BRPI1103372B1 - APPARATUS COMPRISING A LABELING MODULE, A COVERSLIP PLACING MODULE, AN IMAGING MODULE AND A BIOLOGICAL SPECIMEN STORAGE AND PROCESSING METHOD MODULE - Google Patents

Abstract

AUTOMATED SYSTEM AND METHOD FOR PROCESSING BIOLOGICAL SPECIMEN. The present invention relates to an apparatus that includes at least one of a staining module and a coverslip module; an imaging module; a storage module; an automated transport module for transporting at least one slide between at least one of the staining module and the coverslip module, the imaging module and the storage module; and a controller. A method that includes processing at least one slide; determining whether an imaging module is available for imaging a biological specimen on the at least one slide; transporting the at least one slide to the imaging module using an automated transport module; and transporting the at least one slide to a storage module using the automated transport module when it is determined that the imaging module is not available. A system that includes a processing module for processing at least one slide that includes a biological specimen thereon. A machine-readable medium.

Description

BACKGROUND Field

[001] An automated biological specimen processing system.

Background

[002] In many settings, examination of biological specimens is necessary for diagnostic purposes. In general, pathologists and other diagnosticians collect and study samples from patients, and use microscopic examination and other devices to evaluate the samples at the cellular level. Numerous steps are typically involved in the pathology and other diagnostic process, including the collection of biological samples such as blood and tissue, processing of the samples, preparation of microscope slides, staining, examination, retesting or relabeling, collection of additional samples, reexamination of the samples, and, ultimately, the release of the diagnostic results. Numerous medical or veterinary professionals may be involved in the diagnostic process, including surgeons, phlebotomists or other operating professionals who collect samples, pathologists, histologists and other professionals who process, transport and examine the samples, and so on. The complexity of tissue handling procedures from the operating room to the laboratory and back to the diagnosticians or surgeon has become increasingly complex in large medical settings where large volumes of specimens need to be handled, processed and examined on a daily basis.

[003] Various steps of tissue handling procedures have been automated through the use of instruments, each of which is typically controlled by a dedicated computer or integrated computer controller. In some laboratories, information may be shared between automated instruments and/or a networked laboratory or hospital information system, such as to store patient or tracking data. An example of an automated instrument is an automated tissue processing system in which biological specimens are fixed and infiltrated with paraffin in an automated manner. Exemplary tissue processing systems are the TISSUE-TEK® VIP® and TISSUE-TEK® XPRESS® processing systems available from Sakura Finetek USA, Inc. of Torrance, California.

[004] Another example of automation is an automated microscope slide marker and coverslipper, which marks microscope slides and applies coverslips to the slides in an automated manner. Examples of such automated coverslip marker and placement systems are the TISSUE-TEK® PRISMA® and TISSUE-TEK® FILM® combination system and the TISSUE-TEK® PRISMA® and TISSUE-TEK® GlasTMg2 combination system available from Sakura Finetek U.S.A., Inc. of Torrance, California.

[005] Despite the assistance of automated instruments, pathologists, other diagnosticians, and laboratory personnel must typically be involved in numerous steps during the processing and examination of biological samples. For example, once a sample has been stained, the stained sample on a microscope slide may be physically examined under a microscope. This typically involves transporting the microscope slide to a diagnostician who is positioned outside the laboratory or, in other cases, may involve a diagnostician traveling to the laboratory to examine the microscope slide. Alternatively, the stained sample on a microscope slide is imaged with a digital camera and the image of the sample is uploaded for examination by a diagnostician.

[006] Following this initial examination step, the diagnostician assesses whether additional testing is necessary. Such additional testing may involve collecting additional samples from a patient, or additional testing of samples already collected. For example, the diagnostician may require that the existing sample be further divided and a different staining regimen or protocol applied. This may result in iterations of one or more of collection, enlarging, processing, infiltration, embedding, dividing, coverslipping, staining, examination, etc. In addition, different coverslipped slides may require different drying times. Consequently, some slides may be ready for examination while others are not. All of this may result in delay as well as tissue deficiency. Following iterations of additional testing and procedures, the pathologist repeats the examination process and may then order additional tests in an iterative manner until a final conclusion is reached. Even with automated instruments, these processes involve a great deal of human intervention and transportation.

BRIEF DESCRIPTIONS OF THE DRAWINGS

[007] Embodiments of the invention are illustrated by way of example and not by way of limitation in the figures of the accompanying drawings in which like numeral references indicate like elements. It should be noted that references to "a" (indefinite article) or "a" (numeral) embodiment in this description do not necessarily refer to the same embodiment, and such references mean at least one (1).

[008] Figure 1 is a flowchart of one embodiment of a method for automatically processing biological specimens.

[009] Figure 2 illustrates an embodiment of an automated system for processing biological specimens.

[0010] Figure 3 illustrates one embodiment of an automated system for processing biological specimens.

[0011] Figure 4 illustrates a top view of one embodiment of an automated system for processing biological specimens.

[0012] Figure 5 illustrates a side view of the automated system of Figure 4 through line 5-5'.

[0013] Figure 6 illustrates a side view of the automated system of Figure 4 through line 6-6'.

[0014] Figure 7 illustrates a top view of the automated system of Figure 4 showing a slide placed in an imager.

[0015] Figure 8 illustrates a side view of the automated system of Figure 4 through line 8-8'.

[0016] Figure 9 shows a perspective view of an embodiment of a storage module of the automated system of Figure 4.

DETAILED DESCRIPTION

[0017] In the following paragraphs, the present invention will be described in detail by way of example with reference to the accompanying drawings. Throughout this description, the preferred embodiments and examples shown should be considered as exemplary rather than limitations of the present invention. As used herein, the "present invention" refers to any of the embodiments of the invention described herein, and any equivalents. Furthermore, reference to various aspects of the invention throughout this document does not mean that all claimed embodiments or methods must include the related aspects.

[0018] In the overview, a system and process for performing a series of automated operations including tissue processing, imaging, and tissue storage are described. Figure 1 shows a flowchart of one embodiment of a process implemented by a system (i.e., machine-readable program instructions implemented in a processor connected to process control modules). As illustrated in block 102, process 100 includes obtaining, in a material handling system, a biological sample that has been mounted on a slide. The biological sample is transported to a material handling system, for example, via manual transport, a cart, or automated transport. In a hospital embodiment, the specimen may be delivered to a medical laboratory, either on-site or at a remote location.

[0019] In the material handling system, the slide-mounted specimen may be processed through automated operations into a condition suitable for a desired examination. In one embodiment, the processing includes marking the biological sample and applying a coverslip to the slide (block 104). Marking the specimen may be optional. The slide having the specimen thereon is then transferred to a transport module (block 106). In some embodiments, the slide is transferred to the transport module using a robotic transfer device as will be discussed in more detail with reference to FIGS. 4-9.

[0020] The process 100 further includes determining whether the slide is ready for imaging (block 108). Such a determination may be based, for example, on the drying time of the slide. For example, there are different methods of coverslipping and each requires different drying times. Representatively, a glass coverslip may require about a day of drying while a film coverslip may dry in about an hour. In this aspect, coverslipped slides that are not ready (e.g., not dry) for further processing (e.g., imaging) are transported to a storage module to provide them with additional time to dry (block 112). Slides that are dry are determined to be ready for imaging.

[0021] Process 100 further includes determining whether the imager is available for imaging (block 110). Imaging a specimen on a slide typically takes longer than the amount of time it takes to mark, cover slip, and dry the slide, because imaging must be done on individual slides (i.e., one at a time) while marking and coverslipping operations must be done on numerous slides at the same time (e.g., marking a batch of slides). For example, slide imagers can perform a 20x scan of a 15x15 mm tissue in about 2 1/2 to 3 minutes. Higher resolution and z-stacking requirements can double the time. This equates to an imager throughput of about 10 to 24 slides per hour. In contrast, up to about 500 slides per hour can be processed through a coverslipper and/or marker. As a result, the imager is often not ready to image each of the slides once they have exited the coverslipper and/or marker. If the imager is not available, the slides are transported from the coverslipper to a storage module for storage until an imager is available (block 112).

[0022] Once the imager is available, the slide is transported to the imager (block 114) for imaging. At the imager, a digital image of the specimen is captured and stored in a computer memory. After a specimen, or group of specimens, is prepared for examination, the specimen(s) may be examined and the data may be made available to a diagnostician and/or an optional interpretation module that automatically interprets the data (block 116). It should be noted that for use herein, “diagnostician” refers to any person who may wish to view the image data, such as pathologists, surgeons, nurses, researchers, technicians, and administrators.

[0023] The image data may be created, such as by using a digital imager including, for example, CCD technology. The image data is preferably made available for access by a diagnostician if desired, and optionally the diagnostician is notified, such as by electronic notification, such as by electronic mail, pop-up message on a computer screen, banner message, pager message, or automated telephone call. In other embodiments, the image data may also be accessed by, or made available to, an optional interpretation module. The interpretation module may conduct digital processing, such as through the use of pattern recognition technology, to develop a preliminary diagnosis, and generate instructions or recommendations for further processing.

[0024] Further processing, illustrated with block 118, may include collecting additional biological samples, or performing further processing on samples already collected such as performing additional or different testing procedures or labeling protocols. For example, after imaging, a specimen may be transported by the transport module to the storage module. The image of the specimen may be examined and, if it is determined that further imaging is necessary, the specimen is retrieved from the storage module by the transport module and transported to the imager for imaging. Examination, imaging and interpretation of the sample may be continued until the system or diagnostician deems it complete. Such repeated testing and examination is referred to herein as iterative processing, testing or examination. In another aspect of the invention, the diagnostician may access reports that are based on comparison of the data generated by the interpretation module. In a further aspect of the invention, the diagnostician may order or conduct additional iterative processing, testing or further examination.

[0025] Figures 2 through 9 illustrate examples of automated systems for processing biological specimens. In these figures, information trajectories are illustrated with solid lines and/or arrows, and material trajectories are illustrated with double lines and outlined arrows. For use herein, "material" refers to any biological material including histological and cytological specimens that may be examined in a medical, autopsy, veterinary, or research laboratory procedure. Biological material may include tissue samples or specimens, and/or biological fluids such as blood, plasma, etc. Although the illustrated examples are described in relation to tissue, the systems and methods described are not so limited. For use herein, biological material will be referred to interchangeably as a specimen, sample, or material. Additionally, references to processing a "slide" in this document refer to a slide that has biological material on it.

[0026] In the illustrated examples, the material paths represent exemplary transport paths that might be taken by a physical sample in a laboratory or hospital. A typical progression of material from one station or system component to the next is represented by the direction of the arrow. However, it should be understood that the processing stations are provided as examples, as are the directions of material flow. It should be appreciated that a greater, lesser, or other number of processing stations may be used in the practice of the present invention, and/or a greater, lesser, or other number of material paths and directions may be used in the practice of the present invention. Furthermore, the stations may be in any order and in any orientation (e.g., stacked vertically or side by side).

[0027] Any form of conveyance may be used that is sufficient to automatically transport material as indicated by material trajectories. For example, material may be transported by a robotic device from one station to the next as will be discussed in more detail with reference to Figures 4 through 7. The term robot or robotics should be broadly interpreted as a conveyance, transfer device, electromechanical transfer mechanism or device, or automatically controlled, reprogrammable, multi-purpose manipulator programmable in three, four, or more geometric axes. The robotic device may take various forms or configurations, consistent with its purpose. The robotic device may be programmed with an application program, program routine, or other set of instructions. The program or set of instructions may specify one or more operations that the robotic device is to perform autonomously or at least semi-autonomously. Representatively, the program or set of instructions may specify the movements (e.g., coordinates, distances, directions, etc.), timers or triggers, and similar information associated with the operations. In some embodiments, the material may also be, or alternatively, manually transported from one station to the next. Additionally, a machine may perform multiple steps with no physical movement of the material from one station to another being necessary.

[0028] In the embodiment of Figure 2, a specimen mounted on a microscope slide is transported to the marking module 210. Prior to transporting the specimen to the marking module 210, the specimen may be processed through, for example, a reaming station (in the case of non-fluid specimens), a tissue processor where the specimen is treated with a series of reagents, a blocking station where it may be infiltrated with paraffin and embedded, and a microtome station where the specimen is sectioned. Sections of the specimen created at the microtome station are positioned on the microscope slide. Slides requiring deparaffinization may be placed in an oven prior to marking, or placed directly in the marker if the marker is equipped with a built-in oven or can perform a chemical deparaffinization step.

[0029] Any staining or other testing protocol may be performed by staining module 210 as desired. In one embodiment, an automated stainer is used. In one example, hematoxylin and eosin ("H&E") staining is performed in staining module 210. Other staining methods such as spot staining (SS), immunohistochemistry (IHC), and in situ hybridization (ISH) may also be performed.

[0030] In one embodiment, following marking, samples may be transported along material path 217 to coverslip module 220 to be covered by the coverslip.

[0031] After marking and/or coverslipping, the slide may proceed to imager 230 or storage module 202. In some embodiments, where it is desirable to delay imaging of the slide, the slide is transported to storage module 202 for storage until imaging is desired. Representatively, different methods of coverslipping exist and each require different drying times. Coverslipped slides that are not ready (e.g., not dry) for further processing are transported to storage module 202 along material path 203. Once the slides are ready, they may then be transported along material path 205 to imager 235. In this aspect, differences in drying times from slide to slide are automatically resolved by the automated system.

[0032] In some embodiments, the laboratory may select the delay criterion based on the coverslipping technique used and the type of sample (histology v. cytology, single-layer slides v. markers, etc.). For example, the laboratory may determine, based on the coverslipping technique to be used and the type of sample on the slide, that the slide should be stored for a period of time prior to imaging. This information may be contained in an identifier associated with the slide. Examples of identifiers include a radio frequency identification (RFID) tag, a barcode that can be read by a reader associated with the system that provides information to the automated system. The automated system may be the identifier and follow the assigned processing protocol. In this aspect, after coverslipping, the slide is transported to storage module 202 and stored for the predetermined period of time. After this time, the system may alert the transport module to retrieve the slide from the storage module 202 and transport the slide to the imager 230 for imaging.

[0033] In addition to drying times, the availability of the imager 230 may additionally delay imaging. In particular, imaging a specimen on a slide typically takes longer than the amount of time it takes to mark, cover slip, and dry the slide. For example, current commercially available slide imagers can perform a 20x magnification scan of a 15x15 mm tissue in about 2 1/2 to 3 minutes. Higher resolution and z-stacking requirements may double this time. This equates to an imager throughput of about 10 to 24 slides per hour. In contrast, up to about 500 slides per hour may be processed through the coverslipper/marker modules. As a result, the imager is often not ready to image each and every slide as it exits the coverslipper/marker modules. The identifier associated with the slide may store information related to the desired imaging protocol for the slide (e.g., a 10x scan, a 20x scan, or a 40x scan). Upon reading the identifier, the system schedules imaging of the slide with an imager capable of imaging at the desired magnification. If the desired imager is not available when the slide is ready for imaging, the slide is transported from the marking module 210 and/or the coverslipper module 227 of the material 203 to the storage module 202 for storage until the imager 230 is available.

[0034] It is also further contemplated that after a specimen is imaged by imager 230, the specimen slide may be transported along material path 205 to storage module 202. The slide may be stored in storage module 202 for future testing and/or examination.

[0035] Once the specimen is ready for imaging, at least one image of the specimen material is obtained by the imager 230. The imaging protocol for each slide that is to be followed by the imager 230 may be flexible and may be defined at any time, for example, by the diagnostician (e.g., pathologist). In this regard, the diagnostician may have real-time control of the imaging process remotely. For example, a pathologist may examine an image and determine that additional images of the slide are needed. Representatively, the pathologist may determine that images at a different magnification are needed or that the imager should focus deeper into an area of tissue. In accordance with the automated system presented herein, the pathologist may instruct the system to obtain additional images. The system will then retrieve the specimen from the storage module 202 and transport it to the imager 230 for additional imaging if required. The pathologist can receive results as soon as they are requested, as opposed to current imaging systems that often process z-stack and higher resolution images overnight.

[0036] The imager 230 may include one or more imagers. The imager may be any system that generates images that can be manually interpreted or, optionally, automatically interpreted by the interpretation module 290. In the illustrated embodiment, the imager 230 includes a microscope and a camera capable of recording digital images of the microscope's field of view. For example, an optical CCD camera may be used to generate the digital image data. The digital image data may be stored in any manner that provides access to the data as required by the interpretation module 290, the diagnostician's workstation 240 and/or the technician's workstation 250, and/or as desired by any person who needs access to the image data, such as diagnosticians or laboratory personnel. Examples of suitable data storage are local storage devices associated with imager 230 (such as hard drive, removable memory, flash memory, optical memory such as CD or DVD, etc.), and/or networked memory as illustrated diagrammatically by data storage 260. It should be noted that any form of information may be generated by imager 230 in addition to the image data. For example, imager 230 may optionally associate other types of data, such as a patient information log associated with the image data and as discussed later herein. Alternatively, another processing system may associate the image data with other data.

[0037] In one embodiment, the type of information generated is intended to be sufficient for the interpretation module 290 to perform its interpretation processing and generate the desired report. The interpretation module 290 may take any desired form, such as a dedicated computing system, or alternatively, it may be a module that operates within a computing system used for multiple purposes. In addition to the examples, it may be stand-alone, a part of the imager 230, part of the hospital information system 270, part of the laboratory information system 280, or it may be in a location where data can be received from the imager 230. Although the figure depicts a single interpretation module 290, it should be understood that plural interpretation modules 290 may also be used. In additional examples, diagnostician workstations 245 may include interpretation modules 290 or interpretation module clients that enable the diagnostician to locally conduct an interpretation based on available data including, without limitation, image data from imager 230.

[0038] In the embodiment of Figure 2, the interpretation module(s) 290 are in communication via the communications infrastructure 200. The interpretation module 290 may access data as desired, either directly from the imager 230, via the data storage facility 260, or via local data storage. The interpretation module uses the image data and other data to perform an analysis and a recommendation. In one embodiment, the analysis includes a pattern recognition analysis in a pattern recognition system of the interpretation module 290. In one form of pattern recognition, the image data from the imager 230 is compared to a database of known patterns. If a sufficient level of match is found, a matching pattern is located via a recommendation, diagnosis, or further processing instruction may be made. The standard database may be a part of the interpretation module 290, or externally located, such as in the data warehouse 260 or in the laboratory information system 280.

[0039] Following imaging by imager 230, interpretation module 290 may be configured to determine whether the imaged sample should go to the storage module, in which case it proceeds along material path 227, or interpretation module 290 may be configured to determine whether the particular sample needs to undergo further processing, such as it would go to a diagnostician or other professional for personal inspection, in which case it proceeds along material path 237.

[0040] Alternatively, the interpretation module 290 may be configured to determine whether further processing of the tissue represented by the imaged sample is necessary. In such a case, a new sample of the tissue is required for interpretation. In one embodiment, the additional section(s) (samples) of the same tissue may be placed on slide(s) and these slide(s) sent to the storage module 202 with a label linking the slide(s) to the imaged sample. In this embodiment, the slide(s) are not marked or coverslipped, and are kept separate. These slides could be identified as being extra sections that should not be marked and kept in storage until recalled for marking and coverslipped. For example, these extra slide(s) may have the same identifying information as the original or primary slide, perhaps with an additional indicator (e.g., an additional number or letter) to indicate that the slide(s) are extra slide(s). If they are not needed, these slides may be discarded after, for example, a user-defined period of time has elapsed or the case has been completed or terminated. The extra sections are cut and the extra slides prepared and marked only when there is a requirement for further marking protocols. In an automated handling system that also includes handling of tissue blocks, the requirement for further marking would be transferred to the microtomy module 205. In one embodiment, a tissue block, including a formalin-fixed tissue section in a paraffin block from which another tissue section may have been taken and placed on a slide, includes an identifying label such as a barcode or RFID tag. In response to a signal from a controller, the tissue block is automatically retrieved and transported from a storage module (e.g., storage module 202) to the microtomy module 205. The tissue block is stored and can be retrieved via the identification tag. The tissue block would then be forwarded to the microtomy area for further sections to be taken.

[0041] Representatively, once a new sample is placed on a slide, the new sample proceeds to the labeling module 210 where it may undergo operations such as special labeling, immunohistochemistry ("IHC"), in situ hybridization ("ISH"), multiplexing, or other labeling or testing procedures. Subsequently, the new sample may proceed along the material path, e.g., back to the imager 230. Ultimately, it is desirable for a tested and imaged sample to be stored as directed by the storage module 202. In this example, after inspection by a diagnostician or other person, the original sample may be designated for storage, as in the storage module 202, and the new sample from the same tissue section designated and further processed. The new sample may be processed and inspected and sent for storage. The original sample and the new sample are linked by an identification tag. Thereafter, either or both the original and the new sample may optionally be retrieved from storage module 202, if desired.

[0042] Workstations, such as diagnostician workstations 240 or other workstations, such as technician workstations 250, may have any desired structure, including computing systems that serve as controllers in communication via communications infrastructure 200 with other processing stations or system components. Workstations may also optionally include other components that may be useful in a work area, such as material storage units, equipment, telephones, etc. In one embodiment, workstations 240, 250 provide access to information concerning the processing of biological samples, and the results of the processing, including image data from imager 230 and reports and interpretation data from interpretation module 290. Technician workstation 250 may be in communication with data storage 260 via path 257. In another embodiment, a system may not include workstations such as diagnostician workstations 240 and/or technician workstations 250.

[0043] As material proceeds along material pathways and through processing systems, information may be shared among the numerous devices using multiple information pathways that form communications infrastructure 200. It should be noted that communications infrastructure 200 may be any form of communications system enabling communications between and among individual computer systems and/or automated processing systems. Representatively, the communications infrastructure may be a wired or wireless computer network, or a combination of wired and wireless networks. For example, information access points may be wired into the network and/or joined to the network via a wireless gateway. Although the illustrated example shows a networked system in which communications are conducted over a network, direct communications may also be conducted. For example, in one embodiment, the marking module 210 may have a direct communications link with the coverslipper module 220 and may access the communications network through a node in the coverslipper module 220, or alternatively, may have a direct network link. It will be understood that any suitable communications path structure is envisioned that would allow for the appropriate sharing of information between and among multiple stations. Likewise, it will be understood that in other embodiments, not all stations may have a direct communications path. Further, it will be understood that communications paths may take any form, such as digital, analog, wired, wireless, paper, oral, telephonic, etc.

[0044] In one embodiment, a laboratory network may be provided as the portion of the communications infrastructure 200 between and among the laboratory instruments, represented by reference numerals 210, 220, 230, 202, and also the laboratory information system 280 and other workstations 240 and 250 (which may include a computer system such as, for example, one or more personal computers and/or computer servers). The laboratory network may be networked with a hospital network that is also a part of the communications infrastructure 200. In such an embodiment, other devices may have access to the information available in the laboratory information system 280 or other laboratory devices via the communications infrastructure 200. Such other devices include, for example, the diagnostician or administrator workstations 240, the hospital information system 270, and in some embodiments also the interpretation module 290. It should be understood that the flexibility of the information pathways is directed toward enabling the necessary information to flow to track the biological samples being processed however desired, and to distribute the necessary information to the appropriate users. Numerous alternative communications system structures may be selected to meet this need, and the examples illustrated and discussed are provided for illustrative purposes only, not to limit the scope or flexibility of the system.

[0045] Referring to the illustrated example, communications paths 203, 205, 207, 215, 225, 235, 245, 255, 265, 275, 285, 295 represent examples of communications paths between the labeling module 210, the coverslipper module 220, the imager 230, the storage module 202, the diagnostician workstation 240, the technician workstation 250, the local or remote data storage 260 and/or the hospital information system 270, the laboratory information system 280, the interpretation module 290, or any other desired station or component of the system.

[0046] Information sharing may be automated, manual, or conceptual. For example, information may be directly shared by two machines in communication with each other, it may be made available to a user who may manually input it into another device, or a single machine comprising more than one device shown in FIG. 2 may engage in internal communication. This information sharing often involves two-way communication. For example, images of a patient having a chronic condition may be sent to a patient information storage database, and previously obtained information regarding the same patient may be retrieved from the database in order to monitor the progression of the condition. In another embodiment, each station in the material path is capable of communicating via the communications infrastructure 200, and the stations may communicate the progression of the material along the material paths as well as other information, as discussed in detail below.

[0047] In another embodiment, biological specimens, slides, arrays, containers, workpieces, and locations throughout the system may be identified with machine-readable codes, such as provided by RFID tags, shape identifiers, color identifiers, numbers or words, other optical codes, bar codes, etc. The identifiers may be recorded to generate data provided to a database, such as data maintained on a data storage device 260, by a processor (any computing device), the hospital information system 270, the laboratory information system 280, or any combination thereof. Examples of data that may be tracked include patient information and history, information regarding the biological sample(s) collected, arrival and departure times of the biological samples, tests performed on the samples, processes performed on the samples, reagents applied to the samples, diagnoses made, associated images, and so on.

[0048] Figure 3 illustrates one embodiment of a system for automatically processing a biological specimen. The System 300 system includes the transport module 302. The transport module 302 may automate, or at least partially automate, the transfer of slides or other tissue retainers between stations, i.e., between one or more of the marking module 304, the coverslipper module 306, the imagers 308, 310, 312, the storage module 314, and the microtomy module 307. Automatically transporting the slides or other tissue retainers between the marking module 304, the coverslipper module 306, the imagers 308, 310, 312, the storage module 314, and the microtomy module 307 as opposed to manually transferring the slides or other tissue retainers offers certain potential advantages. On the one hand, this can free workers from the need to perform these tedious and often repetitive operations manually. Advantageously, this can allow workers to perform more value-added operations and/or other operations that are less amenable to automation. On the other hand, the transport module can be better suited to perform these operations reliably and in a timely manner than workers, who may at times be distracted by other tasks, or forget or be unable to perform these operations reliably and in a timely manner. In particular, manual transport by workers can result in lost slides, slide breakage during handling, misplacement, or slide misreading by the imager. Additionally, in the case of slide storage, transport by personnel to the storage module may result in misplaced slides, incorrect documentation of slides stored within the storage module, and/or costly and lengthy slide retrieval from the storage module. Advantageously, automated slide transport may allow for improved productivity or throughput by reducing instrument downtime waiting for samples to be manually transferred. Similar advantages may be provided by automating the transfer of tissue blocks between the microtomy module 307 and the storage module 314.

[0049] In one embodiment, the transport module 302 may be a robotic device capable of transporting a blade between stations. In one embodiment, the transport module 302 may be an X-Y-Z robotic device dimensioned to transport one or more blades between stations. Representatively, the transport module 302 may be a rail and elevator system. The rail system may be a conveyor belt or a plate system that transports the blade horizontally in an "x-" direction. In this aspect, one or more slides may be placed on the conveyor and transported between desired stations, for example, between the coverslipper module 306, the imager 308, and the storage module 314. In one embodiment, the conveyor belt system may have two separate conveyor belts such that one conveyor belt transfers the slide in one direction and the other conveyor belt transfers the slide in the opposite direction as illustrated by arrow 316. Alternatively, as described with reference to FIGS. 4-9, a single conveyor belt system may be used to transport the slide in more than one direction. The conveyor module 302 may further include an elevator device. The elevator device transports the slide vertically in a y-direction when it is desired for a slide to be positioned above or below the conveyor belt. The elevator device may further include a component for transporting the blade into and out of the elevator in the z direction.

[0050] The marking module 304 and the coverslipper module 306 may be an integrated coverslipper and slide marker system. Alternatively, the marking module 304 and the coverslipper module 306 may be on separate instruments in different locations. In the case of an integrated system, the marking module 304 and the coverslipper module 306 may be a coverslipper/marking system such as the TISSUE-TEK® PRISMA® and TISSUE-TEK® GLAS®g2 combination system or the TISSUE-TEK® PRISMA® and TISSUE-TEK® FILM® combination system commercially available from Sakura Finetek U.S.A., Inc., Torrance, CA. In one embodiment, the staining module 304 has hematoxylin and eosin (H&E) and spot staining (SS) capabilities. In H&E/SS staining and coverslipping, the biological sample may be subjected to H&E or SS staining and optional coverslipping. Other staining or testing protocols may also be performed.

[0051] During operation, an individual slide or group of slides placed in a basket may be loaded into the marking module 304 and marked according to a desired marking protocol. In the case of a group of slides, the marking protocol may be the same as or selected from a marking protocol list, either by an operator or automatically by reading a barcode, RFID or other protocol identification device. Once the marking protocol is complete, the slide or group of slides within the basket is automatically transferred to the coverslipper module 306 for individual coverslip placement. The identifier associated with each slide is then read as the slides are coverslipped and either placed as a group in a basket or individually fed into the transport module 302.

[0052] In an alternative embodiment, where a group of slides are marked together, the slides may be singulated (separated from the group) in the marking module 304 and placed in the transport module 316. For example, where a group of slides are marked together in a basket, a robotic pick-and-place device in the marking module 304 may transfer the slides individually to the transport module 316. From the transport module 316, the slides may be transported to the coverslipper module 306, or, without a coverslip, to one of the imagers 308, 310, 312 or to the storage module 314.

[0053] Imaging methods (fast scan, 20x, 40x, z-stack, etc.) on imagers 308, 310, 312 may be pre-scanned for each slide according to a laboratory standard or specific instructions from, e.g., a pathologist. In the case of grouped slides in the basket, in one embodiment, each of the slides could be scanned by the same scanning method(s). Individual slides or the basket of slides may be scanned for one of the imagers 308, 310, 312 based on the availability of the imagers or according to rules defined by the laboratory, such as dedicating one or more imagers to a specific scanning method (e.g., fast scan, 20x, 40x, or z-stack) or a plurality of methods.

[0054] In one embodiment, the slide including a biological sample is individually transported by the transport module 302 to one of the imagers 308, 310, 312 and/or to the storage module 314. If the slide is ready for imaging (e.g., dry), the system will check to see if, for example, the imager 308 is available. The imager 308 is determined to be available if, for example, it is functioning properly and is not simultaneously imaging another sample on a slide. If the imager 308 is not available, the availability of the imager 310 is determined. If the imager 310 is not available, the availability of the imager 312 is determined. This process continues until an available imager is found. Alternatively, an imaging schedule between the slide and a particular imager may be predetermined. Representatively, information regarding a period of time sufficient to allow the slide to dry may be evaluated for the slide and imagers 308, 310, and 312 and may be in an imaging schedule. The system may determine which imager will be available after the drying period expires. Once the available imager is determined, the slide is transported by transport module 302 to the available imager. Although three imagers are illustrated in FIG. 3, it is contemplated that fewer than three or more than three imagers may be included in the system 300.

[0055] If none of the imagers 308, 310, 312 are available or other conditions exist that delay imaging (e.g., waiting for slide processing instructions), the transport module 302 transports the slide to the storage module 314. The slide remains in the storage module 314 until one of the imagers 308, 310, 312 becomes available and/or until processing instructions are received. Once an imager is determined to be available, the slide is transferred from the storage module 314 to the transport module 302 using, for example, a robotic device, and transported by the transport module 302 to the available imager for imaging. Upon completion of imaging, the slide may be transported by transport module 302 from imager 308, 310 or 312 to storage module 314. The image may be communicated to a diagnostician, e.g., a pathologist, for immediate examination. By means of a computer (e.g., a personal computer), the pathologist may then examine an image of a specimen on a slide for viewing and to bring back a slide for further imaging work if desired. Alternatively, if it is determined that no further examination of the slide is desired, the slide may be removed from storage module 314.

[0056] In one embodiment, the storage module 314 may include more than one storage module. In this aspect, one or more of the storage modules may act as short-term storage areas for slides that are likely to require further imaging work. In addition, one or more of the storage modules may act as long-term storage areas for slides that are unlikely to require further imaging work in the near future. The long-term storage modules may be located within the laboratory or remotely.

[0057] In one embodiment, the storage module 314 is configured to group slides (and tissue blocks for the block storage system) according to user-defined criteria. For example, slides belonging to a patient kit could be placed in the same area. Then, kits or blocks may be located by production date, physician, provenance, or a combination of these criteria. Representatively, as noted above, a slide may contain an identifier that can be read by a reader (e.g., RFID reader, barcode reader). That identifier (e.g., RFID, barcode) may contain information (e.g., letters, numbers, and/or symbols) indicating a production date, physician, and/or provenance. When the information is read by a reader, the information may be sent to the controller 400 or to other devices over the communications infrastructure.

[0058] The automated system 300 as illustrated in FIG. 3 provides for fully automated movement of slides between the marking module 304, the coverslipper module 306, the imagers 308, 310, 312, and the storage module 314. In this regard, the system 300 provides an uninterrupted and continuous workflow that is in sync with other laboratory processes and eliminates the need for overnight batch processing while reducing errors and personnel liability. It is also noted that there are no touch points from marking to storage in the system 300, so the system 300 is believed to satisfy even the most stringent quality control programs such as Lean and Six Sigma.

[0059] Figure 4 illustrates an embodiment of the system of Figure 3. In this embodiment, the marking module 304 is a TISSUE-TEK® PRISMA® marker and the coverslipper module 306 is a TISSUE-TEK® FILM® coverslipper, both commercially available from Sakura Finetek USA. The TISSUE-TEK® PRISMA® marking module and the TISSUE-TEK® FILM® coverslipper module may be connected to each other, and a loading container used in the coverslipper module to hold one or more racks of slides prior to a coverslipper operation may be moved between the coverslipper module 306 and the marking module 304. A brief description of the interaction between these modules is provided in the following paragraphs.

[0060] For the purpose of automating the movement of the loading container in the coverslipper module 306 between the coverslipper module 306 and the marking module 304, software instructions and a data link are provided between the coverslipper module 306 and the marking module 304. Such instructions and link may be solely between the coverslipper module 306 and the marking module 304. Alternatively, a control system may be connected to each of the marking module 304, coverslipper module 306, imagers 308, 310, 312, storage module 314, and transport module 302 that may be used to transport a slide between the imagers and the modules. 4-9 depict the controller 400 connected to each of the modules and imagers noted. In this case, instructions regarding data transfer and data linking may be established between the modules and imagers and the control system. In this case, the controller 400 may control transfer operations between the marking module 304 and the coverslip module 306. The controller 400 may also control (e.g., direct operation of) the numerous other modules and imagers, as well as control slides relative to the modules and imagers.

[0061] Again referring to the movement of a loading container from the marking module 304 to the coverslip placing module 306, the loading container sits on a plate that is connected to wires that move the plate and the loading container in an x and y direction, respectively, by two stepper motors. The plate can move the loading container in an x direction on the marker.

[0062] In operation, a transfer arm of the marking module 304 retrieves a rack of slides and moves the rack along an xy axis to one or more individual marking stations. The transfer arm transfers a rack of slides to an appropriate marking station and then lowers the rack to that marking station for marking (a z direction). After marking, the transfer arm removes the rack of slides from the marking station and moves in an x and y direction to another marking station or, when all operations are complete, to a transfer station where the rack of slides is to be transferred for marking to the Film® coverslipper module (coverslipper module 306).

[0063] For a transfer operation between the marking module 304 and the coverslipper module 306, the loading container in the coverslipper module 306 is instructed to move from the coverslipper module 306 to the marking module 304 via adjacent inlets in each device. The loading container is moved by the plate on which it is seated along a single plane (xy plane) of the coverslipper to a position within the marking module adjacent to the inlet of the marking module. Once within the marking module, the transfer arm lowers the slide rack into the loading container. The loading container typically contains a solution such as xylene that wets the slides. The loading container then moves in the x-direction plate from the marking module to the coverslipper again via adjacent inlets. A coverslip operation including the placement of a film-type coverslip on individual slides in the slide basket is then performed on the coverslip setter.

[0064] The transport module 302 may be a robotic device capable of transporting a blade between stations. In the embodiment shown in FIG. 4 , the transport module 302 may be a robotic device that includes a conveyor 402 which is a conveyor system for transporting a slide or group of slides horizontally in a loop between the marking module 304/coverslipper module 306, imagers 308, 310, 312, and storage module 314. In this embodiment, the conveyor 402 transports a slide in one direction as illustrated by arrow 403 from the marking module 304 or coverslipper module 306 to the imagers 308, 310, 312 and to the storage module 314 and in an opposite direction as illustrated by arrow 405 from the storage module 314 to the imagers 308, 310, and 312. In one ... 402 may be a conveyor belt or a set of transport pallets arranged in a horizontal plane and dimensioned to transport a blade or group of blades. A conveyor system that is a set of transport pallets may be similar to systems currently used in baggage carousels at commercial airports. Such carousels typically include a deck that is surrounded by support wheel tracks. The support wheel tracks define a path that is often oval in shape. Pallet support members are equally spaced along the wheel tracks. The support wheels are attached to each end of the pallet support members. The support members are configured to be transported along the support wheel tracks by the rolling of the support wheels. The support members are connected to each other at the top by straps that run between the support members. The bottoms are connected to each other by rigid connections. In this way, the support members, support wheels, and straps function in a manner analogous to a train on endless railroads.

[0065] The pallets are attached to the pallet support members. The pallets are designed to overlap one another and are attached to the pallet support members to form a flexible surface. The overlapping configuration of the pallets allows them to slide relative to each other as the pallets move around the corners of the rails. The leading edge of the pallets is attached to the support members by clamps. Each of the pallets may be gently sloped to execute turns in the unit.

[0066] In the embodiment shown in FIG. 4, the conveyor 402 receives a slide from the coverslip module 306 and transports the slide to one of the imagers 308, 310, 312. With reference to the TISSUE-TEK® FILM® coverslip module, the coverslip module 306 individually places a strip of film onto a slide. With the system described with reference to FIG. 4, the slide is then moved to an unloading position in the coverslip module 306 and unloaded onto the conveyor 402 from the coverslip module 306 onto the conveyor 402. An unloading position in the coverslip module may be established at a position downstream of the coverslip operation. Referring to FIG. 4, a slide, such as slide 424, is unloaded onto conveyor 402 in a manner that its length dimension is disposed across a width dimension of conveyor 402. Reader 423, such as an RFID or bar code reader, may be positioned at a discharge point on conveyor 402 or downstream from a discharge point to read an identifier on slide 424. Reader 423 is connected to controller 400 to indicate to controller 400 that slide 424 is on conveyor 402. Once delivered to conveyor 402, conveyor 402 transports slide 424 toward imagers 308, 310, 312.

[0067] As noted previously, in this embodiment, multiple slides are brought to coverslipper module 306 from marking module 304 on a rack. In coverslipper module 306, slides are singulated (separated from other slides on a rack) for coverslip placement. In one embodiment, all of the slides marked in coverslipper module 306 are coverslipped. In another embodiment, a coverslip operation may be skipped. Such skipped may occur at the point of singulation in coverslipper module 306. In accordance with this embodiment, a slide is singulated and either directed to be directly unloaded onto conveyor 402 or to be coverslipped and then unloaded.

[0068] In one embodiment, a blade retaining device is positioned adjacent to or connected to the conveyor 402. The blade retaining device 420, in one embodiment, is an oval-shaped belt or chain (e.g., a continuous loop) having projections 422 extending outwardly therefrom. The projections 422 are spaced apart by approximately one blade width.

[0069] As shown in Figure 4 , the marking module 304, coverslip placing module 306, and imagers 308, 310, 312 are positioned on one side of the conveyor 402. The slide retaining device 420 is positioned on a side of the conveyor 402 opposite the side that includes the marking module 304, coverslip placing module 306, and imagers 308, 310, 312. The projections 422 of the slide retaining device 420 project outwardly in a direction toward the conveyor 402. A length of the slide retaining device 420 is positioned adjacent the conveyor 402 such that the projections 422 extend a distance over the conveyor 402. In one embodiment, the slide retaining device 410 is a synthetic rubber or other plastic material with projections 422 of preferably similar resilient material. The projections 422 have a thickness of 0.5 millimeters (mm) or less, such as 0.25 mm, and a length of 0.5 mm to 1 mm. The blade retaining device 420 projects above the plane defined by the conveyor 402 a distance sufficient to allow a length of projections 422 to be deposited on the conveyor 422 or slightly above (e.g., less than 0.25 mm above) the conveyor 422. In this manner, a blade may be retained on the conveyor 402 between two adjacent projections 422.

[0070] The blade retaining device 420 is rotated by a pulley and moves at the same rate as the conveyor 402. Figure 5 shows a side view of the system of Figure 4 across line 5-5'. As shown in Figure 5, the blade retaining device 420 is connected at one loop end to the pulley 430 and at the other loop end to the pulley 430. The pulley 430 rotates about a shaft 435. The shaft 435 extends a width of the conveyor 402 to an opposite side where a second end of the shaft 435 is connected to the pulley 437. The pulley 437 is connected via a belt to the pulley 440 that drives the conveyor 402.

[0071] As illustrated in Figures 4-6 and 7, slides, such as slide 424, are unloaded from coverslipper module 306 or, optionally, marking module 204 individually and are placed on conveyor 402. Conveyor 402 may be positioned, for example, slightly below outlet port 407 of coverslipper module 306 (and optional outlet port 409 of marking module 304), so that slides are placed onto conveyor 402 by gravity. Ideally, a slide is placed on the carrier 402 between two projections 422 of the slide retaining device 420. However, where a slide is not aligned between projections 422 as the slide exits the coverslip module 306, a force from a projection against an edge of a slide is sufficient to reposition a slide between the projections.

[0072] Conveyor 402 transports a slide to imagers 308, 310, 312. Imagers 308, 310, 312 are, for example, digital imagers and each may additionally contain a reader (e.g., RFID reader, bar code reader) connected to controller 400 for reading an identifier on a slide indicating to controller 400 that a slide is in the imager and for associating a digital image with the identifier. In one embodiment, conveyor 402 stops at each imager and controller 400 assesses the availability of the imager (e.g., receives a signal indicating whether or not an imager is available). If an imager is available and the control system (e.g., controller 400) determines that a slide can be imaged at that time (e.g., the slide is dry), the slide is placed in the imager.

[0073] In one embodiment, a slide is placed in an imager by applying a compressive force to the slide. In this embodiment, associated with each imager 308, 310, 312 and controlled by controller 400 is a set of plungers. 4-7 show a set of plungers 408, 410, and 412 associated with imagers 308, 310, 312, respectively. The set of plungers 408, 410, and 412 is positioned on a side of the conveyor 402 opposite the imagers 308, 310, and 312.

[0074] Each plunger assembly 408, 410, 412 includes an actuator such as an electric motor or air piston that drives a corresponding plunger to extend or retract. A plunger, when activated, moves out of the plunger assembly toward the respective imager. The plunger may be a bar or rod having a thickness equivalent to or greater than a blade thickness. Each plunger assembly is positioned adjacent to the carrier 402 such that when a plunger is extended from a plunger assembly, the plunger will contact a surface of the carrier 402 or extend over the carrier 402 a slight distance (e.g., 0.1 to 0.25 mm). The plunger must be close enough to the conveyor 402 that it is capable of contacting an edge of a blade on the conveyor and compressing the blade away from the conveyor 402 as the conveyor extends. Since the height of the blade retaining device 420 would otherwise prevent a plunger form contacting an edge of a blade, the plunger is made of a material having sufficient weight or density to deflect the blade retaining device 420. For example, a plunger consisting of a steel rod or bar may be made of sufficient weight to deflect the blade retaining device 420 downward from a synthetic rubber belt. In another embodiment, a plunger may extend from a set of plungers at an angle slightly less than horizontal (e.g., less than 5°) such that the plunger deflects the blade retaining device 420 so that it is as parallel as possible with a surface of the conveyor 402.

[0075] If a slide is positioned in front of the (imagers 308, 310, 312) and the imager is available, the plunger will push the slide into the imager. Thus, the plunger is oriented so that it will contact an edge of a slide on the carrier 402. Figure 7 shows an illustration of a slide being pushed from the carrier 402 into the imager 308. Figure 7 shows the plunger 458 moved from the plunger assembly 408 and extending through the carrier 402. Activation of the plunger 458 causes the plunger 458 to contact the slide 424 and push the slide 424 into the imager 308. A cross-sectional view of the imager 308 shows the slide 424 on an imaging stage or platform within the imager 308 and ready for imaging. The sectional view also shows plunger assembly 488 on one side of an imaging stage or platform opposite plunger assembly 488. Plunger assembly 488 is configured to push slide 424 from within imager 308 back over carriage 402 once imaging of slide 475 is complete.

[0076] As noted previously, in one embodiment, the controller 400 is connected to the marking module 304, the coverslipper module 306, the imagers 308, 310, 312, the plunger assemblies 408, 410, 412, which correspond to the plunger assemblies associated with each imager, the storage module 314, and the conveyor 402. In addition to optionally controlling the marking of slides in the marking module 304 and the placement of coverslips on slides in the coverslipper module 306, the controller 400 includes instructions (e.g., a computer program) for controlling the release of a slide from the coverslipper module 306 or, optionally, the marking module 304 onto the conveyor 402 and the movement of the conveyor 402 to bring a slide to the imagers. 308, 310, 312.

[0077] To control the release of a slide onto the conveyor 402 from the coverslip placing module 306, the controller 400 receives data from the coverslip placing module 306 whether a slide is ready for release. In one embodiment, this data is provided to the controller 400 in the form of a signal when a slide is positioned in a designated area on the coverslip placing module 306. The slide may or may not have proceeded from a coverslip placing operation on the coverslip placing module 306. The controller 400 checks to see if a position on the conveyor 402 is free to receive a slide. In the embodiment shown in FIGS. 4-7, the system includes sensor 495 positioned proximately a slide width upstream of exit port 416 of coverslip placement module 306. Sensor 495 may be, for example, a photoelectric sensor that sends a beam of light across a surface of conveyor 402. When the beam is broken, a sensor sends a signal to controller 400 that a slide is present. It will be appreciated that in an embodiment where a slide may be released from marking module 304, a similar technique may be employed with, for example, a sensor similar to sensor 495.

[0078] In one embodiment, the control system stops the conveyor 402 for a brief moment (e.g., three to five seconds) at periodic intervals each time a slide can be positioned in front of an imager. The controller 402 receives a signal if the imager is available to receive a slide for imaging. It may receive the signal in an unsolicited manner (e.g., a sensor associated with the sensor sends a signal if the imager is available) or it may solicit the signal (e.g., the controller sends a signal to a sensor associated with the imager and receives a response to the signal sent from the sensor). If a slide is present on the conveyor 402 and an imager is available, the control system will activate a corresponding set of plungers to place a slide into the imager. Similarly, controller 400 verifies when imaging of a slide is complete and subsequently releases the slide onto conveyor 402. In one embodiment, a sensor, such as a photoelectronic sensor, may be associated with, including connected to or adjacent to, each of plunger assemblies 408, 410, 412 to sense whether a slide is present on conveyor 402 or whether conveyor 402 is free to receive a slide from imagers 308, 310, 312. FIG. 6 shows sensor 496 connected to imager 408. In one embodiment, a corresponding sensor component may be connected to imager 308 directly through sensor 496. Alternatively, a memory associated with controller 400 may track the position of slides on conveyor 402 based on data provided by sensor 495 and coverslip placing module 306 and with From this data, it computes whether the conveyor 402 is free to receive a slide from the imagers 308, 310, 312. The brief stop of the conveyor 402 may also be used to assess whether a slide is on the conveyor 402 upstream of an exit port of the coverslip module 306, such as based on data received from the sensor 495.

[0079] Although plunger assemblies are described for transferring slides between conveyor 402 and imagers 308, 310, 312, it is contemplated that any other type of robotic device suitable for transferring a slide between processing stations may be used. Representatively, a robot arm capable of holding slide 424 and transferring slides between imagers 308, 310, 312 and conveyor 402 may be used. For example, in embodiments where a group of slides is transported within a basket, the slides must be individually removed from the basket for imaging. In this regard, a Gantry or Cartesian coordinate robot, a Selective Compatible Array Robot Arm (SCARA) robot, an articulated arm robot, or a combination thereof (e.g., a SCARA robot coupled to a Gantry robot configuration), may be used to retrieve and deposit individual blades into the basket.

[0080] In one embodiment described with reference to FIGS. 3-7, the marking module 304 and the coverslip module 306 are connected and the slides are conveyed by the marking module 304 to the coverslip module 306 via a commercially available integrated system, although in another embodiment, such conveyance may alternatively be controlled by the controller 400 as part of an overall control system. In another embodiment, the slides may be transferred from the marking module 304 to the conveyor 402 and then conveyed via the conveyor 402 to the coverslip module 306 using, for example, a plunger assembly(ies) as described above or another type of transfer mechanism.

[0081] Figures 4-7 also show conveyor 402 extending into storage module 314. In one embodiment, conveyor 402 has a continuous circle shape with one end of the circle extending into and out of storage module 314.

[0082] Figure 8 illustrates a cross-section of the storage module 314 taken along line 8-8' of Figure 4. In one embodiment, the storage module 314 may include at least one of a drawer, a chamber, a compartment, a cabinet, an enclosure, a cubicle, or the like. A robotic device, such as a transport module 302, may be capable of inserting a slide into the storage module 314 and removing the slide from the storage module 314, for example, via the conveyor 402. The storage module 314 may further include a door that is accessible by the transport module 302.

[0083] In an embodiment where the storage module 314 is a cabinet, the storage module 314 may have a plurality of blade stations 602. Each of the blade stations 602 may be sized to receive and store a blade. In one embodiment, the blade stations 602 are sized to receive and store an individual blade or a group of blades. In the case of a group of blades, the group of blades may be stored in the blade stations 602 in a tray or basket. For example, a tray or basket that holds 10 blades may be stored within one of the blade stations 602. In this aspect, the blade stations 602 are sized to store the tray or basket that has the blades therein.

[0084] In one embodiment, stations 602 may be formed in a grid pattern as illustrated in FIG. 8. Slides stored within stations 602 may be located and retrieved from storage 314 using a classification system that includes, for example, coordinates corresponding to the grid pattern. Representatively, each column may be assigned an identifier and each row may be assigned an identifier different from the column identifiers. For example, the first column starting from the left side of storage module 314 may be assigned the identifier "1" and the first row starting from the top of storage module 314 may be assigned the identifier "A". In this aspect, the location of station 602A may be A1. A slide stored within station 602A may be assigned location A1. When the slide is desired to be retrieved, the system is directed to retrieve the slide at location A1. In other embodiments, the blade stations 602 may be vertically overlapping compartments within the storage module 314.

[0085] The transport module 302 may include one or more elevator devices positioned on the storage module 314 for placing blades into or removing blades from blade stations 602 and transferring blades between blade stations 602 and the conveyor 402.

[0086] The elevator device 614 may be used to move the blade vertically between the conveyor 402 (a y direction with reference to FIG. 4). The elevator device 614 also includes rail member 604 that allows movement of the framing member horizontally in a z direction (with reference to FIG. 4) as illustrated by arrow 606. The elevator device 614 may be positioned between the conveyor belt 402 and the blade stations 602. The elevator device 614 may include the framing member 618 and the elevation member 620 that runs along the framing member 618. A motor and pulley system may be connected to the framing member 618 and the elevation member 620 to drive the elevation member 620 along the framing member 618.

[0087] The elevator device 614 may further include a blade platform 622 positioned within the elevator member 620. The blade platform 622 may be movably coupled to the elevator member 620 so as to elevate the blades horizontally in an x direction to eject the blade or receive the blade within the elevator device 614. The blade platform 622 is sized to receive and retain the blade 624 within the elevator member 620. In one embodiment, the blade platform 622 may be a rectangular shaped box having open ends and of a size configured to contain a single blade (e.g., 1 inch x 1 inch x 3 inches). The blade platform 622 may be at least as wide as the width of the blade so that the blade may be positioned thereon. The blade may be inserted and removed through either side of the blade platform 622. Alternatively, the blade platform 622 may be a planar member (actually a platform) by which the blade may be supported by the blade platform 622.

[0088] The elevator device 614 may be used to transfer the slide 624 between the conveyor 402 and the slide stations 602. Representatively, the conveyor 402 may transport the slide 624, for example, from the coverslip module 306 or the imagers 308, 310, 312, to the slide stations 602. The conveyor 402 moves the slide 624 horizontally in the x-direction until the slide 624 is aligned with the slide platform 622. In this aspect, the lifting member 620 moves vertically in the y-direction along the framing member 618 until the slide platform 622 is aligned with the slide 624. Once the slide platform 622 is aligned with the slide 624, the slide platform 622 moves in the x-direction toward the slide platform 624. to the conveyor 402 until it is positioned about the blade 624. In one or more embodiments, the blade platform 622 may include grippers, claws, nippers, hook-like structures, or other gripping member. The blade platform 622 then moves in the opposite direction (i.e., away from the conveyor 402) with the blade 624 therein. The lifting member 620 raises the blade platform 622 having blade 624 thereon until the blade 624 is aligned with the opening 428 of the blade stations 602. The blade platform 622 then moves in the "X" direction toward the blade stations 602 to insert the blade 624 into the opening of the blade station. Once the blade 624 is within the opening, the blade platform 622 releases the blade 624 and retracts (i.e., moves away from the blade stations 602) thus leaving the blade 624 within the blade stations 602 for storage.

[0089] Once storage is complete, the elevator device 614 may be used to remove a slide 624 from the slide stations 602 and place it back on the conveyor 402 for transport to, for example, the imagers 308, 310, 312.

[0090] Although the elevator device 614 is described for transferring the slide 624 between the conveyor 402 and the slide stations 602, it is contemplated that any other type of robot device suitable for transferring a slide between processing stations may be used. Representatively, a robot arm capable of gripping the slide 624 and transferring the slide 624 between the slide stations 602 and the transport module 302 may be used. For example, in embodiments where a group of slides is transported within a basket, the slides must be individually removed from the basket for imaging. In this regard, a Gantry or Cartesian coordinate robot, a Selective Compatible Array Robot (SCARA) arm robot, an articulated arm robot, or a combination thereof (e.g., a SCARA robot coupled to a Gantry robot configuration) can be used to retrieve and deposit individual blades into the basket.

[0091] As previously discussed, a blade may be inserted and stored at any of the stations 602 that are positioned in a grid pattern. In this regard, the robotic device for inserting and retrieving blades must be capable of moving both vertically in the y-direction and horizontally in the x-direction. To store a blade or retrieve a blade stored at station 602A, the lifting member 620 of the lifting device 614 moves vertically as illustrated by arrow 616 to the top row (e.g., row A) of the storage module 314. The framing member 618 then moves horizontally as illustrated by arrow 606 to the first column (e.g., column 1).

[0092] To store the blade 424 within the station 602A, the blade platform 422 moves in the "z" direction toward the storage module 314 and inserts the blade 424 into the station 602A. Once the blade 424 is positioned within the station 602A, the blade platform 622 moves in a direction away from the storage module 314 leaving the blade 624 behind within the station 602A. To remove the slide 624 from the station 602A, the slide platform 622 is inserted into the station 602A and around the slide 624. Movement of the slide platform 622 away from the station 602A pushes the slide 624 out of the station 602A and into the elevator device 614. The elevator member 620 of the elevator device 614 may then be raised or lowered to transfer the slide 624 to the conveyor 402. The conveyor 402 may then be used to drive the slide 624 to the imager 308, 310, 312.

[0093] The identification, positioning, and removal of a slide within the storage module 314 may be controlled by the controller 400 that is electrically or communicatively connected to the transport module 302. In one or more embodiments, the movement or operation of the transport module 302 may be based on signals exchanged between the controller and the storage module 312. For example, in one embodiment, such a controller may receive a signal from the coverslipper module 306 that indicates that a slide is ready for storage. In response, the controller may signal the transport module 302 to receive the slide from the coverslipper module and transfer the slide to the storage module 314. A reader (e.g., an RFID or barcode reader) may be positioned at the inlet to the storage module to read an identifier associated with the slide. This information is transmitted to the controller 400. The controller may identify an open slide station within the storage module 314 and signal the transport module 302 to insert the slide into the open slide station. The slide location information may be stored by the system. In one embodiment, the slide location may be selected based on a criterion such as patient case, physician or hospital, storage term, etc. When it is desired to retrieve the slide, for example, where a pathologist instructs the system to perform additional imaging of the slide, the controller 400 may determine the location of the desired slide and signal the transport module 302 to retrieve the slide from the appropriate slide station within the storage module 314.

[0094] Figure 9 illustrates a perspective view of the storage module and elevator device of Figure 8. From the view in Figure 9, it can be seen that the elevator member 620 slides vertically along the track 702 formed in the elevator member 620. In this aspect, the elevator member 620 may have protrusions along its outer surface that align with and may be engaged within the track 702. Similarly, the track member 604 includes rails 704 along which the framing member 618 slides.

[0095] Figure 8 and Figure 9 depict a storage module in connection with slide storage. In another embodiment, a storage module is configured to store slides as well as tissue blocks (e.g., tissue blocks containing an identifier tag). In another embodiment, the system includes storage module 202 for storing slides and a separate storage module for storing tissue blocks. A storage module for storing tissue blocks may be configured similarly to storage module 314, including an identifier reader, and coupled to controller 400. In either embodiment, controller 400 is configured to store slide and tissue block information so that a slide(s) may be linked to a tissue block. Figure 4 shows the microtomy module 307 adjacent to the conveyor 402. The microtomy module may include block processing equipment that includes a microtome and an identifier reader connected to the controller 400. In one embodiment, the tissue block may be loaded onto the conveyor 402 from the microtomy module 307 (or unloaded from the conveyor 402 to the microtomy module 307) or loaded/unloaded from the storage module 314 to the conveyor 402 or vice versa similar to the methods discussed previously for loading/unloading slides.

[0096] An automated system for transporting slides between processing stations is described. One skilled in the art will appreciate that the present invention may be practiced by other than the preferred embodiments that are presented in this disclosure for purposes of illustration and not limitation, and the present invention is limited only by the claims that follow. It is noted that equivalents to the particular embodiments discussed in the disclosure may likewise practice the invention. Representatively, in one embodiment, a "Reflex Labeling" procedure may be implemented. In this procedure, the system recommends specific labeling and/or testing of biological samples based on pattern recognition reports from an interpretation module. The reflex labeler may include a labeling system, the imager, and the interpretation module, which are grouped together and implemented as a single automated instrument. Alternatively, they may be in separate instruments at different locations. Processing can be performed by instruments both inside and outside reflex marking, such as, for example, in growth, processing and embedding, microtomy and marking, and coverslipping.

[0097] In some embodiments, the above-described transport module may be deployed in connection with tissue block processing. Representatively, a tissue sample, which has potentially been received and/or fixed in a paraffin block, may be transported by the transport module between a microtome, imager, and storage module. For example, the block having the tissue embedded therein and an identifier may be divided by the microtome and then transported to the storage module. If, upon examination of the tissue section, it is determined that another tissue section is needed, a controller may signal the transport module to remove the block from the storage module and transport it back to the microtome for further division.

[0098] One or more embodiments of the invention may be provided as a program product or other article of manufacture which may include a machine-readable computer medium having stored thereon one or more instructions. The medium may provide instructions, which, if executed by a machine, such as a robot or integration unit, may result in and/or cause the machine to perform one or more of the operations or methods described herein. Suitable machines include, but are not limited to, robots, integration units, computer systems, laboratory equipment, and a wide variety of other machines, to give but a few examples. Representatively, the medium may include recordable media, such as, for example, floppy disk, optical storage medium, optical disc, CD-ROM, magnetic disk, magnetic-optical disk, read-only memory (ROM), programmable ROM (PROM), erasable programmable ROM (EPROM), electrically erasable programmable ROM (EEPROM), random access memory (RAM), static RAM (SRAM), dynamic RAM (DRAM), Flash memory, other types of memory, other types of machine-readable media within programmable logic units used to control robots, and combinations thereof.

[0099] It should be understood that reference throughout this specification to "a (numeral) embodiment," "an (indefinite article) embodiment," or "one or more embodiments," for example, means that a particular feature may be included in the practice of the invention. Similarly, it should be understood that in the description, several features are sometimes grouped together in a single embodiment, figure, or description thereof for purposes of simplifying the description and aiding in the understanding of various inventive aspects. This method of description, however, should not be construed as reflecting an intent that the invention requires more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive aspects may not be found in every feature of a single described embodiment. Accordingly, the claims that follow the Detailed Description are expressly incorporated herein into the Detailed Description, with each claim standing on its own as a separate embodiment of the invention.

[00100] In the foregoing specification, the invention has been described with reference to specific embodiments thereof. It will, however, be apparent that various modifications and changes may be made thereto without departing from the broader spirit and scope of the invention as set forth in the appended claims. The specification and drawings are therefore to be considered in an illustrative rather than a restrictive sense.

Claims (23)

1. Apparatus comprising a marking module (210, 304), a coverslip module (220, 306), an imaging module (230, 308, 310, 312) and a storage module (202, 314), characterized in that it comprises: an automated transport module (302) for transporting a slide between the marking module and the coverslip module, the imaging module and the storage module; and a controller (400) for directly transporting the slide through the transport module (302); wherein the controller (400) is operable to determine whether the imaging module (230, 308, 310, 312) is available and to direct transport of the slide to the storage module (202, 314) when the imaging module (230, 308, 310, 312) is unavailable or the slide is not ready for imaging. 2. The apparatus of claim 1, wherein the storage module (202, 314) comprises an indexing system for identifying a location of the blade within the storage module (202, 314). 3. The apparatus of claim 1, wherein the storage module (202, 314) comprises a plurality of blade storage stations (602). 4. Apparatus according to claim 1, characterized in that the transport module (302) comprises a conveyor (402). 5. Apparatus according to claim 4, characterized in that the transport module (302) comprises a conveyor (402) configured for bidirectional transport. 6. Apparatus according to claim 1, characterized in that the imaging module (230, 308, 310, 312) comprises a plurality of imaging modules. 7. Apparatus according to claim 1, characterized in that the imaging module (230, 308, 310, 312) is a charge-coupled device (CCD). 8. The apparatus of claim 1, wherein the controller (400) comprises machine-readable instructions that, when executed by the controller (400), cause a slide to be disposed in the imaging module (230, 308, 310, 312) when the imaging module (230, 308, 310, 312) is available to receive a slide. 9. The apparatus of claim 1, wherein the imaging module controller (400) comprises machine-readable instructions that, when executed by the controller, cause a slide to be retrieved from the storage module (312) and transported to the imaging module (230, 308, 310, 312). 10. The apparatus of claim 1, wherein the imaging module and storage module (312) are a slide storage module, wherein the apparatus further comprises a tissue block storage module. 11. Apparatus according to claim 10, characterized in that the imaging module, the slide storage module and the tissue block storage module are integrated. 12. The apparatus of claim 10, wherein the imaging module controller (400) comprises machine-readable instructions that, when executed by the controller, cause the controller to retrieve a tissue block from the tissue block storage module. 13. A method comprising the following steps: processing a slide having a biological specimen on it; automatically determining whether an imaging module (230, 308, 310, 312) is available for imaging the biological specimen on the slide; transporting the slide to the imaging module (230, 308, 310, 312) using an automated transport module (302) when it is determined that the imaging module is available (230, 308, 310, 312); and transporting the slide to a storage module (202, 314) using the automated transport module (302) when it is determined that the imaging module (230, 308, 310, 312) is not available. 14. Method according to claim 13, characterized in that the processing comprises marking the biological specimen on the slide. 15. The method of claim 13, wherein the processing comprises applying a coverslip to the slide. 16. The method of claim 13, wherein the imaging module (230, 308, 310, 312) is a first imaging module and the determination further comprises: determining whether a second imaging module is available; and determining whether a third imaging module is available when the first imaging module and the second imaging module are not available. 17. The method of claim 16, wherein the transport comprises transporting the slide to the second imaging module or to the third imaging module using the automated transport module (302) when the first imaging module is not available. 18. The method of claim 13, further comprising: transporting the slide from the storage module (202, 314) to the imaging module (230, 308, 310, 312) using the automated transport module. 19. The method of claim 13, further comprising indexing a location of the blade within the storage module (202, 314). 20. The method of claim 13, further comprising: imaging the biological specimen on the slide as the slide is transported to the imaging module (230, 308, 310, 312); and transporting the slide to the storage module (202, 314) using the automated transport module (302) after imaging. 21. The method of claim 20, further comprising: transporting the slide from the storage module (202, 314) to the imaging module (230, 308, 310, 312) using the automated transport module (302) for further imaging. 22. The method of claim 13, further comprising placing the slide in the imaging module (230, 308, 310, 312) when the imaging module is available; and obtaining a digital image of the biological specimen on the slide. 23. The method of claim 13, further comprising: retrieving a tissue block from the storage module (202, 314); and transporting the tissue block to a microtomy module (307).