HK1205261B

HK1205261B - Cartridge for dispensing a fluid comprising a reagent

Info

Publication number: HK1205261B
Application number: HK15105803.9A
Authority: HK
Inventors: Thorsten BRÜCKNER; Peter Koltay; Norbert Oranth; Jürgen Spinke; Laurent Tanguy
Original assignee: F. Hoffmann-La Roche Ag
Priority date: 2012-05-08
Filing date: 2013-05-07
Publication date: 2017-12-01

Description

Cartridge for dispensing a fluid comprising a reagent

Technical Field

The present invention relates to dispensing of fluids comprising reagents, in particular cartridges for dispensing fluids.

Background

In medical laboratories, in vitro diagnostics are typically performed on biological samples. Such testing may be performed by using a pipette or may be performed by using an automated analyzer. An automated analyzer may automatically add reagents to a biological sample and may measure one or more physical properties of the biological sample during analysis. Automated analyzers are well known in the art. For example, european patent EP 1959257 a2 discloses an automatic analyzer including a reagent cartridge holding mechanism for holding a plurality of reagent cartridges.

International patent application publication WO 2007/122387 discloses a cartridge for dispensing a reagent contained in a reagent reservoir. The cartridge comprises a reservoir defining an enclosed gas space above the reagent. The cartridge further comprises a vent allowing gas to the gas space in use. The vent outlet is located at the base of the reservoir. The vent is placed as low as possible in the reservoir so as to increase the volume of reagent that can be expelled at a constant head pressure. WO 2007/122387 further discloses that the generation of bubbles at the vent outlet results in fluctuations in reservoir pressure and that the pressure increases at the moment bubbles are formed at the vent outlet. This effect is reduced by minimizing the volume of gas space above the reagent.

Disclosure of Invention

The present invention provides a cartridge for dispensing a fluid, an automatic analyzer and a method of dispensing a fluid using an automatic analyzer in the independent claims. Embodiments are given in the dependent claims.

In one aspect, the present invention provides a cartridge for dispensing a fluid. The cartridge comprises a reservoir chamber for receiving the fluid. The reservoir chamber is also operable to receive ventilation gas. The reservoir chamber includes an inlet for receiving ventilation gas. There is an outlet for dispensing fluid from the reservoir. At least a portion of the reservoir chamber is operable to be filled with a ventilation gas when the cartridge is placed in the operational position. The inlet is located within the portion operable to be filled with ventilation gas. The fluid includes a reagent. The cartridge further comprises baffle means for restricting diffusion of gas through the inlet. The reservoir chamber receives ventilation gas via the baffle means. Because the ventilation gas is supplied directly to the gas in the reservoir, no bubbles are formed which would cause a change in pressure in the reservoir chamber. In such an embodiment, the baffle means provides ventilation gas directly to the portion of the reservoir chamber operable to be filled with ventilation gas. Embodiments of the invention may thus have the advantage that there is always a pressure balance between the gas outside the cartridge and inside the reservoir chamber. Embodiments of the invention may also have the advantage that the baffle means reduces gas diffusion into the reservoir chamber which may damage or degrade the fluid. The baffle means may also reduce evaporation of fluid within the reservoir chamber, since diffusion of gas out of the reservoir chamber is also reduced.

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

As used herein, "computer-readable storage medium" encompasses any tangible storage medium that can store instructions executable by a processor of a computing device. Computer-readable storage media may refer to computer-readable non-transitory storage media.

"computer memory" or "memory" is an example of a computer-readable storage medium. Computer memory is any memory that is directly accessible 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" encompasses 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.

In one aspect, the present invention provides a cartridge for dispensing a fluid. The cartridge includes a reservoir chamber operable to receive a fluid and receive a ventilation gas. Ventilation gas as used herein encompasses gas that is used to equalize the pressure outside the reservoir chamber and inside the reservoir chamber when fluid is removed from the reservoir chamber. The reservoir chamber includes an inlet for receiving ventilation gas and an outlet for dispensing fluid. At least a portion of the reservoir chamber is operable to be filled with ventilation gas when in the operating position. The inlet is located within the portion operable to be filled with ventilation gas. In other words: when the cartridge is in the operating position, ventilation gas is added to the reservoir chamber at a location where ventilation gas is already present or is immediately filled with ventilation gas. The fluid includes a reagent. As used herein, a reagent is a substance or compound that is added to a chemical system to bring about a chemical or biochemical reaction or is added to observe whether a reaction occurs.

The cartridge further comprises baffle means for restricting diffusion of gas through the inlet. The reservoir chamber is operable to receive ventilation gas via the baffle means. Baffle means as used herein encompasses structures that cause the gas to follow a particular path in order to reach the inlet. The baffle means provides a means of restricting the diffusion of gases into the inlet and outlet. As such, gas diffusion as used herein may refer to the diffusion of ventilation gas into the cartridge and/or the diffusion of gas already present in the reservoir chamber out. Such an embodiment may be advantageous because it may extend the useful life of the reagents within the cartridge. For example, depending on the reagent, the composition of the ventilation gas may result in the reagent losing efficiency or losing its chemical reactivity; also the gas inside the reservoir chamber may contain vapour from the fluid. The baffle means also restricts the fluid vapour from diffusing out of the inlet. This may help prevent changes in the concentration of particular agents.

In another embodiment, the cartridge comprises a cap for sealing the inlet. The cap may be operable to be moved to an open position to open the inlet. In some embodiments, the cap may directly seal the inlet, which is the sealing effect of the cap at the inlet. In other embodiments, the cap seals the baffle or a portion of the baffle. This indirectly seals the inlet.

A cap as used herein may in some embodiments be a mechanical part operable to open or close an inlet. Examples of caps may include removable plastic pieces, tape pieces, and mechanical parts operable to interlock with the cartridge, such as a screw cap.

In another embodiment, the inlet is operable to maintain a constant pressure within the portion of the reservoir chamber operable to be filled by venting. Such an embodiment may be beneficial because maintaining the pressure at a constant value enables more accurate dispensing of the fluid. In some embodiments, the inlet is operable to maintain a constant pressure within the portion of the reservoir chamber operable to be vent-filled when dispensing the fluid.

For example, in U.S. patent application publication US 2010/0015009 a1, an inlet submerged in a fluid is disclosed. The gas enters the cartridge reservoir by bubbling at the inlet. This bubbling results in small changes within the reservoir. This can lead to inconsistencies in the amount of fluid dispensed. Especially if the fluid volume is in the microfluidic range. Embodiments of the present invention may provide more accurate fluid distribution.

In another embodiment, the inlet is operable to maintain a constant pressure within the portion of the reservoir chamber operable to be filled by ventilation when ten to ninety percent, preferably twenty to eighty percent, of the reservoir chamber is filled with fluid. Such an embodiment may be beneficial because maintaining the pressure at a constant value enables more accurate dispensing of the fluid.

In some embodiments, the cartridge may comprise a filling inlet for filling the fluid into the reservoir chamber.

In some embodiments, the ventilation gas may be normal atmospheric air. In some embodiments, the baffle device is open to the atmosphere.

In another embodiment, the cap is operable to be moved to an open position to open the inlet. The cap may be removable or may be movable but fixed to the cartridge.

In another embodiment, the cap is operable to be moved to the closed position. This may be used to reseal the inlet, for example.

In another embodiment, the cap is operable to be moved from an open position to a closed position.

In another embodiment, the cap is operable to be moved from the closed position to the open position.

In another embodiment, the cartridge comprises a cap for sealing the inlet. The cartridge is operable to form at least a part of the shutter means when the cap is open. Such an embodiment may be beneficial because removing the cap so that the cap is in the operative position forms part of the shutter device.

In another embodiment, the cartridge comprises a thread for attaching a cap. The baffle device includes a diffusion path formed within the threads. For example, the diffusion path may be a tube molded into the threads or a channel cut or molded into the surface of the threads. Such an embodiment may be beneficial because it may provide a cost-effective means of providing and integrating the baffle device into existing structures.

In another embodiment, the diffusion path is a channel within the thread. The cartridge further comprises a cap restraint for limiting the opening of the cap to a predetermined amount. For example, the cap and a portion of the cartridge may each have a tab or stop thereon. When the cap is opened for a so-called quarter or half or three quarter turn it may prevent the cap from rotating further. Such an embodiment may be beneficial because it may provide a means of opening the thread a predetermined amount such that diffusion along the passageway is predictable and consistent from cartridge to cartridge.

In another embodiment the baffle means is at least partially formed on the outer surface of the cartridge. Such an embodiment may be beneficial as it may provide a contact means for integrating the baffle device into the cartridge.

In another embodiment, the baffle means comprises a tube mounted on the outer surface.

In another embodiment, the baffle means is at least partially formed within the reservoir chamber. Such an embodiment may be beneficial in that the baffle means may be added to an existing cartridge or the baffle means may be tailored for a specific fluid. For example, some fluids may require a baffle device that restricts diffusion more than another fluid in order to preserve reagents.

In another embodiment, the baffle means comprises a tube located at least partially within the reservoir chamber. Such an embodiment may be beneficial in that the amount of tubing within the reservoir chamber may be easily adjusted during manufacturing of the cartridge.

In another embodiment, the tube includes an opening and an inlet. The opening may open directly to the atmosphere or to a gas supply. There may be a gas filter at the inlet.

The cap may be mounted, for example, using threads. When the cap is in the closed position, it pushes against and seals the inlet. When the cap is not screwed on, it is removed from the inlet and opens the inlet.

In another embodiment, the tube has a length-to-diameter ratio of at least 2.

In another embodiment, the tube has a length-to-diameter ratio of at least 100.

In another embodiment, at least a portion of the cartridge is injection molded. The baffle means is at least partially formed by said portions.

In another embodiment, the baffle means comprises a gas filter. A gas filter may be beneficial because it may help to further reduce diffusion through the inlet in some embodiments. In some embodiments, the gas filter may be microporous to allow only gas to pass through, and in some embodiments the filter may be hydrophobic. In other embodiments, the gas filter may be: polytetrafluoroethylene (PTFE), carbon fiber, PTFE coated carbon fiber, polymer fiber, or porous form of fluoropolymer fiber.

Such an embodiment may also benefit from the aspect that the gas filter may help to retain fluid within the reservoir chamber.

In another embodiment, the cartridge further comprises a fluid.

In another embodiment, the fluid comprises a blood-setting reagent.

In another embodiment, the fluid comprises a diluent.

In another embodiment, the fluid comprises a solvent.

In another embodiment, the fluid comprises a catalyst.

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 isolation agent.

In another embodiment, the fluid comprises a virus.

In another embodiment, the fluid comprises a biological agent.

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 matrix.

In another embodiment, the fluid includes a dispersant. Dispersants as used herein encompass particles or particulates suspended within a fluid.

In another embodiment, the fluid may comprise latex particles.

In another embodiment, the fluid may comprise nanoparticles.

In another embodiment, the fluid may comprise magnetic particles.

In another embodiment, the cartridge further comprises a dispenser for dispensing the fluid. The dispenser is operable to receive fluid from the outlet. In some embodiments, the dispenser may be a microfluidic dispenser. In other embodiments, the dispenser may be or include a nozzle. For example, the dispenser may be or include a straight tube or it may be or include a nozzle having one or more valves contained therein.

In another embodiment, the dispenser is operable to dispense fluid at a rate independent of the baffle means. In other words, the distribution of the fluid is not regulated or controlled by the baffle means.

For example, in US patent application US 2011/030760 a1, a device for the controlled release of a substance is disclosed. The regulator element restricts the flow of gas into the apparatus and effectively controls the release rate of the fluid. In contrast, embodiments of the present invention can dispense fluid at a rate that is effectively independent of the baffle device. The baffle means will have such a small effect on the dispensing rate that it is much smaller than the actual volume dispensed. This may enable more accurate dispensing of the fluid.

In another embodiment, the dispenser is a microfluidic dispensing assembly.

In another embodiment, the dispenser is operable to dispense any one of: a volume of less than 10 μ L, less than 500nL, less than 200nL, less than 100nL, and less than 20 nL.

In another embodiment, the cap is attached to the cartridge.

In another embodiment, the cap is operable to be removed from the cartridge.

In another embodiment, the cap is movable between an open position and a closed position, wherein the cap opens the shutter means when in the open position.

In another aspect, the present invention provides an automated analyzer for holding and receiving a cartridge according to an embodiment of the present invention. The automated analyzer includes an actuator assembly operable to actuate the dispenser. The automated analyzer further includes a controller for controlling operation of the actuator assembly.

The dispenser may be mechanically, pneumatically, magnetically and/or electrically actuated. Depending on the embodiment and how the dispenser is constructed. In an embodiment, the cartridge is in an operative position when installed in an automatic analyzer.

In another aspect, the present invention provides a method of dispensing a fluid using an automated analyzer. The method comprises the step of providing a cartridge. The cartridge comprises a reservoir chamber. The reservoir chamber is filled with a fluid. The fluid includes a reagent. The reservoir chamber includes an inlet for receiving ventilation gas and an outlet for dispensing fluid. The cartridge further comprises baffle means for restricting diffusion of gas through the inlet. The cartridge further comprises a dispenser for dispensing the fluid. The method further comprises the step of installing the cartridge in an operating position within the automated analyzer. The automated analyzer includes an actuator assembly for actuating the dispenser. The method further comprises the step of receiving fluid from the outlet by use of a dispenser. The method further includes the step of operating the actuator assembly to dispense the fluid. The method further comprises the step of receiving ventilation gas via a baffle device at the inlet. The method further comprises the step of filling at least a portion of the reservoir chamber with a ventilation gas. The inlet is located within the portion operable to be filled with ventilation gas.

In another embodiment, the method further comprises the step of removing the seal from the baffle device to provide air as the ventilation gas.

It is to be understood that one or more of the above-described embodiments of the invention may be combined, as long as the combined embodiments are not mutually exclusive.

Drawings

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

fig. 1 shows a cartridge 100 according to an embodiment of the invention;

FIG. 2 illustrates an automated analyzer 200 according to an embodiment of the present invention;

FIG. 3 shows a flow chart depicting a method according to an embodiment of the invention;

fig. 4 shows a cartridge according to a further embodiment of the invention;

fig. 5 further illustrates the cartridge of fig. 4;

fig. 6 shows a cartridge according to a further embodiment of the invention;

fig. 7 further illustrates the cartridge of fig. 6, which provides a view onto the outer surface of the cartridge of fig. 6;

fig. 8 shows a cartridge according to a further embodiment of the invention;

fig. 9 further illustrates the cartridge of fig. 8; and

fig. 10 shows a cartridge according to a further embodiment of the invention.

Detailed Description

Like-numbered elements in the figures are either equivalent elements or perform the same function. Elements that have been previously discussed will not necessarily be discussed in subsequent figures if they are functionally equivalent.

Fig. 1 shows a cartridge 100 according to an embodiment of the invention. The cartridge 100 comprises a reservoir chamber 102 for holding a fluid 104. The reservoir chamber 102 is only partially filled with the fluid 104. At the top of the reservoir chamber 102 there is a region filled with gas 106. The baffle means 108 is adjacent to the reservoir chamber 102. In this example, the baffle device 108 is a vent 110 to atmosphere. Traveling through the baffle means, there is an optional gas filter 112 covering an inlet 114 to the reservoir chamber 102. The inlet 114 provides ventilation gas to the gas-filled portion 106 of the reservoir chamber 102. The inlet 114 is attached to the baffle means 108. The fluid 104 exits the reservoir chamber 102 via the outlet 116. In such an example, there is an optional distributor 118. In such embodiments, the dispenser may be a mechanism for pumping fluid, or it may simply be a nozzle or tube for dispensing fluid.

Fig. 2 shows an automated analyzer 200 according to an embodiment of the present invention. The automatic analyzer is shown with three cartridges 202, 202', and 202 ". There is an actuator assembly 204 connected to the cartridge 202. There is an actuator assembly 204 'attached to the cartridge 202'. There is an actuator assembly 204 "attached to the cartridge 202". The actuator 204, 204', 204 "is used to actuate the dispenser 118 of the cartridge 202, 202', 202". The automated analyzer 200 is shown with a relative motion device 210 that provides relative motion 212 between the sample holder 206 and the cartridges 202, 202', and 202 ". The sample holder 206 is shown containing a biological sample 208. The cartridge 202, 202', 202 "may be used to add one or more fluids to the biological sample 208. Automated analyzer 200 may optionally include a measurement system 214. The measurement system may comprise one or more sensors for measuring a physical quantity or a physical property of the biological sample 208, for example the measurement system 214 may comprise an NMR system, an optical transmission or reflection measurement system, an electrochemical or optical sensor, a pH meter, a camera system or a chromatography system. The relative motion device 210 is also operable to move the sample holder 206 to the measurement system 214.

The arrangement of the cartridges 202, 202', 202 "and the measurement system 214 is representative. The measurement system 214 may alternatively be part of the sample holder 206. In some embodiments, the sample holder 206 may be held in a fixed position and the cartridge 202, 202', 202 "may be moved. The actuation systems 204, 204', 204 "and the measurement system 214 are shown as being connected to a hardware interface 222 of a computer system 220. The computer system 220 serves as a controller for the automated analyzer 200. Computer 220 is further shown as containing a processor 224 that is capable of controlling the operation and functions of the automated analyzer 200 through the use of a hardware interface 222. The processor 224 is shown as being further connected to a user interface 226, computer storage 228, and computer memory 230. The computer memory 228 is shown as containing an analysis request 232. The analysis request 232 includes a request to analyze the biological sample 208.

The computer memory 228 is shown as further containing sensor data 234 received from the measurement system 214. The computer memory 228 is shown as further containing analysis results 236 that are determined using the sensor data 234. The computer memory 230 includes a control module 240. The control module 240 contains computer executable code that enables the processor 224 to control the operation and function of the automated analyzer 200. For example, the control module 240 may use the analysis request 232 to generate and send commands to the actuation systems 204, 204', 204", the measurement system 214, and the relative motion system 210. The control module 240 may also generate the analysis results 236 by using the sensor data 234.

Fig. 3 shows a flow chart describing a method according to an embodiment of the invention. First in step 300, a cartridge is provided. Thereafter in step 302, the cartridge is installed into the automatic analyzer and the cartridge is in an operating position. Thereafter, in step 304, fluid is dispensed (i.e., received) from the outlet by using the dispenser. Thereafter in step 306, the actuator center operates to dispense fluid. The ventilation gas is then received via a baffle device at the inlet of the fluid reservoir in step 308. Finally in step 310, at least a portion of the reservoir chamber is filled with ventilation gas.

Fig. 4 and 5 show an alternative embodiment of a cartridge 400 according to the invention. In fig. 4 and 5, the two cartridges are integrated into a common housing. The cartridge 400 is designed with a cap 402 secured by threads 404. The reservoir chamber 102 is sealed by a cap 402. There is a channel 406 cut or molded into the threads 404. When the cap 402 is slightly open, as shown in FIG. 5, the passage 406 forms a vent 110 to atmosphere. At the top of the threads 404, the gap between the cap 402 and the threads 404 forms the inlet 114. In some embodiments, the gas filter may flare over the opening of the inlet 14. This position is labeled 500 in fig. 5. The reservoir chamber 102 is sealed and the inlet 114 is closed when the cap 402 is closed. When cap 402 is open, gas can diffuse into channel 406. The amount that cap 402 is opened may be controlled by placing a stop on cap 402 and a corresponding stop on reservoir chamber 102 to prevent cap 402 from being opened too far.

Fig. 6 and 7 show a cartridge 600 according to a further embodiment of the invention. In fig. 6 and 7, the two cartridges are integrated into a common housing, in the embodiment shown in fig. 6 and 7, a tube 602 is used which is attached to the surface of the reservoir chamber 02 or which is molded or partially molded to the reservoir chamber 102. The tube 602 has a vent 110 to atmosphere and follows a coiled path on the outside of the cartridge 600. The tube 602 is then connected to the inlet 114 of the reservoir chamber 102.

Fig. 8 and 9 show a cartridge 800 according to a further embodiment of the invention. In fig. 8 and 9 the two cartridges are integrated into a common housing, in this example with a gas filter 112 mounted at the entrance to the tube 802. The tube is located within the reservoir chamber 102. The tube extends up to the top of the threads on which the cap 402 is mounted. In such embodiments, the gas filter 112 prevents fluid from exiting the cartridge 102 and also prevents external particles or liquids (e.g., dust particles or condensed water droplets) from entering and clogging the tube 802. Fig. 9 shows an example in which the gas filter 112 on one cartridge 800 is removed. Cap 402 is also removed in fig. 9. It can be seen how the inlet 114 is positioned within the reservoir chamber 102 at the highest point. The gas filter 112 prevents fluid from exiting the reservoir chamber 102.

Fig. 10 shows another example of a cartridge 100. This example is used to discuss the diffusion of gas into the cartridge 100. The cartridge 100 includes a reservoir chamber 102 partially filled with a fluid 104 and a gas 106. The baffle means is represented in the figure by a tube 108. The baffle device 108 has a vent 110 to atmosphere and an inlet 114 into the reservoir chamber 102 within the gas-filled region 106. The line labeled 1000 represents gas molecules diffusing through the baffle device 108 to the inlet 114.

The cartridge shown in fig. 10 has both gas and liquid within the reservoir chamber 102. The exterior of the chamber is at atmospheric conditions. The two regions are separated by a tube. The liquid inside the cartridge can gradually degrade due to molecules in the ambient gas. These molecules move from the surrounding environment to the interior of the cartridge by diffusion.

Calculations of how to define the tube diameter and length are detailed to demonstrate how to select these parameters to prevent too rapid a breakdown in the chemistry of the liquid.

Basically, the longer and thinner the tube 108, the slower the diffusion of the molecules 1000 inside the cartridge. A general parameter, referred to herein as impedance, is defined and used to perform calculations that ensure that a cartridge will be usable if it remains open in the same environment for a certain time. Z is defined as the ratio between the difference in concentration of molecules 1000 on the channel and the product of the molecular weight multiplied by the diffusion constant D of the molecules 1000 diffusing in the cartridge.

This impedance can be easily calculated for long and round tubes and used as a reference.

In order to make such a calculation, it is necessary to define or determine the conditions under which the liquid can no longer be used due to contamination or degradation by molecules from the environment. Thus, there is an amount Ncrit, which represents the critical number of molecules 1000 that have diffused inside the reservoir. This amount depends to a large extent on several parameters such as solubility and on different chemical reaction parameters such as temperature or pressure.

To define the important variables, the concentration units are the number of molecules/m³：

-t _ life: desired duration of the reservoir

-C _ 0: the concentration of such molecules in the surrounding environment

-N _ crit: critical number of particles inside the cartridge that should not be obtained during time t _ life

-V _ cart: total volume of cartridge

-V _ gas: volume of gas in cartridge

-C _ gas _ 0: initial concentration of molecules in the gas portion of the reservoir

-D: is the diffusion constant of the molecule under the considered conditions

-Z: geometric inductance

For round and long homogenizing tubes

L: length of

S: cross-sectional surface area (= pi R)²）。

Z is defined as the ratio between the concentration difference over the channel and the product of the molecular weight multiplied by the diffusion constant D.

For simple circular and long geometries, the maximum molecular flow from the outside to the inside can be defined in a steady state approximation:

(number of molecules/second)

Thus, by simple integration, the maximum number of molecules within the cartridge that have diffused internally at time t is:

(number of molecules)

Then, we can deduce that we need the inequality:

more generally:

to be sure to ensure that the lifetime of the liquid inside the reservoir is greater than t, the impedance Z must follow the formula:

as previously mentioned, in the case of a tube that is a homogenous circle, Z can be defined as follows:

thus (for a circular tube):

as long as the impedance Z of the tube is greater than Zcrit, the durability of the liquid and cartridge is maintained for a minimum time t.

Example (c): CO in water₂

- D=0.16e-4m²/s

- V_cart=30ml=30e-6m³

-T life =1 year =365.25 × 24 × 3600 s

- pCO₂=4e-4 x 101325 (CO in air)₂Partial pressure of (2)

- N_crit=N_crit_gas+N_crit_liq

N_crit_gas=Vgas*（Na*pCO₂）/（R*T）

Where Na = avogalois constant, R = ideal gas constant and T = temperature.

N_crit_liq=Vliq*MaxConCO₂

This value is taken to be about 120mg/l, which is much larger than N _ crit _ gas.

When the partial pressure in the gas volume is obtained and CO in the water₂Obtaining CO in the gas at molecular saturation (approximately twice the amount required to saturate the gas)₂Critical number of molecules.

-for one year stability:

Vliq=29ml

l =100cm and D =3.2 mm

L =10cm and D =1 mm

Vliq=15ml

L =100cm and D =2.3 mm

L =10cm and D =726 μm

Vliq=1ml

L =100cm and D =650 μm

L =10cm and D =205 μm.

Vliq is the volume of liquid or fluid in the reservoir chamber. If the length and diameter values of the tube are chosen such that the impedance is above these values, the cartridge will have a desired lifetime of one year. For example, in one embodiment, the baffle device comprises a tube having a length greater than or equal to 10cm and a diameter equal to or less than 1 millimeter. For a diameter tube having a length of 10cm and 1 mm, Z =1.24e5m^-1. In one embodiment of the invention, the impedance of the baffle device as defined above is less than or equal to 1.24e5m^-1. In such an embodiment, the fluid may be a creatinine test reagent.

Similarly, for 15ml liquid in the reservoir chamber, 1ml gas in the cartridge and considering CO₂The diffusion, the length of the tube should be at least 10cm and the diameter less than or equal to 726 μm. In one embodiment of the invention, the impedance of the baffle device as defined above is less than or equal to Z =12.42e5m^-1. In such an embodiment, the fluid may be a creatinine test reagent.

List of reference numerals

100 Cartridge

102 reservoir chamber

104 fluid

106 gas

108 baffle device

110 to atmosphere

112 gas filter

114 inlet port

116 outlet port

118 dispenser

200 automatic analyzer

202 Cartridge

202' cartridge

204 actuator assembly

204' actuator assembly

204 "actuator assembly

206 sample holder

208 biological sample

210 relative movement device

212 relative movement

214 measurement system

220 computer

222 hardware interface

224 processor

226 user interface

228 computer memory

230 computer memory

232 analyze requests

234 sensor data

236 results of analysis

240 control module

400 Cartridge

402 cap

404 thread

406 in the thread

500 gas filter position

600 Cartridge

602 tube

800 Cartridge

802 pipe

1000 diffusion path.

Claims

1. A cartridge (100, 202, 202', 202", 400, 600, 800) for dispensing a fluid (104), wherein the cartridge comprises:

-a reservoir chamber (102) operable to receive the fluid and to receive a ventilation gas (106), wherein the reservoir chamber comprises an inlet (114) for receiving the ventilation gas and an outlet (116) for dispensing the fluid, wherein at least a portion (106) of the reservoir chamber is operable to be filled with the ventilation gas when in an operational position, wherein the inlet is located within the portion operable to be filled with the ventilation gas, wherein the fluid comprises a reagent; wherein the inlet is operable to maintain a constant gas pressure within the portion of the reservoir chamber operable to be filled with the ventilation gas when ten to ninety percent of the reservoir chamber is filled with the fluid;

-baffle means (108, 406, 602, 802) for restricting the diffusion of gas through the inlet, wherein the reservoir chamber is operable to receive the ventilation gas via the baffle means, wherein the inlet is operable to maintain a constant gas pressure within the portion of the reservoir chamber operable to be filled with the ventilation gas; and

-a distributor (118) operable to receive fluid from the outlet, wherein the distributor is operable to distribute fluid at a rate independent of the baffle means.

2. The cartridge of claim 1, wherein the cartridge further comprises a cap (402) for sealing the inlet.

3. The cartridge of claim 2, wherein the cap is operable to be moved to an open position in order to open the inlet.

4. The cartridge of claim 3, wherein the cap is operable to reseal the inlet.

5. The cartridge of claim 2, 3 or 4, wherein the cartridge is operable to form at least a portion of the shutter means when the cap is open.

6. The cartridge of any one of claims 2-4, wherein the cartridge comprises threads for attaching the cap.

7. The cartridge of claim 6, wherein the baffle means comprises a diffusion path formed within the thread.

8. The cartridge of claim 7, wherein the diffusion path comprises a channel (406) within the thread, and wherein the cartridge further comprises a cap restraint for limiting an opening of the cap to a predetermined amount.

9. The cartridge of any one of claims 2-4, wherein the baffle means comprises a tube (802) located at least partially within the reservoir chamber, wherein the tube comprises an opening and the inlet, and wherein the cap is operable to seal the inlet within the reservoir chamber.

10. The cartridge of any one of claims 2-4, wherein the cap is attached to the cartridge.

11. The cartridge of any one of claims 2-4, wherein the cap is operable to be removed from the cartridge.

12. The cartridge of any one of claims 2-4, wherein the cap is movable between an open position and a closed position, and wherein the cap opens the shutter means when in the open position.

13. The cartridge according to claim 1 or 2, wherein the baffle means comprises a tube (802) located at least partially within the reservoir chamber.

14. The cartridge according to any one of the preceding claims 1-4, wherein the baffle means is at least partially formed on an outer surface of the cartridge.

15. The cartridge of claim 14, wherein the baffle means comprises a tube (602) mounted on the outer surface.

16. The cartridge according to any one of the preceding claims 1-4, wherein the baffle means is at least partially formed within the reservoir chamber.

17. The cartridge according to any one of the preceding claims 1-4, wherein at least a portion of the cartridge is injection moulded, and wherein the baffle means is at least partially formed by said portion.

18. The cartridge according to any one of the preceding claims 1-4, wherein the baffle means comprises a gas filter (112, 500).

19. The cartridge according to any one of the preceding claims 1-4, wherein the cartridge further comprises the fluid.

20. The cartridge according to any one of the preceding claims 1-4, wherein the fluid comprises any one of the following: blood-typing agents, solvents, diluents, catalysts, antibodies, enzymes, recombinant proteins, viral separation agents, viruses, biological agents, proteins, salts, detergents, nucleic acids, matrices, dispersants, latex particles, nanoparticles, magnetic particles, and combinations thereof.

21. The cartridge of any one of the preceding claims 1-4, wherein the dispenser is a microfluidic dispensing assembly.

22. The cartridge according to any one of the preceding claims 1-4, wherein the dispenser is operable to dispense any one of the following: a volume of less than 10 μ L, less than 500nL, less than 200nL, less than 100nL, and less than 20 nL.

23. An automated analyzer (200) for analyzing a biological sample; wherein the automatic analyzer is operable to hold a cartridge (100, 202, 202', 202", 400, 600, 800) according to claim 21 or 22; wherein the automatic analyzer is operable to hold the cartridge in the operative position; wherein the automated analyzer comprises an actuator assembly (204, 204', 204 ") operable to actuate the dispenser; and wherein the automated analyzer further comprises a controller (220) for controlling operation of the actuator assembly.

24. A method of dispensing a fluid using an automated analyzer, wherein the method comprises the steps of:

-providing (300) a cartridge (100, 202, 202', 202", 400, 600, 800) according to claim 21 or 22;

-mounting (302) the cartridge into an automatic analyzer (200) in an operating position, wherein the automatic analyzer comprises an actuator assembly (204, 204', 204 ") for actuating the dispenser;

-receiving (304) the fluid from the outlet by using the dispenser;

-operating (306) the actuator assembly so as to dispense the fluid;

-receiving (308) the ventilation gas via the baffle means at the inlet; and

-filling (310) at least a portion (102) of the reservoir chamber with the ventilation gas, wherein the inlet is located within the portion operable to be filled with the ventilation gas.

25. A cartridge (100, 202, 202', 202", 400, 600, 800) for dispensing a fluid (104), wherein the cartridge comprises:

-a reservoir chamber (102) operable to receive the fluid and to receive a ventilation gas (106), wherein the reservoir chamber comprises an inlet (114) for receiving the ventilation gas and an outlet (116) for dispensing the fluid, wherein at least a portion (106) of the reservoir chamber is operable to be filled with the ventilation gas when in an operational position, wherein the inlet is located within the portion operable to be filled with the ventilation gas, wherein the fluid comprises a reagent; wherein the inlet is operable to maintain a constant gas pressure within the portion of the reservoir chamber operable to be filled with the ventilation gas when twenty to eighty percent of the reservoir chamber is filled with the fluid;