U.S. patent application number 12/696506 was filed with the patent office on 2010-05-27 for apparatus and methods for automated handling and embedding of tissue samples.
This patent application is currently assigned to BIOPATH AUTOMATION, L.L.C.. Invention is credited to Douglas P. Allen, Dominic P. DiNovo, Matthew J. Huddleston, Kenneth E. Hughes, George A. Keller, Keith A. Kuisick, Rebeccah P. Quam, Cecil R. Robinson, Jonathan E. Turner, Ernest D. VanHoose, Thomas J. Ward, Warren P. Williamson, IV.
Application Number | 20100129859 12/696506 |
Document ID | / |
Family ID | 32041250 |
Filed Date | 2010-05-27 |
United States Patent
Application |
20100129859 |
Kind Code |
A1 |
Allen; Douglas P. ; et
al. |
May 27, 2010 |
APPARATUS AND METHODS FOR AUTOMATED HANDLING AND EMBEDDING OF
TISSUE SAMPLES
Abstract
An automated machine for handling and embedding tissue samples
contained on microtome sectionable supports. The machine includes
an input member configured to hold a plurality of the microtome
sectionable supports prior to a tissue embedding operation. An
output member is configured to hold a plurality of the microtome
sectionable supports after the tissue embedding operation. A
cooling unit is configured to hold at least one of the microtome
sectionable supports during the tissue embedding operation. A
motorized carrier assembly is mounted for movement and configured
to hold at least one of the microtome sectionable supports. The
carrier assembly moves the support from the input member to the
cooling unit and, finally, to the output member. A dispensing
device dispenses an embedding material onto the microtome
sectionable support and at least one tissue sample carried by the
microtome sectionable support during the embedding operation.
Inventors: |
Allen; Douglas P.; (Del Mar,
CA) ; DiNovo; Dominic P.; (Dublin, OH) ;
Huddleston; Matthew J.; (Blacklick, OH) ; Hughes;
Kenneth E.; (Pataskala, OH) ; Keller; George A.;
(Columbus, OH) ; Kuisick; Keith A.; (Columbus,
OH) ; Quam; Rebeccah P.; (Columbus, OH) ;
Robinson; Cecil R.; (Hilliard, OH) ; Turner; Jonathan
E.; (Lewis Center, OH) ; VanHoose; Ernest D.;
(Columbus, OH) ; Ward; Thomas J.; (Columbus,
OH) ; Williamson, IV; Warren P.; (Loveland,
OH) |
Correspondence
Address: |
WOOD, HERRON & EVANS, LLP
2700 CAREW TOWER, 441 VINE STREET
CINCINNATI
OH
45202
US
|
Assignee: |
BIOPATH AUTOMATION, L.L.C.
Loveland
OH
|
Family ID: |
32041250 |
Appl. No.: |
12/696506 |
Filed: |
January 29, 2010 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
|
|
11010773 |
Dec 13, 2004 |
|
|
|
12696506 |
|
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|
|
PCT/US02/30779 |
Sep 26, 2002 |
|
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11010773 |
|
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Current U.S.
Class: |
435/40.52 ;
435/287.1 |
Current CPC
Class: |
Y10T 436/2575 20150115;
G01N 1/36 20130101; G01N 2001/366 20130101; Y10T 436/2525 20150115;
G01N 35/00732 20130101 |
Class at
Publication: |
435/40.52 ;
435/287.1 |
International
Class: |
G01N 1/30 20060101
G01N001/30; C12M 1/34 20060101 C12M001/34 |
Claims
1. An automated method of embedding tissue samples on microtome
sectionable supports, comprising: loading a plurality of the
microtome sectionable supports, each having a tissue sample
thereon, into an input device, unloading the microtome sectionable
supports from the input device using a motorized carrier, using the
carrier to load the microtome sectionable supports into a plurality
of respective molds, introducing liquid embedding material into the
respective molds, applying heat to the microtome sectionable
supports and the liquid embedding material in the molds, after
applying the heat, hardening the liquid embedding material in each
mold with the tissue sample and associated microtome sectionable
support contained at least partially therein, and unloading the
microtome sectionable supports and embedded tissue samples from the
molds.
2. The method of claim 1, wherein the microtome sectionable
supports further comprise first and second microtome sectionable
supports having different configurations and the molds further
comprise first and second molds having configurations corresponding
to the first and second microtome sectionable supports, and the
method further comprises: detecting the configurations of the
microtome sectionable supports as at least either the first or
second microtome sectionable supports, and loading the microtome
sectionable supports into the first or second mold depending on the
detected configuration.
3. An automated method of embedding tissue samples on microtome
sectionable supports, comprising: loading a plurality of the
microtome sectionable supports, each having a tissue sample
thereon, into an input device, applying heat to the microtome
sectionable supports in the input device, unloading the microtome
sectionable supports from the input device using a motorized
carrier, using the carrier to load the microtome sectionable
supports into a plurality of respective molds, introducing liquid
embedding material into the respective molds, hardening the liquid
embedding material in each mold with the tissue sample and
associated microtome sectionable support contained at least
partially therein, and unloading the microtome sectionable supports
and embedded tissue samples from the molds.
4. An automated method of embedding tissue samples on microtome
sectionable supports contained in frame members, comprising:
loading a plurality of the microtome sectionable supports, each
having a tissue sample thereon, into an input device, unloading the
microtome sectionable supports from the input device using a
motorized carrier, using the carrier to load the microtome
sectionable supports into a plurality of respective molds, staging
the microtome sectionable supports into the respective molds by
moving each microtome sectionable support and the tissue sample
contained thereon through the frame such that the tissue sample is
at least partially exposed outside of the frame, introducing liquid
embedding material into the respective molds, applying heat to the
microtome sectionable supports and the liquid embedding material in
the molds, after applying the heat, hardening the liquid embedding
material in each mold with the tissue sample and associated
microtome sectionable support contained at least partially therein,
and unloading the microtome sectionable supports and embedded
tissue samples from the molds.
5. The method of claim 4, wherein the microtome sectionable
supports further comprise first and second microtome sectionable
supports having different configurations and the molds further
comprise first and second molds having configurations corresponding
to the first and second microtome sectionable supports, and the
method further comprises: detecting the configurations of the
microtome sectionable supports as at least either the first or
second microtome sectionable supports, and loading the microtome
sectionable supports into the first or second mold depending on the
detected configuration.
6. An automated method of embedding tissue samples on microtome
sectionable supports contained in frame members, comprising:
loading a plurality of the microtome sectionable supports, each
having a tissue sample thereon, into an input device, applying heat
to the microtome sectionable supports in the input device,
unloading the microtome sectionable supports from the input device
using a motorized carrier, using the carrier to load the microtome
sectionable supports into a plurality of respective molds, staging
the microtome sectionable supports into the respective molds by
moving each microtome sectionable support and the tissue sample
contained thereon through the frame such that the tissue sample is
at least partially exposed outside of the frame, introducing liquid
embedding material into the respective molds, hardening the liquid
embedding material in each mold with the tissue sample and
associated microtome sectionable support contained at least
partially therein, and unloading the microtome sectionable supports
and embedded tissue samples from the molds.
7. An automated method of embedding tissue samples on microtome
sectionable cassettes contained in frame members, comprising:
loading a plurality of the microtome sectionable cassettes, each
having a tissue sample contained therein, into an input device,
unloading the microtome sectionable cassettes from the input device
using a motorized carrier, using the carrier to load the microtome
sectionable cassettes into a plurality of respective molds, staging
the microtome sectionable cassettes into the respective molds by
moving each microtome sectionable cassette and the tissue sample
contained therein through the frame such that the tissue sample and
a portion of the cassette are at least partially exposed outside of
the frame, introducing liquid paraffin into the respective molds,
applying heat to the microtome sectionable cassettes and the liquid
paraffin in the molds, after applying the heat, cooling and
hardening the liquid paraffin in each mold with the tissue sample
and associated microtome sectionable cassette contained at least
partially therein, and unloading the microtome sectionable
cassettes and embedded tissue samples from the molds.
8. The method of claim 7, wherein the microtome sectionable
cassettes further comprise first and second microtome sectionable
cassettes having different configurations and the molds further
comprise first and second molds having configurations corresponding
to the first and second microtome sectionable cassettes, and the
method further comprises: detecting the configurations of the
microtome sectionable cassettes as at least either the first or
second microtome sectionable cassettes, and loading the microtome
sectionable cassettes into the first or second mold depending on
the detected configuration.
9. An automated method of embedding tissue samples on microtome
sectionable cassettes contained in frame members, comprising:
loading a plurality of the microtome sectionable cassettes, each
having a tissue sample contained therein, into an input device,
applying heat to the microtome sectionable cassettes in the input
device, unloading the microtome sectionable cassettes from the
input device using a motorized carrier, using the carrier to load
the microtome sectionable cassettes into a plurality of respective
molds, staging the microtome sectionable cassettes into the
respective molds by moving each microtome sectionable cassette and
the tissue sample contained therein through the frame such that the
tissue sample and a portion of the cassette are at least partially
exposed outside of the frame, introducing liquid paraffin into the
respective molds, cooling and hardening the liquid paraffin in each
mold with the tissue sample and associated microtome sectionable
cassette contained at least partially therein, and unloading the
microtome sectionable cassettes and embedded tissue samples from
the molds.
10. An automated method of embedding tissue samples on microtome
sectionable cassettes contained in frame members, comprising:
loading a plurality of the microtome sectionable cassettes, each
having a tissue sample contained therein, into an input device,
unloading the microtome sectionable cassettes from the input device
using a motorized carrier, using the carrier to load the microtome
sectionable cassettes into a plurality of respective molds, using a
motorized staging device to move to the respective molds and stage
the microtome sectionable cassettes into the respective molds by
moving each microtome sectionable cassette and the tissue sample
contained therein through the frame such that the tissue sample and
a portion of the cassette are at least partially exposed outside of
the frame, introducing liquid paraffin into the respective molds,
applying heat to the microtome sectionable cassettes and liquid
paraffin in the molds, after applying the heat, cooling and
hardening the liquid paraffin in each mold with the tissue sample
and associated microtome sectionable cassette contained at least
partially therein, and unloading the microtome sectionable
cassettes and embedded tissue samples from the molds into an output
device configured to hold a plurality of the microtome sectionable
cassettes and embedded tissue samples.
11. The method of claim 10, wherein the microtome sectionable
cassettes further comprise first and second microtome sectionable
cassettes having different configurations and the molds further
comprise first and second molds having configurations corresponding
to the first and second microtome sectionable cassettes, and the
method further comprises: detecting the configurations of the
microtome sectionable cassettes as at least either the first or
second microtome sectionable cassettes, and loading the microtome
sectionable cassettes into the first or second mold depending on
the detected configuration.
12. An automated method of embedding tissue samples on microtome
sectionable cassettes contained in frame members, comprising:
loading a plurality of the microtome sectionable cassettes, each
having a tissue sample contained therein, into an input device,
applying heat to the microtome sectionable cassettes in the input
device, unloading the microtome sectionable cassettes from the
input device using a motorized carrier, using the carrier to load
the microtome sectionable cassettes into a plurality of respective
molds, using a motorized staging device to move to the respective
molds and stage the microtome sectionable cassettes into the
respective molds by moving each microtome sectionable cassette and
the tissue sample contained therein through the frame such that the
tissue sample and a portion of the cassette are at least partially
exposed outside of the frame, introducing liquid paraffin into the
respective molds, cooling and hardening the liquid paraffin in each
mold with the tissue sample and associated microtome sectionable
cassette contained at least partially therein, and unloading the
microtome sectionable cassettes and embedded tissue samples from
the molds into an output device configured to hold a plurality of
the microtome sectionable cassettes and embedded tissue
samples.
13. An automated method of embedding tissue samples on microtome
sectionable cassettes contained in frame members, comprising:
loading a plurality of the microtome sectionable cassettes, each
having a tissue sample contained therein, into a perforated input
basket, unloading the microtome sectionable cassettes from the
input basket using gripping fingers on a motorized carrier, using
the gripping fingers to load the microtome sectionable cassettes
into a plurality of respective molds, moving a motorized
staging/filling device adjacent to the respective molds, staging
the microtome sectionable cassettes into the respective molds with
the staging/filling device by moving each microtome sectionable
cassette and the tissue sample contained therein through the frame
such that the tissue sample and a portion of the cassette are at
least partially exposed outside of the frame, introducing liquid
paraffin into the respective molds from the staging/filling device,
applying heat to the microtome sectionable cassettes and the liquid
paraffin in the molds, after applying the heat, cooling and
hardening the liquid paraffin in each mold with the tissue sample
and associated microtome sectionable cassette contained at least
partially therein, and unloading the microtome sectionable
cassettes and embedded tissue samples from the molds into an output
device configured to hold a plurality of the microtome sectionable
cassettes and embedded tissue samples.
14. The method of claim 13, wherein the microtome sectionable
cassettes further comprise first and second microtome sectionable
cassettes having different configurations and the molds further
comprise first and second molds having configurations corresponding
to the first and second microtome sectionable cassettes, and the
method further comprises: detecting the configurations of the
microtome sectionable cassettes as at least either the first or
second microtome sectionable cassettes, and loading the microtome
sectionable cassettes into the first or second mold depending on
the detected configuration.
15. An automated method of embedding tissue samples on microtome
sectionable cassettes contained in frame members, comprising:
loading a plurality of the microtome sectionable cassettes, each
having a tissue sample contained therein, into a perforated input
basket, applying heat to the microtome sectionable cassettes in the
input device, unloading the microtome sectionable cassettes from
the input basket using gripping fingers on a motorized carrier,
using the gripping fingers to load the microtome sectionable
cassettes into a plurality of respective molds, moving a motorized
staging/filling device adjacent to the respective molds, staging
the microtome sectionable cassettes into the respective molds with
the staging/filling device by moving each microtome sectionable
cassette and the tissue sample contained therein through the frame
such that the tissue sample and a portion of the cassette are at
least partially exposed outside of the frame, introducing liquid
paraffin into the respective molds from the staging/filling device,
cooling and hardening the liquid paraffin in each mold with the
tissue sample and associated microtome sectionable cassette
contained at least partially therein, and unloading the microtome
sectionable cassettes and embedded tissue samples from the molds
into an output device configured to hold a plurality of the
microtome sectionable cassettes and embedded tissue samples.
16. An automated method of embedding tissue samples on microtome
sectionable supports, comprising: loading a plurality of the
microtome sectionable supports into an input device, each microtome
sectionable support having a tissue sample thereon, wherein the
microtome sectionable supports include first and second microtome
sectionable supports having different configurations, unloading the
microtome sectionable supports from the input device using a
motorized carrier, detecting the configurations of the microtome
sectionable supports as at least either the first or second
microtome sectionable supports, using the carrier to load the
microtome sectionable supports into a plurality of respective
molds, the molds including first and second molds having
configurations corresponding to the first and second microtome
sectionable supports, wherein loading the microtome sectionable
supports into the first or second mold depends on the detected
configuration, introducing liquid embedding material into the
respective molds, hardening the liquid embedding material in each
mold with the tissue sample and associated microtome sectionable
support contained at least partially therein, and unloading the
microtome sectionable supports and embedded tissue samples from the
molds.
17. A cassette for holding a tissue sample, comprising: a body
including a bottom wall and at least one side wall extending
upwardly with respect to said bottom wall to define an interior
space for receiving the tissue sample; and a sensing element
associated with said body and configured to allow an automated
sensing system to determine at least one characteristic of the
cassette.
18. The cassette of claim 17, wherein the sensing element further
comprises one or more holes.
19. The cassette of claim 17, wherein the sensing element is
machine readable.
20. The cassette of claim 17, wherein the sensing element comprises
machine readable indicia.
Description
[0001] The present application is a divisional of application Ser.
No. 11/010,773, filed Dec. 13, 2004 (pending) which is a
continuation of PCT Serial No. PCT/US02/30779 filed on Sep. 26,
2002 (expired), the disclosures of which are hereby fully
incorporated by reference herein.
FIELD OF THE INVENTION
[0002] The present invention generally relates to apparatus and
methods for handling and embedding tissue samples for biopsy
analysis and, more particularly, for handling and embedding such
samples in an automated manner.
BACKGROUND OF THE INVENTION
[0003] To accurately diagnose various tissue diseases and
conditions, medical personnel must remove one or more samples of
tissue from the body of a patient. This process of harvesting
tissue from the body is known as a biopsy. Once the tissue sample
or samples are removed and sent to a pathology laboratory, the
tissue will go through a series of procedures performed by a
histotechnician and, ultimately, a pathologist, in order to
diagnose the tissue. The present invention generally relates to
those procedures that are normally performed by the histotechnician
to prepare the tissue sample or samples into slides that may be
analyzed under a microscope by the pathologist.
[0004] Although the singular term "sample" is used throughout this
specification, it should be understood that this term likewise
encompasses plural "samples" as well. Once a tissue sample is
removed from the body of a patient, it is typically placed into a
specimen container containing a tissue fixative solution and then
the container is transported to a pathology laboratory. The tissue
will undergo a process known as "grossing-in" in the pathology lab
during which a histotechnician will retrieve the tissue sample from
the container, typically cut the tissue into appropriate sizes for
tissue processing, place individual samples into the appropriate
sized small plastic tissue cassettes, and assign tracking numbers
to each cassette. These tracking numbers are then logged into a
tracking system used in the laboratory. For the smallest tissue
samples, which may only be scrapings, the cassette will have fine
mesh openings on the sides and bottoms. In other situations
involving very small tissue samples, the samples are placed into a
bag that resembles a tea bag and prevents the smallest tissue
samples from escaping. Larger tissue samples are placed into
cassettes having somewhat larger slotted openings which are again
smaller than the tissue sample inside the cassette.
[0005] The cassettes are then placed into a stainless steel
perforated basket and run through a tissue processing machine,
often overnight. This machine uses a combination of vacuum, heat,
and chemicals to remove the interstitial fluids. Once the fluids
have been removed from the tissue samples, the processing machine
immerses the tissues samples in a bath of molten paraffin so that
the interstices in the tissue are replaced with paraffin. The
histotechnician then removes the basket from the machine and
removes the individual tissue cassettes. At an embedding station,
which has a molten paraffin reservoir and dispenser, the
histotechnician will individually remove the tissue from each
cassette. The histotechnician must carefully orient the tissue
sample, based on tissue type, into a stainless steel base mold
which is roughly the size of the tissue cassette and is partially
filled with molten paraffin. The molten paraffin is then rapidly
cooled on a refrigerated plate, which may be a thermal electric
cooler (TEC), to partially solidify the paraffin thereby holding
the tissue sample in the proper orientation. The cassette is then
placed on top of the base mold and paraffin is poured through the
opened top of the cassette into the base mold. The cassette changes
its function at this point in the procedure from a tissue holding
component to a fixation device for later use in taking shavings
from the solidified wax or paraffin. The base mold is chilled until
all of the molten paraffin has solidified and the histotechnician
removes the stainless steel base mold from the block of embedded
paraffin. The tissue sample is thus embedded within a rectangular
block of paraffin with a plastic tissue cassette on the opposite
side. As with the tissue processing machine, the embedding process
is accomplished in a batch fashion during which an average
histotechnician may embed approximately 40 to 60 cassettes per
hour.
[0006] The blocks of hardened paraffin containing the embedded
tissue samples are then ready to be sliced into extremely thin
sections for placement on a microscope slide. This slicing
operation is accomplished in a device known as a microtome. The
histotechnician mounts the embedded tissue block in a chuck on the
microtome which is sized to accept the side of the block that has
the embedded plastic cassette. The histotechnician can then begin
slicing the paraffin block which has the tissue sample embedded
opposite to the plastic cassette surface. This yields a ribbon of
individual slices of the tissue embedded in the paraffin. The
action of the microtome causes the individual slices to stick
together when done properly and, subsequently, these very thin
ribbons of slices are floated into a water bath and a glass slide
is carefully placed underneath the slice. The slice, with the thin
sectioned tissue sample embedded therein, is then adhered to the
top of the slide.
[0007] When the histotechnician has enough slides from the tissue
sample, the slides are placed into an automatic staining machine.
The staining machine goes through a series of infiltrating steps to
stain the different tissue and cells of the slide different colors.
This helps the pathologist identify different structures and makes
it easier to find any abnormalities in the tissue. After the
staining procedure is complete, the slides are cover slipped and
prepared for the pathologist to place under a microscope to
analyze.
[0008] Based on the summary of the procedure provided above, it
will be appreciated that conventional tissue sample handling and
processing is a very labor-intensive process involving several
manual steps performed by a histotechnician. Thus, repetitive
stress injuries such as carpal tunnel syndrome are prevalent. This
is especially true with the tissue sample embedding process. These
multiple manual operations and redundant handling increase the
likelihood of human error and, moreover, require highly trained and
skilled histotechnicians to ensure that the tissue samples
ultimately adhered to the slides for analysis by the pathologist
are in an optimum condition and orientation to make accurate
diagnoses. The conventional methods for preparing tissue biopsy
slides have been batch mode processes, as mentioned above, in which
the histotechnician would move from process step to process step
with a preselected number of cassettes based on the speed at which
that histotechnician can operate.
[0009] One system and method has been developed to increase the
productivity and reduce the occurrences of human error during the
process of preparing tissue samples for biopsy analysis. In this
regard, U.S. Pat. No. 5,817,032, the disclosure of which is hereby
incorporated by reference herein, relates to a tissue trapping and
supporting device, which may be a cassette, and which may be cut
with a microtome. When a cassette is used, the tissue sample is
immobilized within the cassette and subjected to the process for
replacing tissue fluids with wax. Then, the tissue sample and the
cassette are sliced at the same time for mounting on microscope
slides. Because the tissue sample is never removed from the
cassette from the time it is processed in the tissue processing
machine to the time that it is cut with the microtome, a
significant amount of time is saved and the chance for human error
is significantly reduced due to the elimination of separate tissue
handling steps. This patent also generally discusses an automated
process which even further reduces the handling steps during the
entire procedure.
[0010] In spite of the various improvements made in this field,
there is an increasing need for additional reductions in handling
and improvements in throughput production and consistent quality of
embedded tissue samples.
SUMMARY OF THE INVENTION
[0011] The present invention generally relates to an automated
machine for preparing tissue samples in respective microtome
sectionable supports. The machine includes an input member
configured to hold a plurality of the microtome sectionable
supports prior to a tissue embedding operation. An output member is
configured to hold a plurality of the microtome sectionable
supports after the tissue embedding operation. A cooling unit is
preferably configured to hold at least one of the microtome
sectionable supports during the tissue embedding operation. More
preferably, multiple thermal electric cooling (TEC) units are used
for faster production, however, other cooling devices may be
utilized without departing from the inventive principles. TECs are
preferred because they can rapidly cycle between heating and
cooling cycles. In accordance with the invention, initially cycling
the TEC to heat the microtome sectionable support greatly assists
with properly embedding the support. A motorized carrier assembly
is mounted for movement and configured to hold at least one of the
microtome sectionable supports. This carrier assembly moves the
support from the input member to the cooling unit and, finally, to
the output member. A dispensing device dispenses an embedding
material onto the microtome sectionable support and at least one
tissue sample carried by the microtome sectionable support during
the embedding operation.
[0012] Preferably, the microtome sectionable support is received
within a frame and is movable between a first position within the
frame and a second position in which the embedded tissue sample is
exposed for sectioning in a microtome. In this regard, the machine
preferably also includes a staging device which operates to move
the support from the first position to the second position. The
staging device and the dispenser may be part of the same robot such
that they move together between the plurality of cooling units. A
sensor operates to detect an amount of the embedding material
dispensed onto the microtome sectionable support. Another sensor
detects the size and/or configuration of the cassette so that it
may be placed into the properly configured base mold on one of the
cooling units. The input member preferably comprises an elongate
basket which is configured to hold and dispense a plurality of the
microtome sectionable supports. The basket may be held within a
heated receptacle and can include a dispensing opening. A
positioning device urges the microtome sectionable supports toward
the dispensing opening, such as through spring pressure and/or
weights.
[0013] In the preferred embodiment, two different configurations of
microtome sectionable supports may be processed in the machine,
although it will be appreciated that the number of configurations
processed by the machine can change. To this end, the machine
further includes first and second molds thermally coupled with each
cooling unit. The first mold is configured to receive a first
microtome sectionable support and the second mold is configured to
receive a second microtome sectionable support having a
configuration different than the first microtome sectionable
support. This different configuration, for example, may be a
different size, a different shape, or any other characteristic
difference between the first and second microtome sectionable
supports. A cassette detection sensor detects the respective
configurations of the first and second microtome sectionable
supports and, as a result, the carrier assembly transports the
microtome sectionable supports to the corresponding first or second
molds.
[0014] These and other objects, advantages, and features of the
invention will become more readily apparent to those of ordinary
skill in the art upon review of the following detailed description
taken in conjunction with the accompanying drawings.
BRIEF DESCRIPTION OF THE DRAWINGS
[0015] FIG. 1 is a perspective view of an automated machine
constructed in accordance with the preferred embodiment of this
invention for handling and embedding tissue samples.
[0016] FIG. 2 is a rear perspective view showing the inside of the
machine.
[0017] FIG. 3 is an enlarged rear perspective view with the outer
panels of the machine housing removed and also the control
component housing portion removed for clarity.
[0018] FIG. 4 is an exploded perspective view of the input door
section of the machine.
[0019] FIG. 4A is an exploded perspective view of the inside
surface of the input door showing the cassette and frame assembly
dispenser.
[0020] FIG. 4B is a perspective view of one of the input baskets
showing one cassette and frame assembly as well as a retaining clip
being inserted into the basket.
[0021] FIG. 5 is a top view of the inside of the machine.
[0022] FIG. 6 is an enlarged perspective view of the staging robot
in the machine.
[0023] FIG. 7 is a perspective view of the staging robot with the
stager/filler in exploded form.
[0024] FIG. 8 is a cross sectional view taken generally along line
8-8 of FIG. 6.
[0025] FIG. 9 is an enlarged cross sectional view similar to FIG.
8, but illustrating the staging of a cassette through its
associated frame and into a base mold.
[0026] FIGS. 10A and 10B are enlarged cross sectional views similar
to FIG. 9 and also progressively illustrating the staging
operation.
[0027] FIG. 11A is a cross sectional view taken along line 11A-11A
of FIG. 12 and showing the gripper assembly just prior to gripping
a cassette and frame assembly.
[0028] FIG. 11B is a partially cross sectioned top view similar to
FIG. 11A, but illustrating the cassette and frame assembly gripped
by the gripper fingers.
[0029] FIG. 12 is a cross sectional view taken along line 12-12 of
FIG. 5 and illustrating the gripper assembly in the process of
removing a cassette and frame assembly from an input basket.
[0030] FIG. 13 is an enlarged perspective view showing the gripper
assembly placing a cassette and frame assembly in a base mold
associated with a thermal electric cooling (TEC) unit.
[0031] FIG. 14 is an enlarged perspective view illustrating a
cassette and frame assembly being removed by the gripper assembly
after the cooling operation is complete.
[0032] FIG. 15 is a cross sectional view of an output tray
receiving cassette and frame assemblies which have completed the
embedding process within the machine.
[0033] FIG. 16 is a cross sectional view similar to FIG. 15, but
illustrating the removal of the output tray from the machine.
[0034] FIG. 17 is a schematic block diagram of a control system for
the machine of FIG. 1.
[0035] FIG. 18 is a schematic block diagram of a thermal electric 3
state controller used in the control system of FIG. 17.
[0036] FIG. 19 is a schematic block diagram of a solenoid driver
used in the control system of FIG. 17.
[0037] FIG. 20 is a flowchart illustrating a process executed by
the control system of FIG. 17 to continuously load frame and
cassette assemblies from baskets into molds in the machine of FIG.
1.
[0038] FIG. 21 is a flowchart illustrating a process executed by
the control system of FIG. 17 to pickup a frame and cassette
assembly from an input basket in the machine of FIG. 1.
[0039] FIG. 22 is a flowchart illustrating a process executed by
the control system of FIG. 17 to test a frame and cassette assembly
picked up from an input basket in the machine of FIG. 1.
[0040] FIG. 23 is a flowchart illustrating a process executed by
the control system of FIG. 17 to load a frame and cassette assembly
into a mold in the machine of FIG. 1.
[0041] FIG. 24 is a flowchart illustrating a process executed by
the control system of FIG. 17 to dispense paraffin into a mold in
the machine of FIG. 1.
[0042] FIG. 25 is a flowchart illustrating a process executed by
the control system of FIG. 17 to continuously load, fill and unload
frame and cassette assemblies in the machine of FIG. 1.
[0043] FIG. 26 is a flowchart illustrating a process executed by
the control system of FIG. 17 to unload a frame and cassette
assembly from a mold in the machine of FIG. 1.
[0044] FIG. 27 is a flowchart illustrating a process executed by
the control system of FIG. 17 to test a filled frame and cassette
assembly removed from a mold in the machine of FIG. 1.
[0045] FIG. 28 is a flowchart illustrating a process executed by
the control system of FIG. 17 to insert a filled frame and cassette
assembly into an output tray in the machine of FIG. 1.
[0046] FIG. 29 is a flowchart illustrating a process executed by
the control system of FIG. 17 to continuously transfer filled frame
and cassette assemblies from the molds to the output trays in the
machine of FIG. 1.
DETAILED DESCRIPTION OF THE DRAWINGS
[0047] Referring generally to FIGS. 1 and 2, an automated machine
10 constructed in accordance with the invention includes a housing
12 having a main door 14 on its front side. When open as shown in
FIG. 1, main door 14 exposes an input door 16 and four separate
output trays 18a, 18b, 18c, 18d which are removable for purposes to
be described below. Tray 18c is shown partially pivoted outwardly
along its lower edge and ready to be lifted out of the machine 10.
Doors 14 and 16 also pivot outwardly from their lower edges,
however, doors 14 and 16 are attached to housing 12 by respective
hinges 14a, 16a. The front side of housing 12 includes openings 20
which allow relatively cool room air to be drawn into thermal
electric cooling devices as described below. Housing 12 includes a
control panel 22 for operating the machine 10, a paraffin input
opening 24 on its top side, and caster wheels 26 on its lower side.
A lower inside portion 27 of housing 12 includes the various
control components necessary to operate machine 10 as will be
described below. As further shown in FIG. 2, paraffin input 24
leads to a container 28 for holding the liquid paraffin. Container
28 is heated to maintain the liquid paraffin at the proper
temperature of about 60.degree. C. As generally shown in FIG. 2,
input door 16 leads to a cassette and frame assembly dispenser 30
while output trays 18a, 18b, 18c, 18d (FIG. 1) include individual
cassette and frame assembly receivers 32a, 32b, 32c, 32d inside
housing 12. Each receiver 32a-d has two vertical rows of
spring-biased slots, each slot retaining a single cassette and
frame assembly after the embedding operation is complete The
machine 10 is loaded with cassette and frame assemblies each
containing one or more tissue samples, in cassette and frame
assembly dispenser 30. The cassette and frame assemblies or, more
broadly speaking, the microtome sectionable supports, may take any
suitable form. Preferably, these supports are generally of a form
as described in U.S. Pat. No. 5,817,032, and further described
below. The tissue samples are embedded in paraffin using the
components and methods to be described below before being
individually placed within the respective cassette and frame
assembly receivers 32a, 32b, 32c, 32d.
[0048] Referring now to FIG. 3, a pick and place robot 40 includes
a pick and place head 42 which is movable along three axes.
Specifically, a base 44 rides left and right on rails 46, 48 along
a horizontal x-axis as viewed from the front of machine 10. Pick
and place head 42 further rides on rails 56, 58 along a horizontal
y-axis, that is, toward and away from the front of machine 10. A
vertical support 50 carries pick and place head 42 and rides up and
down on rails 52, 54 along a vertical z-axis. To achieve these
respective movements, three separate motor and drive screw
assemblies 60, 62 and 64 are provided. Motor 60a and drive screw
60b move base 44 along rails 46, 48. Motor 62a and drive screw 62b
move pick and place head 42 vertically along rails 52, 54. Motor
64a and drive screw 64b move pick and place head 42 in opposite
directions along rails 56, 58. Although belt driven screws are
shown, it will be appreciated that direct drives or any other types
of motive devices may be used instead. For all of the various
electrical wiring that is necessary for the motors and control
components, flexible conduits 66, 68, 70 are provided to facilitate
the various movements of the pick and place robot 40.
[0049] Still referring to FIG. 3, pick and place robot 40 moves the
cassette and frame assemblies from dispenser 30 to respective base
mold modules or TEC units 80 and, more specifically, to one of two
selectable base molds 82, 84 located on top of each TEC unit 80.
Several TEC units 80 are removed for clarity. The use of TECs as
integrated into units or modules 80 is advantageous because TECs
may be quickly cycled between heating and cooling functions. As
described below, each TEC unit 80 may be used to initially heat
base mold 82 or base mold 84 such that liquid paraffin flows more
completely into and throughout the cassette containing one or more
tissue samples. This avoids air pockets in the paraffin after
hardening which could lead to difficulties in subsequent steps
taken by the histotechnician or pathologist. The number and type of
cooling/heating units may be varied. Also, a greater or smaller
number of base molds 82, 84 may be used, for example, to
accommodate a range of configurations and/or sizes of cassette and
frame assemblies to be processed in machine 10. The size and/or
configuration of the cassette and frame assembly is detected with a
suitable sensor 86 prior to transferring that cassette and frame
assembly to a corresponding base mold 82 or 84. For example, a
small biopsy cassette may have one or more holes detected by sensor
86, while a large cassette may not have such holes. Alternatively,
machine readable indicia may be placed on the cassette and frame
assemblies, such as a bar code, and then read by an appropriate
device mounted in any suitable location. Thus, the cassette and
frame assemblies may be identified and tracked within the machine.
Thus, the machine control can identify which base mold 82 or 84 to
place the cassette within.
[0050] Once the cooling process is complete (in a manner more fully
described below) the pick and place robot 40 moves the cassette and
frame assembly from a TEC unit 80 to respective slot receptacles 90
in one of the receivers 32a, 32b, 32c, 32d. Sensors 92, 94 are
provided on each receiver 32a-d to indicate to the control system
whether the associated receiver 32a-d holds any cassette and frame
assemblies. Latch assemblies 96 are provided to retain trays 18a,
18b, 18c, 18d with their respective cassette and frame assembly
receivers 32a-d on the front of housing 12. Preferably, these latch
assemblies 96 are solenoid-operated to allow the control system of
the machine 10 to monitor whether or not any particular tray 18a-d
has been removed. If one has been removed, then machine 10 may stop
operating or at least stop delivering embedded cassette and frame
assemblies to the location of the removed tray.
[0051] Turning to FIGS. 4, 4A and 4B, a plurality of, for example,
four input baskets 100 are provided to hold the cassette and frame
assemblies and their respective tissue samples for dispensing
purposes. Access by pick and place head 42 is provided by an
opening 101a in an interior cover 101. Each basket 100 is retained
in a heated receptacle 102 on the inside surface of door 16.
Preferably, receptacles 102 each include one or more cartridge
style heaters 103 which maintain baskets 100 and the cassette and
frame assemblies therein at an elevated temperature designed to
keep any remnant paraffin remaining from the previous tissue
processing procedure in a liquefied state until the start of the
cooling process. That is, solidification of the paraffin is
prevented so that the various components which need to move are
able to without jamming. Suitable thermal insulation 105 may be
provided between receptacles 102. Solidified or partially
solidified paraffin on the baskets 100 and/or the cassette and
frame assemblies therein may also tend to cause jamming of baskets
100 in receptacles 102 or jamming of the cassette and frame
assemblies in baskets 100. Baskets 100 are preferably transferred
by the operator, such as a histotechnician, directly into
receptacles 102 from a tissue processing machine, however, this may
instead be an automated transferring operation. Baskets 100 are
perforated and constructed of a material suitably resistant to
heat, chemicals, microwaves, or other environmental conditions
present during tissue processing. A suitable material is
Ultem.RTM., available from General Electric Co. Baskets 100 may be
accessed by opening door 16 via hinge mechanisms 16a, 104 (FIG. 4)
and then opening a spring-loaded hinged closure 106 at the top of a
basket receptacle 102. Each basket receptacle 102 further includes
a lower, spring-loaded retaining member 110 which flips outwardly
as a cassette and frame assembly is withdrawn from basket 100 and
is then biased to the vertical position shown to retain the next
successive cassette and frame assembly in position to be grasped by
the pick and place head 42. A basket presence sensing assembly 112
is mounted to the inside surface of door 16 and is actuated when a
basket 100 is fully inserted downwardly into receptacle 102 to
thereby indicate to the control system that a basket 100 is
present. Although such sensors may take many forms, in this case an
actuation member 114 (FIG. 4A) is received in a slot 116 of basket
100 and is thereby moved downwardly such that an attached element
118 moves vertically into and is sensed by a presence sensor
119.
[0052] As further shown in FIG. 4, a positioning assembly 120 is
used to ensure that all of the cassette and frame assemblies within
each basket 100 are automatically and continuously moved to their
lowermost positions ready for individual dispensing. Assembly 120
includes an upper plate 124 and a lower plate 126 coupled together
by respective rods 128a, 128b. Rods 128a, 128b carry respective
fingers 130 for vertical movement while preventing pivotal motion.
It will be appreciated that although two rods 128a, 128b are shown
coupled with each finger 130, other methods of preventing pivotal
movement or otherwise ensuring the correct orientation of fingers
130 may be used instead. Fingers 130 are biased in a downward
direction by preloaded springs 132. In addition, or alternatively,
fingers 130 may carry weights, such as one to two pound weights
(not shown), so that a constant downward force is applied to the
cassette and frame assemblies 150 in baskets 100. This ensures that
each successive cassette and frame assembly is moved into position
for gripping and extraction as described below. A movable plate 134
is operated by a motor 136 and a screw 138 threaded into a nut 140.
Plate 134 is moved upwardly from the position shown in FIG. 4 to
move each of the fingers 130 to an uppermost home position thereby
allowing removal of one or more of the baskets 100 from receptacles
102. Nut 140, which is rigidly attached to plate 134, carries a
flange member 142 which actuates presence sensors 144, 146 at the
respective end-of-travel positions to indicate to the control
system when to stop motor 136 in each direction.
[0053] As illustrated in FIG. 4B, a retainer clip 148 is used to
retain a stack of cassette and frame assemblies 150 (containing
tissue samples, not shown) within basket 100. For illustration
purposes, only one cassette and frame assembly 150 is shown.
Assembly 150 includes an inner cassette 150a preferably constructed
in accordance with the disclosure set forth in the
above-incorporated U.S. Pat. No. 5,817,032 or in International
Patent Application Serial No. PCT/US02/30775, the disclosure of
which is fully incorporated herein by reference, and an outer frame
150b also preferably constructed in accordance with the referenced
patent or patent application. Typically, basket 100 will be filled
with, for example, 30-40 cassettes and frame assemblies 150, and
retaining clip 148 will be used at the top of the stack of
assemblies 150 to prevent any shifting of assemblies 150 within the
basket 100 during handling. Basket 100 includes a pair of slots
152, 154 through which the lowermost cassette and frame assembly
150 is grasped by the pick and place head 42. Basket 100 further
includes a removable cover 156 for allowing access to its interior.
Cover 156 includes a slot 156a through which an extension 130a of
one of the previously described fingers 130 (FIG. 4) will be
inserted to bear against the top of the stack of cassette and frame
assemblies 150 ensuring that a cassette and frame assembly 150 is
always positioned adjacent slots 152, 154 for gripping purposes.
The lower end of cover 156 also includes recesses 158, 160 to allow
access by gripper fingers of the pick and place head 42 to be
described below.
[0054] Referring now to FIGS. 5-7, a staging robot 170 is also
mounted for movement within housing 12 and includes a stager/filler
172 movable along three axes (u, v, w, see FIG. 6). Staging robot
170 is movable right and left (w-axis) via a motor 174 and drive
screw 176 along rails 178, 180. Stager/filler 172 is further
movable up and down (v-axis) along a rail 182 via a motor 184 and
drive screw 186 (FIG. 7). Staging robot 170 is movable in opposite
directions front to back (u-axis) along rails 188, 190 by a motor
192 and drive screw 194. Flexible conduits 191, 193 contain the
electrical wiring and paraffin tubing as necessary during operation
of staging robot 170. Once the pick and place robot 40 has placed a
cassette and frame assembly 150 in one of the base molds 82 or 84,
the staging robot 170 is moved along rails 178, 180 and 188, 190 to
the correct position directly over the base mold 82 or 84 holding
the cassette and frame assembly 150. Motor 184 and drive screw 186
are used to then vertically position stager/filler 172 as will be
described below.
[0055] Referring to FIGS. 7-10A and 10B, stager/filler 172 more
specifically includes a support assembly 195 which is rigidly
fastened to four linear bushings or bearing blocks 188a, 190a
riding along rails 188, 190. Support assembly 195 is also rigidly
fastened to a mounting member 196 which rides along screw 194 via a
nut 197. Thus, motor 192 turns screw 194 through nut 197 and
thereby moves support assembly 195 along rails 188, 190. A
generally U-shaped support member 198 is a rigid part of assembly
195. As previously discussed, another motor 184 provides the motive
force for vertical movement of stager/filler 172. Motor 184
includes a mounting portion 184a rigidly coupled to a mounting
portion 195a of support assembly 195 and a rotatable portion 184b.
A bearing 199 is held within a mounting hole 198b and supports
screw 186 during rotation. Rotatable portion 184b of motor 184 is
rigidly coupled to screw 186 such that screw 186 may be rotated
within U-shaped support member 198. Stager/filler 172 further
includes a vertical support member 202 carrying a nut 204 which
engages screw 186. Vertical support member 202 is thereby moved
along rail 182 via linear bushings 182a which are rigidly fastened
to vertical support member 202. Rail 182 is rigidly fastened to a
portion 195b of support assembly 195. Vertical support member 202
carries four fingers or pushers 203 which push cassette 150a
through frame 150b and within base mold 82 to the position shown in
FIGS. 9 and 10. Heaters 205 are also coupled to pushers 203 to
maintain them at an elevated temperature (e.g.,
60.degree.-65.degree. C.). Vertical movement of pushers 203 is
accomplished by activating motor 184 and screw 186 such that
vertical support member 202 carried by nut 204 moves downwardly
along rail 182 and, as a result, moves pushers 203 downwardly
against the top corner portions of cassette 150a. Simultaneously,
vertical support member 202 moves four spring-loaded holding
members 206 (only two shown) downwardly against the top corner
portions of frame 150b to immobilize the frame 150b during the
staging and paraffin filling process (FIG. 10A). After the staging
process is complete, the bottom of the cassette 150a is exposed
outwardly of the frame 150b and within the interior of the base
mold 84.
[0056] At this point, as shown in FIG. 10B, the fingers or pushers
203 are withdrawn upwardly by motor 184 to a position at which they
will not contact any paraffin 205 while the spring-loaded holding
members 206 still retain frame 150b against base mold 84 with some
spring pressure. Liquid paraffin 205 is then dispensed into base
mold 84 and throughout the cassette 150a to thereby embed the
tissue sample 210. To this end, a dispensing tube 212 receives the
paraffin from a suitable valve 214 and tubing 216 (FIG. 9) which is
coupled to container 28 (FIGS. 2 and 3). As with all components
which will be in close thermal contact with the paraffin, these
components are preferably maintained at an elevated temperature of
about 60.degree.-65.degree. C. Dispensing tube 212 is preferably
heated by a cartridge heater 220 controlled by an RTD and thermal
fuse assembly 224. Tubing 216 may be similarly heated, if
necessary. The paraffin is preferably dispensed by gravity,
although a pump may be used if necessary. Limit switches 230, 232
(FIG. 9) monitor the position of the vertical support member 202 at
upper and lower limits. The intermediate position used during the
filling procedure to raise pushers 203 above the paraffin level may
be controlled by simply rotating the screw 186 a predetermined
amount. An ultrasonic level sensor 234 (Model No. ML102 obtained
from Cosense, Inc. of Hauppauge, Long Island, N.Y.) is mounted to
the stager/filler 172 to sense when the level of liquid paraffin is
correct, that is, preferably near the top of frame member 150b. At
this point, the valve 214 is closed to stop dispensing paraffin
from the dispensing tube 212. Level sensing is preferred because
various amounts of paraffin will need to be added to each base mold
depending on the amount of tissue in each cassette 150a. Thus,
level sensing assures that there is no overflow or underfill of
paraffin in the base mold 82 or 84.
[0057] After the filling operation is complete, the TEC unit 80 is
activated to cool and solidify the liquid paraffin within the base
mold 84 into a hardened block. This may take, for example, from one
to three minutes. Since TECs are reversible between heating and
cooling operations due to their use of a peltier-type of device,
the TEC unit 80 may initially be used to heat the base mold 84 to
allow better flow of liquid paraffin through the perforations of
the cassette 150a. Better flow is achieved as a result of the
lowered viscosity of the paraffin in the heated condition. This
helps prevent air entrapment and assures that a preferred solid
block of hardened paraffin is ultimately formed. As shown best in
FIG. 8, each TEC unit 80 is constructed with two TECs which
comprise conventional ceramic/metal plate assemblies and operate as
peltier devices to provide surface cooling (or heating) through
conduction with the bottoms of base molds 82, 84. Each TEC unit 80
includes an air flow passage 238 below TECs 236 with inlet and
outlet fans 240, 242 for drawing air in through the openings 20 in
the front of machine housing 12 (FIG. 1) and exhausting the air
through a suitable exhaust conduit 244 leading to a lower portion
of housing 12. This allows for heat to be appropriately transferred
away from units 80 during the cooling cycle.
[0058] FIGS. 11A and 11B illustrate the specific gripping mechanism
250 used for grasping cassette and frame assemblies 150 on pick and
place head 42. Specifically, a pair of opposed gripper fingers 252,
254 include respective projections 252a, 252b and 254a, 254b which
register with indentations 256 (FIG. 14) in each frame 150b. An
over-center type mechanism is used, operated by a solenoid 260, for
moving fingers 252, 254 between an open or release position shown
in FIG. 11A and a closed or gripping position shown in FIG. 11B.
Linkages 262, 264 move between the position shown in FIG. 11A to
the pivoted, over-center position shown in FIG. 11B. An actuating
member 266 is connected to a reciprocating output 268 of solenoid
260 and pivotally connected to respective pivot points 270, 272 on
each linkage 262, 264. Each linkage 262, 264 is further pivotally
coupled to the gripper fingers 252, 254 at points 274, 276 such
that reciprocating motion of actuating member 266 pivots the
linkages 262, 264 and, at the same time, moves the gripping fingers
252, 254 inwardly or outwardly depending on whether the solenoid
output 268 is moved outwardly or inwardly with respect to the
solenoid 260. It will be appreciated that many other types of
gripping devices may be used as alternatives to this type of
device. In the preferred embodiment, an infrared presence sensor
280 is also carried on the gripping mechanism 250 to indicate
whether a cassette and frame assembly 150 is present in the basket
100. If the presence sensor 280 does not detect a cassette and
frame assembly 150, then the control system can direct the pick and
place robot 40 to move the pick and place head 42, together with
the gripper mechanism 250, to the next basket 100.
[0059] The operation of machine 10 will now be described in
connection with the previously described figures, as well as FIGS.
12-16. As shown in FIG. 4, receptacles 102 are loaded with respect
with input baskets 100 each containing a number of cassette and
frame assemblies 150. These input baskets 100 preferably are taken
directly from a tissue processing machine (not shown) in which the
tissue samples 210 (FIG. 10) contained in each cassette 150a have
been processed in a known manner to replace the fluid in the tissue
samples 210 with paraffin or another suitable material. In order to
load the baskets 100 into the receptacles 102, the cassette
positioning device 120 must be raised to its uppermost position
allowing the input door 16 to be opened. When the input door 16 is
then closed, the positioning device 120 lowers plate 134 thereby
allowing fingers 130, 130a to lower under the force generated by
springs 132 and/or weights (not shown). As shown in FIG. 12, pick
and place robot 40 is moved such that pick and place head 42 and,
more specifically, gripper fingers 252, 254 enter opening 101a and
the dispensing slots 152, 154 of one of the baskets 100 (FIGS. 4,
4B). The gripper fingers 252, 254 grasp the lowermost cassette and
frame assembly 150. Pick and place robot 40 then carries the
gripped cassette and frame assembly 150 to sensor 86 (FIG. 3).
Based on the reading from cassette sensor 86, the cassette and
frame assembly 150 is carried to one of the base molds 82 or 84
which is empty and also corresponds to the configuration (e.g.,
size and/or shape) of the detected cassette and frame assembly 150.
The pick and place head 42 drops the cassette and frame assembly
150 into the selected base mold 82 or 84 and then the pick and
place robot 40 moves back to the input basket 100 to repeat the
process during the initial start up. During normal operation, pick
and place robot 40 will move to a cooled/hardened assembly 150 to
one of the output slots 90 (FIG. 15), and then return to the input
basket 100.
[0060] The staging robot 170 is then moved into position over the
cassette and frame assembly 150 just loaded into the corresponding
base mold 82, as shown in FIG. 6. As shown and described above in
connection with FIGS. 8-10, the cassette 150a is staged (i.e.,
moved) into the base mold 82 and the base mold 82 is filled with
liquid paraffin from dispensing tube 212. When the dispensing
operation is complete, as detected by sensor 234, the staging robot
170 moves to the next position above another base mold 82 or 84 of
a TEC unit 80 at which the pick and place robot 40 has loaded
another cassette and frame assembly 150. The staging and filling
operation is then repeated on the next successive cassette and
frame assembly 150. As shown in FIG. 14, the pick and place head 42
is moved to the position of an embedded cassette and frame assembly
150 which has completed the cooling or hardening process on a TEC
unit 80 and the cassette and frame assembly 150 is gripped using
gripper fingers 252, 254. Pick and place robot 40 then moves the
pick and place head 42 with the gripped cassette and frame assembly
150, now including a hardened block 290 of paraffin containing
tissue sample 210, to one of the output trays 18a having slots 90
as shown in FIG. 15. The embedded cassette and frame assembly 150
is held within slot 90 by a spring loaded clip member 300 which
frictionally engages the embedded cassette and frame assembly 150.
At this point, the gripper fingers 252, 254 release the cassette
and frame assembly 150. As shown in FIG. 16, output tray 18a may be
removed by actuating solenoid 96, pivoting tray 18a outwardly, and
lifting the tray 18a from the machine 11.
[0061] The operation of the machine 10 is controlled by a system
control 350 illustrated in FIG. 17. The system control 350 includes
a control 352 that is connected to a user I/O 354, for example, a
touch screen monitor. The control 352 is also, optionally,
connected to an ethernet 356 to provide communication between the
control 352 and another computer (not shown). The control 352
receives inputs from various sensors on the machine 10, for
example, an ultrasonic receiver 358 that, in turn, receives inputs
from the paraffin fill sensor 234 and reservoir level sensor 359.
Other control inputs are connected to a digital I/O interface 360
that, in turn, is connected to various sensors, for example, the
frame/cassette sensor 86, receiver sensors 92, 94, the frame
present sensor 280 and the basket present sensor 112.
[0062] The control 352 provides command signals to stepper motor
controllers 362 that, in turn, provide comparable command signals
to the stepping motors 60a, 62a, 64a, and 192, 174, 184 and 136 in
a known manner. The controllers 362 receive feedback signals from
limit switches, for example, limit switches 230, 232 detecting the
limits of travel along the v-axis. In addition, encoders 364 are
coupled to respective stepper motors and provide respective
feedback signals to respective stepper motor controllers 362, so
that the commanded motion of each of the stepper motors can be
confirmed. If a stepper motor controller 362 fails to detect a
commanded motion of a respective stepper motor, the controller
provides an error signal back to the control 352 for display on the
monitor 354.
[0063] The control 352 is further connected to a thermal electric
3-state controller 366 that controls the operation of each of the
16 TEC plates 236 associated with each of the 8 pairs of base molds
82, 84. Each TEC plate 236 has a corresponding RTD 368 that
provides a temperature feedback signal to the controller 366
representing the temperature of its respective TEC plate 236.
Referring to FIG. 18, the thermal electric 3-state controller 366
has a microcontroller 370 driven by a clock 372. It should be noted
that although the machine has only 16 TEC plates 236, the
controller 366 is built to accommodate 24 TEC plates 236. The
microcontroller 370 includes software modules providing a system
interface 374, a TEC loop state machine 376, a calibration
algorithm 378 and an A/D converter and signal processor 380. The
controller 370 controls all 16 TEC plates 236 and can be configured
to control fewer or more TEC plates 236. In order to accommodate
such a large number of devices, that is, 24 TEC plates 236 and 24
RTDs 368, a complex programmable logic device ("CPLD") 388 is used
as an interface device between the microcontroller 370 and the TEC
plates 236 and RTDs 368. A loop clock 382 provides successive time
windows that are adjustable by the loop clock state machine 393 of
the CPLD 388. During each time window, in response to a command
from the microcontroller 370, the A/D converter state machine 389
within the CPLD 388 causes outputs from all of the RTDs to be
multiplexed into the A/D converter 384. During each time window,
RTD outputs are read by the microcontroller 370 as part of the
microcontroller 370 regulating the operation of each of the TEC
plates 236 in response to commands from the control 352 (FIG. 17).
If the operating state of any of the TEC plates 236 is to be
changed, a state of a MOSFET current switch 395 within the TEC
interface 392 must be changed; and that new state is transferred to
the MOSFET control state machine 391 of the CPLD 388. That new
state is then supplied via a respective driver 390 to a respective
current switch 395. Thus, the measured temperatures provided by
respective RTDs 368 are maintained in close correspondence to the
temperatures commanded by the control 352 (FIG. 17).
[0064] Referring back to FIG. 17, the control 352 provides command
signals to a solenoid driver 394 that is operatively connected to
the gripper solenoid 260, paraffin valve 214 and each of the four
tray latch solenoids 97. Referring to FIG. 19, the solenoid driver
has a clock 397 for a microcontroller 398 that includes software
modules providing a system interface 400, a gripper control 402,
pulse width modulators 404, 406 and an I/O control 408. The I/O
control 408 provides output signals to the I/O interface 410 to
drive solenoid status LEDs 412. In order to minimize heat within
the machine 10, the solenoid driver 394 is designed to provide the
minimum current necessary to operate the various solenoids on the
machine 10. For example, the gripper control 402 operates the
gripper solenoid 260 by first providing an actuation current to a
driver 414 that, in turn, provides an output current to the
solenoid 260 via amplifier 415. That actuation current is effective
to rapidly actuate and change the state of the solenoid 260 and the
gripper 250; and thereafter, the gripper control 402 provides a
hold current to a driver 416 that, in turn, provides the minimum
current necessary to hold the solenoid 260 in its current
state.
[0065] A signal requesting one of the four tray latches be opened
can be provided by input devices 417, for example, a push button on
the machine or a button on the touchscreen of the user I/O 354
(FIG. 17), In response to that request, microcontroller 398
operates the pulse width modulator ("PWM") 404 to provide output
signals to a PWM selection switch 418 that, in turn, provides
actuation and hold currents via an amplifier 422 to an appropriate
one of the MOSFET current switches 423. That MOSFET current switch
423 operates a respective one of the four tray latch solenoids 97,
thereby releasing a latch or interlock so that a tray can be
pivoted outward and removed. Similarly, in response to a command
from the control 352, the microcontroller 398 operates the PWM 406
to provide actuation and hold currents signals to a valve solenoid
215 via two-way PWM switch selection 420, amplifier 424 and MOSFET
current switches 425.
[0066] Referring back to FIG. 17, a heater controller 426 is
responsive to commands from the control 352 to control the heaters
220 associated with the reservoir 28, valve 214, nozzle 212, feed
tube 216 and the eight receptacles 102 on the input door 16. The
heater controller 426 is operative to turn the heaters 220 on and
off in order to maintain the temperature commanded by the control
352. The heaters are both resistive AC and DC heaters, and RTDs 124
are located close to respective ones of the heaters 220 to provide
temperature feedback signals representing the temperatures of the
respective devices being heated. In order for a heater control
microcontroller to control such a large number of heaters and RTDs,
a loop state machine and CPLD can be used in a manner similar to
that described with respect to the TEC controller of FIG. 18. Zero
crossing TRIAC current switches can be used in a known manner to
control the operation of the DC and AC heaters, respectively.
[0067] In use, in order to load the baskets 100 into the
receptacles 102, an operator uses the touchscreen monitor 354 to
command the cassette positioning device 120 to raise to its
uppermost position, thereby allowing the input door 16 to be
opened. After the baskets 100 have been placed within the machine
10, the input door 16 is then closed. The operator again utilizes
the touchscreen monitor to command the positioning device 120 to
lower plate 134, thereby allowing fingers 130, 130a to lower under
the force generated by springs 132 and/or weights (not shown). As
will be appreciated, the process of moving the cassette positioning
device 120 and opening and closing the input door 16 can be fully
automated. In addition, the operator loads output trays 18 into the
machine 10.
[0068] The processing of frames and cassette assemblies 150 is
conducted in three operating modes. In a first load molds mode,
frame and cassette assemblies are successively transferred from
baskets 100 to one of the molds 82, 84 (FIG. 3) of each of the
eight pairs of molds; and the filling and cooling cycles are
initiated. After the eight molds 82 or 84 have been loaded, filled
and are cooling, the control 352 initiates a continuous processing
mode, in which cooled frame and mold assemblies 150 are
successively moved from the molds 82 or 84 to output trays 18. The
emptied molds are immediately reloaded with another frame and
cassette assembly 150 from a basket 100, and the continuous mode
continues until all of the assemblies 150 have been unloaded from a
basket 100. Thereafter, the control 352 initiates an unload molds
mode in which the remaining cooled frame and cassette assemblies
are moved from the molds 82, 84 to the trays 18.
[0069] To initiate processing, the operator again utilizes the
touchscreen monitor 354 to command a cycle start. In response to
that command, the control 352 executes a load molds cycle as shown
in FIG. 20. The control 352 first, at 450, determines whether
transport robot 40 and staging robot 170 are at their home
positions by monitoring the states of limit switches 364. The home
position of the transport robot 40 is defined at the x-axis travel
limit closest to the first mold to be filled, the upper z-axis
limit and the forward, relative to the machine 10, y-axis limit.
The home position of the staging robot 170 is defined at the x-axis
travel limit closest to the last mold to be filled, the upper
z-axis limit and the forward, relative to the machine 10, y-axis
limit. If either of the robots is not at its home position, the
control 352 provides, at 452, command signals to the stepper motor
controllers 362 to operate the stepping motors and move the robots
to their home position. After determining, at 454, that a pause
timer is not operating, the control 352 commands the controllers
362 to move, at 456, the gripper 250 to a position outside but
immediately adjacent to an opening 101 (FIG. 4) adjacent a basket
100. Thereafter, the control 352 executes, at 458, an input basket
pickup subroutine illustrated in more detail in FIG. 21.
[0070] In executing this subroutine, the control 352 first, at 602,
commands the solenoid driver 394 to actuate the gripper solenoid
260 and open the gripper fingers 252 (FIG. 11A). Thereafter, the
control 352 commands, at 604, the appropriate controller 362 to
operate the stepper motor 64a and move the gripper fingers 252
through the opening 101a (FIG. 12) and into the basket 100. The
control 352 then commands, at 606, the gripper fingers 252 to close
(FIG. 11B); and, at 608, the stepping motor 64a to reverse its
motion and return the gripper fingers 252 to their original
position immediately adjacent the opening 101a. Thereafter, the
control 352 reads, at 610, the state of the frame sensor 280
located on the gripper 250. The operation of the load molds cycle
of FIG. 20 continues by the control 352 determining, at 460,
whether a frame 150b is present in the gripper 250.
[0071] If so, the control 352 commands, at 462, the stepping motors
to move the gripper 250 to the cassette sensor 86 (FIG. 3). At 464,
the control 352 executes a load cassette test subroutine
illustrated in more detail in FIG. 22. Several tests are performed
utilizing the sensor 86 to determine, at 620, that a frame and
cassette assembly 150 is properly oriented in the gripper 250. For
example, it is possible that the assembly 150 may have
inadvertently been loaded upside down or inadvertently rotated
front to back. Next, the control determines, at 622, that a
cassette 150a (FIG. 4B) is located in the frame 150b. The sensor
280 on the gripper 250 is only capable of detecting the presence of
a frame portion 150b of the frame and cassette assembly 150; and
therefore, it is important to determine that the frame 150b does
support a cassette 150a. Further, the machine 10 is capable of
processing cassettes of two different sizes; and therefore, at 624,
the control 352 manipulates the gripper 250 such that the sensor 86
can be used to detect which size cassette is currently in the
gripper. When a size is detected, an appropriate flag is set at
626, 628. If an error is detected in any of the tests, the control
352 provides, at 630, a display of the error on the monitor 354;
and it ends its cycle of operation until the error has been
corrected.
[0072] Returning to the load molds cycle of FIG. 20, after the load
cassette tests have been successfully completed, the control 352,
at 466, commands the gripper 250 to be moved to a vertical
clearance position above one of the mold pairs that is empty and
corresponds to the cassette size that was detected, for example, a
first one of the molds 82 (FIG. 3). In addition, the control 352
commands the staging robot 170 to move from its home position to
the right to a position immediately adjacent the mold 82. Further,
the control 352 provides an output signal commanding the thermal
electric controller 366 to turn on the TEC plate 236 associated
with the mold 82. The thermal electric controller 366 utilizes the
temperature feedback signal from the RTD 368 to operate the TEC
plate 236 such that the mold 82 is heated to a desired
temperature.
[0073] After the transport robot 40 has moved the gripper to the
vertical clearance position, the control 352 executes, at 468, a
load frame in mold subroutine illustrated in more detail in FIG.
23. First, the control 352 commands, at 632, the stepping motor 62a
to lower the gripper 250 such that the frame and cassette assembly
150 is on or slightly above the mold 82a (FIG. 13). Thereafter, the
control 352 commands, at 634, the gripper fingers 252 to open (FIG.
11A); and then, at 636, the control 352 reverses the operation of
the stepping motor 62a to raise the gripper 250 to its vertical
clearance position. The control then, at 638, reads the frame
sensor 280 to confirm that a frame 150b is no longer present in the
gripper 250. If a frame is detected, the control 352 displays an
appropriate error signal, at 640, and ceases operation.
[0074] Next, the control 352 commands the stepper motor 174 to move
the staging robot 170 over the mold. Thereafter, the control, at
472, starts an internal pause timer and then initiates, at 474, a
mold fill cycle subroutine as shown in more detail in FIG. 24. In
executing the mold fill cycle, the control 352 first commands, at
650, the stepper motor 184 to lower the stager/filler 172 (FIG. 8).
The vertical support member 202 moves the four spring biased
holding members 206 downwardly against the top corners of the frame
150b to immobilize the frame during the paraffin filling process.
Simultaneously, the pushers 203 (FIG. 9) are moved downward against
the top corner portions of the cassette 150a, thereby firmly
pushing the cassette and frame assembly 150 firmly into the mold
84. The control 352 then commands, at 652, the motor 184 to raise
the stager/filler 172 to a position at which the pushers 203 will
not contact any paraffin during the filling process. It should be
noted that the holding members 206 still retain the frame 150b
against the mold with spring pressure. Thereafter, at 654, the
control 352 provides an output signal to the solenoid driver 394
commanding the paraffin valve 214 to open and the mold to begin
filling with paraffin (FIG. 10). In addition, the control 352
initiates the operation of an internal cool-on timer. It has been
determined through experimentation that a higher quality process is
achieved if the cooling of the mold is initiated slightly prior to
the end of the mold filling cycle. However, the exact time that the
TEC should be switched to a cool mode is application dependent.
Therefore, after the control 352 determines, at 656, that the
cool-on timer has expired; the control 352 switches, at 658, the
operation of the respective TEC plate 236 from the heat mode to a
cool mode and in addition, initiates the operation of an internal
cool-off timer. The control 352 then determines, at 660, when it
receives a signal from the paraffin fill sensor 234 indicating that
the mold 84 is filled. At that point, the control 352 then
provides, at 662, output signals to the solenoid driver 394
commanding the fill valve to close. In addition, the control 352
commands the stepper motor 184 to raise the stager/filler 172 to
its uppermost position.
[0075] Returning to FIG. 20, upon initiating the mold fill cycle
subroutine 476, the control 352 also determines whether the current
mold being filled is the last mold to be filled. If not, the
control then determines, at 454, whether the pause timer has
expired. The pause timer simply causes the operation of the
transport robot 40 to pause for a short period of time. If it has,
the control then commands the stepper motors 60a, 62a, 64a to move
the gripper to a position adjacent the opening of the basket. The
process described with respect to steps 454-476 is repeated for
each of the eight mold positions. When the last mold is being
filled as detected at 476 by the control 352, the control then
commands, at 478, the motor 60a to move the gripper 250 to the
vertical clearance position over the first mold; and thereafter,
the load molds cycle of FIG. 20 ends. It should be noted that, if
at 460, the control 352 determines that a frame 150b is not present
in the gripper 250, it then checks, at 480, whether the current
basket is empty. The control 352 maintains a count of the frame and
cassette assemblies 150 removed from the current basket. If a
number of frame and cassette assemblies have been removed from the
current basket equal to its maximum capacity, then the control, at
482, determines whether all baskets are empty. If not, the control
commands the gripper then to move to the opening of the adjacent
basket on the input door 16.
[0076] After all the molds are initially filled with frame and
cassette assemblies and fill cycles are initiated, the control 352
switches to a continuous run mode as illustrated in FIG. 25. The
first step of that mode is to confirm, at 500, that the load molds
mode is complete. It should be remembered that the transport robot
40 is currently positioned at the vertical clearance height above
the first mold. The control 352 then determines, at 502, whether
the cool-off timer for that mold has expired. When it does, the
control then, at 504, executes an unload frame from mold subroutine
illustrated in FIG. 26.
[0077] To unload a frame and cassette assembly from the mold 84, as
shown in FIG. 14, the control 352 provides output signals at steps
670-676 to command the gripper fingers 252 to open, the stepper
motor 64a to lower the gripper to the mold, the gripper fingers 252
to close and the stepper motor 62a to raise the gripper back to its
vertical clearance position. Thereafter, the control 352 reads the
state of the frame sensor 280 to determine whether a frame is
present. If not, the control displays an error, at 680, and the
cycle ends.
[0078] Referring back to FIG. 25, the control thereafter provides,
at 506, command signals to the stepper motors 60a, 62a, 64a to move
the gripper to the sensor 86 (FIG. 3). When in that position, the
control 352 initiates, at 508, an unload cassette test subroutine
shown in more detail in FIG. 27. First, the control 352 commands
the stepper motors 60a, 62a, 64a to move the gripper 250 with
respect to the sensor 86 such that by monitoring output signals
from the sensor 86, the control 352 can determine, at 682, that a
frame 150b is present. Thereafter, the control commands the gripper
250 to be moved to positions permitting the control 352 to
determine, at 684, whether a cassette 150a is present in the frame.
It is possible that in the filling and cooling process or in the
unloading process, that the cassette became separated from the
frame. It is also possible that the frame is not being properly
held in the gripper. For example, referring to FIG. 11A, the frame
150b may be held by only the forward pins 252a, 254a of the
gripper. In that scenario, the frame is slightly rotated such that
the rearward pins 252b, 254b are not properly secured in the frame.
To detect this situation, the control 352 commands the gripper 250
to be moved to positions permitting, at 686, the control to
determine that the frame is properly secured in the gripper. If any
error is detected, the control provides, at 688, an error display
on the monitor 354 and the cycle ends.
[0079] If the unload cassette test subroutine is successfully
executed, returning to FIG. 25, the control 352 commands motors
60a, 62a, 64a to move the gripper with the cassette and frame
assembly 150, now including a hardened block 290 of paraffin
containing tissue sample 210, adjacent one of the slots 90 of one
of the output trays 18a as shown in FIG. 15. Thereafter, the
control 352 initiates a frame release subroutine illustrated in
more detail in FIG. 28. To release the frame and cassette assembly
150, the control 352 first, at 690, commands the stepper motor 62a
to move the gripper fingers 25 into the tray slot 90. The embedded
cassette and frame assembly 150 is held within slot 90 by a spring
loaded clip member 300 which frictionally engages the embedded
cassette and frame assembly 150. Thereafter, at 692, the control
commands the gripper fingers 252 to open and further commands the
stepper motor 62a, at 694, to reverse motion, thereby removing the
gripper fingers from the tray slot. Next, the control 352 reads the
state of the frame sensor 280 to determine, at 696, whether a frame
is present. If a frame is detected, the control 352 provides an
error display to the monitor 354.
[0080] Returning to FIG. 25, the control then, at 514, provides
command signals to the stepper motors 60a, 62a, 64a to move the
gripper to a basket opening. The transport robot 40 then proceeds
in response to commands from the control 352 to load another frame
and cassette assembly from the input basket in accordance with
steps 514-532. That loading operation is identical to the loading
operation previously described with respect to steps 456 through
470 of FIG. 20. After loading another frame and cassette assembly
150 into the first mold, the control then, at 534, initiates a mold
fill cycle as previously described with respect to FIG. 24.
Simultaneously with initiating the mold fill cycle, the control 352
provides, at 536, a command signal to the stepper motor 60a to move
the gripper over the next mold to be emptied. The controller then,
at 502, determines whether the cool-off timer for that mold has
expired. The process of steps 502-536 continues until the control
352 determines, at 522, that all the input baskets are empty. At
that point, the continuous run mode ends and the control 352
switches to the clear molds cycle illustrated in FIG. 29.
[0081] After confirming, at 540, that the continuous run mode is
complete, the control 352 commands, at 542, the stepper motors 174,
184 and 192 to move the staging robot to its home position.
Thereafter, the control 352 determines, at 544, whether the
cool-off timer for the current mold has expired. If so, the control
352 unloads a frame from that mold in accordance with process steps
546-554 that are identical to the process steps 504-512 previously
described with respect to FIG. 25. That process iterates until the
control 352 detects, at 556, that all molds are empty. At this
point, the output trays can be removed from the machine 10. As
shown in FIG. 16, output tray 18a may be removed by actuating
solenoid 96, pivoting tray 18a outwardly, and lifting the tray 18a
from the machine 10.
[0082] While the present invention has been illustrated by a
description of a preferred embodiment and while the embodiment has
been described in some detail, it is not the intention of
Applicants to restrict or in any way limit the scope of the
appended claims to such detail. Additional advantages and
modifications will readily appear to those skilled in the art. The
various features of the invention may be used alone or in numerous
combinations depending on the needs and preferences of the user.
For example, in the described embodiment, eight pairs of molds are
used in order to accommodate cassettes of two different cassette
sizes. As will be appreciated, in other embodiments, three
different cassette sizes can be accommodated by providing 24 molds
in a matrix of three molds in each of the eight rows of molds.
[0083] In the described embodiment, the sensor 86 is used to test
the frame and cassette assemblies after being picked up from a
basket and after being removed from a mold. As will be appreciated,
another sensor can be placed in another location to test the frame
and cassette assemblies after being removed from the mold. Such a
different sensor may be desirable to improve the cycle time of the
machine 10. As will be further appreciated, different types of
sensors may change the process of checking the frame and cassette
assemblies.
[0084] This has been a description of the present invention, along
with the preferred methods of practicing the present invention as
currently known. However, the invention itself should only be
defined by the appended claims.
* * * * *