US20020182115A1 - Chemical dispensing system and method - Google Patents
Chemical dispensing system and method Download PDFInfo
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- US20020182115A1 US20020182115A1 US10/056,511 US5651102A US2002182115A1 US 20020182115 A1 US20020182115 A1 US 20020182115A1 US 5651102 A US5651102 A US 5651102A US 2002182115 A1 US2002182115 A1 US 2002182115A1
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Images
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N1/00—Sampling; Preparing specimens for investigation
- G01N1/28—Preparing specimens for investigation including physical details of (bio-)chemical methods covered elsewhere, e.g. G01N33/50, C12Q
- G01N1/30—Staining; Impregnating ; Fixation; Dehydration; Multistep processes for preparing samples of tissue, cell or nucleic acid material and the like for analysis
- G01N1/31—Apparatus therefor
- G01N1/312—Apparatus therefor for samples mounted on planar substrates
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- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N35/00—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor
- G01N35/00009—Automatic analysis not limited to methods or materials provided for in any single one of groups G01N1/00 - G01N33/00; Handling materials therefor provided with a sample supporting tape, e.g. with absorbent zones
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/11—Automated chemical analysis
- Y10T436/112499—Automated chemical analysis with sample on test slide
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
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Definitions
- FIG. 1 illustrates an outside perspective view of cassette 1 which is part of an improved tissue staining system.
- cassette is taken to include any housing for containing a tissue sample to facilitate the application of chemicals onto the tissue sample.
- the cassette in FIG. 1 is substantially rectangular and contains an optional protective covering on its top surface that covers the interior portion of the cassette. It is to be appreciated that the cassette could have any of a variety of shapes (e.g., circular, triangular, etc.).
- Cassette 1 preferably contains a film access door 2 that may be located on the top, bottom, or side of the cassette.
- Cassette 1 preferably further includes a container access door 3 to allow access to an interior portion of the cassette.
- the first chemical is preferably positively displaced through relief port 21 out of head space 10 b by the second chemical and/or the pressure within the head space derived from piston 16 .
- Film 12 preferably carries a chemically filled container 13 a to a position adjacent to injection port 17 .
- Piston 16 is preferably aligned with injection port 17 .
- cassette driver 25 a may automatically start running because starting switch 31 is triggered by the pressure of cassette 1 .
- Splined shaft 18 preferably extends up from cassette driver 25 a and into cassette 1 where it rotates to cause cam 59 to displace piston 16 .
- Piston 16 may push container 13 a against a sharp end of injection port 17 .
- Members 76 may help guide piston 16 so that it remains aligned with container 13 a .
- the pointed end of injection port 17 may puncture the wall of container 13 a , forming an opening in the wall.
Abstract
A system and method for applying one or more chemicals to a tissue sample is provided. The system preferably includes a cassette for housing a slide device, a film, and an injection system. The slide device preferably includes a specimen slide for containing the tissue sample and a cover plate connected to the specimen slide. The film is preferably moveable through the cassette along guide rollers and preferably contains a plurality of containers containing one or more chemicals. The injection system may include a piston for displacing the chemicals from the containers through an injection port to the tissue sample. The cassette may be placed on a cassette driver that contains a motor-driven shaft for driving the piston and moving the film.
Description
- 1. Field of the Invention
- This present invention relates to histological and molecular pathology and more specifically to an immunohistochemistry staining system for staining tissue samples with a variety of chemicals to facilitate examination of the samples.
- 2. Description of the Related Art
- Staining tissue with chemicals is generally well known in the field of molecular pathology. Tissue samples may be subjected to histological and molecular pathological tests including in-situ hybridization, polymerase, and to chemical stains which are commonly referred to as “special stains”. A variety of chemicals may be used in the staining process, including biological reagents, antibodies, buffers, and deionized water. After a tissue is stained and rinsed with certain chemicals, one skilled in the art can identify the tissue type and any abnormalities in the tissue. Such methods may be used to identify various diseases in the tissue. Several methods of staining tissue are currently in use.
- One conventional method utilizes capillary action in which a chemical in liquid state is drawn up a narrow space between two slides due to the attraction between the molecules of the chemical and the slides. One of the slides contains a tissue sample to be contacted with the chemical. An operator is generally required to pipette the appropriate staining chemicals into containers into which the slides are placed. Filling the containers tends to require a substantial amount of time. The slide pair is then manually or mechanically inserted vertically into each container in an order dependent on the type of chemical in each container. Manually placing the slide pair in the correct container may be difficult if the containers are not labeled for the appropriate chemical. The method may be also be difficult when performed mechanically if a mechanical arm is not properly programmed to move the slide pair sequentially to the proper containers. A computer may be used to program the movements of a mechanical arm. The length of time that the slide pair is in each container is determined by using a watch or a computer.
- Another method for staining tissue uses an automated dispensing head or nozzle to drop or spray chemicals onto a slide's upper surface which contains the tissue sample. This may also be performed manually. An evaporation inhibitor is placed over the slide after a chemical agent is placed onto the tissue sample. The movable dispensing head draws the desired chemical from a container and dispenses the chemical on top of the appropriate slide. One limitation of this method is that a drop of liquid may form at the tip of the head after each dispensing operation and may drop onto another slide as the head moves. Also, the containers need to be filled with chemicals before they are dispensed, which requires labor. The length of time that elapses before each chemical is washed from a slide may be controlled by a computer.
- A similar method involves dispensing a chemical from a dispenser pre-packaged with the chemical so that a person does not have to fill the dispenser. After each dispensing operation, the dispenser withdraws the drop remaining on the tip of its nozzle to prevent the drop from falling on a slide. The dispenser is placed in a rotating tray located above a slide tray. The tray moves the dispenser above the slide on which a chemical is dispensed. A computer is used to control the movement of the tray and to determine the length of time before a chemical is washed from a slide.
- U.S. Pat. No. 5,232,664 relates to a dispenser for delivering small amounts of liquid to a sample. The dispenser includes a reservoir chamber linked to a dispense chamber. The dispense chamber communicates with a nozzle through an outlet line. A number of such dispensers are positionable within a reagent tray that is rotated by a drive carousel to perform an immunoassay. This patent is incorporated by reference as if fully set forth herein.
- Turning to another method, chemicals may also be dispensed manually or from a mechanical transfer head into a gap between a cover plate and a slide containing a tissue sample. The slide and cover plate are in vertical positions. Gravity forces the chemicals through the gap. The surface tension between the slides prevents chemicals from flowing immediately out of the bottom of the gap. The transfer head may be filled with the appropriate chemical after each dispensing. Such a method requires significant time and labor. A computer may be used to control the movements of the transfer head and to time how long a slide is exposed to each chemical.
- The methods presented above tend to be problematic. Some of the methods involve steps that are manually performed and require a significant amount of time. For example, an operator may be required to pipette a chemical onto a slide and/or fill chemical containers used for staining tissue. The operator may also have to carefully label these containers and time how long each chemical contacts the tissue. Such processes are labor-intensive and may be subject to significant variation due to human error. Further, some of the methods require the use of expensive automated equipment and a computer to control the equipment.
- It is therefore desirable that an improved tissue staining system be derived which is less labor intensive. Further, it is desirable that the system requires less expensive equipment to stain the tissue. A system with these features would tend to increase the quality of the resulting stained tissue while reducing operating costs.
- The problems outlined above are in large part solved by an improved tissue staining system and method of the present invention. That is, the system hereof does not require expensive equipment such as a computer in order to function. Further, the system may be automated such that less labor is needed to operate the system.
- An embodiment of the system includes a cassette for housing the staining system. The cassette preferably has an open end into which a removable slide device may be placed. The slide device preferably includes a specimen slide for holding a tissue sample and a cover plate located above the specimen slide. A film is preferably located within the cassette for delivering one or more chemicals to the slide device. As described herein, a “chemical” is taken to mean any substance added to the tissue sample to facilitate testing or examination of the tissue sample, is including but not limited to a biological reagent, an antibody, a buffer, a label, a chromogen, a solvent, a resin and/or deionized water. Each chemical may be reactive or unreactive with the tissue sample.
- The specimen slide and cover plate are preferably attached together in spaced relation to form a head space therebetween. A plastic (e.g., mylar) spacer may be placed between the cover plate and specimen slide. This spacer preferably creates the head space and preferably seals the outer edges of the slide device. The slide device may be held together with a slide holder. Alternately, the specimen slide and the cover plate may be constructed such that they can be snapped together to form a fixable engagement On opposite ends of the slide device, an injection port and a relief port preferably communicate with the head space formed within the slide device. The injection port preferably includes a conduit, and that conduit preferably has a pointed end. A chemical may be passed through the injection port into the head space and then out of the head space through the relief port.
- The slide device may be placed into the open end of the cassette. An injection piston preferably located within the cassette adjacent to the injection port may reciprocate in a direction toward the injection port. This reciprocating motion preferably enables the injection piston to contact containers disposed on the film. The containers contain one or more chemicals to be applied to the tissue sample, and holders may be used to attach the containers to the film. The film preferably extends along the edge of the cassette and forms a loop (e.g., in a horseshoe shape) in the interior of the cassette. Guide rollers within the cassette preferably move the film through the cassette such that the containers disposed within the film are passed to a location between the injection piston and the injection port.
- The reciprocating motion of the injection piston is preferably synchronized with the movement of the film such that the piston contacts each holder of the film. In the case that a container is disposed within the holder contacted by the piston, the piston preferably forces the container against the pointed conduit end within the injection port. The pointed conduit end preferably punctures the container. The container preferably ruptures, causing the chemical(s) within the container to be released into the injection port. The piston preferably creates pressure within the injection port to cause the released chemical(s) to be positively displaced through the injection port and into the head space to stain the tissue sample. In the case that the head space contains a chemical that has been previously injected, such previously injected chemical is preferably displaced out of the head space by the pressure derived from the piston. The displaced waste chemical is preferably passed through the relief port and into a waste tank. The waste tank preferably contains absorbent material to facilitate collection of such waste chemicals.
- The holders of the containers are preferably spaced apart by equal distances along the length of the film. The contact time between a chemical and a tissue sample is preferably determined by the distance between containers on the film. A specified number of holders may be left empty to create a predetermined amount of time between (a) the injection of a first chemical into the head space and (b) the injection of a second chemical into the head space and the simultaneous displacement of the first chemical from the head space. The motion of the film and the displacement of the injection piston are preferably synchronized such that each holder in the film is contacted by the injection piston.
- The containers may hold more than one chemical. In an embodiment, two or more chemicals within the containers are separated by an interior wall within the container to prevent the chemicals from mixing before injection. When a container holding more than one chemical is forced against the pointed conduit end, each of the wall segments within the container is preferably punctured to allow the chemicals to mix before being injected into the slide device.
- In an embodiment, the cassette may be placed onto a cassette driver for driving the guide rollers and the injection piston. The cassette driver preferably includes a shaft which may extend from the top of the cassette driver into the bottom of the cassette. The shaft is preferably a spline joint shaft which may be connected to the guide rollers and the piston. A gear drive motor preferably rotates the shaft at a constant speed, causing the guide rollers and the piston to move at a constant speed.
- The cassette driver also preferably includes a heat pad and a thermostat for controlling the temperature of the chemicals in the head space of the slide device. The heat pad may be used to heat or cool the tissue sample and chemicals in the head space. The thermostat may maintain the heat pad within a predetermined temperature range or it may cause pulse changes in the temperature of the heat pad. In this way, the tissue and chemicals may be subjected to any predefined temperature profile. Maintaining the temperature of the tissue sample and chemicals within a selected range may facilitate or control reaction of the injected chemicals with the tissue sample. The cassette may be engaged with the cassette driver such that the heat pad is positioned under the slide device. The cassette driver preferably contains a pressure sensitive switch enabling automatic activation of the cassette driver motor when the cassette is detected on top of the cassette driver. A pre-set timing device may be used to stop the motor after a predetermined amount of chemicals have contacted the tissue sample.
- In an embodiment, the tissue staining system includes a plurality of cassette drivers and a control panel for individually operating each of the cassette drivers. The control panel is preferably coupled to the motor and heat pad of each of the cassette drivers. A plurality of cassettes may be placed on the cassette drivers to allow a plurality of tissue samples to be stained simultaneously.
- In an alternate embodiment, a portable cassette includes a battery operated solenoid piston for injecting chemicals into a slide device. The slide device is preferably located proximate the center of the cassette. The portable cassette preferably includes a twin drive motor for rotating guide rollers to move a film. The film preferably delivers containers to the solenoid piston. The portable cassette preferably includes a heat pad located under the slide device and a waste tank for collecting chemicals which are displaced from the slide device. The portable cassette may include printed contacts for activating the heat pad and/or the solenoid piston.
- Each of the embodiments discussed above may be combined or used individually.
- Further advantages of the present invention will become apparent to those skilled in the art with the benefit of the following detailed description of the preferred embodiments and upon reference to the accompanying drawings.
- FIG. 1a is a perspective view of a cassette, a slide device, and a slide holder which are part of a tissue staining system.
- FIG. 1b depicts a cross-section of the slide device.
- FIG. 1c depicts a side view of an alternate embodiment of the slide device.
- FIG. 2 is a perspective view of the cassette depicting the slide device engaged within the cassette.
- FIG. 3a is a top plan view of an interior portion of the cassette.
- FIG. 3b is a side view of the interior portion of the cassette.
- FIG. 3c is a cross-sectional view along plane II of FIG. 3a
- FIG. 3d is a cross-sectional view along plane 111 of FIG. 3a
- FIG. 4a is a top plan view of an injection end of the slide device and a portion of a film.
- FIG. 4b is a front view of a portion of the film.
- FIG. 5 is a perspective view of a cassette driver.
- FIG. 6 is a perspective view of a multiple cassette driver unit.
- FIG. 7 is a perspective view of a multiple cassette driver system.
- FIG. 8 is a perspective view of a portable cassette.
- FIG. 9 is a cross-sectional view of a portion of a tissue staining system, including a cassette and a cassette driver.
- FIG. 10 is a cross-sectional view of a tissue staining system, including a cassette and a cassette driver.
- FIG. 11 is a cross-sectional view of the locking mechanism of a chemical container which belongs to a tissue staining system.
- FIG. 12a is a perspective view of a portion of a cassette and a portion of a film belonging to a tissue staining system.
- FIG. 12b is a cross-sectional view of a portion of a film belonging to a tissue staining system.
- While the invention is susceptible to various modifications and alternative forms, specific embodiments thereof are shown by way of example in the drawings and will herein be described in detail. It should be understood, however, that the drawings and detailed description thereto are not intended to limit the invention to the particular form disclosed, but on the contrary, the intention is to cover all modifications, equivalents and alternatives falling within the spirit and scope of the present invention as defined by the appended claims.
- Turning now to one embodiment of the present invention, FIG. 1 illustrates an outside perspective view of
cassette 1 which is part of an improved tissue staining system. As described herein, “cassette” is taken to include any housing for containing a tissue sample to facilitate the application of chemicals onto the tissue sample. The cassette in FIG. 1 is substantially rectangular and contains an optional protective covering on its top surface that covers the interior portion of the cassette. It is to be appreciated that the cassette could have any of a variety of shapes (e.g., circular, triangular, etc.).Cassette 1 preferably contains afilm access door 2 that may be located on the top, bottom, or side of the cassette.Cassette 1 preferably further includes acontainer access door 3 to allow access to an interior portion of the cassette. - FIG. 1a illustrates
slide device 5 into which atissue sample 6 may be placed.Slide device 5 preferably includes aspecimen slide 9 and acover plate 8. Aspacer 10 a is preferably placed betweenspecimen slide 9 and coverplate 8. The spacer may be made of a plastic such as mylar.Spacer 10 a preferably extends along the length ofslide device 5 and seals the outer edges of the slide device to maintain chemical between the specimen slide and the cover plate. Aslide holder 7 preferably holdsslide device 5 together by clampingspecimen slide 9 to coverplate 8 at one end ofslide device 5. Anopen end 4 ofcassette 1 is preferably shaped to receiveslide device 5. - FIG. 1b depicts a cross-section of
slide device 5 taken along planeI. Cover plate 8 is preferably located abovespecimen slide 9.Spacer 10 a is preferably located betweencover plate 8 and specimen slide 9 at their outer edges. The thickness ofspacer 10 a is preferably in the range between about 0.0005 inch and about 0.004 inch, more preferably between about 0.001 inch and about 0.002 inch, and even more preferably about 0.0015 inch. The thickness ofspacer 10 a preferably creates ahead space 10 b betweencover plate 8 andspecimen slide 9. The head space betweencover plate 8 andspecimen slide 9 preferably has a width that is the same as the thickness ofspacer 10 a. When chemicals are injected intoslide device 5, they preferably fillhead space 10 b and interact withtissue sample 6.Spacer 10 a may be disposed about the entire perimeter of the slide device to surround the head space. - In an alternate embodiment,
specimen slide 9 and coverplate 8 are capable of being attached in fixable engagement withoutslide holder 7. The specimen slide and cover plate may be snapped together. Alternately, the cover plate may contain substantially L-shapedmembers 50 as depicted in FIG. 1c, which depicts a cross sectional view ofslide device 5. The L-shaped members serve as a base for supportingspecimen slide 9, which may be slid into engagement withcover plate 8. The tolerance between the specimen slide and the cover plate is preferably sufficiently low to prevent liquid chemical from exiting head space 10 through the outer edges of the slide device. - FIG. 2 illustrates
slide device 5 positioned withinopen end 4. Awaste tank 11 a is preferably placed inopen end 4 near the end ofslide device 5. The waste tank may be used to collect waste chemical that exitshead space 10 b. The waste tank is preferably detachable from the end ofslide device 5 to allow it to be removed and replaced. In an embodiment, the waste tank contains absorbent material to facilitate removal of the waste chemical. Preferably, this absorbent material is an absorbent non-woven structure. - FIG. 3a depicts a top plan view of an interior portion of
cassette 1.Slide device 5 and waste tank 11 are preferably located inopen end 4 ofcassette 1 during the tissue staining process. Afilm 12 is preferably used to deliver chemicals to slidedevice 5 for application onto the tissue sample. The film is preferably substantially flexible and may be a polymeric film, a ribbon film, or any belt-like member that is sufficiently flexible to be drawn aroundguide rollers cassette 1.Film 12 may be loaded into and removed from the cassette throughfilm access door 2.Film 12 preferably extends about the perimeter ofcassette 1 and may form a horseshoe-shaped loop within the interior portion of the cassette. -
Guide rollers film 12. The guide rollers are preferably connected toshaft 18 viasecondary shafts 58.Shaft 18 is preferably a splined shaft that is rotatable to causeguide rollers 14 to rotate. Rotation of the guide rollers preferably causes movement of the film throughout the cassette. A plurality ofcontainers 13 a are preferably disposed on the film. Eachcontainer 13 a preferably contains between about 50 microliters and about 200 microliters of chemical, and more preferably between about 100 microliters and about 150 microliters of chemical. -
Guide rollers 15 preferably engagefilm 12 and rotate to move the film about the cassette and through the horseshoe-shaped loop depicted in FIG. 3a. The cassette preferably includes an injection system for injecting chemicals intoinjection port 17. The injection system preferably includes aninjection piston 16 located near an end ofslide device 5.Piston 16 is preferably attached to rotatingshaft 18 viacam 59 which displaces the piston in a direction toward thefilm 12 at a location proximate the apex of the horseshoe-shaped loop.Piston 16 preferably reciprocates along an imaginary axis that extends longitudinally throughinjection port 17.Piston 16 preferablycontacts container 19 and ruptures the container to release chemical intoinjection port 17.Injection port 17 andrelief port 21 preferably communicate with the head space and may be disposed on opposite ends of the slide device. The piston preferably creates pressure withininjection port 17 to force the chemical through the injection port and into thehead space 10 b where it contacts the tissue sample. - FIG. 4a depicts a top plan view of
conduit 22 which preferably forms a portion ofinjection port 17 ofslide device 5.Conduit 22 preferably includes a sharp or pointed end for puncturing containers as depicted in FIG. 4a The piston preferably contacts the containers and forces them againsthollow conduit 22. The containers preferably rupture as a result of the contact withconduit 22 andpiston 16 and the chemical within the ruptured container is preferably directed throughconduit 22 into the head space under pressure derived from the reciprocating motion of the piston.Film 12 preferably carriescontainer 13 a to a location adjacent to the sharp end ofconduit 22. The film is preferably sufficiently flexible to bend to allowcontainer 13 a to be pressed against the end ofconduit 22. - In an embodiment,
container 13 a contains two or more chemicals to be injected intoslide device 5. In some cases it may be necessary to simultaneously apply two or more chemicals to the tissue sample without mixing the chemicals beforehand.Container 13 a may contain an interior wall having one ormore wall segments 13 c for compartmentalizing the container to prevent the mixing of two or more chemicals within the container prior to injection.Wall 13 c is preferably punctured byconduit 22 during injection to allow the chemicals to mix as they are injected intoslide device 5. The chemicals are preferably positively displaced fromcontainer 13 a intohead space 10 b where they contact the tissue sample. In the case that a first chemical resides inhead space 10 b at the time a second chemical is injected intocontainer 13 a, the first chemical is preferably positively displaced throughrelief port 21 out ofhead space 10 b by the second chemical and/or the pressure within the head space derived frompiston 16. - FIG. 3b depicts a side view of
cassette 1.Film 12 preferably includes a plurality ofholders 13 b for attachingcontainers 13 a to the film.Holders 13 b offilm 12 are preferably spaced apart by equal distances. Thecontainers 13 a are preferably removable and replaceable on the film to allow the film to be reused after the tissue staining process has been completed.Container access door 3 preferably enables access to an interior portion of the cassette to allow containers to be placed into empty holders of the film after the film has been loaded into the cassette. In this manner, user-specified chemicals may be added to the film to be injected intoslide device 5 to allow for customized staining protocols with respect to selection of the applied chemical. - The time of contact between a chemical and a tissue sample may be predetermined by the spacing between containers on the film. Selected holders may be left empty to increase the spacing between adjacent containers, thereby lengthening the contact time between a given chemical and the tissue sample. In operation, the reciprocation of the piston and the movement of the film preferably occur at constant speeds and are synchronized such that the piston contacts each holder on the film.
- FIG. 3c further illustrates a cross-section of
cassette 1 along plane II of FIG. 3a, depictingguide rollers 15 and an end ofslide device 5. FIG. 3d is a cross-sectional view along plane III of FIG. 3a. Aheat pad 20 is preferably located underslide device 5 to control the temperature of chemicals and tissue sample withinhead space 10 b. Althoughheat pad 20 is shown in FIG. 3a to extend through an opening inbase 52, it also may reside entirely withincassette 1 betweenbase 52 andslide device 5.Heat pad 20 may be used to heat or cool the chemicals and tissue sample to control any reaction that may occur between the chemicals and the tissue sample. The temperature of theheat pad 20 is preferably controlled to maintain the temperature of the tissue sample and chemical within a predetermined range. The temperature of the heat pad may be continuously adjusted as a function of the type and/or amount of chemical(s) injected into the head space.Heat pad 20 may be any conventional heat exchange of thermoelectric device. Heating coils or conduits adapted to contain a heat transfer medium may be contained withinheat pad 20 to control the temperature at its surface. -
Waste tank 11 a is preferably placed at the end ofslide device 5 during the tissue staining process. Anabsorbent material 11 b is preferably located in the bottom ofwaste tank 11 a Theabsorbent material 11 b preferably absorbs waste chemical passing fromrelief port 21 and facilitates the disposal of the waste chemical. - FIG. 4b shows a side view of a portion of
film 12 which preferably containsopenings 23. Each of the guide rollers may contain teeth 54 (shown in FIG. 3a), which may be placed inopenings 23 to attachfilm 12 to the guide rollers. The teeth preferably maintain the engagement between the film and the guide rollers as the film is moved through the cassette. Alternately, the guide rollers may be smooth and a frictional engagement betweenguide rollers 15 andfilm 12 is sufficient to allow the film to be moved when the guide rollers are rotated. The slide device may contain an indention 56 shaped to receivecontainer 13 a. Indention 56 preferably surroundsconduit 22 to allowcontainer 13 a to be forced within the indention during release of chemical from the container intoconduit 22. - FIG. 5 depicts a
cassette driver 25 a for drivingcassette 1. The bottom orbase 52 of the cassette may be attached to the upper surface of the cassette driver.Shaft 18 preferably extends from the top ofcassette driver 25 a through an opening inbase 52 ofcassette 1.Shaft 18 is preferably a splined shaft.Shaft 18 is preferably rotated by amotor 26 at a constant speed.Motor 26 may be a gear drive motor.Shaft 18 preferably drives the motion offilm 12 andpiston 16 such that they are synchronized to allow eachholder 13 a infilm 12 to be struck bypiston 16. -
Heat pad 20 is preferably located on the upper surface ofcassette driver 25 a. The cassette may contain an opening inbase 52 sized to receive the heat pad such that the slide device engages the heat pad. The temperature ofheat pad 20 is preferably controlled bythermostat 27. The heating contact leads 28 a and 28 b, the thermostat contact leads 29 a and 29 b, and the motor contact leads 30 a and 30 b are preferably located at one end ofcassette driver 25 a. - A pressure-
sensitive switch 31 is preferably located on top ofcassette driver 25 a Whencassette 1 is placed on top ofcassette driver 25 a,switch 31 is preferably depressed to activatemotor 26. Atiming device 32 is preferably used to stopmotor 26 after a predetermined amount of time that is sufficient to allow a selected amount of chemicals to be applied to the tissue sample. - FIG. 6 illustrates a multiple
cassette driver unit 25 b.Cassette drivers 25 a are preferably located within adriver housing 25 c. Acassette 1 may be placed on eachcassette driver 25 a to stain several tissue samples simultaneously. The cassettes may be removed from the cassette driver and the slide device and film may be replaced before the cassette is reinserted on the cassette driver to stain a new tissue sample. - Multiple cassette driver unit preferably includes a
control panel 60 for independently operating each of the cassette drivers. The control panel preferably includes a plurality ofcontrollers 62 corresponding to each of the cassette drivers. Each controller is preferably electrically coupled to themotor 26 andheat pad 20. The controller may comprise atimer 32 for stoppingmotor 26 after a predetermined amount of running time. The controller may be further adapted to adjust the operating speed (rpm) ofmotor 26 to adjust the speed at which the film is moved and thus the rate that chemicals are applied to the tissue sample. The controller preferably includes manual switches to activate and stopmotor 26. The controller may include a computer and a digital display indicating the temperature of the heat pad and the amount of time remaining ontimer 32. The temperature of the heat pad may be adjusted manually usingcontroller 62. - A system of multiple
cassette driver units 25 b is depicted in FIG. 7. A plurality ofdriver housings 25 c preferably hold a plurality ofcassette drivers 25 a.Tray 25 d preferably supports the multiplecassette driver units 25 b, which are arranged vertically. - FIG. 8 depicts an alternate embodiment of the tissue staining system. The
portable cassette 42 preferably includes a positivedisplacement slide device 31 into which the tissue sample may be placed. Theportable cassette 42 preferably includes afilm 32 which carries containers 33 to asolenoid piston 34.Solenoid piston 34 is operated bybattery 35. Thesolenoid piston 34 preferably forces a chemical from each container 33 intoslide device 31.Guide rollers 36 preferably rotate to movefilm 32, and theguide rollers 36 are preferably operated by atwin drive motor 37. Awaste tank 38 is preferably located near the end ofslide device 31 for collecting a chemical which exitsslide device 31. Aheat pad 39 is preferably located underslide device 31 which may control the temperature of chemicals withinslide device 31. The presence or absence of contacts along the length offilm 32 may produce closed or open circuits which in turn prevent or allow the passage of current. The current may activate the heat pad or actuate the solenoid. Contacts such ascontacts 40 andcontacts 41 may be placed in multiple rows alongfilm 32 to allow multiple circuits to be opened or closed simultaneously or independently as the contacts pass by and come in contact with switches (e.g., switch 66) withincassette 42. The switches may be in electrical communication with the heat pad or the solenoid. - Turning to FIG. 9, another embodiment of the tissue staining system is presented.
Cassette 1 is preferably shaped to receive different elements of the staining system.Cassette 1 preferably includes acavity 71 and aremovable cap 72 which acts as a closure device forcavity 71.Cap 72 is preferably shaped to snap into a wall surrounding a top portion ofcavity 71. Whencap 72 is removed,plate 8 may be positioned across the bottom ofcavity 71.Cassette 1 may further include a raisedprotrusion 74 on sides ofcavity 71.Specimen slide 9 may be placed a predetermined distance aboveplate 8 such that a sealing element 68 (i.e., a spacer) is located between the edges ofspecimen slide 9 and eachprotrusion 74 to form ahead space 10 b betweenplate 8 andspecimen slide 9. Thus, unlike previously depicted embodiments,specimen slide 9 is not connected to plate 8 whiletissue sample 6 is being stained. The side ofspecimen slide 9 which containstissue sample 6 preferably faceshead space 10 b. Therefore,tissue sample 6 may protrude downward fromslide 9. Another sealingelement 70 may be placed above the outer edges ofslide 9, andcap 72 may be snapped intocassette 1 such that it abutts sealingelement 70.Cap 72 preferably locksspecimen slide 9 andplate 8 withincavity 71.Injection port 17 andrelief port 68 are preferably formed withincassette 1 and communicate withhead space 10 b.Injection port 17 andrelief port 68 are preferably located at opposite ends ofhead space 10 b to allow a chemical to pass into and out ofhead space 10 b. Awaste tank 11 a may be disposed withincassette 1 underneathrelief port 21 to collect any chemical exiting fromhead space 10 b. -
Film 12 preferably carries a chemically filledcontainer 13 a to a position adjacent toinjection port 17.Piston 16 is preferably aligned withinjection port 17. Whencassette 1 is placed ontocassette driver 25 a,cassette driver 25 a may automatically start running because startingswitch 31 is triggered by the pressure ofcassette 1.Splined shaft 18 preferably extends up fromcassette driver 25 a and intocassette 1 where it rotates to causecam 59 to displacepiston 16.Piston 16 may pushcontainer 13 a against a sharp end ofinjection port 17.Members 76 may help guidepiston 16 so that it remains aligned withcontainer 13 a. The pointed end ofinjection port 17 may puncture the wall ofcontainer 13 a, forming an opening in the wall. The chemical withincontainer 13 a may then flow freely intoinjection port 17 through this opening.Heat pad 20 ofcassette driver 25 a may be used to heat chemicals passing throughhead space 10 b since it may be positioned underplate 8. Afterfilm 12 has delivered all chemicals necessary for the staining procedure, a mounting medium may be injected intohead space 10 b to form a glue-like substance betweenspecimen slide 9 andplate 8. The “mounting medium” is taken to mean any translucent substance capable of adhering to slide 9 and toplate 8. Thus,specimen slide 9 andplate 8 are permanently connected to form a unit which can be removed fromcassette 1 and placed under a microscope for inspection. - FIG. 10 depicts another embodiment of a tissue staining system which is similar to the embodiment of FIG. 9, with a few exceptions. For example, an
upper portion 77 ofcassette 1 may be folded back, allowing access to acavity 71 withincassette 1. One end ofupper portion 77 may be lifted upward (shown by dashed line 78) while the opposite end remains attached tocassette 1 so that it works like a door. The end ofupper portion 77 attached tocassette 1 may be flexible to enable the lifting mechanism. Upon openingupper portion 77, a sealingelement 80 followed byspecimen slide 9 may be placed across the bottom ofcassette 1.Slide 9 is preferably oriented so that the side containingtissue sample 6 faces upward.Cover plate 9 may be placed a predetermined distance aboveplate 9 such that sealingelement 68 is located underneath the edges ofplate 9, forminghead space 10 b betweenslide 9 and coverplate 8. Sealingelement 70 is then preferably placed on top of portions ofslide 9.Upper portion 77 may be seated upon sealingelement 70 andcover plate 8 when it is closed. The operation of this system is basically the same as that of the system depicted in FIG. 9. - Turning to FIG. 11, an embodiment of a
chemical container 13 a is depicted. Chemical container 113 a is preferably connected to film 12 and includes acavity 81. Hereafter, “cavity” is taken to mean a space and a wall partially enclosing the space.Container 13 a may haveprotrusions 82 spaced along an inner surface of awall 83 surrounding a portion ofcavity 81.Container 13 a may be filled with a chemical and then sealed to prevent the chemical from escaping. Acontainer cap 86 may be used to sealcontainer 13 a. A portion ofcap 86 may be disposed withincavity 81 to plugcontainer 13 a A second set ofcomplementary protrusions 84 preferably line a portion of the outer surface ofcap 86.Protrusions 84 are preferably shaped to fit betweenprotrusions 82 so thatcap 86 may be locked to the inner surface ofwall 83. A slit 87 preferably extends through the center ofcap 86 and preferably terminates at anotherwall 88. Whencap 86 is positioned withincavity 81, a chemical withincontainer 13 a may enterslit 87. However,wall 88 preferably prevents the chemical from exiting fromslit 87. During injection of a chemical intocassette 1,wall 88 may be forced against a pointed end ofconduit 22, causingwall 88 to be punctured and releasing a chemical intoconduit 22. - Turning to FIG. 12a, a portion of
cassette 1 and a portion offilm 12 are illustrated in an embodiment.Cassette 1 may have a substantially V-shapededge 94. This edge is preferably sharp enough to cut throughwall 88 which protrudes from a side of eachcontainer 13 a. In one embodiment,film 12 carriescontainers 13 a sequentially toinjection port 17. Aswall 88 of eachcontainer 13 a comes into contact withedge 94,wall 88 may be removed fromcontainer 13 a viaedge 94 cutting through itContainer 13 a preferably abuttssurface 92 ofcassette 1 to prevent chemicals withincontainer 13 a from escaping through the opening created by the removal ofwall 88. Then, ascontainer 13 a passes byinjection port 17, a chemical may flow fromcontainer 13 a intoinjection port 17 via the opening. Further, acavity 90 ofcontainer 13 a is preferably located opposite to the opening. A piston may be propelled intocavity 90 to help force the chemical intoinjection port 17.Cavity 90 preferably includes a flexible wall which does not break open under pressure of the piston. FIG. 12b depicts a cross-sectional view of the top offilm 12 havingcontainers 13 a. - Experiment
- The slide device depicted in FIG. 3 was used to apply various chemicals to tissue samples. Tissue samples were placed into eight positive displacement slide devices having a specimen slide and a cover plate. Each of the slide devices contained a head space between the specimen slide and the cover plate that had a width ranging from 0.0005 inch to 0.004 inch. Sixteen control tissue samples that were each three micrometers thick were mounted in pairs on the eight specimen slides.
- Each of the tissue samples was stained as follows using quality-controlled, standardized immunohistochemistry procedures. The slide device and tissue samples were dried at 58° C. for one hour. Pure xylene having essentially no dissolved contaminates of paraffin was injected under pressure into the slide device three sequential times. The third injection of xylene remained in the head space of the slide device for ten minutes before a 100% alcohol composition was injected into the head space. The injection of the alcohol through the injection port forced the excess xylene out of the head space. Three minutes later, peroxide/methanol was injected into the head space to prevent blood and other portions of the tissue from interacting with chemicals which would subsequently be injected. The peroxide remained in the head space for thirty minutes.
- The tissue was then rehydrated via injection of a 95% alcohol solution into the head space. After three minutes a deionized water rinse was injected into the head space. Then tissue revival was performed by heating the slide device and sequentially injecting an immunohistochemistry (IHC) rinse into the head space three times. Immediately after injecting the third rinse, a primary antibody for staining the tissue was injected into the head space. The primary antibody remained in the head space for fifteen minutes. An injection of an IHC wash buffer was then performed and immediately followed by an injection of a secondary antibody known as link into the head space. After the link had been in the head space for ten minutes, an IHC wash buffer was injected again. Immediately thereafter, a chemical known as label was injected into the head space where it remained for ten minutes.
- Next, an IHC wash buffer was injected into the slide device. Immediately thereafter, a chromogen was injected into the head space to colorize the stains. An optimum 4:1 ratio of desired stained tissue parts to undesired background stained parts was reached after a time period that ranged from approximately thirty seconds to five minutes among the tissue samples, and then a deionized water rinse was injected into the head space. The ratio of desired stained tissue parts to background stained parts was determined using a standardized scoring system well known to those skilled in the art in which 4 is the highest intensity of staining and1 is the lowest intensity of background. A counterstain was injected to produce color contrast. The counterstain remained in the head space for forty-five seconds and then a deionized water rinse was injected into the head space. Finally, a translucent mounting medium was injected into the head space which acted as a “glue” to seal the cover plate to the head space permanently. The specimen slide and cover plate could then be placed under a microscope as a unit.
- The above experiment required only small, efficient amounts of a chemical for staining tissue. Due to varied head space distances the required injected volumes varied from 50 microliters to 200 microliters. The deionized water rinses were quick and completely cleaned the head spaces because previous chemicals were positively displaced from the slide devices. Further, uniform and complete staining was achieved on all sixteen tissue samples.
- The above-mentioned results suggest that positive-displacement injection of chemicals such as antibodies and buffers is a viable method for the procedures of immunohistochemisty. The positive displacement of a previously injected chemical from a slide device was found to prevent dilution or mixing between an injected chemical and the previously injected chemical. Chemical waste is reduced as compared to conventional methods, and the flow of chemicals under pressure over tissue tends to cause the tissue to be stained evenly and completely.
- Further modifications and alternative embodiments of various aspects of the invention will be apparent to those skilled in the art in view of this description. Accordingly, this description is to be construed as illustrative only and is for the purpose of teaching those skilled in the art the general manner of carrying out the invention. It is to be understood that the forms of the invention shown and described herein are to be taken as the presently preferred embodiments. Elements and materials may be substituted for those illustrated and described herein, parts and processes may be reversed, and certain features of the invention may be utilized independently, all as would be apparent to one skilled in the art after having the benefit of this description of the invention. Changes may be made in the elements described herein without departing from the spirit and scope of the invention as described in the following claims. For example, integrated circuit devices which embody central processing units and pre-programmed and/or re-programmable memory may be utilized in the cassette and/or drive unit to control the function of motors, piston actuators, heating pads, and status displays. Such electronic control methodologies could supplement or replace mechanical methodologies described herein.
Claims (20)
1. A system for applying a chemical to a tissue sample, comprising:
a cassette;
a slide device for holding the tissue sample, the slide device being adapted to be housed within the cassette during use and comprising a specimen slide and a cover plate, the cover plate being attachable to the specimen slide such that a head space exists therebetween, the slide device farther comprising an injection port communicating with the head space; and
a film adapted to be located within the cassette for delivering a chemical to the injection port, the film comprising a container for holding the chemical.
2. The system as recited in claim 1 , wherein the cassette further comprises an open end for receiving the slide device.
3. The system as recited in claim 1 , wherein the slide device comprises a spacer for defining the head space, the spacer being disposed between the specimen slide and the cover plate, the spacer being located around outer edges of the specimen slide and the cover plate.
4. The system as recited in claim 1 , wherein the cassette comprises (1) a cavity being adapted to house the cover plate and (2) a raised protrusion on a side of the cavity, and further comprising a spacer being disposed between the raised protrusion and the specimen slide such that the specimen slide is a pre-determined distance from the cover plate, the cover plate being within the cavity and being unconnected to the specimen slide.
5. The system as recited in claim 1 , wherein the cassette further comprises a cavity, the cavity being adapted to house the slide device.
6. The system as recited in claim 1 , wherein the cassette further comprises a cavity and a removable cap adapted to cover at least a portion of the cavity.
7. The system as recited in claim 1 , wherein the specimen slide and the cover plate are adapted to be snapped together.
8. The system as recited in claim 1 , further comprising a slide holder for attaching the specimen slide to the cover plate.
9. The system as recited in claim 1 , wherein the head space is between about 0.0005 inch and about 0.004 inch.
10. The system as recited in claim 1 , wherein the head space is between about 0.0015 inch and about 0.0025 inch.
11. The system as recited in claim 1 , wherein the slide device further comprises a first end, a second end, and a relief port, the first end being opposite to the second end, and wherein the injection port communicates with the head space at the first end, and wherein the relief port communicates with the head space at the second end.
12. The system as recited in claim 1 , wherein the slide device further comprises a first end, a second end, and a relief port, and wherein the injection port communicates with the head space at the first end, and wherein the injection port comprises a conduit, the conduit communicating with the head space to allow the chemical to pass through the conduit into the head space.
13. The system as recited in claim 1 , wherein the film comprises a plurality of holders for holding chemically filled containers.
14. The system as recited in claim 1 , wherein the container comprises a cavity for holding the chemical, a plurality of protrusions extending from an inner surface of the cavity, and a cap for sealing the cavity, the cap comprising a plurality of complementary protrusions adapted to mate with the protrusions of the cavity.
15. The system as recited in claim 1 , wherein the container comprises a cavity for holding the chemical and a removable cap for sealing the cavity, the cap comprising: (a) a slit terminating in a wall, the slit being adapted to deliver the chemical from the cavity to the injection port; and (b) a plurality of protrusions extending from an outer surface of the cap.
16. The system as recited in claim 1 , wherein the container comprises (a) a cavity for holding the chemical; (b) a plurality of protrusions extending from an inner surface of the cavity; (c) and a cap shaped to mate with a portion of the cavity for sealing the cavity, the cap comprising a plurality of complementary protrusions adapted to be inserted between the protrusions of the cavity for locking the cap within the cavity.
17. The system as recited in claim 1 , wherein the film extends along an edge of the cassette and forms a substantially horseshoe-shaped loop at an interior portion of the cassette.
18. The system as recited in claim 1 , wherein the container comprises a wall to separate two or more chemicals within the container.
19. The system as recited in claim 1 , further comprising a guide roller located within the cassette, the guide roller engaging the film and being adapted to rotate to move the film during use.
20. The system as recited in claim 1 , further comprising a waste tank containing absorbent material for collecting chemical that exists the slide device, the waste tank being connected to an end of the slide device.
Priority Applications (1)
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US10/056,511 US20020182115A1 (en) | 1997-04-18 | 2002-01-31 | Chemical dispensing system and method |
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US08/844,553 US6489171B1 (en) | 1997-04-18 | 1997-04-18 | Chemical dispensing system and method |
US10/056,511 US20020182115A1 (en) | 1997-04-18 | 2002-01-31 | Chemical dispensing system and method |
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Publication number | Priority date | Publication date | Assignee | Title |
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DK2389116T3 (en) | 2009-01-22 | 2018-02-12 | Biopath Automation Llc | BIOPSY SUPPORT TO ORIENT TESTS FOR SECTION IN A MICROTOM |
DE102009015596A1 (en) * | 2009-03-30 | 2010-10-21 | Dcs Innovative Diagnostik-Systeme Dr. Christian Sartori Gmbh & Co. Kg | Method and device for the treatment of carrier-fixed material |
JP2014132228A (en) * | 2013-01-04 | 2014-07-17 | Sony Corp | Liquid injection jig set |
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Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SE7801564L (en) * | 1978-02-10 | 1979-08-11 | Lkb Produkter Ab | DEVICE FOR INSERTING BIOLOGICAL PRODUCTS |
US4731335A (en) * | 1985-09-13 | 1988-03-15 | Fisher Scientific Company | Method for treating thin samples on a surface employing capillary flow |
US5225325A (en) | 1990-03-02 | 1993-07-06 | Ventana Medical Systems, Inc. | Immunohistochemical staining method and reagents therefor |
US5595707A (en) | 1990-03-02 | 1997-01-21 | Ventana Medical Systems, Inc. | Automated biological reaction apparatus |
US5232664A (en) | 1991-09-18 | 1993-08-03 | Ventana Medical Systems, Inc. | Liquid dispenser |
AT403096B (en) * | 1992-09-08 | 1997-11-25 | Sitte Hellmuth | METHOD AND DEVICE FOR PREPARING MICROSCOPIC, IN PARTICULAR ELECTRON MICROSCOPIC PREPARATIONS FOR THE CUT PREPARATION |
US5804141A (en) * | 1996-10-15 | 1998-09-08 | Chianese; David | Reagent strip slide treating apparatus |
-
1997
- 1997-04-18 US US08/844,553 patent/US6489171B1/en not_active Expired - Lifetime
-
2002
- 2002-01-31 US US10/056,511 patent/US20020182115A1/en not_active Abandoned
Cited By (31)
Publication number | Priority date | Publication date | Assignee | Title |
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US20020094583A1 (en) * | 2000-08-03 | 2002-07-18 | Jens-Peter Seher | Pressure-variation fluid transport, in particular for body-fluid analysis |
US6936225B2 (en) * | 2000-08-03 | 2005-08-30 | Koninklijke Philips Electronics N.V. | Pressure-variation fluid transport, in particular for body-fluid analysis |
US11249095B2 (en) | 2002-04-15 | 2022-02-15 | Ventana Medical Systems, Inc. | Automated high volume slide processing system |
US11092611B2 (en) | 2002-04-15 | 2021-08-17 | Ventana Medical Systems, Inc. | Automated high volume slide processing system |
US10302665B2 (en) | 2002-04-15 | 2019-05-28 | Ventana Medical Systems, Inc. | Automated high volume slide processing system |
US9518899B2 (en) | 2003-08-11 | 2016-12-13 | Sakura Finetek U.S.A., Inc. | Automated reagent dispensing system and method of operation |
US11815518B2 (en) | 2005-04-27 | 2023-11-14 | Ventana Medical Systems, Inc. | Automated high volume slide processing system |
US10900982B2 (en) | 2005-04-27 | 2021-01-26 | Ventana Medical Systems, Inc. | Automated high volume slide processing system |
US8459509B2 (en) | 2006-05-25 | 2013-06-11 | Sakura Finetek U.S.A., Inc. | Fluid dispensing apparatus |
US9914124B2 (en) | 2006-05-25 | 2018-03-13 | Sakura Finetek U.S.A., Inc. | Fluid dispensing apparatus |
US9498791B2 (en) | 2009-11-13 | 2016-11-22 | Ventana Medical Systems, Inc. | Opposables and automated specimen processing systems with opposables |
US10746752B2 (en) | 2009-11-13 | 2020-08-18 | Ventana Medical Systems, Inc. | Opposables and automated specimen processing systems with opposables |
US8911815B2 (en) | 2009-11-13 | 2014-12-16 | Ventana Medical Systems, Inc. | Thin film processing apparatuses for adjustable volume accommodation |
US9618430B2 (en) | 2009-11-13 | 2017-04-11 | Ventana Medical Systems, Inc. | Thin film processing apparatuses for adjustable volume accommodation |
US9016526B2 (en) | 2011-02-01 | 2015-04-28 | Sakura Finetek U.S.A., Inc. | Fluid dispensing system |
US8752732B2 (en) | 2011-02-01 | 2014-06-17 | Sakura Finetek U.S.A., Inc. | Fluid dispensing system |
US10295444B2 (en) | 2011-09-21 | 2019-05-21 | Sakura Finetek U.S.A., Inc. | Automated staining system and reaction chamber |
US9005980B2 (en) | 2011-09-21 | 2015-04-14 | Sakura Finetek U.S.A., Inc. | Traceability for automated staining system |
US8932543B2 (en) | 2011-09-21 | 2015-01-13 | Sakura Finetek U.S.A., Inc. | Automated staining system and reaction chamber |
US8580568B2 (en) | 2011-09-21 | 2013-11-12 | Sakura Finetek U.S.A., Inc. | Traceability for automated staining system |
US10228382B2 (en) * | 2012-11-01 | 2019-03-12 | Leica Biosystems Melbourne Pty Ltd | Fluid transport system and method for treating one or more tissue samples on a slide |
US20150276772A1 (en) * | 2012-11-01 | 2015-10-01 | Leica Biosystems Melbourne Pty Ltd | Fluid transport system |
USD772424S1 (en) | 2013-03-15 | 2016-11-22 | Ventana Medical Systems, Inc. | Arcuate member for moving liquids along a microscope slide |
USD728120S1 (en) | 2013-03-15 | 2015-04-28 | Ventana Medical Systems, Inc. | Arcuate member for moving liquids along a microscope slide |
US20150104826A1 (en) * | 2013-07-28 | 2015-04-16 | Xmd, Llc | Devices and cartridges for extracting bio-sample regions and molecules of interest |
US10429279B2 (en) * | 2013-07-28 | 2019-10-01 | Xmd, Llc | Devices and cartridges for extracting bio-sample regions and molecules of interest |
US11415492B2 (en) | 2013-07-28 | 2022-08-16 | Xmd, Llc | Devices and cartridges for extracting bio-sample regions and molecules of interest |
US10794805B2 (en) | 2013-12-13 | 2020-10-06 | Ventana Medical Systems, Inc. | Automated histological processing of biological specimens and associated technology |
US11614387B2 (en) | 2013-12-13 | 2023-03-28 | Ventana Medical Systems, Inc. | Automated histological processing of biological specimens and associated technology |
CN104614516A (en) * | 2014-01-09 | 2015-05-13 | 南京医科大学第一附属医院 | Slide incubator ensuring good experimental results |
CN104101529A (en) * | 2014-07-27 | 2014-10-15 | 李强 | Pathological dyeing device |
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