US20060063265A1 - Advance programmed sample processing system and methods of biological slide processing - Google Patents

Advance programmed sample processing system and methods of biological slide processing Download PDF

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Publication number
US20060063265A1
US20060063265A1 US10/539,035 US53903505A US2006063265A1 US 20060063265 A1 US20060063265 A1 US 20060063265A1 US 53903505 A US53903505 A US 53903505A US 2006063265 A1 US2006063265 A1 US 2006063265A1
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Prior art keywords
automated
sample processing
parameter
automated sample
input
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Rosanne Welcher
Marc Key
Gorden Feingold
Doug Sweet
John Favuzzi
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Dako Denmark ApS
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DakoCytomation Denmark AS
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Assigned to DAKOCYTOMATION DENMARK A/S reassignment DAKOCYTOMATION DENMARK A/S ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: WELCHER, ROSANNE, FAVUZZI, JOHN, KEY, MARC, SWEET, DOUG
Assigned to DAKOCYTOMATION DENMARK A/S reassignment DAKOCYTOMATION DENMARK A/S ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: WELCHER, ROSANNE, FAVUZZI, JOHN, KEY, MARC, SWEET, DOUG
Assigned to DAKOCYTOMATION DENMARK A/S reassignment DAKOCYTOMATION DENMARK A/S ASSIGNMENT OF ASSIGNORS INTEREST (SEE DOCUMENT FOR DETAILS). Assignors: FEINGOLD, GORDON
Assigned to DAKO DENMARK A/S reassignment DAKO DENMARK A/S CHANGE OF NAME (SEE DOCUMENT FOR DETAILS). Assignors: DAKOCYTOMATION DENMARK A/S
Publication of US20060063265A1 publication Critical patent/US20060063265A1/en
Abandoned legal-status Critical Current

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Definitions

  • This application relates to the field of sample processing systems and methods of entering information for the processing of samples.
  • the present invention may be directed to the automated processing, treatment, or even staining of samples arranged on carriers, such as slides, and in some embodiments, directed to the continuous or batch processing of samples and carriers.
  • Embodiments may further relate to control systems for sample processing and data input, acquisition, maintenance, and retrieval for sample processing.
  • Applications to which the present invention may especially relate include immunohistochemistry, in-situ hybridization, fluorescent in-situ hybridization, special staining, and cytology, as well as potentially other chemical and biological applications.
  • Sample processing in immunohistochemical (IHC) applications and in other chemical and biological analyses may require one or a number of various processing sequences or protocols as part of an analysis of one or more samples.
  • the sample, processing sequences or protocols may be defined by the individual or organization requesting an analysis, such as a pathologist or histologist of a hospital, and may be further defined by the dictates of a particular analysis to be performed.
  • a biological sample may be acquired by known sample acquisition techniques and may comprise, for example in IHC applications, tissues generally or even in some applications one or a plurality of isolated cells, such as in microarray samples, and may be presented on a sample carrier including but not limited to microscope slides. Furthermore, the sample may be presented on the carrier variously and potentially in some form of preservation. As one example, a sample such as a layer or slice of skin may be preserved in formaldehyde and presented on a carrier with one or more paraffin or other chemical layers infiltrating the sample.
  • Immunologic applications may require processing sequences or protocols that comprise steps such as deparaffinization, target retrieval, reagent application, and staining, especially for in-situ hybridization (ISH) techniques.
  • steps such as deparaffinization, target retrieval, reagent application, and staining, especially for in-situ hybridization (ISH) techniques.
  • ISH in-situ hybridization
  • these steps may have been performed manually, potentially creating a time-intensive protocol and necessitating personnel to be actively involved in the sample processing.
  • Even when performed automatically there have been inefficiencies in such systems. Attempts have been made to automate sample processing to address the need for expedient sample processing and a less manually burdensome operation.
  • such previous efforts may have not fully addressed certain specific needs for an automated sample processing system.
  • Previous efforts to automate sample processing may be deficient in several aspects that prevent more robust automated sample processing, such as: the lack of sufficient computer control and monitoring of sample processing; the lack of information sharing for processing protocol and processing status, especially for individual samples; the lack of practical information input and process definition entry capabilities; the lack of diagnostic capabilities; and the lack of real-time or adaptive capabilities for multiple sample batch processing.
  • the present invention presents an automated sample processing system that greatly simplifies and make extremely more practical the functions of inputting information for automated sample processing.
  • sample processing can be accomplished as disclosed herein.
  • the various examples and designs disclosed for sample processing and other disclosed techniques are not meant to limit the present invention to any particular embodiment, whether apparatus, method, or otherwise. These descriptions are provided rather to describe various sample processing techniques in a manner in which the present invention can be understood. The descriptions incorporated by reference and the various examples should not be construed to limit the present invention to only such techniques. This disclosure, however, may be understood to incorporate the various techniques in the context of the various embodiments of the present invention.
  • the techniques and systems of sample processing are addressed in a fashion that may provide the processing of one or more samples or of a plurality of groups of one or more samples in sequential or non-sequential fashion. Processing of samples may be determined by the protocol to be followed for each sample or a protocol for multiple samples. Aspects of the present invention may be especially applicable to sample processing having one or a plurality of processing steps to be performed on one, a portion, or an entirety of samples, such protocols identified in some instances by individual carriers presenting the samples or by the individual samples themselves.
  • the present invention may be especially applicable to immunohistochemistry (IHC) techniques, as well as in-situ hybridization (ISH) and fluorescent in-situ hybridization (FISH), special staining of samples, and microarrays; especially techniques incorporating target retrieval or the staining of samples.
  • IHC immunohistochemistry
  • ISH in-situ hybridization
  • FISH fluorescent in-situ hybridization
  • embodiments may be directed to processing sequences addressing issues of processing control.
  • Embodiments of the invention may further relate to automated control systems for sample processing.
  • Embodiments may also be directed to data acquisition, input, maintenance, and retrieval for sample processing, as well as information sharing of processing protocol and processing information, and real-time or adaptive capabilities for processing.
  • the invention may comprise an automated sample processing system comprising a plurality of drawers, a plurality of sample carrier elements that may even be each removably configured with one of the drawers, and an adaptive or other sample processing control system.
  • the sample carriers may be both movable and removable.
  • the sample processing control system may automate the sample processing system such that one or more samples may be processed according to one or more protocols, potentially indicated by information on slides or otherwise input to the system.
  • This sample processing may comprise one or more sampling protocols and steps, such as deparaffinization, target retrieval, and staining.
  • a sensor may be provided in some embodiments that may automatically identify information from one or more samples, sample carriers, or slides.
  • protocol information may be provided or made available by the sample processing control system.
  • the sample processing system may then process one or more samples or perhaps slides, or one or more batches of slides, concurrently, sequentially, or in any other temporal fashion, potentially in accordance with protocol information previously provided for a sample by a user or other decision maker. This information can then be made available for use by the sample processing control system. Sample batches or individual slides may even be inserted or removed during processing protocol steps by the control and monitoring accomplished by the adaptive sample processing control system.
  • Another embodiment of the present invention may achieve the foregoing and other objects of invention may comprise a method of sample processing, comprising the steps of: accessing at least one of a plurality of samples or sample drawers, providing at least one sample carrier or perhaps a sample carrier retainment assembly configured with at least one sample, configuring at least one of the drawers with the at least one sample carrier, and adaptively processing the sample.
  • the step of processing or perhaps even adaptive processing may be applied to automate the processing of samples and may allow for either or both continuous or batch processing of samples or slides. It may also afford multiple independent sample or slide processing and in some embodiments slide processing to process each slide independently.
  • Embodiments of the invention may further comprise a method of automated sample processing, comprising the steps of: acquiring or accepting or accessing information such as protocol information, transmitting such information to at least one sample processing system or even a stand alone processing system, and processing samples. Furthermore, embodiments may provide: for handling, maintaining, sharing, and using the sample processing information. These and other aspects may be provided for individual samples or multiple batch processing, and in a real-time manner. It may also be accomplished in and adaptive manner, perhaps for multiple batch processing or the like.
  • IHC immunohistochemistry
  • ISH in-situ hybridization
  • FISH fluorescent in-situ hybridization
  • embodiments are directed to processing sequences addressing issues of processing control, and may be particularly applied to slide processing systems.
  • FIG. 1 is a depiction of an embodiment of an overall system incorporating some of the features of the invention.
  • FIG. 2 is a depiction of an embodiment of a portion of a sample carrier assembly of one embodiment of the invention.
  • FIG. 3 is a depiction of an embodiment of a robotic movement aspect of one embodiment of the invention.
  • FIG. 4 is a flow chart of some representative process steps of an embodiment of the invention.
  • FIG. 5 is a block diagram of an embodiment of the invention.
  • FIG. 6 is a depiction of an embodiment of a device incorporating some of the features of the invention.
  • FIG. 7 is a depiction of an embodiment connecting one stainer with one manager & database and one label printer.
  • FIG. 8 is a depiction of an embodiment connecting multiple stainers with multiple managers and multiple label printers.
  • FIG. 9 is a depiction of an embodiment connecting a system to a lab network and lab information system.
  • FIG. 10 is a block diagram showing some of the internal software features.
  • FIG. 1 shows one embodiment of a sample processing system 101 in accordance with the present invention.
  • the sample processing system 101 is configured to achieve an appropriate sequence of events that achieves a desires result to some degree. In achieving this sequence in an automated fashion to some degree the sample processing system is deemed an automated sample processing system and achieves automatic processing of at least one sample.
  • This automated sequence may be controlled by hardware, software, or some combination of them to accomplish a desired sequence with limited human intervention. Regardless how achieved, the automated control is provided by a process operation control system 171 to direct the various activities. As shown in FIG. 10 , this (as well as other functionalities discussed) may be software programming or subroutines; again, it may also include hardware or the like.
  • the sample 198 processed may be any material, but is most likely a biologic material such as a biological sample or a biological specimen, perhaps such as a histological sample, e.g. tissue and cell specimens, cells, collections of cells, or tissue samples, the definition to include cell lines, proteins and synthetic peptides, tissues, cell preps, cell preparations, blood, bodily fluids, bone marrow, cytology specimens, blood smears, thin-layer preparations, and micro arrays. It should also be understood to include slide-based biological samples. As used, a sample may be arranged on a carrier element 197 such as a slide or the like that may maintain the sample's position or integrity. The carrier element 197 may be configured to move and thus reposition the sample 198 . As such, it may be considered a movable carrier element. In processing a slide, the automated sample processing system may serve as an automated slide processing system.
  • a biological sample or a biological specimen perhaps such as a histological sample, e.g. tissue
  • a particular design may include cabinet sections 102 that may form outer portions of the system and serve to address general structural considerations of the system (a top cabinet section is not shown in FIG. 1 ).
  • the sample processing system may also comprise a plurality of drawers 104 used for the handling and processing of samples and sample carriers such as slides, potentially microscope slides. Other sample carriers may be accommodated consistent with the present invention.
  • Each drawer may be configured to accommodate carrier retainment assemblies that hold one or, most likely, a number of the particular carriers, slides, or samples involved.
  • the carrier retainment assembly serves as a slide retainment assembly 106 .
  • a slide retainment assembly 106 is shown in FIG. 2 .
  • the slide retainment assembly, and indeed the generic carrier retainment assembly may comprise a slide rack, module, or a number of magazines.
  • the slide retainment assembly 106 may be configured to accommodate a plurality of slides in at least one configuration in corresponding sample carrier retention devices 108 .
  • the sample carrier retainment assemblies are utilized in the processing of samples as further described below. It should be further noted that the sample carrier retainment assembly can be removably configured with the drawers 104 , and may be stackable or nested within other retainment assemblies.
  • the general sample processing system 101 and even one or more drawers 110 in the sample processing system 101 may accommodate processing materials such as reagent containers 199 for sample processing, also further described-below.
  • a processing material retainment assembly such as a container rack 111 , shown in FIG. 1 , may be utilized to accommodate reagent containers 199 or other processing materials within each of drawers 110 .
  • Bottle inserts may be preferably configured with the retainment assembly to ensure proper processing material positioning within the processing material retainment assembly and the drawer.
  • Multiple drawers 104 may be included to allow for one or a plurality of sample processing protocols to be performed by the system 101 .
  • Past efforts at sample processing may have been limited to processing sequences for an entire batch of carriers within the system.
  • the present invention in part by providing a plurality of drawers and carrier retainment assemblies, may allow for individual, batch, or multiple batch processing, including real-time or adaptive capabilities, as further described below.
  • Indicator elements 112 may be provided to indicate a status of the drawers and the carriers or materials within each drawer for an operator of the system.
  • visual indicators such as light emitting diodes in preferred embodiments, may be used to indicate if a drawer is available during operation of the sample processing system, and may indicate conditions such as a locked or open condition of a corresponding drawer, carrier capacity status of the drawer or of a carrier retainment assembly within the drawer, and chemical status of the sample processing system, such as reagent loading status or capacity.
  • a warning indication may be given by these or other indicator elements, as well as other indicative signals.
  • One or a plurality of sensors may be utilized to determine the status of the drawer as indicated by the indicator elements 112 and to further provide processing status as further described below.
  • a processing material unit may be utilized to provide various processing material to the sample processing system 101 and to afford the segregation of waste produced during sample processing and the avoidance of cross-contamination.
  • the processing material unit may be configured to accommodate one or a plurality of containers such as deparaffin solution or other material utilized in sample processing.
  • the unit may also accommodate waste containers to provide for the collection of waste material from the sample processing.
  • Tubing or other fluid transmission elements may be connected with the containers and the sample processing system 101 .
  • Tubing or other fluid transmission elements may also be connected with the waste containers and the system 101 .
  • embodiments of the present invention may include robotic sample process functions or a robotic motion system 172 responsive to the process operation control system 171 to achieve the desired operation steps.
  • This may further comprise an arm 120 utilized in sample processing, potentially having robotic movement, and in some embodiments, Cartesian movement.
  • the arm 120 may comprise, in some preferred embodiments, one or more elements, such as an actuator probe 122 , a syringe or probe 124 , a sensor element and a non-discrete or other volume fluid and/or air applicator.
  • the actuator probe may be utilized in the configuration and manipulation of the carriers in sample processing, further described below.
  • the actuator probe 122 configures and manipulates the configuration of slides in the sample carrier retention devices 108 by actuation of carrier adjustment element 130 (see for example FIG. 2 ), and in some embodiments, by contact with the slides.
  • carrier adjustment element 130 see for example FIG. 2
  • manipulation or movement of the slides or the samples may be accommodated. This movement may result in a horizontal or vertical configuration of the slides to facilitate sample processing as described below.
  • arm 120 may comprise syringe 124 .
  • the syringe 124 may be considered a probe in some embodiments, depending upon the requirements of protocols to be performed.
  • Syringe 124 may be fluidically connected with and may apply one or more of the following: rinse agents, such as water; containers, potentially removably fluidically connected for the aspiration of reagents, such as aspiration of reagents from containers and to the samples presented with the carriers; and blow off or other removal agents such as an air source.
  • Syringe 124 may be utilized to pierce processing material containers such as reagent containers.
  • a reservoir may be provided with the arm 120 to allow for various volumes to be aspirated by the syringe 124 . The unique configuration of the reservoir allows for efficient cleaning and drying of the internal portions of the syringe while allowing for the accurate pipetting or otherwise aspiration of a wide range of volumes.
  • Arm 120 may, in some preferred embodiments, comprise a sensor element
  • the sensor element may be used to automatically determine location and other status information of components of the sample processing system, such as reagent containers, or other processing material containers, or sample carriers. This may be used to teach the system proper and/or actual locations, and to calibrate, self-calibrate, or self-align the system, or the like.
  • the sample processing system 101 may include an automatic slide identification element. This may be controlled to achieve the act of automatically identifying said plurality of slides. This may also be more generic such as there may be some type of sensor element and it may even comprise a reader or scanner, such as a CCD camera, utilized to determine status information of processing materials, such as reagents as well as to identify slides.
  • the sensor element may read, detect, or otherwise determine information in the sample processing system 101 , for example, from processing material containers, such as, for example, reading a code provided on the container to determine reagent type and reagent location within the system.
  • the sensor element may also determine status information of sample carriers.
  • slides configured with a slide retainment assembly may be provided with informational indicia, such as a code, that may indicate information about the sample presented on the slide or the processing protocol to be performed.
  • the sensor element may read the code of the slide to determine the protocol to be performed for the particular slide and sample.
  • a cleaning station 140 may be included to clean one or more elements of arm 120 , and in preferred embodiments, may function to clean or otherwise sterilize syringe 124 .
  • the cleaning station 140 may be configured to allow a drop off and pick up of elements such as syringes for cleaning while allowing the processing throughput of the sample processing system to continue.
  • the syringe may be sterilized, for example, with a water rinse through the syringe while the syringe is positioned at the cleaning station.
  • the cleaning station may be configured to clean or otherwise sterilize elements of arm 120 , such as syringe 124 , while such elements are configured with arm 120 .
  • multiple probes or syringes may be used to apply fluids required for the staining of histological tissues samples mounted or otherwise presented on slides. This may encompass automatic staining accomplished through a slide stain element such as the items included on the robotic motion system 172 discussed above.
  • the sample processing system may drop off a “dirty”, contaminated, or used probe or syringe and swap it for a “clean”, uncontaminated, sterilized or an unused one.
  • One or more probes or syringes may be cleaned while the system continues processing of samples, such as applying reagent or stain with an alternate probe or syringe.
  • the system may access, use and wash multiple probes or syringes for pipetting or otherwise aspirating fluids required for the staining of samples mounted or otherwise presented on slides.
  • a system with a single reusable probe may wash the probe between each fluid applied.
  • the task of washing the probe can have a large impact on the throughput of the overall system.
  • the present invention may allow for multiple probes to be available to the system for use.
  • the system may continuously have a clean, uncontaminated, sterilized, or an unused probe available to use and sample processing is not impacted by the required cleaning routine.
  • the cleaning routine may be necessary to eliminate the possible cross contamination of fluids and, in some embodiments, may take up to about 1 minute to accomplish.
  • the cumulative impact of the cleaning routine on a series of processing steps can add time to the throughput capabilities of the system.
  • the addition of multiple probes or syringes may eliminate this impact and significantly decreases the time required to process the samples.
  • Embodiments of the present invention may comprise a mixing station 150 , shown in FIG. 1 .
  • the system may mix component fluids, such as dyes, buffers, or other processing materials, preferably on demand and as the processing steps and protocols dictate. Fluids required during the processing steps may sometimes need to be mixed with other fluids to create a final activated fluid. However, the activity levels of these mixtures can be time sensitive and may therefore only be effective for a short period of time.
  • the on demand mixing of fluids is advantageous in that it allows the fluids to be mixed immediately before being used.
  • the syringe or probe 124 in preferred embodiments, will aspirate fluids into and from the mixing station 150 to mix component fluids. A rinse may further be dispensed into the mixing station to sterilize the station.
  • slides are movable and configurable in both vertical and horizontal positions as required for the pretreatment and staining process. This allows for the automation of the pretreatment and staining of slides in various manners, including pretreatment and staining as accepted in conventional manual laboratory methods.
  • the slides are initially loaded into the carrier retention assemblies, such as slide racks, and drawers in the horizontal position. If pretreatment is required, such as deparaffinization, the system rotates the slide into the vertical position and lowers these samples into a processing tank, further described below, filled with the required fluids. In some embodiments, the slide rack is lowered to affect lowering of the slides (see FIG. 2 ).
  • the System rotates or moves the slide to the horizontal position and a syringe or probe applies fluid to the sample, providing a horizontal staining of the sample.
  • a syringe or probe applies fluid to the sample, providing a horizontal staining of the sample.
  • Each slide can be rotated independently allowing for the independent processing of different samples with different requirements.
  • a processing tank may be provided.
  • components of each processing tank may be configured within a drawer 104 .
  • the fluids volume needed to perform pre-treatment processes are maintained but instead of the slide orientation with each other being face-to-face, as in conventional systems, they are side-to-side, although other slide configurations are not disclaimed.
  • the processing tanks provide even distribution of fluids across the face of the slide.
  • the processing tanks have the ability to heat the slides. Heat may also be applied to each individual slide by a thermal device. The precision and physical application of the heat can result in standardization and repeatability of process steps. Filling and heating tasks are performed by a computer controlled scheduler, as further described below. Fluid volume may be adjusted to account for the presence or absence of any number of slides.
  • the individual fluids used for pretreatment may be contained in the system cabinet.
  • Deparaffinization fluids except DI water
  • Containers are as listed for fluids one through six.
  • the “clean” containers may be moved up to the dirty position, and then fresh fluid added to clean position.
  • DI water may be drawn from the large system DI water container, and discarded after each use.
  • Target retrieval solution may be drawn from dedicated containers, and may be recycled or discarded after each use.
  • an imaging device such as an image-capture 2 -D optical sensor, perhaps a CCD camera, may be used to determine the position of the sample on the slide, providing for greater accuracy during sample processing.
  • Embodiments of the sample processing system 101 may further provide sample diagnostic capabilities. Accordingly, in some embodiments, a device may analyze samples. A camera may be used for diagnostic purposes. In some embodiments, the sample may be scanned for further analysis, potentially by computer. The camera can also be used 1) as an area locator, 2) to locate a tissue area, 3) to apply reagent based on location and area. The scanned image may be analyzed for reagent analysis or other analyses.
  • the processing of samples may be accomplished according to some preferred embodiments as shown in FIG. 4 and consistent with features of the present invention. Variants of these protocols and processing steps, or other processing steps, may be accomplished consistent with the present invention.
  • One processing sequence may broadly comprise the pre-processing of a sample, if needed, such as deparaffinization (as previously described), and further comprise target or epitope retrieval (as previously described), and sample staining.
  • ISH in-situ hybridization
  • Embodiments of ISH may require a small volume of agent, such as 15 microliters, to be placed on the sample. Heat control may be maintained between about 95-100 C and kept constant for a period of time. Temperature may then be lowered in a controlled manner.
  • fluorescent staining or tagging in IHC or ISH may be performed consistent with the features of the present invention.
  • the sample processing system may automate the processing of samples mounted on carriers or slides.
  • This configuration of the system allows for the flexibility for both continuous, individual, and batch processing of slides with the design lending itself to meet established laboratory workflow demands.
  • the multiple independent and redundant slide processing subsystems found within the system may also maintain its ability to process each slide independently.
  • the automatic processing may be achieved by designing a system with automated process operation capability or sequencing through at least some steps without human intervention that may be controlled by or act in response to a process operation control system 171 .
  • the user needs the ability to specify the nature and sequence of the various steps or acts desired.
  • This can be accomplished by an input parameter capability 173 through the inclusion of even a sample process parameter input 173 .
  • This input can be retained by the creation of stored parameter process data 174 .
  • the input parameter capability 173 may be configured as an independent process parameter input with respect to the process operation control system 171 , such that acts caused by the process operation control system 171 are unaffected by any action with respect to the independent process parameter input.
  • the input parameter capability 173 may also be configured as an autonomous input functionality through the inclusion of an autonomous input element.
  • the input parameter capability 173 may not only act independent of the automated process operation capability, but it may be fully functional even without the presence or operability of the automated process operation capability (which itself may or may not be in a process device). This may be achieved in a variety of manners, including by providing a separate full function computer 181 (e.g., separate from the capability provided or required by a process system) or that may be programmed to accomplish the input
  • the input parameter capability 173 may be configured to provide a simplified entry parameter input functionality or as a simplified entry parameter input element.
  • the input element such as hardware or software may be configured to accept a variety of information, such as, but not limited to: inputting at least some individual slide process information through inclusion of an individual slide process-information input element, inputting at least some group slide process information through inclusion of a group slide process information input element, inputting at least some slide identification information through inclusion of a slide identification element, inputting at least some preferred stainer information through inclusion of a preferred stainer information input element, inputting user operation information through inclusion of a user information input element, inputting patient identification information through inclusion of a patient identification input element, inputting HIPPA-compliant identification information through inclusion of a HIPPA-compliant identification input element, inputting coded identification information through inclusion of a coded identification input element, inputting internal identification information through inclusion of an internal identification input element, inputting process protocol information through inclusion of a process protocol information input element, inputting at least some process scheduling information through inclusion of a process scheduling information input element, inputting at least some process sequence information through inclusion of a process sequence information input element, inputting at least some process schedule
  • the slide identification information may represent any information unique to a particular slide, such as a serial number, patient number, patient name, unique image, or the like. In keeping with privacy concerns, there may also be coded identification information or internal identification information that others cannot use to identify the particular patient involved or the like.
  • the overall system may include a number of stainers and thus the input can include preferred stainer information (which may or may not be indicated or accepted by the automated system). Provision can also be included to achieve a rushed test and as such there may be a stat process request information element. Such may also be linked with a user privileges information so that only certain individuals may displace other tests to create a different priority. Of course all permutations and combinations of the above may be included.
  • the input may create data such as parameter process data 174 that may be stored at some location.
  • it may be independently stored perhaps in a physically independent memory even at a location remote from an actual stainer itself. This may be accomplished by utilizing a primary or secondary storage perhaps of a separate full function computer programmed or configured to accept and/or store data. In such a fashion, the computer may contain what could be considered as an independent process parameter memory 174 . Since the computer is likely physically separate, it may be considered to have a physically independent memory perhaps even a remote location memory if it is remote from the process equipment.
  • the system may facilitate full operational functionality of the automated process operation capability. Since the automated process operation capability is fully operational during operation of either the memory or input, the storing or inputting or other function can be conducted without interrupting the process operation. Thus the inputs can be later accessed at a process time independent of the time of accomplishing slide process parameter input or storing. In addition, entry or storing may also be accomplished at least in part concurrently with the processing of certain samples. This processing may even be initiated significantly after completion of the slide process parameter input action. Such may occur at least about one hour after the input, at least about three hours after the input, at least about eight hours after the input, at least about one day after the input, at least about two days after the input, and at least about one week after the input.
  • the system may be comprised of independent or perhaps redundant slide staining modules (some embodiments may comprise eight modules) as shown for some embodiments in FIGS. 1 and 6 .
  • Throughput may be based on the time to first result with the system allowing access to completed slides as soon as a staining module has completed the scheduled staining tasks.
  • the multiple independent or redundant staining modules may allow for both continuous and batch processing of slides. Additionally, each independent staining module may also allow for the independent pre-treatment and staining of each slide.
  • a carrier retainment assembly such as a slide retainment assembly, may be used to introduce slides to be processed into the drawer 104 , the drawer, slide retainment assembly, and components thereof forming a stain module.
  • the slides may occupy one or more positions of the slide retainment assembly, such as at carrier retention devices, up to the capacity of the slide retainment assembly with the potential for each slide being processed independently of other slides configured with the slide rack.
  • Embodiments of the stain modules, drawers, slide racks, and components thereof are also shown in FIG. 6 .
  • FIG. 6 also provides other embodiments of system features, such as an embodiment of the arm 120 and the component features of the arm.
  • Slide retainment assemblies having one or more slides may be introduced into the staining modules by introduction into drawers 104 one at a time or in any combination until all or an appropriate number of staining modules are appropriately occupied. There may be no restrictions as to the order, number or timing of when the slide retainment assemblies are introduced into the system, the system may also allow for adaptive scheduling of sample loading. Staining modules, and in some embodiments the drawers of the staining modules, may lock out access to the slides during the processing period and may release them to the operator upon completion of the staining or other process on the last slide of that module. In some embodiments, the order in which the slide retainment assemblies are released may be dependant on the time required to process the last slide of the retainment assembly.
  • Slides may even be processed in the most time efficient manner independently of the order to which they were introduced into the system.
  • the system may provide an optimum or merely an enhanced temporal scheduling of the various sample process steps.
  • the system may automatically schedule steps that are interspersed for an enhanced time result.
  • This interspersing may be an interleaving of a number of process operations and even an interleaving of a number of individual sample operations.
  • the system may sequence the individual sample operations. Regardless as to how programmed, it may be configured through hardware or software or a combination of each to provide an enhanced temporal scheduler element 179 , a process operations interleave element, an individual sample operations interleave element, or even an individual sample operations sequence element.
  • These can be created by integrating the automated process operation capability and either the parameter data or perhaps some replicated portion of that parameter process data (as mentioned later) and can thus act to create an interspersial robotic control functionality 175 .
  • control of the processing samples may be accomplished according to the following preferred embodiments, one preferred embodiment shown in FIG. 5 , although other processing may be accomplished consistent with the present invention.
  • a sample processing system manager such as a computer server may be connected with a number of individual sample processing systems. These may represent automated slide stainers or even stand alone automated slide processing system such that they are fully capable of functioning with connection to other devices. In systems where a connection does exist, the capability of electronically connecting a number of automated slide stainers or automated sample processing systems or label printers 200 may be provided. As mentioned earlier, there may be one or more separate full function computers connected. These may be connected through a hub 193 .
  • connection whether for input or other operation may also be a remote link (including able to be made remote such as in detachable memory) such as an internet connection element, a telephone line connection element, a wireless communication element, or even a detachable memory element.
  • a remote link including able to be made remote such as in detachable memory
  • connection among perhaps a number of process systems and perhaps a number of computers, such as workstations and a server may be achieved by use of a local area network, such as a group of computers and associated devices that share a common communications line or perhaps wireless link and may even share the resources of a single processor, memory, or server within a small geographic area (for example, within an office building or complex).
  • a local area network such as a group of computers and associated devices that share a common communications line or perhaps wireless link and may even share the resources of a single processor, memory, or server within a small geographic area (for example, within an office building or complex).
  • a local area network for this type of system may also include features such as but not limited to: an Ethernet element, a token ring element, an arcnet element, a fiber distributed data interface element, an industry specification protocol, a bluetooth-based element (named but not contemporary to King Harald Bluetooth of Denmark in the mid-tenth century!), a telecommunications industry specification using a frequency band of 2.45 GHz, a communication specification applying an IEEE 802 standard, a frequency hop communication specification, a shared common link element, a transmission control protocol/internet protocol communication element, a packetized information protocol, a shared protocol, a proprietary protocol, and even a layered protocol exchange system.
  • the local area network such as the stainer network 183 (a network dedicated to only the stainer or perhaps sample processing resources for integrity, security, and other purposes) in one embodiment may transmit a electronic memory address to achieve access to the appropriate information. Connection may also be established to a lab network or even a lab information system 195 such as through a bridge 194 .
  • connection may be accomplished over internet connections but more preferably is accomplished over LAN connections.
  • Each sample processing system may be individually controlled, in some embodiments, by a PC attached with, internal to, or otherwise provided. Data sharing between sample processing systems and the system manager may be performed to allow identification, tracking, and status of sample batches, reagents, and other agents and components of the sample processing system. A determination of which system has which reagents, reagent type, slides and protocols may be performed. Log files for each processing sequence, protocol, or slide can be generated for monitoring processing status. Database maintenance (including but not limited to purge, compact, back-up, database/list functions) and system diagnostics (including but not limited to exercising active system components to verify proper operation and assisting in troubleshooting efforts) may be accomplished manually or automatically.
  • the system may be configured to automatically access the required data through operation of the process operation control system 171 by inclusion of an automatic memory access element.
  • This access may be achieved by specifying an electronic memory address that may be transmitted by a electronic memory address element 178 perhaps over a local area network and may be followed by automatically replicating that data on some a memory aspect appropriate for operation such as an automatic data replication memory.
  • This memory may include but not be limited to: a volatile memory functionality as implemented by a volatile memory element, a random access memory functionality as implemented by a random access memory element, a non-volatile memory functionality as implemented by a non-volatile memory element, an electrically erasable programmable read only memory functionality as implemented by an electrically erasable programmable read only memory element, a main storage functionality as implemented by a main storage element, a secondary storage functionality as implemented by a secondary storage element, a cache memory functionality as implemented by a cache memory element, and even a detachable memory functionality as implemented by a detachable memory element.
  • a control interface may be provided for the operator, such as a graphical user interface (GUI), and may accommodate various languages. Help menus may be provided to assist in sample processing. Password protection features can be provided and even administrator control over at least some aspects. This may include the capability to include administrator limitations on the functional availability of any aspect of the system or of specific stainer availability or functionality, certain reagent availability functionality, certain protocol availability functionality, patient identification information access functionality, process priority request functionality, and stat process request functionality.
  • GUI graphical user interface
  • the system may have an administrator-implemented user limitation element, a specific stainer availability limitation element, a certain reagent availability limitation element, a certain protocol availability limitation element, a patient identification information access limitation element, a process priority request limitation element, a stat process request limitation element, a user privileges input element, and even a user group privileges configuration or input element.
  • Control of the sample processing may be accomplished by a dynamic scheduling algorithm, and in some embodiments, in accordance with continuous, or batch processing previously described.
  • the processing sequence may be controlled, in preferred embodiments, such that the various steps of a protocol for samples may be automated by one or more algorithmic controls.
  • user or other input may be accommodated as follows: 1) selecting a first protocol step, 2) selecting a second protocol from a restricted list of menu items that are compatible with the first protocol step, and 3) selecting subsequent protocol steps from a restricted list of menu items that are compatible with the preceding protocol step.
  • the system may act to determine operational readiness by inclusion of an operational readiness determination element 177 that may be programmed to assess if appropriate resources, drawers, slides, reagents, or other aspects are present or available to the system. Once an appropriate operational readiness is determined, the system may prompt initiation of access of the input data to electronically determine operational availability of a variety of items.
  • an individual sample element through inclusion of an individual sample readiness determination element may include but are not limited to: an individual sample element through inclusion of an individual sample readiness determination element, a defined group of samples through inclusion of a defined group of samples readiness determination element, a physically grouped collection of samples through inclusion of a physically grouped collection of samples readiness determination element, a slide drawer component through inclusion of a slide drawer component readiness determination element, a stand alone automated slide processing system through inclusion of an stand alone automated slide processing system readiness determination element, a slide stainer system element through inclusion of a slide stainer system readiness determination element, and even a user initiated prompt signal such as might occur to force or activate the system manually by the inclusion of a user initiated prompt signal determination element.
  • the present invention focuses on an automated staining apparatus and a method of automated treating of samples.
  • the present invention relates to an automated staining apparatus for treating samples arranged on carrier elements or means, such as but not limited to microscope slides, located at defined positions close to or in the apparatus by removing a portion of selected reagent from a station containing a plurality of reagents and thereafter applying the reagent to a sample, e.g. a tissue, organic cells, bacteria etc., arranged on the carrier means.
  • a sample e.g. a tissue, organic cells, bacteria etc.
  • This aspect of the invention facilitates that two or more reagents are mixed and the mixture applied to a sample. It also relates to a method of automated treating of samples by mixing reagents and applying the mixture to the sample.
  • Staining apparatuses for staining and treating samples by means of probes normally comprises a first station for containing one or more reagent vials; a second station for mounting slides, a probe arranged for removing a portion of reagent from a selected reagent vial and applying the reagent to a slide on which the sample is arranged and a drive means for moving the probe between the various stations.
  • An object of this aspect of the present invention is to improve the known apparatuses for staining samples as well as the method for automatic staining of samples by facilitating a wider range of available processes or procedures used to implement treatment, so as to ease the implementation of different staining and/or treatment processes that may be performed automatically, alternatively or additionally to provide an increased quality of some specific staining processes.
  • staining is used for the end product of the process, by which certain parts of the sample may be stained, i.e. has obtained a different colour, either in the optic range or in another electromagnetic range, such as ultra violet, or the staining may be an detectable, preferably automatically detectable, change in properties, such as fluorescent properties, magnetic properties, electrical properties or radioactive properties.
  • the sample normally has to undergo a series of treatment steps, such as washing, binding of reagents to the specific parts of the sample, activation of the reagents, etc. and each treatment step may include a plurality of individual treatments.
  • staining processes it may be required for one or more treatments to use a mixture of reagents prepared from two or more separate reagents which may be somewhat incompatible e.g. unmixable, such as a water based and an oil based reagent, or insoluble, and therefore requires that the two or more reagents are manually prepared and introduced into a reagent vial shortly before starting the staining process in order to obtain the best possible staining result for the selected examination purposes.
  • different staining process steps require a mixture of the same two reagents but in different dissolution ratios.
  • Some process steps require mixtures of two or more reagents that, when mixed, have a limited time window of usability because internal chemical processes deteriorate the mixture.
  • staining apparatus having an automated mixer integrated therein
  • these types of staining processes can be performed automatically instead of requiring human interaction or manual performance of some process steps in a much more automated process, and the quality of the staining process may be improved as a desired degree of mixing of reagents may be provided or an optimal application time window for a deteriorating mixture may be reached.
  • the carrier elements or perhaps means are preferably arranged in groups or series on trays or the like, so that a plurality of carrier means may be removed from or situated in the apparatus simultaneously, and the apparatus preferably also comprises means for performing the intermediate storage of the carrier means with samples thereon and the removal of the carrier means from the apparatus automatically.
  • control means typically a computer having a central processing unit and one or more memory unit associated therewith, means for controlling the various operations of the apparatus by controlling step motors, solenoids, valves and/or other drive or control parts of the apparatus.
  • the control means may have one or more data communication ports for enabling data communication with external computers by wire or wireless elements.
  • the control element or perhaps means does not have to be physically arranged within the apparatus itself but may be a computer external to the staining apparatus and connected to the apparatus via a data transmission port thereof.
  • the present invention also relates to a method of fully automated treating of samples arranged on carrier elements by means of a staining apparatus controlled by means of a control element or means, wherein the method comprises the steps of situating a plurality of carrier means intermediately in a carrier means station, each carrier means having a sample arranged thereon, applying a portion of a first reagent selected from a plurality of reagents to a mixing cup, applying a portion of a second reagent selected from a plurality of reagents to the mixing cup, mixing the reagents in the mixing cup by means of mixing means, moving a probe to the mixing cup by means of a probe drive means, removing a portion of the mixed reagents from the mixing cup by means of the probe, moving the probe to a selected one of said carrier means, and applying the mixed reagents to the selected carrier means, so as to perform a treatment of the sample arranged on the selected carrier means.
  • the present invention further relates to the use of an apparatus of the present invention as described above for exercising the method of the present invention.
  • the staining apparatus 201 may comprise a rectangular frame 204 surrounding a first station 202 comprising an array of compartments wherein each compartment a reagent vial 203 is placed, and a second station 205 wherein a number of separate racks 206 is placed, and where each rack may comprise a number of microscope slides 207 mounted side by side in the rack 206 .
  • each rack may hold up to 17 slides, but the rack may be designed to hold any suitable number of slides.
  • the shown embodiments may hold up to 136 slides 207 each having a sample, e.g. a tissue mounted on the upper side of the slide, so that reagent may be applied from above to the sample on each slide.
  • a robot arm to move a probe 210 in X and Y direction as indicated by the arrows X and Y may be arranged above the frame 204 of the staining apparatus.
  • the robot arm may therefore position the probe 210 above all reagent vials 203 as well as above all the microscope slides 207 , and may further operate the probe 210 to remove portions of a reagent contained in any of the vials or containers 203 , to transfer the portion of reagent and apply it to any of the slides 207 in order to provide a selected staining or treatment of the sample on each slide 207 .
  • a suitable control element e.g. a computer having the appropriate software, subroutines, or input data for the purpose, this staining apparatus 201 may be able to automatically stain or treat samples requiring different staining or treatment reagents and processes.
  • the control element or perhaps means of the apparatus may operate the robot arm to commence a staining or treatment run by firstly moving the probe to a first reagent vial or container 203 , into which the probe tip is inserted and liquid is aspirated up into the probe 210 in an amount corresponding to the number of samples to be stained or treated, in accordance with the input data provided to the control element.
  • the instrument may be required to perform a reagent inventory before a staining or treatment run can commence. This inventory may be accomplished by use of the probe tip to actually touch the liquid surface in each reagent vial 203 .
  • a cleaning of the probe 210 or at least the probe tip may be required after each measurement of a reagent level.
  • the probe 210 may be moved by the robot arm towards the slide rack system 205 in which the slides 207 are mounted.
  • the slides 207 may be situated with the surface horizontally oriented and the probe 124 may dispense the required amount of reagent on the appropriate slides in accordance with the input data.
  • the probe 124 may be moved by the robot arm towards the reagent mixer 209 where it may release reagent into the cup of the reagent mixer 209 , and may be subsequently moved to the probe washing station 208 , where the probe 210 may be released into a free washing station 208 , and another probe situated in another washing station 208 may be connected to the robot arm.
  • the robot arm may move the new clean probe to a second selected reagent vial 203 for collecting a selected amount of reagent from the second vial 203 , and the probe may thereafter by means of the robot arm be moved to the reagent mixer 209 , where the reagent in the probe 210 may be released into the cup of the mixer containing the first selected reagent. This may be commenced several times if more than two reagents are to be mixed for a specific staining or treatment process.
  • An object of the present invention is to provide a staining apparatus and a method for automatic staining of samples, in which the total process time for completing or even entering the staining protocol may be reduced.
  • the basic concepts of the present invention may be embodied in a variety of ways. It involves both sample processing techniques as well as various systems, assemblies, and devices to accomplish sample processing, input, and other functions.
  • the sample processing techniques are also disclosed as part of the results shown to be achieved by the various systems, assemblies, and devices described and as steps which are inherent to utilization. They should be understood to be the natural result of utilizing the devices as intended and described.
  • some devices are disclosed, it should be understood that these not only accomplish certain methods but also can be varied in a number of ways. Importantly, as to all of the foregoing, all of these facets should be understood to be encompassed by this disclosure.
  • each of the various elements of the invention and claims may also be achieved in a variety of manners.
  • This disclosure should be understood to encompass each such variation, be it a variation of an embodiment of any apparatus embodiment, a method or process embodiment, or even merely a variation of any element of these.
  • the words for each element may be expressed by equivalent apparatus terms or method terms—even if only the function or result is the same.
  • Such equivalent, broader, or even more generic terms should be considered to be encompassed in the description of each element or action. Such terms can be substituted where desired to make explicit the implicitly broad coverage to which this invention is entitled.
  • each of the sample processing systems and subsystems as herein disclosed and described ii) the related methods disclosed and described, iii) similar, equivalent, and even implicit variations of each of these systems, assemblies, devices and methods, iv) those alternative designs which accomplish each of the functions shown as are disclosed and described, v) those alternative designs and methods which accomplish each of the functions shown as are implicit to accomplish that which is disclosed and described, vi) each feature, component, and step shown as separate and independent inventions, vii) the applications enhanced by the various systems or components disclosed, viii) the resulting products produced by such systems or components, and ix) methods and systems, assemblies, devices, and apparatuses substantially as described hereinbefore and with reference to any of the accompanying examples, x) the various combinations and permutations of each of the elements disclosed, xi) each potentially dependent claim or concept as a dependency on each and every one of the independent claims or concepts presented, xii) processes performed with the aid of
US10/539,035 2002-12-20 2003-12-19 Advance programmed sample processing system and methods of biological slide processing Abandoned US20060063265A1 (en)

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US43560102P 2002-12-20 2002-12-20
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US10/539,035 US20060063265A1 (en) 2002-12-20 2003-12-19 Advance programmed sample processing system and methods of biological slide processing

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US10/731,316 Active 2025-12-23 US7648678B2 (en) 2002-12-20 2003-12-08 Method and system for pretreatment of tissue slides
US10/539,035 Abandoned US20060063265A1 (en) 2002-12-20 2003-12-19 Advance programmed sample processing system and methods of biological slide processing
US10/538,964 Active 2027-05-21 US8257968B2 (en) 2002-12-20 2003-12-19 Method and apparatus for automatic staining of tissue samples
US10/539,561 Active 2027-04-06 US7960178B2 (en) 2002-12-20 2003-12-19 Enhanced scheduling sample processing system and methods of biological slide processing
US10/538,745 Expired - Lifetime US7400983B2 (en) 2002-12-20 2003-12-19 Information notification sample processing system and methods of biological slide processing
US10/539,308 Active 2028-03-30 US8216512B2 (en) 2002-12-20 2003-12-19 Apparatus for automated processing biological samples
US10/741,628 Abandoned US20040266015A1 (en) 2002-12-20 2003-12-19 Automated sample processing apparatus and a method of automated treating of samples and use of such apparatus
US10/539,562 Expired - Lifetime US8298815B2 (en) 2002-12-20 2003-12-22 Systems and methods of sample processing and temperature control
US10/539,192 Active 2029-02-04 US9778273B2 (en) 2002-12-20 2003-12-22 Isolated communication sample processing system and methods of biological slide processing
US12/076,516 Active 2024-06-01 US7937228B2 (en) 2002-12-20 2008-03-19 Information notification sample processing system and methods of biological slide processing
US12/630,665 Expired - Lifetime US7758809B2 (en) 2002-12-20 2009-12-03 Method and system for pretreatment of tissue slides
US13/073,345 Expired - Fee Related US8386195B2 (en) 2002-12-20 2011-03-28 Information notification sample processing system and methods of biological slide processing
US13/102,181 Expired - Fee Related US8394635B2 (en) 2002-12-20 2011-05-06 Enhanced scheduling sample processing system and methods of biological slide processing
US13/493,969 Expired - Lifetime US8529836B2 (en) 2002-12-20 2012-06-11 Apparatus for automated processing biological samples
US13/567,308 Expired - Lifetime US8663978B2 (en) 2002-12-20 2012-08-06 Method and apparatus for automatic staining of tissue samples
US13/625,115 Expired - Lifetime US9040284B2 (en) 2002-12-20 2012-09-24 Systems and methods of sample processing and temperature control
US13/747,949 Expired - Lifetime US8788217B2 (en) 2002-12-20 2013-01-23 Information notification sample processing system and methods of biological slide processing
US13/758,810 Expired - Lifetime US8673642B2 (en) 2002-12-20 2013-02-04 Enhanced scheduling sample processing system and methods of biological slide processing
US13/964,562 Expired - Lifetime US8784735B2 (en) 2002-12-20 2013-08-12 Apparatus for automated processing biological samples
US14/053,977 Abandoned US20140038232A1 (en) 2002-12-20 2013-10-15 Enhanced Scheduling Sample Processing System and Methods of Biological Slide Processing
US14/151,130 Expired - Lifetime US9599630B2 (en) 2002-12-20 2014-01-09 Method and apparatus for automatic staining of tissue samples
US14/182,616 Expired - Lifetime US8969086B2 (en) 2002-12-20 2014-02-18 Enhanced scheduling sample processing system and methods of biological slide processing
US14/299,178 Abandoned US20140286838A1 (en) 2002-12-20 2014-06-09 Apparatus for automated processing biological samples
US14/306,606 Expired - Lifetime US9229016B2 (en) 2002-12-20 2014-06-17 Information notification sample processing system and methods of biological slide processing
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US10/539,561 Active 2027-04-06 US7960178B2 (en) 2002-12-20 2003-12-19 Enhanced scheduling sample processing system and methods of biological slide processing
US10/538,745 Expired - Lifetime US7400983B2 (en) 2002-12-20 2003-12-19 Information notification sample processing system and methods of biological slide processing
US10/539,308 Active 2028-03-30 US8216512B2 (en) 2002-12-20 2003-12-19 Apparatus for automated processing biological samples
US10/741,628 Abandoned US20040266015A1 (en) 2002-12-20 2003-12-19 Automated sample processing apparatus and a method of automated treating of samples and use of such apparatus
US10/539,562 Expired - Lifetime US8298815B2 (en) 2002-12-20 2003-12-22 Systems and methods of sample processing and temperature control
US10/539,192 Active 2029-02-04 US9778273B2 (en) 2002-12-20 2003-12-22 Isolated communication sample processing system and methods of biological slide processing
US12/076,516 Active 2024-06-01 US7937228B2 (en) 2002-12-20 2008-03-19 Information notification sample processing system and methods of biological slide processing
US12/630,665 Expired - Lifetime US7758809B2 (en) 2002-12-20 2009-12-03 Method and system for pretreatment of tissue slides
US13/073,345 Expired - Fee Related US8386195B2 (en) 2002-12-20 2011-03-28 Information notification sample processing system and methods of biological slide processing
US13/102,181 Expired - Fee Related US8394635B2 (en) 2002-12-20 2011-05-06 Enhanced scheduling sample processing system and methods of biological slide processing
US13/493,969 Expired - Lifetime US8529836B2 (en) 2002-12-20 2012-06-11 Apparatus for automated processing biological samples
US13/567,308 Expired - Lifetime US8663978B2 (en) 2002-12-20 2012-08-06 Method and apparatus for automatic staining of tissue samples
US13/625,115 Expired - Lifetime US9040284B2 (en) 2002-12-20 2012-09-24 Systems and methods of sample processing and temperature control
US13/747,949 Expired - Lifetime US8788217B2 (en) 2002-12-20 2013-01-23 Information notification sample processing system and methods of biological slide processing
US13/758,810 Expired - Lifetime US8673642B2 (en) 2002-12-20 2013-02-04 Enhanced scheduling sample processing system and methods of biological slide processing
US13/964,562 Expired - Lifetime US8784735B2 (en) 2002-12-20 2013-08-12 Apparatus for automated processing biological samples
US14/053,977 Abandoned US20140038232A1 (en) 2002-12-20 2013-10-15 Enhanced Scheduling Sample Processing System and Methods of Biological Slide Processing
US14/151,130 Expired - Lifetime US9599630B2 (en) 2002-12-20 2014-01-09 Method and apparatus for automatic staining of tissue samples
US14/182,616 Expired - Lifetime US8969086B2 (en) 2002-12-20 2014-02-18 Enhanced scheduling sample processing system and methods of biological slide processing
US14/299,178 Abandoned US20140286838A1 (en) 2002-12-20 2014-06-09 Apparatus for automated processing biological samples
US14/306,606 Expired - Lifetime US9229016B2 (en) 2002-12-20 2014-06-17 Information notification sample processing system and methods of biological slide processing
US14/959,741 Expired - Lifetime US10156580B2 (en) 2002-12-20 2015-12-04 Information notification sample processing system and methods of biological slide processing

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EP1573297A1 (fr) 2005-09-14
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US20140234170A1 (en) 2014-08-21
US7400983B2 (en) 2008-07-15
US8969086B2 (en) 2015-03-03
EP1573408A4 (fr) 2011-10-12
US20160084862A1 (en) 2016-03-24
EP1579190A4 (fr) 2011-12-28
EP1573312A4 (fr) 2011-10-12
US20110167930A1 (en) 2011-07-14
EP1579194A4 (fr) 2011-12-28
US20140286838A1 (en) 2014-09-25
AU2003299740B2 (en) 2011-04-21
US8216512B2 (en) 2012-07-10
US8788217B2 (en) 2014-07-22
CA2507960A1 (fr) 2004-07-15
WO2004058404A2 (fr) 2004-07-15
EP1573311B1 (fr) 2020-01-22
WO2004059288A3 (fr) 2005-01-27
WO2004059288A2 (fr) 2004-07-15
CA2508000A1 (fr) 2004-07-15
US20060172426A1 (en) 2006-08-03
CA2508323A1 (fr) 2004-07-08
US20050064535A1 (en) 2005-03-24
US20080241876A1 (en) 2008-10-02
AU2003299798A1 (en) 2004-07-22
EP1576376A4 (fr) 2011-12-28
US9599630B2 (en) 2017-03-21
US20130330252A1 (en) 2013-12-12
US7648678B2 (en) 2010-01-19
CA2508113A1 (fr) 2004-07-15
US20060085140A1 (en) 2006-04-20
CA2511032A1 (fr) 2004-07-15
CA2508370A1 (fr) 2004-07-15
US20060045806A1 (en) 2006-03-02
WO2004059287A2 (fr) 2004-07-15
WO2004059441A2 (fr) 2004-07-15
US7937228B2 (en) 2011-05-03
US8673642B2 (en) 2014-03-18
US20130084567A1 (en) 2013-04-04
WO2004059284A2 (fr) 2004-07-15
CA2508070C (fr) 2019-01-22
US20130217108A1 (en) 2013-08-22
US9229016B2 (en) 2016-01-05
US20110269238A1 (en) 2011-11-03
AU2003303390A1 (en) 2004-07-22
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US8386195B2 (en) 2013-02-26
AU2003303390B2 (en) 2009-07-23
WO2004059441A3 (fr) 2005-01-20
CA2508001A1 (fr) 2004-07-15
US9778273B2 (en) 2017-10-03
AU2003301103B2 (en) 2010-06-10
EP1579194A2 (fr) 2005-09-28
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US20060046298A1 (en) 2006-03-02
US8298815B2 (en) 2012-10-30
AU2003297369B2 (en) 2010-01-14
US20140186218A1 (en) 2014-07-03
EP1573311A2 (fr) 2005-09-14
EP1573311A4 (fr) 2011-12-28
CA2507960C (fr) 2017-02-07
CA2508113C (fr) 2017-10-31
AU2003297369A1 (en) 2004-07-22
US7758809B2 (en) 2010-07-20
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AU2003287895B2 (en) 2009-07-23
EP1579190A1 (fr) 2005-09-28
US8784735B2 (en) 2014-07-22
WO2004059287A3 (fr) 2005-01-27
WO2004057307A1 (fr) 2004-07-08
AU2003299798B2 (en) 2010-04-01
EP1576376A2 (fr) 2005-09-21
US20130029409A1 (en) 2013-01-31
US20040266015A1 (en) 2004-12-30
US9040284B2 (en) 2015-05-26
CN1955711A (zh) 2007-05-02
AU2003300291B2 (en) 2010-09-09
US8663978B2 (en) 2014-03-04
WO2004058404A3 (fr) 2004-09-10
EP1572979A4 (fr) 2011-10-19
CN100472197C (zh) 2009-03-25
AU2003300291A1 (en) 2004-07-22
AU2008202863A1 (en) 2008-07-24
WO2004058950A1 (fr) 2004-07-15
US8394635B2 (en) 2013-03-12
US8257968B2 (en) 2012-09-04
US20130203103A1 (en) 2013-08-08
US20060088940A1 (en) 2006-04-27
US20140356935A1 (en) 2014-12-04
WO2004059284A3 (fr) 2004-11-25
WO2004059297A1 (fr) 2004-07-15
US8529836B2 (en) 2013-09-10
US20140038232A1 (en) 2014-02-06
CA2508001C (fr) 2019-03-19
AU2003301103A1 (en) 2004-07-22
EP1573312A2 (fr) 2005-09-14
US20120310422A1 (en) 2012-12-06
AU2003303390B8 (en) 2009-08-06
US10156580B2 (en) 2018-12-18
CA2508070A1 (fr) 2004-07-15
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AU2008202863B2 (en) 2011-07-28
CA2974221A1 (fr) 2004-07-15
US20060088928A1 (en) 2006-04-27
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US7960178B2 (en) 2011-06-14
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US20100081167A1 (en) 2010-04-01
CN1726386A (zh) 2006-01-25

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