Sélection de la langue

Search

Sommaire du brevet 2800136 

Énoncé de désistement de responsabilité concernant l'information provenant de tiers

Une partie des informations de ce site Web à été fournie par des sources externes. Le gouvernement du Canada n'assume aucune responsabilité concernant la précision, l'actualité ou la fiabilité des informations fournies par les sources externes. Les utilisateurs qui désirent employer cette information devraient consulter directement la source des informations. Le contenu fournit par les sources externes n'est pas assujetti aux exigences sur les langues officielles, la protection des renseignements personnels et l'accessibilité.

Disponibilité de l'Abrégé et des Revendications

L'apparition de différences dans le texte et l'image des Revendications et de l'Abrégé dépend du moment auquel le document est publié. Les textes des Revendications et de l'Abrégé sont affichés :

  • lorsque la demande peut être examinée par le public;
  • lorsque le brevet est émis (délivrance).
(12) Brevet: (11) CA 2800136
(54) Titre français: CASSETTE POUR UN APPAREIL DE TRAITEMENT AUTOMATISE ET INTEGRATION DES ECHANTILLONS DE TISSUS
(54) Titre anglais: CASSETTE FOR APPARATUS FOR AUTOMATED HANDLING AND EMBEDDING OF TISSUE SAMPLES
Statut: Périmé
Données bibliographiques
(51) Classification internationale des brevets (CIB):
  • G01N 1/36 (2006.01)
(72) Inventeurs :
  • ALLEN, DOUGLAS P. (Etats-Unis d'Amérique)
  • DINOVO, DOMINIC P. (Etats-Unis d'Amérique)
  • HUDDLESTON, MATTHEW J. (Etats-Unis d'Amérique)
  • HUGHES, KENNETH E. (Etats-Unis d'Amérique)
  • KELLER, GEORGE A. (Etats-Unis d'Amérique)
  • KUISICK, KEITH A. (Etats-Unis d'Amérique)
  • QUAM, REBECCAH P. (Etats-Unis d'Amérique)
  • ROBINSON, CECIL R. (Etats-Unis d'Amérique)
  • TURNER, JONATHAN E. (Etats-Unis d'Amérique)
  • VANHOOSE, ERNEST D. (Etats-Unis d'Amérique)
  • WARD, THOMAS J. (Etats-Unis d'Amérique)
  • WILLIAMSON, WARREN P. (Etats-Unis d'Amérique)
(73) Titulaires :
  • BIOPATH AUTOMATION, L.L.C. (Etats-Unis d'Amérique)
(71) Demandeurs :
  • BIOPATH AUTOMATION, L.L.C. (Etats-Unis d'Amérique)
(74) Agent: MACRAE & CO.
(74) Co-agent:
(45) Délivré: 2014-07-08
(22) Date de dépôt: 2002-09-26
(41) Mise à la disponibilité du public: 2004-04-08
Requête d'examen: 2012-12-21
Licence disponible: S.O.
(25) Langue des documents déposés: Anglais

Traité de coopération en matière de brevets (PCT): Non

(30) Données de priorité de la demande: S.O.

Abrégés

Abrégé français

L'invention comprend une cassette adaptée pour l'utilisation dans un appareil pour la manipulation automatisée des échantillons de tissu. La cassette est adaptée pour porter un échantillon de tissu et comprend un corps doté d'une paroi inférieure et d'au moins une paroi latérale s'étendant vers le haut par rapport à ladite paroi inférieure afin de définir un espace intérieur permettant de recevoir l'échantillon de tissu et un élément détectant associé au dit corps et configuré de façon à permettre un système de détection automatisé de déterminer au moins une caractéristique de la cassette. Dans d'autres variantes préférées, l'élément détectant comprend un ou plusieurs trous, est lisible à la machine ou porte des marques lisibles à la machine.


Abrégé anglais

The invention comprises a cassette adapted for use in an apparatus for automated handling and embedding of tissue samples. The cassette is adapted to hold a tissue sample and comprises 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. In further preferred embodiments, the sensing element comprises one or more holes, is machine readable or comprises machine readable indicia.

Revendications

Note : Les revendications sont présentées dans la langue officielle dans laquelle elles ont été soumises.



-28-

CLAIMS:

1. A cassette for holding a tissue sample during a
microtome slicing operation in which the cassette and the
tissue sample are sliced prior to mounting and examination
of the tissue sample on a microscope slide, the cassette
comprising:
a microtome sectionable 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, whereby the microtome
sectionable body and the tissue sample are together
sectionable with a microtome for mounting a sliced section
of the tissue sample on the microscope slide; and
a sensing element associated with said body and
configured to allow an automated sensing system to detect
a first physical configuration and a second, different
physical configuration of the cassette.
2. The cassette of claim 1, wherein the sensing element
is machine readable.
3. The cassette of claim 1, wherein the sensing element
comprises machine readable indicia.
4. The cassette of claim 1, in combination with a frame,
said frame receiving said microtome sectionable body in a
manner allowing movement of said body from a first
position to a second position suitable for microtome
sectioning of said body.
5. The cassette of claim 1, wherein the sensing element
is configured to detect the size of the cassette.
6. The cassette of claim 1, wherein the sensing element
is configured to detect the shape of the cassette.

Description

Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.



CA 02800136 2012-12-21

CASSETTE FOR APPARATUS FOR AUTOMATED HANDLING AND
EMBEDDING OF TISSUE SAMPLES

Field of the Invention
The present invention generally relates to a cassette for use in an
apparatus for handling and embedding tissue samples for biopsy analysis.
Background of the Invention

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.

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.


CA 02800136 2012-12-21
-2-

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.

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,


CA 02800136 2012-12-21
-3-

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.

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.

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.

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. Patent No. 5,817,032 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


CA 02800136 2012-12-21

-4-
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.
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
In a preferred embodiment, the invention comprises a cassette
adapted for use in an apparatus for automated handling and embedding of tissue
samples. The cassette is adapted to hold a tissue sample and comprises 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.
In further preferred embodiments, the sensing element comprises one or more
holes, is machine readable or comprises machine readable indicia.
Another aspect of 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.


CA 02800136 2012-12-21
-4a-

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


CA 02800136 2012-12-21
WO 2004/029584
-5-
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.

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.

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

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.
Fig. 2 is a rear perspective view showing the inside of the machine.


CA 02800136 2012-12-21
-6-

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.

Fig. 4 is an exploded perspective view of the input door section of the
machine.
Fig. 4A is an exploded perspective view of the inside surface of the input
door
showing the cassette and frame assembly dispenser.

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.

Fig. 5 is a top view of the inside of the machine.

Fig. 6 is an enlarged perspective view of the staging robot in the machine.

Fig. 7 is a perspective view of the staging robot with the stager/filler in
exploded
form.

Fig. 8 is a cross sectional view taken generally along line 8-8 of Fig. 6.

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.

Figs. 1 OA and 1 OB are enlarged cross sectional views similar to Fig. 9 and
also
progressively illustrating the staging operation.

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.

Fig. 11 B is a partially cross sectioned top view similar to Fig. 11 A, but
illustrating
the cassette and frame assembly gripped by the gripper fingers.

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.

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.

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.


CA 02800136 2012-12-21
-7-

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.

Fig. 16 is a cross sectional view similar to Fig. 15, but illustrating the
removal of
the output tray from the machine.

Fig. 17 is a schematic block diagram of a control system for the machine of
Fig.
1.

Fig. 18 is a schematic block diagram of a thermal electric 3 state controller
used
in the control system of Fig. 17.

Fig. 19 is a schematic block diagram of a solenoid driver used in the control
system of Fig. 17.

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.

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.

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.

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.

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.

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.
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.

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.


CA 02800136 2012-12-21
-8-

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.
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.

to test a filled frame and cassette assembly removed from a mold in the
machine of Fig. 1.
Detailed Description of the Drawings

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 1 4a, 1 6a. 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 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,
1 8d (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


CA 02800136 2012-12-21
-9-

supports are generally of a form as described in U.S. Patent 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.

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.

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


CA 02800136 2012-12-21
-10-

and/or sizes of cassette and frame assemblies to be processed in machine 10.
In
a preferred embodiment, the cassette is adapted for holding a tissue sample
and
comprises 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. 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.
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.
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


CA 02800136 2012-12-21
-10a-

previous tissue processing procedure in a liquified 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


CA 02800136 2012-12-21
-11-

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 UltemO, 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.

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


CA 02800136 2012-12-21
-12-

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.
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 and an
outer frame 150b preferably constructed in accordance with the disclosure set
forth in U.S. Patent No. 5,817,032. In a preferred embodiment, the cassette is
adapted for holding a tissue sample and comprises 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. In further preferred
embodiments, the sensing element comprises one or more holes, is machine
readable or comprises machine readable indicia. 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.


CA 02800136 2012-12-21
-12a-

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).


CA 02800136 2012-12-21
-13-

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.

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 1 50a 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 - 65 C). Vertical movement
of pushers
203 is accomplished by activating motor 184 and screw 186 such that vertical
support member


CA 02800136 2012-12-21
-14-

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 1 50a. Simultaneously,
vertical support
member 202 moves four spring-loaded holding members 206 (only two shown)
downwardly
against the top corner portions of frame 1 50b to immobilize the frame 150b
during the staging

and paraffin filling process (Fig. 1 OA). After the staging process is
complete, the bottom of the
cassette 1 50a is exposed outwardly of the frame 150b and within the interior
of the base mold
84.

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 -65 C. Dispensing tube 212 is preferably heated by a cartridge heater
220
controlled by a Resistance Temperature Detector ("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. ML 102
obtained from Cosense, Inc. of Hauppauge, Long Island, New York) 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.


CA 02800136 2012-12-21
-15-

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 1 50a. 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 pettier 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.

Figs. 11 A and 11 B 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. 11 A and a closed or gripping position shown
in Fig. 11 B.
Linkages 262, 264 move between the position shown in Fig. 11 A to the pivoted,
over-center
position shown in Fig. 11 B. 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


CA 02800136 2012-12-21
-16-

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.

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 101 a 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.


CA 02800136 2012-12-21
-17-

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.

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.


CA 02800136 2012-12-21
-18-

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 364.

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


CA 02800136 2012-12-21
-19-

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).

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.

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


CA 02800136 2012-12-21
-20-

valve solenoid 215 via two-way PWM switch selection 420, amplifier 424 and
MOSFET current
switches 425.

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.

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.

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


CA 02800136 2012-12-21
-21-

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.

To initiate processing, the operator again utilizes the touchscreen monitor
364 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.

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. 11 B); 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 101 a.
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.


CA 02800136 2012-12-21
-22-

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 1 50b
of the frame and
cassette assembly 150; and therefore, it is important to determine that the
frame 150b does

support a cassette 1 50a. 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.

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.

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


CA 02800136 2012-12-21
-23-

(Fig. 13). Thereafter, the control 352 commands, at 634, the gripper fingers
252 to open (Fig.
11 A); 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.

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 1
50b 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 1 50a,
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


CA 02800136 2012-12-21
-24-

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.

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 1 50b 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.

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.

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.


CA 02800136 2012-12-21
-25-

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.

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. 11 A, the frame 1 50b 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.

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,


CA 02800136 2012-12-21
-26-

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.
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.

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.

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


CA 02800136 2012-12-21
-27-

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.

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.

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.

Dessin représentatif
Une figure unique qui représente un dessin illustrant l'invention.
États administratifs

Pour une meilleure compréhension de l'état de la demande ou brevet qui figure sur cette page, la rubrique Mise en garde , et les descriptions de Brevet , États administratifs , Taxes périodiques et Historique des paiements devraient être consultées.

États administratifs

Titre Date
Date de délivrance prévu 2014-07-08
(22) Dépôt 2002-09-26
(41) Mise à la disponibilité du public 2004-04-08
Requête d'examen 2012-12-21
(45) Délivré 2014-07-08
Expiré 2022-09-26

Historique d'abandonnement

Il n'y a pas d'historique d'abandonnement

Historique des paiements

Type de taxes Anniversaire Échéance Montant payé Date payée
Requête d'examen 800,00 $ 2012-12-21
Le dépôt d'une demande de brevet 400,00 $ 2012-12-21
Taxe de maintien en état - Demande - nouvelle loi 2 2004-09-27 100,00 $ 2012-12-21
Taxe de maintien en état - Demande - nouvelle loi 3 2005-09-26 100,00 $ 2012-12-21
Taxe de maintien en état - Demande - nouvelle loi 4 2006-09-26 100,00 $ 2012-12-21
Taxe de maintien en état - Demande - nouvelle loi 5 2007-09-26 200,00 $ 2012-12-21
Taxe de maintien en état - Demande - nouvelle loi 6 2008-09-26 200,00 $ 2012-12-21
Taxe de maintien en état - Demande - nouvelle loi 7 2009-09-28 200,00 $ 2012-12-21
Taxe de maintien en état - Demande - nouvelle loi 8 2010-09-27 200,00 $ 2012-12-21
Taxe de maintien en état - Demande - nouvelle loi 9 2011-09-26 200,00 $ 2012-12-21
Taxe de maintien en état - Demande - nouvelle loi 10 2012-09-26 250,00 $ 2012-12-21
Taxe de maintien en état - Demande - nouvelle loi 11 2013-09-26 250,00 $ 2013-08-09
Taxe finale 300,00 $ 2014-04-23
Taxe de maintien en état - brevet - nouvelle loi 12 2014-09-26 250,00 $ 2014-08-15
Taxe de maintien en état - brevet - nouvelle loi 13 2015-09-28 250,00 $ 2015-08-12
Taxe de maintien en état - brevet - nouvelle loi 14 2016-09-26 250,00 $ 2016-08-11
Taxe de maintien en état - brevet - nouvelle loi 15 2017-09-26 450,00 $ 2017-08-14
Taxe de maintien en état - brevet - nouvelle loi 16 2018-09-26 450,00 $ 2018-08-14
Taxe de maintien en état - brevet - nouvelle loi 17 2019-09-26 450,00 $ 2019-09-04
Taxe de maintien en état - brevet - nouvelle loi 18 2020-09-28 450,00 $ 2020-08-24
Taxe de maintien en état - brevet - nouvelle loi 19 2021-09-27 459,00 $ 2021-08-26
Titulaires au dossier

Les titulaires actuels et antérieures au dossier sont affichés en ordre alphabétique.

Titulaires actuels au dossier
BIOPATH AUTOMATION, L.L.C.
Titulaires antérieures au dossier
S.O.
Les propriétaires antérieurs qui ne figurent pas dans la liste des « Propriétaires au dossier » apparaîtront dans d'autres documents au dossier.
Documents

Pour visionner les fichiers sélectionnés, entrer le code reCAPTCHA :



Pour visualiser une image, cliquer sur un lien dans la colonne description du document. Pour télécharger l'image (les images), cliquer l'une ou plusieurs cases à cocher dans la première colonne et ensuite cliquer sur le bouton "Télécharger sélection en format PDF (archive Zip)" ou le bouton "Télécharger sélection (en un fichier PDF fusionné)".

Liste des documents de brevet publiés et non publiés sur la BDBC .

Si vous avez des difficultés à accéder au contenu, veuillez communiquer avec le Centre de services à la clientèle au 1-866-997-1936, ou envoyer un courriel au Centre de service à la clientèle de l'OPIC.


Description du
Document 
Date
(yyyy-mm-dd) 
Nombre de pages   Taille de l'image (Ko) 
Abrégé 2012-12-21 1 16
Description 2012-12-21 30 1 364
Revendications 2012-12-21 1 15
Dessins 2012-12-21 27 1 386
Dessins représentatifs 2013-01-23 1 16
Page couverture 2013-02-04 2 57
Revendications 2013-08-27 1 40
Dessins représentatifs 2014-06-13 1 19
Page couverture 2014-06-13 2 57
Correspondance 2013-01-14 1 41
Correspondance 2013-01-14 1 22
Cession 2012-12-21 5 145
Poursuite-Amendment 2013-03-05 2 44
Poursuite-Amendment 2013-02-27 1 29
Poursuite-Amendment 2013-08-27 4 155
Correspondance 2014-04-23 1 31