1. Field
A fluid dispensing system, specifically a fluid dispensing apparatus that may be used in a biological sample processing system.
2. Background
In various settings, processing and testing of biological specimens is required for diagnostic purposes. Generally speaking, pathologists and other diagnosticians collect and study samples from patients, and utilize microscopic examination, and other devices to assess the samples at cellular levels. Numerous steps typically are involved in pathology and other diagnostic process, including the collection of biological samples such as blood and tissue, processing the samples, preparation of microscope slides, staining, examination, re-testing or re-staining, collecting additional samples, re-examination of the samples, and ultimately the offering of diagnostic findings.
While conducting biological tests, it is often necessary to dispense liquids, such as reagents, onto test slides containing the biological specimens. When analyzing tumor tissue for example, a thinly sliced section of the tissue might be placed on a slide and processed through a variety of steps, including dispensing predetermined amounts of liquid reagents onto the tissue. Automated reagent fluid dispensing systems have been developed to precisely apply a sequence of pre-selected reagents to test slides.
A representative reagent dispensing system includes a reagent dispensing tray which supports multiple reagent containers and is capable of positioning selected reagent containers over slides to receive reagent. The system further includes an actuator to facilitate ejection of a reagent out of the reagent container. During operation, the reagent dispensing tray positions a reagent container adjacent the actuator. The actuator (e.g. piston) contacts, for example, a spring loaded displacement member associated with the reagent container, effecting movement of the displacement member, which in turn causes reagent fluid to be applied over the slides.
Embodiments of the invention are illustrated by way of example and not by way of limitation in the figures of the accompanying drawings in which like references indicate similar elements. It should be noted that references to “an” or “one” embodiment in this disclosure are not necessarily to the same embodiment, and such references mean at least one.
In the following paragraphs, the invention will be described in detail by way of example with reference to the accompanying drawings. Throughout this description, the embodiments and examples shown should be considered as exemplars, rather than as limitations on the invention. Furthermore, reference to various aspects of the embodiments disclosed herein does not mean that all claimed embodiments or methods must include the referenced aspects.
Housing 104 may be a rigid housing that is constructed from a fluid impermeable material. It should also be appreciated that housing 104 may be constructed from any material suitable for holding liquid such as a chemically inert plastic, for example polyethylene or polypropylene. In addition to containing a fluid, housing 104 may further provide a grasping surface for handling and a marking surface so information may be recorded on the cartridge, for example, by writing on the surface or affixing a label. The label may be, for example, a bar code or a radio frequency identification (RFID) tag which identifies the contents of reservoir 102 and/or a processing protocol.
In some embodiments, housing 104 is a clam shell housing having first portion 104A and a second portion 104B. First portion 104A and second portion 1048 may be separate pieces which are positioned around metering chamber 110 and attached together to form housing 104. In some embodiments, first portion 104A and second portion 1048 are held together by, for example, a detent or snap fit mechanism. It is contemplated that in some embodiments, when first portion 104A and second portion 104B are secured to one another, air is allowed to pass through the seam formed by the portions. In this aspect, the seam provides a venting mechanism for air to enter into and equalize a pressure within housing 104. In such embodiments, a liquid within housing 104 may be within a fluid bladder or liner positioned within housing 104 as will be described in more detail in reference to
Metering chamber 110 extends from a base of fluid reservoir 102 and housing 104 (as viewed). In one embodiment, metering chamber 110 is a cylindrical member, for example a tubular structure of a deformable material. Metering chamber 110 will be described in more detail in reference to
Nozzle 120 may be positioned at an end of metering chamber 110. An outer surface of nozzle 120 may include cut outs 174 to help reduce the amount of material needed to make nozzle 120 and in turn, a weight of nozzle 120. Nozzle 120 may be secured to metering chamber 110 with nozzle locking mechanism 134. Nozzle locking mechanism 134 may be a cylindrical piece which encircles metering chamber 110 and includes arms that attach to nozzle 120 to hold nozzle 120 onto metering chamber 110. Representatively, the arms of nozzle locking mechanism 134 may include hooks which hook under protruding regions formed within nozzle 120. (see
In some embodiments, collar 116 and extenders 136,138 may encircle an upper region of metering chamber 110. Collar 116 secures an end of metering chamber 110 within the opening of housing 104. Extenders 136, 138 may facilitate connection of metering chamber 110 to a compression assembly designed to drive ejection of fluid from metering chamber 110.
Cover 140 may further be provided to cover and protect metering chamber 110 during shipping of cartridge 100. Cover 140 may have any dimensions suitable for covering the portion of metering chamber 110 extending outside of housing 104. Representatively, cover 140 may be a hollow, cylindrical plastic structure which tapers in diameter. Hooks 142, 144 extending from the edges forming the open end of cover 140 may be used to attach cover 140 to housing 104. Hooks 142, 144 include barbed ends 146, 148, respectively. Housing 104 may include openings 150, 152 on opposite sides of metering chamber 110. Openings 150, 152 are dimensioned to receive hooks 142, 144. When barbed ends 146, 148 of hooks 142, 144 are inserted within openings 150, 152, respectively, barbed ends 146, 148 catch on the edges of openings 150, 152 to hold cover 140 in place. Cover 140 may be removed by squeezing cover 140 to dislodge barbed ends 146, 148 and pulling cover 140 in a direction away from housing 104. Although a hook type fastening mechanism is disclosed, it is further contemplated that any other mechanism suitable for securing cover 140 to housing 104 may be used.
In some embodiments, a fluid within fluid reservoir 102 is held within fluid bladder or liner 106. Bladder 106 may be positioned within the interior chamber defined by housing 104. Bladder 106 may contain a predetermined amount of a fluid (e.g., reagent or a rinsing fluid) therein. Bladder 106 may be expandable such that it expands to conform to the dimensions of the interior chamber of housing 104. In this aspect, a maximum amount of fluid may be held within bladder 106 and in turn, housing 104. It should be appreciated that bladder 106 may be made of any suitable material that is substantially fluid impermeable and is flexible. Bladder 106 may be, for example, a bladder such as that available from TechFlex Packaging, LLC of Hawthorne, Calif. under model number TF-480.
Bladder 106 assists with reducing ambient air contamination and extending the shelf life of the fluid contained in it. In some embodiments, bladder 106 includes pleats to facilitate expansion of bladder 106 from a collapsed to an expanded configuration. Bladder 106 may have a quadrilateral cross section in the expanded configuration. For example, in embodiments where housing 104 has a trapezoidal cross section, bladder 106 may also have a trapezoidal cross section in the expanded configuration. In other embodiments, bladder 106 may have any dimensions suitable for holding the desired amount of fluid, for example, an elliptical cross section. Bladder 106 will be described in further detail in reference to
Bladder 106 may be coupled to metering chamber 110 via connector 108. Connector 108 may be a substantially rigid member having cylindrical conduit 112 therethrough. Connector 108 may be made of any material suitable for holding liquid such as a chemically inert plastic, for example polyethylene or polypropylene. In this aspect, fluid from bladder 106 flows through connector 108 and into metering chamber 110. One end of connector 108 may be sealed (e.g. heat sealed) to bladder 106 at an opening formed at an end of bladder 106. An opposite end of connector 108 may be inserted within an end of metering chamber 110 and through opening 114 formed through a base portion of housing 104. In some embodiments, bladder 106 having metering chamber 110 attached thereto may be inserted within housing 104 by a user. In this aspect, bladder 106 having metering chamber 110 attached may be replaceable by the user. In other embodiments, housing 104 having bladder 106 and metering chamber 110 already positioned therein may be provided to the user.
Connector 108 may include upper portion 154 and lower portion 158. Bladder 106 is sealed around upper portion 154. Lower portion 158 is inserted within metering chamber 110. Upper portion 154 provides a first flange to help secure upper portion 154 within bladder 106. As illustrated in
Lower portion 158 includes second flange 156 and third flange 160. Second flange 156 is positioned along an exterior surface of bladder 106 opposite the first flange. Third flange 158 is positioned at an end of lower portion 158 positioned within metering chamber 110.
In some embodiments, collar 116 may further be positioned at opening 114 to ensure a fluid tight seal between connector 108 and metering chamber 110. Collar 116 may be a ring shaped structure positioned within opening 114 and outside of metering chamber 110. Collar 116 is dimensioned to secure metering chamber 110 to connector 108 and prevent any gaps between the two structures. In this aspect, collar 116 may have a diameter small enough to fit within opening 114 and yet large enough to fit around metering chamber 110 to clamp or seal the end of metering chamber 110 to connector 108. In some embodiments, collar 116 may be made of a same or different material as connector 108, for example, a chemically inert plastic.
Collar 116 may include annular ring 162 formed around an inner surface of collar 116. Ring 162 is positioned slightly above third flange 160 of connector 108 (as viewed) so that it pinches a portion of metering chamber 110 between ring 162 and third flange 160. This configuration helps to secure metering chamber 110 around connector 108 and prevent metering chamber 110 from separating from connector 108 and, in turn, housing 104.
Collar 116 may further include annular groove 164 formed around an upper edge of collar 116. Annular groove 164 is dimensioned to receive upper flange 166 extending from an upper portion of metering chamber 110. Positioning of upper flange 166 within annular groove 164 further helps to inhibit separation of metering chamber 110 from housing 104.
Metering chamber 110 may be a fluid reservoir configured to hold fluid therein. In this aspect, metering chamber 110 provides a holding space for a predetermined volume of fluid that has passed from bladder 106 within fluid reservoir 102 into metering chamber 110 prior to being ejected from cartridge 100. Metering chamber 110 may be any desired size or shape. Metering chamber 110 may have a volume that is larger than the volume dispensed during each dispensing cycle of cartridge 100. In some embodiments, metering chamber 110 holds a volume of from about 1.5 ml to 4 ml. Representatively, metering chamber 110 may be a tubular structure having a diameter of from about 0.25 inches to about 1.25 inches, a length of about 2 inches to about 3 inches and hold a volume of from about 1.5 ml to 4 ml. According to this embodiment, a volume of about 5 μl to about 400 μl±5 μl may be dispensed from metering chamber 110 during each ejection cycle.
Metering chamber 110 may extend from housing 104 and provide a conduit for fluid to travel from bladder 106 to an underlying sample. In one embodiment, metering chamber 110 may be a cylindrical member, for example a tubular structure. In one embodiment, metering chamber 110 may be a tubular structure having substantially the same diameter along its length. In other embodiments, metering chamber 110 may be a tubular structure that is tapered in shape. Metering chamber 110 may further include upper flange 166 and lower flange 168 to facilitate attachment of chamber 110 to housing 104 and nozzle 120 respectively.
In one embodiment, to secure metering chamber 110 to housing, metering chamber 110 may be inserted into opening 114 at the end of housing 104 and around connector 108 extending through opening 114. As previously discussed, upper flange 166 of metering chamber 110 is positioned within annular groove 164 of connector 108 to help secure metering chamber 110 to housing 104. Collar 116 may further be placed around metering chamber 110 to ensure a fluid tight seal between metering chamber 110 and connector 108.
Metering chamber 110 may be made of a substantially flexible or compressible material. Preferably, the material of metering chamber 110 is a material which minimizes chemical permeability and returns to an original shape after compression. Representatively, metering chamber 110 may be made of a material such as silicone, polyvinyl chloride (PVC) or the like. In this aspect, metering chamber 110 may be deformed between a rest and an eject position. In the rest position, a fluid may be contained within metering chamber 110. Application of a compressive force to metering chamber 110 compresses metering chamber 110 causing the fluid within metering chamber 110 to be ejected out an opening in the end of metering chamber 110. The amount of stroke of a compression mechanism applying the compressive force may be used to control the volume of fluid ejected. In some embodiments, the dispense volume may be adjustable. In other embodiments, the dispense volume may be fixed.
The flow of fluid from metering chamber 110 is regulated by valve 118. Valve 118 is located generally at the end of metering chamber 110. Valve 118 may be a liquid retention valve. Representatively, valve 118 may have deformable flaps that seal against each other when the valve is closed and separate from each other to form a gap when the valve is opened. When metering chamber 110 is in a rest position, valve 118 remains closed and retains fluid within metering chamber 110. When metering chamber is in an eject position (i.e. compressed), valve 118 opens. The pressure created within metering chamber 110 due to the compressive force causes the fluid to be ejected out of open valve 118. In some embodiments, valve 118 is integrally formed at an end of metering chamber 110. In this aspect, valve 118 is made of the same material as metering chamber 110. In other embodiments, valve 118 is a separate piece which is attached (e.g. glued or heat sealed) to an open end of metering chamber 110 and may be made of the same or different material than metering chamber 110. Valve 118 will be discussed in further detail in reference to
Nozzle 120 may be positioned at an end of metering chamber 110 such that a fluid from valve 118 passes through nozzle 120 before exiting cartridge 100. Nozzle 120 is used to control a direction and/or velocity of fluid flowing from metering chamber 110 out of cartridge 100. In this aspect, nozzle 120 may include reservoir 122 dimensioned to receive an end of metering chamber 110. Nozzle 120 may further include fluid conduit 132 extending between reservoir 122 and opening 124 at an end of nozzle 120. The dimensions of fluid conduit 132 and opening 124 may be selected to control a direction of fluid flow and/or velocity of fluid ejected through valve 118. Representatively, fluid conduit 132 may have a length and width dimension and opening 124 may have a width dimension selected to control a direction of fluid flow and a velocity of fluid ejection.
In one embodiment, opening 124 may be defined by counter bore 170 formed at the end portion of fluid conduit 132. In this aspect, opening 124 may have a width dimension greater than a width of fluid conduit 132. Formation of counter bore 170 within the end portion of fluid conduit 132 helps to prevent excess fluid not dispensed onto an underlying sample from remaining along an outer surface of nozzle 120. In particular, fluid which would normally collect on an outer surface of nozzle 120 instead remains within counter bore 170. When fluid remains on an outer surface of nozzle 120, it is not dispensed onto the sample. This causes the actual volume of fluid dispensed onto the sample to be less than the intended volume and can affect sample treatment. Counter bore 170 allows for this excess fluid to be captured within nozzle 120 and dispensed during the next dispensing cycle. Thus, a volume of fluid is dispensed more accurately from cartridge 100.
When nozzle 120 is positioned around metering chamber 110, flange 168 extending from metering chamber 110 rests along the top edge of nozzle 120. Nozzle locking mechanism 134, which encircles metering chamber 110, is then placed on a side of flange 168 opposite nozzle 120. Arms of nozzle locking mechanism 134 extend beyond flange 168 toward nozzle 120 and are inserted within nozzle 120 to lock nozzle 120 to metering chamber 110.
In some embodiments, in addition to nozzle locking mechanism 134, an adhesive, glue or hot-melt process may be used to secure nozzle 120 to metering chamber 110. In some embodiments, an outer surface of the end of metering chamber 110 and an inner surface of nozzle 120 may have complimentary ribbing or threading such that nozzle 120 is screwed around an end of metering chamber 110. In other embodiments, nozzle 120 may be integrally formed with the end of metering chamber 110. Nozzle 120 is described in further detail in reference to
Fluid may be ejected from metering chamber 110 through valve 118 and nozzle 120 by squeezing metering chamber 110. In one embodiment, compression assembly 126 coupled to metering chamber 110 squeezes metering chamber 110. Although specific compression assemblies are disclosed herein, it is contemplated that compression assembly 126 may be any type of compressive device which squeezes metering chamber 110 starting at the top end (i.e. end closest to reservoir 102) and moving down to the bottom end (i.e. end furthest from reservoir 102). In this aspect, fluid is prevented from flowing past compression assembly 126 and back toward fluid reservoir 102. Since fluid is prevented from flowing past compression assembly 126 during the ejection cycle, a second valve at a proximal end of metering chamber 110 (i.e. end closest to reservoir 102) to prevent fluid backflow into fluid reservoir 102 is unnecessary. In this aspect, a fluid conduit 112 of connector 108 positioned within metering chamber 110 is unopposed by, for example, a valve, and allows for unobstructed fluid flow from reservoir 102 into metering chamber 110. Additional valves may, however, be included at each end of metering chamber 110 if desired.
Compression assembly 126 may include compression members 128 and 130. Compression members 128 and 130 may be of any size and shape suitable for compressing metering chamber 110. Representatively, in one embodiment, compression members 128 and 130 are elongated plate like structures such as those illustrated in
To compress metering chamber 110, compression members 128 and 130 may be advanced toward one another in a direction of metering chamber 110. Compression members 128, 130 compress (i.e. squeeze) metering chamber 110 along its length causing valve 118 to open and a predetermined amount of fluid to be ejected there from. Upon ejection of the predetermined amount of fluid, compression members 128 and 130 may be released allowing metering chamber 110 to return to its original configuration. Expansion of metering chamber 110 back to its original, resting configuration creates an initial vacuum within metering chamber 110 which draws the “last drop” hanging on the end of nozzle 120 back into counter bore 170 of nozzle 120 for ejection during the next cycle. The phrase “last drop” as used herein refers to an amount of fluid which, due to the surface tension of the liquid, forms a drop and remains at the end of nozzle 120 after the rest of the fluid is ejected. The presence or absence of the last drop from the ejected fluid changes the amount of fluid applied to the underlying sample. It is therefore important that the last drop be accounted for by either ensuring that it is ejected with the initial amount of fluid or drawn back into the metering chamber and ejected with the next amount of fluid applied to the sample.
In some embodiments, metering chamber 200 further includes ribbing 230 formed around an outer surface of tubular portion 210 to facilitate attachment of nozzle 220. Representatively, ribbing 230 may be formed around an end portion of tubular portion 210. An inner surface of nozzle 220 may include ribbing 280 complimentary to ribbing 230. Nozzle 220 may be attached to tubular portion 210 by positioning the end of tubular portion 210 having valve 240 within reservoir 290 of nozzle 220 and positioning ribbing 280 of nozzle 220 between ribbing 230 of valve 240.
Once nozzle 220 is positioned around valve 240 as previously discussed, nozzle locking mechanism 234, which is positioned around tubular portion 210, may be pushed down tubular portion 210 and into slots within nozzle 220 to lock nozzle 220 to tubular portion 210. As previously discussed, flange 268 extending from tubular portion 210 may be positioned between nozzle 220 and nozzle locking mechanism 234. In still further embodiments, nozzle 220 may be secured to tubular portion 210 by an adhesive, glue or hot melt. When nozzle 220 is attached to tubular portion 210, fluid ejected from tubular portion 210 flows out of nozzle 220 through opening 270.
When tubular portion 210 of metering chamber 200 is compressed, valve 240 opens deflecting skirt member 250 outward. This deflection of skirt member 250 causes skirt member 250 to press against the adjacent surface of nozzle 220. In this aspect, skirt member 250 creates a seal between skirt member 250 and nozzle 220 which prevents any fluid from flowing back up along the sides of nozzle 220. Instead, any fluid back up is contained within a region of nozzle 220 defined by skirt 250. Such feature is important to ensuring that an accurate amount of fluid is delivered to the sample. In particular, if during dispensing of the fluid, the fluid were to escape out of the sides of nozzle 220, the amount of fluid dispensed would actually be less than that which is expected. Sealing of skirt member 250 against nozzle 220 will be discussed in more detail in reference to
Skirt member 250 is positioned within recessed region 610 of nozzle 220. As can be seen from
Fluid dispensing cartridge 800 generally includes fluid reservoir 802 that is in fluid communication with metering chambers 810 and 812. Fluid reservoir 802 is generally a container that is configured to hold a predetermined amount of a fluid, such as a reagent or a rinsing fluid. In some embodiments, reservoir 802 includes housing 804. Housing 804 may be a rigid housing that is constructed from a fluid impermeable material similar to housing 104 discussed in reference to
In some embodiments, housing 804 may be a clam shell type housing similar to housing 104 discussed in reference to
Housing 804 may be dimensioned to accommodate fluid bladder 806 and fluid bladder 808. Bladders 806, 808 may be positioned within the interior chamber defined by housing 804. In some embodiments, bladders 806, 808 are positioned side by side within housing 804. In other embodiments, housing 804 may include a wall dividing the interior chamber into two chambers in order to separate bladders 806, 808.
Bladders 806, 808 may contain a predetermined amount of a fluid (e.g., reagent or a rinsing fluid) therein. The fluids contained in bladders 806, 808 may be the same or different. For example, in some embodiments, it may be desirable to use two different fluids which must be kept separate prior to application to a sample. In this aspect, one of the fluids may be contained in bladder 806 and the other fluid in bladder 808. The fluids will not mix until they are ejected from metering chambers 810, 812 coupled to bladders 806, 808, respectively.
Bladders 806, 808 may be expandable. Bladders 806, 808 may expand to conform to the dimensions of the interior chamber of housing 804. In this aspect, a maximum amount of fluid may be held within bladders 806, 808 and in turn, housing 804. It should be appreciated that bladders 806, 808 may be made of any suitable material that is substantially fluid impermeable and is flexible. Bladder 106 may be, for example, a bladder such as that available from TechFlex Packaging, LLC of Hawthorne, Calif. under model number TF-480. Use of bladders 806, 808 may assist with reducing ambient air contamination and extending the shelf life of the fluid contained in it.
In some embodiments, bladders 806, 808 include pleats to facilitate expansion of bladders 806, 808 from a collapsed to an expanded configuration. Bladders 806, 808 may have a quadrilateral cross section in the expanded configuration. For example, in embodiments where housing 804 has a trapezoidal cross section or an elliptical cross section, bladders 806, 808 may also have a trapezoidal cross section in the expanded configuration such that the two bladders combined conform to the internal dimensions of housing 804. It is contemplated that bladders 806, 808 may have the same or different dimensions. Bladders 806, 808 may be in fluid communication with metering chambers 810, 812, respectively.
Nozzles 834 and 836 may be positioned around ends of metering chambers 810, 812, respectively. Similar to nozzle 120 described in reference to
Compression assembly 852 may be coupled to metering chambers 810, 812 to facilitate fluid ejection. Compression assembly 852 may include compression members 854, 856 similar to those described in reference to
As illustrated in
Connector 814 may include upper portion 860 and lower portion 868. Upper portion 860 is positioned inside of bladder 806 and lower portion 868 is inserted within metering chamber 810. Upper portion 860 provides a first flange to help secure upper portion 860 within bladder 806. As illustrated in
Lower portion 868 includes second flange 864 and third flange 872. Second flange 864 is positioned along an exterior surface of bladder 806 opposite the first flange. Third flange 872 is positioned at an end of lower portion 868 positioned within metering chamber 810.
In some embodiments, collar 826 may further be positioned at opening 822 to ensure a fluid tight seal between connector 814 and metering chamber 810. Collar 826 may be a ring shaped structure positioned within opening 822 and outside of metering chamber 810. Collar 826 is dimensioned to secure metering chamber 810 to connector 814 and prevent any gaps between the two structures. In this aspect, collar 826 may have a diameter small enough to fit within opening 822 and yet large enough to fit around metering chamber 810 to clamp or seal the end of metering chamber 810 to connector 814. In some embodiments, collar 826 may be made of a plastic material or the like
Collar 826 may include annular ring 870 formed around an inner surface of collar 826. Ring 870 is positioned between second flange 864 and third flange 872. Ring 870 catches a portion of metering chamber 810 between third flange 872 and ring 870 to prevent separation of metering chamber 810 from housing 804. Collar 826 further includes annular groove 878 formed around an upper edge of collar 826. Annular groove 878 is dimensioned to receive upper flange 880 formed by metering chamber 810. Positioning of upper flange 880 within annular groove 878 further helps to prevent separation of metering chamber 810 from housing 804.
Connector 816 may be similar to connector 814. Representatively, connector 816 may include upper portion 862 having a first flange and lower portion 876 having second flange 866 and third flange 874. Collar 828 similar to collar 826 may further be provided at opening 824 to ensure a fluid tight seal between connector 816 and metering chamber 812. Collar 828 may include annular ring 886 positioned between second flange 866 and third flange 874 to prevent separation of metering chamber 812 from housing 804. Collar 828 may further include an annular groove 882 formed around an upper edge for receiving upper flange 884 of metering chamber 810. Although collar 826 and collar 828 are described separately, it is contemplated that collars 826, 828 may be separate structures or may be integrally formed such that they are connected together.
Metering chambers 810, 812 may be substantially the same as metering chamber 110 described in reference to
Metering chambers 810, 812 may be made of a substantially flexible or compressible material. Preferably, the material of metering chambers 810, 812 is a material which minimizes chemical permeability and returns to an original shape after compression. Representatively, metering chambers 810, 812 may be made of a material such as silicon, polyvinyl chloride (PVC) or the like. In this aspect, metering chambers 810, 812 may be deformed between a rest and an eject position. In the rest position, a fluid may be contained within metering chambers 810, 812. Application of a compressive force to metering chambers 810, 812 compresses metering chambers 810, 812 causing the fluid within metering chambers 810, 812 to be ejected out an opening in the end of metering chambers 810, 812.
Each of metering chambers 810, 812 includes valve 830, 832, respectively, to regulate fluid flow from chambers 810, 812. Valves 830, 832 may be substantially the same as, for example, valve 118 described in reference to
Nozzle 834 may be positioned at an end of metering chamber 810 around valve 830. Similarly, nozzle 836 may be positioned at an end of metering chamber 812 around valve 832. Nozzles 834, 836 are used to regulate fluid flow from metering chambers 810, 812, respectively, out of cartridge 800. Nozzles 834, 836 may be substantially similar to nozzle 120 described in reference to
A fluid tight seal may be provided between nozzles 834, 836 and metering chambers 810, 812, respectively, to secure nozzles 834, 836 to metering chambers 810, 812, respectively. Representatively, nozzle 834 may be secured around the end of metering chamber 810 using an adhesive, glue or hot-melt. In some embodiments, an outer surface of metering chamber 810 may have ribbing 894 and an inner surface of nozzle 834 may have complimentary ribbing 896 that can be positioned between ribbing 894 to help secure nozzle 834 around an end portion of metering chamber 810. In other embodiments, metering chamber 810 and the inner surface of nozzle 834 have complimentary threading. In still further embodiments, nozzle 834 may be integrally formed with the end of metering chamber 810. Nozzle 836 may be attached to metering chamber 812 in a similar or different manner than that used to attach nozzle 834 to metering chamber 810. Representatively, nozzle 836 may be attached to metering chamber 812 using an adhesive and/or complimentary ribbing 888, 898 or threading as previously discussed.
In some embodiments, once nozzles 834, 836 are attached to the ends of metering chambers 810, 812 they can be attached to one another. Representatively, when nozzles 834, 836 are placed on metering chambers 810, 812, the adjacent surfaces of nozzle 834, 836 may be flat so that they can be placed next to one another without modifying a vertical position of metering chambers 810, 812. One of nozzles 834, 836 may include a protruding portion and the other of nozzles 834, 836 may include a receiving portion dimensioned to receive the protruding portion. When nozzles 834, 836 are pressed together, protruding portion is inserted into receiving portion to hold nozzles 834, 836 together. In some embodiments, each of nozzles 834, 836 may include a protruding portion and a receiving portion.
Stabilizer 846 may be connected to metering chambers 810, 812 and nozzles 834, 836. In some embodiments stabilizer 846 may be a substantially oblong shaped cylindrical structure which encircles metering chambers 810, 812 and nozzles 834, 836. Compartments may be formed within stabilizer 846 which are dimensioned to receive portions of metering chambers 810, 812 and nozzles 834, 836. In some embodiments, stabilizer 846 is a separate structure from metering chambers 810, 812 and nozzles 834, 836 which is fit around metering chambers 810, 812 and nozzles 834, 836 once they are assembled. Representatively, stabilizer 846 may include two halves which may be snap fit together around chambers 810, 812 and nozzles 834, 836. In other embodiments, nozzles 834 and 836 may be connected to and extend from one end of stabilizer 846.
Each of metering chambers 810, 812 further include lower flanges 893, 897 positioned between nozzles 834, 836 and nozzle locking mechanisms 864, 866 to help secure nozzles 834, 836 to metering chambers 810, 812.
Pleat 1306 may have a depth D. Depth D of pleat 1306 may be determined based upon the desired fluid volume of bladder 1302. Representatively, as depth D of pleat 1306 increases, the fluid volume of bladder 1302 further increases. Representatively, in one embodiment where bladder 1302 has a length of about 5 inches and a width of about 4 inches in the unexpanded configuration, pleat 1306 may have a depth D of about 1 inch giving bladder 1302 a fluid volume of from about 250 mL to about 350 mL in an expanded configuration. In other embodiments, the depth D of pleat 1306 may vary from 0.60 inches to about 1.5 inches.
In still further embodiments, pleats may be included along edges 1310, 1312 of bladder 1302 and end 1304 may not include a pleat.
Compression members 1406, 1408 are substantially flat members having curved ends. A length of the flat region of compression members 1406, 1408 may be modified to control a volume of fluid dispensed from metering chamber 1404. Representatively, when compression members 1406, 1408 having a flat region length of between about 0.5 inches and about 0.6 inches are compressed against metering chamber 1404, a volume of from about 380 μL to about 480 μL may be dispensed.
Compression members 1406, 1408 may be attached to support members 1410, 1412, respectively. Support members 1410, 1412 drive movement of compression members 1406, 1408. Support members 1410, 1412 are pivotally attached (e.g. by a pin, screw or the like) to compression guides 1414, 1416, respectively. Compression guides 1414, 1416 help to support and position compression members 1406, 1408 around metering chamber 1404. Compression guides 1414, 1416 are rotatably connected to each other by pivot mechanism 1422. In this aspect, movement of compression guides 1414, 1416, and in turn support members 1410, 1412 in a direction toward one another drives movement of compression members 1406, 1408 toward metering chamber 1404. Spring 1424 is connected between support member 1410 and compression guide 1414. In this aspect, when compression guide 1414 is in the open position as illustrated in
Actuator 1428 is attached to support member 1412 by link plate 1430. Link plate 1430 is pivotally attached at opposite ends to actuator 1428 and support member 1412.
To compress metering chamber 1404, actuator 1428 pushes link plate 1430 in a direction toward metering chamber 1404. This movement of link plate 1430 causes support member 1412 attached to compression member 1408 to move in a direction toward metering chamber 1404. Support member 1410 and compression member 1406 also move in a direction toward metering chamber 1404. This initial movement causes the curved ends of compression members 1406, 1408 to contact metering chamber 1404. Further movement by actuator 1428 in a direction of metering chamber 1404 causes the curved ends of compression members 1406, 1408 to compress metering chamber 1404 at the same position as illustrated in
As illustrated in
When the flat portions of compression members 1406, 1408 are parallel as illustrated in
During compression of metering chamber 1404, the upper most compressed portion of metering chamber 1404 (see
In this embodiment, compression members 1506, 1508 may be rollers. Rollers 1506, 1508 may roll along a length dimension of metering chamber 1504 to compress metering chamber 1504. Rollers 1506, 1508 may rotate around drive shafts 1522, 1524, respectively. Drive shafts 1522, 1524 may be positioned within tracks 1510, 1512 formed within housing 1516. Housing 1516 may enclose compression assembly 1500. Drive shafts 1522, 1524 may move along tracks 1510, 1512 to guide rollers 1506, 1508 along metering chamber 1504. Tracks 1510, 1512 may be parallel to one another along a substantial portion of the length of metering chamber 1504 and then flare out at one end. In this aspect, when drive shafts 1522, 1524 of rollers 1506, 1508 are within the flared end of tracks 1510, 1512, rollers 1522, 1524 are farther apart and do not compress metering chamber 1504 as illustrated in
Support member 1514 may be provided to drive shafts 1506, 1508 along tracks 1510, 1512. Support member 1514 may include recessed regions 1518, 1520 which receive ends of drive shafts 1522, 1524. Recessed regions 1518, 1520 are deep enough to allow drive shafts 1506, 1508 to move in a horizontal direction, e.g. toward or away from metering chamber 1504. In this aspect, when support member 1514 is moved in a vertical direction to the flared ends of tracks 1510, 1512, rollers 1506, 1508 move away from one another and are a distance apart so as not to compress metering chamber 1504 as illustrated in
Drive member 1526 may be connected to support member 1514 to move support members 1514, 1515 in a vertical direction. In some embodiments, drive member 1526 may be a rod attached to, and extending from, support member 1514. A robotic arm or other mechanism capable of driving movement in a vertical direction may be attached to drive member 1526 to move drive member, and in turn drive shaft 1522 and roller 1506 vertically along metering chamber 1504. Movement of drive member 1526 may be driven by a unit including a cam-crank and motor.
In this embodiment, compression members 1606, 1608 may be rollers. Rollers 1606, 1608 may be positioned around drive shafts 1622, 1624, respectively, which facilitate rotation of rollers 1606, 1608. Drive shafts 1622, 1624 may be attached to pivot arms 1610, 1612. Pivot arms 1610, 1612 pivot about shafts 1626, 1628, respectively, so as to drive the attached drive shafts 1622, 1624 and in turn rollers 1606, 1608 vertically along the length of metering chamber 1604.
Spreader 1642 may be positioned between rollers 1606, 1608 once they reach a bottom portion of metering chamber 1604 to increase a distance between rollers 1606, 1608 as they travel back up metering chamber 1604. If rollers 1606, 1608 are not spread apart before traveling back up metering chamber 1604, a vacuum is created in the lower portion of metering chamber 1604 (region between rollers 1606, 1608 and the valve). This vacuum causes air to be sucked into metering chamber 1604. The air travels up metering chamber 1604 and into fluid reservoir 1602. The addition of air to the fluid within reservoir 1602 could negatively affect the fluid. For example, the addition of air to a reagent within fluid reservoir 1602 increases oxidation of the reagent.
Spreader 1642 includes base member 1648 positioned around metering chamber 1604 and side member 1650 extending vertically between rollers 1606, 1608. Side member 1650 has a substantially triangular shape with the widest portion positioned near base member 1648 such that a distance between rollers 1606, 1608 is increased as rollers 1606, 1608 reach an end of metering chamber 1604. Spreader 1642 is movably positioned along rod 1644. Representatively, side member 1650 of spreader 1642 includes a channel (not shown) dimensioned to fit around a portion of rod 1644 and allow spreader 1642 to slide along rod 1644. Rod 1644 includes spring 1646 encircling an upper region of rod 1644, above spreader 1642 to bias spreader 1642 in a direction away from housing 1602. A second side member, rod and spring (not shown) identical to side member 1650, rod 1644 and spring 1646 are found at an opposite side of spreader 1642. During operation, rollers 1606, 1608 roll along metering chamber 1604 and spreader 1642 until they reach a lower portion of metering chamber 1604. When they reach the lowest portion of metering chamber 1604, spreader 1642 spreads rollers 1606, 1608 apart. As rollers 1606, 1608 travel back up a length of metering chamber 1604, spreader 1642 may remain between rollers 1606, 1608 for a portion of the length to ensure that rollers remain a sufficient distance apart as they travel back up metering chamber 1604 to the open position. Spreader 1642 is eventually released and pushed by down toward a base of support member 1618 by spring 1646.
Gears 1614, 1616 control movement of rollers 1606, 1608. Gears 1614, 1616 may include complimentary teeth or cogs such that rotation of one drives rotation of the other. Representatively, when compression assembly 1600 is in the open configuration as illustrated in
Gears 1614, 1616 may be driven by a motorized device or other similar device suitable for driving gears. In still further embodiments, gears 1614, 1616 may be driven manually by the user.
Gears 1614, 1616 and any motorized device associated therewith may be supported by support member 1618. Support member 1618 may be any structure suitable for supporting and coupling gears 1614, 1616 to the fluid dispensing cartridge.
In some embodiments, rollers 1606, 1608 may include spring assemblies 1630, 1632, respectively. Spring assemblies 1630, 1632 allow rollers 1606, 1608 to be retracted as necessary. For example, in order for rollers 1606, 1608 to compress metering chamber 1604 along its length as illustrated in
Fluid dispensing system 1700 also optionally includes receiving assembly 1710 retaining a plurality of receiving members 1712. Receiving members 1712 may be any item on which it is desired to dispense fluids from cartridges 1706. Examples of suitable receiving members 1712 are slides, trays and mixing baths. In a preferred embodiment, receiving members 1712 are microscope slides supported on support members. The microscope slides may have substrates mounted thereon. Examples of suitable substrates are thin slices of tissue samples.
Generally speaking, receiving assembly 1710 is positioned beneath mounting assembly 1702 taking advantage of gravity to deliver fluids dispensed from cartridges 1706. Preferably, mounting assembly 1702 and receiving assembly 1710 are movable with respect to one another so that the plurality of cartridges 1706 can be positioned to dispense fluids on any desired receiving member 1712. Any combination of movability of the mounting assembly 1702 and the receiving assembly 1712 may be selected. For example, both may be movable or only one may be movable and the other stationary. Still further, mounting assembly 1702 may be a carousel that is rotatable about a central axis so as to align the cartridges 1706 with the desired receiving member 1712. Mounting assembly 1702 may also be linearly translatable such that it may move from one receiving member 1712 to the next. As shown in
In one example of operation of the dispensing system 1700, mounting assembly 1702 is rotated so that individual cartridges 1706 are selectively positioned adjacent one or both of actuator assembly 1720. Alternatively, system 1700 may include a plurality of actuator assemblies 1720 which are positioned adjacent to each cartridge 1706 such that rotation of mounting assembly 1702 to align each cartridge 1706 with actuator assembly 1720 is not required.
Actuator assembly 1720 can be any activation device that triggers cartridge 1706 to emit a controlled amount of fluid. Representatively, actuator assembly 1720 may include a piston mechanism that aligns with, for example, actuator 1428 of compression assembly 1400 (see
Mounting assembly 1702 may be both translated and rotated with respect to receiving assembly 1710 so that an individual cartridge 1706 can be selectively positioned above any receiving member 1712. Once cartridge 1706 is positioned above one of receiving members 1712, actuator assembly 1720 triggers cartridge 1706 to emit a controlled amount of fluid onto receiving member 1712.
As seen in
Although receiving members 1712 are shown linearly positioned within receiving assembly 1710, it is further contemplated that receiving members 1712 may be divided into two or more rows. In this aspect, actuator assembly 1720 may optionally include two or more actuators, for example, two actuators 1714, 1716 used to dispense fluid onto two rows of receiving members. In operation, actuator 1714 is adapted to dispense fluids onto receiving members 1712 in one row and actuator 1716 is adapted to dispense fluids onto receiving members 1712 in another row. It is further contemplated that any number of actuators and/or receiving members can be employed without departing from the scope of the present invention.
As shown in
As illustrated in the exploded view of cartridge 1706 and station 1704, cartridge 1706 (including the metering chamber(s)) is removably positioned within station 1704. Station 1704 including a compression assembly mounted thereto is fixedly mounted to support member 1722. In this aspect, once cartridge 1706 is empty, cartridge 1706 and its associated metering chamber(s) is removed from station 1704 while the compression assembly remains mounted to the dispensing system at station 1704. A replacement cartridge and metering chamber(s) may then be placed in station 1704. In other embodiments, the compression assembly may be mounted to cartridge 1706. In this aspect, each of cartridges 1706 includes a compression assembly and removal of cartridge 1706 also removes the compression assembly.
Turning now to the structure of cartridges 1706, in some embodiments, a horizontal cross-sectional shape of the cartridges 1706 lacks symmetry. In this way, mounting aperture 1708 in mounting assembly 1702 is similarly shaped requiring insertion to be in a particular desired orientation. For example, a substantially trapezoidal shape may be selected promoting the desired placement orientations.
Optionally a mounting mechanism can be utilized to releasably attach cartridge 1706 within a corresponding mounting aperture 1708 of mounting assembly 1702. In one example, as shown in
As previously discussed in reference to
With reference to
It should also be appreciated that reference throughout this specification to “one embodiment”, “an embodiment”, or “one or more embodiments”, for example, means that a particular feature may be included in the practice of the invention. Similarly, it should be appreciated that in the description various features are sometimes grouped together in a single embodiment, Figure, or description thereof for the purpose of streamlining the disclosure and aiding in the understanding of various inventive aspects. This method of disclosure, however, is not to be interpreted as reflecting an intention that the invention requires more features than are expressly recited in each claim. Rather, as the following claims reflect, inventive aspects may lie in less than all features of a single disclosed embodiment. Thus, the claims following the Detailed Description are hereby expressly incorporated into this Detailed Description, with each claim standing on its own as a separate embodiment.
In the foregoing specification, the invention has been described with reference to specific embodiments thereof. It will, however, be evident that various modifications and changes can be made thereto without departing from the broader spirit and scope of the invention as set forth in the appended claims. For example, although a fluid dispensing system is disclosed in the context of tissue staining and histology in general, other non-infringing uses of dispensers such as those disclosed herein are contemplated such as use of the dispensers in systems that may be employed to dispense pigments from multiple dispensers to make paints. The specification and drawings are, accordingly, to be regarded in an illustrative rather than a restrictive sense.
Number | Name | Date | Kind |
---|---|---|---|
1621097 | Zammataro | Mar 1927 | A |
2709025 | Scott | May 1955 | A |
2772817 | Jauch | Dec 1956 | A |
3008611 | Mancusi, Jr. | Nov 1961 | A |
3066832 | Rossetti | Dec 1962 | A |
3294290 | Erickson et al. | Dec 1966 | A |
3741439 | Vehrs | Jun 1973 | A |
3752366 | Lawrence, Jr. | Aug 1973 | A |
3881641 | Pliml, Jr. et al. | May 1975 | A |
3904079 | Kross | Sep 1975 | A |
3987938 | Cooprider et al. | Oct 1976 | A |
4018363 | Cassia | Apr 1977 | A |
4025241 | Clemens | May 1977 | A |
4039775 | Andra | Aug 1977 | A |
4099483 | Henderson | Jul 1978 | A |
4130224 | Norman et al. | Dec 1978 | A |
4143853 | Abramson | Mar 1979 | A |
4149573 | Cassia | Apr 1979 | A |
4149633 | Nilson | Apr 1979 | A |
4199558 | Henderson | Apr 1980 | A |
4256242 | Christine | Mar 1981 | A |
4258759 | Achen | Mar 1981 | A |
4334640 | van Overbruggen et al. | Jun 1982 | A |
4345627 | Cassia | Aug 1982 | A |
4349133 | Christine | Sep 1982 | A |
4356727 | Brown et al. | Nov 1982 | A |
4394938 | Frassanito | Jul 1983 | A |
4440323 | Benson | Apr 1984 | A |
4513885 | Hogan | Apr 1985 | A |
4515294 | Udall | May 1985 | A |
4561571 | Chen | Dec 1985 | A |
4573612 | Maddison et al. | Mar 1986 | A |
4601411 | van Overbruggen | Jul 1986 | A |
4604964 | Gordon et al. | Aug 1986 | A |
4607764 | Christine | Aug 1986 | A |
4615476 | Hobbs et al. | Oct 1986 | A |
4621749 | Kanfer | Nov 1986 | A |
4646945 | Steiner et al. | Mar 1987 | A |
4651898 | Bell | Mar 1987 | A |
4667854 | McDermott et al. | May 1987 | A |
4673109 | Cassia | Jun 1987 | A |
4678752 | Thorne et al. | Jul 1987 | A |
4722372 | Hoffman et al. | Feb 1988 | A |
4731335 | Brigati | Mar 1988 | A |
4741461 | Williamson et al. | May 1988 | A |
4741898 | Mallik et al. | May 1988 | A |
4764342 | Kelln et al. | Aug 1988 | A |
4776495 | Vignot | Oct 1988 | A |
4790640 | Nason | Dec 1988 | A |
4798311 | Workum | Jan 1989 | A |
4801431 | Cuomo et al. | Jan 1989 | A |
4834019 | Gordon et al. | May 1989 | A |
4838457 | Swahl et al. | Jun 1989 | A |
4846636 | Danby et al. | Jul 1989 | A |
4867347 | Wass et al. | Sep 1989 | A |
4880149 | Scholefield et al. | Nov 1989 | A |
4886192 | Cassia | Dec 1989 | A |
4895276 | Maldonado | Jan 1990 | A |
4917265 | Chiang | Apr 1990 | A |
4921136 | Roggenburg, Jr. | May 1990 | A |
4927061 | Leigh et al. | May 1990 | A |
4932624 | Holm | Jun 1990 | A |
4946076 | Hackmann et al. | Aug 1990 | A |
4955512 | Sharples | Sep 1990 | A |
4961508 | Weimer et al. | Oct 1990 | A |
4969581 | Seifert et al. | Nov 1990 | A |
4972978 | DeLuca | Nov 1990 | A |
4974754 | Wirz | Dec 1990 | A |
4978036 | Burd | Dec 1990 | A |
4978502 | Dole et al. | Dec 1990 | A |
4985206 | Bowman et al. | Jan 1991 | A |
5002736 | Babbitt et al. | Mar 1991 | A |
5033656 | Blette et al. | Jul 1991 | A |
5033943 | Durrum et al. | Jul 1991 | A |
5035350 | Blette et al. | Jul 1991 | A |
5042691 | Maldonado | Aug 1991 | A |
5068091 | Toya | Nov 1991 | A |
5073504 | Bogen | Dec 1991 | A |
5082150 | Steiner et al. | Jan 1992 | A |
5105992 | Fender et al. | Apr 1992 | A |
5225325 | Miller et al. | Jul 1993 | A |
5232664 | Krawzak et al. | Aug 1993 | A |
5242081 | van der Heyden et al. | Sep 1993 | A |
5242083 | Christine et al. | Sep 1993 | A |
5244787 | Key et al. | Sep 1993 | A |
5252293 | Drbal et al. | Oct 1993 | A |
5253774 | Honig et al. | Oct 1993 | A |
5255822 | Mease et al. | Oct 1993 | A |
5265770 | Matkovich et al. | Nov 1993 | A |
5273905 | Muller et al. | Dec 1993 | A |
5275309 | Baron et al. | Jan 1994 | A |
5316452 | Bogen et al. | May 1994 | A |
5322771 | Rybski et al. | Jun 1994 | A |
5338358 | Mizusawa et al. | Aug 1994 | A |
5355439 | Bernstein et al. | Oct 1994 | A |
5356039 | Christine et al. | Oct 1994 | A |
5390822 | Lataix | Feb 1995 | A |
5418138 | Miller et al. | May 1995 | A |
5421489 | Holzner, Sr. et al. | Jun 1995 | A |
5424036 | Ushikubo | Jun 1995 | A |
5425918 | Healey et al. | Jun 1995 | A |
5433351 | Okuyama et al. | Jul 1995 | A |
5439649 | Tseung et al. | Aug 1995 | A |
5474212 | Ichikawa et al. | Dec 1995 | A |
5492247 | Shu et al. | Feb 1996 | A |
5501372 | Daansen | Mar 1996 | A |
5525300 | Danssaert et al. | Jun 1996 | A |
5534114 | Cutright et al. | Jul 1996 | A |
5561556 | Weissman et al. | Oct 1996 | A |
5578452 | Shi et al. | Nov 1996 | A |
5579945 | Ichikawa et al. | Dec 1996 | A |
5580523 | Bard | Dec 1996 | A |
5595707 | Copeland et al. | Jan 1997 | A |
5597093 | Lee | Jan 1997 | A |
5602674 | Weissman et al. | Feb 1997 | A |
5609822 | Carey et al. | Mar 1997 | A |
5626262 | Fitten et al. | May 1997 | A |
5639423 | Northrup et al. | Jun 1997 | A |
5645114 | Bogen et al. | Jul 1997 | A |
5650327 | Copeland et al. | Jul 1997 | A |
5654199 | Copeland et al. | Aug 1997 | A |
5654200 | Copeland et al. | Aug 1997 | A |
5675715 | Bernstein et al. | Oct 1997 | A |
5700346 | Edwards | Dec 1997 | A |
5810204 | Devlin et al. | Sep 1998 | A |
5819842 | Potter et al. | Oct 1998 | A |
5836482 | Ophardt et al. | Nov 1998 | A |
5839091 | Rhett et al. | Nov 1998 | A |
5843700 | Kerrod et al. | Dec 1998 | A |
5846396 | Zanzucchi et al. | Dec 1998 | A |
5851488 | Saul et al. | Dec 1998 | A |
5855302 | Fisscher | Jan 1999 | A |
5857595 | Nilson | Jan 1999 | A |
5885530 | Babson et al. | Mar 1999 | A |
5909828 | Salisbury | Jun 1999 | A |
5938414 | Kayahara et al. | Aug 1999 | A |
5947167 | Bogen et al. | Sep 1999 | A |
5948359 | Kalra et al. | Sep 1999 | A |
5950874 | Sindoni | Sep 1999 | A |
5950878 | Wade et al. | Sep 1999 | A |
5954167 | Richardson et al. | Sep 1999 | A |
5958341 | Chu | Sep 1999 | A |
5964454 | Volpel | Oct 1999 | A |
5965454 | Farmilo et al. | Oct 1999 | A |
5968731 | Layne et al. | Oct 1999 | A |
5971223 | Fisscher | Oct 1999 | A |
6001309 | Gamble et al. | Dec 1999 | A |
6012613 | Chen | Jan 2000 | A |
6017495 | Ljungmann | Jan 2000 | A |
6020995 | Dreyer et al. | Feb 2000 | A |
6045759 | Ford et al. | Apr 2000 | A |
6068162 | De Winter et al. | May 2000 | A |
6076583 | Edwards | Jun 2000 | A |
6092695 | Loeffler | Jul 2000 | A |
6093574 | Druyor-Sanchez et al. | Jul 2000 | A |
6096271 | Bogen et al. | Aug 2000 | A |
6131773 | Wade et al. | Oct 2000 | A |
6142343 | Wade et al. | Nov 2000 | A |
6152330 | Polan | Nov 2000 | A |
6180061 | Bogen et al. | Jan 2001 | B1 |
6183693 | Bogen et al. | Feb 2001 | B1 |
6189740 | Wade et al. | Feb 2001 | B1 |
6192945 | Ford et al. | Feb 2001 | B1 |
6206238 | Ophardt | Mar 2001 | B1 |
6216916 | Maddox et al. | Apr 2001 | B1 |
6238910 | Custance et al. | May 2001 | B1 |
6244474 | Loeffler | Jun 2001 | B1 |
6259956 | Myers et al. | Jul 2001 | B1 |
6273298 | Post | Aug 2001 | B1 |
6286725 | Gerber | Sep 2001 | B1 |
6296809 | Richards et al. | Oct 2001 | B1 |
6335166 | Ammann et al. | Jan 2002 | B1 |
6343716 | Baudin et al. | Feb 2002 | B1 |
6349264 | Rhett et al. | Feb 2002 | B1 |
6352861 | Copeland et al. | Mar 2002 | B1 |
6387326 | Edwards et al. | May 2002 | B1 |
6415961 | Bonningue | Jul 2002 | B2 |
6416713 | Ford et al. | Jul 2002 | B1 |
6451551 | Zhan et al. | Sep 2002 | B1 |
6472217 | Richards et al. | Oct 2002 | B1 |
6489171 | Aghassi et al. | Dec 2002 | B1 |
6495106 | Kalra et al. | Dec 2002 | B1 |
6516620 | Lang | Feb 2003 | B2 |
6534008 | Angros | Mar 2003 | B1 |
6540117 | Powling | Apr 2003 | B2 |
6541261 | Bogen et al. | Apr 2003 | B1 |
6543652 | Kelder et al. | Apr 2003 | B1 |
6544798 | Christensen et al. | Apr 2003 | B1 |
6553145 | Kang et al. | Apr 2003 | B1 |
6568561 | Studer et al. | May 2003 | B2 |
6580056 | Tacha | Jun 2003 | B1 |
6582962 | Richards et al. | Jun 2003 | B1 |
6594537 | Bernstein et al. | Jul 2003 | B1 |
6605213 | Ammann et al. | Aug 2003 | B1 |
6607103 | Gerenraich et al. | Aug 2003 | B2 |
6632598 | Zhang et al. | Oct 2003 | B1 |
6635225 | Thiem et al. | Oct 2003 | B1 |
6656428 | Clark et al. | Dec 2003 | B1 |
6673620 | Loeffler et al. | Jan 2004 | B1 |
6703247 | Chu | Mar 2004 | B1 |
6707873 | Thompson et al. | Mar 2004 | B2 |
6720888 | Eagleson et al. | Apr 2004 | B2 |
6729502 | Lewis et al. | May 2004 | B2 |
6735531 | Rhett et al. | May 2004 | B2 |
6746851 | Tseung et al. | Jun 2004 | B1 |
6758360 | Van Giezen et al. | Jul 2004 | B2 |
6783733 | Bogen et al. | Aug 2004 | B2 |
6805264 | Houvras | Oct 2004 | B2 |
6814262 | Adams et al. | Nov 2004 | B1 |
6827900 | Thiem et al. | Dec 2004 | B2 |
6827901 | Copeland et al. | Dec 2004 | B2 |
6855292 | Angros | Feb 2005 | B2 |
6855552 | Towne et al. | Feb 2005 | B2 |
6855559 | Christensen et al. | Feb 2005 | B1 |
6899283 | Ohnishi et al. | May 2005 | B2 |
6943029 | Copeland et al. | Sep 2005 | B2 |
6945128 | Ford et al. | Sep 2005 | B2 |
6991934 | Walton et al. | Jan 2006 | B2 |
6998270 | Tseung et al. | Feb 2006 | B2 |
7004356 | Sayers | Feb 2006 | B1 |
7007824 | Danby et al. | Mar 2006 | B2 |
7025937 | Plank | Apr 2006 | B2 |
7057808 | Dooling | Jun 2006 | B2 |
7070951 | Zhang et al. | Jul 2006 | B2 |
7083106 | Albany | Aug 2006 | B2 |
7118918 | Copeland et al. | Oct 2006 | B2 |
7156814 | Williamson et al. | Jan 2007 | B1 |
7165722 | Shafer et al. | Jan 2007 | B2 |
7169601 | Northrup | Jan 2007 | B1 |
7178416 | Whelan et al. | Feb 2007 | B2 |
7179424 | Williamson, IV et al. | Feb 2007 | B2 |
7187286 | Morris et al. | Mar 2007 | B2 |
7199712 | Tafas et al. | Apr 2007 | B2 |
7201295 | Sitzberger | Apr 2007 | B1 |
7209042 | Martin et al. | Apr 2007 | B2 |
7217392 | Bogen et al. | May 2007 | B2 |
7220589 | Richards et al. | May 2007 | B2 |
7226788 | De La Torre-Bueno | Jun 2007 | B2 |
7233250 | Forster | Jun 2007 | B2 |
7250301 | Angros | Jul 2007 | B2 |
7264142 | Py | Sep 2007 | B2 |
7270785 | Lemme et al. | Sep 2007 | B1 |
7275682 | Excoffier et al. | Oct 2007 | B2 |
7278554 | Armstrong | Oct 2007 | B2 |
7294478 | Hinchcliffe | Nov 2007 | B1 |
7303725 | Reinhardt et al. | Dec 2007 | B2 |
7314238 | Robert | Jan 2008 | B2 |
7323491 | Lohray et al. | Jan 2008 | B2 |
7338803 | Mizzer et al. | Mar 2008 | B2 |
7382258 | Oldham et al. | Jun 2008 | B2 |
7395974 | Albany | Jul 2008 | B2 |
7400983 | Feingold et al. | Jul 2008 | B2 |
7405056 | Lam et al. | Jul 2008 | B2 |
7425306 | Kram | Sep 2008 | B1 |
7435381 | Pugia et al. | Oct 2008 | B2 |
7435383 | Tseung et al. | Oct 2008 | B2 |
7468161 | Reinhardt et al. | Dec 2008 | B2 |
7470401 | Morales | Dec 2008 | B2 |
7470541 | Copeland et al. | Dec 2008 | B2 |
7476362 | Angros | Jan 2009 | B2 |
7501283 | Hersch et al. | Mar 2009 | B2 |
7553672 | Bogen | Jun 2009 | B2 |
7584019 | Feingold et al. | Sep 2009 | B2 |
7593787 | Feingold et al. | Sep 2009 | B2 |
7603201 | Feingold et al. | Oct 2009 | B2 |
7622077 | Angros | Nov 2009 | B2 |
7632461 | Angros | Dec 2009 | B2 |
7639139 | Tafas et al. | Dec 2009 | B2 |
7642093 | Tseung et al. | Jan 2010 | B2 |
7651010 | Orzech et al. | Jan 2010 | B2 |
7665630 | McGill | Feb 2010 | B2 |
7718435 | Bogen et al. | May 2010 | B1 |
7722811 | Konrad et al. | May 2010 | B2 |
7735694 | Brown et al. | Jun 2010 | B2 |
7744817 | Bui | Jun 2010 | B2 |
7760428 | Sieckmann | Jul 2010 | B2 |
7806301 | Ciavarella et al. | Oct 2010 | B1 |
7838283 | Erickson et al. | Nov 2010 | B2 |
7850912 | Favuzzi et al. | Dec 2010 | B2 |
7861890 | McGill | Jan 2011 | B2 |
7880617 | Morris et al. | Feb 2011 | B2 |
7887755 | Mingerink et al. | Feb 2011 | B2 |
7897106 | Angros | Mar 2011 | B2 |
7901941 | Tseung et al. | Mar 2011 | B2 |
7922986 | Byrnard et al. | Apr 2011 | B2 |
7937228 | Feingold et al. | May 2011 | B2 |
7951612 | Angros | May 2011 | B2 |
7960178 | Key et al. | Jun 2011 | B2 |
8007720 | Angros | Aug 2011 | B2 |
8007721 | Angros | Aug 2011 | B2 |
8039262 | Konrad et al. | Oct 2011 | B2 |
8052927 | Angros | Nov 2011 | B2 |
8058010 | Erickson et al. | Nov 2011 | B2 |
8071023 | Angros | Dec 2011 | B2 |
8071026 | Rapp et al. | Dec 2011 | B2 |
8092742 | Angros | Jan 2012 | B2 |
8137619 | Ford et al. | Mar 2012 | B2 |
8142739 | Tseung et al. | Mar 2012 | B2 |
8216846 | Ljungmann et al. | Jul 2012 | B2 |
8236255 | Takayama et al. | Aug 2012 | B2 |
8257968 | Sweet et al. | Sep 2012 | B2 |
8283176 | Bland et al. | Oct 2012 | B2 |
8288086 | Metzner et al. | Oct 2012 | B2 |
8298815 | Buchanan et al. | Oct 2012 | B2 |
8315899 | Samuhel et al. | Nov 2012 | B2 |
8386195 | Feingold et al. | Feb 2013 | B2 |
8394322 | Windeyer et al. | Mar 2013 | B2 |
8394635 | Key et al. | Mar 2013 | B2 |
8396669 | Cocks | Mar 2013 | B2 |
8486714 | Favuzzi et al. | Jul 2013 | B2 |
8529836 | Winther et al. | Sep 2013 | B2 |
20010044603 | Harold | Nov 2001 | A1 |
20020013194 | Kitano et al. | Jan 2002 | A1 |
20020079318 | Wurzinger | Jun 2002 | A1 |
20020110494 | Lemme et al. | Aug 2002 | A1 |
20020114733 | Copeland et al. | Aug 2002 | A1 |
20020182115 | Aghassi et al. | Dec 2002 | A1 |
20020192806 | Custance et al. | Dec 2002 | A1 |
20030100043 | Kalra et al. | May 2003 | A1 |
20030157545 | Jevons et al. | Aug 2003 | A1 |
20030203493 | Lemme et al. | Oct 2003 | A1 |
20040033163 | Tseung et al. | Feb 2004 | A1 |
20040033169 | Shah | Feb 2004 | A1 |
20040091395 | Ward et al. | May 2004 | A1 |
20040120862 | Lang et al. | Jun 2004 | A1 |
20040191128 | Bogen et al. | Sep 2004 | A1 |
20040197230 | Lemme et al. | Oct 2004 | A1 |
20040266015 | Favuzzi et al. | Dec 2004 | A1 |
20050019902 | Mathies et al. | Jan 2005 | A1 |
20050035156 | Hersch et al. | Feb 2005 | A1 |
20050064535 | Favuzzi et al. | Mar 2005 | A1 |
20050135972 | Lemme et al. | Jun 2005 | A1 |
20050150911 | Bach | Jul 2005 | A1 |
20050153453 | Copeland et al. | Jul 2005 | A1 |
20050164374 | Kram | Jul 2005 | A1 |
20050186114 | Reinhardt et al. | Aug 2005 | A1 |
20050191214 | Tseung et al. | Sep 2005 | A1 |
20050250211 | Reinhardt et al. | Nov 2005 | A1 |
20050281711 | Testa et al. | Dec 2005 | A1 |
20060019332 | Zhang et al. | Jan 2006 | A1 |
20060040341 | Bland et al. | Feb 2006 | A1 |
20060045806 | Winther et al. | Mar 2006 | A1 |
20060063265 | Welcher et al. | Mar 2006 | A1 |
20060088928 | Sweet et al. | Apr 2006 | A1 |
20060088940 | Feingold et al. | Apr 2006 | A1 |
20060105359 | Favuzzi et al. | May 2006 | A1 |
20060120921 | Elliot et al. | Jun 2006 | A1 |
20060127283 | Tseung et al. | Jun 2006 | A1 |
20060134793 | Key et al. | Jun 2006 | A1 |
20060147351 | Falb et al. | Jul 2006 | A1 |
20060148063 | Fauzzi et al. | Jul 2006 | A1 |
20060151051 | Py et al. | Jul 2006 | A1 |
20060169719 | Bui | Aug 2006 | A1 |
20060171857 | Stead et al. | Aug 2006 | A1 |
20060172426 | Buchanan | Aug 2006 | A1 |
20060190185 | Ford et al. | Aug 2006 | A1 |
20060191952 | Kalra et al. | Aug 2006 | A1 |
20060239858 | Becker | Oct 2006 | A1 |
20060252025 | Nitta et al. | Nov 2006 | A1 |
20060263268 | Tseung et al. | Nov 2006 | A9 |
20060265133 | Cocks et al. | Nov 2006 | A1 |
20060269985 | Kitayama | Nov 2006 | A1 |
20070010912 | Feingold et al. | Jan 2007 | A1 |
20070038491 | Samuhel et al. | Feb 2007 | A1 |
20070068969 | Orzech et al. | Mar 2007 | A1 |
20070160494 | Sands | Jul 2007 | A1 |
20070270714 | Cushner et al. | Nov 2007 | A1 |
20070272710 | Bui | Nov 2007 | A1 |
20080035677 | Daansen | Feb 2008 | A1 |
20080102006 | Kram et al. | May 2008 | A1 |
20080118378 | Baron et al. | May 2008 | A1 |
20080135583 | Caswell et al. | Jun 2008 | A1 |
20080215625 | Veitch et al. | Sep 2008 | A1 |
20080217246 | Benn et al. | Sep 2008 | A1 |
20080226508 | Byrnard et al. | Sep 2008 | A1 |
20080235055 | Mattingly et al. | Sep 2008 | A1 |
20080254503 | Ljungmann et al. | Oct 2008 | A1 |
20080286753 | Erickson et al. | Nov 2008 | A1 |
20080305515 | Burgart et al. | Dec 2008 | A1 |
20090004691 | Erickson et al. | Jan 2009 | A1 |
20090028757 | Lihl et al. | Jan 2009 | A1 |
20090241751 | Walter | Oct 2009 | A1 |
20090308887 | Woo et al. | Dec 2009 | A1 |
20090325309 | Favuzzi et al. | Dec 2009 | A1 |
20100017030 | Feingold et al. | Jan 2010 | A1 |
20100028978 | Angros | Feb 2010 | A1 |
20100068757 | Angros | Mar 2010 | A1 |
20100089921 | Ellenkamp-Van Olst et al. | Apr 2010 | A1 |
20100099133 | Egle et al. | Apr 2010 | A1 |
20100178668 | Elliot et al. | Jul 2010 | A1 |
20110079615 | Ophardt et al. | Apr 2011 | A1 |
20110167930 | Feingold et al. | Jul 2011 | A1 |
20110176977 | Tseung et al. | Jul 2011 | A1 |
20110269238 | Key et al. | Nov 2011 | A1 |
20120003679 | Haberkorn | Jan 2012 | A1 |
20120179293 | Feingold et al. | Jul 2012 | A1 |
20120309044 | Ljungmann et al. | Dec 2012 | A1 |
20130029409 | Sweet et al. | Jan 2013 | A1 |
20130084567 | Buchanan et al. | Apr 2013 | A1 |
20130203103 | Feingold et al. | Aug 2013 | A1 |
20130217108 | Key et al. | Aug 2013 | A1 |
Number | Date | Country |
---|---|---|
2390207 | Aug 2000 | CN |
385159 | Nov 1923 | DE |
3902476 | Aug 1990 | DE |
0185330 | Jun 1986 | EP |
557871 | Sep 1993 | EP |
1028320 | Aug 2000 | EP |
2037255 | Jul 1980 | GB |
61200966 | Dec 1986 | JP |
3148067 | Jun 1991 | JP |
6510860 | Dec 1994 | JP |
10501167 | Feb 1998 | JP |
11170558 | Jun 1999 | JP |
11258243 | Sep 1999 | JP |
2000167318 | Jun 2000 | JP |
2001-095495 | Apr 2001 | JP |
2001509727 | Jul 2001 | JP |
2001512823 | Aug 2001 | JP |
2001522033 | Nov 2001 | JP |
2002507738 | Mar 2002 | JP |
2002522065 | Jul 2002 | JP |
2003057246 | Feb 2003 | JP |
2004533605 | Nov 2004 | JP |
WO-9508774 | Mar 1995 | WO |
WO-9526796 | Oct 1995 | WO |
WO-9639260 | Dec 1996 | WO |
WO-9908090 | Feb 1999 | WO |
WO-9922867 | May 1999 | WO |
WO-0009650 | Feb 2000 | WO |
WO-0012994 | Mar 2000 | WO |
WO-0141918 | Jun 2001 | WO |
WO-02072264 | Sep 2002 | WO |
WO-03054553 | Jul 2003 | WO |
WO-03091710 | Nov 2003 | WO |
WO-03106033 | Dec 2003 | WO |
WO-2004059288 | Jul 2004 | WO |
WO-2004074847 | Sep 2004 | WO |
WO-2005000731 | Jan 2005 | WO |
Entry |
---|
English Translation of DE385159, 2 Pages. |
Sakura Finetek, Australian Office Action mailed Jan. 3, 2012 for 2007267881., 5 pages. |
Sakura Finetek, Chinese office action dated Jan. 18, 2012 for CN 200780019204.8, 14 pages. |
Sakura Finetek, Non-Final Office Action mailed Mar. 27, 2012 for U.S. Appl. No. 11/441,668., 15 pages. |
Sakura Finetek, Japanese Office Action mailed Jan. 30, 2012 for Application No. 2009-512152, 6 pages. |
Sakura Finetek, Non-final Office Action mailed Aug. 2, 2011 for U.S. Appl. No. 11/441,668., 17 pages. |
Sakura Finetek U.S.A., Third Office Action mailed Jun. 9, 2011 for CN Appln. No. 200610007365.2, 6 pgs. |
Sakura Finetek U.S.A., Sixth Office Action mailed Mar. 31, 2011 for Chinese Appln. No. 200610007366.7, 6 pgs. |
Sakura Finetek, Final Office Action mailed May 1, 2012 for U.S. Appl. No. 11/349,663. |
Sakura Finetek, Extended Search Report mailed Jun. 4, 2012 for European App No. 12153210.5, 6 pages. |
Sakura Finetek., Final Office Action mailed Aug. 31, 2011 for U.S. Appl. No. 11/349,663. |
Sakura Finetek., Non-Final Office Action mailed Jan. 31, 2012 for U.S. Appl. No. 11/349,663. |
Sakura Finetek, Japanese Office Action mailed Mar. 1, 2012 for App No. 2008-141687, 8 pages. |
Sakura Finetek, Final Office Action mailed Mar. 5, 2012 for U.S. Appl. No. 11/349,663. |
Sakura Finetek, Chinese Office Action mailed Feb. 16, 2012 for Chinese App 200610004479.1, 23 pages. |
Sakura Finetek, CN Office Action dated Mar. 31, 2011 for Chinese Appln. No. 200610007366.7, 6 pages. |
Sakura Finetek, Final Office Action mailed Jan. 19, 2011 for U.S. Appl. No. 11/349,663. |
Sakura Finetek, Japanese Office Action dated Jul. 19, 2012 for Appln. No. 2009-512152. |
Sakura Finetek, Office Action dated Jun. 9, 2011 for China Application 2006100073652. |
Sakura Finetek, Japanese office action dated Jul. 6, 2011 for JP Appln. No. 2008-141687. |
Sakura Finetek, First office action mailed Mar. 31, 2011 for EP Appln. No. 04780745.8, 3 pgs. |
Sakura Finetek, Office Action mailed Jun. 25, 2012; European Appln No. 07795292.7, 6 pages. |
Sakura Finetek, Non-final Office Action mailed Feb. 18, 2011 for U.S. Appl. No. 11/441,668. |
Sakura Finetek U.S.A. Inc., CN Office Action dated May 10, 2010 for Chinese Appln. No. 200610007366.7. |
Sakura Finetek U.S.A. Inc., Final office action dated May 25, 2010 for U.S. Appl. No. 11/441,668. |
Sakura Finetek U.S.A., Inc. , Office Action mailed Feb. 26, 2009 for U.S. Appl. No. 11/441,668. |
Sakura Finetek U.S.A., Inc., CN Office Action dated May 8, 2009 for Chinese Appln. No. 200610007366.7. |
Sakura Finetek U.S.A., Inc., European Office Action dated Mar. 18, 2008 for EP Appln No. 06101497.3. |
Sakura Finetek U.S.A., Inc., Office Action dated Jul. 21, 2010; Australian Application No. 2008229802. |
Sakura Finetek U.S.A., Inc., Office Action dated Aug. 13, 2010; Australian Appln No. 2006200549. |
Sakura Finetek U.S.A., Inc., Office Action mailed Oct. 11, 2010; European Appln No. 07795292.7-1234. |
Sakura Finetek U.S.A., Inc., EP Office Action data Jun. 27, 2008, EP Appln No. 06101498.1, 9 pages. |
Sakura Finetek U.S.A., Inc., EP Search Report dated Jun. 20, 2006, EP Appln No. 06101498.1, 6 pages. |
Sakura Finetek U.S.A., Inc., EP Search Report dated Jun. 20, 2006, EP Appln No. 06101497.3, 6 pages. |
Sakura Finetek U.S.A., Inc., EP Search Report mailed Dec. 18, 2006, EP Appln No. 06101495.7, 10 pages. |
Sakura Finetek U.S.A., Inc., JP Office Action dated Dec. 26, 2008, Japanese Appln No. 2006-34547. |
Sakura Finetek U.S.A., Inc., JP Office Action dated Nov. 30, 2007, Japanese Appln No. 2006523317, 9 pages. |
Sakura Finetek U.S.A., Inc., Office Action mailed Jul. 23, 2007, EPO Application No. 06101495.7. |
Sakura Finetek U.S.A., Inc., PCT Search Report dated Aug. 8, 2006, PCT Appln No. PCT/US04/25960, 10 pages. |
Sakura Finetek U.S.A., Inc., PCT Search Report mailed Nov. 16, 2007, PCT Appln No. PCT/US2007/012400, 13 pages. |
Shi, Shan-Rong, et al., “Enhancement of immunochemical staining in aldehyde-fixed tissue”, Reissue U.S. Appl. No. 11/249,180, filed Oct. 11, 2005. |
Zhang, Guangrong, et al., “Deparaffinization compositions and methods for their use”, Reissue U.S. Appl. No. 11/250,142, filed Oct. 13, 2005. |
Sakura Finetek, Australian Office Action mailed Sep. 21, 2012 for Application No. 2007267881. |
Sakura Finetek U.S.A., Inc., Non-Final Office Action mailed Nov. 29, 2012 for U.S. Appl. No. 13/238,511. |
Sakura Finetek USA, Inc., Non-Final Office Action mailed Jan. 25, 2013 for U.S. Appl. No. 13/238,575. |
Sakura Finetek USA, Inc., Canadian Office Action dated Feb. 25, 2013 for Appln. No. 2652898. |
Sakura Finetek USA, Inc., Final Office Action dated Apr. 5, 2013 for U.S. Appl. No. 13/238,511. |
Number | Date | Country | |
---|---|---|---|
20120193376 A1 | Aug 2012 | US |