U.S. patent application number 11/558257 was filed with the patent office on 2007-04-19 for automated molecular pathology apparatus having fixed slide platforms.
Invention is credited to David Bryant, Devon Campbell, Andrew Ghusson, Charles LEMME, Kurt Reinhardt, William Richards, Vincent Rizzo, Wayne Showalter.
Application Number | 20070086917 11/558257 |
Document ID | / |
Family ID | 29270685 |
Filed Date | 2007-04-19 |
United States Patent
Application |
20070086917 |
Kind Code |
A1 |
LEMME; Charles ; et
al. |
April 19, 2007 |
AUTOMATED MOLECULAR PATHOLOGY APPARATUS HAVING FIXED SLIDE
PLATFORMS
Abstract
Apparatus and methods for automatically staining or treating
multiple tissue samples mounted on slides are provided, in which
the slides and reagent bottles are held in fixed position, and the
reagent, wash and coverslipping solutions brought to the slides.
Alternatively, the slides are held in fixed position, while the
reagent, wash and coverslipping solutions brought to the
slides.
Inventors: |
LEMME; Charles; (Tucson,
AZ) ; Campbell; Devon; (Tucson, AZ) ; Ghusson;
Andrew; (Tucson, AZ) ; Bryant; David; (Tucson,
AZ) ; Reinhardt; Kurt; (Tucson, AZ) ;
Richards; William; (Tucson, AZ) ; Rizzo; Vincent;
(Tucson, AZ) ; Showalter; Wayne; (Tucson,
AZ) |
Correspondence
Address: |
HAYES, SOLOWAY P.C.
3450 E. SUNRISE DRIVE, SUITE 140
TUCSON
AZ
85718
US
|
Family ID: |
29270685 |
Appl. No.: |
11/558257 |
Filed: |
November 9, 2006 |
Related U.S. Patent Documents
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Application
Number |
Filing Date |
Patent Number |
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10424372 |
Apr 28, 2003 |
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11558257 |
Nov 9, 2006 |
|
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60375679 |
Apr 26, 2002 |
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Current U.S.
Class: |
422/63 |
Current CPC
Class: |
G01N 1/312 20130101;
Y10T 436/11 20150115; Y10T 436/115831 20150115; Y10T 436/111666
20150115; Y10T 436/112499 20150115; Y10T 436/2575 20150115 |
Class at
Publication: |
422/063 |
International
Class: |
G01N 33/00 20060101
G01N033/00 |
Claims
1. An automatic slide processing apparatus comprising: (a) a slide
support; (b) a reagent support; (c) a nozzle support; and (d) a
reagent dispenser, wherein the slide support and the reagent
support are operatively fixedly positioned, and the nozzle support
is selectively rotatably movable relative to the slide support and
the reagent support.
2. An apparatus as claimed in claim 1, wherein the slide support
carries a plurality of spaced slide support platforms.
3. An apparatus according to claim 2, wherein said slide support
platforms include heaters and/or temperature sensors.
4. An apparatus as claimed in claim 1, wherein said slide support
includes at least one liquid drain.
5. An apparatus according to claim 1, wherein said slide support is
slidably mounted in the apparatus to permit loading and unloading
of slides in the slide support.
6. An apparatus according to claim 5, wherein said slide support is
slidably mounted on rails.
7. An apparatus according to claim 6, and further including a
damper for damping smoothing movement of the rails.
8. An apparatus according to claim 1, wherein said slide support is
vertically adjustably supported on a lift mechanism.
9. An apparatus according to claim 1, wherein said reagent
dispenser is selectively moveable relative to the reagent
support.
10. An apparatus according to claim 9, wherein said reagent
dispenser comprises robotic dispensing pipettes.
11. An apparatus according to claim 10, wherein said robotic
dispensing pipettes are vertically moveable between an operating
position and a transport position.
12. An apparatus according to claim 9, wherein said reagent
dispenser comprises two spaced robotic dispensing pipettes.
13. An apparatus according to claim 1, wherein the nozzle support
carries at least one vortex air jet or jet drain.
14. An apparatus according to claim 1, wherein the nozzle support
carries at least one applicator for applying a cover fluid to the
slide.
15. An apparatus according to claim 1, wherein the nozzle support
is rotatably moveable plus or minus approximately 180.degree. from
a home position.
16. An apparatus according to claim 9, wherein said reagent
dispenser is rotatably moveable plus or minus approximately
185.degree. from a home position.
17. An apparatus according to claim 1, and further comprising a
slide bar code reader carried on the nozzle support and/or carried
with the reagent dispenser.
18. An apparatus according to claim 1, and further comprising a
processor for controlling movement of the nozzle support, and the
reagent dispenser.
19. An apparatus according to claim 1, and further comprising a
dispenser wash station mounted on the nozzle support.
20. An apparatus according to claim 19, and comprising two
dispenser wash stations mounted spaced from one another on the
nozzle support.
21. (canceled)
22. A method for processing a plurality of slides each having
biological samples thereon comprising the steps of: (a) preparing a
first slide for biological treatment with a reagent; (b) moving a
reagent dispenser to a selected reagent container; (c) drawing a
pre-selected volume of reagent from the reagent container into the
reagent dispenser; (d) moving the reagent dispenser to the first
slide; (e) dispensing said pre-selected volume of reagent from the
reagent dispenser onto the first slide; (f) preparing a second
slide for treatment with a reagent; (g) cleaning the reagent
dispenser; (h) moving a reagent dispenser to a selected reagent
which may be the same or different from the reagent of step (b);
(i) drawing a pre-selected amount of reagent from the reagent
container selected in step (h) into the reagent dispenser; (j)
moving the reagent dispenser to said second slide; (k) dispensing
said pre-selected volume of reagent selected in step (h) from the
reagent dispenser onto said second slide; (l) cleaning the reagent
dispenser; and (m) repeating steps (h)-(l).
23. The method of claim 22, wherein two reagent dispensers are
provided, and including the step of cleaning one of the reagent
dispensers while the other reagent dispenser is employed to draw
and dispense reagent onto a selected slide.
24. A method according to claim 22, wherein said reagent dispenser
comprises a robotic syringe, and reagent is taken up by
aspiration.
25. An automatic slide processing apparatus comprising: (a) a slide
support; (b) a reagent support; (c) a nozzle support; and (d) a
reagent dispenser, wherein the slide support is operatively fixedly
positioned, and the nozzle support and reagent support are
selectively independently movable relative to the slide
support.
26. An apparatus as claimed in claim 25, wherein the slide support
carries a plurality of spaced slide support platforms.
27. An apparatus according to claim 26, wherein said slide support
platforms include heaters and/or temperature sensors.
28. An apparatus as claimed in claim 25, wherein said slide support
includes at least one liquid drain.
29. An apparatus according to claim 25, wherein said slide support
is slidably mounted in the apparatus to permit loading and
unloading of slides in said slide support.
30. An apparatus according to claim 29, wherein said slide support
is slidably mounted on rails.
31. An apparatus according to claim 30, and further including a
damper for damping smoothing movement of the rails.
32. An apparatus according to claim 30, wherein said slide support
is vertically adaptably supported on a lift mechanism.
33. An apparatus according to claim 29, wherein a reagent dispenser
activator is selectively rotatably moveable relative to the reagent
support.
34. An apparatus according to claim 33, wherein said reagent
dispenser activator is fixed to move in synchronization with said
nozzle support.
35. An apparatus according to claim 34, wherein said reagent
dispenser activator comprises a hammer or piston.
36. An apparatus according to claim 35, wherein the nozzle support
carries at least one vortex air jet and/or jet drain.
37. An apparatus according to claim 25, wherein the nozzle support
carries at least one applicator for applying a cover fluid to the
slide.
38. An apparatus according to claim 25, wherein the nozzle support
is rotatably moveable plus or minus approximately 180.degree. from
a home position.
39. An apparatus according to claim 25, wherein said reagent
support is rotatably moveable in either direction from a home
position.
40. An apparatus according to claim 25, and further comprising a
slide bar code reader carried on the nozzle support.
41. An apparatus according to claim 25, and further comprising a
reagent bar code reader operatively positioned relative to said
reagent support.
42. An apparatus according to claim 25, and further comprising a
processor for controlling movement of the nozzle support and
reagent dispenser.
43. A method for processing a plurality of slides each having
biological samples thereon comprising the steps of: (a) preparing a
first fixedly positioned slide for biological treatment with a
reagent; (b) moving a selected reagent dispenser to the first
slide; (c) dispensing a pre-selected volume of reagent from the
reagent dispenser onto the first slide; (d) preparing a second
fixedly positioned slide for treatment with a reagent; (e) moving a
selected reagent dispenser which may be the same or different from
the reagent dispenser of step (b) to the second slide; (f)
dispensing a pre-selected volume of reagent from the reagent
dispenser onto said second slide; and (g) repeating steps
(d)-(f).
44. A method according to claim 43, wherein a reagent dispenser
activator is moved independently of said reagent dispensers.
45. An automatic slide processing apparatus comprising: (a) a slide
support; (b) heating elements for heating the slides; (c) a nozzle
support having nozzles for applying liquids, said nozzle support
and said slide support moving relative to one another such that the
nozzles may apply liquids to the slides; (d) a reagent support; and
(e) a reagent dispenser wherein said reagent dispenser is operative
to directly access the slide support.
46. An apparatus as claimed in claim 45, wherein the slide support
carries a plurality of spaced slide support platforms.
47. An apparatus as claimed in claim 45, wherein said slide support
includes at least one liquid drain.
48. An apparatus according to claim 45, wherein said slide support
is slidably mounted in the apparatus to permit loading and
unloading of slides in the slide support.
49. An apparatus according to claim 48, wherein said slide support
is slidably mounted on rails.
50. An apparatus according to claim 49, and further including a
damper for damping smoothing movement of the rails.
51. An apparatus according to claim 45, wherein said slide support
is vertically adjustably supported on a lift mechanism.
52. The apparatus according to claim 45, wherein said reagent
dispenser is selectively moveable relative to the reagent
support.
53. An apparatus according to claim 45, wherein said reagent
dispenser comprises at least one robotic dispensing pipette.
54. An apparatus according to claim 46, wherein said robotic
dispensing pipette(s) is/are vertically moveable between an
operating position and a transport position.
55. An apparatus according to claim 45, wherein said reagent
dispenser comprises two spaced robotic dispensing pipettes.
56. An apparatus according to claim 45, wherein the nozzle support
carries at least one vortex air jet or jet drain.
57. An apparatus according to claim 45, wherein the nozzle support
carries at least one applicator for applying a cover fluid to the
slide.
58. (canceled)
59. An apparatus according to claim 45, wherein the nozzle support
is rotatably moveable plus or minus approximately 180.degree. from
a home position.
60. An apparatus according to claim 45, wherein said reagent
dispenser is rotatably moveable plus or minus approximately
185.degree. from a home position.
61. An apparatus according to claim 45, and further comprising a
slide bar code reader carried on the nozzle support and/or carried
with the reagent dispenser.
62. An apparatus according to claim 45, and further comprising a
processor for controlling movement of the nozzle support, reagent
support and the reagent dispenser.
63. An apparatus according to claim 45, and further comprising a
dispenser wash station mounted on the nozzle support.
64. An apparatus according to claim 62, and comprising two
dispenser wash stations mounted spaced from one another on the
nozzle support.
65. (canceled)
Description
CROSS REFERENCE TO RELATED APPLICATION
[0001] This Application claims benefit of priority from U.S.
Provisional Application Ser. No. 60/375,679 filed Apr. 26,
2002.
FIELD OF THE INVENTION
[0002] The present invention is directed to apparatus for use in
diagnostic molecular pathology and, more particularly, to such
apparatus used for the automated staining and/or treating of tissue
samples mounted on microscope slides.
BACKGROUND OF THE INVENTION
[0003] Molecular pathology is the examination at a molecular level
of the DNA, mRNA, and proteins that cause or are otherwise
associated with disease. From this examination important
information about patient diagnosis, prognosis, and treatment
options can be elucidated. The practice of molecular pathology is
generally divided into two main areas: (i) analysis of DNA, mRNA,
and proteins in intact cells (in-situ), and (ii) analysis of these
biological materials after they have been extracted from tissues.
The first category, to which the present invention is primarily
directed, has the advantage that it allows the pathologist or
scientist to study the histopathologic architecture or morphology
of the tissue specimen under the microscope at the same time that
the nucleic acid or proteins are being assayed. These techniques
include immunohistochemistry (IHC) which looks at proteins, in-situ
hybridization (ISH) which looks at nucleic acids, histochemistry
(HC) which looks at carbohydrates, and enzyme histochemistry (EHC)
which looks at enzyme chemistry. For example, ISH can be used to
look for the presence of a genetic abnormality or condition such as
amplification of cancer causing genes specifically in cells that,
when viewed under a microscope, morphologically appear to be
malignant. ISH is also useful in the diagnosis of infectious
diseases as it allows detection not only of a microbial sequence
but also of precisely which cells are infected. This may have
important clinicopathologic implications and is an effective means
to rule out the possibility that positive hybridization signal may
have come from an adjacent tissue of no clinical concern or from
blood or outside contamination.
[0004] IHC utilizes antibodies which bind specifically with unique
epitopes present only in certain types of diseased cellular tissue.
IHC requires a series of treatment steps conducted on a tissue
section or cells (e.g. blood or bone marrow) mounted on a glass
slide to highlight by selective staining certain morphological
indicators of disease states. Typical steps include pretreatment of
the tissue section to remove the paraffin and reduce non-specific
binding, retrieval of antigens or cell conditioning masked by
cross-linking of the proteins from the chemical fixatives, antibody
treatment and incubation, enzyme-labeled secondary antibody
treatment and incubation, substrate reaction with the enzyme to
produce a fluorophore or chromophore highlighting areas of the
tissue section having epitopes binding with the antibody,
counterstaining, and the like. Most of these steps are separated by
multiple rinse steps to remove unreacted residual reagent from the
prior step. Incubations can be conducted at elevated temperatures,
usually around 37.degree. C., and the tissue must be continuously
protected from dehydration. ISH analysis, which relies upon the
specific binding affinity of DNA or RNA probes with unique or
repetitive nucleotide sequences from the cells of tissue samples or
bodily fluids, requires a similar series of process steps with many
different reagents and is further complicated by varying
temperature requirements.
[0005] In view of the large number of repetitive treatment steps
needed for both IHC and ISH, automated systems have been introduced
to reduce human labor and the costs and error rate associated
therewith, and to introduce uniformity. Examples of automated
systems that have been successfully employed include the ES.RTM.,
NexES.RTM., DISCOVERY.TM., BENCHMARK.TM. and Gen II.RTM. staining
Systems available from Ventana Medical Systems (Tucson, Ariz.).
These systems employ a microprocessor-controlled system including a
revolving carousel supporting radially positioned slides. A stepper
motor rotates the slide carousel placing each slide under one of a
series of reagent dispensers positioned above the slides. As
described in U.S. Pat. No. 6,352,861 B1, bar codes on the slides
and reagent dispensers fully automate the computer-controlled
actuation of the dispensers onto the slides so that different
reagent treatments can be performed for each of the various tissue
samples.
[0006] Instrumentation such as the Ventana Medical Systems ES.RTM.,
Gen II.RTM. NexES.RTM., BENCHMARK.RTM. and DISCOVERY.RTM. systems
are fundamentally designed to sequentially apply reagents to tissue
sections mounted on one by three inch glass microscope slides under
controlled environmental conditions. The instrument must perform
several basic functions such as reagent application, washing (to
remove a previously applied reagent), jet draining (a technique to
reduce the residual buffer volume on a slide subsequent to
washing), Liquid Coverslip.TM. application (a light oil application
used to contain reagents and prevent evaporation), and other
instrument functions.
[0007] The Ventana Medical Systems staining instruments mentioned
above process slides on a rotating slide carousel. The
instrumentation described herein has the slides fixed in a
stationary position and rotates the basic processing stations above
the fixed slides. The following details of how the slides are
processed, the process algorithm, is the same regardless of the
physical configuration.
[0008] The process of staining tissue on a slide consists of the
sequential repetition of the basic instrument functions described
above. Essentially a reagent is applied to the tissue then
incubated for a specified time at a specific temperature. When the
incubation time is completed the reagent is washed off the slide
and the next reagent is applied, incubated, and washed off, etc,
until all of the reagents have been applied and the staining
process is complete.
[0009] It is desirable to permit any staining protocol for any of
the slides being run, i.e. any combination of reagents and
incubation times. In addition, to stain multiple slides as quickly
as possible the instrument should process the slides
simultaneously. This is feasible given that most of the time slides
are just incubating, thus freeing up time to perform the washing,
reagent application and other functions on other slides.
[0010] One algorithm to accomplish simultaneous staining (sometimes
referred to as the "random access" method) is to create a task and
time schedule for each slide in the run, then perform each task on
each slide when the schedule calls for it. The problem with this
method is that incubation times will not be accurate if the
instrument is busy performing a task on one slide when it is time
to be washing another slide (thereby completing incubation on that
slide). The variation in incubation times will be unpredictable
since the total number of slides and the slide protocols vary.
[0011] Slide processing using a lock-step algorithm insures that
all incubation times are accurate and predictable irrespective of
the number of slides processed or the variation in slide protocols.
While incubation times are assured, the lock step algorithm implies
that incubation times must be an increment of the fundamental
incubation time period. For example, with an incubation cycle of
two minutes, the total incubation times must be multiples of two,
i.e., two, four, six, eight etc. minutes in duration. However, the
preferred embodiment of the present invention uses a four minute
incubation time. Generally this is not a particular limitation
since typical incubation times are an order of magnitude longer
than the fundamental incubation period.
[0012] Prior art staining systems typically include either
convection or radiation to warm the samples above laboratory
ambient temperatures for steps requiring elevated temperatures.
Heating the slide improves staining quality by acceleration of the
chemical reaction and can permit a reaction temperature more
closely matching body temperature (about 37.degree. C.) at which
antibodies are designed to react. While such convection or radiant
heating systems have been generally suitable for IHC, which is
antibody-based, they are less suitable for ISH, which is nucleic
acid-based and requires higher and more precise temperature control
in order to denature DNA. In order to denature the DNA double helix
of both the target sample and the probe so as to render them single
stranded, the temperature must be raised above the melting point of
the duplex, usually about 94.degree. C. Precise temperature control
is also required in ISH to effect probe hybridization at the
desired stringency. The selected temperature must be low enough to
enable hybridization between probe and target, but high enough to
prevent mismatched hybrids from forming.
[0013] Hot air convection, conduction or radiant heat heating units
typically employed with prior art automated tissue stainers do not
permit the temperature of individual slides to be separately
controlled. With prior art systems all of the slides are heated to
the same temperature at any given time during the process. For
example, U.S. Pat. Nos. 5,645,114 and 6,180,061 to Bogen et al.
disclose a dispensing assembly adapted to carry a plurality of
microscope slides. Individual slide holders containing resistive
heating units are provided. However, with the assembly taught by
Bogen et al., all of the slides would be heated to a common
temperature because no means are disclosed for separate heating
controls or for shielding slides from heat generated by adjacent
slides.
[0014] Other difficulties frequently encountered in both IHC and
ISH testing results from the manner in which the tissues are
typically preserved. The mainstay of the diagnostic pathology
laboratory has been for many decades the formalin-fixed,
paraffin-embedded block of tissue, sectioned and mounted upon glass
slides. Fixation in such a preservative causes cross-linking of
macromolecules, both amino acids and nucleic acids. These
cross-linked components must be removed in the case of ISH, to
allow access of the probe to the target nucleic acid, and, in the
case of IHC, to allow the antibody to recognize the corresponding
antigen. "Unmasking" the antigen and/or nucleic acid is typically
accomplished manually with multiple pretreatment, protolytic
digestion, and wash steps.
[0015] Prior to staining, complete removal of the paraffin is also
required so that it does not interfere with antibody or probe
binding. Manual deparaffinization normally is achieved by the use
of two or three successive clearing reagents that are paraffin
solvents such as xylene, xylene substitutes or toluene. However,
new automated methods that are largely based on physical separation
mechanisms are revealed in U.S. Pat. No. 6,544,798 B1 to
Christensen et al., which do not require toxic solvents and are
aqueous-based.
[0016] The foregoing discussion of the prior art largely derives
from Richards et al. U.S. Pat. No. 6,296,809, assigned to Ventana
Medical Systems, in which there is described apparatus and methods
for automatically staining or treating multiple tissue samples
mounted on microscope slides so that each sample can receive an
individualized staining or treatment protocol even when such
protocols require different temperature parameters. More
specifically, there is described in the '809 patent apparatus
comprising a computer controlled, bar code driven, staining
instrument that automatically applies chemical and biological
reagents to tissue or cells mounted or affixed to standard glass
microscope slides. According to the '809 patent, a plurality of
slides are mounted in a circular array on a carousel which rotates,
as directed by the computer, to a dispensing location placing each
slide under one of a series of reagent dispensers on a second
rotating carousel positioned above the slides. Each slide receives
the selected reagents (e.g. DNA probe) and is washed, mixed and/or
heated in an optimum sequence and for the required period of
time.
[0017] According to the '809 patent, individual slides are carried
on thermal platforms radially mounted to the carousel. Temperature
sensors are also mounted to the slide carousel, individually
monitoring and controlling each thermal platform separately.
Apparatus made in accordance with the '809 patent is available
commercially from Ventana Medical Systems, of Tucson, Ariz. as the
DISCOVERY.RTM. or BENCHMARK.RTM. systems.
[0018] The present invention is a modification and improvement over
the prior art including the apparatus and methods described in the
'809 patent. More particularly, the present invention rather than
bringing the slides to the reagent, stain, and wash stations,
brings the reagent, stain and wash stations to fixedly positioned
slides. That is to say, in the present invention the slides are
fixedly positioned in the apparatus, and the various washing,
staining and reagent fluids are selectively delivered to the
slides. Fixing the slides in position in the apparatus simplifies
wiring to the heaters, and also eliminates the potential that a
slide may be dislocated by rapid start and stop movement of the
slide carousel, which, in a worst case scenario could result in a
domino or train-wreck effect where one dislocated slide hits the
neighboring slide causing that slide to dislocate, and so
forth.
BRIEF DESCRIPTION OF THE DRAWINGS
[0019] Further features and advantages of the present invention
will be seen from the following detailed description, taken in
conjunction with the accompanying drawings, wherein like numerals
depict like parts, and wherein:
[0020] FIG. 1 is a perspective view of a first embodiment of an
apparatus of the present invention shown with the slide cabinet
shell removed, and FIG. 1A is an enlarged view showing details of
portions of the reagent transfer probes;
[0021] FIG. 2 is a perspective view of the apparatus of FIG. 1,
first embodiment shown in conjunction with a computer and other
instruments with which it operates;
[0022] FIG. 3 is a perspective view and FIG. 3A is a partially
exploded view of details of the nozzle support portion of FIG. 1,
first embodiment;
[0023] FIG. 4 is an exploded view of details of the slide plate
portion of FIG. 1, first embodiment;
[0024] FIGS. 5 and 6 are perspective views, from the top and the
bottom, respectively, of portions of the slide plate portion of
FIG. 1, first embodiment;
[0025] FIG. 7 is a perspective view of the reagent support portion
of FIG. 1, first embodiment;
[0026] FIG. 8 is a partially exploded perspective view showing two
reagent bottles of FIG. 1, first embodiment;
[0027] FIG. 8A is a cross-sectional view of a reagent bottle, cap
and insert, first embodiment;
[0028] FIG. 9 is a top plan view of two reagent bottles of FIG. 1,
first embodiment;
[0029] FIGS. 10A-10B are flow charts of the operation and control
of FIG. 1, first embodiment;
[0030] FIG. 11 is a perspective view of an alternative embodiment
and apparatus of the present invention shown with the slide cabinet
shell removed;
[0031] FIG. 12 is a perspective view of the FIG. 11 alternative
embodiment shown in conjunction with a computer and other
instruments with which it operates;
[0032] FIG. 13 is a perspective view showing details of the nozzle
support portion of the FIG. 11 alternative embodiment;
[0033] FIG. 14 is an exploded view of details of the FIG. 11
alternative embodiment;
[0034] FIGS. 15 and 16 are perspective views, from the top and the
bottom, respectively, of portions of the slide plate portion of the
FIG. 11 alternative embodiment;
[0035] FIGS. 17A and 17B are front and rear perspective views of
the reagent dispenser and dispenser carrier portion of the FIG. 11
alternative embodiment;
[0036] FIG. 18 is a perspective view showing details of the reagent
dispenser activator portion of the FIG. 11 alternative embodiment;
and
[0037] FIGS. 19A and 19B are flow charts of the operation and
control of the FIG. 11 alternative embodiment.
DETAILED DESCRIPTION OF THE INVENTION
[0038] Referring now in detail to the drawings wherein like parts
are designated by like reference numerals throughout, there is
illustrated in FIG. 1 a perspective view of the molecular pathology
apparatus according to a first embodiment of the present invention
which is designated generally by reference numeral 10. For the
purposes of clarity, several of the reagent bottles, as well as the
cabinet shell, and liquid and air supply tubing and electrical
wiring are omitted from the drawings. Apparatus 10 is designed to
automatically stain or otherwise treat tissue mounted on microscope
slides with nucleic acid probes, antibodies, and/or other reagents
in a desired sequence, time and temperature. Tissue sections so
stained or treated are then to be viewed under a microscope by a
medical practitioner who reads the slide for purposes of patient
diagnosis, prognosis, or treatment selection.
[0039] In the first embodiment, apparatus 10 functions as one
component or module of a system 12 (FIG. 2) which also comprises a
host computer 14 preferably a personal computer, monitor 16,
keyboard 18, mouse 20, bulk fluid containers 22, waste container 23
and related equipment. Additional staining modules or other
instruments may be added to system 12 to form a network with
computer 14 functioning as a server. Alternatively, some or all of
these separate components could be incorporated into apparatus 10
making it a stand-alone instrument.
[0040] Referring also to FIGS. 3, 3A and 4-7, as set forth in
greater detail below, a plurality of slide platforms 50 (FIGS. 4,
5) are mounted radially about a center point 32 of drawer 34 (FIG.
1) upon which standard glass slides 60 with tissue samples may be
placed. Drawer 34 is slidably mounted in housing 30 on rails 40 or
the like. The temperature of each slide may be individually
controlled by means of sensors and a microprocessor, i.e. as taught
in the above-mentioned '809 patent.
[0041] Each of the slide platforms 50 is connected through
individual wires to a multiplexer (not shown) which is then in turn
connected to a microprocessor (not shown). A feature and advantage
of the present invention which results from fixedly mounting the
slide platforms in drawer 34 is that each of the heaters and
thermal sensors may be hardwired thereby eliminating the need for a
slip ring assembly or rotor couplings, as well as complex stepping
motors, etc. for locating and positioning a rotating slide carousel
as required in prior art devices. Also, the possibility that a
slide or slides may be shifted or dislocated during rapid start and
stop rotation of the slide carousel is eliminated.
[0042] In one embodiment, a plurality of slots or channels are
formed on the top surface of each of the slide heaters, i.e. the
interface surface between the slide heater and the slide, for
gathering and venting gas bubbles as may form during heating, i.e.
in accordance with co-pending U.S. application Ser. No. 09/953,417,
filed Sep. 11, 2001, and assigned to the common assignee, which
disclosure is incorporated herein by reference.
[0043] Referring also to FIGS. 1, 2, 5 and 6, drawer 34 supports a
slide support tray 33 which in turn supports a circular pan 35
having a peripherial wall 36 serving as a splash guard, a
peripheral trough 37 and a central drain 38, i.e. at center point
32, both connected to drain lines 39 which in turn are connected to
waste container 23. Drawer 34 is slidably mounted in housing 30 on
rails 40. Rails 40, in a preferred embodiment, comprise three piece
telescoping rails so that the drawer 34 may be slid clear of
housing 30 to permit access to all of the slide platforms 50 for
slide loading and removal. A damping means such as a pneumatic
means, electromotive means, mechanical spring damper or the like
preferably is provided to smooth movement of the drawer whereby to
avoid possible dislodging of slides, particularly when the drawer
is closed. Slide support tray 33 is supported on a lift mechanism
such as pneumatic cylinders 52 (see FIG. 1), which automatically
index to permit the slide support tray 33 to move up and down so
that the slide support tray 33 and circular pan 35 may be dropped
to permit wall 36 to clear the nozzle support 100 when the drawer
is slid in and out of the apparatus.
[0044] Slide drawer 34 is divided into thirty-five equal pie-shaped
sections 70. Thirty of the pie-shaped sections 70 are occupied by
slide platforms 50 while the five remaining pie-shaped sections 70A
(FIG. 4) at the rear of the drawer are devoid of slide platforms
50. In other words, a row of thirty slide platforms 50 are radially
mounted on drawer 34 and evenly spaced from one another, except at
the ends of the row.
[0045] However, the invention is not limited to thirty active slide
locations, and more or fewer slide locations may be employed. An
alternative embodiment may be implemented by aligning the platforms
50 linearly, which results in potentially limitless number of
platforms.
[0046] Referring to FIGS. 1 and 3, a nozzle support 100 is
concentrically and rotatably mounted above slide drawer 34. Nozzle
support 100 is mounted on a shaft (not shown) supported by a bridge
110, and driven by a computer controlled stepping motor and drive
belt (not shown), and rotates plus or minus approximately
180.degree. from a home position 104 at the rear of the drawer. The
computer controlled stepper motor and drive belt are conventional
in this art. Accordingly, details are omitted for the sake of
clarity.
[0047] Nozzle support 100 carries the various slide treatment
stations, other than the reagent dispensing location. Thus, nozzle
support 100 carries dual rinse nozzle block 102, volume
adjust/stringency block 103, Liquid Coverslip.TM. evaporation
inhibitor liquid application block 105, vortex mixer air jet block
106, jet drain 108, and the like, all for preparing a slide for
staining, stain removal, and the like, and to clear bar codes (not
shown) carried on the slides, and a bar code reader 109, all as
described in detail in U.S. Pat. Nos. 5,595,707; 5,650,327;
5,654,199; or 5,654,200 to Copeland et al, which disclosures are
incorporated herein by reference. In other words, nozzle support
100 carries all of the functions for slide preparation, cleaning,
reagent mixing, Liquid Coverslip.TM. application, etc. other than
reagent application, as described, e.g. in the '707 patent to
Copeland et al., plus wash stations 121, 122 for the reagent
application probes as will be described in detail below.
[0048] Preferably, but not necessarily, the various rinse nozzle
blocks, vortex mixer air jet blocks, jet drain, etc. are arranged
adjacent to one another so that the nozzle support 100 may be
indexed and advanced in a "lock-step" manner to sequentially treat
a slide according to an accepted protocol. For example, jet drain
108 may be arranged immediately adjacent rinse nozzle blocks 102 so
that nozzle support 100 may be advanced in "lock step" manner past
a selected slide, and the slide rinsed and fluid stripped, etc.
Also, if desired, vortex mixer air jet blocks 106 may be oriented
to impinge simultaneously on two adjacent slides.
[0049] For the sake of clarity, fluid and air supply tubing for the
several slide treatment stations have been omitted from the
drawings. It will be understood, however, that the fluid and air
supply tubing are made long enough to permit the valve plate to
rotate plus or minus approximately 190.degree. from a home position
at the rear of the apparatus so that each slide treatment station
can reach each slide 60. A pair of wash stations 121, 122 spaced
two thirty-fifths of a revolution (approximately 20.degree.) apart
as will be described in detail hereinafter, are also attached to
and radially extend beyond the periphery of the nozzle support 100,
and rotate with the nozzle support 100.
[0050] Reagent support 300 is fixedly mounted to bridge 110
vertically above nozzle support 100, which arch in turn is fixedly
mounted within housing 30. A plurality of reagent bottles 302 are
removably mounted within recesses 304 formed equally spaced
adjacent the periphery of reagent support 300. In the illustrated
embodiment, a total of thirty-five reagent bottles are mounted on
the reagent support 300, spaced approximately one thirty-fifth
(approximately 10.degree.) apart.
[0051] The reagents may include any chemical or biological material
conventionally applied to slides including nucleic acid probes or
primers, polymerase, primary and secondary antibodies, digestion
enzymes, pre-fixatives, post-fixatives, readout chemistry,
counterstains, and the like.
[0052] Referring also to FIG. 8, the reagent bottles 302 each
comprise a cylindrical hollow body 305 closed at the bottom end by
an integrally formed bottom wall. Preferably, the inside bottom
wall of each bottle is cone shaped, i.e. as shown in phantom at 303
to facilitate reagent pick-up by reagent transfer probes as will be
described in detail below. Each bottle 302 includes an integrally
formed bracket 306 which serves to maintain the bottles 304 at a
desired height in reagent support 300, and which may serve also to
permit the stringing together of a plurality of like bottles 302.
Accordingly, each bracket 306 includes a hinge element 308 for
cooperating with a hinge element 310 of an adjacent bottle 302. In
the illustrated embodiment, hinge elements 308 and 310 are shown as
conventional pin-hinges in which the upper hinge 310 includes a pin
312 which fits into the lower hinge 308, i.e. similar to a
conventional door hinge. However, bottles 302 may be hinged
together in a variety of ways.
[0053] Bracket 306 preferably includes a flat surface 314 upon
which is carried a bar code 316 for identifying the contents of the
bottle 302. Bottles 302 also include an insert 318 having a tapered
top surface 320 and inlet 319 fitted in the top end of the bottles
for locating a reagent transfer probe 328 as will be described in
detail hereinafter, and a cap 322 which may be either twist or
snap-fitted to the bottle 302 for sealing the bottle 302.
[0054] Probe 328 is tapered at a lower end to fit closely in
tapered conical bottom 303 of bottle 302. A vent 321 is formed in
insert 318 for equalizing air pressure as reagent is removed. Cap
322 includes a tapered inner surface and plug 323 for sealing inlet
319.
[0055] Making brackets 306 attachable to one another permits one to
assemble a chain of reagents for use, and also to remove the chain
of reagents so that the reagents may be refrigerated, for example,
overnight when not in use.
[0056] Referring next to FIGS. 7, 8 and 9, the side walls 324 of
brackets 306 are tapered so that a pie-shaped space 326 is formed
between two bottles when two bottles are fastened together in a
string, and mounted in recesses 304 in the reagent support 300,
thereby exposing holes 328 formed through reagent support 300.
Holes 328 are formed in the same concentric circle as recesses 304,
and are spaced equidistant between adjacent recesses 304. The
purpose of pie-shaped spaces 326 and holes 328 is to provide
clearance for reagent transfer probes 402, 404 as will be described
in detail below.
[0057] Referring again to FIG. 1, an arm 400 is rotatably mounted
on arch 405 concentrically above reagent support 300, and carries a
pair of reagent transfer probes 402, 404 located at the distal end
of arm 400 and spaced approximately 10.degree. apart. Arm 400 also
carries a bar code reader 406 for reading bar codes 316 on the
reagent bottles. Arm 400 is rotatably driven by a computer driven
stepping motor (not shown), and rotates plus or minus approximately
185.degree. in either direction from a home position 410.
[0058] Reagent transfer probes 402 and 404, which are identical to
one another, preferably comprise automatic pipette
metering/dispensing pick-up devices designed to aspirate or "sip"
reagent from a reagent bottle, move to a slide, and then "spit" or
deposit the reagent onto the slide. "Sip" and "spit" automatic
pipette/metering dispensing pick-up devices are described in
published PCT Application No. PCT/US99/04379, which disclosure is
incorporated herein by reference. Reagent transfer probes 402 and
404 are carried on the distal end of arm 400 and are spaced from
one another so that when one of the probes, e.g. probe 402 is
located centrally over a slide 60, the other reagent transfer probe
404 may be centrally positioned over one of the two probe wash
stations 121 or 122. Pneumatic cylinders 403a, 403b selectively
raise and lower probes 402 and 404 into one of the following
positions: a raised transport position above the tops of the
bottles 302 where the arm 400 is free to rotate; a reagent drawing
position wherein one of the probes is inserted into a selected
reagent bottle 302 wherein a measured amount of reagent may be
drawn into the probe; a reagent dispensing position wherein a
reagent transfer probe containing reagent is disposed in the
pie-shaped space 326 between two reagent bottles, above a selected
slide to dispense reagent thereon; and a cleaning position wherein
the other probe, i.e. the probe not being used to dispense reagent,
is operatively disposed in one of probe washing stations 121 or 122
which straddle the slide being dispensed upon. While the apparatus
of the present invention could be made with only a single reagent
transfer probe, providing two spaced reagent transfer probes
improves cycle speed since reagent metering may be accomplished
using one of the two reagent transfer probes while the other of the
two reagent transfer probes is going through the wash cycle as will
be described below. That is to say, while one of the reagent
transfer probes, e.g. reagent transfer probe 402 is dispensing
reagent onto a slide, the other reagent transfer probe, i.e. idle
reagent transfer probe 404 may be lowered to a probe wash station
121 where the idle reagent transfer probe may be rinsed inside and
out at the same time.
[0059] Referring to FIGS. 10A and 10B, the overall process is as
follows:
[0060] A plurality of specimen-bearing slides 60 are mounted on the
slide platforms 50, selected reagent bottles 302 mounted in the
reagent support 300, the slide drawer is closed and the slide and
reagent bar codes are read. The computer calculates the master
protocol and then downloads the run steps for the entire run, the
nozzle support 100 is indexed to the first slide, and the slide is
washed and prepared for staining or other treatment in accordance
with the pre-programmed run steps by advancing the nozzle support
100 in "lock-step" manner. In the meanwhile, probe arm 400 is
rotated to the appropriate reagent bottle 302, one of the two
reagent transfer probes 402 or 404 is indexed over the selected
reagent bottle, and the probe lowered to aspirate a measured amount
of the desired reagent. The reagent-containing transfer probe is
then raised, and the arm 400 moved to the selected slide where the
loaded reagent transfer probe is lowered to just over the slide,
and the reagent dispensed on the slide. In the meanwhile, the idle
reagent transfer probe is lowered into one of the washing stations
121 or 122, wherein the reagent transfer probe is washed inside and
out. Both reagent transfer probes 402 and 404 are then raised, and
the process repeated, but using the reagent transfer probe just
cleaned in the previous step to aspirate and dispense reagent onto
the next slide. As before, simultaneously with dispensing the
reagent onto the slide as in the previous case, the idle reagent
transfer probe is washed while the active reagent transfer probe is
dispensing reagent onto the new slide.
[0061] The foregoing steps are repeated until all of the slides are
processed. For convenience, in the illustrated embodiment, the
dwell time at each slide station is six and two-thirds seconds.
This comes from dividing a four minute cycle time into thirty-six
time spaces, one time space for each of the thirty slide positions
plus five blank slide positions for overtravel of the slide
support, plus one "virtual" slide position for returning the nozzle
support 100 from the last slide position to the first slide
position. The virtual slide position allows the nozzle support 100
to return to the other end of its travel range in an uninterrupted
fashion.
[0062] The staining algorithm used on the aforesaid Ventana systems
avoids scheduling problems associated with random access methods by
using a "lock step" method. The lock step algorithm requires that
the nozzle support 100 which holds the processing functions be
rotated one slide position index every "n" seconds, termed the
slide index time. The slide index time is preferably as short as
possible but long enough that the function that requires the
longest time can be completed within the index time. In the
embodiments of the inventions herein, "n" is six and two-thirds
seconds. Index times are usually on the order of several seconds.
The time for one complete rotation of the nozzle support 100,
termed the fundamental incubation period, will then be "n" times
the number of slide positions, including blank and virtual slide
positions. (For example, if the slide index time is six seconds and
there are twenty slide positions, the incubation time period will
be 120 seconds or two minutes.)
[0063] Throughout the entire run the nozzle support 100 is indexed
one slide position every "n" seconds. After the index, the system
checks the schedule to see if any of the slides at each of the
processing stations require the function of that station. For
example, if the slide at the washing station is scheduled for
washing, that slide is washed. Similarly if the slide at the
reagent application station is scheduled for the application of a
new reagent, then the new reagent is applied.
[0064] The above-described invention has several advantages over
the prior art. For one, making the slide plate fixed in position
eliminates the possibility of a slide being dislocated (and the
sample dislodged) during the rapid start-stop rotational movement
of a conventional rotating slide carousel. Also, employing two
transfer syringes insures better cleaning of transfer syringes
without increasing cycle time.
[0065] Also, since none of the moving elements, i.e. nozzle support
100 and probe support arm 400 need travel more than approximately
190.degree. in either direction, all electrical connections, and
air and fluid connections can be achieved without the need for slip
ring or rotary connections, since the hoses and wires are quite
capable of taking twistings of 190.degree. plus.
[0066] The instrumentation described herein may or may not have the
ability to continuously rotate the nozzle support. The nozzle
support 100 may need to return to a starting position before
rotation has exceeded 360 degrees. This may also be required when
the slides are rotated on a carousel and the processing functions
are fixed above the slides. Similarly, other non-rotating designs
are possible such as linear or two dimensional configurations. In
these cases there will be a requirement to move the slides or
processing functions back to the original starting position during
the staining run. In most cases it is likely that the time required
to do this will exceed the index time which violates the
fundamental requirement of the lock step algorithm. The lock step
algorithm can still be utilized through the concept of the "virtual
slide" previously mentioned. The virtual slide is added to the
total number of actual slide positions so that the index time
period assigned to the virtual slide may be used to move the slides
or processing stations back to the starting position. Thus accurate
and predictable incubation times are maintained.
[0067] While one embodiment of the invention has been described,
the invention is susceptible to modification. For example, instead
of using one or a pair of transfer syringes on an overhead arm, the
reagent carousel could carry a plurality of micro-delivery reagent
fluid dispensers such as described in U.S. Pat. Nos. 6,045,759;
6,416,713; or 6,192,945. Moreover, while the use of individually
heated thermal platforms is preferred, the slides may be heated
using conventional heating techniques.
[0068] Referring to FIGS. 11-19, there is illustrated a second
embodiment of the present invention. FIG. 11 is a perspective view
of a molecular pathology apparatus according to the second
embodiment which is designated generally by reference numeral 1000.
For the purposes of clarity, all but one of the reagent dispensers
and dispenser carriers, as well as the cabinet shell, and liquid
and air supply tubing and electrical wiring are omitted from the
drawings. Apparatus 1000 is designed to automatically stain or
otherwise treat tissue mounted on microscope slides with nucleic
acid probes, antibodies, and/or other reagents in a desired
sequence, time and temperature. Tissue sections so stained or
treated are then to be viewed under a microscope by a medical
practitioner who reads the slide for purposes of patient diagnosis,
prognosis, or treatment selection.
[0069] In one embodiment, apparatus 1000 (FIG. 12) functions as one
component or module of a system which also comprises a host
computer 1014 preferably a personal computer, bulk fluid containers
1022, waste container (not shown) and related equipment. Additional
staining modules or other instruments may be added to the system to
form a network with computer 1014 functioning as a server.
Alternatively, some or all of these separate components could be
incorporated into apparatus 1000 making it a stand-alone
instrument.
[0070] Referring also to FIGS. 14, 15 and 18, as set forth in
greater detail below, a plurality of slide platforms 1050 are
mounted radially about a center point 1032 of slide support
assembly 1099 upon which standard microscope glass slides 1060 with
tissue samples may be placed. Drawer 1034 is slidably mounted in
housing 1030 on rails 1040 or the like. The temperature of each
slide may be individually controlled by means of temperature
sensors and a microprocessor, i.e. as taught in the above-mentioned
'809 patent.
[0071] As in the case of the first embodiment, each of the slide
platforms 1050 is connected through individual wires to a
multiplexer (not shown) which is then in turn connected to a
microprocessor (not shown). Also, as in the case of the first
embodiment, a plurality of slots or channels are formed on the top
surface of each of the slide heaters, i.e. the interface surface
between the slide heater and the slide, for gathering and venting
gas bubbles as may form during heating, i.e. in accordance with
co-pending U.S. application Ser. No. 09/953,417, filed Sep. 11,
2001, and assigned to the common assignee, which disclosure is
incorporated herein by reference.
[0072] Referring to FIGS. 14-16, drawer 1034 supports a slide
support assembly 1099 which is comprised of a slide support 1033
which in turn supports a circular pan 1035 having a peripheral wall
1036 serving as a splash guard, a peripheral trough 1037 and a
central drain 1038, i.e. at center point 1032, both connected to
drain lines 1039 which in turn are connected to waste container
1023. Drawer 1034 is slidably mounted in housing 1030 on rails
1040. Rails 1040, in a preferred embodiment, comprise three-piece
telescoping rails so that the drawer 1034 may be slid clear of
housing 1030 to permit access to all of the slide platforms 1050
for slide loading and removal. A damping means such as a pneumatic
means, electromotive means, mechanical spring damper or the like
(not shown) preferably is provided to smooth movement of the drawer
whereby to avoid possible dislodging of slides, particularly when
the drawer is closed. Slide support assembly 1099 is supported on a
lift mechanism such as pneumatic cylinders 1052 (see FIG. 11),
which automatically index to permit the slide support assembly 1099
to move up and down so that the slide support plate 1033 and
circular pan 1035 may be dropped to permit wall 1036 to clear the
nozzle support 1100 when the drawer is slid in and out of the
apparatus.
[0073] Slide support assembly 1099 is allocated into thirty-five
equal pie-shaped sections 1070. Thirty of the pie-shaped sections
1070 are occupied by slide platforms 1050 while the five remaining
pie-shaped sections 1070A (FIG. 15) at the rear of the drawer are
devoid of slide platforms 1050. In other words, a row of thirty
slide platforms 1050 are radially mounted within slide support
assembly 1099 and evenly spaced from one another, except at the
ends of the row.
[0074] However, the invention is not limited to thirty active slide
locations, and more or fewer slide locations may be employed. An
alternative embodiment may be implemented by aligning the platforms
1050 linearly, which results in potentially limitless number of
platforms.
[0075] Referring to FIGS. 11, 14 and 18, a nozzle support 1100 is
concentrically and rotatably mounted above slide support assembly
1099. Nozzle support 1100 is mounted on a shaft 1113 which in turn
is rotatably mounted on a bridge 1112, and driven by a computer
controlled stepping motor and drive belt (not shown), and rotates
plus or minus approximately 190.degree. from a home position at the
rear of the drawer. The computer controlled stepper motor and drive
belt are conventional in this art. Accordingly, details are omitted
for the sake of clarity.
[0076] With respect to FIG. 13, nozzle support 1100 carries the
various slide treatment stations, other than the reagent dispensing
station. Thus, nozzle support 1100 carries dual rinse nozzle block
1102, volume adjust/stringency block 1103, Liquid Coverslip.TM.
evaporation inhibitor liquid application block 1105, vortex mixer
air jet block 1106, jet drain 1108, and the like, all for preparing
a slide for staining, stain reagent removal, and the like, and to
clear the bar codes (not shown) carried on the slides, and a bar
code reader 1109, all as described in detail in U.S. Pat. No.
5,595,707 to Copeland et al, which disclosure is incorporated
herein by reference. In other words, nozzle support 1100 carries
all of the functions for slide preparation, cleaning, reagent
mixing, Liquid Coverslip.TM. application, etc. other than reagent
application, as described in the '707 patent to Copeland et al.
[0077] Preferably, but not necessarily, the various rinse nozzle
blocks, vortex mixer air jet blocks, jet drain, etc. are arranged
adjacent to one another so that the nozzle support 1100 may be
indexed and advanced in a "lock-step" manner to sequentially treat
a selected slide according to an accepted protocol. For example,
jet drain 1108 may be arranged immediately adjacent rinse nozzle
blocks 1106 so that nozzle support 1100 may be advanced in "lock
step" manner past a selected slide, and the slide rinsed and fluid
stripped, etc. Also, if desired, vortex mixer air jet blocks 1106
may be oriented to impinge simultaneously on two adjacent
slides.
[0078] For the sake of clarity, fluid and air supply tubing for the
several slide treatment stations have been omitted from the
drawings. It will be understood, however, that the fluid and air
supply tubing are made long enough to permit the valve plate to
rotate plus or minus approximately 190.degree. from a home position
at the rear of the apparatus so that each slide treatment station
can reach each slide 1060.
[0079] With respect to FIGS. 11 and 14, reagent support 1300 is
fixedly mounted to a cage 1110 vertically above nozzle support
1100, which cage in turn is rotatably mounted for rotation on a
shaft 1113, which in turn is driven by a stepper motor and belt
(not shown). A plurality of reagent dispensers 1302 are removably
mounted equally spaced adjacent the periphery of reagent support
1300. In the illustrated embodiment, a total of thirty-five reagent
dispensers are carried by the reagent support 1300, spaced
approximately one thirty-fifth (approximately 10.degree.) apart.
Preferably, the reagent dispensers are mounted on curved dispenser
carriers 1303, which in turn are mounted on reagent support 1300
(see FIG. 17A).
[0080] Curved dispenser carrier 1303 permits a lab worker to
assemble a kit of reagent dispensers for use, and also to remove
the kit of reagent dispensers so that the reagents may be
refrigerated, for example, overnight when not in use.
[0081] The reagents may include any chemical or biological material
conventionally applied to slides including nucleic acid probes or
primers, polymerase, primary and secondary antibodies, digestion
enzymes, pre-fixatives, post-fixatives, readout chemistry,
counterstains, and the like.
[0082] Referring in particular to FIGS. 17A and 17B, the reagent
dispensers 1302, are shown mounted on dispenser carrier 1303.
[0083] Referring to both FIGS. 17A and 17B, each of the dispensers
1302 carries a plate 1307 upon which may be mounted a bar code
which may be read by a bar code reader (not shown).
[0084] Referring also to FIG. 18, a hammer or piston 1400 is
carried by an arm 1402 which is mounted on shaft 1113 for rotation
with the shaft. Hammer 1400 is keyed to move with the nozzle
support 1100, and is vertically and concentrically operatively
aligned over the reagent dispensers 1302. Hammer or piston 1400
comprises a servo or piston 1404 for moving vertically into
engagement with the top of a selected reagent dispenser, and force
a metered quantity of reagent from the dispenser i.e. as explained
in detail in U.S. Pat. No. 6,192,945. Thus, in order to dispense a
selected reagent on a selected slide, the nozzle support 1100 is
rotatably moved to a dispense position vertically over the selected
slide which had been previously prepared, e.g. washed, etc., by the
treatment stations carried on the nozzle support 1100. Since the
hammer is keyed to move with the nozzle support 1100, there is no
time wasted in moving the hammer or piston, and the hammer or
piston is vertically aligned. A particular feature and advantage of
the present invention is that the reagent support 1300 requires
neither electrical nor plumbing connections. Thus, the reagent
support 1300 is free to rotate in any direction, without
limitation.
[0085] Referring to FIGS. 19A and 19B, the overall process is as
follows:
[0086] A plurality of specimen-bearing slides 1060 are mounted on
the slide platforms 1050, and selected reagent dispensers 1302 are
mounted on the reagent support 1300. The slide drawer is closed and
the slide and reagent bar codes are read. The computer calculates
the master protocol and then downloads the run steps for the entire
run, the nozzle support 1100 and hammer or piston 1400 are indexed
to the first slide, and the slide is washed and prepared for
staining or other treatment in accordance with the pre-programmed
run steps by advancing the nozzle support 1100 in "lock-step"
manner. In the meanwhile, reagent support 1300 is rotated to locate
a selected reagent dispenser 1302 over the selected slide 1060, and
the hammer or piston 1400 activated to dispense a measured amount
of the desired reagent. The process is repeated for a second
selected slide, and so forth.
[0087] Still other changes may be made without departing from the
spirit and scope of the invention.
* * * * *