U.S. patent application number 10/539035 was filed with the patent office on 2006-03-23 for advance programmed sample processing system and methods of biological slide processing.
This patent application is currently assigned to DakoCytomation Denmark A/S. Invention is credited to John Favuzzi, Gorden Feingold, Marc Key, Doug Sweet, Rosanne Welcher.
Application Number | 20060063265 10/539035 |
Document ID | / |
Family ID | 32682266 |
Filed Date | 2006-03-23 |
United States Patent
Application |
20060063265 |
Kind Code |
A1 |
Welcher; Rosanne ; et
al. |
March 23, 2006 |
Advance programmed sample processing system and methods of
biological slide processing
Abstract
A sample processing system (101) that may be automated and
methods are disclosed where sample(s) (198) are arranged on a
carrier element (197) and a process operation control system (171)
automatically processes the sample(s) perhaps robotically with a
sample process parameter input (173) that may be independent and an
independent process parameter memory that does not interrupt
process operation when being used. There may be an interspersial
robotic control element responsive to an automatic data replication
memory and to which a robotic motion system is responsive.
Inventors: |
Welcher; Rosanne; (Ventura,
CA) ; Key; Marc; (Ojai, CA) ; Feingold;
Gorden; (Santa Barbara, CA) ; Sweet; Doug;
(Santa Barbara, CA) ; Favuzzi; John; (Santa
Barbara, CA) |
Correspondence
Address: |
SANTANGELO LAW OFFICES, P.C.
125 SOUTH HOWES, THIRD FLOOR
FORT COLLINS
CO
80521
US
|
Assignee: |
DakoCytomation Denmark A/S
Produktionsvej 42
Glostrup
DK
2600
|
Family ID: |
32682266 |
Appl. No.: |
10/539035 |
Filed: |
December 19, 2003 |
PCT Filed: |
December 19, 2003 |
PCT NO: |
PCT/US03/40519 |
371 Date: |
June 14, 2005 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
60435601 |
Dec 20, 2002 |
|
|
|
Current U.S.
Class: |
436/43 ;
422/65 |
Current CPC
Class: |
G01N 1/312 20130101;
Y10T 436/25 20150115; G01N 2035/00891 20130101; Y02A 90/22
20180101; G01N 2035/00089 20130101; G01N 2035/00326 20130101; G01N
2035/0091 20130101; Y10S 901/02 20130101; G01N 35/00732 20130101;
Y10T 436/114998 20150115; G01N 2035/00435 20130101; Y10T 436/114165
20150115; G01N 1/30 20130101; G01N 2035/00376 20130101; Y10T
436/2575 20150115; G01N 2035/00366 20130101; G01N 2035/00306
20130101; G01N 2035/009 20130101; Y02A 90/26 20180101; G16H 50/20
20180101; Y10T 436/112499 20150115; Y10T 436/113332 20150115; G01N
1/31 20130101; G01N 2035/00039 20130101; G01N 35/0099 20130101;
Y10T 436/11 20150115; G01N 35/00871 20130101; G01N 35/0092
20130101; Y02A 90/10 20180101; Y10S 901/41 20130101; G01N
2035/00881 20130101; G01N 35/00712 20130101 |
Class at
Publication: |
436/043 ;
422/065 |
International
Class: |
G01N 35/00 20060101
G01N035/00 |
Claims
1. A method of automated sample processing comprising the steps of:
establishing an automated sample processing system having an
automated process operation capability to which robotic sample
process functions are responsive; providing an input parameter
capability independent of said automated process operation
capability; accomplishing sample process parameter input to said
input parameter capability without interrupting said automated
process operation capability; independently storing at least a
portion of said parameter input for later access; establishing
stored parameter process data; automatically accessing at least a
portion of said stored parameter process data through operation of
said automated process operation capability; automatically
replicating at least a portion of said stored parameter process
data for use by said automated process operation capability;
integrating said automated process operation capability and said
replicated portion of said stored parameter process data to create
an interspersial robotic control functionality; controlling at
least some of said robotic sample process functions in response to
said interspersial robotic control functionality; and automatically
processing at least one sample through operation of said robotic
sample process functions at a process time independent of the time
said step of accomplishing slide process parameter input to said
input parameter capability without interrupting said automated
process operation capability is accomplished.
2. A method of automated sample processing as described in claim 1
wherein said step of establishing an automated sample processing
system having an automated process operation capability to which
robotic sample process functions are responsive comprises the step
of establishing an automated slide processing system.
3. A method of automated sample processing as described in claim 2
wherein said step of automatically processing at least one sample
comprises the steps of: arranging a plurality of slides on a
carrier retainment assembly; applying a reagent to said plurality
of slides; and automatically staining said plurality of slides.
4. A method of automated sample processing as described in claim 3
wherein said step of establishing an automated sample processing
system having an automated process operation capability to which
robotic sample process functions are responsive comprises the steps
of: establishing a plurality of automated slide stainers; and
electronically connecting said plurality of automated slide
stainers.
5. A method of automated sample processing as described in claim 1
wherein said step of establishing an automated sample processing
system comprises the step of establishing a stand alone automated
slide processing system, and wherein said step of providing an
input parameter capability independent of said automated process
operation capability comprises the steps of: utilizing a separate
full function computer programmed to accomplish said input; and
electronically connecting said separate full function computer to
said stand alone automated slide processing system.
6. A method of automated sample processing as described in claim 1
and further comprising the step of establishing a local area
network electronically connected to said automated sample
processing system.
7. A method of automated sample processing as described in claim 6
wherein said step of establishing a local area network
electronically connected to said automated sample processing system
comprises the step of incorporating a system having a feature
selected from a group consisting of: an Ethernet element, a token
ring element, an arcnet element, a fiber distributed data interface
element, an industry specification protocol, a bluetooth-based
element, a shared common link element, a transmission control
protocol/internet protocol communication element, a packetized
information protocol, a shared protocol, a proprietary protocol,
and a layered protocol exchange system.
8. A method of automated sample processing as described in claim 3
and further comprising the step of holding said plurality of slides
on at least one movable carrier retainment assembly.
9. A method of automated sample processing as described in claim 8
and further comprising the step of automatically identifying said
plurality of slides.
10. A method of automated sample processing as described in claim 1
wherein said step of providing an input parameter capability
independent of said automated process operation capability
comprises the step of providing an autonomous input
functionality.
11. A method of automated sample processing as described in claim 1
wherein said step of providing an input parameter capability
independent of said automated process operation capability
comprises the step of utilizing a multitasked central processing
unit resource.
12. A method of automated sample processing as described in claim 1
wherein said step of providing an input parameter capability
independent of said automated process operation capability
comprises the step of utilizing a plurality of central processing
units without implementing a multitasked central processing unit
resource.
13. A method of automated sample processing as described in claim 1
and further comprising the step of providing full operational
functionality of said automated process operation capability while
accomplishing said sample process parameter input.
14. A method of automated sample processing as described in claim 1
wherein said step of providing an input parameter capability
independent of said automated process operation capability
comprises the step of utilizing a remote link to said automated
sample processing system.
15. A method of automated sample processing as described in claim
10 wherein said step of establishing an automated sample processing
system having an automated process operation capability to which
robotic sample process functions are responsive comprises the steps
of: establishing a plurality of automated slide stainers; and
electronically connecting said plurality of automated slide
stainers.
16. A method of automated sample processing as described in claim
10 wherein said step of establishing an automated sample processing
system comprises the step of establishing a stand alone automated
slide processing system, and wherein said step of providing an
input parameter capability independent of said automated process
operation capability comprises the steps of: utilizing a separate
full function computer programmed to accomplish said input; and
electronically connecting said separate full function computer to
said stand alone automated slide processing system.
17. A method of automated sample processing as described in claim
10 and further comprising the step of establishing a local area
network electronically connected to said automated sample
processing system.
18. A method of automated sample processing as described in claim
17 wherein said step of establishing a local area network
electronically connected to said automated sample processing system
comprises the step of incorporating a system having a feature
selected from a group consisting of: an Ethernet element, a token
ring element, an arcnet element, a fiber distributed data interface
element, an industry specification protocol, a bluetooth-based
element, a shared common link element, a transmission control
protocol/internet protocol communication element, a packetized
information protocol, a shared protocol, a proprietary protocol,
and a layered protocol exchange system.
19. A method of automated sample processing as described in claim
14 wherein said step of utilizing a remote link to said automated
sample processing system comprises the step of utilizing a remote
link having a feature selected from a group consisting of: an
internet connection element, a telephone line connection element, a
wireless communication element, and a detachable memory
element.
20. A method of automated sample processing as described in claim 1
wherein said step of providing an input parameter capability
independent of said automated process operation capability
comprises the step of utilizing a simplified entry parameter input
functionality.
21. A method of automated sample processing as described in claim 1
wherein said step of providing an input parameter capability
independent of said automated process operation capability
comprises the step of utilizing a batch processing parameter input
functionality.
22. A method of automated sample processing as described in claim 1
wherein at least a portion of said step of automatically processing
occurs at least in part concurrently with at least a portion of
said step of accomplishing slide process parameter input.
23. A method of automated sample processing as described in claim 1
wherein the initiation of said step of automatically processing for
certain samples occurs significantly after completion of said step
of accomplishing slide process parameter input for said certain
samples.
24. A method of automated sample processing as described in claim
23 wherein said step of automatically processing for certain
samples is initiated at a time after the completion of said step of
accomplishing slide process parameter input for said certain
samples, said time selected from a group consisting of: at least
about one hour, at least about three hours, at least about eight
hours, at least about one day, at least about two days, and at
least about one week.
25. A method of automated sample processing as described in claim 1
wherein said step of accomplishing sample process parameter input
to said input parameter capability without interrupting said
automated process operation capability comprises the step of
utilizing an autonomous input functionality.
26. A method of automated sample processing as described in claim 1
wherein said step of accomplishing sample process parameter input
to said input parameter capability without interrupting said
automated process operation capability comprises the step of
utilizing a multitasked central processing unit resource.
27. A method of automated sample processing as described in claim 1
wherein said step of accomplishing sample process parameter input
to said input parameter capability without interrupting said
automated process operation capability comprises the step of
utilizing a plurality of central processing units without
implementing a multitasked central processing unit resource.
28. A method of automated sample processing as described in claim 1
wherein said step of accomplishing sample process parameter input
to said input parameter capability without interrupting said
automated process operation capability comprises the step of
inputting at least some slide identification information.
29. A method of automated sample processing as described in claim
28 wherein said step of inputting at least some slide
identification information comprises the step of inputting
information selected from a group consisting of: user operation
information, patient identification information, HIPPA-compliant
identification information, coded identification information, and
internal identification information.
30. A method of automated sample processing as described in claim 1
wherein said step of accomplishing sample process parameter input
to said input parameter capability without interrupting said
automated process operation capability comprises the step of
inputting at least some process scheduling information.
31. A method of automated sample processing as described in claim 1
wherein said step of accomplishing sample process parameter input
to said input parameter capability without interrupting said
automated process operation capability comprises the step of
inputting at least some process sequence information.
32. A method of automated sample processing as described in claim
31 wherein said step of inputting at least some process sequence
information comprises the step of inputting at least some schedule
priority information.
33. A method of automated sample processing as described in claim
31 wherein said step of inputting at least some process sequence
information comprises the step of inputting at least some stat
process request information.
34. A method of automated sample processing as described in claim 1
wherein said step of accomplishing sample process parameter input
to said input parameter capability without interrupting said
automated process operation capability comprises the step of
inputting at least some process protocol information.
35. A method of automated sample processing as described in claim 1
and further comprising the step of providing for administrator
control over at least some aspects of said automated sample
processing system.
36. A method of automated sample processing as described in claim
35 wherein said step of providing for administrator control over at
least some aspects of said automated sample processing system
comprises the step of permitting administrator limitations on the
functional availability of at least some functionality of said
automated sample processing system.
37. A method of automated sample processing as described in claim
36 wherein said step of permitting administrator limitations on the
functional availability of at least some functions of said
automated sample processing system comprises the step of permitting
administrator limitations on automated sample processing system
functionality selected from a group consisting of: specific stainer
availability functionality, certain reagent availability
functionality, certain protocol availability functionality, patient
identification information access functionality, process priority
request functionality, and stat process request functionality.
38. A method of automated sample processing as described in claim 1
wherein said step of accomplishing sample process parameter input
to said input parameter capability without interrupting said
automated process operation capability comprises the step of
inputting at least some user privileges information.
39. A method of automated sample processing as described in claim 1
wherein said step of accomplishing sample process parameter input
to said input parameter capability without interrupting said
automated process operation capability comprises the step of
inputting at least some individual slide process information.
40. A method of automated sample processing as described in claim 1
wherein said step of accomplishing sample process parameter input
to said input parameter capability without interrupting said
automated process operation capability comprises the step of
inputting at least some group slide process information.
41. A method of automated sample processing as described in claim 1
wherein said step of accomplishing sample process parameter input
to said input parameter capability without interrupting said
automated process operation capability comprises the step of
inputting at least some preferred stainer information.
42. A method of automated sample processing as described in claim 1
wherein said step of independently storing at least a portion of
said parameter input for later access comprises the step of storing
at least a portion of said parameter input on a physically
independent memory.
43. A method of automated sample processing as described in claim 1
wherein said step of storing at least a portion of said parameter
input on a physically independent memory comprises the step of
storing at least a portion of said parameter input at a location
remote from said automated sample processing system.
44. A method of automated sample processing as described in claim
42 wherein said step of storing at least a portion of said
parameter input on a physically independent memory comprises the
steps of: utilizing a separate full function computer programmed to
accept and store at least a portion of said parameter input; and
electronically connecting said separate full function computer to a
stand alone automated slide processing system.
45. A method of automated sample processing as described in claim
44 wherein said step of automatically accessing at least a portion
of said stored parameter process data through operation of said
automated process operation capability comprises the step of
specifying an electronic memory address for at least a portion of
said stored parameter process data.
46. A method of automated sample processing as described in claim
45 wherein said step of automatically accessing at least a portion
of said stored parameter process data through operation of said
automated process operation capability further comprises the step
of transmitting said electronic memory address over a local area
network electronically connected to said automated sample
processing system.
47. A method of automated sample processing as described in claim 1
wherein said step of automatically accessing at least a portion of
said stored parameter process data through operation of said
automated process operation capability comprises the step of
utilizing a remote link to said automated sample processing
system.
48. A method of automated sample processing as described in claim
47 wherein said step of utilizing a remote link to said automated
sample processing system comprises the step of utilizing a remote
link having a feature selected from a group consisting of: an
internet connection element, a telephone line connection element, a
wireless communication element, and a detachable memory
element.
49. A method of automated sample processing as described in claim 1
wherein said step of automatically accessing at least a portion of
said stored parameter process data through operation of said
automated process operation capability comprises the steps of:
determining operational readiness of at least a portion of said
automated sample processing system functionality; and prompting
initiation of access of at least a portion of said stored parameter
process data in response to said step of determining operational
readiness of at least a portion of said automated sample processing
system functionality.
50. A method of automated sample processing as described in claim
49 wherein said step of determining operational readiness of at
least a portion of said automated sample processing system
functionality comprises the step of electronically determining
operational availability of an automated sample processing system
aspect selected from a group consisting of: an individual sample
element, a defined group of samples, a physically grouped
collection of samples, a slide drawer component, an stand alone
automated slide processing system, a slide stainer system element,
and a user initiated prompt signal.
51. A method of automated sample processing as described in claim 1
wherein said step of automatically replicating at least a portion
of said stored parameter process data for use by said automated
process operation capability comprises the step of automatically
replicating on a memory aspect selected from a group consisting of:
a volatile memory functionality, a random access memory
functionality, a non-volatile memory functionality, an electrically
erasable programmable read only memory functionality, a main
storage functionality, a secondary storage functionality, a cache
memory functionality, and a detachable memory element.
52. A method of automated sample processing as described in claim 1
wherein said step of integrating said automated process operation
capability and said replicated portion of said stored parameter
process data to create an interspersial robotic control
functionality comprises the step of accomplishing enhanced temporal
scheduling of a plurality of sample process steps.
53. A method of automated sample processing as described in claim
52 wherein said step of integrating said automated process
operation capability and said replicated portion of said stored
parameter process data to create an interspersial robotic control
functionality comprises the step of interleaving a plurality of
process operations.
54. A method of automated sample processing as described in claim 1
wherein said step of integrating said automated process operation
capability and said replicated portion of said stored parameter
process data to create an interspersial robotic control
functionality comprises the step of interleaving a plurality of
individual sample operations.
55. A method of automated sample processing as described in claim 1
wherein said step of integrating said automated process operation
capability and said replicated portion of said stored parameter
process data to create an interspersial robotic control
functionality comprises the step of sequencing a plurality of
individual sample operations.
56. An automated sample processing system comprising: at least one
sample arranged on a carrier element; a process operation control
system configured to at least partially process said sample;
robotic motion system responsive to said process operation control
system; an independent process parameter input configured
independent from said process operation control system; an
independent process parameter memory responsive to said process
parameter input configured to store at least some parameter process
data; an automatic memory access element; an automatic data
replication memory responsive to said automatic memory access
element and at least a portion of said parameter process data; and
an interspersial robotic control element responsive to said
automatic data replication memory and to which said robotic motion
system is responsive.
57-104. (canceled)
Description
TECHNICAL FIELD
[0001] 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.
BACKGROUND
[0002] 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.
[0003] In preparation for sample analysis, 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.
[0004] Immunologic applications, for example, 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. In
some applications, 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. However, 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.
[0005] Past efforts at automated sample processing for samples
presented on carriers such as slides, such as U.S. Pat. No.
6,352,861 to Ventana Medical Systems, Inc. and U.S. Pat. No.
5,839,091 to LabVision Corporation, have not afforded the various
advantages and other combinations of features as presented
herein.
[0006] One of the various aspects that has not been adequately
addressed in even automated process system is that of information
entry. In practical terms, entry has often required both detailed
knowledge of an often-sophisticated process system and physical
access to such systems. It has also been frequently limited to
entry or input of data at or about the time the actual processing
was to occur. In spite of the fact that many have appreciated the
practical needs of users and institutions in this regard, such
aspects have not been an adequately address to date.
DISCLOSURE OF INVETION
[0007] 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. As described, sample processing can be
accomplished as disclosed herein. In providing this disclosure, it
should be understood that 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.
[0008] 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. As mentioned, 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. Furthermore, embodiments may be directed to
processing sequences addressing issues of processing control.
[0009] 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.
[0010] To disclose the foregoing and other objects and in
accordance with the purposes of the present invention, as broadly
embodied and described herein, the present invention is
characterized in various claims and in explanatory disclosure. None
of these should be understood as limiting. Further, all claims
presented at any time are incorporated in the specification to
afford all opportunities of presentation. Claims potentially to be
pursued for some of the initially presented aspects of the
invention may include any aspects described.
[0011] To achieve the foregoing and other objects of invention, and
as may be further disclosed and claimed throughout this
description, 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.
[0012] A sensor may be provided in some embodiments that may
automatically identify information from one or more samples, sample
carriers, or slides. In embodiments, 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.
[0013] Another embodiment of the present invention that 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.
[0014] 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.
[0015] Again, as mentioned, many of the various aspects of the
present invention are applicable to immunohistochemistry (IHC), as
well as in-situ hybridization (ISH) and fluorescent in-situ
hybridization (FISH), special staining of samples, microarray
processes, and techniques incorporating target retrieval or the
staining of samples. Furthermore, embodiments are directed to
processing sequences addressing issues of processing control, and
may be particularly applied to slide processing systems.
BRIEF DESCRIPTION OF THE DRAWINGS
[0016] The accompanying figures, are incorporated in and form a
part of the description, illustrate some of the preferred
embodiments of the present invention. Together with the written
description and disclosures of the specification, they serve to
explain principles of the invention and to enable each of the
disclosed embodiments.
[0017] FIG. 1 is a depiction of an embodiment of an overall system
incorporating some of the features of the invention.
[0018] FIG. 2 is a depiction of an embodiment of a portion of a
sample carrier assembly of one embodiment of the invention.
[0019] FIG. 3 is a depiction of an embodiment of a robotic movement
aspect of one embodiment of the invention.
[0020] FIG. 4 is a flow chart of some representative process steps
of an embodiment of the invention.
[0021] FIG. 5 is a block diagram of an embodiment of the
invention.
[0022] FIG. 6 is a depiction of an embodiment of a device
incorporating some of the features of the invention.
[0023] FIG. 7 is a depiction of an embodiment connecting one
stainer with one manager & database and one label printer.
[0024] FIG. 8 is a depiction of an embodiment connecting multiple
stainers with multiple managers and multiple label printers.
[0025] FIG. 9 is a depiction of an embodiment connecting a system
to a lab network and lab information system.
[0026] FIG. 10 is a block diagram showing some of the internal
software features.
BEST MODES FOR CARRYING OUT THE INVENTION
[0027] The following descriptions are provided to describe various
embodiments of the present invention in a manner to facilitate a
more detailed understanding some of the inventive features. The
variously described examples and preferred embodiments should not
be construed to limit the present invention to only the explicitly
described systems, techniques, and applications. This description
may further be understood to incorporate the various systems,
techniques, and applications, both singularly and in various
combinations consistent with the various inventive features and
embodiments of the present invention. Accordingly, the following is
a detailed description of a number of specific embodiments of the
invention.
[0028] 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.
[0029] 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.
[0030] In holding slides the carrier retainment assembly serves as
a slide retainment assembly 106. There may also be carrier racks,
modules, or magazines encompassed within each of the two broad
terms. As one embodiment of a sample carrier retainment assembly, 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.
[0031] 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.
[0032] 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, as previously
described, may have been limited to processing sequences for an
entire batch of carriers within the system. The present invention,
however, 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.
[0033] 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. In one embodiment, 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.
[0034] 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. In one
embodiment of the present invention, 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. In some embodiments, 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.
[0035] In accordance with the desire for an automated processing
system, 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. In some preferred embodiments, 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. As mentioned, in some
embodiments, 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.
[0036] As previously mentioned, 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. In some
embodiments, 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.
[0037] 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.
[0038] In preferred embodiments, 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, for example, 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. For example, in some embodiments, 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.
[0039] A cleaning station 140, shown in FIG. 1, 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. In one embodiment, 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. In other embodiments of the
present invention, 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.
[0040] In some embodiments, 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.
[0041] 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.
To eliminate cross contamination, 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.
[0042] 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.
[0043] In preferred embodiments, 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). To perform the staining
process on the slides, as described below, 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. Each slide can be rotated independently allowing for the
independent processing of different samples with different
requirements.
[0044] The system automates, and in some embodiments mimics or
otherwise corresponds to the procedure and physical attributes of
the supplies used manually to perform these same pre-treatment
processes. Accordingly, a processing tank may be provided. In some
embodiments, components of each processing tank may be configured
within a drawer 104. In some preferred embodiments, 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.
[0045] In some embodiments, 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.
[0046] In some embodiments, the individual fluids used for
pretreatment may be contained in the system cabinet.
Deparaffinization fluids (except DI water) may be drawn into the
processing tanks, then returned to their containers for reuse.
Containers are as listed for fluids one through six. On a periodic
basis, the material in the "dirty" containers may be discarded. 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.
[0047] In some embodiments, 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.
[0048] 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.
[0049] 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.
[0050] In some embodiments, specifics of in-situ hybridization
(ISH) may be addressed. 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.
[0051] Furthermore, fluorescent staining or tagging in IHC or ISH
(FISH) may be performed consistent with the features of the present
invention.
[0052] As mentioned, 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.
[0053] 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. Of course, 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. In order to facilitate uninterrupted processing, 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. Further, the input parameter
capability 173 may also be configured as an autonomous input
functionality through the inclusion of an autonomous input element.
In this manner, 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
In addition, in order to accomplish a goal of addressing practical
and institutional needs, the input parameter capability 173 may be
configured to provide a simplified entry parameter input
functionality or as a simplified entry parameter input element. In
this manner, only the input functions need to be available in a
highly simplified level of detail. This may be a "wizard" type of
system where there is a "step-by-step" method of adding slides or
achieving the desired input. Such an aspect may even be simple,
regimented, and somewhat inflexible. This can facilitate input by
persons not required to have the full spectrum of skills necessary
to be responsible for the operation of the sample processing system
101.
[0054] 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 scheduler
information through inclusion of a process scheduler information
input element, inputting schedule priority information through
inclusion of a schedule priority information input element,
inputting stat process request information through inclusion of a
stat process request input element, inputting at least some user or
operator identification information through inclusion of a user id
input element or an operator id input element, inputting at least
some user or operator privileges information through inclusion of a
user or operator privileges information input element, and batch
processing parameter input functionality through inclusion of a
batch processing parameter input element. Each of these types of
elements may, of course, represent hardware, software, a
subroutine, or some combination thereof and may be simply the
facilitation and perhaps even the simplification of the input of
the mentioned information. The inputs may also be configured
independent from the automated process operation capability.
[0055] As used above, 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. As discussed below and as shown in FIGS. 8 & 9,
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.
[0056] For automated operation, the input may create data such as
parameter process data 174 that may be stored at some location. To
provide autonomous operation, 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.
[0057] By using independent memory and independent other
functionality, 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.
[0058] In some embodiments, 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.
[0059] 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. To accomplish this, 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. In addition to interleaving steps,
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.
[0060] The 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.
[0061] As shown in FIGS. 8 & 9, in expanded systems, 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. There may be a
multitasked central processing unit resource on either the stainer
or the computer or there may be a number of central processing
units that are configured to avoid using or implementing a
multitasked central processing unit resource relative to the
process operations in order to maintain full independence or
perhaps even autonomous operation. The 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. In a
preferred embodiment, connection among perhaps a number of process
systems and perhaps a number of computers, such as workstations and
a server (the latter residing either separately or as part of a
workstation), 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 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. By providing an electronic connection 176
between various resources, the local area network (LAN) 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.
[0062] As mentioned, 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.
[0063] 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.
[0064] 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. By
including an administrator control element 180, 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.
[0065] 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. As part of
input to establish the desired control functionality, 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.
[0066] After all data is input, 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. These 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.
[0067] One aspect of the invention focuses on an automated staining
apparatus and a method of automated treating of samples. As to this
aspect, 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. 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.
[0068] 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.
[0069] 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.
[0070] The term 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. To
obtain the staining, 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.
[0071] In some 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. For other
processes, 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. By providing a 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.
[0072] 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.
[0073] The operation of the staining apparatus will generally be
controlled by means of 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.
[0074] 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.
[0075] 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.
[0076] The embodiment shown in the figures and described in details
below is only an example of an apparatus in accordance with the
present invention and is not limiting the wider scope of the
invention as described in the enclosed claims.
[0077] As shown in FIG. 6, a detailed description of one embodiment
of this aspect of the invention involves staining apparatus 201;
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. In the embodiment shown, each
rack may hold up to 17 slides, but the rack may be designed to hold
any suitable number of slides. With eight racks arranged side by
side; 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.
[0078] 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. By use of 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.
[0079] Having the appropriate input data, 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.
Additionally, under certain conditions, 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. To prevent cross-contamination between the
reagents in the various vials 203, a cleaning of the probe 210 or
at least the probe tip may be required after each measurement of a
reagent level.
[0080] 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.
Alternatively, 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.
[0081] 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. In particular, it is an object of this
aspect of the invention to reduce the amount of time needed in
general.
[0082] As can be easily understood from the foregoing, 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. In this application, 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. In addition, while
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.
[0083] The discussion included in this application is intended to
serve as a basic description. The reader should be aware that the
specific discussion may not explicitly describe all embodiments
possible; many alternatives are implicit. It also may not fully
explain the generic nature of the invention and may not explicitly
show how each feature or element can actually be representative of
a broader function or of a great variety of alternative or
equivalent elements. Again, these are implicitly included in this
disclosure. Where the invention is described in device-oriented
terminology, each element of the device implicitly performs a
function. Importantly, neither the description nor the terminology
is intended to limit the scope of the claims which may be included
at any time.
[0084] It should also be understood that a variety of changes may
be made without departing from the essence of the invention. Such
changes are also implicitly included in the description. They still
fall within the scope of this invention. A broad disclosure
encompassing both the explicit embodiment(s) shown, the great
variety of implicit alternative embodiments, and the broad methods
or processes and the like are encompassed by this disclosure and
may be relied upon at any time.
[0085] Further, 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. Particularly, it should be understood that as the
disclosure relates to elements of the invention, 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. As but one example, it should be understood that all
actions may be expressed as a means for taking that action or as an
element which causes that action. Similarly, each physical element
disclosed should be understood to encompass a disclosure of the
action which that physical element facilitates. Regarding this last
aspect, as but one example, the disclosure of a "retention element"
should be understood to encompass disclosure of the act of
"retaining"--whether explicitly discussed or not--and, conversely,
were there effectively disclosure of the act of "retaining", such a
disclosure should be understood to encompass disclosure of a
"retention element" and even a "means for retaining". It should
also be understood that in jurisdictions where specific language
may be construed as limiting, as but one example in the United
States where some interpretations of "means for" elements can be
construed narrowly, broader equivalent language may be used and
should be understood as encompassed by this specification. Such
changes and alternative terms are to be understood to be explicitly
included in the description.
[0086] Any patents, patent applications, publications, or other
references mentioned in this application for patent are hereby
incorporated by reference. In addition, as to each term used it
should be understood that unless its utilization in this
application is inconsistent with such interpretation, common
dictionary definitions should be understood as incorporated for
each term and all definitions, alternative terms, and synonyms such
as contained in the Random House Webster's Unabridged Dictionary,
second edition are hereby incorporated by reference as well as the
definitions presented by searchstorage.com, such to be considered
as representing the meaning of the terms as understood by computer
professionals. Finally, any priority case for this application is
hereby appended and hereby incorporated by reference.
[0087] Thus, the applicant(s) should be understood to have support
to claim at least: i) 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 or on a computer as described
throughout the above discussion, xiii) a programmable system as
described throughout the above discussion, xiv) a computer readable
memory encoded with data to direct a computer comprising means or
elements which function as described throughout the above
discussion, xv) a computer configured as herein disclosed and
described, xvi) individual or combined subroutines and programs as
herein disclosed and described, xvii) the related methods disclosed
and described, xviii) similar, equivalent, and even implicit
variations of each of these systems and methods, xix) those
alternative designs which accomplish each of the functions shown as
are disclosed and described, xx) those alternative designs and
methods which accomplish each of the functions shown as are
implicit to accomplish that which is disclosed and described, xxi)
each feature, component, and step shown as separate and independent
inventions, and xxii) the various combinations and permutations of
each of the above.
[0088] Further, if or when used, the use of the transitional phrase
"comprising" or the like is used to maintain the "open-end" claims
herein, according to traditional claim interpretation. Thus, unless
the context requires otherwise, it should be understood that the
term "comprise" or variations such as "comprises" or "comprising"
or the like, are intended to imply the inclusion of a stated
element or step or group of elements or steps but not the exclusion
of any other element or step or group of elements or steps. Such
terms should be interpreted in their most expansive form so as to
afford the applicant the broadest coverage legally permissible.
[0089] Any claims set forth at any time are hereby incorporated by
reference as part of this description of the invention, and the
applicant expressly reserves the right to use all of or a portion
of such incorporated content of such claims as additional
description to support any of or all of the claims or any element
or component thereof, and the applicant further expressly reserves
the right to move any portion of or all of the incorporated content
of such claims or any element or component thereof from the
description into the claims or vice-versa as necessary to define
the matter for which protection is sought by this application or by
any subsequent continuation, division, or continuation-in-part
application thereof, or to obtain any benefit of, reduction in fees
pursuant to, or to comply with the patent laws, rules, or
regulations of any country or treaty, and such content incorporated
by reference shall survive during the entire pendency of this
application including any subsequent continuation, division, or
continuation-in-part application thereof or any reissue or
extension thereon.
* * * * *