HK1208261B

HK1208261B - Cartridge for dispensing a fluid

Info

Publication number: HK1208261B
Application number: HK15108757.9A
Authority: HK
Inventors: Christoph Böhm; Peter Kupser; Norbert Oranth; Jürgen Spinke; Thorsten BRÜCKNER; Timo Klein
Original assignee: F. Hoffmann-La Roche Ag
Priority date: 2012-05-08
Filing date: 2012-11-15
Publication date: 2019-05-10

Description

Cartridge for dispensing a fluid

Technical Field

The present invention relates to a cartridge for dispensing a fluid. The invention further relates to an automatic analyzer for dispensing fluids using the cartridge.

Background

In medical laboratories, in vitro diagnostics are typically performed on biological samples, such as blood, urine, plasma, and saliva. Such tests may be performed manually using a pipette, or may be performed using an automated analyzer. An automated analyzer may automatically add a reagent to a biological sample and may measure one or more parameters of the biological sample during analysis. Automatic analyzers are known in the prior art. For example, european patent EP 1959257 a2 discloses an automatic analyzer including a cartridge holding mechanism for holding a plurality of cartridges.

US 7,955,302B 2 discloses a dosing device for a fluid administration system comprising a dosing unit having a variable volume and at least one opening in fluid connection with the variable volume.

Disclosure of Invention

The invention provides a cartridge for dispensing a fluid and an automatic analyzer in the independent claims. Embodiments are described in the dependent claims.

The present invention provides a cartridge for dispensing a fluid. In some embodiments, the cartridge comprises a rotary valve that can be moved in a circumferential manner to place the pumping chamber tubing from the pumping chamber. Rotation of the rotary valve enables the pumping chamber conduit to be connected to one of a plurality of other conduits. The pumping chamber is formed by a cavity within the rotary valve and by a plunger operable to vary the volume of the pumping chamber. In some other embodiments, a linear valve is used to place the pumping chamber tubing.

The cartridge includes a container for storing the fluid and an outlet conduit for dispensing the fluid. A reservoir conduit connects the reservoir and the valve. In some embodiments, an outlet guide conduit connects the outlet nozzle to the valve. When the valve is moved at different positions, the pumping chamber conduit can be placed either at the container conduit or at the outlet conduit. In some embodiments, the valve and the plunger may be capable of being operated or actuated independently of each other. This embodiment of the cartridge may have the advantage that it can be operated such that the cartridge does not lose any fluid or that fluid loss due to priming can be reduced.

As used herein, a controller includes a device, machine, or apparatus for controlling the operation and/or functioning of one or more other devices. Examples of controllers may include, but are not limited to: computers, processors, embedded systems or controllers, programmable logic controllers, and microcontrollers. As used herein, a "computing device" or "computer" includes any device that includes a processor. As used herein, a "processor" includes an electronic component capable of executing a program or machine-executable instructions.

As used herein, a "computer-readable storage medium" includes any tangible storage medium that can store instructions executable by a processor of a computing device. The computer-readable storage medium may be referred to as a computer-readable non-transitory storage medium.

"computer memory" or "memory" is an example of a computer-readable storage medium. Computer memory is any memory that has direct access to a processor or other controller. "computer memory" or "memory" is an example of a computer-readable storage medium. Computer memory is any non-volatile computer-readable storage medium.

As used herein, a "user interface" is an interface that allows a user or operator to interact with a computer or computer system.

As used herein, "hardware interface" includes an interface that enables a processor or other controller to interact with and/or control an external computing device and/or apparatus. The hardware interface may allow the processor to send control signals or instructions to an external computing device and/or apparatus. The hardware interface may enable a processor or other controller to receive sensor data and to control the dispensing of fluid. In some embodiments, a hardware interface may be used to form a closed control loop.

In one aspect, the present invention provides a cartridge for dispensing a fluid. The cartridge includes a valve. The valve includes a pumping chamber for pumping fluid. The valve is operable to position the pumping chamber conduit. The pumping chamber conduit is connected to the pumping chamber. The valve further includes a plunger operable to vary the volume of the pumping chamber. The valve further includes a container conduit (124, 1214) for connecting the container to the valve, wherein the valve is operable to position the pumping chamber conduit for connection to the container conduit. The valve further comprises an outlet conduit for dispensing the fluid. The rotary valve is further operable to rotate the pumping chamber conduit to connect with the outlet conduit.

In another aspect, the present invention provides a cartridge for dispensing a fluid. The cartridge includes a rotary valve. The rotary valve comprises a pumping chamber for pumping the fluid. The rotary valve is operable to rotate the pumping chamber conduit. The pumping chamber conduit is connected to the pumping chamber. In other words, there is a rotary valve having a pumping chamber conduit connected to a pumping chamber therein. By rotating the rotary valve, the pumping chamber conduit can be rotated into different positions, thereby allowing the pumping chamber to be connected to other conduits.

The cartridge further includes a plunger operable to vary the volume of the pumping chamber. The rotary valve and the plunger are operable to be actuated independently. In other words, the plunger and the rotary valve can be operated such that the plunger can be used to change the volume of the pumping chamber without affecting the position of the rotary valve, and vice versa. This enables a larger set of pumping actions to be performed by the pumping chamber.

The cartridge further comprises a container for storing the fluid. The container can be constructed in a variety of ways. In some embodiments, the container may be a hard-walled chamber, preferably made of plastic using an injection molding or thermoforming process. In some embodiments, the container may be a chamber with flexible walls. In some embodiments, the container can be a pouch or bladder. In other embodiments, the container can be a pouch or bladder supported by an external reservoir. In other embodiments, the container can be a tube.

The cartridge further comprises a container conduit for connecting the container to the rotary valve. The rotary valve is operable to rotate the pumping chamber conduit to connect to the container conduit. When the pumping chamber conduit is rotated to the correct position, then there is communication between the pumping chamber and the container.

The cartridge further comprises an outlet conduit for dispensing the fluid and for connecting to a rotary valve. The rotary valve is further operable to rotate the pumping chamber conduit to connect to the outlet conduit. This embodiment may have the advantage that a large variety of pumping actions can be performed by the pumping chamber by controlling the rotational position of the rotary valve and operating the plunger correctly. For example, a rotary valve may be placed such that the pumping chamber conduit is connected to the container conduit. In this case, the plunger may be used to either draw fluid from the container into the pumping chamber or may be used to pump fluid from the pumping chamber back into the container.

The present embodiment may use the pumping chamber to enable other types of actions. For example, the plunger may be used repeatedly to increase and decrease the volume of the pumping chamber when the pumping chamber conduit is aligned with or connected to the container conduit. This allows the fluids in the container to be mixed. Also, the ability to return fluid to the container can reduce the amount of fluid that is wasted.

This embodiment may also enable a so-called waste-reduced activation or waste-free activation function of the pumping chamber, whereby no, or possibly only a very small amount of fluid is wasted or discarded when the fluid is pumped out through the outlet conduit. For example, when the pumping chamber conduit is connected with the outlet conduit, the plunger may be used to reduce the volume of the pumping chamber and thereby force or dispense fluid out through the outlet conduit. During this process, it may be that fluid within the outlet conduit does not exit the outlet conduit. After the correct amount of fluid has been dispensed, a plunger may then be used to increase the volume of the pumping chamber, thereby drawing fluid that may remain within the outlet conduit back into the pumping chamber. The fluid can then be held in the pumping chamber or if the rotary valve is rotated into alignment with the container conduit, the fluid previously within the outlet conduit can be pumped back into the container.

The rotary valve may also provide a means of preventing fluid from accidentally leaking from the container. For example, in some embodiments, the rotary valve may be capable of being rotated to a position that is not aligned with either the outlet conduit or the container conduit. This may prevent fluid and/or gas from exiting the outlet conduit and/or prevent fluid and/or gas in the container from leaking or discharging into the pumping chamber.

In another embodiment, the cartridge further comprises an outlet nozzle connected to the outlet conduit. As used herein, an outlet nozzle includes a nozzle designed to minimize fluid waste and to allow the drip to drip cleanly during the dosing process. For example, in a simple tube, a drop of fluid may hang outside the nozzle after a plunger is used to reduce the volume of the pumping chamber. The shape or function of the outlet nozzle can be designed to reduce the chance of a fluid droplet hanging thereon. For example, the outlet nozzle may have a so-called duckbill shape and be a duckbill nozzle.

In other embodiments, the cassette may have additional containers and additional container conduits that enable the pumping chamber to be connected to these additional containers. Typically, a cartridge may contain only a single fluid or reagent. In some embodiments, it may be a diluent used or required for a variety of tests. There may also be a plurality of containers each connectable to a conduit that can access the pumping chamber conduit at a particular rotational position of the rotary valve.

For example, there may be two containers for many clinical tests, and two or three different fluids in different containers for immunoassays. In some variations of this embodiment, the cassette may have multiple pumping units, each of which is connected to one or more containers by its rotary valve. In this way the immunoassay is dispensed using separate pumping units and it is not mixed by the pumping process.

In another embodiment, the cartridge further comprises a return conduit connected to the container. The pumping chamber conduit is operable to receive fluid from the first portion of the container. The return conduit is operable to return fluid to the second portion of the container. The rotary valve is further operable to rotate the pumping chamber conduit to connect to the return conduit. This embodiment may be advantageous, for example, because it may reduce the effects of potentially creating air bubbles when the fluid is returned to the container. This embodiment may further have the advantage of reducing the number of bubbles in the first portion of the container by transferring the bubbles to the second portion of the container.

For example, fluid can be drawn from the container when the rotary valve is rotated such that the pumping chamber conduit is aligned with the container conduit. After a quantity of fluid has been dispensed through the outlet conduit, the rotary valve may be rotated to a position such that the pumping chamber conduit is aligned with the return conduit. The container conduit may draw fluid from one portion of the container and the return conduit is used to return fluid to a different portion of the container. For example, the two locations of the reservoir conduit and the return conduit can be sufficiently far apart that bubbles entering the reservoir through the return conduit are less likely to be drawn into the reservoir conduit as fluid is drawn from the reservoir into the pumping chamber.

In another embodiment, the cartridge further comprises an auxiliary container. The cartridge further comprises an auxiliary container conduit. The rotary valve is further operable to rotate the pumping chamber conduit to connect to the auxiliary container conduit. This embodiment may be advantageous because it may allow a second or different fluid to be stored and dispensed through the use of a cartridge, which may also allow wasted fluid to be placed in the auxiliary container.

It should be noted that by adding third containers and third container conduits, fourth containers and fourth container conduits, and the like, additional containers may be added to the cassette such that any number of containers and container conduits may be added to the cassette.

In another embodiment, the cartridge further comprises a connecting conduit. The connecting conduit is operable to transfer fluid between the auxiliary container and the container. This embodiment may be advantageous because the connecting conduit may enable the auxiliary container to be used as a location for storing fluid in order to return it to the container.

In another embodiment, the cassette comprises a membrane blocking the connecting duct. The membrane is permeable to the fluid. This embodiment may be advantageous in that it may provide a means of filtering the fluid or blocking air bubbles as the fluid is returned from the auxiliary container to the container.

In another embodiment, the auxiliary container comprises a bubble directing structure. As used herein, bubble directing structure includes structure used to direct bubbles to a predetermined location in the container or toward the vent. In some applications, the bubble directing structure may allow the fluid to pass around the bubble as the fluid moves through the container. For example, the bubble structure may be a set of ridges that are used to place and guide the bubbles. The structure and ridge may be spaced sufficiently close together that the surface tension of the fluid prevents the gas bubble from entering the area where the fluid is allowed to pass around the bubble. This may be advantageous because if the bubbles are not properly confined, they may become trapped at a particular location in the auxiliary container and not allowed to travel to the top of the auxiliary container, or allow fluid to return to the container in the presence of connecting tubing.

In another embodiment, the container and/or the auxiliary container comprises a vent hole. As used herein, a vent is a structure that allows air bubbles or other volumes of gas to enter or exit the cartridge. Alternatively, the container comprises such a vent, or both the container and the auxiliary container comprise such a vent.

In another embodiment, the vent is covered or sealed by a filter. The filter is operable to seal fluid in the cartridge. In some embodiments, the filter may be hydrophobic. In some embodiments, the gas filter may have pores to allow only gas to pass through, but not liquid. In some embodiments, the filter may be, but is not limited to: polytetrafluoroethylene in the form of pores, carbon fibers coated with PTFE, carbon nanotubes, polymer fibers or fluoropolymer fibers.

In another embodiment, the fluid comprises magnetic beads.

In another embodiment, the fluid comprises latex beads.

In another embodiment, the fluid comprises a blood typing reagent.

In another embodiment, the fluid comprises an immunological agent.

In another embodiment, the fluid comprises an antibody.

In another embodiment, the fluid comprises an enzyme.

In another embodiment, the fluid comprises a recombinant protein.

In another embodiment, the fluid comprises a viral isolate.

In another embodiment, the fluid comprises a virus.

In another embodiment, the fluid comprises a biological agent.

In another embodiment, the fluid comprises a solvent.

In another embodiment, the fluid comprises a diluent.

In another embodiment, the fluid comprises a dispersoid.

In another embodiment, the fluid comprises nanoparticles.

In another embodiment, the fluid comprises a protein.

In another embodiment, the fluid comprises a salt.

In another embodiment, the fluid comprises a cleaning agent.

In another embodiment, the fluid comprises nucleic acids.

In another embodiment, the fluid comprises an acid.

In another embodiment, the fluid comprises a base.

In another embodiment, the fluid may include a dispersion of particles, a liquid agent, a liquid binder, a liquid food product, a metallic liquid (e.g., solder), and/or any other liquid.

In another embodiment, the cartridge further comprises a sensor operable to determine the fluid dispensed by the outlet conduit. This sensor may be, for example, a capacitive or optical sensor.

In another embodiment, the cartridge further comprises a coupling assembly for attaching the rotary valve and the plunger to the actuator assembly. This embodiment may be advantageous because it may enable the rotary valve and the plunger to be conveniently connected to the actuator. In some embodiments, the coupling assembly may enable the rotary valve and the piston to be independently actuated by the actuator assembly.

In some embodiments, it is possible to have a cartridge with its own actuator. In this case, the cartridge further includes an actuator. In some cases, the actuator may be connected to the linkage assembly, or the actuator may be designed or operable to independently actuate the rotary valve and the plunger directly.

A pumping unit as used herein comprises a rotary valve and a plunger for pumping a fluid. There may be one actuator per pumping unit when installed into the automatic analyzer, or one actuator that is moved and used to actuate all cartridges in the automatic analyzer. In this case, there may be a mechanism for moving the relative position between the cartridge and the single actuator. There may also be actuators for a set of cartridges.

For example, different configurations exist for the cassette. In some embodiments, the cassette may have a single pumping unit. This single pumping unit may have conduits connected to different containers. This may enable the cassette to pump different types of fluids from the same cassette. In another example, the cassette may have multiple pumping units, where each pumping unit is connected to one or more containers through its rotary valve.

In some embodiments, the cassette includes a pumping unit and an attachable container. This embodiment may be advantageous in that a universal pumping unit can be produced and the container attached thereto when required. This may help to have a greater variety of available fluids. Different volumes of containers may also be selected. Different pumping units may also be selected. For example, such different pumping units may have plungers with different strokes and/or diameters. This may affect the volume of the pumping unit. In some applications, it may be desirable to more accurately pump larger volumes, and in other applications smaller but more accurately pumped volumes may be desirable. Thus, the use of a pumping unit and an attachable container allows for a modular concept, which allows for combining containers comprising different types and/or volumes of fluid with a defined volume of pumping unit optimized to dispense this fluid. This modular concept allows to provide a large series of optimized cassettes based on a small series of pumping units and/or containers that can be combined in different ways. The assembly of the pumping unit and the attachable container can be performed at the production site as a manufacturing step during the production of the cartridge or at the user site, e.g. by assembling the pumping unit with the attachable container before inserting the cartridge into the automatic analyzer.

In another embodiment, the rotary valve includes a cylindrical body portion. The pumping chamber is a cavity within the rotary valve. The pumping chamber is formed by a cavity and a plunger. The cartridge includes a cartridge body with a cylindrical space for receiving the cylindrical portion. The rotary valve is operable to rotate within the cylindrical volume.

In another embodiment, the container conduit and the outlet conduit are located on the cylindrical space. The pumping chamber conduit is located on the cylindrical portion.

In another embodiment, the cassette comprises a plurality of pumping units.

In another embodiment, the cartridge comprises a plurality of containers.

In another embodiment, multiple containers are filled with different fluids.

In another aspect, the present invention provides an automated analyzer for analyzing a biological sample. An automated system is operable to hold a cartridge according to an embodiment of the present invention. The automated analyzer includes an actuator assembly operable for actuation of the plunger and the valve. The automatic analyzer further includes a controller (520, 1920) for controlling operation of the actuator assembly.

In another aspect, the invention provides an automated analyzer for holding a cartridge according to an embodiment of the invention. An automated analyzer, as used herein, includes a system for automatically analyzing a biological sample. The automated analyzer includes an actuator assembly operable for linear actuation of the plunger and for rotational actuation of the rotary valve. The actuator assembly is further operable to independently actuate the plunger and the rotary valve. The automatic analyzer further includes a controller for controlling operation of the actuator assembly.

In some embodiments, an automated analyzer can be retrofitted to hold multiple cartridges according to embodiments of the present invention. In this case, there may be a mechanism for providing relative movement between the cartridge and the reaction tube/cuvette. There may be one actuator per pumping unit, or there may be one actuator used for multiple cassettes. In this case, there may be a mechanism or robotic system for providing relative motion between the cartridge and the actuator. There are also embodiments in which each of a plurality of actuators is used for a set of cartridges. The set of cassettes can be predetermined or the set of cassettes can be determined on the fly. Alternatively, multiple actuators may be used with a cartridge or a group of cartridges, e.g., for different purposes, like a front dispense or a back dispense action.

In another embodiment, an automated analyzer includes a cartridge.

In another embodiment, the controller is operable to control the actuator assembly to connect the pumping chamber conduit with the container conduit by rotating the rotary valve. The controller is further operable to control the actuator assembly to fill the pumping chamber by increasing the volume of the pumping chamber using the plunger. The controller is further operable to control the actuator assembly to rotate the pumping chamber conduit to connect with the outlet conduit by rotating the rotary valve. The controller is further operable to control the actuator assembly to pump fluid through the outlet conduit by reducing the volume of the pumping chamber using the plunger. This embodiment may be advantageous in that it provides a way of pumping fluid through the outlet conduit.

In another embodiment, the controller is operable to control the actuator assembly to receive fluid from the outlet conduit by increasing the volume of the pumping chamber using the plunger.

In another embodiment, the controller is operable to control the actuator assembly to rotate the pumping chamber conduit to connect with the container conduit by rotating the rotary valve. The controller is further operable to control the actuator assembly to return fluid to the container by reducing the volume of the pumping chamber using the plunger. This embodiment may be advantageous because it provides operation without priming of the pump. 100% or nearly 100% of the fluid may be used.

In another embodiment, the controller is operable to control the actuator assembly to rotate the pumping chamber conduit into connection with the container conduit by rotating the rotary valve. The controller is further operable to control the actuator assembly to mix the fluid in the container by repeatedly increasing and decreasing the volume of the pumping chamber using the plunger. In the case where the fluid comprises beads or particles, such as magnetic beads or latex beads, this embodiment may be used to mix the fluid and the mixture thereof.

In another embodiment, the cartridge includes an outlet nozzle. The automated analyzer further includes a meniscus detector for detecting the meniscus of the fluid. The controller is operable to control the actuator to force fluid through the outlet nozzle. The controller is further operable to use the meniscus detector to detect meniscus. The controller is further operable to control the actuator to stop forcing fluid through the outlet when the meniscus is in the predetermined position. This embodiment may be advantageous because it may allow more accurate and precise dispensing of the fluid. This embodiment may be advantageous because when fluid dispensing begins, if the menisci are in the same position, the dispensing of fluid may thereby be more accurate, precise, and/or more reproducible. The meniscus may be medial or lateral to the outlet nozzle. For example, the outlet nozzle may be a long tubular structure, and the meniscus may have a specific location within the tube. In other embodiments, the meniscus may be formed by a drop of fluid suspended from an outlet nozzle. In many applications, the meniscus is preferably placed right at the mouth of the outlet nozzle.

In another embodiment, the controller is further operable to control the actuator to force a predetermined volume of fluid through the outlet. In some embodiments, the actuator may be controlled to force a predetermined volume of fluid through the outlet nozzle after the meniscus is in a predetermined position.

In another embodiment, the meniscus detector is any one of the following: capacitive sensors, optical sensors and cameras. When the meniscus is inside the nozzle, a capacitive sensor may be used to detect the position of the meniscus. In the case where the nozzle is optically transparent, the optical sensor may also be used to determine the location of the meniscus within the nozzle. If the meniscus extends beyond the nozzle, a capacitive sensor, optical sensor, or camera may be used to determine the location of the meniscus.

In another embodiment, the automated analyzer is operable to hold a plurality of cartridges. Each of the plurality of cartridges is according to an embodiment of the present invention.

In another embodiment, the automated analyzer further comprises a plurality of cartridges.

Embodiments with multiple cartridges may be implemented in a variety of ways. For example, each pumping unit may have its own actuator assembly. This may be a parallel operation. In further examples, the cassettes may be moved and placed on the same actuator assembly, or the actuator assembly may be moved between different cassettes or even between different pumping units of portions of the same cassette. In still further embodiments, there may be multiple actuators with the cartridge being moved between the multiple actuators by a mechanical robotic system.

In another embodiment, the automated analyzer includes a sensor or assay system operable to measure or assay the dispensing of a fluid. The controller is operable to control the dispensing of fluid in accordance with measurements or data received from the sensor or assay system. In other words, the controller is operable to form a closed loop control system with the sensor or assay system for controlling the dispensing of the fluid.

In another aspect, the invention provides a method of operating a cassette according to an embodiment of the invention. The method comprises the following steps: rotating the rotary valve to rotate the pumping chamber conduit to connect it with the container conduit; increasing the volume of the pumping chamber using a plunger to fill the pumping chamber; rotating the rotary valve to rotate the pumping chamber conduit to connect it with the outlet conduit; the volume of the pumping chamber is reduced using a plunger to pump fluid through the outlet conduit.

In another embodiment, the method further comprises the step of increasing the volume of the pumping chamber using a plunger to recover fluid from the outlet conduit.

In another embodiment, the method further comprises the steps of: rotating the rotary valve to rotate the pumping chamber conduit to connect it with the container conduit; and reducing the volume of the pumping chamber using the plunger to return the fluid into the container.

In another embodiment, the method further comprises the steps of: rotating the rotary valve to rotate the pumping chamber conduit to connect with the container conduit; and mixing the fluid in the container using the plunger to repeatedly increase and decrease the volume of the pumping chamber.

In one aspect, the present invention provides a cartridge for dispensing a fluid. The cartridge includes a slide valve. The slide valve has a linear motion. The sliding valve may also be referred to as a linear valve. The sliding valve includes a pumping chamber for pumping fluid. The slide valve is operable to displace the pumping chamber conduit. The pumping chamber conduit is connected to the pumping chamber. The cartridge further comprises a plunger operable to vary the volume of the pumping chamber. The cartridge further comprises a container for storing the fluid. The cartridge further comprises a container conduit for connecting the container to the slide valve. The slide valve is operable to displace the pumping chamber to connect it with the container conduit. The cartridge further comprises an outlet conduit for dispensing the fluid. The slide valve is further operable to divert the pumping chamber conduit to connect with the outlet conduit. This embodiment may be advantageous because the combination of the sliding valve and the plunger allows for accurate dispensing of the fluid. Additional embodiments may also enable a reduction in the amount of fluid wasted when dispensing fluid through the cartridge.

Embodiments may also have the advantage that a large series of pumping actions is possible by the pumping chamber. This embodiment may have the advantage that by controlling the displacement position of the sliding valve and operating the piston properly, a variety of pumping actions can be performed by the pumping chamber. For example, a slide valve may be placed such that the pumping chamber conduit is connected to the container conduit. In this case, the plunger may be used to either draw fluid from the container into the pumping chamber or may be used to pump fluid from the pumping chamber back into the container.

The present embodiment enables other types of actions by using a pumping chamber. For example, the plunger may be used repeatedly to increase and decrease the volume of the pumping chamber when the pumping chamber conduit is aligned with or connected to the container conduit. Which may cause the fluids within the container to be mixed. And the ability to return fluid to the container reduces the amount of fluid wasted.

This embodiment may also enable a so-called waste-reduced activation or waste-free activation function of the pumping chamber to take place, whereby no or possibly only a very small amount of fluid is wasted or discarded when the fluid is pumped out through the outlet conduit. For example, when the pumping chamber conduit is connected with the outlet conduit, the plunger may be used to reduce the volume of the pumping chamber and thereby force or dispense fluid out through the outlet conduit. During this process, it may be that fluid within the outlet conduit does not exit the outlet conduit. After the appropriate amount of fluid has been dispensed, a plunger may then be used to increase the volume of the pumping chamber, thereby drawing fluid that may remain within the outlet conduit back into the pumping chamber. The fluid can then be held in the pumping chamber or if the sliding valve is moved into alignment with the container conduit, the fluid previously within the outlet conduit can be pumped back into the container.

The slide valve may also provide a means of preventing fluid from accidentally leaking from the container. For example, in some embodiments, the slide valve may be capable of being moved to a position that is not aligned with either the outlet conduit or the container conduit. This may prevent fluid and/or gas from exiting the outlet conduit and/or prevent fluid and/or gas in the container from leaking or discharging into the pumping chamber.

In some embodiments, the cassette includes a pumping unit and an attachable container. This embodiment may be advantageous in that a universal pumping unit can be produced and the container attached thereto when required. This may help to have a greater variety of available fluids. Different volumes of containers may also be selected. Different pumping units may also be selected. Such different pumping units may for example have plungers with different strokes and/or diameters. This may affect the volume of the pumping unit. In some applications, it may be desirable to more accurately pump larger volumes, and in other applications smaller but more accurately pumped volumes may be desirable.

The use of a pumping unit and an attachable container may allow to realize a modular system that allows to combine a container comprising different types and/or volumes of fluid with a defined volume of pumping unit optimized to dispense this fluid. Such a modular system may provide a large family of optimized cassettes based on a small family of pumping units and/or containers that can be combined in different ways. The assembly of the pumping unit and the attachable container can be performed at the production site as a manufacturing step during the production of the cartridge or at the user site, e.g. by assembling the pumping unit with the attachable container before inserting the cartridge into the automatic analyzer.

The container can be constructed in a variety of ways. In some embodiments, the container may be a hard-walled chamber, preferably made of plastic using an injection molding or thermoforming process. In some embodiments, the container may be a chamber with flexible walls. In some embodiments, the container can be a pouch or bladder. In other embodiments, the container can be a pouch or bladder supported by an outer container. In other embodiments, the container can be a tube.

In some embodiments, the pumping chamber conduit is aligned with the container conduit and/or the outlet conduit using mechanical stops. As an alternative to using mechanical stops, the alignment can also be achieved by other means. For example by spatially defining a change in a physical or geometric property, for example by a change in coefficient of friction or diameter. In other embodiments, mechanical stops are not used, and alignment is implemented by an actuation system attached to the cartridge during use.

In another embodiment, the cartridge further comprises an outlet nozzle connected to the outlet conduit. As used herein, an outlet nozzle includes a nozzle designed to minimize fluid waste and to allow the drip to drip cleanly during the dosing process. For example, in a simple test tube, a fluid droplet may hang outside the nozzle after a plunger is used to reduce the volume of the pumping chamber. The shape or function of the outlet nozzle can be designed to reduce the chance of a fluid droplet hanging thereon. For example, the outlet nozzle may have a so-called duckbill shape and be a duckbill nozzle.

In other embodiments, the cassette may have additional containers and additional container conduits that enable the pumping chamber to be connected to these additional containers. Typically, a cartridge may contain only a single fluid or reagent. In some embodiments, it may be a diluent used or required for a variety of tests. There may also be a plurality of containers each connectable to a conduit that can access the pumping chamber conduit at a particular in-line position of the slide valve.

For example, there may be two containers for many clinical tests, and two or three different fluids in different containers for immunoassays. In some variations of this embodiment, the cassette may have multiple pumping units, each of which is connected to one or more containers through its sliding valve. In this way the immunoassay is dispensed using separate pumping units and it is not mixed by the pumping process.

In some embodiments, the slide valve and the plunger are operable to be actuated independently. In other embodiments, a plunger or actuation of a plunger is also used to actuate the sliding valve.

In another embodiment, the cartridge further comprises a return conduit connected to the container. The pumping chamber conduit is operable to receive fluid from the first portion of the container. The return conduit is operable to return fluid to the second portion of the container. The slide valve is further operable to move the pumping chamber conduit to connect to the return conduit. This embodiment may further have the advantage of reducing the number of bubbles in the first portion of the container by transferring the bubbles to the second portion of the container.

For example, fluid can be drawn from the container when the slide valve is moved such that the pumping chamber conduit is aligned with the container conduit. After a quantity of fluid has been dispensed through the outlet conduit, the slide valve may be moved to a position such that the pumping chamber conduit is aligned with the return conduit. The container conduit may draw fluid from one portion of the container and the return conduit is used to return fluid to a different portion of the container. For example, the two locations of the reservoir conduit and the return conduit can be sufficiently far apart that bubbles entering the reservoir through the return conduit are less likely to be drawn into the reservoir conduit as fluid is drawn from the reservoir into the pumping chamber.

In another embodiment, the cartridge further comprises an auxiliary container. The cartridge further comprises an auxiliary container conduit. The sliding valve is further operable to move the pumping chamber conduit to connect to the auxiliary container conduit. This embodiment may be advantageous because it may allow a second or different fluid to be stored and dispensed through the use of a cartridge, which may also allow wasted fluid to be placed in the auxiliary container.

In another embodiment, the auxiliary container comprises a vent. As used herein, a vent is a structure that allows air bubbles or other volumes of gas to enter or exit the cartridge. Alternatively, the container comprises such a vent, or both the container and the auxiliary container comprise such a vent.

It should be noted that by adding third containers and third container conduits, fourth containers and fourth container conduits, and the like, additional containers may be added to the cassette such that any number of containers and container conduits may be added to the cassette. The additional container may also include a vent.

In another embodiment, the cartridge comprises a membrane or a grid or a filter located within the connecting duct. If a membrane is used, the membrane is permeable to the fluid. Such Membranes are described, for example, in "unified Permation of Water thread-light graph-Based Membranes" (R.R.Nair et al; Science 335, 442 (2012)). If a grid or mechanical filter is used, the size of the mesh or holes has to be smaller than the bubble size to prevent the bubbles from transferring through the grid or filter. This embodiment may be advantageous in that it may provide a means of filtering the fluid or preventing air bubbles when the fluid is returned from the auxiliary container to the container.

In another embodiment, the container and/or the auxiliary container comprises a vent hole. The vent holes are sealed using a filter. The filter is permeable to air. The filter is operable to seal fluid in the cartridge. In some embodiments, the filter may be hydrophobic. In some embodiments, the gas filter may have pores to allow only gas to pass through, but not liquid. In some embodiments, the filter may be, but is not limited to: polytetrafluoroethylene in the form of pores, carbon fibers coated with PTFE, carbon nanotubes, polymer fibers or fluoropolymer fibers.

In another embodiment, the fluid comprises magnetic beads.

In another embodiment, the fluid comprises latex beads.

In another embodiment, the fluid comprises a blood typing reagent.

In another embodiment, the fluid comprises an immunological agent.

In another embodiment, the fluid comprises an antibody.

In another embodiment, the fluid comprises an enzyme.

In another embodiment, the fluid comprises a recombinant protein.

In another embodiment, the fluid comprises a viral isolate.

In another embodiment, the fluid comprises a virus.

In another embodiment, the fluid comprises a biological agent.

In another embodiment, the fluid comprises a solvent.

In another embodiment, the fluid comprises a diluent.

In another embodiment, the fluid comprises a dispersoid.

In another embodiment, the fluid comprises nanoparticles.

In another embodiment, the fluid comprises a protein.

In another embodiment, the fluid comprises a salt.

In another embodiment, the fluid comprises a cleaning agent.

In another embodiment, the fluid comprises nucleic acids.

In another embodiment, the fluid comprises an acid.

In another embodiment, the fluid comprises a base.

In another embodiment, the fluid may comprise a dispersion of particles, a liquid agent, a liquid binder, a liquid food product, a metallic liquid (e.g., solder), or any other liquid.

In another embodiment, the cartridge further comprises a sensor operable to determine the fluid dispensed by the outlet nozzle. This sensor may be, for example, a capacitive or optical sensor.

In another embodiment, the cartridge further comprises a coupling assembly for attaching the slide valve and the plunger to the actuator assembly. In some embodiments, the coupling assembly is attached to the plunger only. In further embodiments, the coupling assembly may be coupled to both the sliding valve and the plunger such that they may be actuated independently.

In some embodiments, it is possible to have a cartridge with its own actuator. In this case, the cartridge further includes an actuator. In some cases, the actuator may be connected to the linkage assembly, or the actuator may be designed or operable to independently actuate the sliding valve and the plunger directly.

A pumping unit as used herein comprises a sliding valve and a plunger for pumping fluid. There may be one actuator per pumping unit when installed into the automatic analyzer, or one actuator that is moved and used to actuate all cartridges in the automatic analyzer. In this case, there may be a mechanism for moving the relative position between the cartridge and the single actuator. There may also be actuators for a set of cartridges.

For example, different configurations exist for the cassette. In some embodiments, the cassette may have a single pumping unit. This single pumping unit may have conduits connected to different containers. This may enable the cassette to pump different types of fluids from the same cassette. In another example, the cassette may have multiple pumping units, where each pumping unit is connected to one or more containers through its sliding valve.

In another embodiment, the cassette comprises a plurality of pumping units.

In another embodiment, the cartridge comprises a plurality of containers.

In another embodiment, multiple containers are filled with different fluids.

In another embodiment, the sliding valve comprises a piston. The pumping chamber is a cavity within the piston. The pumping chamber is formed by a cavity and a plunger. The piston is operable for translational movement within the volume.

The piston and the volume may have different cross-sectional shapes corresponding to each other. For example, the piston and corresponding volume may have a circular, elliptical, or other cross-sectional shape.

In another embodiment, the piston and the sliding valve are operable for collinear movement. In other words, the piston and the sliding valve are operable to have parallel or in the same direction of movement.

In another embodiment, the slide valve includes a reservoir conduit mechanical stop for aligning the pumping chamber conduit with the reservoir conduit. In other words, there is a mechanical stop in alignment with the piston so that the pumping chamber conduit is aligned with the reservoir conduit.

In another embodiment, the slide valve includes an outlet conduit mechanical stop for aligning the pumping chamber conduit with the outlet conduit. In other words, the sliding valve has a mechanical stop aligned with the piston such that the pumping chamber conduit is aligned with the outlet conduit.

In another embodiment, the piston includes two plunger mechanical stops for limiting movement of the plunger relative to the piston. The plunger is operable to actuate the piston. This embodiment may be advantageous in that it enables the cartridge to be operated by a single linear actuator. This is especially true when there are embodiments that also have a combination of container conduit mechanical stops and outlet conduit mechanical stops.

In another aspect, the present invention provides an automated analyzer for analyzing a biological sample. The automated analyzer is operable to hold a cartridge according to an embodiment of the present invention. The automated analyzer includes an actuator assembly operable for linear actuation of the plunger and the slide valve. The actuator assembly may have either one or two actuators depending on the design of the cartridge. For example, in some embodiments, the linear actuator may only actuate the plunger. In other embodiments, there may be a linear actuator that independently actuates the slide valve and the plunger. The automatic analyzer further includes a controller for controlling operation of the actuator assembly.

In another embodiment, an automated analyzer includes a cartridge.

In another embodiment, an automated analyzer is operable to hold a cartridge according to an embodiment. The piston includes two plunger mechanical stops for limiting movement of the plunger relative to the piston, and wherein the plunger is operable to actuate the piston. The actuator assembly is operable for linear actuation of the plunger. This embodiment may be advantageous in that only a single linear actuator is used.

Actuation of the sliding valve is accomplished by or via a plunger.

In another embodiment, the actuator assembly is operable for linear actuation of the plunger and for linear actuation of the sliding valve. In this embodiment, there are two linear actuators in the actuator assembly, and the plunger and the sliding valve are actuated independently. This embodiment may be advantageous because it enables more complex behavior or pumping protocols by the automatic analyzer.

In another embodiment, the controller is operable to control the actuator assembly to connect the pumping chamber conduit with the container conduit by moving the slide valve. The controller is further operable to control the actuator assembly to fill the pumping chamber by increasing the volume of the pumping chamber using the plunger. The controller is further operable to control the actuator assembly to move the pumping chamber conduit to connect with the outlet conduit by moving the sliding valve. The controller is further operable to control the actuator assembly to pump fluid through the outlet conduit by reducing the volume of the pumping chamber using the plunger.

The moving slide valve herein is equivalent to the moving piston in those embodiments where the slide valve has a piston.

In another embodiment, the controller is operable to control the actuator assembly to move the pumping chamber conduit to connect with the container conduit by moving the sliding valve. The controller is further operable to control the actuator assembly to return fluid to the container by reducing the volume of the pumping chamber using the plunger. This embodiment may be advantageous because it provides operation without priming of the pump. 100% or nearly 100% of the fluid may be used.

In another embodiment, the controller is operable to control the actuator assembly to move the pumping chamber conduit into connection with the container conduit by moving the slide valve. The controller is further operable to control the actuator assembly to mix the fluid in the container by repeatedly increasing and decreasing the volume of the pumping chamber using the plunger. In the case where the fluid comprises beads or particles, such as magnetic beads or latex beads, this embodiment may be used to mix the fluid and the mixture thereof.

In another embodiment, the controller is further operable to control the actuator assembly to recover fluid from the outlet conduit by increasing the volume of the pumping chamber using the plunger.

In another embodiment, the cartridge includes an outlet nozzle. The automated analyzer further includes a meniscus detector for detecting the meniscus of the fluid. The controller is further operable to control the actuator assembly to force fluid through the outlet nozzle. The controller is further operable to use the meniscus detector to detect meniscus. The controller is further operable to control the actuator to stop forcing fluid through the outlet when the meniscus is in the predetermined position. This embodiment may be advantageous because it may allow more accurate and precise dispensing of the fluid. This embodiment may be advantageous because when fluid dispensing begins, if the menisci are in the same position, the dispensing of fluid may thereby be more accurate, precise, and/or more reproducible. The meniscus may be medial or lateral to the outlet nozzle. For example, the outlet nozzle may be a long tubular structure, and the meniscus may have a specific location within the tube. In other embodiments, the meniscus may be formed by a drop of fluid suspended from an outlet nozzle. In many applications, the meniscus is preferably placed right at the mouth of the outlet nozzle.

Embodiments with multiple cartridges may be implemented in a variety of ways. For example, each pumping unit may have its own actuator assembly. This may be a parallel operation. In further examples, the cassettes may be moved and placed on the same actuator assembly, or the actuator assembly may be moved between different cassettes or even between different pumping units that are part of the same cassette. In still further embodiments, there may be multiple actuators with the cartridge being moved between the multiple actuators by a mechanical robotic system.

In another embodiment, the automated analyzer is operable to hold a plurality of cartridges. Each of the plurality of cartridges is according to an embodiment of the present invention. In this case, there may be a mechanism for providing relative movement between the cartridge and the reaction tube/cuvette. There may be one actuator per pumping unit, or there may be one actuator used for multiple cassettes. In this case, there is a mechanism or robotic system for providing relative motion between the cartridge and the actuator. There are also embodiments in which each of a plurality of actuators is used for a set of cartridges. The set of cassettes can be predetermined or the set of cassettes can be determined on the fly. Alternatively, multiple actuators may be used with a cartridge or a group of cartridges, e.g., for different purposes, like a front dispense or a back dispense action.

In another aspect, the invention provides a method of operating a cartridge according to an embodiment of the invention. The steps of the method include moving a slide valve to move the pumping chamber conduit to connect with the container conduit. The method further includes the step of increasing the volume of the pumping chamber using a plunger to fill the pumping chamber. The method further includes moving the slide valve to move the pumping chamber conduit to connect with the outlet conduit. The method further includes the step of reducing the volume of the pumping chamber using a plunger to pump the fluid through the outlet conduit.

The described embodiments of the automated analyzer may also be applied to automated systems for dispensing fluids.

In another aspect, the present invention provides an automated system for dispensing a fluid. The automation system is operable to hold a cartridge according to an embodiment of the invention. The automated system includes an actuator assembly (200, 400, 904', 904 ") operable for linear actuation of the plunger and the sliding valve. The automation system further includes a controller (920) for controlling operation of the actuator assembly.

In another embodiment, the actuator assembly is operable for linear actuation of the plunger.

In another embodiment, the automated system is operable for linear actuation of the plunger and for linear actuation of the slide valve.

In another embodiment, the cartridge includes an outlet nozzle (126). The automated analyzer further includes a meniscus detector (1002, 1002') for detecting the meniscus of the fluid. The controller is operable to: controlling the actuator assembly to force fluid through the outlet nozzle; detecting the meniscus using a meniscus detector; and controlling the actuator to stop forcing fluid through the outlet when the meniscus is in the predetermined position.

It should be understood that one or more claims and/or embodiments may be combined as long as the combined elements are not mutually exclusive.

Drawings

Embodiments of the invention are explained in more detail below, by way of example only, with reference to the accompanying drawings, in which:

FIG. 1 shows a cartridge and actuator assembly according to an embodiment of the invention;

FIG. 2 shows how the cassette may be used to pump fluid through the outlet conduit;

FIG. 3 shows a pumping method similar to that shown in FIG. 2, except that additional steps are performed to remove fluid from the outlet conduit;

fig. 4A and 4B show how fluid can be pumped through the outlet conduit, where fluid is withdrawn from the container, and then excess fluid is pumped from the outlet nozzle and the outlet conduit into the auxiliary container;

FIG. 5 shows an automated analyzer according to an embodiment of the present invention;

FIG. 6 shows bubble guidance according to an embodiment of the invention;

FIG. 7 shows an automated analyzer according to a further embodiment of the invention;

FIGS. 8A, 8B, 8C and 8D show the operation of the cassette using a meniscal probe;

FIG. 9 shows the correlation of target volume and measurement volume for an embodiment of a rotary valve;

FIG. 10 shows a plot indicating accuracy and coefficient of variation of fluid distribution for different viscosities and surface tensions from an embodiment of a rotary valve;

FIG. 11 shows a cartridge according to an embodiment;

FIG. 12 shows the cassette of FIG. 1 connected to an actuator assembly;

FIG. 13A shows a cartridge according to a further embodiment;

FIG. 13B shows a cartridge according to a further embodiment;

FIG. 14 shows the cassette of FIG. 2 attached to an actuator assembly;

FIGS. 15A and 15B show views of the slide valve and plunger of the embodiment shown in FIG. 1 at various stages;

FIGS. 16A and 16B show a sliding valve and piston combination according to further embodiments;

FIG. 17 shows two views of a slide valve and plunger combination according to further embodiments;

18A and 18B illustrate one way of operating the sliding valve and piston of the embodiment shown in FIG. 3;

FIG. 19 shows an automated analyzer according to an embodiment;

FIG. 20 shows an automatic analyzer according to further embodiments;

FIG. 21 shows a cartridge according to a further embodiment;

FIG. 22 shows an alternative slide valve design;

FIG. 23 shows an alternative slide valve design;

FIG. 24 shows an alternative slide valve design;

FIG. 25 shows an alternative slide valve design;

FIG. 26 shows an alternative slide valve design; and

fig. 27 shows an alternative slide valve design.

Detailed Description

Identically numbered elements within these figures may either be equivalent elements or perform the same functions. Elements that have been previously discussed, if functionally equivalent, will not necessarily be discussed in subsequent figures.

Fig. 1 shows a cartridge 100 and an actuator assembly 102 according to an embodiment of the invention. The actuator assembly 102 includes a linear actuator 104 that is actuatable in a direction 105. The actuator assembly 102 further includes a rotary actuator 106 that is actuatable in a direction 107.

The cartridge 100 includes a plunger 108 and a rotary valve 110. The cartridge 100 includes a cartridge body 112 having a cylindrical space 116. In this case, the cylindrical space 116 is formed of a bearing material. The rotary valve 110 has at least one cylindrical portion 114 adapted to fit into a cylindrical space 116 of the cartridge body 112. The rotary valve 110 has a hollow space forming a pumping chamber 118, the pumping chamber 118 being formed by the hollow space and the plunger 108. The pumping chamber 118 has a pumping chamber conduit 120 formed in the wall of the rotary valve 110. The rotary valve 110 is operable to rotate within the cylindrical space 116 to place the pumping chamber conduit 120 at different angular positions.

The cartridge 100 further comprises a container 122 for being filled with a liquid. Although not shown in fig. 1, the cartridge 100 may also include a vent for allowing gas to be vented into the reservoir 122. The cartridge 100 further includes a container conduit 124. The reservoir tubing 124 allows the reservoir 122 to access the pumping chamber tubing 120 when the pumping chamber tubing is in the proper rotational position. The cartridge 100 also includes an optional outlet nozzle 126 for dispensing the fluid. The outlet nozzle 126 is connected to an outlet conduit 128. Outlet conduit 128 allows pumping chamber 118 to dispense fluid. The outlet conduit 128 in this embodiment is connected to the outlet nozzle 126 when the pumping chamber conduit 120 is in the proper rotational position. A coupling assembly 130 is further shown coupling the actuator assembly 102 to the cartridge 100. The coupling assembly 130 is designed for actuating the piston 108 in the linear direction 105 and in this direction. The coupling assembly 130 is also adapted to be able to independently rotate the rotary valve 110. For example, there may be grooves cut into the rotary valve 110 and there may be shapes on the coupling assembly 130 that fit into the grooves of the rotary valve 110. The example shown in FIG. 1 is merely one way in which the rotary valve 110 and the piston 108 may be actuated. Other equivalent mechanisms may also be used to actuate and attach to the rotary valve 110 and the piston 108.

Fig. 2 shows four views 200, 202, 204, 206 of the cartridge 100. Fig. 2 shows how the cassette 100 may be used to pump fluid through the outlet conduit 128. In view 200, the pumping chamber tube 120 is aligned with the reservoir tube 124. The plunger 108 is fully depressed and the pumping chamber 118 has no volume or is very small. In this example, the plunger 108 is fully depressed. However, full depression of the plunger 108 is not necessary for operation. In the examples described herein, relative movement of the plungers is relevant. For example, depressing the plunger 108 causes the volume of the pumping chamber to decrease and thus forces fluid through the outlet conduit.

Next in view 202, the plunger is retracted in direction 208. This causes fluid to enter the pumping chamber 118 from the reservoir 122. Next in view 204, the rotary valve 110 is rotated 210 such that the pumping chamber conduit 120 is aligned with the outlet conduit 128. The pumping chamber 118 is now separated from the reservoir 122. Next in view 206, plunger 108 is depressed in direction 212 and fluid 214 exits via outlet conduit 128.

Fig. 3 shows a pumping method similar to that shown in fig. 2, except that additional steps are performed to remove fluid from the outlet nozzle 126 and the outlet conduit 128. The same views 202, 204 and 206 are shown again. There are three additional views 300, 302, and 304 of the box 100 shown. The steps according to view 300 are performed after view 206. Plunger 108 is retracted in direction 306 to draw fluid from outlet nozzle 126 in outlet conduit 128. In this example, the plunger 108 is retracted enough that a bubble 208 is formed in the pumping chamber 118. Next in view 302, the rotary valve 110 is rotated in direction 310 such that the pumping chamber conduit 120 is aligned with the reservoir conduit 124. Finally, in view 304, plunger 108 is depressed in direction 312, thereby forcing fluid out of pumping chamber 118 into reservoir 122. In addition, bubbles 308 are also forced into the reservoir 122.

Fig. 4A and 4B show seven views 400, 402, 404, 406, 408, 410, 412 of different embodiments of a cartridge 414. In this embodiment, the cartridge 412 has a container 122 and an auxiliary container 416. Fig. 4 shows how fluid 214 can be pumped through outlet conduit 128 where it is withdrawn from container 122 and then excess fluid is pumped from outlet nozzle 126 and outlet conduit 128 into auxiliary container 416. In this box 414, it can be seen that there is a connecting duct 418 between the container 122 and the auxiliary container 416. The connecting duct 418 need not be present in all embodiments. In some alternative embodiments, there may also be membranes permeable to fluids placed in the connecting conduit 418. View 400 shows the plunger 108 when fully depressed, and the pumping chamber tube 120 aligned with the reservoir tube 124. Next in view 402, the plunger is retracted in direction 420, filling pumping chamber 118 with fluid 214. Next in view 404, the rotary valve 110 is rotated such that the pumping chamber conduit 120 is aligned with the outlet conduit 128.

The rotary valve is rotated in direction 422. Next in view 406, plunger 108 is depressed in direction 424 and fluid 214 is forced out of outlet conduit 128. Next in view 408, plunger 108 is retracted in direction 426 to retract fluid 214 previously in outlet conduit 128 and in pumping chamber conduit 120 back to pumping chamber 118. Next in view 410, the rotary valve 110 is rotated in direction 428 to align the pumping chamber conduit 120 with the auxiliary container conduit 430. Finally, in view 412, plunger 108 is depressed in direction 432, driving bubble 308 and fluid 126 into auxiliary chamber 416. In some embodiments, the auxiliary chamber 416 may have a vent to atmosphere. In some embodiments, the vents may be covered by a filter that allows gas to pass through but prevents fluid 416 from exiting cartridge 414. In view 412, the pumping chamber tube 120 and auxiliary container channel 430 are shown filled with bubbles 308.

Fig. 5 shows an automated analyzer 500 according to an embodiment of the present invention. This automatic analyzer is shown with three cartridges 502, 502', and 502 ". There is an actuator assembly 504 connected to the cassette 502. There is an actuator assembly 504 'connected to the cassette 502'. There is an actuator assembly 504 "connected to the cassette 502". The actuator assembly 504, 504 ', 504 "is used to actuate the rotary valves and plungers of the cartridges 502, 502', 502". The automated analyzer 500 is shown having a relative motion device 510 that provides relative motion 512 between the reagent containers or cuvettes 506 and the cassettes 502, 502', and 502 ". A reagent container or cuvette 506 is shown containing a biological sample 508. The cartridges 502, 502', 502 "may be used to add one or more fluids to the biological sample 508. The automated analyzer 500 is shown as further comprising a sensor system 514. The sensor system comprises one or more sensors for measuring a quantity or a physical or chemical or biochemical property of the biological sample 508. For example, sensor system 514 may include a Nuclear Magnetic Resonance (NMR) system, an optical transmission or reflectance measurement system, a pH meter, a camera system, a Polymerase Chain Reaction (PCR) device, an Electrochemiluminescence (ECL) device, a spectroscopic assay system, an electrochemical or optical sensor, and a chromatography system. The relative motion device 510 is also operable to move the reagent containers or cuvettes 506 to the sensor system 514.

The arrangement of the cassettes 502, 502', 502 "and the sensor system 514 is representative. In some embodiments, the reagent containers or cuvettes 506 may be held in a fixed position and the cassettes 502, 502', 502 "may be moved. The actuation systems 504, 504', 504 "and the sensor system 514 are shown connected to a hardware interface 522 of a computer system 520. Computer system 520 serves as a controller for automated analyzer 500. The computer 520 is further shown to include a processor 524 capable of controlling the operation and operation of the automated analyzer 500 using a hardware interface 522. The processor 524 is further shown connected to a user interface 526, computer storage 528 and computer memory 530. The computer memory 528 is shown containing an analysis request 532. The analysis request 532 includes a request to analyze the biological sample 508.

The computer memory 528 is further shown to contain sensor data 534 received from the sensor system 514. The computer memory 528 is further shown to contain analysis results 536 determined using the sensor data 534. The computer memory 530 includes a control module 540. The control module 540 contains computer executable code that enables the processor 524 to control the operation and operation of the automatic analyzer 500. For example, the control module 540 may use the analysis request 532 to generate commands to generate and send to the actuation systems 504, 504', 504 ", the sensor system 514, and the relative motion system 510. Using the sensor data 534, the control module 540 can also generate an analysis result 536.

In various embodiments, a variety of algorithms may be used to control the dispensing of fluid. For example, the actuator assembly may be controlled by the processor to implement a series of predetermined actions to dispense the fluid. In another example, a sensor or assay system can be integrated into an automated analyzer to measure the dispensing of fluid. In this case, the algorithm uses the actuator assembly and the sensor to form a closed loop feedback to accurately control or determine the dispensing of the fluid.

Fig. 6 shows a bubble leading structure 600 according to an embodiment of the present invention. For example, the bubble leading structure 600 may be located within a container or an auxiliary container of the cartridge according to an embodiment of the present invention. Bubble directing structure 600 includes a bubble channel 602 surrounded by a plurality of fluid channels 604. Bubble channel 602 provides a path for bubble 606. Fluid channel 604 has a sufficiently narrow space or width 608 such that bubble 606 is prevented from entering fluid channel 604 due to the surface tension of the fluid. The bubble channel 602 confines the bubble 606 and allows the bubble to rise as the fluid 610 is allowed to travel around the bubble.

Fig. 7 shows an automated analyzer 700 according to an embodiment of the invention similar to the embodiment shown in fig. 5. The automated analyzer 700 is similar to the automated analyzer 500 shown in fig. 5. The autoanalyzer 700 of fig. 7 additionally has meniscus detectors 702, 702', 702 ". Each meniscal probe 702, 702' is positioned adjacent to the outlet nozzle 126. Each meniscal probe 702, 702', 702 "is connected to a hardware interface 522. This allows the processor 524 to control the actuator assemblies 504, 504', 504 "to control the position of the meniscus. This may enable the processor to more accurately and or reproducibly dispense fluids from the cartridges 502, 502', 502 ", for example.

Fig. 8 shows 11 views 800, 802, 804, 806, 808, 810, 812, 814, 816, 818, 822 illustrating the functionality of a cassette 100 incorporating a meniscal probe 702. In these examples, meniscus detector 702 is an optical sensor. The use of the optical sensor 702 is exemplary. Other types of sensors may also be used.

In view 800, the pumping chamber tube 120 has been rotated into a position such that it is aligned with the container tube 124. In this view 800, the plunger 108 is shown fully depressed. Thus, the pumping chamber 118 is very small and not visible in this view 800. The position of this plunger 108 in this position is not necessarily required as long as the plunger 108 is still able to add or withdraw a reasonable amount of fluid 214 from the reservoir 122. Next in view 802, plunger 108 is retracted to increase the volume of pumping chamber 118 and draw fluid 214 from reservoir 122 into pumping chamber 118. Next in view 804, the pumping chamber tube 120 is rotated into a position such that it is aligned with the outlet tube 128.

In view 806, plunger 108 is depressed, which reduces the volume of pumping chamber 118. This forces the fluid 214 into the outlet conduit 128 and the outlet nozzle 126. The plunger 108 is controlled in accordance with the meniscal probe 702. When the meniscus 822 reaches a predetermined position, the meniscus detector 702 is used to detect it and the depression of the plunger 108 is stopped. Next in view 808, the pumping chamber tube 120 is again rotated into alignment with the reservoir tube 124. In view 810, the plunger 108 is retracted, thereby increasing the volume of the pumping chamber 118 and drying the fluid 214 from the reservoir 122. Next in view 812, the pumping chamber tube 120 is rotated into a position such that it is aligned with the outlet tube 128. The pumping chamber 118 is filled with fluid and meniscus a 22 is in a predetermined position. Next in view 814, the plunger 108 is depressed, forcing fluid out of the outlet nozzle 126. In view 814 it can be seen that there is still fluid present within the outlet conduit 128 and the outlet nozzle 126. Next in view 816, the plunger 108 is retracted to draw the fluid 214 in both the outlet tubing 128 and the outlet nozzle 126 back into the pumping chamber 118, and in view 818, the pumping chamber tubing 120 is rotated into position with the container tubing 124. Finally then in view 820 a20, the plunger 108 is depressed forcing fluid back into the container 122. The bubbles 308 in the pumping chamber are forced out of the pumping chamber and into the reservoir 122.

Fig. 9 shows the target volume versus measured volume for an embodiment of a rotary valve comprising a pumping chamber with a volume of 10 mul. Fig. 9 shows a plot of a target volume (in μ L) 900 and a measurement volume (in μ L) 902. The measurement points are connected by a linear fit as shown by dashed line 904. For each data point, water was used as the test fluid. The measurement volume has been determined by using a graduated scale. Each data point represents the average of three experiments performed for the same target volume. The pumping was repeated 24 times in each test or run. In other words, three tests or runs are performed for each target volume. For each of these three runs, the fluid was dispensed 24 times and averaged. The data shown in fig. 9 illustrates that there is both very high accuracy (small errors are drawn with lines even for very small target volumes) and linearity (linear fit very close to the ideal bisector) over the wide range of target volumes that can be achieved by using a rotary valve according to the present invention.

Figure 10 shows a plot indicating the accuracy and Coefficient of Variation (CV) of fluid distribution for fluids of different viscosities and surface tensions with an embodiment of a rotary valve including a pumping chamber volume of 10 mul. The X-axis 1000 indicates the viscosity in mPas of the different fluids a-S in 19. The Y-axis 1002 on the left indicates the surface tension in mN/m for each of these fluids. A plot of the viscosity versus surface tension for each fluid is shown by line 1004. The measurement volume has been determined by using a graduated scale. For each fluid, an experiment involving 21 consecutive dispenses of a target volume of 1 μ Ι _ has been performed.

The right Y-axis 1006 indicates the accuracy 1008 (left bar, in%) of the dispense for each fluid, and the coefficient of variation 1010 (right bar, in%).

The data shown in fig. 10 show that by using a rotary valve according to the invention, the accuracy and reproducibility of the dispensing that can be achieved is very high and (almost) independent of the viscosity and/or surface tension of the fluid being dispensed: if the accuracy and CV values of different fluids a-S are compared, taking into account their increased viscosity (indicated on the X-axis), the effect of viscosity cannot be determined on both accuracy and CV. Likewise, if the accuracy and CV values of the different fluids a-S are compared, taking into account their respective surface tensions (shown in 1004 and indicated on the left Y-axis), the effect of surface tension cannot be determined on both accuracy and CV.

Fig. 11 shows a cassette 1100 according to an embodiment of the invention. The cartridge includes a plunger 1108 that is slidable within a piston 1114. Piston 1114 and volume 1116 form slide valve 1110. The volume 1116 may be formed in the housing 1117 or in a portion of the cartridge 1100. The slide valve 1110 can have a linear motion. As piston 1114 moves, there is a pumping chamber conduit 1120 that is moved along piston 1114. There is a hole in piston 1114 into which plunger 1108 can move. This hole in the piston 1114 forms a pumping volume 1118 with the plunger 1108.

Piston 1114 is able to move pumping chamber tube 1120 into different positions. In this view, it is shown aligned with reservoir tubing 1124. The reservoir conduit 1124 connects to a reservoir 1122 that is filled with fluid through the pumping chamber 1118. The container 1122 is surrounded by the cartridge body 1112. In this position, the plunger 1134 can be moved so that the volume of the pumping chamber 1118 can be increased or decreased. When the plunger 1108 is moved to increase the volume of the pumping chamber 1118, fluid can be drawn from the container 1122 when the piston 1114 is in this position.

Piston 1114 can be moved such that pumping chamber conduit 1120 is aligned with outlet conduit 1128. An outlet conduit 1128 provides an inlet to an outlet nozzle 1126. By reducing the volume of the pumping chamber 1118, fluid can be expelled from the pumping chamber 1118 through the nozzle 1126 when the pumping chamber conduit 1120 is aligned with the outlet conduit 1128.

In this embodiment, the piston 1114 is shown as having a first plunger mechanical stop 1130 and a second plunger mechanical stop 1132. In this example, the plunger has a mechanical extension 1134 operable to contact either the first plunger mechanical stop or the second plunger mechanical stop. In this embodiment, the entire pumping arrangement may be accomplished by merely actuating the plunger 1108. When the mechanical extension 1134 contacts the first plunger mechanical stop 1130, the plunger 1108 can push the piston 1114 such that the pumping chamber conduit 120 is aligned with the reservoir conduit 1124. When the mechanical extension 1134 contacts the second plunger mechanical stop 1132, the plunger 1108 is able to move the piston 1114 such that the pumping chamber conduit 1120 is aligned with the outlet conduit 1128.

The first plunger mechanical stop 1130, the second plunger mechanical stop 1132, and the plunger mechanical extension 1134 may not be present in all embodiments.

In an alternative embodiment, the cartridge may have a container mechanical stop. The mechanical stop of the container can be in contact with the contact surface. This provides a mechanical stop for the reservoir to substantially align pumping chamber conduit 1120 with reservoir conduit 1124. In some embodiments, there may also be an outlet mechanical stop and a corresponding contact surface for aligning the pumping chamber conduit with the outlet conduit.

In an alternative embodiment, the ends of the volume 1116 may provide mechanical stops for aligning the pumping chamber conduit 1120 with the reservoir conduit. For example, in this example, volume 1116 is closed at one end except for air vent 1140. In some embodiments, the end surface 1142 may also be used as a mechanical stop for the piston 1114.

In some embodiments, plunger 1134 may operate in the position of piston 1114 without using a container mechanical stop or even a conduit mechanical stop. For example, the surface between the piston 1114 and the volume 1116 may be configured such that it is more difficult to move the piston 1114 than to move the plunger 1108, e.g., because the static friction between the piston 1114 and the volume 1116 is greater than the static friction between the plunger 1108 and a corresponding hole in the piston 1114. In this case, the plunger 1108 can be moved without unseating the piston 1114 unless the plunger 1108 contacts one of the first mechanical stop 1130 or the second mechanical stop 1132.

Fig. 12 shows the cartridge 1100 of fig. 11 attached to an actuator assembly 1200. Actuator assembly 1200 includes a linear actuator 1202 that moves along a linear guide 1204 in a direction 1206. The linear actuator 1202 is coupled to the plunger 1108 by a coupling assembly 1208.

Fig. 13A shows a further example of a cartridge 1300. The example in fig. 13 is similar to the examples shown in fig. 11 and 12, with several additional features. In this embodiment, there is an auxiliary container 1322. The auxiliary vessel 1322 is connected to an auxiliary vessel conduit 1324 that can be aligned with the pumping chamber conduit 1120. There is an optional connection for connecting conduit 1326 between vessel 1122 and auxiliary vessel 1322. In this example, there is also an optional membrane 1327 covering the surface of the connecting duct 1326. For example, membrane 1327 may prevent air bubbles from entering reservoir 1122 from auxiliary reservoir 1322. For example, this configuration may be useful for pumping fluid 1302 out of reservoir 1122 and returning unused fluid 1302 to auxiliary reservoir 1322. The receptacle 1122 has an optional vent 1328 and the auxiliary receptacle 1322 has an optional vent 1330. There is a side wall 1332 that divides the container 1122 from the auxiliary container 1322. In some embodiments, where the primary container forms a first portion of the container and the secondary container 1332 forms a second portion of the container, this dividing wall 1332 may not be present. In this example, plunger 1108 and piston 1114 are actuated independently. Such a configuration for the plunger 1108 and piston 1114 may also be used as an alternative configuration to that shown in fig. 11.

Fig. 13B shows an alternative example of a cartridge 1350 similar to the cartridge 1300 shown in fig. 13A. In the embodiment of fig. 13B, there is a separate container 1122 'and a separate auxiliary container 1322'. Connecting conduit 1326 of fig. 13A is not present. The reservoir 1122 ' may contain the first fluid 1302 and the auxiliary reservoir 1322 ' may contain the second fluid 1302 '. The first fluid 1302 and the second fluid 1302' may be different fluids.

Fig. 14 shows the cartridge 1300 of fig. 13 attached to an actuator assembly 1400. In this embodiment, both plunger 1108 and piston 1114 are actuated independently. There is a linear actuator 1202 that moves along a linear guide 1204, where the linear guide 1204 is coupled to a plunger 1108 by a coupling assembly 1208. There is a linear actuator 1402 that moves along a linear guide 1404, where the linear guide 1404 is connected to a piston 1114 by a linkage assembly 1408. Both linear actuators 1202 and 1402 are able to move along direction 1206. The actual implementation of the actuator assembly 1400 is intended to be representative, and other actual configurations may be used.

Fig. 15A and 15B show five different views 1500, 1502, 1504, 1506, 1508 of the embodiment shown in fig. 11 of a sliding valve 1110 with a plunger 1108 and a piston 1114. Fig. 15A and 15B show an example of how the piston 1114 and plunger 1108 can be used to pump fluid from the container chamber through the outlet nozzle 1126. In view 1500, pumping chamber conduit 1120 is aligned with reservoir conduit 1124. The pumping chamber volume 1118 is at its smallest volume. The mechanical extension 1134 is in contact with the first plunger mechanical stop 1130. Next in view 1502, plunger 1108 is retracted along direction 1510. The plunger is retracted until the mechanical extension 1134 contacts the second plunger mechanical stop 1132. In this embodiment, to move, the piston 1114 requires more force than the plunger 1108. In other words, plunger 1108 slides more easily than piston 1114. This can be accomplished by designing plunger 1108 such that plunger 1108 has less friction than piston 1114. This enables the piston 1114 and plunger 1108 to be operated using a single actuator. Mechanical stops 1130 and 1132 are used to limit the movement of the plunger 1108. When a linear force is applied to the plunger 1108, friction on the plunger causes the plunger 1108 to move first, and when the plunger 1108 hits the mechanical stops 1130, 1132, then the plunger 1108 and piston 1114 move together.

The pumping chamber 1118 is filled with fluid from the fluid container. Next in view 1504, the plunger 1108 is further retracted. The mechanical extension 1134 contacts the second plunger mechanical stop 1132, and thus the plunger 1108 exerts a force on the piston 1114. Plunger 1108 is moved so far that piston 1114 moves pumping chamber conduit 1120 into alignment with outlet conduit 1128. Next in view 1506, the plunger 1108 is moved in direction 1514, fluid is forced out of the pumping chamber 1118 by the plunger 1108 and through the outlet conduit 1128. The fluid exits the outlet nozzle 1126 and forms a droplet 1516 that exits the cartridge through the outlet nozzle 1126.

Finally, in view 1508, further depression 1516 of plunger 1108 causes mechanical extension 1134 to exert a force on second plunger mechanical stop 1132 to force piston 1114 to realign pumping chamber conduit 1120 with reservoir conduit 1124. In this embodiment, there are no mechanical stops to align the piston with reservoir tube 1124. This will most likely be implemented by the actuator controlling the plunger 1108. View 1508 is substantially identical to view 1500. At this point, the pumping process can begin again.

Fig. 16A and 16B show an alternative embodiment of the slide valve 1110 of fig. 11. In the embodiment shown in fig. 16A and 16B, the sliding valve includes a piston 1114 with a plunger 1108. The operation of this alternative embodiment is also illustrated in fig. 16A and 16B by views 1600, 1602, 1604, 1606 and 1608. In the embodiment shown in fig. 16A and 16B, the linear position of the receptacle conduit 1124 and the outlet conduit 1128 are inverted relative to the position in fig. 15A and 15B. In contrast to the embodiment shown in fig. 15A and 15B, piston 1114 requires less force to move than plunger 1108. In other words, piston 1114 slides more easily than plunger 1108. This can be accomplished by designing plunger 1108 to have more friction than piston 1114. As described below, the mechanical stops 1130, 1132, 1609, and 1610 in combination with the frictional plunger 1108 enable pumping to be accomplished using a single actuator. This embodiment has an outlet mechanical stop 1610 aligned with the piston 1114 such that the pumping chamber conduit 1120 is aligned with the outlet conduit 1128. This embodiment also has a container mechanical stop 1609 shown extending from slide valve 1110. The piston has a contact surface 1611, and when contact surface 1611 contacts reservoir mechanical stop 1609, reservoir conduit 1124 is aligned with pumping chamber outlet 1120. There is also an outlet mechanical stop 1610 on the slide valve 1110 operable to come into contact with the contact surface 1613. When the outlet mechanical stop 1610 is in contact with the contact surface 1613, the pumping chamber conduit 1120 is aligned with the outlet conduit 128.

In view 1600, pumping chamber conduit 1120 is aligned with reservoir conduit 1124. The pumping chamber 1118 is at its minimum and the contact surface 1611 of the piston 1114 is in contact with the container mechanical stop 1609. Slide valve 1110 is shown having a first plunger mechanical stop 1130 and a second plunger mechanical stop 1132. When the mechanical extension 1134 contacts the first plunger mechanical stop 1130, then the volume of the pumping chamber 1118 is at a minimum. When the mechanical extension 1134 contacts the second plunger mechanical stop 1132, then the volume of the pumping chamber 1118 is at a maximum.

The piston 1108 has its mechanical extension 1134 in contact with the first plunger mechanical stop 1130. Next in view 1602, plunger 1108 is retracted along direction 1612. The volume of the pumping chamber 1118 increases and fluid is drawn from the reservoir chamber until the mechanical extension 1134 contacts the second plunger mechanical stop 1132. The container mechanical stop 1609 prevents the piston 1114 from moving during this time.

Next in view 1604, plunger 1108 is moved in direction 1614. The volume of the pumping chamber 1118 remains the same and the contact surface 1613 of the piston 1114 comes into contact with the outlet mechanical stop 1610 so that the pumping chamber conduit 1120 is aligned with the outlet conduit 1128.

Next in step 1606, the plunger 1108 is depressed further until the mechanical extension 1134 contacts the first plunger mechanical stop. The piston 1114 has come into contact with the outlet pumping chamber conduit mechanical stop 1610. When plunger 1108 is depressed in direction 1616, piston 1114 is not able to move any further. The plunger 1108 thus forces fluid out of the pumping chamber 1118 through the outlet conduit 1128 and the nozzle 1126. A droplet of fluid 1516 forms an exit cartridge. The plunger 1108 can be depressed until the mechanical extension 1134 comes into contact with the first plunger mechanical stop 1130.

Next, at step 1608, plunger 1108 is moved in direction 1618. The plunger is moved in reverse direction 1618 until contact surface 1611 of piston 1114 contacts container mechanical stop 1609. Piston 1114 and plunger 1108 are now in their same position in view 1600. The pumping cycle has been completed. This process may be repeated to pump more fluid 1516 from the cartridge.

Fig. 17 shows two views 1700, 1702 of the combination of the sliding valve 1110 and the plunger 1108, which is an alternative combination to that shown in fig. 11. In this embodiment, there is no mechanical stop and the piston 1114 and plunger 1108 can be operated independently. In view 1700, piston 1114 has been moved such that pumping chamber conduit 1120 is aligned with reservoir conduit 1124. Fluid may be pumped into the pumping chamber 1118 by moving the plunger 1108 outward. Fluid may also be moved back into the container conduit 1124. For example, the fluid used may be moved back to the container chamber 1124, or the plunger 1108 may be reciprocated to mix the fluids. View 1702 shows piston 1114 in a different position such that pumping chamber conduit 1120 is aligned with outlet conduit 1128. Piston 1108 can be moved in direction 1704 to pump fluid through outlet conduit 1128 and outlet nozzle 1126, thereby forcing droplet 1516 of fluid out of the cartridge.

Fig. 18A and 18B show one way of operating the slide valve 1110 of the embodiment shown in fig. 13. The methods shown in fig. 18A and 18B show how the amount of waste of fluid during operation can be reduced. The method is shown in eight different views 1800, 1802, 1804, 1806, 1808, 1810, 1812 and 1814. The piston 1114 and plunger 1108 are operated independently. The method begins in view 1800. In view 1800, pumping chamber conduit 1120 is aligned with container conduit 1124. The plunger 1108 is at a location where the pumping chamber 1118 has a relatively small volume. In view 1802, plunger 1108 is retracted in direction 1816. This causes fluid to be drawn from the fluid container into the pumping chamber 1118. Next in view 1804, both plunger 1816 and piston 1818 are simultaneously retracted in directions 1820, 1818. Both piston 1114 and plunger 1108 are moved the same amount. Both of which are moved until pumping chamber conduit 1120 is aligned with outlet conduit 1128.

Next in view 1806, the piston 1114 remains in the same position and the plunger 1108 is pressed along 1822. This forces fluid out of the pumping chamber 1118 and through the outlet conduit 1128. This forces fluid 1516 in the form of droplets out of the outlet nozzle 1126.

Next in view 1808, to remove fluid remaining within outlet conduit 1128, plunger 1108 is retracted in direction 1824 while piston 1114 remains in the same position. The plunger 1108 has been retracted sufficiently that a majority of the fluid has been removed from the outlet conduit 1128. A dosed amount of air that also forms bubbles 1862 may also be withdrawn. This causes the fluid left in the outlet duct 1128 to be completely emptied and thus avoids drying of the fluid mixture inside this outlet duct 1128. Due to this complete emptying of the outlet conduit 1128, no washing or "priming" step is required before the next dispensing step, which results in a maximum efficiency of the fluid volume usage within the container. Thus, the amount of fluid used for cleaning purposes has been reduced, however the presence of air bubbles may cause inaccuracies in the fluid dispensing.

Next in view 1810, to eliminate this problem, both piston 1114 and plunger 1108 are simultaneously retracted in directions 1830, 1832. Both piston 1114 and plunger 1108 are moved the same amount. It is moved so that the pumping chamber conduit 1120 is aligned with the auxiliary container conduit 1324.

Next in view 1812, piston 1114 remains stationary and plunger 1108 is depressed in direction 1834. This forces the bubble 1826 into the secondary container. This has removed bubbles 1826 from pumping chamber 1118 and pumping chamber conduit 1120. The bubble 1826 is no longer able to interfere with the proper metering of fluid in the pumping chamber 1118.

Finally in view 1814, both piston 1114 and plunger 1108 are pressed simultaneously in directions 1836, 1838 by the same amount. The pumping chamber outlet 1120 is again aligned with the reservoir conduit 1124 and the pumping cycle is complete. The pump can be reused without the bubble 1826 interfering with the proper measurement or determination of the fluid.

Fig. 19 shows an automated analyzer 1900 according to an embodiment of the invention. This automatic analyzer is shown with three cartridges 1902, 1902', 1902 ". There is an actuator assembly 1904 connected to the cartridge 1902. There is an actuator assembly 1904 'attached to the cartridge 1902'. There is an actuator assembly 1904 "attached to the cartridge 1902". The actuator assemblies 1904, 1904 ', 1904 "are sliding valves and plungers for actuating the cartridges 1902, 1902', 1902". The automated analyzer 1900 is shown with relative motion means 1910 that provide relative motion 1912 between the reagent containers or cuvettes 1906 and the cassettes 1902, 1902', 1902 ". A reagent container or cuvette 1906 is shown containing a biological sample 1508.

The cartridges 1902, 1902', 1902 "may be used to add one or more fluids to a biological sample 1908. The automated analyzer 1900 is shown as further comprising a sensor system 1914. The sensor system includes one or more sensors for measuring a quantity or a physical or chemical or biochemical property of the biological sample 1908. For example, sensor 1914 may include a Nuclear Magnetic Resonance (NMR) system, an optical transmission or reflectance measurement system, a pH meter, a camera system, a Polymerase Chain Reaction (PCR) device, an Electrochemiluminescence (ECL) device, a spectroscopic assay system, an electrochemical or optical sensor, and a chromatography system. The relative motion device 1910 is also operable to move reagent containers or cuvettes 1906 to a sensor system 1914.

The arrangement of the cartridges 1902, 1902', 1902 "and the sensor system 1914 is representative. In some embodiments, the reagent containers or cuvettes 1906 may be held in a fixed position and the cassettes 1902, 1902', 1902 "may be moved. The actuation systems 1904, 1904', 1904 "and the sensor system 1914 are shown connected to a hardware interface 1922 of a computer system 1920. The computer system 1920 serves as a controller for the automatic analyzer 1900. The computer 1920 is further shown to include a processor 1924 capable of controlling the operation and execution of the automatic analyzer 1900 using a hardware interface 1922. The processor 1924 is further shown connected to a user interface 1926, computer storage 1928 and computer memory 1930. The computer memory 1928 is shown containing an analysis request 1932. The analysis request 1932 includes a request to analyze the biological sample 1908.

The computer memory 1928 is further shown to contain sensor data 1934 received from the sensor system 1914. The computer memory is further displayed to contain analysis results 1936 determined using sensor data 1934. Computer memory 1930 includes a control module 1940. Control module 1940 contains computer executable code that enables processor 1924 to control the operation and execution of automatic analyzer 1900. For example, the control module 1940 may use the analysis request 1932 to generate commands to generate and send to the actuation systems 1904, 1904', 1904 ", the sensor system 1914, and the relative motion system 1910. Using the sensor data 1934, the control module 1940 may also generate analysis results 1936.

Fig. 20 shows an automatic analyzer 2000 according to an embodiment of the invention similar to the embodiment shown in fig. 19. The automated analyzer 2000 is similar to the automated analyzer 1900 shown in fig. 19. The autoanalyzer 2000 of fig. 20 additionally has meniscus detectors 2002, 2002', 2002 ″. Each meniscal probe 2002, 2002' is positioned adjacent to an outlet nozzle 1126. Each meniscal probe 2002, 2002', 2002 "is connected to a hardware interface 1922. This enables the processor 1924 to control the actuator assemblies 1904, 1904', 1904 "to control the position of the meniscus. This may enable the processor to more accurately and/or reproducibly dispense fluids from the cartridges 1902, 1902', 1902 ", for example.

Fig. 21 shows a further example of a cartridge 2100. The cartridge 2100 shown in fig. 21 is similar to that shown in fig. 11. The cartridge 2100 shown in fig. 21 includes two portions. There is attachable container 2102 and pumping unit 2104. Pumping unit has first connection 2106 and attachable container 2102 has second connection 2108. The first connection 2106 is operable to connect to the second connection 2108. This attaches attachable container 2102 to pumping unit 2104. Attachable container 2102 is shown with vent 1328 in this example. Near second connection 2108, container 1122 is sealed by seal 2110. Near first connection 2106, there is a knife edge 21122 operable to open the seal 2110 when first connection 2106 is connected to second connection 2108.

The embodiment shown in fig. 21 allows for greater flexibility and economy in preparing multiple cartridges. For example, the volume of the attachable container and the type of fluid filling container 1122 can be varied. The pumping unit 2104 may also be varied. For example, the diameter of the plunger 2108 and its stroke can vary. This may allow for the selection of either more accurate, or large volume pumping units.

Fig. 22-25 show various embodiments of a slide valve 1110. All of the embodiments shown in fig. 22-25 show the plunger 1108 with a mechanical extension 1134 on the plunger. As illustrated in fig. 11, in each of these embodiments the piston 1114 has a first plunger mechanical stop 1130 and a second plunger mechanical stop 1132.

The embodiment of slide valve 1110 shown in fig. 22 does not have air vent 1140. There is also no mechanical limit to the vessel or mechanical limit to the outlet. Accurate alignment of the pumping chamber conduit 1120 with the reservoir conduit 1124 or the outlet conduit 1128 may be accomplished or provided by an actuator.

In fig. 23, slide valve 1110 is shown to include air vent 1140, as shown in fig. 11. Slide valve 1110 is shown to include a container mechanical stop 1609 for contacting surface 1611 of piston 1114. Container mechanical stops 1609 align pumping chamber conduit 1120 with container conduit 1124. However, there are no mechanical stops that align outlet conduit 1128 with pumping chamber conduit 1120. Accurate alignment of the pumping chamber conduit 1122 and the outlet conduit 1128 may be accomplished by a linear actuator.

The air vents are not shown in fig. 24. In the embodiment shown in fig. 24, the sliding valve 1110 includes an outlet mechanical stop 1610 for contacting a surface 1613 of the piston 1114. Outlet mechanical stop 1610 is operable to align outlet conduit 1128 with pumping chamber conduit 1120. However, there are no mechanical stops for aligning pumping chamber conduit 1120 with reservoir conduit 1124. Accurate alignment of the vessel conduits may be provided by a linear actuator.

Air vent 1140 is shown in fig. 25. The embodiment shown in fig. 25 includes a mechanical reservoir stop 1609 for contacting surface 1611 of piston 1114. Container mechanical stops 1609 align pumping chamber conduit 1120 with container conduit 1124. The embodiment shown in fig. 25 also shows an outlet mechanical stop 1610 on the slide valve 1110. The outlet mechanical stop 1610 is operable to contact a cutout surface 1613 of the piston 1114. Outlet mechanical stop 1610 is operable to align pumping chamber conduit 1120 with outlet conduit 1128.

The examples shown in fig. 22-25 are intended to be exemplary, and are not all possible combinations of how slide valve 1110 can be configured. For example, the relative positions of the receptacle conduit 1124 and the outlet conduit 1128 can be linearly juxtaposed.

Fig. 26 and 27 show how the friction between the plunger 1108 and the piston 1114 can be increased. In fig. 26, slide valve 1110 is shown with vent 1110 as shown in fig. 11. The slide valve 1110 further includes a reservoir mechanical stop 1610 and an outlet mechanical stop 1609 for contacting the piston 1114. As previously described, these mechanical stops 1609, 1610 act to align the pumping chamber conduit 1120 with the reservoir conduit 1124 and the outlet conduit 1128. Plunger 1108 is shown having a mechanical extension 1134. However, in the embodiment shown in fig. 26, there is no first plunger mechanical stop 1130 and no second plunger mechanical stop 1132 as previously shown. Mechanical extension 1134 contacts surface 2600 within piston 1114. Contact of mechanical extension 1134 with surface 2600 increases friction between plunger 1108 and piston 1114. This allows the piston 1114 to be actuated by movement of the plunger 1108. Since there is no plunger mechanical stop in this embodiment, the movement of the plunger 1108 will be controlled by the linear actuator.

Fig. 18 shows an embodiment of a slide valve 1110 similar to that shown in fig. 26. The embodiment shown in fig. 27 is similar to that shown in fig. 26, except that a first plunger mechanical stop 1130 and a second plunger mechanical stop 1132 have been added to limit the travel of the plunger 1108 relative to the piston 1114. The mechanical extension 1134 still contacts the surface 2600, which surface 2600 increases friction between the plunger 1108 and the piston 1114. This enables the piston 1114 to be actuated by the plunger 1108.

List of reference numerals

100 box

102 actuator assembly

104 linear actuator

105 direction of linear motion

106 rotary actuator

107 direction of rotational movement

108 plunger

110 rotary valve

112 box body

114 cylindrical body portion

116 cylindrical space

118 pumping chamber

120 pumping chamber pipeline

122 container

124 container conduit

126 outlet nozzle

128 outlet conduit

130 coupling assembly

200 first view

202 second view

204 third view

206 fourth view

208 retracted plunger

210 rotating rotary valve

212 plunger pressed

214 fluid

300 fifth view

302 sixth view

304 seventh view

306 retracted plunger

308 bubble

310 rotating rotary valve

312 plunger of pressing

400 first view

402 second view

404 third view

406 fourth view

408 fifth view

410 sixth view

412 seventh view

414 Box

416 auxiliary container

418 connecting pipe

430 auxiliary container conduit

500 automatic analyzer

502 box

502' box

504 actuator assembly

504' actuator assembly

506 reagent container or cuvette

508 biological sample

510 relative movement device

512 relative movement

514 sensor system

520 computer

522 hardware interface

524 processor

526 user interface

528 computer storage

530 computer memory

532 analyze request

534 sensor data

536 results of analysis

540 control module

600 bubble guide structure

602 bubble channel

604 fluid passage

606 bubble

608 space

610 fluid

700 automatic analyzer

702 meniscus detector

800 rotating rotary valve

802 retracting plunger

804 rotating rotary valve

806 depressed plunger

808 rotating rotary valve

810 withdrawn plunger

812 rotating rotary valve

814 plunger with press

816 retracting plunger

818 rotary valve

820 plunger of pressing

900 target volume

902 measure volume

904 Linear fitting

1000 tack

1002 surface tension

1004 viscosity ratio surface tension

1006 percent

1008 accuracy

1010 Coefficient of Variation (CV)

1100 box

1108 plunger

1110 sliding valve

1112 box body

1114 piston

1116 volume

1117 casing

1118 pumping chamber

1120 pumping chamber conduit

1122 container

1122' container

1124 container pipeline

126 outlet nozzle

1128 outlet conduit

1130 first plunger mechanical stop

1132 second plunger mechanical stop

1134 mechanical extension of plunger

1140 air vent

1142 inner surface

1200 actuator assembly

1202 linear actuator

1204 Linear guide

1206 direction of actuation

1208 coupling assembly

1300 box

1302 a fluid

1302' fluid

1322 auxiliary container

1322' auxiliary container

1324 auxiliary container conduit

1326 connecting pipe

1327 membranes

1328 vent

1330 vent hole

1332 separating wall

1400 actuator assembly

1402 linear actuator

1404 linear guide rail

1408 coupling assembly

1500 slide valve and plunger views

1502 views of a slide valve and plunger

1504 view of a slide valve and plunger

1506 slide valve and plunger views

1508 view of a sliding valve and plunger

1510 retracting plunger

1512 retracted plunger

1514 depressed plunger

1516 micro-droplet

1600 slide valve and plunger views

1602 view of a slide valve and plunger

1604 slide valve and plunger view

1606 slide valve and plunger views

1608 view of sliding valve and plunger

1609 mechanical limit for container

1610 outlet mechanical limit

1611 contact surface

1612 retracting plunger

1613 contact surface

1614 pressing plunger

1616 depressed plunger

1618 retracting plunger

1700 view of sliding valve and plunger

1702 slide valve and plunger view

1704 pressing plunger

1800 slide valve and plunger views

1802 view of a sliding valve and plunger

1804 slide valve and plunger views

1806 slide valve and plunger views

1808 slide valve and plunger views

1810 view of a sliding valve and plunger

1812 view of a slide valve and plunger

1814 view of a slide valve and plunger

1816 retracting plunger

1818 retracting plunger

1820 retracting piston

1822 plunger pressed

1824 retracting plunger

1830 retracting piston

1832 retracting plunger

1834 pressing plunger

1836 pressing piston

1838 pressing plunger

1900 automatic analyzer

1902 Box

1902' box

1904 actuator assembly

1904' actuator assembly

1904 "actuator assembly

1906 reagent container or test tube

1908 biological samples

1910 relative movement device

1912 relative movement

1914 sensor system

1920 computer

1922 hardware interface

1924A processor

1926 user interface

1928 computer memory

1930 computer memory

1932 analyzing requests

1934 sensor data

1936 results of analysis

1940 control module

2000 automatic analyzer

2002 meniscus detector

2002' meniscus detector

2100 box

2102 attachable container

2104 pumping unit

2106 first connection

2108 second connection

2110 sealing member

2112 cutting edge

2600 contact the surface.

Claims

1. A cartridge (100, 414, 502 ', 502 ", 1100, 1300, 1350, 1902 ', 1902") for dispensing a fluid (214, 610, 1302 ', 1516), comprising:

a valve (110, 1100), wherein the valve comprises a pumping chamber (118, 1118) for pumping a fluid, wherein the pumping chamber is a cavity within the valve, wherein the valve is operable to place a pumping chamber conduit (120, 1120), wherein the pumping chamber conduit is permanently connected with the pumping chamber;

a plunger (1108) operable to change a volume of the pumping chamber, wherein the pumping chamber is formed by the cavity and the plunger;

a container conduit (124, 1214) for connecting a container to the valve, wherein the valve is operable for placing the pumping chamber conduit in connection with the container conduit; and

an outlet conduit (128, 1128) for dispensing fluid, wherein the valve is further operable to place the pumping chamber conduit in connection with the outlet conduit

Wherein the same opening of the pumping chamber conduit is in contact with either the container conduit or the outlet conduit.

2. The cartridge (1100, 1300, 1350, 1902', 1902 ") of claim 1, wherein the valve is a sliding valve (1110), wherein the sliding valve is operable to move a pumping chamber conduit (1120); wherein the slide valve is operable to move a pumping chamber conduit to connect with the container conduit; and wherein the slide valve is further operable to move the pumping chamber conduit to connect with the outlet conduit.

3. The cartridge of claim 2, wherein the cartridge further comprises a return conduit (1324) connected to the container, wherein the pumping chamber conduit is operable to receive fluid through the container conduit, wherein the return conduit is operable to return fluid to a second portion (1322) of the container, wherein the slide valve is further operable to move the pumping chamber conduit to connect to the return conduit.

4. The cartridge according to claim 2 or 3, wherein the cartridge further comprises:

an auxiliary container (1322'); and

an auxiliary reservoir conduit (1324), wherein the sliding valve is further operable to move the pumping chamber conduit to connect to the auxiliary reservoir conduit.

5. The cartridge of claim 4, wherein the cartridge further comprises a connecting conduit, wherein the connecting conduit is operable to convey fluid between the auxiliary container and the container, and wherein the cartridge comprises a membrane that blocks the connecting conduit, and wherein the membrane is permeable to fluid.

6. The cartridge of claim 2 or 3, wherein the cartridge further comprises a coupling assembly for attaching the sliding valve and the plunger to an actuator assembly.

7. The cartridge of claim 2 or 3, wherein the sliding valve comprises a piston (1114), wherein the cartridge comprises a volume (1116) for receiving the piston, and wherein the piston is operable for moving movement within the volume.

8. The cartridge of claim 7, wherein the piston (1114) and the sliding valve (1110) are operable for collinear movement.

9. The cartridge of claim 7, wherein the sliding valve includes a reservoir conduit mechanical stop (1609) for aligning the pumping chamber conduit with the reservoir conduit and/or an outlet conduit mechanical stop (1610) for aligning the pumping chamber conduit with the outlet conduit.

10. The cartridge of claim 7, wherein the piston includes two plunger mechanical stops (1130, 1132) for limiting movement of the plunger relative to the piston, wherein the plunger is operable to actuate the piston.

11. The cartridge (100, 414, 502', 502 ") of claim 1, wherein the valve is a rotary valve (110), wherein the rotary valve is operable to rotate a pumping chamber conduit (120), wherein the rotary valve and the plunger are operable to be independently actuated, wherein the rotary valve is operable to rotate the pumping chamber conduit to connect with the container conduit, and wherein the rotary valve is further operable to rotate the pumping chamber conduit to connect with the outlet conduit.

12. The cartridge of claim 11, wherein the cartridge further comprises a return line connected to the container, wherein the pumping chamber line is operable to receive fluid from a first portion of the container, wherein the return line is operable to return fluid to a second portion of the container, wherein the rotary valve is further operable to rotate the pumping chamber line to connect to the return line.

13. The cartridge according to claim 11 or 12, wherein the cartridge further comprises:

an auxiliary container (416); and

an auxiliary reservoir conduit (430), wherein the rotary valve is further operable to rotate the pumping chamber conduit to connect to the auxiliary reservoir conduit.

14. The cartridge of claim 13, wherein the cartridge further comprises a connecting conduit (418), wherein the connecting conduit is operable to transfer fluid between the auxiliary container and the container.

15. The cartridge of claim 14, wherein the cartridge comprises a membrane that blocks the connecting conduit, and wherein the membrane is permeable to a fluid.

16. The cartridge of claim 14, wherein the auxiliary container comprises a bubble directing structure (600).

17. The cartridge of claim 14, wherein the auxiliary container comprises a vent, wherein the vent is sealed by a filter, wherein the filter is permeable to air, and wherein the filter is operable to seal fluid in the cartridge.

18. The cartridge of claim 11 or 12, wherein the fluid comprises any one of: magnetic beads, latex beads, dispersoids, nanoparticles, blood typing reagents, immunoreagents, antibodies, enzymes, recombinant proteins, viral isolates, viruses, biological agents, solvents, diluents, proteins, salts, detergents, nucleic acids, bases, and combinations thereof.

19. The cartridge of claim 11 or 12, wherein the cartridge further comprises a sensor operable to determine the fluid dispensed by the outlet nozzle.

20. The cartridge of claim 11 or 12, wherein the cartridge further comprises a coupling assembly (130) for attaching the rotary valve and the plunger to an actuator assembly.

21. The cartridge of claim 11 or 12, wherein the rotary valve comprises a cylindrical body (114), wherein the cartridge comprises a cartridge body (112) with a cylindrical space (116) for receiving the cylindrical body, and wherein the rotary valve is operable to rotate within the cylindrical space.

22. An automated analyzer (500, 1900, 2000) for analyzing a biological sample (508, 1908), wherein the automated system is operable to hold a cartridge according to any one of the preceding claims, wherein the automated analyzer comprises:

an actuator assembly (504, 504 ', 504 ", 1200, 1400, 1904', 1904") operable for actuation of the plunger and the valve;

a controller (520, 1920) for controlling operation of the actuator assembly.

23. The automated analyzer (1900, 2000) of claim 22, wherein the automation system is operable to hold a cartridge of any one of claims 2 to 10, and wherein the actuator assembly (1200, 1400, 1904', 1904 ") is operable for linear actuation of the plunger and the sliding valve.

24. The automated analyzer of claim 23, wherein the automated analyzer is operable to hold the cartridge of claim 10, wherein the actuator assembly is operable for linear actuation of the plunger.

25. The automated analyzer of claim 23, wherein the actuator assembly is operable for separate linear actuation of the plunger and for linear actuation of the sliding valve.

26. The automated analyzer of claim 23, 24 or 25, wherein the cartridge includes an outlet nozzle (1126), wherein the automated analyzer further includes a meniscus detector (2002, 2002', 2002 ") for detecting a meniscus of fluid, wherein the controller is operable to:

controlling the actuator assembly to force fluid through the outlet nozzle;

detecting a meniscus using the meniscus detector; and

controlling the actuator to stop forcing fluid through the outlet when the meniscus is in the predetermined position.

27. The automatic analyzer according to claim 25, wherein the controller is operable to:

controlling (1516, 1618, 1836, 1838) the actuator assembly to connect with the container conduit by moving the sliding valve to move the pumping chamber conduit;

controlling (1510, 1612, 1816) the actuator assembly to increase the volume of the pumping chamber by using a plunger to fill the pumping chamber;

controlling (1512, 1614, 1818, 1820) the actuator assembly to connect with the outlet conduit by moving the sliding valve to move the pumping chamber conduit; and

controlling (1514, 1616, 1704, 1822) the actuator assembly to reduce the volume of the pumping chamber by using a plunger to pump fluid through the outlet conduit.

28. The automated analyzer (500) of claim 22, wherein the automated analyzer is operable for holding a cartridge (100, 414, 502 ', 502 ") of any of claims 11-21, wherein the valve is a rotary valve, and wherein the actuator assembly (504, 504', 504") is operable for separate linear actuation (105, 208, 212, 306, 312, 420, 424, 426, 432) of the plunger and for rotational actuation (107, 210, 310, 422, 428) of the rotary valve.

29. The automatic analyzer according to claim 28, wherein the controller is operable to:

controlling (200) the actuator assembly to rotate the pumping chamber conduit to connect with the container conduit by rotating the rotary valve;

controlling (202) the actuator assembly to increase (208) the volume of the pumping chamber by using a plunger to fill the pumping chamber;

controlling (204) the actuator assembly to connect with the outlet conduit by rotating the rotary valve to rotate (210) the pumping chamber conduit; and

controlling (206) the actuator assembly to reduce the volume of the pumping chamber by using a plunger to pump (212) fluid through the outlet conduit.

30. The automated analyzer of claim 28 or 29, wherein the controller is operable to control (300) the actuator assembly to increase (306) a volume of the pumping chamber by using a plunger to recover fluid from the outlet conduit.

31. The automatic analyzer according to claim 28 or 29, wherein the controller is operable to:

controlling (302) the actuator assembly to rotate (310) the pumping chamber conduit to connect with the container conduit by rotating the rotary valve; and

controlling (304) the actuator assembly to reduce (312) a volume of the pumping chamber by using a plunger to return fluid to the container.

32. The automatic analyzer according to claim 28 or 29, wherein the controller is operable to:

controlling the actuator assembly to connect with the container conduit by rotating the rotary valve to rotate the pumping chamber conduit; and

the actuator assembly is controlled to repeatedly increase and decrease the volume of the pumping chamber by using a plunger to mix fluids in a container.

33. The automated analyzer of claim 28 or 29, wherein the cartridge comprises an outlet nozzle, wherein the automated analyzer further comprises a meniscus detector (702, 702', 702 ") for detecting a meniscus of the fluid, wherein the controller is operable to:

controlling the actuator to force fluid through the outlet nozzle;

detecting a meniscus using the meniscus detector; and

controlling the actuator to stop forcing fluid through the outlet when the meniscus is in a predetermined position.

34. The automated analyzer of claim 28 or 29, wherein the automated analyzer is operable to hold a plurality of cartridges (504, 504', 504 "), wherein each of the plurality of cartridges is in accordance with any of claims 1 to 12.

35. A method of operating a cartridge according to any one of claims 2 to 10, wherein the method comprises the steps of:

moving (1516, 1618, 1836, 1838) the sliding valve to move the pumping chamber conduit to connect with the container conduit;

increasing (1510, 1612, 1816) the volume of the pumping chamber using the plunger to fill the pumping chamber;

moving (1512, 1614, 1818, 1820) the slide valve to move the pumping chamber conduit to connect with the outlet conduit; and

reducing (1514, 1616, 1704, 1822) the volume of the pumping chamber using the plunger to pump fluid through the outlet conduit.

36. The method of claim 35, wherein the method further comprises recovering fluid from the outlet conduit by increasing (1824) a volume of the pumping chamber using the plunger.

37. The method according to claim 35 or 36, wherein the method further comprises the steps of:

moving (1830, 8132) the pumping chamber conduit to connect with the container conduit by moving the sliding valve; and

returning (1834) fluid to the container by reducing a volume of the pumping chamber using the plunger.

38. A method of operating a cartridge according to any one of claims 11 to 21, wherein the method comprises the steps of:

rotating the rotary valve to rotate the pumping chamber conduit to connect with the container conduit;

increasing the volume of the pumping chamber using a plunger to fill the pumping chamber;

rotating the rotary valve to rotate the pumping chamber conduit to connect with the outlet conduit; and

reducing the volume of the pumping chamber using the plunger to pump fluid through the outlet conduit.

39. An automated system (900, 1000) for dispensing a fluid (908), wherein the automated system is operable to hold a cartridge according to any of claims 2 to 10, wherein the automated system comprises:

an actuator assembly (200, 400, 904', 904 ") operable for linear actuation of the plunger and the sliding valve;

a controller (920) for controlling operation of the actuator assembly.

40. The automated system of claim 39, wherein the automated system is operable to hold the cartridge of claim 9, wherein the actuator assembly is operable for linear actuation of the plunger.

41. The automated system of claim 40, wherein the actuator assembly is operable for separate linear actuation of the plunger and for linear actuation of the sliding valve.

42. The automated system of any of claims 39, 40 or 41, wherein the cartridge comprises an outlet nozzle (126), wherein the automated analyzer further comprises a meniscus detector (1002, 1002', 1002 ") for detecting a meniscus of the fluid, wherein the controller is operable to:

controlling the actuator assembly to force fluid through the outlet nozzle;

detecting the meniscus using the meniscus detector; and