JP2005506532A - Vial system and method for processing liquid-based specimens - Google Patents

Abstract

Vial-based systems and methods are provided for handling and processing particulate-containing liquids directly in vials. A processing assembly including a stirring member and a particulate material separation chamber is releasably coupled to the inside of the vial cover. When the vial is opened to introduce the specimen, the processing assembly remains in the cover. When a specific external force is applied to a closed vial, the processing assembly is detached from the cover, and the processing assembly remains in the vial so that subsequent access to the automatic or manual laboratory equipment is removed when the cover is removed. It becomes possible.

Description

【Technical field】
[0001]
Cross-reference of related applications
This application claims the benefits of US Provisional Patent Application No. 60 / 330,092 filed on October 19, 2001, and US Provisional Patent Application No. 60 / 372,080 filed on April 15, 2002. Are both incorporated herein by reference. This application is also a continuation-in-part of US Non-Provisional Patent Application No. 10 / 122,151, filed April 15, 2002, which is incorporated herein by reference. In addition, this application is a commonly owned US non-provisional patent application entitled “Automated System and Method for Processing Multiple Liquid-Based Specimens”. ) "(Inventors Norman J. Pressman and William J. Mayer), which application is also incorporated herein by reference.
[0002]
Technical field
The present invention relates to an apparatus and method for collecting and processing fluid specimens, such as biological fluid specimens, and for preparing cells for subsequent examination or analysis, eg, cytological examination or analysis. Including a process of collecting and depositing a particulate material such as a uniform layer.
[Background]
[0003]
Background art
The ability and / or equipment to separate a substance, in particular particulate matter, from a fluid is a critical component of the ability to test for the presence or absence of a substance in a fluid in a variety of techniques. Too many of the obstacles associated with sample preparation can make certain processes unreliable or too expensive to obscure target particles. These problems are common to a variety of testing areas, including environmental investigations involving detection and / or diagnosis, radiation studies, cancer screening through cytological testing, microbiology testing, and hazardous waste contamination. is there.
[0004]
Sample cytology begins with taking a specimen containing a sample of cells from a patient, which typically involves scraping, wiping, or brushing the area, as is the case with cervical samples. Alternatively, it is performed by collecting a body fluid obtained from the thoracic cavity, bladder, spinal column, or the like, or performing aspiration using a fine needle or biopsy using a fine needle. In conventional manual cytological preparation, cells in a fluid are transferred to a viewing glass slide either directly or by a process based on centrifugation. In conventional automated cytological preparation, the filter assembly is placed in suspension and the filter assembly captures the filter while dispersing the cells. Thereafter, the filter is removed and placed in contact with the microscope slide glass.
[0005]
In all of these efforts, the limiting factor in the sample preparation protocol is that the solids are properly separated from the fluid carrier, and the solids are easily and efficiently collected and concentrated for easy examination under a microscope. This is the stage where the shape can be used. Diagnostic microbiology and / or cytology, particularly in the field of clinical pathology, makes a diagnosis based on microscopic examination of cells and other microscopic analysis. The accuracy of diagnosis, and the accuracy of preparing optimally interpretable specimens, typically depends on appropriate sample preparation. In this respect, an ideal specimen consists of a monolayer of cells that are substantially equally spaced. Newer methodologies such as immunocytochemistry and image analysis require reproducible, rapid, biohazardous and inexpensive preparations.
[0006]
Currently, biological samples are collected using special containers for cytological examination. These containers often contain a storage solution for storing cytological specimens during transport from the collection point to the diagnostic cytology laboratory. In addition, cytological specimens collected from body cavities using swabs, smears, spatulas, or brushes can also be used with fixatives (eg, alcohol) before transferring the cells onto glass slides or membranes for staining or examination. Or stored in a special container containing acetone fixative.
[0007]
Liquid-based biological specimens can be processed directly in the container to obtain a substantially uniform layer of cells on the collection site (the filter housing that defines the particulate separation chamber) associated with the container itself. Sample containers are known. See, for example, US Pat. Nos. 5,301,685, 5,471,994, 6,296,764, and 6,309,362, all of which are incorporated herein by reference. However, these type specimen containers are designed to mate with a filter housing and a suction device (e.g., a syringe or mechanized vacuum source) used to aspirate liquid from the container and draw it through the filter, Requires a specially configured aperture cover and an adapter for this cover. When removing the filter so that the collected cells can be transferred to the slide glass by pressing the filter against the microscope slide glass, disassemble the cooperating part of the cover and / or the adapter attached to the cover. There must be. When this process is performed using an automated device, a special handling device for performing such disassembly is required. This complexity adds time, materials, and labor costs to the processing required before performing the actual cytological examination.
DISCLOSURE OF THE INVENTION
[0008]
Summary of the invention
The present invention relates to a complete processing assembly, typically a processing assembly for holding a filter capable of agitating a liquid-based specimen therein and collecting a uniform layer of cells from the specimen. A specimen vial containing It is assumed that the specimen vial is prepackaged with a liquid storage solution as is usually done.
[0009]
This processing assembly is coupled to a simple cover for the vial by a simple, inexpensive, releasable bond. When the cover is removed at the medical site (clinic, clinic, hospital, etc.), the treatment assembly remains in the cover so that the health care worker can easily access the inside of the container and vial the biological specimen. Can be put in. The cover, together with the processing assembly coupled to the cover, is repositioned to seal the vial. Vials may be sent to the laboratory for processing.
[0010]
Manipulating in a simple manner with the vial closed, the processing assembly can be detached from the cover, stay in the vial, and then accessed by automatic or manual inspection equipment when the cover is removed It becomes. In a preferred embodiment, the processing assembly is detached from the cover by simply applying a downward force to the center of the cover. In contrast to the prior art specimen vials described above, the vials of the present invention do not need to interact further with the cover, which can be removed with a simple cover removal device and discarded to avoid contamination. .
[0011]
Accordingly, a first aspect of the invention includes a container having an opening at the top, a cover removably coupled to the container, a cover for closing the opening, and a processing assembly releasably coupled to the cover. The invention relates to a method for treating a liquid containing particulate matter in a vial. The method includes detaching the processing assembly from the cover while the cover is positioned on the container, removing the cover to expose the detached processing assembly in the container, and manipulating the processing assembly. And a step of treating the particulate matter-containing liquid in the container. The desorbing step includes applying an external force to the closed vial. An external force can be applied to the central portion of the cover to deform the cover inward.
[0012]
The processing assembly may include a dispersion member, and the step of manipulating may include at least moving the dispersion member to disperse the particulate material in the liquid. The dispersion member may be rotated to stir the liquid. Prior to such agitation, the dispersion member may first be lifted slightly to ensure a gap between the processing assembly and the container.
[0013]
The processing assembly may include a particulate material separation chamber located at the top of the processing assembly adapted to hold the filter assembly, and a tube communicating with the separation chamber and extending downwardly from the separation chamber. In such an arrangement, the operation steps include placing the filter assembly in the separation chamber, sealing the separation chamber, applying a vacuum to the separation chamber, and sucking the particulate-containing liquid upward through the tube. Contacting the filter assembly and collecting particulate matter on the surface of the filter assembly. Thereafter, the filter assembly may be removed from the separation chamber, the particulate matter collected on the filter assembly may be brought into contact with the slide glass, and the collected particulate matter may be transferred to the slide glass.
[0014]
Another aspect of the present invention relates to a vial for holding and processing a particulate material-containing liquid. The vial has a container with an opening at the upper end, a cover removably coupled to the container, and a cover for closing the opening, and can be removed from the container while remaining attached to the cover. Includes a processing assembly that is releasably coupled to the cover so that it is selectively detached from the cover while it is on the container and then remains in the container when the cover is removed.
[0015]
The releasable bond between the cover and the processing assembly includes mating joints carried on the inside of the cover and on the top of the processing assembly, respectively, which are coupled by a holding force and have an external force exceeding the holding force. Detach when applied to a vial. The joint can be engaged and disengaged by relative movement in the axial direction, i.e. parallel to the central axis of the container. The holding force can be a frictional force and the joints can be pressed together.
[0016]
The joint may take the form of a closely fitting protrusion, which may be annular. The top of the processing assembly includes a bottom wall extending in a direction transverse to the container axis, an annular protrusion on the processing assembly that extends upwardly from the bottom wall to define a cup-shaped recess (these are filter A particulate material separation chamber adapted to hold the assembly may be defined). The bottom wall may have a central hole, in which case the tube communicates with the hole and extends downwardly from the bottom wall. The tube has at least one dispersion member for dispersing the particulate matter in the liquid.
[0017]
The cover has a central protrusion that extends into the cup-shaped recess when coupled to the cover of the processing assembly, the distal end of the central protrusion being in contact with or in close proximity to the bottom wall. . When an external force is applied to the center of the cover and the cover is deflected inward, the center protrusion pushes the bottom wall and pushes the bottom wall and the annular protrusion on the bottom wall away from the cover. Since the annular protrusion on the bottom wall can fit within the annular protrusion on the cover, the external force deflects the annular protrusion on the cover outward and away from the annular protrusion on the bottom wall.
[0018]
Another aspect of the present invention relates to a vial for holding and processing a particulate material-containing liquid. This vial has a container with an opening at the top, a cover removably coupled to the container, and a cover for closing the opening, located completely within the container and engaged by external operating means after removal of the cover Includes possible processing assemblies. The container has a central axis that extends through the opening in the length of the container and a wall surrounds the axis. The portion of the container peripheral wall below the opening supports the processing assembly so that the upper portion of the processing assembly is disposed in the vicinity of the opening when not engaged by the operating means.
[0019]
The support portion of the container wall may include at least three spaced inwardly extending supports on which the processing assembly settles. These supports may include ribs (preferably four ribs) extending in the length direction of the container.
[0020]
The processing assembly is carried by a particulate material separation chamber located at the top of the processing assembly, adapted to hold a filter assembly, a tube communicating with the separation chamber and extending downwardly from the separation chamber, and a tube. A dispersion member may be included. The upper portion of the processing assembly has a peripheral portion located near the peripheral wall and settled on the rib. The processing assembly can be rotated about the central axis to agitate the particulate material-containing liquid with the dispersing member, and when the processing assembly is lifted slightly from the rib by the rotating operating means, the peripheral wall Dimension so that it can freely rotate in the container without touching. The closely fitted surrounding portion of the processing assembly prevents liquid from spilling out of the container during agitation and minimizes biohazard exposure. The ribs help to disperse the particulate material in the liquid.
[0021]
Yet another aspect of the invention relates to a container for holding and processing a liquid specimen. The container includes a peripheral wall, an opening located at an upper end of the peripheral wall, a bottom wall closing the lower end of the peripheral wall, and a processing assembly supported in the container by a part of the peripheral wall but not fixed to the container. 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 drooping tube through which liquid flows out of 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. Have.
[0022]
Preferred embodiments incorporating the best mode for carrying out the invention are described in detail below, by way of example only, with reference to the accompanying drawings.
[0023]
It is to be understood that the invention is not limited in its application to the preferred mode of construction and the arrangement of components described in detail below and illustrated in the drawings. Further, while preferred embodiments are disclosed as being primarily useful in collecting and processing biological fluids for cytological purposes, the present invention is directed to a sample of particulate matter such as It will be understood that it can be applied in any field that will be prepared from a liquid containing particulate material.
[0024]
Detailed description of the best mode
With reference to FIGS. 1, 2 a, and 2 b, a vial 10 according to the present invention includes a container 20, a cover 30, and a processing assembly 40. The processing assembly 40 is designed to perform a number of functions, including agitation, and therefore the preferred rotary embodiment is referred to as a stirrer for convenience. The container 20 is molded from plastic, preferably polypropylene, and has a substantially cylindrical wall 21 that surrounds the long axis of the container, and this wall 21 is joined to a conical bottom wall 22. A small portion 24 of the wall 21 is preferably flat and the outer surface of this flat is adapted to receive an indication, eg a bar code label, containing information about the specimen placed in the vial. Although only one flat portion is shown, the container may be configured with two or more flat portions, each adapted to receive an indication. Alternatively, the display can be arranged on the curved surface portion of the wall 21. The lower end of the flat portion 24 has an arcuate notch 25, which is an automated laboratory processing equipment designed to cradle the container and move various processing stations. When handling the container, it acts to hold the container in the proper orientation. From the wall 21, four longitudinal ribs 26 protrude inward. When the processing assembly 40 is detached from the cover 30 (see FIG. 8a), the upper end 27 of the rib 26 forms a support for the processing assembly. The top of the container 20 has an opening 28 and a standard right-handed spiral thread 29 that preferably extends half a turn and mates with a similar screw on the cover 30. Other types of cover-container coupling may be used, such as plug-in coupling, snap-fit arrangements, and the like.
[0025]
The cover 30 includes a commercially available simple threaded cap 31 that is plastic molded and a new liner 32 held within the cap. The cap 31 has an outwardly carved drooping flange with a flat, hard top and an inner helical thread 33 protruding therefrom and mating with a thread 29 on the container 20. With respect to FIG. 4, the liner 32 is molded from a plastic material, preferably polyethylene, and is dimensioned to fit snugly behind the thread 33 in the cap 31 so that the liner does not easily come off the cap. It has a flat substrate 34. As can be seen from FIG. 1, the liner substrate 34 serves as a gasket-type sealant between the cap 31 and the edge of the container wall 21.
[0026]
The liner substrate 34 is preferably slightly conical and has a joint in the form of an annular protrusion 35 that preferably forms an angle of about 5 ° with respect to the central axis. In other words, the inner diameter of the annular joint 35 is larger at the proximal end coupled to the liner substrate 34 than at the distal end. The liner substrate 34 also has a central annular boss 36 that projects beyond the annular joint 35 from the base 34 to interact with the processing assembly 40, as described below. While it is preferred to use a separate liner that fits into a standard cap, the cover can be integrally formed into a single piece that includes an annular joint 35 and a central annular boss 36. Such a one-part cover (or a two-part cover as described above) instead protrudes towards the inside edge of the container wall 21 and seals the inside of the edge. It can be formed to act as a stop.
[0027]
With reference to FIGS. 1, 3, and 5, the processing assembly 40 takes the form of a stirring member molded from plastic, preferably polypropylene, which has a centrally inclined circular shape with a central inlet port 42. The base or bottom wall 41; a centrally suspended suction tube 43 with a suction port 44 positioned diametrically near the bottom of the tube; and a dispersing (mixing) member in the form of vanes 45 extending laterally. The top of the agitation member 40 has a cup-shaped particulate material separation chamber or manifold 46 defined by a base 41 and an upstanding annular wall 47. The upper edge of the wall 47 is preferably beveled, and the inner edge 48 is preferably beveled to facilitate placement of the filter assembly F in the manifold 46, as will be described later.
[0028]
The annular wall 47 serves as a joint for releasably coupling the agitating member 40 to the cap liner 32 and is therefore dimensioned to fit snugly within the annular joint 35 (see FIG. 1). Specifically, because of the frictional force or press fit between fittings 35 and 47, normal handling of closed vials and removal from container 20 (eg, for placing biological specimens in containers) When the cover 30 is normally handled, the stirring member does not leave the cover. The joint 47 is dimensioned such that the initial diametric interference with the joint 35 is very small, preferably about 0.31 mm. Since the joint 47 is harder than the joint 35, when the stirring member is attached to the cover, a slight deformation mainly occurs on the side of the joint 35. As a result, a frictional force is generated and the stirring member is engaged with the cover. Will remain. When an external force exceeding the frictional holding force is applied to the vial, the stirring member 40 is detached from the cover 30 and further falls into the container 20 by gravity (see FIG. 8a).
[0029]
The separation force from the outside is preferably applied to the central portion of the cover 30 (see arrow in FIG. 8a), which causes the cap 31 and liner 32 to deflect inward. As shown in FIG. 1, the central protrusion 36 on the liner 32 is dimensioned such that its distal end is just in contact with or very close to the base 41 of the agitation member. Therefore, when the center portion of the cover is recessed, the central protrusion 36 bends ahead of the annular joint 35 on the liner 32, and the stirring member 40 is pushed to disengage the joint 35. Further, when the liner 32 bends inward, the joint 35 spreads outward, the holding force is reduced, and the stirring member is easily detached. The force applied to the cover 30 necessary to remove the stirrer should be in the range of 10-30 pounds, preferably about 12 pounds.
[0030]
Another method of detaching the stirring member from the cover is to apply an abrupt upward external force manually or mechanically (automatically) to the vial to obtain an acceleration force that exceeds the holding force due to friction. Effectively pulling away from engagement with the cover. This can be done, for example, by moving the closed vial rapidly downwards and tapping the bottom of the container 20 against a hard surface. The automatic vial handling device pushes the closed vial into the carrier that will hold the vial during subsequent processing steps, eg, mechanically and / or pneumatically, or the vial is passed through the chute into the carrier. This method can be performed by dropping the stirring member at a distance sufficient to desorb. Another way to apply a sudden upward external force on the vial is to strike the bottom of the container 20 with a striking member. In the case of an automatic vial handling device, this can be achieved, for example, by cradle the container 20 and momentarily pushing the striking member into the bottom of the container, for example by hitting the bottom of the container through an opening in the vial carrier. A method can be achieved. These designs, and the design of suitable automated mechanism variants to accomplish these tasks, are within the purview of those skilled in the mechanical arts.
[0031]
When the stirring member 40 is detached from the cover 30, the stirring member 40 settles on the upper end 27 of the rib 26. See Figure 8a. Thus, the particulate material separation chamber (manifold) 46 is stably supported near the container opening and is easily accessed by the processing device, whether automatic or manual, thereby manipulating the agitating member and placing the sample in the container. Direct processing is possible. In order to stably support the stirring member, at least three ribs 26 are required. However, it is preferable to provide four ribs because the particulate matter is more fully dispersed in the liquid during stirring.
[0032]
A small portion of patient specimens contain large cell masses, artifacts, and / or cells and non-cellular debris, as found in gynecological Papanicolaou tests and other types of specimens. These large objects, when collected and deposited on glass slides, obscure the visibility of the cells being diagnosed, resulting in interpretation of slide glass samples and the accuracy of the diagnosis. There are also things that damage it. Since most of these features are not diagnostic relevant, it is generally desirable to be removed from the sample. For this purpose, the suction pipe 43 of the stirring member is advantageously used for precise control at the interface between the bottom of the suction pipe 43 and the small protrusion 23 located at the center of the bottom wall 22 of the container 20. The inner side suction port 44 is preferably eliminated (see FIG. 8b). This interface effectively forms a metering valve whose shape (orifice) 23a is created when the stirring member 40 settles on the rib 26 of the container 20. By properly dimensioning the annular inflow orifice 23a, small objects that may be useful in diagnosis are allowed to pass while large objects are prevented from entering the suction tube 43. Orifice 23a has a narrow passage and a small metering area, but due to its large diameter, clogging is not a problem. The annular orifice 23a preferably has an outer diameter of about 0.105 inches and an inner diameter of 0.071 inches, resulting in a passage width of about 0.017 inches. This dimension of the orifice is optimized for gynecological specimens.
[0033]
FIG. 14 shows an overview of one form of an automated (computer-controlled) device for handling specimen vials according to the present invention, and some details. This device is referred to as a “LBP” device (for liquid-based slide preparation) and can be integrated into a fully automated laboratory system. For further details on the LBP apparatus and system, see the above provisional patent application 60 / 372,080 and the above co-filed non-provisional patent application “Automated System and Method for Processing Multiple Liquid-Based Specimens”. System and Method for Processing Multiple Liquid-Based Specimens).
[0034]
In the LBP system, the conveyor 100 hung around the sprockets 102 and 104 is driven stepwise according to a defined operating protocol to advance specimen vials from each operating head to the next operating head along the processing path. Let The conveyor 100 has 30 vial carriers 106 (numbered 1-30) connected in series by pins 108. The vial carrier 106 takes the form of a receptacle that is keyed to receive the container 20 in only one direction (ie, aligned with the notch 25 in the container 20). The loading of the vials onto the conveyor 100 can be done manually or automatically by the pick and place automatic loading device 110. The removal of the processed containers can also be done manually or by the same or another pick and place automatic loading device.
[0035]
After the sample vial is loaded into the receptacle 106, data relating to the sample in the vial, including patient identification information, is first acquired at the barcode reading station 112. This data determines the specific protocol to be performed. The vial then moves to the cap removal station 120, where a cap removal head with a lead screw driven plunger (not shown) first applies a downward force to the center of the cover (see Figure 8a). Remove stirrer 40 from the cover, then grip the notched edge of the cover (eg, using a tapered gripping jaw (not shown)) and twist the counterclockwise to remove the cover, then Discard. FIG. 9 schematically shows the stage of removing the cover, and shows a state where the stirring member settles on the rib 26 after the cover is removed.
[0036]
After removing the cap, the vial moves to the station 130 where the pretreatment is performed. The pre-processing station is a place where a pre-processing operation, for example, an operation of dispersing the sample in the container is performed before the container and its sample move to the sample acquisition station. Pre-processing stations typically perform distributed operations. In a preferred embodiment, the dispersing operation is performed by mechanical mixing means that rotate in the specimen container at a constant speed for a fixed time. In this example, the mixing means disperses large particles and fine particles, such as human cells, within the liquid-based sample by homogenizing the sample. Alternatively, the specimen may contain sub-cellular objects, such as crystals or other higher-order form of molecules. In such cases, chemicals can be introduced into the specimen at the pretreatment station without mechanical agitation, for example to dissolve specific crystal structures and to disperse the molecules throughout the liquid-based specimen through a chemical diffusion process Can be made. In this example, a chemical pretreatment station introduces the dispersant through the pretreatment head.
[0037]
In the illustrated embodiment, high speed agitation is performed at station 130. Here, (see FIG. 10), the action of the lead screw (not shown) causes the stirring head including the expansion collet 132 to move downward into the open upper recess (manifold) 46 of the stirring member 40. Then, it expands toward the annular wall 47 and grips the stirring member. The collet lifts the stirring member slightly away from the rib 26 and then rotates the stirring member according to the sample specific stirring protocol determined by the barcode reader 112. The stirrer base or bottom wall 41 acts as a slinger to push the liquid rising along the stirrer back toward the container wall 21 and prevent the liquid from leaking out of the container. When the stirring is completed, the collet 132 dissociates the stirring member and rises away from the container, so that the container can be moved.
[0038]
At the next station 140, the filter assembly F is loaded into the particulate material separation chamber (manifold) 46 located at the upper end of the stirring member. See FIG. The filter assembly is dispensed by a lead screw driven extruder 142 from a magazine 144 having eight filter tubes 146 that can accommodate different types of filters. The filter to be dispensed is determined by the processing protocol specific to each specimen.
[0039]
When the filter assembly F is loaded, the vial moves to the specimen acquisition station 150. Here, when the lead screw (not shown) is operated, the suction head 152 (see FIG. 12) is lowered and engaged with the upper portion of the stirring member 40. The suction head has an O-ring 153 that seals the outside of the annular wall 47 and two concentric O-rings 154 and 155 that seal the top of the filter assembly F. The inner suction line 156 evacuates the filter F according to the specimen-specific processing protocol, sucks the particulate material-containing liquid from the container through the suction tube 43 to the particulate material separation chamber (manifold) 46, and through the filter assembly F. When aspirated, a monolayer of cells remains on the lower surface of the filter, as described below. The specimen may be stirred again before aspiration, this time more slowly, resuspending the particulate material in the liquid. This agitation is performed by a suction head 152 that is rotated by a timing belt 151 and is rotatably mounted.
[0040]
When the suction of the specimen is completed, the suction head 152 is raised. At the same time, the inner part 158 of the suction head is extended by the action of a pneumatic cylinder (not shown). As the suction head 152 is raised, the outer portion 157 of the suction head is detached from the stirring member 40 (see FIG. 13), but a vacuum is applied through the suction line 159 to the annular space between the O-rings 154 and 155. Thereby, the filter assembly F is held on the inner part 158 of the suction head. In this way, the suction head 152 can remove the filter assembly F from the agitating member, and continues to apply light suction through the filter via the suction line 156 to remove moisture from the cellular material on the filter as desired. It can also be controlled to the extent. Thereafter, the suction head 152 pivots around the axis 161 (see FIG. 14), and the filter is placed on the microscope slide glass S fed out from the slide cassette 162 of the slide glass presentation station 160. Next, the suction head moves downward, the filter is pressed against the slide glass S, and the cell monolayer is transferred to the slide glass. The phantom line in FIG. 13 shows the change in the position of the suction head 152 and the contact of the filter with the slide glass S. Next, a few drops of fixative is applied to the specimen on the glass slide, and the glass slide is folded back to its original position in the slide cassette.
[0041]
After obtaining the specimen, the container moves to a cap remounting station 170 where a new cap, such as a heat sealing foil, is applied to the container and the container is sealed.
[0042]
FIG. 6 shows some details of the filter assembly F and the functional cooperation of the filter assembly F with the agitator manifold 46 and the inner portion 158 of the suction head 152. The filter assembly F includes a filter holder 200 that can accommodate the filter 202. The filter 202 includes a porous frit 203 and a filter membrane 205 that is positioned to cover the lower surface of the frit 203 and is sealed around the holder 200 by, for example, ultrasonic welding. There is a single central opening 204 at the top of the filter holder 200. The filter 202 (and thus the entire filter assembly F) is surrounded by a series of ribs 48a provided at its periphery at the base 41 of the stirrer member between which a radial channel 49 is defined. Supported (see FIG. 3). O-rings 154 and 155 of the inner part 158 of the suction head seal the top of the filter holder 200. Applying a suction force through port 156 creates a vacuum around the central opening 204 and inside the filter holder 200, thereby sucking liquid into the separation chamber (manifold) 46 and through the filter 202. The This flow is vertical through the filter and over the filter membrane surface due to the radial flow path 49. See FIG. 7 (particulate matter (cells) are indicated by circles and flow is indicated by arrows). This bi-directional channel configuration facilitates the formation of a cell monolayer on the filter. See, for example, U.S. Pat. No. 5,471,994, cited above (the concept of this bidirectional flow path is outlined). Since the bottom wall 41 of the manifold 46 is inclined, the formation of a monolayer of cells is further promoted. For details on the structure of the filter assembly and the cooperation of the filter assembly and the manifold 46 with the inclined bottom, see above provisional patent application No. 60 / 372,080 and the above-mentioned non-provisional patent filed simultaneously. The application “Automated System and Method for Processing Multiple Liquid-Based Specimens” is described.
[0043]
The present invention is an efficient, inexpensive, convenient, and safe vial-based system and method for collecting, handling, and processing biological specimens and other particulate-containing liquid specimens. I will provide a. The present invention is ideal for use in automated equipment that provides consistent and reliable processing tailored to the specific needs of the sample. Even if the stirrer is inadvertently removed from the cover at the point-of-care site, the doctor or assistant simply places the stirrer gently so that the stirrer is lowered into the specimen. Then, just turn the cover as usual and cover it. This operation is not difficult because the ribs in the vial allow insertion in only one direction of the stirring member. Once the vial is closed with the sample in it, the agitating member will remain in the vial throughout the process and will be sealed in the vial when the cap is remounted.
[0044]
Various modifications that may be made without departing from the scope of the invention as defined in the appended claims will be apparent to those skilled in the art.
[0045]
Industrial applicability
The vial systems and methods described above are safe, effective, accurate, accurate, reproducible, inexpensive and efficient for collecting, handling and processing liquid-based cell specimens, Closely inseparable from the rapid and convenient system and method, it provides a complete integrated management of specimens and information in a complete diagnostic cytology laboratory system.
[Brief description of the drawings]
[0046]
FIG. 1 is a longitudinal cross-sectional view of a sample vial of the present invention, showing the processing assembly in the vial coupled to a cover.
FIG. 2a is a front view of the container portion of the vial. FIG. 2b is a top view of the container with the processing assembly removed.
FIG. 3 is a top view of the processing assembly.
FIG. 4 is a bottom view of a liner that fits within a cover.
FIG. 5 is an exploded longitudinal cross-sectional view of a processing assembly and a filter assembly adapted for use in the processing assembly.
FIG. 6 is a vertical cross-sectional view of the upper portion of the processing assembly, showing a state where the filter assembly is placed in the particulate matter separation chamber and engaged by the suction head.
(FIG. 7) A partial schematic view of the configuration shown in FIG. 6, showing the flow of liquid and particulate matter separated from the liquid.
FIG. 8a is a longitudinal sectional view of a sample vial similar to FIG. 1, but showing the processing assembly detached from the cover. FIG. 8b is a partial longitudinal section similar to FIG. 8a, showing a modification of the processing assembly.
(FIGS. 9-13) Longitudinal sectional views of a container according to the present invention, showing the container through various stages of automated laboratory operation as follows.
FIG. 9 shows the step of removing the cap from the container (cover removal).
FIG. 10 shows the primary stirring of the specimen.
FIG. 11 shows the placement of the filter in the particulate material separation chamber of the processing assembly.
FIG. 12 shows specimen acquisition on the filter by aspirating liquid through the processing assembly.
FIG. 13 shows removal of the filter and transfer of the specimen to a microscope slide.
FIG. 14 is a top view of an automated apparatus for handling vials according to the present invention and for performing the sample processing steps illustrated in FIGS. 9-13.

Claims (55)

Process liquid containing particulate matter in a vial that includes a container having an opening at the top, a cover removably coupled to the container, and a processing assembly releasably coupled to the cover. A method for
Detaching the processing assembly from the cover while the cover is positioned on the container;
Removing the cover to expose the desorbed processing assembly in the container; and manipulating the processing assembly to process the particulate-containing liquid in the container. The method of claim 1, wherein the desorbing step comprises applying an external force to the closed vial. 3. The method of claim 2, wherein the step of detaching includes the step of applying an external force to the central portion of the cover to deflect the cover inward. 4. The method of claim 1, claim 2, or claim 3, wherein the processing assembly includes a dispersion member and the step of manipulating includes at least moving the dispersion member to disperse the particulate material in the liquid. 5. The method of claim 4, wherein moving the dispersion member comprises agitating the particulate material-containing liquid with the dispersion member by rotating the processing assembly. The step of moving the dispersion member includes first lifting the treatment assembly slightly to ensure a gap between the treatment assembly and the container, and then rotating the treatment assembly to cause the particulate material-containing liquid at the dispersion member. 5. The method of claim 4, comprising the step of stirring. A processing assembly includes and operates a particulate material separation chamber located on top of the processing assembly, adapted to hold a filter assembly, and a tube communicating with and extending downwardly from the separation chamber. The steps include placing the filter assembly in the separation chamber, sealing the separation chamber, and applying a vacuum to the separation chamber and sucking the stirred particulate material-containing liquid upward through the tube, 6. The method of claim 5, further comprising contacting the volume and collecting particulate matter on the surface of the filter assembly. 8. The method of claim 7, further comprising the step of removing the filter assembly from the separation chamber, contacting the particulate material collected on the filter assembly with the glass slide, and transferring the collected particulate material to the glass slide. . A vial for holding and processing a liquid containing particulate matter,
A container having an opening at the top;
A cover removably coupled to the container for closing the opening; and the cover so that it can be removed from the container while it is coupled to the cover and remains in the container when the cover is later removed. A vial containing a processing assembly that is releasably coupled to a cover so that it can be selectively detached from the cover while still coupled to the container. The releasable coupling between the cover and the processing assembly includes mating joints respectively carried by the inside of the cover and the upper part of the processing assembly, and these mating joints are coupled and retained by holding forces. 10. The vial according to claim 9, wherein the vial is detached when an external force exceeding the force is applied to the vial. 11. A vial according to claim 10, wherein the container has a central axis extending through the opening in the length of the container, and the fitting is engaged and disengaged by relative movement in the axial direction. 12. A vial according to claim 11, wherein the holding force is a frictional force. 13. A vial according to claim 12, wherein the fittings are press fit together. 14. A vial according to claim 13, wherein the fitting includes a closely fitting protrusion. 15. A vial according to claim 14, wherein the protrusion is annular. 16. The top of the processing assembly includes a bottom wall extending across the axis and an annular protrusion on the processing assembly extending upwardly from the bottom wall to define a cup-shaped recess. Vials. 17. The vial of claim 16, wherein the bottom wall has a central hole and the tube communicates with the hole and extends downwardly from the bottom wall. 18. A vial according to claim 17, wherein the tube has at least one dispersion member for dispersing particulate matter in the liquid. When the processing assembly is coupled to the cover, the cover has a central protrusion that extends into the cup-shaped recess, and the distal end of the central protrusion contacts or is in close proximity to the bottom wall; 19. A vial according to claim 16 or claim 18. 20.The external force is applied to the center of the cover and the cover is deflected inward to press the center protrusion against the bottom wall and push the bottom wall and the annular protrusion on the bottom wall away from the cover. Vials. 21. The annular protrusion on the bottom wall fits within the annular protrusion on the cover, and the external force deflects the annular protrusion on the cover outward and away from the annular protrusion on the bottom wall. Vials. The vial of claim 9, wherein the releasable bond between the cover and the processing assembly comprises a frictional bond. 23. The vial of claim 22, wherein the frictional coupling includes press fit of mating joints respectively carried on the inside of the cover and on the top of the processing assembly. The processing assembly includes a particulate material separation chamber located at the top of the processing assembly adapted to hold a filter assembly, and a tube communicating with and extending downwardly from the separation chamber. 9. The vial according to 9. 25. The vial of claim 24, wherein the processing assembly further comprises a dispersion member carried by the tube for dispersing the particulate material in the liquid. 26. The vial of claim 25, wherein the separation chamber includes an open top recess defined by a bottom wall and an upstanding annular protrusion, the annular protrusion being releasably coupled to the cover. 27. A vial according to claim 24, claim 25, or claim 26, wherein the wall of the container surrounding the processing assembly supports the processing assembly when the processing assembly is detached from the cover. 28. The vial of claim 27, wherein the container wall supports the processing assembly to prevent the processing assembly from settled to the bottom of the container. The container wall has at least three spaced apart inwardly extending supports, and the process assembly settles on the support when the process assembly is detached from the cover. The vial according to 28. 30. The vial of claim 29, wherein the inwardly extending support comprises a rib extending the length of the container. 32. The vial of claim 30, comprising four ribs. 27. The vial of claim 26, wherein the container wall surrounding the processing assembly supports the bottom wall of the separation chamber when the processing assembly is detached from the cover. 35. The vial of claim 32, wherein the container wall has at least three spaced inwardly extending supports and the bottom wall of the separation chamber settles on the support. 34. The vial of claim 33, wherein the inwardly extending support comprises a rib extending in the length direction of the container. 35. The vial of claim 34, comprising four ribs. 10. The vial of claim 9, wherein the container wall surrounding the processing assembly supports the processing assembly so that the processing assembly is prevented from settling on the bottom of the container when the processing assembly is removed from the cover. The container wall has at least three spaced apart inwardly extending supports, and the process assembly settles on the support when the process assembly is detached from the cover. 36. The vial according to 36. 38. The vial of claim 37, wherein the inwardly extending support comprises a rib extending in the length direction of the container. 40. The vial of claim 38, comprising four ribs. 11. A vial according to claim 10, wherein the fitting carried inside the cover is located on a liner held in the cover. The liner has a central projection that extends inwardly toward the processing assembly, and an external force is applied to the central portion of the cover to deflect the cover and liner inward, thereby causing the central projection to 11. The vial of claim 10, wherein the vial is pressed toward and away from the cover. 42. A vial according to claim 40 or claim 41, wherein the liner serves as a seal between the cover and the container. A vial for holding and processing a liquid containing particulate matter,
A container comprising an opening located at the upper end, a central axis extending through the opening in the length of the container, and a wall surrounding the axis;
A cover for closing the opening, removably coupled to the container; and a processing assembly located completely within the container and engageable by external operating means after removing the cover; A vial in which a portion of the peripheral wall of the container below the opening supports the processing assembly so that the upper portion of the processing assembly is positioned in the vicinity of the opening when not engaged by. 44. The vial of claim 43, wherein the support portion of the container wall includes at least three spaced inwardly extending supports and the processing assembly settles on the support. 45. The vial of claim 44, wherein the inwardly extending support comprises a rib extending in the length direction of the container. 46. The vial of claim 45, comprising four ribs. The processing assembly is carried by a particulate material separation chamber located at the top of the processing assembly, adapted to hold the filter assembly, in communication with the separation chamber and extending downwardly from the separation chamber. 44. The vial of claim 43, comprising a dispersion member, wherein the upper portion of the processing assembly has a peripheral portion located in the vicinity of the peripheral wall and settled on a support portion of the peripheral wall. When the processing assembly is rotatable about the central axis so as to agitate the particulate-containing liquid with the dispersing member, and when the processing assembly is lifted slightly from the support portion of the peripheral wall by the rotating operation means, 48. The vial of claim 47, wherein the vial is dimensioned to rotate freely in the container without contacting the peripheral wall. 49. The vial of claim 48, wherein the support portion of the container wall includes at least three spaced inwardly extending supports, and a peripheral portion of the processing assembly settles on the support. 50. The vial of claim 49, wherein the inwardly extending support includes ribs extending the length of the container to aid in the dispersion of particulate material in the liquid as the processing assembly rotates. 52. The vial of claim 50, comprising four ribs. The processing assembly has an open tube that extends downward and allows liquid to flow out of the container, and when the processing assembly is supported by the wall of the container, it fits closely within the open end of the tube 44. The vial of claim 43, wherein the bottom of the container has an upward projection that forms a liquid efflux metering orifice. A container for holding and processing a liquid specimen, which is supported in the container by a peripheral wall, an opening located at the upper end of the peripheral wall, a bottom wall closing the lower end of the peripheral wall, and a part of the peripheral wall. Includes an unfixed processing assembly that is engageable through the opening by an external device adapted to remove fluid from the container through the processing assembly, wherein the processing assembly includes a liquid assembly. A container having an open depending tube that flows out of 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 flow metering orifice. 54. A container according to claim 53, wherein the peripheral wall is symmetric with respect to a central axis extending through the opening in the length direction of the container, and the tubes and protrusions are aligned with the central axis. 55. The container of claim 54, wherein the peripheral wall supports the processing assembly such that an upper portion of the processing assembly is disposed proximate the opening.

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