Note : Les descriptions sont présentées dans la langue officielle dans laquelle elles ont été soumises.
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VIAL SYSTEM AND METHOD FOR PROCESSING LIQUID-BASED SPECIMENS
CROSS-REFERENCE TO RELATED APPLICATIONS
TECHNICAL FIELD
The present invention is directed to an apparatus and a method for collecting
and
processing fluid specimens, e.g., biological fluid specimens, including
collecting uniform
layers of particulate matter therefrom, e.g., cells, for subsequent testing or
analysis, such as in
cytology protocols.
BACKGROUND ART
In a wide variety of technologies, the ability and/or facility in separating
matter,
typically particulate matter, from a fluid is a critical component in the
ability to test for the
presence of substances in the fluid. Too often, interference associated with
sample
preparation obscures the target particles to such a degree that the process is
not sufficiently
reliable, or too costly. Such problems exist in various fields of examination
which involve
detection and/or diagnosis, including environmental testing, radiation
research, cancer
screening through cytological examination, microbiological testing, and
hazardous waste
contamination, to name just a few.
Cytological examination of a sample begins with obtaining specimens including
a
sample of cells from the patient, which can typically be done by scraping
swabbing, or
brushing an area, as in the case of cervical samples, or by collecting body
fluids, such as
those obtained from the chest cavity, bladder, or spinal column, or by fine
needle
aspiration or fine needle biopsy. In a conventional manual cytological
preparation, the
cells in the fluid are then transferred directly or by centrifugation-based
processing steps
onto a glass slide for viewing. In a conventional automated cytological
preparation, a
filter assembly is placed in the liquid suspension and the filter assembly
both disperses the
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cells and captures the cells on the filter. The filter is then removed and
placed in contact with
a microscope slide.
In all of these endeavors, a limiting factor in the sample preparation
protocol is
adequately separating solid matter from its fluid carrier, and in easily and
efficiently
collecting and concentrating the solid matter in a form readily accessible to
examination
under a microscope. Diagnostic microbiology and/or cytology, particularly in
the area of
clinical pathology, bases diagnoses on a microscopic examination of cells and
other
microscopic analyses. The accuracy of the diagnosis and the preparation of
optimally
interpretable specimens typically depends upon adequate sample preparation. In
this regard
the ideal specimen would consist of a monolayer of substantially evenly spaced
cells. Newer
methodologies such as inununocytochemistry and image analysis require
preparations that
are reproducible, fast, biohazard-free and inexpensive.
Currently, biological samples are collected for cytological examinations using
special
containers. These containers usually contain a preservative solution for
preserving the
cytology specimen during shipment from the collection site to the diagnostic
cytology
laboratory. Further, cytology specimens collected from the body cavities using
a swab, smear,
spatula or brush are also preserved in special containers with fixatives
(e.g., alcohol or
acetone fixatives) prior to transferring cells onto the slide or membrane for
staining or
examination.
Specimen containers are known that allow a liquid-based biological specimen to
be
processed directly in the container so as to obtain a substantially uniform
layer of cells on a
collection site (in a filter housing defining a particulate matter separation
chamber) that is
associated with the container itself. See, for example, U.S. patent Nos.
5,301,685; 5,471,994;
6,296,764; and 6,309,362. However, these types of specimen containers require
specially
configured apertured covers and adapters therefor that are designed to mate
with the filter
housing, and with suction equipment (e.g., a syringe or a mechanized vacuum
source) used to
aspirate liquid from the container and draw it through the filter. Further,
extraction of the
filter so that it can be pressed against a microscope slide to transfer
collected cells to the slide
requires disassembly of the cooperating parts of the cover and/or adapters
associated
therewith. If the processing is done by automated equipment, special handling
devices are
required to carry out such disassembly. All of this complexity adds time and
material and
labor cost to the processing required prior to the actual cytology
examination.
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SUMMARY DISCLOSURE OF THE INVENTION
The present invention concerns a specimen vial that houses a complete
processing
assembly, typically one for stirring the liquid-based specimen therein and for
holding a
filter on which a uniform layer of cells can be collected from the specimen.
It is expected
that the specimen vial would be prepackaged with a liquid preservative
solution, as is
commonplace.
The processing asseinbly is coupled to a simple cover for the vial by means of
a
simple and inexpensive releasable coupling. When the cover is removed at the
point-of-
care site (doctor's office, clinic, hospital, etc.), the processing assembly
remains with the
cover to allow medical personnel easy access to the container interior for
insertion of a
biological specimen into the vial. The cover, along with the attached
processing assembly,
is then replaced to seal the vial. The vial may then be sent to a laboratory
for processing.
When the vial is manipulated in a simple way while still closed, the
processing
assembly detaches from the cover and remains in the vial for access by
automated or
manual laboratory equipment when the cover is subsequently removed. In a
preferred
embodiment, a downward force on the center of the cover is all that is
required to detach
the processing assembly from the cover. In contrast with the prior art
specimen vials
discussed above, the vial of the present invention requires no further
interaction with the
cover, which can be removed by a simple uncapping device and is discarded to
avoid
contamination.
Accordingly, a first aspect of the invention concerns a method for processing
particulate matter-containing liquid in a vial comprising a container having
an opening at
its upper end, a cover removably coupled to the container to close the
opening, and a
processing assembly releasably coupled to the cover.. The method comprises the
steps of
detaching the processing assembly from the cover while the cover is on the
container,
removing the cover to expose the detached processing assembly in the
container, and
manipulating the processing assembly so as to process the particulate matter-
containing
liquid in the container. The detaching step comprises applying an external
force to the
closed vial. The external force may be applied to the central portion of the
cover to deflect
the cover inwardly.
The processing assembly may comprise a dispersing element, and the
manipulating
step may comprise moving at least the dispersing element to disperse the
particulate matter
in the liquid. The dispersing element may be rotated to stir the liquid.
Before such
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rotation, the dispersing element may first be lifted slightly to insure
clearance between the
processing assembly and the container.
The processing assembly may comprise a particulate matter separation chamber
at
the upper portion thereof adapted to hold a filter assembly, and a tube
communicating with
the separation chamber and extending downwardly therefrom. With such an
arrangement
the manipulating step may comprise placing a filter assembly in the separation
chamber,
sealing the separation chamber, and applying a vacuum to the separation
chamber to draw
the stiiTed particulate matter-containing liquid upwardly through the tube and
into contact
with the filter assembly so as to collect particulate matter on a surface of
the filter
assembly. Then the filter assembly may be removed from the separation chamber,
and the
particulate matter collected on the filter assembly contacted with a slide so
as to transfer
collected particulate matter to the slide.
Another aspect of the invention concerns a vial for holding and processing
particulate matter-containing liquid. The vial comprises a container having an
opening at
its upper end, a cover removably coupled to the container to close the
opening, and a
processing asseinbly releasably coupled to the cover so as to be removable
from the
container with the cover while still coupled thereto, and selectively
detachable from the
cover while the cover is on the container so as to remain in the container
when the cover is
subsequently removed.
The releasable coupling between the cover and the processing assembly may
comprise mating couplers, respectively carried by the inside of the cover and
the upper
portion of the processing assembly, that are held together by a retention
force and
disengage upon application of an external force to the vial that overcomes the
retention
force. The couplers may mate and disengage by relative motion in the axial
direction, i.e.,
parallel to the central axis of the container. The retention force may be
frictional, and the
couplers may be press-fit together.
The couplers may talce the form of closely fitting projections, which may be
annular. The upper portion of the processing assembly may comprise a bottom
wall
extending transversely of the container axis, the annular projection on the
processing
assembly extending upwardly from the bottom wall to form a cup-shaped recess
(which
may define a particulate matter separation chamber adapted to hold a filter
assembly). The
bottom wall may have a central hole, in which case a tube communicates with
the hole and
extends downwardly from the bottom wall. The tube has at least one dispersing
element
for dispersing particulate matter in the liquid.
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The cover may have a central boss that extends into the cup-shaped recess when
the processing assembly is coupled to the cover, the distal end of the central
boss
contacting or lying close to the bottom wall. When an external force is
applied to the
central portion of the cover so as to deflect the cover inwardly, the central
boss presses
5 against the bottom wall and pushes the bottom wall and the annular
projection thereon
away from the cover. The annular projection on the bottom wall may fit within
the
annular projection on the cover, so the external force deflects the annular
projection on the
cover outwardly, away from the annular projection on the bottom wall.
Yet another aspect of the invention concerns a vial for holding and processing
particulate matter-containing liquid. The vial comprises a container having an
opening at
its upper end, a cover removably coupled to the container to close the
opening, and a
processing assembly wholly within the container and engageable by an external
maiiipulator after the cover is removed. The container has a central axis
extending
lengthwise thereof through the opening, and a wall surrounding the axis. A
portion of the
surrounding container wall below the opening supports the processing assembly
when it is
not engaged by a manipulator such that the upper portion of the processing
assembly is
disposed near the opening.
The supporting portion of the container wall may comprise at least three
spaced
inwardly extending supports on which the processing assembly rests. These
supports may
comprise ribs (preferably four) that extend lengthwise of the container.
The processing assembly may comprise a particulate matter separation chamber
at
the upper portion thereof adapted to hold a filter assembly, a tube
coinmunicating with the
separation chamber and extending downwardly therefrom, and a dispersing
element
carried by the tube. The upper portion of the processing asseinbly has a
peripheral portion
that lies close to the surrounding wall and rests on the ribs. The processing
assembly may
be rotated about the central axis so as to cause the dispersing element to
stir the particulate
matter-containing liquid, the processing assembly being dimensioned to rotate
freely in the
container without contacting - the surrounding wall when lifted slightly off
the ribs by a
rotating manipulator. The close-fitting peripheral portion of the processing
assembly
prevents liquid from splashing out of the container during stirring, thus
minimizing
biohazard exposure. The ribs aid in the dispersion of particulate matter in
the liquid.
Still another aspect of the invention concerns a container for holding and
processing a fluid specimen. The container has a surrounding wall, an opening
at the
upper end of the surrounding wall, a bottom wall closing the bottom end of the
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surrounding wall, and a processing assembly supported within the container,
but not
attached thereto, by a portion of the surrounding wall. The processing
assembly is
engageable through the opening by an external device adapted to remove fluid
from the
container through the processing assembly. The processing assembly has an open-
ended
depending tube through which liquid exits the container, and the bottom of the
container
has an upward projection that fits closely within the open end of the tube to
form an
annular fluid outflow metering orifice.
BRIEF DESCRIPTION OF THE DRAWING FIGURES
A preferred embodiment that incorporates the best mode for carrying out the
invention is described in detail below, purely by way of example, with
reference to the
accompanying drawing, in which:
Fig. 1 is a vertical sectional view througll a specimen vial according to the
invention, showing the processing assembly in the vial coupled to the cover;
Fig. 2a is a front elevational view of the container portion of the vial;
Fig. 2b is a top plan view of the container, shown with the processing
assembly
removed;
Fig. 3 is a top plan view of the processing asseinbly;
Fig. 4 is a bottom plan view of the liner that fits within the cover;
Fig. 5 is an exploded vertical sectional view of the processing assembly and a
filter
assembly adapted for use in the processing assembly;
Fig. 6 is a vertical sectional view of the upper portion of the processing
assembly,
showing the filter assembly in place in the particulate matter separation
chamber and
engaged by a suction head;
Fig. 7 is a partial schematic view of the arrangement depicted in Fig. 6,
showing
the flow of liquid and particulate matter separated therefrom;
Fig. 8a is a vertical sectional view of the specimen vial similar to Fig. 1,
but
showing the processing assembly detached from the cover;
Fig. 8b is a partial vertical sectional view similar to Fig. 8a, showing a
modification of the processing assembly;
Figs. 9-13 are vertical sectional views of a container according to the
invention
undergoing various stages of automated laboratory handling, as follows:
Fig. 9 shows uncapping of the container (cover removal);
Fig. 10 shows primary stirring of the specimen;
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Fig. 11 shows placement of a filter in the particulate matter separation
chamber of
the processing assembly;
Fig. 12 shows acquisition of a specimen on the filter by aspiration of liquid
through
the processing assembly;
Fig. 13 shows removal of the filter and transfer of the specimen to a
microscope
slide; and
Fig. 14 is a top plan view of an automated apparatus for handling vials
according
to the invention and carrying out the specimen processing steps illustrated in
Figs. 9-13.
It is to be understood that the invention is not limited in its application to
the
details of construction and the arrangement of components of the preferred
embodiment
described below and illustrated in the drawing figures. Further, while the
preferred
embodiment is disclosed as primarily useful in the collection and processing
biological
fluids for cytology examination, it will be appreciated that the invention has
application in
any field in which samples of particulate matter are to be prepared from a
liquid that
contains such particulate matter.
DETAILED DESCRIPTION OF BEST MODE
Referring to Figs. 1, 2a and 2b, a vial 10 according to the invention
coinprises a
container 20, a cover 30 and a processing assembly 40. Processing assembly 40
is
designed to carry out several functions, among them mixing, and for this
preferred rotary
embodiment will be referred to as a stirrer for the sake of convenience.
Container 20
preferably is molded of plastic, preferably polypropylene, and has a
substantially
cylindrical wall 21, surrounding its longitudinal axis, joined to a conical
bottom wall 22.
A small portion 24 of wall 21 preferably is flat, the outer surface of the
flat portion
adapted to receive indicia, e.g., a bar code label, containing information
concerning the
specimen placed in the vial. Although only one flat portion is shown, the
container could
be configured with two or more flat portions, each adapted to receive indicia.
Alternatively, the indicia could be located on a curved portion of wa1121. The
bottom end
of flat portion 24 has an arcuate notch 25 which acts to keep the container in
a proper
orientation when handled by automated laboratory processing equipment designed
to
cradle the container and move it through various processing stations. Four
longitudinal
ribs 26 project inwardly from wall 21. The upper ends 27 of ribs 26 form rests
for the
processing assembly 40 when it is detached from cover 30 (see Fig. 8a). The
top of
container 20 has an opening 28 and a standard right-hand helical thread 29
that preferably
extends for one and one half turns and mates with a similar thread on cover
30. Other
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types of cover-to-container coupling may be used, such as a bayonet coupling,
snap-fit
arrangement, etc.
Cover 30 comprises a commercially available simple molded plastic threaded cap
31, and a novel liner 32 retained in the cap. Cap 31 has a flat solid top, and
an externally
knurled depending flange with an internal helical thread 33 that mates with
thread 29 on
container 20. Referring to Fig. 4, liner 32 is molded of plastic material,
preferably
polyethylene, and has a substantially flat base 34 sized to fit snugly within
cap 31, behind
thread 33, so that the liner is not readily separated from the cap. As seen in
Fig. 1, liner
base 34 serves as a gasket-type seal between the cap 31 and the rim of the
container wall
21.
Liner base 34 has a coupler in the form of an annular projection 35 that
preferably
is slightly conical in shape, preferably forming an angle of about 5 to its
central axis. In
other words, the inner diameter of annular coupler 35 is greater at its
proximal end, where
it joins liner base 34, than at its distal end. Liner base 34 also has a
central annular boss
36 that projects further from base 34 than annular coupler 35 so as to
interact with
processing assembly 40, as described below. While the use of a separate liner
mated to a
standard cap is preferred, the cover could be integrally molded in one piece
to include the
annular coupler 35 and the central amlular boss 36. Such a one-piece cover (or
even the
two-piece cover described above) could instead be configured to act as a plug-
type seal by
projecting into and sealing against the inside of the rim of container wall
21.
Referring to Figs. 1, 3 and 5, processing assembly 40 is in the form of a
stirrer
molded of plastic, preferably polypropylene, having a circular base or bottom
wall 41,
sloped at its center, with a central inlet port 42; a central depending
suction tube 43 with
two diametrically opposed suction ports 44 near the bottom of the tube; and a
dispersing
(mixing) element in the forn of laterally extending vanes 45. The upper
portion of the
stirrer 40 has a cup-shaped particulate matter separation chamber or manifold
46 defined
by base 41 and an upstanding annular wall 47. The upper edges of wall 47 are
beveled,
the inner edge 48 preferably being beveled to a greater degree to facilitate
placement of a
filter assembly F in manifold 46, as described below.
Annular wall 47 serves as a coupler for releasably coupling the stirrer 40 to
cap
liner 32, and is therefore dimensioned to fit snugly within annular coupler 35
(see Fig. 1).
Specifically, there is a friction or press fit between couplers 35 and 47 such
that normal
handling of the closed vial, and normal handling of cover 30 when removed from
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container 20 (e.g., to place a biological specimen in the container) will not
cause
separation of the stirrer from the cover. Coupler 47 is dimensioned relative
to coupler 35
so that there is a very slight initial diametrical interference, preferably
about 0.31 mm.
Coupler 47 is stiffer than coupler 35, so assembly of the stirrer to the cover
involves slight
deformation principally of coupler 35, resulting in a frictional force that
keeps the stirrer
and the cover engaged. Application of an external force to the vial that
overcomes this
frictional retention force will cause stirrer 40 to detach from cover 30 and
drop by gravity
further into container 20 (see Fig. 8a).
The external separation force preferably is applied to the central portion of
cover
30 (see the arrow in Fig. 8a), which deflects cap 31 and liner 32 inwardly. As
illustrated
in Fig. 1, central boss 36 on liner 32 is dimensioned such that its distal end
just contacts or
lies very close to base 41 of the stirrer. Thus, when the central portion of
the cover is
depressed, central boss 36 will deflect further than annular coupler 35 on
liner 32 and push
stirrer 40 out of engagement with coupler 35. Inward deflection of liner 32
also causes
coupler 35 to spread outwardly, thereby lessening the retention force and
facilitating
detachment of the stirrer. The separation force applied to cover 30 and
required to detach
the stirrer should be in the range of 10 to 301bs., preferably about 12 lbs.
Another way to detach the stirrer from the cover is to exert an abrupt upward
external force on the vial, either manually or mechanically (automatically),
to yield an
acceleration force that overcomes the frictional retention force and
effectively pulls the
stirrer out of engagement with the cover. This can be done by, e.g., moving
the closed vial
rapidly downwardly to rap the bottom of the container 20 against a rather hard
surface.
Automated vial handling machinery can accomplish this by, e.g., mechanically
and/or
pneumatically thrusting the closed vial into the carrier that will hold the
vial during the
subsequent processing steps, or by dropping the vial' down a chute into the
carrier a
sufficient distance to dislodge the stirrer. Another way to exert an abrupt
upward external
force on the vial is to strike the bottom of the container 20 with a striking
member.
Automated vial handling machinery can accomplish this by, e.g., cradling the
container 20
and momentarily thrusting a striker against the bottom of the container, e.g.
tlirough a
bottom opening in the vial carrier. The design of these and other variants of
suitable
automated mechanisms for accoinplishing these tasks should be within the grasp
of those
skilled in the mechanical arts.
Once detached from the cover 30, stirrer 40 comes to rest on the upper ends 27
of
ribs 26. See Fig. 8a. The particulate matter separation chamber (manifold) 46
thus is
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stably supported near the container opening and easily accessed by processing
equipment,
whether manual or automatic, which will manipulate the stirrer so as to
process the
specimen directly in the container. At least three ribs 26 are required to
form a stable
support for the stirrer, but four are preferred because that number seems to
promote more
5 thorough dispersion of the particulate matter in the liquid during stin-
in.g.
A small percentage of patient specimens, as may be found in gynecological Pap
test and other specimen types, contain large clusters of cells, artifacts, and
/or cellular or
noncellular debris. Some of these large objects, if collected and deposited on
a slide, can
obscure the visualization of diagnostic cells and, consequently, result in a
less accurate
10 interpretation or diagnosis of the slide sample. Since most of these
features are not of
diagnostic relevance, their elimination from the sample is, in general,
desirable. To
achieve this result, the side suction ports 44 in the stirrer suction tube 43
preferably are
eliminated (see Fig. 8b) in favor of close control of the interface between
the bottom of the
suction tube 43 and the small projection 23 at the center of bottom wall 22 of
the container
20. This interface effectively forms a metering valve whose geometry (orifice)
23a is
created when the stirrer 40 rests on the ribs 26 of the container 20. Proper
sizing of the
annular flow orifice 23a prevents large objects from entering the suction tube
43, while
allowing the passage of smaller objects that may be diagnostically useful.
While the
orifice 23a has a thin passage section and a small metering area, clogging is
not an issue
due to its large diameter. The annular orifice 23a preferably has an outside
diameter on
the order of 0.105 in. and an inside diameter on the order of 0.071 in.,
yielding a passage
width on the order of 0.017 in. This orifice size is optimized for
gynecological specimens.
Fig. 14 shows an overview and'some details of one form of automated (computer-
controlled) device for handling specimen vials according to the invention. The
device is
referred to as an "LBP" device (for liquid-based slide preparation), and can
be integrated
into a complete automated laboratory system. Further details of the LBP device
and the
system are set forth in US patent publication no. 2003/0092186.
In the LBP device a conveyor 100 trained around sprockets 102, 104 is driven
stepwise in accordance with a specified operating protocol to advance specimen
vials
along a processing path from one operating head to another. Conveyor 100 has
thirty vial
carriers 106 (numbered 1-30) serially linked by pins 108. Vial carriers 106
are in the form
of receptacles that are keyed to accept containers 20 in only one position
(i.e., keyed to
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notches 25 in containers 20). Loading of vials into conveyor 100 can be done
manually,
or automatically by a pick-and-place auto loader 110. Unloading of processed
containers
can be done manually, or by the same or a different pick-and-place auto
loader.
After a specimen vial is loaded into a receptacle 106, data concerning the
specimen
therein, including the identity of the patient, is first acquired at a bar
code reading station
112. This data governs the particular operating protocol to be carried out.
The vial then
moves to an uncapping station 120, where an uncapping head having a lead screw-
driven
plunger (not shown) first applies a downward force to the center of the cover
(see Fig. 8a)
to dislodge stirrer 40 from the cover, and then grips the knurled rim of the
cover (e.g.,
using a tapered gripping jaw, not shown), twists it counterclockwise to remove
the cover,
and then discards it. Fig. 9 schematically illustrates the cover removal step,
and shows the
stirrer resting on ribs 26 after the cover is removed.
After uncapping the vial moves to a station 130 where preprocessing occurs.
The
preprocessing station is the location at which preprocessing operations, such
as specimen
dispersal within its container, are performed prior to the container and its
specimen
moving to the specimen acquisition station. The preprocessing station
typically performs
a dispersal operation. In the preferred embodiment, the dispersal operation is
perfonned
by a mechanical mixer, which rotates at a fixed speed and for a fixed duration
within the
specimen container. In this example, the mixer serves to disperse large
particulates and
microscopic particulates, such as human cells, within the liquid-based
specimen by
homogenizing the specimen. Alternatively, the specimen may contain subcellular
sized
objects such as molecules in crystalline or other conformational forms. In
that case, a
chemical agent may be introduced to the specimen at the preprocessing station
to, for
example, dissolve certain crystalline structures and allow the molecules to be
dispersed
throughout the liquid-based specimen through chemical diffusion processes
without the
need for mechanical agitation. In this example, the chemical preprocessing
station
introduces its dispersing agent through the preprocessing head.
In the illustrated einbodiment, high-speed stirring is carried out at station
130.
Here (see Fig. 10) a stirring head comprising an expanding collet 132 moves
downwardly
by action of a lead screw (not shown) into the open upper recess (manifold) 46
of the
stirrer 40, and expands against annular wall 47 to grip the stirrer. The
collet lifts the stirrer
very slightly so that it clears the ribs 26, and then spins the stirre'r in
accordance with the
sample-specific stirring protocol as determined by the bar code reader 112.
The base or
bottom wall 41 of the stirrer acts as a slinger to thrust any liquid that may
rise along the
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stirrer against the container wal121, and prevents the escape of liquid from
the container.
When stirring is complete, the collet 132 releases the stirrer and rises to
clear the container
so that it can move on.
At the next station 140 a filter assembly F is loaded into the particulate
matter
separation chamber (manifold) 46 at the upper end of the stirrer. See Fig. 11.
The filter
assembly is dispensed by a lead screw-driven pusher 142 from a magazine 144
having
eight filter tubes 146 which can house filters of different types. The filter
dispensed is
determined by the specimen-specific processing protocol.
After a filter assembly F is loaded the vial moves to a specimen acquisition
station
150. Here a suction head 152 (see Fig. 12) descends by operation of a lead
screw (not
shown) to engage the upper portion of the stirrer 40. The suction head has an
O-ring 153
that seals against the outside of annular wall 47, and two concentric 0-rings
154, 155 that
seal against the top of filter assembly F. An inner suction line 156 draws a
vacuum on
filter F, in accordance with the specimen-specific processing protocol, to
aspirate
particulate matter-containing liquid from the container through suction tube
43, into the
particulate matter separation chamber (manifold) 46 and through the filter
assembly F,,
leaving a monolayer of cells on the bottom surface of the filter as described
below. Prior
to aspiration the specimen may be stirred again, this time more slowly, to re-
suspend the
particulate matter in the liquid. This is done by the rotatably mounted
suction head 152,
whicli is turned by a timing belt 151.
When aspiration of the specimen is complete, the suction head 152 is raised.
The
inner portion 158 of the suction head is extended at the same time by action
of a
pneumatic cylinder (not shown). As the suction head 152 is raised, the outer
portion 157
of the suction head disengages from the stirrer 40 (see Fig. 13), but the
filter assembly F is
retained on the imler portion 158 of the suction head by application of vacuum
through
suction line 159 to the annular space between O-rings 154 and 155. Thus the
suction head
152 removes filter assembly F from the stirrer, and can continue to apply
light suction via
suction line 156 through the filter to effect a desired degree of moisture
control of the
cellular material on the filter. The suction head 152 then pivots about an
axis 161 (see Fig.
14) to position the filter over a microscope slide S delivered from a slide
cassette 162 at a
slide presentation station 160. The suction head then moves downwardly to
press the filter
against the slide S and transfer the monolayer of cells thereto. The phantom
lines in Fig.
13 show this change in position of suction head 152 and contact of the filter
with slide S.
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13
A few drops of liquid fixative are then applied to the specimen on the slide,
and the slide is
shuttled back to its original position in the slide cassette.
After the specimen has been acquired, the container moves to a recapping
station
170 where a new cap, e.g., a heat-sealed foil, is applied to seal the
container.
Fig. 6 shows some details of the filter assembly F and its functional
cooperation
with the stirrer manifold 46 and the inner portion 158 of suction head 152.
Filter assembly
F comprises a filter holder 200 that accommodates a filter 202. Filter 202
comprises a
porous frit 203 and a filter membrane 205 that lies over the lower surface of
the frit 203
and is sealed to the periphery of holder 200, e.g., by sonic welding. There is
a single,
central opening 204 in the top of filter holder 200. The filter 202 (and hence
the entire
flter assembly F) is supported at its periphery on stirrer base 41 by an array
of ribs 48a
that define between them radial flow passages 49 (see Fig. 3). The 0-rings
154, 155 of
inner suction head portion 158 seal against the top of filter holder 200.
Suction applied
through port 156 creates a vacuum around central opening 204 and within the
filter holder
200, which draws liquid into the separation chamber (manifold) 46 and through
the filter
202. The flow is vertical through the filter and also across the filter
membrane face
because of the radial flow passages 49. See Fig. 7, which shows particulate
matter (cells)
as circles and indicates the flow by arrows. This dual-flow configuration
promotes the
formation of a monolayer of cells on the filter. See, e.g., the aforementioned
US patent
No. 5,471,994, which describes this dual-flow concept in general. The sloped
bottom wall
41 of the manifold 46 further promotes the formation of a monolayer of cells.
The
constructional details of the filter assembly and its cooperation with the
sloped-bottom
,manifold 46 are set forth in US patent publication no. 2003/0092186.
The invention thus provides an efficient, inexpensive, convenient and safe
vial-
based system and method for collecting, handling and processing biological
specimens
and other specimens of particulate matter-containing liquid. It is ideally
suited for use in
automated equipment that provides consistently reliable processing tailored to
sample-
specific needs. Should the stirrer inadvertently become detached from the
cover at the
point-of-care site, the physician or an assistant simply places the stirrer
loosely in the vial
so that it descends into the specimen and then screws the cover on as usual.
This is not
difficult because the ribs in the vial allow insertion of the stirrer in only
one direction.
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WO 03/034035 PCT/US02/33459
14
Once the vial is closed with the specimen inside, the stirrer remains in the
vial throughout
processing and is sealed therein when the vial is re-capped.
Various modifications will be apparent to those skilled in the art without
departing
from the scope of the invention, which is defined by the appended claims.
INDUSTRIAL APPLICABILITY
The above-described vial system and method is an integral part of a safe,
effective,
accurate, precise, reproducible, inexpensive, efficient, fast and convenient
system and
method for collecting, handling and processing liquid-based cellular
specimens, providing
fully integrated specimen and information management in a complete diagnostic
cytology
laboratory system.
