of the glass slide when the glass slide is pulled into the slide rack 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.

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 opposing edges of a 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.

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

The digital slide scanning device may also 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 a longitudinal axis of the recessed slot on the stage and a longitudinal axis of a slot in the slide holder. The stage may also include a spring arm configured to press a long edge of a glass slide toward the reference edge to prevent the yaw rotation of the glass slide. The digital slide scanning apparatus can also 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 the yaw rotation of the glass slide as the glass slide is pulled from the stage into the slide holder.

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 of a slide rack onto a scanning stage of a digital slide scanning device so as to position a long edge of the glass slide 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 of the slide rack; 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 of the slide holder, wherein the side of the reference edge prevents yaw rotation of the glass slide when the glass slide is pulled into the slot of the slide holder. The method can also include controlling a spring arm on the scan stage to press the long edge of the glass slide toward the side of the reference edge to prevent the yaw rotation of the glass slide as the glass slide is pulled into the slot of the slide holder.

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.

Drawings

The structure and operation of the present invention will be understood by reading the following detailed description and drawings, in which like reference numerals refer to like parts and in which:

figure 1A is a perspective view illustrating an example push/pull assembly of a digital slide scanning device, according to one embodiment;

fig. 1B is a perspective view illustrating an example push/pull assembly, slide rack, and scanning stage of a digital slide scanning device, according to one embodiment;

figure 2A is a perspective view illustrating an example scanning stage having a reference edge and a glass slide, according to one embodiment;

figure 2B is a perspective view illustrating an example scanning stage with a reference edge and a glass slide, according to one embodiment;

FIG. 3A is a block diagram illustrating an example processor-enabled device that may be used in conjunction with various embodiments described herein;

FIG. 3B is a block diagram illustrating an example line scan camera with a single linear array, according to one embodiment;

FIG. 3C is a block diagram illustrating an example line scan camera with three linear arrays, according to one embodiment; and

fig. 3D is a block diagram illustrating an example line scan camera with multiple linear arrays, according to one embodiment.

Detailed Description

Certain embodiments disclosed herein provide a fixed reference edge to facilitate loading and unloading of slides from and to a slide rack into slots of the slide rack. 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, while various embodiments of the present invention will be described herein, it is to be 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 or breadth of the present invention as set forth in the appended claims.

1. Example push/Pull Assembly

Fig. 1A is a perspective view illustrating an example push/pull assembly 100 of a digital slide scanning device, 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 embodiment shown, there are two pull fingers 112 and two push fingers 122. However, in alternative embodiments, there may be 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.). Further, the number of pull fingers 112 may be the same as the number of push fingers 122 or different (e.g., less or more) than the number of push fingers 122.

In one embodiment, the pull finger 112 is configured to be raised to bring the finger 112 out of contact with the edge of the glass slide 585 and lowered to bring the finger 112 into contact with the edge of the glass slide 585. For example, the pull finger 112 may rotate up and down through a range of rotation about the longitudinal axis of the pull rod 110. In contrast, the push finger 122 may be fixedly positioned.

In one embodiment, the one or more pull fingers 112 and the one or more push fingers 122 are positioned along the same linear axis X-X and are spaced apart by an opening 130 between an end of the pull fingers 112 and an end of the push fingers 122. The width of the opening 130 orthogonal to the linear axis X-X may be at least as wide as the short edge of the glass slide 585, while the length of the opening 130 along the linear axis X-X 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 in the shape of the letter "C" and has a slide rack opening 130 configured to allow at least a portion of the slide rack 300 and a slide 585 within the slide rack 300 to be positioned between the pull finger 112 and the push finger 122, wherein the pull finger 112 and the push finger 122 are oriented within the width of the short edge of a glass slide 585 stored in the slide rack 300.

Fig. 1B is a perspective view illustrating an example push/pull assembly 100 operating within a digital slide scanning device in conjunction with a scanning stage 200 and a slide holder 300, according to one embodiment. In the operation shown, the 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 of the slide rack 300 onto the scanning stage 200 or unload glass slides 585 from the scanning stage 200 into slots of the slide rack 300.

2. Example scanning stage

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

Fig. 2A is a perspective view illustrating an example scanning stage 200 having a reference edge 210 and a glass slide 585, according to one embodiment. In the embodiment shown, the scanning stage 200 includes a reference edge 210 positioned such that the first side is adjacent to a 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 a 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, in order to avoid contacting the glass slide 585 or at least to avoid applying pressure to the glass slide 585.

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

In one embodiment, the edges 212 and 222 defined in the recessed slot into 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 embodiment shown, the glass slide 585 has at least three sides in a recessed slot in which it is loaded onto the scanning stage 200. One of the three sides is formed by the 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.

Fig. 2B is a perspective view illustrating an example scanning stage 200 having a reference edge 210 and a glass slide 585, according to one embodiment. In the embodiment shown, the spring arm 220 applies a positive pressure to the long edge of the glass slide 585 as the glass slide 585 is unloaded from the scanning stage 200 into the slide holder 300. For example, as the glass slide 585 is unloaded from the scanning stage 200, the processor 555 of the digital slide scanning device 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 and apply pressure to the glass slide 585. 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.

In the embodiment shown, the scanning stage 200 further comprises a through-hole 240 configured to allow illumination of the glass slide 585 from below during scanning. There are one or more support surfaces along the perimeter of the through-hole 240. The support surface is parallel to the top surface of the scanning stage 200, but recessed below the top surface of the scanning stage 200 to form a recessed insertion slot for the slide 585. In one embodiment, the depth of the recessed slot can be less than the thickness of a conventional glass slide 585. In one embodiment, the spring arm 220 is similarly recessed below the top surface of the scanning stage 200 to allow the spring arm 220 to contact the edge of the glass slide 585.

3. Example embodiments

In one embodiment, a digital slide scanning device includes a stage on which a glass slide is positioned for scanning, the stage including a reference edge positioned adjacent a long edge of the glass slide when the glass slide is positioned on the stage for scanning. The digital slide scanning device also includes a push/pull assembly configured to push the slide out of the slide holder directly onto the stage, the push/pull assembly further configured to pull the slide from the stage directly back into the slide holder, wherein the reference edge prevents yaw rotation of the glass slide when the slide is pulled back into the slide holder.

In one embodiment, the reference edge extends along the entire long edge of the glass slide when the glass slide is positioned on the stage for scanning. 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 a surface of the scanning stage, the at least two support surfaces configured to support at least two edges of the glass slide when the glass slide 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.

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

In one embodiment, the push/pull assembly stage includes a push rod configured to push the slide directly out of the slide holder onto the stage for scanning and a pull rod configured to pull the glass slide directly back into the slide holder from the stage. In one embodiment, the pusher 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 rack onto the scanning stage. In one embodiment, the pull rod includes at least one pull finger configured to engage the glass slide and pull the glass slide from the stage directly back into the slide holder. In one embodiment, the pull rod includes at least one pull finger configured to extend into the one or more finger grooves to engage and pull the glass slide from the stage directly back into the slide holder. In one embodiment, the push/pull assembly further includes a slide rack opening between the push rod and the pull rod, the slide rack opening configured to allow passage of the slide rack.

In one embodiment, a method of safely loading and unloading slides from a slide rack includes using a motor to drive a push/pull assembly to push a first glass slide directly from a first slot of the slide rack onto a scanning stage of a digital slide scanning device, 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 a side of the first slot of the slide rack. The method also includes scanning the first glass slide using the digital slide scanning device, and after scanning the first glass slide, driving the push/pull assembly using the motor to pull the first glass slide from the scanning stage into the first slot of the slide rack, wherein the first side of the reference edge prevents yaw rotation of the first glass slide when the first glass slide is pulled into the first slot. In one embodiment, the method further includes pressing a long edge of the first glass slide against a first side of the reference edge to prevent yaw rotation of the first glass slide when the first glass slide is pulled into the first slot.

4. Example digital slide scanning device

Fig. 3A is a block diagram illustrating an example processor-enabled device 550 that may be used in conjunction with various embodiments described herein. As the skilled person will appreciate, alternative forms of the device 550 may also be used. In the illustrated embodiment, the device 550 is presented as a digital imaging device (also referred to as a digital slide scanning apparatus, a digital slide scanner, a scanner system, a digital imaging device, etc.) that 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 supporting one or more glass slides 585 with one or more samples 590; one or more illumination systems 595 that illuminate the sample; one or more objective lenses 600 each defining an optical path 605 that travels along an optical axis; one or more objective lens positioners 630; one or more optional epi-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 scanning cameras 620, each of which defines a separate field of view 625 on the sample 590 and/or glass slide 585. The various elements of the scanner system 550 are communicatively coupled via one or more communication buses 560. Although there may be one or more of each of the various elements of the scanner system 550, for simplicity of description, these elements will be described in the singular, unless described in the plural to convey appropriate information.

The 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 the one or more processors 555 may include multiple core processors capable of processing instructions in parallel. Additional separate processors may also be provided to control certain components or to perform certain functions, such as image processing. For example, the additional processors may include an auxiliary processor for managing data input, an auxiliary processor for performing floating point mathematical operations, a dedicated processor (e.g., a digital signal processor) having an architecture suitable for quickly performing signal processing algorithms, a slave processor (e.g., a back-end processor) subordinate to the main processor, additional processors for controlling the line scanning camera 615, stage 580, objective lens 225, and/or a display (not shown). Such additional processors may be separate discrete processors or may be integrated with the processor 555. The one or more processors 555 can be configured to control the motors driving the push/pull assembly 100 and also configured to control the movement of the scanning stage 200 and slide rack 300, thereby controlling the overall workflow of the digital imaging device and the loading of glass slides 585 onto the stage 200 from the slide rack 300 and the unloading of glass slides 585 from the stage 200 into the slide rack 300.

Memory 565 provides storage of data and instructions for programs that may be executed by processor 555. Memory 565 may include one or more volatile and/or nonvolatile computer-readable storage media that store data and instructions, including for example random access memory, read only memory, hard disk drive, removable storage drive, and the like. The processor 555 is configured to execute instructions stored in the memory 565 and communicate with various elements of the scanner system 550 via the communication bus 560 to implement the overall functionality of the scanner system 550.

The one or more communication buses 560 may include a communication bus 560 configured to communicate analog electrical signals, and may include a communication bus 560 configured to communicate digital data. Thus, communications from the processor 555, motion controller 570, and/or interface system 575 via the 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.

Motion control system 570 is configured to precisely control and coordinate the X-Y-Z movement of stage 580 and objective 600 (e.g., via objective 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 and the like in the epi-illumination system 635.

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

An illumination system 595 is configured to illuminate a portion of the sample 590. The illumination system 595 may include, for example, a light source and illumination optics. The light source may be a variable intensity halogen light source with a concave reflector 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 a transmissive mode such that line scan camera 615 and/or area scan camera 620 senses optical energy transmitted through sample 590. Alternatively or additionally, the illumination system 595 can be configured to illuminate the sample 590 in a reflective mode such that the line scan camera 615 and/or the area scan camera 620 sense optical energy reflected from the sample 590. In general, the illumination system 595 is configured to be suitable for interrogating the microscope sample 590 in any known mode of optical microscopy.

In one embodiment, scanner system 550 optionally includes epi-illumination system 635 to optimize scanner system 550 for fluorescence scanning. A fluorescence scan is a scan of a sample 590 that includes fluorescent molecules, which are photon-sensitive molecules that can absorb light (excitation) at a particular wavelength. These photon-sensitive molecules also emit light (emission) at higher wavelengths. Since the efficiency of this photoluminescence phenomenon is very low, the amount of emitted light is generally very low. Such low amounts of emitted light typically prevent conventional techniques (e.g., transmission mode microscopy) for scanning and digitizing the sample 590. Advantageously, in an optional fluorescence scanner system embodiment of scanner system 550, line scan camera 615 (e.g., a Time Delay Integration (TDI) line scan camera) comprising a plurality of linear sensor arrays is used to increase the sensitivity of the line scan camera to light by exposing the same area of sample 590 to each of the plurality of linear sensor arrays of line scan camera 615. This is particularly useful when scanning weakly fluorescent samples with low emission light.

Thus, in a fluorescence scanner system implementation, the line scan camera 615 is preferably a monochrome TDI line scan camera. Advantageously, monochromatic 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, the fluorescent sample 590 may be labeled with a variety of fluorescent dyes that emit light at different wavelengths, also referred to as "channels.

Furthermore, since the low-end and high-end signal levels of the 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 that the line scan camera 615 can sense be similarly broad. Thus, in a fluorescence scanner embodiment, the line scan camera 615 used in the fluorescence scanning system 550 is a monochrome 10-bit 64 linear 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 implementation of the scanning system 550.

The moveable stage 580 is configured for precise X-Y axis movement under the control of the processor 555 or motion controller 570. The moveable stage may also be configured to move in 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 capture by the line scan camera 615 and/or the area scan camera. The movable stage is also configured to accelerate the sample 590 to a substantially constant velocity in the scan direction, and then maintain the substantially constant velocity during image data capture by the line scan camera 615. In one embodiment, scanner system 550 may employ a highly accurate and closely coordinated X-Y grid to help position sample 590 on movable stage 580. In one embodiment, movable stage 580 is a linear motor based X-Y stage, in which high precision encoders are employed in both the X and Y axes. For example, a very precise nano-encoder may be used on an axis in the scan direction and on an axis in a direction perpendicular to and in the same plane as the scan direction. The stage is also configured to support a glass slide 585 on which the sample 590 is disposed.

Sample 590 can be anything that can be interrogated by optical microscopy. For example, glass microscope slide 585 is often used as a viewing substrate for a sample that includes tissue 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. The sample 590 can also be an array of any type of DNA or DNA-related material (such as cDNA, RNA, or protein) deposited on any type of slide or other substrate, including any and all samples commonly referred to as microarrays. The sample 590 can be a microtiter plate, such as a 96-well plate. Other examples of sample 590 include integrated circuit boards, electrophoretic recording, petri dishes, membranes, semiconductor materials, forensic materials, and machined parts.

Objective lens 600 is mounted on an objective lens positioner 630, which in one embodiment may employ a very precise linear motor to move objective lens 600 along an optical axis defined by objective lens 600. For example, the linear motor of objective positioner 630 may include a 50 nanometer encoder. The relative positions of stage 580 and objective lens 600 in the X-Y-Z 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 programmed steps for the overall operation of scanning system 550.

In one embodiment, objective lens 600 is an APO infinity corrected objective lens having a numerical aperture corresponding to a desired maximum spatial resolution, wherein objective lens 600 is suitable for transmission mode illumination microscopy, reflection mode illumination microscopy, and/or epi-illumination mode fluorescence microscopy (e.g., Olympus 40X,0.75NA or 20X,0.75 NA). Advantageously, the objective lens 600 is capable of correcting chromatic and spherical aberrations. Since objective lens 600 is infinity corrected, focusing optics 610 may be placed above objective lens 600 in optical path 605, where the light beam passing through the objective lens becomes a collimated beam. The focusing optics 610 focus the optical signals captured by the objective lens 600 onto the light responsive elements of the line scan camera 615 and/or the area scan camera 620 and may include optical components (such as filters, magnification changer lenses, etc.). The objective lens 600 in combination with the focusing optics 610 provides the overall magnification to the scanning system 550. In one embodiment, the focusing optics 610 may comprise a tube lens and an optional 2X magnification changer. Advantageously, the 2X magnification changer allows the native 20X objective 600 to scan the sample 590 at 40X magnification.

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

Image data generated by line scanning camera 615 is stored in a portion of memory 565 and processed by processor 555 to generate successive digital images of at least a portion of sample 590. The sequential digital images may be further processed by processor 555, and the processed sequential digital images may also be stored in memory 565.

In embodiments having two or more line scanning cameras 615, at least one of the line scanning cameras 615 may be configured to operate as a focus sensor operating in combination with at least one of the line scanning cameras 615 configured to operate 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 with respect to the scanning direction of the scanner system 550. In one embodiment, where at least one line scan camera 615 is used 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, allowing scanner system 550 to adjust the relative distance between sample 590 and objective lens 600 to maintain focus on the sample during scanning. Additionally, in one embodiment, at least one line scan camera 615, which functions as a focus sensor, may be oriented such that each of a plurality of individual pixels of the focus sensor are positioned at different logical heights along optical path 605.

In operation, the various components of the scanner system 550, as well as the programmed modules stored in memory 565, enable automated scanning and digitization of a specimen 590 disposed on a glass slide 585. The glass slide 585 is securely placed on the movable stage 580 of the scanner system 550 to scan the sample 590. Under the control of processor 555, movable stage 580 accelerates sample 590 to a substantially constant speed for sensing by line scan camera 615, where the stage speed is synchronized with the line rate of line scan camera 615. After scanning the image data strip, movable stage 580 decelerates and sample 590 is brought to a substantially complete stop. The movable stage 580 then moves orthogonal to the scan direction to position the sample 590 for scanning of subsequent image data strips (e.g., adjacent strips). Additional bands are then scanned until the entire portion of sample 590 or the entire sample 590 is scanned.

For example, during a digital scan of sample 590, successive digital images of sample 590 are acquired as a plurality of successive fields of view that combine to form an image strip. A plurality of adjacent image strips are similarly combined together to form a continuous digital image of a portion of sample 590 or the entire sample 590. Scanning of sample 590 may include acquiring vertical image strips or horizontal image strips. The scan of the sample 590 may be top-to-bottom, bottom-to-top, or both (bi-directional), and may begin at any point on the sample. Alternatively, the scan of the sample 590 may be left to right, right to left, or both (bi-directional), and may begin at any point on the sample. Additionally, image strips need not be acquired in a contiguous or continuous manner. Further, the resulting image of the sample 590 may be an image of the entire sample 590 or only a portion of the sample 590.

In one embodiment, computer-executable instructions (e.g., programmed modules or other software) are stored in the memory 565 and, when executed, enable the 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 that is used to store and provide computer-executable instructions to the scanning system 550 for execution by the processor 555. Examples of such media include memory 565 and any removable or external storage media (not shown) that is directly or indirectly communicatively coupled (e.g., via a network) to scanning system 550.

Fig. 3B illustrates a line scan camera having a single linear array 640, which may be implemented as a charge coupled device ("CCD") array. The single linear array 640 includes a plurality of individual pixels 645. In the embodiment shown, a 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 in a linear fashion to define the field of view 625 of the linear array 640. The size of the field of view varies according to the magnification of the scanner system 550.

Fig. 3C shows a line scan camera with three linear arrays, each of which may be implemented as a CCD array. The three linear arrays are combined to form a color array 650. In one implementation, each individual linear array in color array 650 detects a different color intensity (e.g., red, green, or blue). The color image data from each individual linear array in color array 650 is combined to form a single field of view 625 of color image data.

Fig. 3D illustrates a line scan camera having a plurality of linear arrays, each of which may be implemented as a CCD array. Multiple linear arrays are combined to form TDI array 655. Advantageously, a TDI line scan camera can provide significantly better SNR in its output signal by summing the intensity data from previously imaged regions of the sample, resulting in an increase in SNR proportional to the square root of the number of linear arrays (also called integration stages). TDI line scan cameras may include a greater number of linear arrays. For example, common formats for TDI line scan cameras include linear arrays of 24, 32, 48, 64, 96, 120, and even more.

The previous description of the disclosed embodiments is provided to enable any person skilled in the art to make or use the present invention. Various modifications to these embodiments will be readily apparent to those skilled in the art, and the generic principles described herein may be applied to other embodiments without departing from the spirit or scope of the invention. It is, therefore, to be understood that the description and drawings presented herein represent a presently preferred embodiment of the invention and are therefore representative of the subject matter which is broadly contemplated by the present invention. It is also to be understood that the scope of the present invention fully encompasses other embodiments that may become obvious to those skilled in the art and that the scope of the present invention is accordingly not limited.