Patent Description:
The present invention generally relates to a digital slide scanning apparatus and more particularly relates to processing of individual slides (e.g., glass slides) housed in slide racks by a digital slide scanning apparatus (e.g., for digital pathology).

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

Glass slides that are processed by a digital slide scanning apparatus are very fragile and highly valuable. In some instances, slides in a slide rack may be improperly positioned. This can cause conventional digital slide scanners to damage the glass slides when the glass slides are processed, for example by attempting to retrieve an improperly positioned glass slide from a slide rack and load the glass slide onto the scanning stage. Therefore, what is needed is a system and method that overcomes these significant problems found in the conventional systems as described above. <CIT> relates to a system and method for calibrating the orientation or arrangement of slides in a storage receptacle. A reflective marking is asymmetrically applied to a side or edge of a slide, forming reflective and non-reflective sections. Light is directed to the slide, and a sensor detects light that is reflected by the reflective sections and generates signal or data representing an orientation of the slide. A controller processes the signal or data to determine whether the slide is properly oriented on a tray in the storage receptacle, e.g., whether the slide is flat or at an angle, upside down, rotated. The marking can be reflective ink, paint or an adhesive. Reflective and non-reflective markings can also be formed by laser etching, polishing, or by frosting. <CIT> relates to systems and methods including a design of a microscope slide scanner for digital pathology applications which provides high quality images and automated batch-mode operation at low cost. The instrument architecture is advantageously based on a convergence of high performance, yet low cost, computing technologies, interfaces and software standards to enable high quality digital microscopy at very low cost. Also provided is a method based in part on a stitching method that allows for dividing an image into a number of overlapping tiles and reconstituting the image with a magnification without substantial loss of accuracy. A scanner is employed in capturing snapshot images. The method allows for overlapping images captured in consecutive snapshots. <CIT> relates to a system and method for determining whether one or more slides are loaded properly within a cassette. Each slide includes one or more transparent regions and one or more non-transparent regions. The slides are between a light source and a sensor. The light source generates light that is directed towards the sensor through the slides. If the sensor is able to detect light from the light source, then the slides are properly loaded in the cassette. Slides are not properly loaded if the light is blocked by a non-transparent region before reaching the sensor. The sensor or a separate controller can generate a signal or data to provide an indication to a user or to processing equipment that the slides are or are not properly loaded. For example, a speaker or an indicator light can be used to provide an indication to the user. The signal or data can also be used for other functions, such as displaying a message on a screen indicating whether the slides are properly loaded. <CIT> relates to a blood image analyzer comprising: an image capturing unit for capturing a blood image of a sample; an analyzing part for analyzing the sample based on the blood image; an identification information reader for reading, from the sample, identification information assigned to the sample; a transportation part for transporting the sample to the identification information reader and the image capturing unit; a first detector for detecting the sample at a first detection position on a pathway of the sample transported by the transportation part; a display; and a controller for controlling the display, so as to display, based on a detection result by the first detector, a screen including a first identification information display region, wherein the first identification information display region displays identification information of the sample being at the first detection position. <CIT> relates to an apparatus and a slide cassette for removably retaining or securing a slide. The cassette includes trays for holding a slide. Each tray has a retaining lip at an end thereof. A first edge of a slide contacts a support member within the cassette when the slide that is placed in a slot. The support member can be an elastomeric member, a spring, a foam member, or an insert with slide retention surfaces. The support member pushes or urges the slide in the opposite direction so that an opposite edge of the slide contacts the retaining lips of the trays. As a result, the slide is removably retained or secured on the trays and between the retaining lips and the support member(s).

Accordingly, a slide rack inventory and reinsertion system is described herein for use with a digital slide scanning apparatus. In an embodiment, the system is configured to determine a status of each slot in a slide rack as properly occupied, improperly occupied, or empty. The system includes a sensor mount with a first arm and an opposing second arm that are 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 mount, with one of the transmitter or receive on a first arm and the other of the transmitter or receiver on the second arm. The transmitter and receiver are positioned such that they have an operational line-of-sight between them and such that the line-of-sight passes through each slot of a slide rack as the slide rack is conveyed through the opening between the two arms. The line-of-sight is also substantially parallel to a plane of a glass slide on a scanning stage of the digital slide scanning apparatus. The line-of-sight is also positioned such that as the slide rack is conveyed through the opening between the two arms, a rear portion of each glass slide passes through the line-of-sight of the sensor pair. The rear portion of a glass slide is the portion that is further away from the opening through which a glass slide is inserted to or removed from the slide rack.

In operation as the slide rack is conveyed through the opening, the sensor pair sends a signal to a processor that analyzes the signal to determine if a glass slide is present in each slot of the slide rack. The status for each slot in the slide rack may be empty, occupied, stacked or askew.

Additionally, when the scanning of a slide is completed, the slide is inserted back into the slide rack. Because the line-of-sight of the sensor pair is substantially parallel to the plane of the glass slide being conveyed from the scanning stage to the slide rack, the sensor pair sends a signal to the processor that analyzes the signal to determine if the glass slide has been properly reinserted into the slide rack.

In an embodiment, a digital slide scanning apparatus comprises a motor configured to position a slide rack within the digital slide scanning apparatus, the slide rack configured to hold a plurality of glass slides in a plurality of slots, wherein each slot has an opening at a first end of the slot and a barrier at a second end of the slot. The digital slide scanning apparatus also includes 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 mount and the receiver element positioned on a second side of the sensor mount. The digital slide scanning apparatus also includes a processor configured to control the motor to move the slide rack to pass a rear portion of each of the plurality of slots of the slide rack 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 a status of each slot of the slide rack.

In an embodiment, is a method in a digital slide scanning apparatus that comprises a motor configured to position a slide rack within the digital slide scanning apparatus, the slide rack configured to hold a plurality of glass slides in a plurality of slots, a sensor pair comprising a transmitter element and a receiver element relatively positioned for line-of-sight communication, and at least one processor. The method comprises, by the at least one processor, driving the motor to move the slide rack between the transmitter element and the receiver element, passing a rear portion of each of the plurality of slots of the slide rack through the line-of-sight communication of the sensor pair during said movement of the slide rack, receiving a signal from the sensor pair during movement of the slide rack, correlating at least a portion of the signal from the sensor pair to each of the plurality of slots of the slide rack, analyzing the portion of the signal from the sensor pair corresponding to each of the plurality of slots, and determining a status of each of the plurality of slots based on the analysis.

In an embodiment, a digital slide scanning apparatus comprises a motor configured to position a slide rack having a plurality of slots and holding a plurality of glass slides, a sensor pair comprising a transmitter element and a receiver element positioned for line-of-sight communication passing through a rear portion of a first slot of the slide rack, and a processor configured to receive a signal from the sensor pair during reinsertion of a first glass slide into the first slot of the slide rack and analyze the signal to determine a reinsertion status of the first slide into the first slot.

In an embodiment is a method in a digital slide scanning apparatus that comprises a motor configured to position a slide rack within the digital slide scanning apparatus, the slide rack configured to hold a plurality of glass slides in a plurality of slots, a sensor pair comprising a transmitter element and a receiver element positioned for line-of-sight communication passing through a rear portion of a first slot of the slide rack, and at least one processor. The method comprises, by the at least one processor, receiving a signal from the sensor pair during reinsertion of a first glass slide into the first slot of the slide rack, and analyzing the signal to determine a reinsertion status of the first slide into the first slot.

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

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

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

<FIG> is a front view diagram illustrating an example slide rack <NUM> with a plurality of slides <NUM> in the slide rack <NUM> slots <NUM> according to an embodiment. In the illustrated embodiment, the slide rack <NUM> includes a plurality of slots <NUM> for glass slides <NUM>. The slide rack <NUM> has a specific up and down orientation with a top slot <NUM> and a bottom slot <NUM>. The slide rack <NUM> is conveyed by a slide rack mover <NUM> that is powered by a motor <NUM>. The slide rack mover <NUM> is configured to move the slide rack <NUM> along a linear axis and pass the slide rack <NUM> between the arms <NUM> of a sensor mount <NUM>. In one embodiment, the sensor mount <NUM> is configured to adjust up and down to fine tune the alignment of the transmit element <NUM> and receive element <NUM> of the sensor <NUM> with a properly positioned glass slide <NUM> in a slide rack <NUM>.

Each arm <NUM> of the sensor mount <NUM> includes one half of a pair of transmit <NUM> and receive <NUM> elements of a sensor <NUM>. The transmit <NUM> element and the receive <NUM> element are relatively positioned in a line-of-sight <NUM> orientation and the plane of the line-of-sight <NUM> is substantially parallel to a plane of a glass slide <NUM> on the scanning stage and/or substantially parallel to a plane of a glass slide <NUM> being inserted into the slide rack <NUM>. In operation, the slide rack mover <NUM> moves the slide rack <NUM> in a fashion that causes each of the slots <NUM> of the slide rack <NUM> to pass through the line-of-sight <NUM> of the sensor <NUM> pair. In alternative embodiments, the transmit <NUM> and receive <NUM> elements may be oriented such that the transmit <NUM> element is closer to the glass slide <NUM> than the receive <NUM> element or such that the transmit <NUM> element is further from the glass slide <NUM> than the receive <NUM> element or such that the transmit <NUM> element is the same distance from the glass slide <NUM> as the receive <NUM> element. A processor (not shown) receives a signal from the sensor <NUM> pair (comprising the transmit <NUM> element and the receive <NUM> element) and analyzes the signal to determine a status for each slot <NUM> of the slide rack <NUM>. In one embodiment, the status can be occupied or empty and more specifically, occupied can be occupied-normal, occupied-stacked, occupied-askew or occupied-abnormal. Occupied normal is when a single slide <NUM> is appropriately positioned in the slot <NUM>. Occupied-stacked is when two slides <NUM> are stacked on top of each other in a single slot <NUM>. Occupied-askew is when a single slide <NUM> is positioned at an angle and occupies two adjacent slots <NUM>. Occupied-abnormal is when a single slide <NUM> is broken or otherwise improperly positioned in a single slot <NUM>. The processor is also configured to determine a status for the slide rack <NUM> as a whole.

In an alternative embodiment, the transmit <NUM> and receive <NUM> elements are positioned for optical communication in accordance with a refraction of the transmit signal through the glass slide <NUM>. For example, the transmit <NUM> and the receive <NUM> elements may be offset from a direct line of sight orientation. Additionally, the transmit <NUM> and receive <NUM> elements may also be oriented such that the transmit <NUM> element is closer to the glass slide <NUM> than the receive <NUM> element or such that the transmit <NUM> element is further from the glass slide <NUM> than the receive <NUM> element or such that the transmit <NUM> element is the same distance from the glass slide <NUM> as the receive <NUM> element.

In operation, the motor <NUM> (e.g., under control of the processor) causes the slide rack mover <NUM> to lift the slide rack <NUM> and pass each slot <NUM> through the line-of-sight <NUM> of the sensor <NUM> pair. The processor receives a signal from the sensor <NUM> pair and correlates the received signal to each slot <NUM>. The processor analyzes the signal for each slot <NUM> to determine the status of each slot <NUM>. If any slot <NUM> is determined to be improper (e.g., occupied-stacked or occupied-askew) then the entire rack <NUM> may be rejected for scanning. Alternatively, the improperly occupied slots <NUM> may just be skipped when processing the glass slides <NUM> and/or the rack <NUM>. Empty slots <NUM> may also be skipped to decrease overall scanning operation time.

<FIG> is a block diagram illustrating an example sensor pair output signal <NUM> corresponding to a slide rack <NUM> inventory according to an embodiment. In the illustrated embodiment, when an inventory of the slide rack <NUM> is performed before scanning the glass slide <NUM> in a first slot, the sensor pair sends a continuous signal <NUM> to the processor. As the slide rack <NUM> is passed through the line-of-sight (or refraction oriented sight line) of the sensor pair, the signal <NUM> from the sensor pair is either 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 also configured to generate an ON signal in the presence of any structure in the line-of-sight. Advantageously, at a rear portion of the slide rack <NUM> where the sensor pair is located, there is no structure of the slide rack <NUM> between the top of the slide rack and the bottom of the slide rack. As shown in <FIG>, the sensor pair generates the illustrated signal <NUM> when a slide inventory is conducted on the illustrated slide rack <NUM>. The processor is configured to receive the signal <NUM> from the sensor pair and correlate the signal <NUM> to each slot <NUM> of the slide rack <NUM> and analyze the signal <NUM> for each slot <NUM> to determine a status <NUM> for each slot <NUM> in the slide rack <NUM>. In the illustrated embodiment, the status <NUM> for nearly all slots <NUM> is normal, including the empty slot <NUM>, which has a status of NORMAL - NO SLIDE. However, the status <NUM> of each of two adjacent slots <NUM> is ABNORMAL - ASKEW because a single slide <NUM> is angled between the two adjacent slots <NUM>. Similarly, the status <NUM> of a single slide is ABNORMAL - BROKEN because a single slide <NUM> is broken in the slot <NUM>. Not shown is a status of ABNORMAL - STACKED, which would be where two glass slides <NUM> are stacked on top of each other in a single slot <NUM>.

In one embodiment, because the status <NUM> of at least a single slot <NUM> is ABNORMAL, the status of the entire slide rack <NUM> is ABNORMAL. Accordingly, the processor may generate an error status and stop processing of the slide rack <NUM>. Alternatively, the processor may generate an error status and continue processing of the normal slots <NUM> in the slide rack <NUM>. In one embodiment, if the status <NUM> of all slots <NUM> is NORMAL (including NORMAL - NO SLIDE) then the status of the entire slide rack <NUM> is NORMAL and the processor is configured to process each glass slide <NUM> in the slide rack <NUM>, while skipping the slot <NUM> without a glass slide <NUM> to save time.

<FIG> is a top view diagram illustrating an example slide reinsertion check for a slide rack <NUM> made by a first manufacturer according to an embodiment. In the illustrated embodiment, the sensor mount <NUM> supports a sensor <NUM> pair comprising a transmit element <NUM> and a receive element <NUM>. An output of the sensor <NUM> is coupled to the processor (not shown). The sensor <NUM> pair is positioned such that the line-of-sight <NUM> is positioned toward the back end of the slide rack <NUM> made by the first manufacturer. Advantageously, the positioning of the sensor <NUM> pair places the line-of-sight <NUM> toward the back end of any slide rack made by any manufacturer. This positioning of the sensor <NUM> pair on the sensor mount <NUM> operates for both the slide inventory process and the slide reinsertion check process.

In the slide reinsertion check process, when the processing (e.g., scanning) of a glass slide <NUM> is completed, the glass slide <NUM> is inserted back into the slide rack <NUM>. This is done by pushing the glass slide <NUM> through an opening in a front portion of the slot and into the slide rack <NUM>. Advantageously, the slide rack <NUM> comprises a barrier <NUM> at a rear portion of the slide rack <NUM> that prevents the glass slide <NUM> from passing completely through the slide rack <NUM> when the slide is pushed into a slot of the slide rack <NUM>.

In some instances, reinsertion of the glass slide <NUM> may be unsuccessful. Advantageously, the positioning of the line-of-sight <NUM> of the sensor <NUM> pair near the back of a slide rack <NUM> allows the processor to analyze a signal from the sensor <NUM> pair to confirm that a slide <NUM> has been reinserted properly, e.g., completely pushed into the rack slot. For example, if a slide <NUM> is properly and fully reinserted into the slide rack <NUM> such that the back edge <NUM> of the slide <NUM> engages a barrier <NUM> that prevents the glass slide <NUM> from passing , the line-of-sight <NUM> of the sensor <NUM> pair is interrupted by at least a portion of the back edge <NUM> of the slide <NUM>. However, if a slide <NUM> is not properly reinserted, the line-of-sight <NUM> of the sensor <NUM> pair is not interrupted. The processor is configured to analyze a signal from the sensor <NUM> pair to confirm whether or not a slide <NUM> has been properly reinserted into the slide rack <NUM>. If a slide <NUM> is not properly reinserted, the processor may cause the reinsertion process to abort and retry or alternatively operation of the digital slide scanning apparatus may be suspended and an alert generated to request operator intervention.

<FIG> is a top view diagram illustrating an example slide reinsertion check for a slide rack <NUM> made by a second manufacturer according to an embodiment. In the illustrated embodiment, the sensor mount <NUM> supports a sensor <NUM> pair comprising a transmit element <NUM> and a receive element <NUM>. An output of the sensor <NUM> is coupled to the processor (not shown). The sensor <NUM> pair is positioned such that the line-of-sight <NUM> is positioned toward the back end of the slide rack <NUM> made by the second manufacturer. Advantageously, the positioning of the sensor <NUM> pair places the line-of-sight <NUM> toward the back end of any slide rack made by any manufacturer. This positioning of the sensor <NUM> pair on the sensor mount <NUM> operates for both the slide inventory process and the slide reinsertion check process.

As discussed above, in the slide reinsertion check process, when the processing (e.g., scanning) of a glass slide <NUM> is completed, the glass slide <NUM> is inserted back into the slide rack <NUM>. This is done by pushing the glass slide <NUM> through an opening in a front portion of the slot and into the slide rack <NUM>. Advantageously, the slide rack <NUM> similarly comprises a barrier <NUM> at a rear portion of the slide rack <NUM> that prevents the glass slide <NUM> from passing completely through the slide rack <NUM> when the slide is pushed into a slot of the slide rack <NUM>.

In the slide reinsertion check process, when the processing (e.g., scanning) of a glass slide <NUM> is completed, the glass slide <NUM> is inserted back into the slide rack <NUM>. In some instances, reinsertion of the glass slide <NUM> may be unsuccessful. Advantageously, the positioning of the line-of-sight <NUM> of the sensor <NUM> pair near the back of a slide rack <NUM> allows the processor to analyze a signal from the sensor <NUM> pair to confirm that a slide <NUM> has been reinserted properly, e.g., completely pushed into the rack slot. For example, if a slide <NUM> is properly reinserted, the line-of-sight <NUM> of the sensor <NUM> pair is interrupted. However, if a slide <NUM> is not properly reinserted, the line-of-sight <NUM> of the sensor <NUM> pair is not interrupted. The processor is configured to analyze a signal from the sensor <NUM> pair to confirm whether or not a slide <NUM> has been properly reinserted into the slide rack <NUM>. If a slide <NUM> is not properly reinserted, the processor may cause the reinsertion process to abort and retry or alternatively operation of the digital slide scanning apparatus may be suspended and an alert generated to request operator intervention.

In one embodiment, a digital slide scanning apparatus 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 glass slides. The motor is also configured to position the slide rack for processing of a first slide from a first slot, for example a slide occupying the bottom slot. The digital slide scanning apparatus also includes a sensor pair comprising 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 is positioned on a first side of a sensor mount and a second one of the transmitter element or the receiver element positioned on a second side of a sensor mount. When the slide rack is positioned for processing the first slide, each of the plurality of slots of the slide rack is passed through the line-of-sight of the sensor pair. The digital slide scanning apparatus also includes a processor configured to control the motor to position the slide rack for processing of the first slide. The processor is also configured to receive a signal from the sensor pair and correlate the signal to each of the plurality of slots. The processor is also configured to analyze the signal corresponding to each of the plurality of slots to determine a status of each of the plurality of slots.

In one embodiment, the status of each of the plurality of slots is one of: occupied or empty. In one embodiment, the status of each occupied slot is one of: normal or askew. In one embodiment, the status of each of the plurality of slots is determined prior to scanning the first slide.

In one embodiment, subsequent to determining the status for each of the plurality of slots, the first slide is unloaded from the first slot for processing and later reinserted to the first slot after processing. In this embodiment, the processor is further configured to receive a signal from the sensor pair corresponding to the first slot during reinsertion and analyze the signal corresponding to the first slot during reinsertion to determine a reinsertion status of the first slide into the first slot. In one aspect of this embodiment, the reinsertion status is one of: proper or improper.

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

In one embodiment, a method includes using a motor to position a slide rack for processing of glass slides in the slide rack. In this embodiment, the slide rack comprises a plurality of slots including a top slot and a bottom slot and the slide rack holds a plurality of glass slides. Also, the position for processing of glass slides in the slide rack is a position for loading a first slide occupying a first slot onto a scanning stage. In this method, using the motor to position the slide rack for processing of glass slides in the slide rack comprises moving the slide rack between first and second sides of a sensor mount supporting a sensor pair comprising 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 is positioned on a first side of the sensor mount and a second one of the transmitter element or the receiver element is positioned on a second side of a sensor mount such that moving the slide rack comprises passing each of the plurality of slots of the slide rack through the line-of-sight of the sensor pair. The method also includes using a processor to control the motor to position the slide rack for processing of the first slide, using the processor to receive a signal from the sensor pair and correlate the signal to each of the plurality of slots, using the processor to analyze the signal corresponding to each of the plurality of slots, and using the processor to determine a status of each of the plurality of slots.

In one embodiment, the status of each of the plurality of slots is one of: occupied or empty. In one embodiment, the status of each occupied slot is one of: normal or askew. In one embodiment, the method also includes determining the status of each of the plurality of slots prior to scanning the first slide. In one embodiment, the method also includes subsequent to determining the status for each of the plurality of slots, unloading the first slide from the first slot for processing, reinserting the first slide to the first slot after processing, using the processor to receive a signal from the sensor pair corresponding to the first slot during reinsertion, and using the processor to analyze the signal corresponding to the first slot during reinsertion to determine a reinsertion status of the first slide into the first slot.

In one embodiment, the reinsertion status is one of: proper or improper. In one embodiment, using the motor to position the slide rack for processing of glass slides in the slide rack comprises positioning the sensor pair such that a plane of the line-of-sight of the sensor pair is substantially the same as a plane occupied by the glass during scanning.

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

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

In one embodiment, the processor <NUM> is configured to control movement of the slide rack and to receive and analyze the signal from the sensor <NUM> pair to determine the presence, absence or misalignment of glass slides <NUM> in a slide rack <NUM>. In one embodiment, the processor <NUM> is configured to control reinsertion of a glass slide <NUM> into the slide rack <NUM> and to receive and analyze the signal <NUM> from the sensor <NUM> pair to determine proper reinsertion of the glass slide <NUM> into the slide rack <NUM>.

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

Claim 1:
A digital slide scanning apparatus (<NUM>), comprising:
a motor (<NUM>) configured to power a slide rack mover which is configured to convey a slide rack (<NUM>; <NUM>) within the digital slide scanning apparatus, the slide rack including a plurality of slots (<NUM>) configured to hold a plurality of glass slides (<NUM>; <NUM>),
wherein each slot has an opening at a first end of the slot in a front portion of the slot and wherein each slot has a barrier (<NUM>) at a second end of the slot at a rear portion of the slide rack, wherein when a slide is reinserted into the slide rack the back edge of the slide engages a barrier (<NUM>) that prevents the glass slide from passing completely through the slide rack;
a sensor pair (<NUM>) comprising a transmitter element (<NUM>) and a receiver element (<NUM>) positioned for line-of-sight (<NUM>) communication, the transmitter element positioned on a first side of a sensor mount (<NUM>) and the receiver element positioned on a second side of the sensor mount (<NUM>); and
a processor (<NUM>) configured to control the motor to move the slide rack to pass a rear portion of each of the plurality of slots of the slide rack through the line-of-sight communication of the sensor pair, the processor further configured to receive a signal (<NUM>) from the sensor pair and analyze the signal to determine a status (<NUM>) of each slot of the slide rack.