Slide counting and reinsertion system

Abstract

A slide rack counting and reinsertion system for use with a digital slide scanning apparatus is provided that determines that each slot in a slide rack is in a suitable occupancy, inappropriate occupancy, or empty state prior to scanning slides in the slide rack. The system also determines whether a slide that has been removed from the slide rack for processing has been correctly reinserted into the slide rack.

Description

[0001] This application is a divisional application of the patent application for invention with application number 201880062682.5 and invention name "Slide Counting and Reinsertion System", which was filed on October 4, 2018.

[0002] Cross - reference to related applications

[0003] This application claims the benefit of priority of U.S. Provisional Patent Application No. 62 / 568,195, filed on October 4, 2017, which is hereby incorporated by reference in its entirety as if fully set forth herein. Background of the invention Technical field

[0005] The present invention generally relates to a digital slide scanning device, and more particularly to processing individual slides (e.g., glass slides) (e.g., for digital pathology) contained in a slide rack by a digital slide scanning device. Background art

[0006] Digital pathology is an image - based information environment enabled by computer technology that allows management of information generated from physical slides. Digital pathology is partially enabled by virtual microscopy, which is the practice of scanning samples on a physical glass slide and creating digital slide images that can be stored, viewed, managed, and analyzed on a computer monitor. With the ability to image an entire glass slide, the field of digital pathology has grown rapidly and is currently considered one of the most promising approaches in diagnostic medicine for achieving better, faster, and cheaper diagnosis, prognosis, and prediction of serious diseases such as cancer.

[0007] The glass slides processed by a digital slide scanning device are very fragile and very valuable. In some cases, the slides in a slide rack may be mispositioned. This can cause damage to the slide when a conventional digital slide scanner processes the slide, for example, by attempting to retrieve a mispositioned slide from the slide rack and loading the slide onto the scanning stage. Therefore, there is a need for a system and method that overcomes these significant problems found in conventional systems as described above. Summary of the invention

[0008] Accordingly, this document describes a slide rack inventorying and reinsertion system for use with a digital slide scanning device. In one embodiment, the system is configured to determine the status of each slot in a slide rack as properly occupied, improperly occupied, or empty. The system includes a sensor bracket having a first arm and an opposing second arm, the first arm and the opposing second arm being positioned to define an opening through which a slide rack can be conveyed. A sensor having a transmitter and a receiver is attached to the sensor bracket, where one of the transmitter or the receiver is on the first arm and the other of the transmitter or the receiver is on the second arm. The transmitter and the receiver are positioned such that there is an operative line of sight therebetween and such that when a slide rack is conveyed through the opening between the two arms, the line of sight passes through each slot of the slide rack. The line of sight is also substantially parallel to the plane of the slides on the scanning stage of the digital slide scanning device. The line of sight is also positioned such that when a slide rack is conveyed through the opening between the two arms, the rear portion of each slide passes through the line of sight of the sensor pair. The rear portion of the slide is the portion that is remote from the opening through which the slide is inserted into or removed from the slide rack.

[0009] In operation, when a slide rack is conveyed through the opening, the sensor pair sends a signal to a processor that analyzes the signal to determine whether a slide is present in each slot of the slide rack. The status of each slot in the slide rack can be empty, occupied, stacked, or skewed.

[0010] Additionally, when the scanning of the slides is complete, the slides are reinserted into the slide rack. Since the line of sight of the sensor pair is substantially parallel to the plane of the slides conveyed from the scanning stage to the slide rack, the sensor pair sends a signal to a processor that analyzes the signal to determine whether the slides have been properly reinserted into the slide rack.

[0011] In one embodiment, a digital slide scanning device includes a motor configured to position a slide rack within the digital slide scanning device, the slide rack being configured to hold a plurality of slides in a plurality of slots, where each slot has an opening at a first end of the slot and a baffle at a second end of the slot. The digital slide scanning device also includes a sensor pair including a transmitter element and a receiver element positioned for line-of-sight communication, the transmitter element being located on a first side of a sensor bracket and the receiver element being located on a second side of the sensor bracket. The digital slide scanning device also includes a processor configured to control the motor to move the slide rack such that the rear portion of each of the plurality of slots of the slide rack passes through the line-of-sight communication of the sensor pair, the processor also being configured to receive a signal from the sensor pair and analyze the signal to determine the status of each slot of the slide rack.

[0012] In one embodiment, a method in a digital slide scanning device, the digital slide scanning device comprising: a motor configured to position a slide holder within the digital slide scanning device, the slide holder configured to hold a plurality of slides in a plurality of slots; a sensor pair comprising a transmitter element and a receiver element positioned relative to each other for line-of-sight communication; and at least one processor. The method includes driving, by the at least one processor, the motor to move the slide holder between the transmitter element and the receiver element; during the movement of the slide holder, passing the rear portion of each of the plurality of slots of the slide holder through the line-of-sight communication of the sensor pair; receiving, during the movement of the slide holder, a signal from the sensor pair; correlating at least a portion of the signal from the sensor pair with one of the plurality of slots of the slide holder; analyzing portions of the signal from the sensor pair corresponding to each of the plurality of slots; and determining, based on the analysis, the status of each of the plurality of slots.

[0013] In one embodiment, a digital slide scanning device includes: a motor configured to position a slide holder having a plurality of slots and holding a plurality of slides; a sensor pair including a transmitter element and a receiver element positioned such that line-of-sight communication passes through the rear portion of a first slot of the slide holder; and a processor configured to receive a signal from the sensor pair during reinsertion of a first slide into the first slot of the slide holder and analyze the signal to determine the reinsertion status of the first slide in the first slot.

[0014] In one embodiment, a method in a digital slide scanning device, the digital slide scanning device comprising: a motor configured to position a slide holder within the digital slide scanning device, the slide holder configured to hold a plurality of slides in a plurality of slots; a sensor pair including a transmitter element and a receiver element positioned such that line-of-sight communication passes through the rear portion of a first slot of the slide holder; and at least one processor. The method includes receiving, by the at least one processor, a signal from the sensor pair during reinsertion of a first slide into the first slot of the slide holder and analyzing the signal to determine the reinsertion status of the first slide in the first slot.

[0015] After reading the following detailed description and the accompanying drawings, other features and advantages of the present invention will become more apparent to those of ordinary skill in the art. BRIEF DESCRIPTION OF THE DRAWINGS

[0016] The structure and operation of the present invention will be understood by reading the following detailed description and the drawings, in which like reference numerals refer to like components, and in the drawings:

[0017] Figure 1 is a front view showing an exemplary slide rack having a plurality of slides in a slide rack slot according to one embodiment;

[0018] Figure 2 is a block diagram showing an exemplary sensor pair output signal corresponding to slide rack inventory according to one embodiment;

[0019] Figure 3A is a top view showing an exemplary reinspection of slides of a first manufacturer's slide rack according to one embodiment;

[0020] Figure 3B is a top view showing an exemplary reinspection of slides of a second manufacturer's slide rack according to one embodiment;

[0021] Figure 4A is a block diagram showing an exemplary processor-enabled device 550 that can be used in conjunction with the various embodiments described herein;

[0022] Figure 4B is a block diagram showing an exemplary line scan camera having a single linear array;

[0023] Figure 4C is a block diagram showing an exemplary line scan camera having three linear arrays; and

[0024] Figure 4D is a block diagram showing an exemplary line scan camera having a plurality of linear arrays. DETAILED DESCRIPTION

[0025] The embodiments disclosed herein provide a slide rack inventory and slide loading verification system for use with a digital slide scanning device configured to determine the status of each slot in a slide rack as properly occupied, improperly occupied, or empty. After reading this description, it will become apparent to those skilled in the art how to implement the present invention in various alternative embodiments and alternative applications. However, although various embodiments of the present invention will be described herein, it should be understood that these embodiments are presented by way of example and not limitation. Accordingly, this detailed description of the various alternative embodiments should not be construed as limiting the scope or breadth of the present invention as set forth in the appended claims.

[0026] Figure 1is a front view showing an exemplary slide rack 10 having a plurality of slides 20 in the slots 30 of the slide rack 10 according to one embodiment. In the illustrated embodiment, the slide rack 10 includes a plurality of slots 30 for the slides 20. The slide rack 10 has a specific up and down orientation, with a top slot 40 and a bottom slot 50. The slide rack 10 is conveyed by a slide rack prime mover 60 powered by a motor 70. The slide rack prime mover 60 is configured to move the slide rack 10 along a linear axis and to move the slide rack 10 between the arms 80 of the sensor support 90. In one embodiment, the sensor support 90 is configured to be adjusted up and down to fine-tune the alignment of the transmitting element 100 and the receiving element 110 of the sensor 120 with the slides 20 properly positioned in the slide rack 10.

[0027] Each arm 80 of the sensor support 90 includes one half of a pair of transmitting elements 100 and receiving elements 110 of the sensor 120. The transmitting element 100 and the receiving element 110 are oppositely oriented in the orientation of the line of sight 130, and the plane of the line of sight 130 is substantially parallel to the plane of the slide 20 on the scanning table and / or substantially parallel to the plane in which the slide 20 is inserted into the slide rack 10. In operation, the slide rack prime mover 60 moves the slide rack 10 such that each of the slots 30 of the slide rack 10 passes through the line of sight 130 of the pair of sensors 120. In an alternative embodiment, the transmitting element 100 and the receiving element 110 may be oriented such that the transmitting element 100 is closer to the slide 20 than the receiving element 110, or such that the transmitting element 100 is farther from the slide 20 than the receiving element 110, or such that the transmitting element 100 and the receiving element 110 are equidistant from the slide 20. A processor (not shown) receives signals from the sensor pair 120 (including the transmitting element 100 and the receiving element 110) and analyzes the signals to determine the status of each slot 30 of the slide rack 10. In one embodiment, the status may be occupied or empty, and more specifically, occupied may be normal occupancy, stacked occupancy, skewed occupancy, or abnormal occupancy. Normal occupancy is a single slide 20 properly positioned in the slot 30. Stacked occupancy is two slides 20 stacked on top of each other in a single slot 30. Skewed occupancy is a single slide 20 angled and occupying two adjacent slots 30. Abnormal occupancy is a single slide 20 damaged or otherwise improperly positioned in a single slot 30. The processor is also configured to determine the status of the slide rack 10 as a whole.

[0028] In an alternative embodiment, the emission element 100 and the receiving element 110 are positioned for optical communication based on the emission signal refracted through the slide 20. For example, the emission element 100 and the receiving element 110 may be oriented off of a direct line of sight. Additionally, the emission element 100 and the receiving element 110 may also be oriented such that the emission element 100 is closer to the slide 20 than the receiving element 110, or such that the emission element 100 is farther from the slide 20 than the receiving element 110, or such that the emission element 100 and the receiving element 110 are equidistant from the slide 20.

[0029] In operation, the motor 70 (e.g., under the control of a processor) causes the slide rack prime mover 60 to lift the slide rack 10 and align each slot 30 with the line of sight 130 of the sensor pair 120. The processor receives signals from the sensor pair 120 and correlates the received signals with each slot 30. The processor analyzes the signals of each slot 30 to determine the status of each slot 30. If it is determined that any slot 30 is not appropriate (e.g., stack occupied or skewed occupied), then the entire slide rack 10 may be rejected from scanning. Optionally, when processing the slide 20 and / or the rack 10, the inappropriately occupied slots 30 may be skipped. Empty slots 30 may also be skipped to reduce the overall scan operation time.

[0030] Figure 2 is a block diagram showing an exemplary sensor pair output signal 200 corresponding to an inventory of the slide rack 10 according to one embodiment. In the illustrated embodiment, when performing an inventory of the slide rack 10 prior to scanning the slide 20 in the first slot, the sensor pair sends a continuous signal 200 to the processor. When the slide rack 10 passes through the line of sight (or refracted line of sight) of the sensor pair, the signal 200 from the sensor pair is OFF or ON. In one embodiment, the sensor pair is configured to generate an OFF signal in the absence of any structure in the line of sight and is also configured to generate an ON signal in the presence of any structure in the line of sight. Advantageously, at the rear of the slide rack 10 where the sensor pair is located, there is no structure of the slide rack 10 between the top and the bottom of the slide rack. As Figure 2As shown, when performing slide counting on the shown slide rack 10, the sensor pair generates the shown signal 200. The processor is configured to receive the signal 200 from the sensor pair, associate the signal 200 with each slot 30 of the slide rack 10, and analyze the signal 200 of each slot 30 to determine the status 210 of each slot 30 in the slide rack 10. In the shown embodiment, the status 210 of almost all slots 30 is normal, including the empty slot 30, whose status is normal - no slide. However, because a single slide 20 is angled between two adjacent slots 30, the status 210 of each of the two adjacent slots 30 is "abnormal - skewed". Similarly, because a single slide 20 is damaged in the slot 30, the status 210 of the single slide is "abnormal - damaged". The "abnormal - stacked" status, which is the state where two slides 20 are stacked on top of each other in a single slot 30, is not shown.

[0031] In one embodiment, because the status 210 of at least a single slot 30 is abnormal, the status of the entire slide rack 10 is abnormal. Thus, the processor can generate an error status and stop processing the slide rack 10. Optionally, the processor can generate an error status and continue processing the normal slots 30 in the slide rack 10. In one embodiment, if the status 210 of all slots 30 is "normal" (including normal - no slide), then the status of the entire slide rack 10 is "normal", and the processor is configured to process each slide 20 in the slide rack 10 while skipping the slots 30 without slides 20 to save time.

[0032] Figure 3A is a top view showing an exemplary re - insertion inspection of slides of a slide rack 300 manufactured by a first manufacturer according to one embodiment. In the shown embodiment, the sensor bracket 90 supports the sensor pair 120, which includes a transmitting element 100 and a receiving element 110. The output of the sensor 120 is coupled to a processor (not shown). The sensor pair 120 is positioned such that the line of sight 130 is positioned towards the rear end of the slide rack 300 manufactured by the first manufacturer. Advantageously, the positioning of the sensor pair 120 places the line of sight 130 towards the rear end of any slide rack manufactured by any manufacturer. This positioning of the sensor pair 120 on the sensor bracket 90 functions for both the slide counting process and the slide re - insertion inspection process.

[0033] During the slide re-insertion inspection process, when the processing (e.g., scanning) of the slide 310 is completed, the slide 310 is re-inserted into the slide rack 300. This is accomplished by pushing the slide 310 through the opening at the front of the slot and into the slide rack 300. Advantageously, the slide rack 300 includes a baffle 330 at the rear of the slide rack 300, which prevents the slide from passing completely through the slide rack 300 when the slide 310 is pushed into the slot of the slide rack 300.

[0034] In some cases, the re-insertion of the slide 310 may not be successful. Advantageously, the positioning of the line of sight 130 of the pair of sensors 120 near the rear of the slide rack 300 allows the processor to analyze the signals from the pair of sensors 120 to confirm that the slide 310 has been properly re-inserted, e.g., fully pushed into the slide rack slot. For example, if the slide 310 is properly and fully re-inserted into the slide rack 300 such that the rear edge 320 of the slide 310 engages the baffle 330 that prevents the slide 310 from traveling further, then at least a portion of the line of sight 130 of the pair of sensors 120 is interrupted by the rear edge 320 of the slide 310. However, if the slide 310 is not properly re-inserted, then the line of sight 130 of the pair of sensors 120 is not interrupted. The processor is configured to analyze the signals from the pair of sensors 120 to confirm whether the slide 310 has been properly re-inserted into the slide rack 300. If the slide 310 is not properly re-inserted, the processor may abort the re-insertion process and retry, or alternatively may pause the operation of the digital slide scanning device and generate an alert to request operator intervention.

[0035] Figure 3B is a top view showing an exemplary slide re-insertion inspection of a slide rack 400 manufactured by a second manufacturer according to one embodiment. In the illustrated embodiment, the sensor bracket 90 supports the pair of sensors 120, which includes a transmitting element 100 and a receiving element 110. The output of the sensor 120 is coupled to a processor (not shown). The pair of sensors 120 is positioned such that the line of sight 130 is oriented towards the rear end of the slide rack 400 manufactured by a second manufacturer. Advantageously, the positioning of the pair of sensors 120 places the line of sight 130 towards the rear end of any slide rack manufactured by any manufacturer. This positioning of the pair of sensors 120 on the sensor bracket 90 serves both the slide inventory process and the slide re-insertion inspection process.

[0036] As discussed above, during the slide reinsertion inspection process, when the processing (e.g., scanning) of the slide 410 is completed, the slide 410 is reinserted into the slide rack 400. This is accomplished by pushing the slide 410 through an opening in the front of the slot and into the slide rack 400. Advantageously, the slide rack 400 similarly includes a baffle 430 at the rear of the slide rack 400, which prevents the slide from passing completely through the slide rack 400 when the slide 410 is pushed into the slot of the slide rack 400.

[0037] During the slide reinsertion inspection process, when the processing (e.g., scanning) of the slide 410 is completed, the slide 410 is reinserted into the slide rack 400. In some cases, the reinsertion of the slide 410 may not be successful. Advantageously, the positioning of the line of sight 130 of the pair of sensors 120 near the rear of the slide rack 400 allows the processor to analyze the signals from the pair of sensors 120 to confirm that the slide 410 has been properly reinserted, e.g., fully pushed into the rack slot. For example, if the slide 410 is properly reinserted, the line of sight 130 of the pair of sensors 120 is interrupted. However, if the slide 410 is not properly reinserted, the line of sight 130 of the pair of sensors 120 is not interrupted. The processor is configured to analyze the signals from the pair of sensors 120 to confirm whether the slide 410 has been properly reinserted into the slide rack 400. If the slide 410 is not properly reinserted, the processor may abort and retry the reinsertion process, or alternatively may pause the operation of the digital slide scanning device and generate an alert to request operator intervention.

[0038] Exemplary embodiments

[0039] In one embodiment, a digital slide scanning device includes a motor configured to position a slide rack having a plurality of slots, the slide rack having a top slot and a bottom slot and holding a plurality of slides. The motor is further configured to position the slide rack to process a first slide from a first slot, e.g., a slide occupying the bottom slot. The digital slide scanning device further includes a pair of sensors including a transmitter element and a receiver element positioned in a line of sight orientation, a first one of the transmitter element or the receiver element being located on a first side of a sensor bracket, and a second one of the transmitter element or the receiver element being located on a second side of the sensor bracket. When the slide rack is positioned for processing the first slide, each of the plurality of slots of the slide rack passes through the line of sight of the pair of sensors. The digital slide scanning device further includes a processor configured to control the motor to position the slide rack to process the first slide. The processor is further configured to receive signals from the pair of sensors and associate the signals with each of the plurality of slots. The processor is further configured to analyze the signals corresponding to each of the plurality of slots to determine the status of each of the plurality of slots.

[0040] In one embodiment, the state of each of the plurality of slots is one of the following: occupied or empty. In one embodiment, the state of each occupied slot is one of the following: normal or skewed. In one embodiment, the state of each of the plurality of slots is determined before scanning the first glass slide.

[0041] In one embodiment, after determining the state of each of the plurality of slots, the first glass slide is unloaded from the first slot for processing and then reinserted into the first slot after processing. In this embodiment, the processor is further configured to receive a signal corresponding to the first slot from the sensor pair during reinsertion and analyze the signal corresponding to the first slot during reinsertion to determine the reinsertion state of the first glass slide in the first slot. In one aspect of this embodiment, the reinsertion state is one of the following: proper or improper.

[0042] In one embodiment, the sensor pair is positioned such that the plane of the line of sight of the sensor pair is substantially the same as the plane occupied by the glass during scanning.

[0043] In one embodiment, a method includes using a motor to position a glass slide holder to process glass slides in the glass slide holder. In this embodiment, the glass slide holder includes a plurality of slots, the plurality of slots including a top slot and a bottom slot, and the glass slide holder holds a plurality of glass slides. Moreover, the position for processing the glass slides in the glass slide holder is the position for loading a first glass slide occupying a first slot onto a scanning stage. In this method, using a motor to position the glass slide holder to process the glass slides in the glass slide holder includes moving the glass slide holder between a first side and a second side of a sensor support, the sensor support supporting a sensor pair that includes a transmitter element and a receiver element positioned in a line of sight orientation. The first of the transmitter element or the receiver element is positioned on the first side of the sensor support, and the second of the transmitter element or the receiver element is positioned on the second side of the sensor support such that moving the glass slide holder includes passing each of the plurality of slots of the glass slide holder through the line of sight of the sensor pair. The method further includes using a processor to control the motor to position the glass slide holder to process the first glass slide, using the processor to receive signals from the sensor pair and correlate the signals with each of the plurality of slots, using the processor to analyze the signals corresponding to each of the plurality of slots, and using the processor to determine the state of each of the plurality of slots.

[0044] In one embodiment, the state of each of the plurality of slots is one of: occupied or empty. In one embodiment, the state of each occupied slot is one of: normal or skewed. In one embodiment, the method further includes determining the state of each of the plurality of slots before scanning a first slide. In one embodiment, the method further includes, after determining the state of each of the plurality of slots, unloading a first slide from a first slot for processing, reinserting the first slide into the first slot after processing, receiving, using a processor, signals corresponding to the first slot from a sensor during reinsertion, and analyzing, using the processor, the signals corresponding to the first slot during reinsertion to determine the reinsertion state of the first slide in the first slot.

[0045] In this embodiment, the reinsertion state is one of: proper or improper. In one embodiment, positioning a slide holder using a motor to process a slide in the slide holder includes positioning a sensor pair such that the plane of the line of sight of the sensor pair is substantially the same as the plane occupied by the sensor pair during scanning.

[0046] Figure 4A FIG. is a block diagram showing an exemplary processor-enabled device 550 that may be used in conjunction with the various embodiments described herein. As will be understood by those skilled in the art, alternative forms of device 550 may also be used. In the illustrated embodiment, device 550 is presented as a digital imaging device (also referred to herein as a scanner system, scanning system, scanning device, digital scanning device, digital slide scanning device, etc.), the digital imaging device including 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 removable platforms 580 (each supporting one or more slides 585 having one or more samples 590), one or more illumination systems 595 for illuminating the samples, one or more objective lenses 600 (each defining an optical path 605 traveling 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 additional cameras 620 (e.g., a line scan camera or a frame scan camera), each of which defines a separate field of view 625 on the sample 590 and / or the slide 585. The various elements of 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 scanner system 550, for simplicity, these elements will be described herein in the singular unless it is necessary to describe them in the plural to convey appropriate information.

[0047] One or more processors 555 may include, for example, a central processing unit (“CPU”) capable of processing instructions in parallel and a separate graphics processing unit (“GPU”), 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, the additional processors may include an auxiliary processor for managing data input, an auxiliary processor for performing floating-point mathematical operations, a dedicated processor having an architecture suitable for rapidly executing signal processing algorithms (e.g., a digital signal processor), a slave processor subordinate to the main processor (e.g., a backend processor), an additional processor for controlling the line scan camera 615, the platform 580, the 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.

[0048] In one embodiment, the processor 555 is configured to control the movement of the slide holder and receive and analyze signals from the sensor pair 90 to determine the presence, absence, or misalignment of the slide 20 in the slide holder 10. In one embodiment, the processor 555 is configured to control the reinsertion of the slide 20 into the slide holder 10 and receive and analyze the signals 200 from the sensor pair 90 to determine that the slide 20 is properly reinserted into the slide holder 10.

[0049] The memory 565 provides storage for data and instructions for programs that may be executed by the processor 555. The 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 drives, removable storage drives, etc. The processor 555 is configured to execute instructions stored in the memory 565 and communicate with the various elements of the scanner system 550 via the communication bus 560 to perform the overall functions of the scanner system 550.

[0050] One or more communication buses 560 may include a communication bus 560 configured to transmit analog electrical signals and may include a communication bus 560 configured to transmit digital data. Thus, communication from the processor 555, the motion controller 570, and / or the interface system 575 via one or more communication buses 560 may include both electrical signals and digital data. The processor 555, the motion controller 570, and / or the 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.

[0051] The motion control system 570 is configured to precisely control and coordinate the X, Y, and / or Z motion of the stage 580 (e.g., within the X-Y plane) and / or the objective lens 600 (e.g., along the Z axis orthogonal to the X-Y plane via the objective lens positioner 630). The motion control system 570 is also configured to control the motion of any other moving components in the scanner system 550. For example, in a fluorescence scanner embodiment, the motion control system 570 is configured to coordinate the motion of filters in the epi-illumination system 635, etc.

[0052] The interface system 575 allows the scanner system 550 to interact with other systems and human operators. For example, the interface system 575 may include a user interface to directly provide information to the operator and / or allow direct input from the operator. The interface system 575 is also configured to facilitate communication and data transfer between the scanning system 550 and one or more directly connected external devices (e.g., printers, removable storage media) or external devices such as an image server system, an operator station, a user station, and a management server system connected to the scanner system 550 via a network (not shown).

[0053] The illumination system 595 is configured to illuminate a portion of the sample 590. The illumination system may include, for example, a light source and illumination optics. The light source may include a variable-intensity halogen light source having a concave mirror for maximizing light output and a KG-1 filter for suppressing heat. The light source may also include any type of arc lamp, laser, or other light source. In one embodiment, the illumination system 595 illuminates the sample 590 in transmission mode such that the line scan camera 615 and / or the camera 620 senses the light energy transmitted through the sample 590. Optionally or in combination, the illumination system 595 may also be configured to illuminate the sample 590 in reflection mode such that the line scan camera 615 and / or the camera 620 senses the light energy reflected from the sample 590. The illumination system 595 may be configured to be suitable for examining the microscope sample 590 in any known mode of an optical microscope.

[0054] 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 that includes fluorescent molecules, which are photon-sensitive molecules that can absorb photons of a specific wavelength of light (excitation). These photon-sensitive molecules also emit light of a higher wavelength (emission). Because the efficiency of this photoluminescence phenomenon is very low, the amount of light emitted is typically very low. This small amount of emitted light is usually frustrating for conventional techniques (e.g., transmission mode microscopy) that are used to scan and digitize the sample 590. Advantageously, in an alternative fluorescence scanner system embodiment of the scanner system 550, the use of a line scan camera 615 that includes a plurality of linear sensor arrays (e.g., a time delay integration (“TDI”) line scan camera) increases the light sensitivity of the line scan camera by exposing the same area of the sample 590 to each of the plurality of linear sensor arrays of the line scan camera 615. This is particularly useful when scanning faint fluorescent samples with low emitted light.

[0055] Accordingly, in the fluorescence scanner system embodiment, the line scan camera 615 is preferably a monochromatic TDI line scan camera. Advantageously, monochromatic images are desirable in fluorescence microscopy because they provide a more accurate representation of the actual signals from the individual channels present on the sample. As will be understood by those skilled in the art, the fluorescent sample 590 can be labeled with a variety of fluorescent dyes that emit light of different wavelengths, which are also referred to as “channels”.

[0056] In addition, because the low and high signal levels of various fluorescent samples exhibit a wide spectrum of wavelengths for the line scan camera 615 to sense, it is desirable that the low and high signal levels that the line scan camera 615 can sense be equally wide. Accordingly, in the fluorescence scanner embodiment, the line scan camera 615 used in the fluorescence scanning system 550 is a monochromatic 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 used in conjunction with the fluorescence scanner embodiment of the scanning system 550.

[0057] The movable platform 580 is configured to perform precise X-Y motion under the control of the processor 555 or the motion controller 570. The movable platform may also be configured to perform Z motion under the control of the processor 555 or the motion controller 570. The movable platform 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 platform is also configured to accelerate the sample 590 to a substantially constant speed along the scan direction and then maintain a substantially constant speed during image data capture by the line scan camera 615. In one embodiment, the scanner system 550 may employ a high-precision and tightly coordinated X-Y grid to assist in positioning the sample 590 on the movable platform 580. In one embodiment, the movable platform 580 is a linear motor-based X-Y platform that employs high-precision encoders on both the X and Y axes. For example, very precise nano-encoders may be used on the axis in the scan direction and on the axis in the direction perpendicular to the scan direction and in the same plane as the scan direction. The platform is also configured to support the slide 585 on which the sample 590 is disposed.

[0058] The sample 590 can be anything that can be examined by an optical microscope. For example, glass microscope slides 585 are often used as a viewing substrate for samples that include tissue and cells, chromosomes, DNA, proteins, blood, bone marrow, urine, bacteria, beads, biopsy materials, or any other type of biological material or substance that is expired or unexpired, stained or unstained, labeled or unlabeled. The sample 590 can also be an array of any type of DNA or DNA-related material deposited on any type of slide or other substrate, such as cDNA or RNA or protein, including any and all samples commonly referred to as microarrays. The sample 590 can be a microtiter plate (e.g., a 96-well plate). Other examples of the sample 590 include integrated circuit boards, electrophoresis recording plates, culture dishes, membranes, semiconductor materials, forensic materials, or mechanical parts.

[0059] The objective lens 600 is mounted on the objective lens locator 630, which in one embodiment employs a very precise linear motor to move the objective lens 600 along the optical axis defined by the objective lens 600. For example, the linear motor of the objective lens locator 630 may include a 50-nanometer encoder. The relative positions of the platform 580 and the objective lens 600 on the X, Y, and / or Z axes are coordinated and controlled in a closed-loop manner using the motion controller 570 under the control of the processor 555, which employs the memory 565 to store information and instructions that include computer-executable programming steps for operating the entire scan system 550.

[0060] In one embodiment, the objective lens 600 is a planar apochromatic ("APO") infinity-corrected objective lens, the numerical aperture of which corresponds to the highest required spatial resolution, where the objective lens 600 is suitable for a transmission-mode illumination microscope, a reflection-mode illumination microscope, and / or an epi-illumination-mode fluorescence microscope (e.g., Olympus 40X, 0.75NA or 20X, 0.75NA). Advantageously, the objective lens 600 is capable of correcting chromatic aberration and spherical aberration. Since the objective lens 600 is infinity-corrected, the focusing optics 610 can be placed in the optical path 605 above the objective lens 600, in which the light beam passing through the objective lens becomes a collimated beam. The focusing optics 610 focuses the optical signal 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 for the scanning system 550. In one embodiment, the focusing optics 610 may include a tube lens and an optional 2X magnification changer. Advantageously, the 2X magnification changer allows the native 20X objective lens 600 to scan the sample 590 at 40X magnification.

[0061] The line-scan camera 615 includes at least one linear array of image elements ("pixels"). The line-scan camera can be monochromatic or color. A color line-scan camera typically has at least three linear arrays, while a monochromatic line-scan camera can have a single linear array or a plurality of linear arrays. Any type of single or plural linear arrays can also be used, whether packaged as part of a 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 monochromatic TDI can also be used. TDI line-scan cameras typically provide a significantly better signal-to-noise ratio ("SNR") in the output signal by summing the intensity data from previously imaged areas of the sample, resulting in an SNR increase proportional to the square root of the number of integration stages. The TDI line-scan camera includes a plurality of linear arrays. For example, the 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 formats with 512 pixels, some formats with 1024 pixels, and other formats with up to 4096 pixels. Similarly, linear arrays with various pixel sizes can also be used in the scanner system 550. The overriding requirement for selecting any type of line-scan camera 615 is that the movement of the platform 580 can be synchronized with the line speed of the line-scan camera 615 such that the platform 580 can move relative to the line-scan camera 615 during the digital image capture of the sample 590.

[0062] The image data generated by the line scan camera 615 is stored in a portion of the memory 565 and processed by the processor 555 to generate a continuous digital image of at least a portion of the sample 590. The continuous digital image can be further processed by the processor 555 and the modified continuous digital image can also be stored in the memory 565.

[0063] In embodiments having two or more line scan cameras 615, at least one of the line scan cameras 615 can be configured to function as a focus sensor that operates in conjunction with at least one of the other line scan cameras 615 configured to function as an imaging sensor. Relative to the scan direction of the scanner system 550, the focus sensor can be logically positioned on the same optical axis as the imaging sensor, or the focus sensor can be logically positioned before or after the imaging sensor. In such embodiments where at least one line scan camera 615 functions as a focus sensor, the image data generated by the focus sensor is stored in a portion of the memory 565 and processed by one or more processors 555 to generate focus information to allow the scanner system 550 to adjust the relative distance between the sample 590 and the objective 600 to maintain focus on the sample during scanning. Additionally, in one embodiment, at least one line scan camera 615 functioning as a focus sensor can be oriented such that each of a plurality of individual pixels of the focus sensor is positioned at a different logical height along the optical path 605.

[0064] In operation, the various components of the scanner system 550 and the programming modules stored in the memory 565 effect the automatic scanning and digitization of the sample 590, which is disposed on the slide 585. The slide 585 is securely placed on the movable platform 580 of the scanner system 550 to scan the sample 590. Under the control of the processor 555, the movable platform 580 accelerates the sample 590 to a substantially constant speed for sensing by the line scan camera 615, where the speed of the platform is synchronized with the line speed of the line scan camera 615. After scanning a strip of image data, the movable platform 580 decelerates and brings the sample 590 to a substantially complete stop. Then, the movable platform carriage 580 moves orthogonally to the scan direction to position the sample 590 for scanning a subsequent strip of image data, such as an adjacent strip. Additional strips are then scanned until an entire portion or the entire sample 590 has been scanned.

[0065] For example, during the digital scanning of sample 590, sequential digital images of sample 590 are obtained as multiple sequential fields of view that are combined together to form an image strip. Multiple adjacent image strips are similarly combined together to form a sequential digital image of a portion or the entire sample 590. The scanning of sample 590 can include obtaining vertical image strips or horizontal image strips. The scanning of sample 590 can be top-to-bottom, bottom-to-top, or both (bidirectional), and can start at any point on the sample. Optionally, the scanning of sample 590 can be left-to-right, right-to-left, or both (bidirectional), and can start at any point on the sample. Additionally, the image strips need not be obtained in an adjacent or sequential manner. Further, the resulting image of sample 590 can be an image of the entire sample 590 or only a portion of sample 590.

[0066] In one embodiment, computer-executable instructions (e.g., programming modules and software) are stored in memory 565 and, when executed, cause scanning system 550 to be capable of performing the various functions described herein. In this description, the term "computer-readable storage medium" is used to refer to any medium that stores computer-executable instructions and provides 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 communicatively coupled to scanning system 550 directly or indirectly via a network (not shown).

[0067] Figure 4B A line scan camera having a single linear array 640 is shown, and the single linear array 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 4096 pixels. In alternative embodiments, the linear array 640 can have more or fewer pixels. For example, common formats for linear arrays include 512, 1024, and 4096 pixels. The pixels 645 are arranged linearly to define the field of view 625 of the linear array 640. The size of the field of view 625 varies according to the magnification of the scanner system 550.

[0068] Figure 4C A line scan camera having three linear arrays is shown, and each linear array 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, such as red, green, or blue. The color image data from each individual linear array in the color array 650 is combined to form a single field of view 625 of color image data.

[0069] Figure 4DA line scan camera having a plurality of linear arrays is shown, each linear array being implementable as a CCD array. The plurality of 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 summing the intensity data from the previously imaged regions of the sample, resulting in an SNR increase proportional to the square root of the number of linear arrays (also known as integration stages). The TDI line scan camera can include a greater number of linear arrays, for example, common formats of the TDI line scan camera include 24, 32, 48, 64, 96, 120, and more linear arrays.

[0070] The foregoing 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 readily apparent to those skilled in the art, and the general principles described herein may be applied to other embodiments without departing from the spirit or scope of the invention. Thus, it should be understood that the description and drawings presented herein represent the current preferred embodiments of the invention and thus represent the broad subject matter contemplated by the invention. It should also be understood that the scope of the invention fully encompasses other embodiments that will become apparent to those skilled in the art, and accordingly, the scope of the invention is not limited.

Claims

1. A digital slide scanning device, comprising: A motor configured to position a slide holder within the digital slide scanning device, the slide holder configured to hold a plurality of slides in a plurality of slots, wherein each slot has an insertion opening at a first end of the front portion of the slot and a baffle at a second end of the rear portion of the slot, wherein the slide is inserted into the slot from the insertion opening, and wherein when the slide is pushed into the slot, the baffle engages the rear edge of the slide and prevents the slide from passing completely through the slide holder; A sensor pair comprising a transmitter element and a receiver element positioned for line-of-sight communication, the transmitter element positioned on a first side of a sensor bracket, and the receiver element positioned on a second side of the sensor bracket, wherein the sensor pair is disposed on a side of the baffle facing the insertion opening; And A processor configured to control the motor to move the slide holder such that the rear portion of each of the plurality of slots of the slide holder passes through the line-of-sight communication of the sensor pair, the processor further configured to receive a signal from the sensor pair and analyze the signal to determine the status of each slot of the slide holder.

2. The digital slide scanning device according to claim 1, wherein the status of each of the plurality of slots is one of: normal or abnormal.

3. The digital slide scanning device according to claim 1, wherein if the status of a single slot is abnormal, the status of the slide holder is abnormal.

4. The digital slide scanning device according to claim 1, wherein if the status of each of the plurality of slots is normal, the processor is further configured to start scanning a first slide from a first slot.

5. The digital slide scanning device according to claim 1, wherein the sensor pair is positioned such that the line of sight of the sensor pair lies in a plane occupied by the slide during scanning of the slide by the digital slide scanning device.

6. The digital slide scanning device according to claim 1, wherein the line-of-sight communication includes optical communication.

7. The digital slide scanning device according to claim 6, wherein the optical communication occurs according to the refraction of an emitted signal through the slide.

8. A method in a digital slide scanning device, comprising A motor configured to position a slide holder within the digital slide scanning device, the slide holder configured to hold a plurality of slides in a plurality of slots, wherein each slot has an insertion opening at a first end of the front portion of the slot and a baffle at a second end of the rear portion of the slot, wherein the slide is inserted into the slot from the insertion opening, and wherein when the slide is pushed into the slot, the baffle engages the rear edge of the slide and prevents the slide from passing completely through the slide holder, A sensor pair comprising a transmitter element and a receiver element positioned opposite to each other for line-of-sight communication, wherein the sensor pair is disposed on a side of the baffle facing the insertion opening, and At least one processor, The method includes, by the at least one processor: Driving the motor to move the slide holder between the emitter element and the receiver element; During the movement of the slide holder, causing the rear portion of each of the plurality of slots of the slide holder to communicate through the line of sight of the pair of sensors; Receiving a signal from the pair of sensors during the movement of the slide holder; Associating at least a portion of the signal from the pair of sensors with one of the plurality of slots of the slide holder; Analyzing the portions of the signal from the pair of sensors corresponding to each of the plurality of slots; And Determining the status of each of the plurality of slots based on the analysis.

9. The method according to claim 8, wherein the status of each of the plurality of slots is one of the following: normal or abnormal.

10. The method according to claim 9, wherein if the status of a single slot is abnormal, the status of the slide holder is abnormal.

11. The method according to claim 8, wherein if the status of each of the plurality of slots is normal, the at least one processor starts the scanning process of the first slide.

12. The method according to claim 8, wherein causing the rear portion of each of the plurality of slots of the slide holder to communicate through the line of sight of the pair of sensors during the movement of the slide holder includes causing the rear portion of each of the plurality of slots of the slide holder to pass through the line of sight of the pair of sensors.

13. The method according to claim 8, wherein the line-of-sight communication includes optical communication.

14. The method according to claim 13, wherein the optical communication occurs according to the refraction of the emitted signal through the slide.

15. A digital slide scanning device, comprising: A motor configured to position a slide holder having a plurality of slots and holding a plurality of slides, wherein each slot has an insertion opening at a first end of the front portion of the slot and a baffle at a second end of the rear portion of the slot, wherein the slide is inserted into the slot from the insertion opening, and wherein when the slide is pushed into the slot, the baffle engages the rear edge of the slide and prevents the slide from passing completely through the slide holder; A pair of sensors including an emitter element and a receiver element, the emitter element and the receiver element being positioned such that line-of-sight communication passes through the rear portion of the first slot of the slide holder, wherein the pair of sensors is disposed on a side of the baffle facing the insertion opening; And A processor configured to receive a signal from the pair of sensors during the reinsertion of the first slide into the first slot of the slide holder and analyze the signal to determine the reinsertion status of the first slide in the first slot.

16. The digital slide scanning device according to claim 15, wherein the reinsertion status is one of the following: proper or improper.

17. A method in a digital slide scanning device, which includes A motor configured to position a slide holder within the digital slide scanning device, the slide holder configured to hold a plurality of slides in a plurality of slots, each slot having an insertion opening at a first end of the front portion of the slot and a baffle at a second end of the rear portion of the slot, wherein a slide is inserted into the slot through the insertion opening, and wherein when the slide is pushed into the slot, the baffle engages the rear edge of the slide and prevents the slide from passing completely through the slide holder. A sensor pair including a transmitter element and a receiver element, the transmitter element and the receiver element being positioned such that line-of-sight communication passes through the rear portion of a first slot of the slide holder, wherein the sensor pair is disposed on a side of the baffle facing the insertion opening, and At least one processor, The method includes, by the at least one processor: Receiving a signal from the sensor pair during reinsertion of a first slide into the first slot of the slide holder; and Analyzing the signal to determine a reinsertion state of the first slide in the first slot.

18. The method according to claim 17, wherein the reinsertion state is one of: proper or improper.

19. The digital slide scanning device according to claim 1, wherein when there is no slide in the slot, the state of the slot is normal.

20. The method according to claim 8, wherein when there is no slide in the slot, the state of the slot is normal.

21. The digital slide scanning device according to claim 15, wherein when there is no slide in the slot, the reinsertion state is proper.

22. The method according to claim 17, wherein when there is no slide in the slot, the reinsertion state is proper.

Images