Patent Grant
7472803
Diagnostic laboratories have long used archaic, manual, and cumbersome techniques that often lead to poorly reproducible and inaccurate results. Even today, most molecular and cell-based diagnostic systems use outdated and non-integrated technologies unable to cost-effectively perform massively parallel-scale analyses. System capabilities are further stressed by the genomics revolution that has accelerated demand for potential markers for use in target validation in drug discovery and development. Consequently, additional automation and parallelism are sought to enable efficient specimen handling, processing and analysis.
With the emphasis on lowering costs throughout the health-care industry, efforts are continuously being made to reduce the amount of labor involved, and the associated cost. The primary cost component of preparing and staining a specimen on a slide is labor. Accordingly, many efforts have been devoted to reduce the labor cost component of preparing a slide.
Microscope slide covers are typically thin, fragile, and have relatively accurately plane polished surfaces so that when stacked together they tend to adhere to one another and are difficult to separate. Separation can only reliably be accomplished by sliding one over its immediate neighbor, but this in practice is not easy to accomplish because groups of the slips tend to slide as packs from an end of a stack of such slips and the extraction of a single slip from such a pack requires care and dexterity. Where large numbers of covers have to be routinely applied to microscope slides, this operation can represent a significant proportion of the total workload of the technicians.
In accordance with an embodiment, an automated dispensing assembly includes a base, and a shuttle mounted in the base and movable under automated control between a loading position and a dispensing position. The shuttle includes a cavity configured to carry an object, such as cover. The depth of the cavity in the shuttle is approximately the same as the thickness of one of the objects but less than two objects. A storage module is mounted proximate the shuttle. The storage module is configured to store a plurality of objects and includes an opening exposing the next object to be dispensed. The cavity is positioned adjacent the opening in the storage module in the loading position and an edge of the cavity separates the object to be dispensed from the other objects in the storage module as the shuttle moves to the dispensing position.
Embodiments of the invention relating to both structure and method of operation, may best be understood by referring to the following description and accompanying drawings whereby:
Referring to
Actuator 106 includes an extendable and retractable arm 110 coupled to shuttle 102 via link 112. In the embodiment shown in
Shuttle 102, storage module 104, and actuator 106 can be coupled to base 114. In the embodiment shown, storage module 104 is fastened to base 106, and shuttle 102 is positioned to move relative to storage module 104 by moving back and forth in channel 116 in base 114. In still further embodiments, both storage module 104 and shuttle 102 can be configured to move relative to one another. Channel 116 can be configured with an elongated opening 502 (
Base 114 and/or channel 116 can include means for reducing friction in the movement of shuttle 102 (and/or storage module 104). For example, in some embodiments, base 114 and/or shuttle 102 can be fabricated with oil-impregnated material to reduce the coefficient of friction between moving surfaces. Channel 116 and/or shuttle can also include one or more rails 118 to reduce the amount of surface area in contact between channel 116 and shuttle 102. In some embodiments, rails 118 are configured as slightly raised fillets along at least a portion of the junction of the sides and bottom of channel 116. In other embodiments, one or more rails 118 can be configured in the central portion of channel 116. In such embodiments, one or more corresponding slots (not shown) can be included on the bottom of shuttle 102 to engage the rails 118. In further embodiments, ball-bearings or other suitable friction-reducing components can be used instead of or in addition to rails 118 to facilitate movement between storage module 104, shuttle 102, base 114, and channel 116.
One or more alignment guides 124 can also be included on shuttle 102, channel 116, storage module 104, or other suitable component in apparatus 100 to help maintain cavity 202 in alignment with respect to channel 116 and/or storage module 104. For example, shuttle 102 can include alignment guide 124 configured as a slot that engages guide member 702 (
Apparatus 100 can include one or more sensors 120 that are adapted to indicate to automated controller 122 whether a cover is available to be retrieved from cavity 202 by a cover handling system. For example, sensor 120 can detect and generate signals indicating the position of shuttle 102, link 112, and/or arm 110 of actuator 106. In the embodiment shown, sensor 120 is an optical sensor positioned at one of channel 116. One component of optical sensor emits a light that is detected by another sensor component a short distance away. Tab 206 can be positioned on one end of shuttle 102 to move into the space between sensor components and prevent the light from being detected when shuttle 102 moves to the dispensing position. Interruption of the light causes a change in the signal sent to controller 122 by optical sensor 120.
Controller 122 includes a computer processor with continuously-executing logic instructions that determine when the signal from optical sensor 120 changes to a state that indicates when a cover 204 is available in cavity 202. Controller 122 can then generate signals to operate a cover handling system (not shown) by retrieving cover 204 and place cover 204 over a prepared specimen, such as a biological sample on a microscope slide. Cavity 202 can include an opening 206 to help prevent a vacuum from forming between cover 204 and cavity 202, thereby facilitating removal of cover 204 from cavity 202. Opening 206 can also prevent a vacuum from forming and causing an error condition when a cover handling device attempts to use suction to pick up a cover 204, and cover 204 is not present in cavity 202.
In some embodiments a cover handling system can be equipped to clean, add substance(s), create a boundary, or otherwise prepare cover 204 before retrieving cover 204 and placing cover 204 over a specimen. Additionally, cavity 202 and/or cover 204 can include detectable components to enable the cover handling system to determine the position and/or orientation of the cover 204 in cavity 202. For example, the cover handling system can include sensors that detect a pre-determined pattern of paint or other substance that can be included on the surface of cavity 202 and/or cover 204.
The cover handling system can send one or more signals to controller 122 indicating the processing state of cover 204, including when cover 204 has been removed from cavity 202. Controller 122 can be coupled to send drive signals to actuator 106 to move shuttle 102 (and/or storage module 104) to load another cover 204 in cavity 202, as required.
Actuator 106 can send feedback signals to controller 122 indicating the position of arm 110. Controller 122 can use the position information to determine when to stop sending drive signals to actuator 106. For example, controller 122 can be programmed with, or have access to, information regarding the size, shape, orientation, and/or location of components in apparatus 100. Logic instructions can be included in controller 122 to determine when cavity 202 is positioned so that another cover 204 can be loaded in cavity 202. Sensor 120 will typically also change state when tab 206 is moved from between sensor components. Controller 122 can use the changed state information to determine that shuttle 102 has moved.
Other suitable means for controlling the position of moving components in apparatus 100 can be included, such as mechanical stop(s), and/or sensors on link 112 or other suitable portions of apparatus 100. For example, cavity 202 can include a weight and/or optical sensor that detects when a cover 204 is in cavity 202 and provides a signal to controller 122 indicating such a condition. Signals between components on apparatus 100 can be transmitted and received via wireless and/or wired communication interfaces. Controller 122 can also interface to a central control unit as well as one or more other component controllers that operate other components in an automated processing system.
Referring now to
As shown in
In the embodiment shown, storage module 104 includes two other opposing sidewalls 612, which, along with sidewalls 608, form a square, rectangular, or other suitably shaped inner cavity 602 where covers 204 can be placed.
Note that multiple cover storage modules 104 configured to accommodate different sizes and shapes of covers 204 can be provided, along with corresponding shuttles 102 with appropriately configured cavities 202. Note further that covers 204 can be fed through storage modules 104 using gravitational and/or applied force. For example, storage module 104 can be spring loaded to apply suitable pressure to the top of a stack of covers 204.
Storage module 104 and shuttle 102 can be oriented in any suitable direction. In the embodiments shown in
In some embodiments, slot 812 can be angled to place cover 810 in a more accessible location/orientation. The sidewalls of cavity 804 can be tapered and cavity 804 can include an opening to facilitate releasing cover 810. Shuttle 802 can return to the loading position once cover 810 is dispensed into slot 812. Note that slot 812 can be configured so that a portion of cover 810 can be grasped from two sides and/or along two edges. Such a configuration allows cover 810 to be grasped by a mechanical gripper as well as other devices such as a suction cup or electrostatic device. Note also that storage module 806 includes means for applying force, shown as a spring-loaded cap 818, to move the vertical stack of covers 810 toward shuttle 802 without binding movement of shuttle 802.
In other embodiments, components in apparatus 100 and 800 can be arranged so that storage modules 104, 806 move relative to stationary shuttles 102, 802. Further, any suitable type and number of actuators 106 can be used to move component(s) in apparatus 100, 800, such as actuators that are driven pneumatically, hydraulically, electromagnetically, piezoelectrically, mechanically, and/or electro-mechanically, among others.
Shuttle 102 can also be configured with two or more cavities 202, 804. Further, shuttle 102, 802 can be implemented using alternative structures, such as a conveyer belt with a series of cavities 202, 804 that move past storage module 104, 806 and dispense individual or multiple covers 204, 810. For example, the length of slot 812 can be dimensioned to accommodate a series of dispensed covers 810, one after another, that are available for use by one or more automated sample processing systems. The movement of shuttle 802 can move the series of covers 810 along the slot as each cover 810 is dispensed.
Referring to
In some embodiments, sample processing system 900 includes a platform 930 and rack 942 that can be held by the platform 930 or coupled to the platform 930 and adapted to hold multiple reagent containers 944. Rack 942 can also be configured with one or more individually controllable heating elements to maintain the reagents at different selected temperatures. Sample processing system 900 can also be configured to independently maintain a plurality of specimens 902 at different environmental conditions, such as different temperature, light, and/or humidity levels.
In some embodiments, robotic device 940 is mounted on a movable arm 914 that can be positioned in one, two, and/or three dimensions relative to platform 930. Robotic device 940 can be configured to accept different types of attachments to perform various different operations and functions, such as gripping and releasing covers; positioning and removing a cover from a specimen; loading and dispensing substances; loading and dispensing sealant to create a barrier around a specimen; mixing specimen contents; washing a specimen 902; and drying a specimen 902, among others.
In some embodiments, robotic device 940 includes a cover handling device 906 adapted to dispense covers of one or more sizes on reservoirs to form the specimens 902. Cover dispensing apparatus 100, 800 can be included in system 900 to enable covers to be automatically dispensed one at a time. Cover handling device 906 can be adapted to retrieve loose covers from a cavity 202 of cover dispensing apparatus 100 and/or other suitable location in or around cover dispensing apparatus 100, 800 or sample processing system 900. Robotic head 940 can further include a metering pump, a vacuum pump, cable train and printed circuit board containing components and devices for controlling robotic head 940.
Storage module 104 can be refillable and constructed from aluminum, stainless steel, plastic, or other suitable material.
Sample processing system 900 can be configured with one or more sensors to detect the position and orientation of the covers on the specimens 902 or other locations in sample processing system 900. In some embodiments, one or more of the sensors can be located on or in the movable arm 914 and/or robotic device 940. The sensors can also be located in a stationary position, in addition to, or instead of, being co-located with the movable arm 914 and/or robotic device 940.
In some embodiments, the sample processing system 900 can include a substance dispensing device 904 that is adapted to dispense one or more substances, such as a reagent, on specimens 902. Cover handling device 906 can operate in combination with the substance dispensing device 904 to automate placement and removal of the covers over specimens at the appropriate time(s) during processing.
Controller 908 can be included in the sample processing system 900 to execute logic instructions that control operations and functionality of components in the sample processing system 900, such as substance dispensing device 904, cover dispensing apparatus 100, and cover handling device 906. Controller 908 can also be adapted to operate components in sample processing system 900 to control the microenvironment of specimens 902. Programmed logic instructions associated with particular protocols and processes can specify actions to be taken at particular times such as placing a cover on a specimen 902, removing a cover from specimen 902, heating or cooling a reagent, dispensing a specified reagent to specimen 902; heating or cooling specimen 902, and/or washing specimen 902 and/or cover, among others. For example, a particular process can be associated with a particular specimen 902 or group of specimens 902 via a user interface. The process can specify dispensing a first reagent to a reservoir containing a sample, placing and sealing a cover on specimen 902, removing the cover from specimen 902, washing the reagent from specimen 902, drying specimen 902, dispensing a second selected reagent to specimen 902, again covering specimen 902, and selectively repeating the various actions.
Referring to
When vacuum sensor 1028 indicates increased pressure, logic in controller 908 assumes that a cover is obstructing an opening in effector 1024 through which vacuum pressure is exerted by the vacuum pump 1030. After a cover is placed in position, vacuum pump 1030 is turned off and air valve 1034 opens, enabling positive air pressure to push the cover off vacuum pad effector 1024. The operation prevents the cover from adhering to vacuum pad effector 1024.
In the various embodiments, controller 908 controls operation of robotic head 1004 and effectors 1006, 1024, 1042, 1062. Logic instructions executed by controller 908 can be adapted to control placement and removal of covers 204 from specimens in a manner that minimizes formation of air bubbles and disturbance to the specimen. For example, robotic head 1004 and effectors 1006, 1024, 1042, 1062 can be operated to place a dispensed cover 204 on a specimen by starting on one edge or corner and slowly lowering the cover 204 to minimize air bubbles. Various processes to remove covers 204 can be used after completion of the reaction, e.g., peeling off the edge of the cover 204 from the specimen, followed by blowing or washing off the specimen and/or cover 204, or disposing of used covers 204 into a waste tray.
In some embodiments, effector 1006, 1024, 1042, 1062 and robotic head 1004 may be configured to move independently of one another. Note that other suitable devices can be utilized, in addition to, or instead of effectors 1006, 1024, 1042, 1062 to handle covers 204.
Note also that other mechanisms can be used to dispense covers 204. For example, one or more belts, pads, or rollers mounted on a spindle or shaft that is driven by a suitable motor, such as a stepper motor, servo motor, or DC motor, can be used to dispense covers 204 one at a time instead of shuttle 102. The belts/rollers/pads can be fabricated from rubber, plastic, glass, or other suitable material. The belts/rollers/pads can include sprockets that engage holes on the edges of covers 204 to move covers 204 one at a time as the spindle rotates. Covers 204 can be dispensed one at a time onto a platform, into a caddy, into a container or other suitable location as the shaft rotates.
In some embodiments, a rack of covers 204 can be inclined and configured to allow one cover 204 at a time to be dispensed from the stack of covers 204. Covers 204 with different thickness and shapes can be included in such stacks.
In other embodiments, needles or probes can be mounted on robotic device 940 that can be manipulated to lift and lower covers 204 via holes in the edges of covers 204. The needles can be inserted in the holes to pick up and carry a cover 204 to a desired specimen. The needles can be moved in one or more dimension by any suitable actuator, motor, or other mechanism.
In still further embodiments, covers 204 can be placed in a round tray (carousel) that can include sockets to retain covers 204. The tray can driven to move in a circular motion by a motor or other suitable mechanism so that one or more covers 204 can be accessed by effectors 1006, 1024, 1042, 1062 at a time.
In other embodiments, covers 204 can be included in an enclosure mounted on robotic device 940. One or more covers 204 at a time can be dispensed from the enclosure onto a specimen. Covers 204 can be ejected from a slot in the enclosure by a suitably shaped piston or other mechanism.
Covers 204 can be configured in a continuous roll of plastic or other suitable material that may be peeled off by an electromechanical gripper or other suitable device. The roll of cover material can be dispensed from robotic device 940 or other suitable location in system 900. Covers 204 may be perforated to facilitate removal from the roll, or a cutting edge or device can be included on the robotic device 940 or other suitable location to cut a desired length of cover material. The dispensing can be controlled by a laser sensor senses the length of one cover 204 at a time, a mechanical ejector that is geared to dispense a measured portion of cover material, or other suitable mechanism.
Controller 908 can be adapted to automatically mount and dismount enclosures containing cover 204, as well as rolls of cover material, on robotic device 940. Controller 908 can further be adapted to sense or count the number of covers remaining or dispensed to determine when the enclosure is empty and needs to be replaced. The replacement enclosures can be provided in a location in system 900 that is accessible by robotic device 940. Empty enclosures can be discarded in a waste bin provided with system 900 or other suitable location. Controller 908 can be configured to issue a re-fill alert message when a predetermined amount and/or all of the covers 204 have been dispensed.
Individual covers 204 can be spaced in a rack or separated by a suitable spacer, such as a thin piece of paper, to help prevent covers 204 from adhering to one another. Covers 204 can include chemical coatings (entirely or partially, e.g. paint lines on the edges) or other separators that allow removal of one cover 204 at a time from a stack with an effector 1006, 1024, 1042, 1062. Stacks of covers 204 can also be provided in a variety of configurations such as a continuous strip of fan-folded covers 204 where the edges of covers 204 are at least partially connected to one another. The connection between the edges can be separated by force from effectors 1006, 1024, 1042, 1062, or other suitable separating/cutting device.
While cover dispensing apparatus 100, 800 can be used to dispense covers 204 in automated sample processing system 900, dispensing apparatus 100, 800 can also be adapted to dispense objects other than cover slips, such as coins, and other substantially flat objects. Virtually any size, shape, and number of objects can be dispensed, one or more at a time, for access by an automated processing machine or even by a human.
While the present disclosure describes various embodiments, these embodiments are to be understood as illustrative and do not limit the claim scope. Many variations, modifications, additions and improvements of the described embodiments are possible. For example, those having ordinary skill in the art will readily implement the steps necessary to provide the structures and methods disclosed herein, and will understand that the process parameters, materials, and dimensions are given by way of example only. The parameters, materials, and dimensions can be varied to achieve the desired structure as well as modifications, which are within the scope of the claims. For example, although particular systems are described that include many novel features, each of the different features may be implemented in a system that either includes or excludes other features while utility is maintained.
In the claims, unless otherwise indicated the article “a” is to refer to “one or more than one”.
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| Number | Date | Country | |
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