FIELD OF THE INVENTION

The present invention relates to a system and a method for determining a residual volume of a container unit. More particularly, the present invention relates to a system and a method for determining a remaining volume of fluid, preferably liquid, left in a primary or a secondary container of the container unit. The system and method of the invention may advantageously be used for determining a degree of filling of a container, in particular a cassette containing chemical fluids.

BACKGROUND OF THE INVENTION

It is often desirable to be able to determine a residual volume in a container, e.g. in order to ensure that the container is replaced by a full container before or as soon as the container is emptied, thereby ensuring a substantially continuous supply of a liquid contained in the container. This is particularly desirable in the case that the container contains a medical drug, a reagent to be supplied to an analysis apparatus, oil or the like to be supplied to an engine, or other fluids which are crucial to proper operation of an apparatus.

However, it is sometimes difficult to gain access to the container in a manner which allows the residual volume to be measured directly. This is, e.g., the case if the container is positioned inside a cassette, or if the container is a substantially hermetically closed tank. In such cases it is desirable to be able to reliably determine the residual volume in other ways.

EP 1 666 864 discloses a measuring operation for a leakage determination comprising a pressurizing step, a balance step, a measuring step and an exhaust step. In the pressurizing step volume data on the measurement object is automatically estimated. In the automatic estimation of this volume data, rather than performing the measurement in a transient state such as during the starting phase of the pressurization, the pressurization is temporarily stopped and the pressure measurement using a gauge pressure sensor is performed after the pressure in an endoscope and a pipe including the gauge pressure sensor becomes uniform, thereby estimating the volume of the measurement object such as the endoscope.

SUMMARY OF THE INVENTION

It is an object of the invention to provide a system and a method for determining a residual volume of a container, the system and the method being reliable without requiring direct access to the container.

It is a further object of the invention to provide a system and a method for determining a residual volume of a container, the system and the method being capable of determining small volumes more accurately than prior art systems and methods.

According to a first aspect of the invention the above and other objects are fulfilled by providing a system for determining a residual volume of a container unit, the system comprising:

- a container unit comprising at least a primary container,

- means for applying a pressure inside the primary container,

- a flow restrictor fluidly connected between the primary container and a position exterior of the primary container,

- means for measuring a rate of pressure change of a pressure of the container unit, and - means for determining a residual volume of the container unit based on a measured rate of pressure change.

In the present context the term 'residual volume' should be interpreted to mean a volume which remains of a content, or a volume which is available for filling. The container unit comprises at least a primary container. The container unit may simply be the primary container, in which case the residual volume is preferably a volume of a remaining content of the primary container or a volume which is available for filling. In the case that the container unit comprises one or more additional containers, the residual volume may be a volume of the remaining content of one or more of the additional containers. This will be described further below.

A flow restrictor is fluidly connected between the primary container and a position exterior of the primary container. Thus, it is possible to lead fluid, preferably in a gaseous state, from the primary container to a position exterior of the primary container in a controlled manner, via the flow restrictor. The exterior position may be the exterior of the container unit, e.g. the ambient environment. Alternatively, it may be an additional container either forming part of the container unit or being arranged outside the container unit.

The system comprises means for applying a pressure inside the primary container and means for measuring a rate of pressure change of a pressure of the container unit. Thus, it is possible to apply a pressure to the primary container and to monitor the rate of pressure change as fluid leaves the primary container via the flow restrictor.

A residual volume of the container unit is determined based on a measured rate of pressure change.

According to an embodiment, the system may be operated in the following manner. Initially a pressure is applied to the primary container. The applied pressure may be the pressure which is applied to the primary container during normal operation, or it may be a somewhat higher pressure which is applied immediately before it is intended to determine the residual volume. Next the means for applying a pressure is stopped, or a fluid connection between the means for applying a pressure and the primary container is interrupted, and fluid, preferably a fluid in a gaseous form which was supplied by the means for applying a pressure, is allowed to leave the primary container via the flow restrictor. Thereby the pressure in the primary container will adapt to the pressure of the exterior position. Knowing the flow resistance of the flow restrictor, and preferably the ambient pressure, which may have been measured, a measurement of the rate of pressure change of the pressure inside the primary container as the fluid leaves the container via the flow restrictor, provides information of the volume which is available to the fluid supplied by the means for applying a pressure. Based on this information, it is possible to determine the desired residual volume of the container unit. According to this embodiment the pressure inside the primary container is measured, and possibly also an ambient pressure.

In an alternative embodiment, the measured pressure of the container unit may be a pressure inside a third container which is fluidly connected to the primary container via the flow restrictor, or it may be a difference in pressure between the pressure inside the primary container and the pressure inside such a third container. Measuring the pressure inside the third container is advantageous because it is very simple. Measuring the difference in pressure is advantageous because it provides a more accurate basis for calculating the residual volume than merely measuring the pressure inside the third container.

Thereby a system has been provided which can be used for reliably determining a residual volume of a container without requiring direct access to the container. Furthermore, the system is capable of determining a small residual volume in a more precise manner than known systems, e.g. the system shown in EP 1 666 864. The system may further comprise means for measuring a temperature at or near the system. This may be desirable since the temperature affects the viscosity of a fluid, and thereby the flow rate of the fluid through a flow restrictor. It may therefore be relevant to include the temperature in the determination process described above, in particular when a very precise measurement of the volume is necessary or desired.

According to one embodiment the container unit may further comprise at least one secondary container, the primary container and each of the secondary container(s) being separated by at least one movable wall, and the primary container and the secondary container(s) may be arranged relative to each other in such a manner that the sum of the volumes of the primary container and each of the secondary container(s) is substantially constant, and the means for determining a residual volume may comprise means for determining a residual volume of the secondary container(s).

According to this embodiment the container unit is shaped in such a manner that the sum of the volumes of the primary container and each of the secondary containers remains substantially constant. Thus, if the volume of one container increases, the volume of one or more of the other containers must decrease and vice versa. Thus, if the volume occupied by one container is determined, the total volume occupied by the remaining containers can easily be determined by subtracting the determined volume from the substantially constant sum of the volumes. Accordingly, once the volume of the primary container has been determined as described above, the combined volume occupied by all of the secondary containers can be determined. Since the primary container is separated from each of the secondary containers by a movable wall, the combined volume of the secondary containers determined in this manner is or corresponds to the contents remaining in the secondary containers, i.e. it is representative of a residual volume of the secondary container(s).

Each secondary container may advantageously contain a fluid, preferably a liquid, which is supplied from the secondary container, while the primary container contains a fluid in gaseous form. The pressure in the primary container is preferably sufficiently high to drive fluid out of the secondary containers. In this case the determined residual volume may advantageously be the amount of liquid remaining in the secondary containers. It is desirable to be able to determine this in order to know when to replace or replenish the secondary containers and thereby ensure a continuous operation of the apparatus which receives liquid from the secondary containers.

The movable wall(s) may be flexible wall(s). In this case one or more of the secondary containers may be in the form of flexible bags arranged inside the primary container. As an alternative, the movable wall(s) may be in the form of a piston being movable inside the container unit.

Each of the secondary container(s) may be fluidly connected to a mixing unit in such a manner that a pressure in the primary container drives fluid from the secondary container(s) towards the mixing unit. As described above, the secondary container(s) is/are in this case capable of delivering a fluid, preferably a liquid, to the mixing unit. The liquid may, e.g., be analysis liquid or reagent used for analysing samples, e.g. samples of body fluids, such as blood, or tissue.

As an alternative, the container unit may comprise only the primary container. In this case the determined residual volume is a residual volume of the primary container. The residual volume may be a volume of a liquid remaining in the primary container (i.e. 'how much liquid do we have left'), or it may be a volume of the primary container which is not occupied by a liquid (i.e. 'how much volume is still available for filling'). The former is relevant in a situation where the primary container is being emptied, i.e. the liquid in the container is being supplied for some purpose, and the latter is relevant in a situation where the container is being filled.

The means for determining a residual volume may comprise means for comparing a measured rate of pressure change with empirical or theoretical data. According to this embodiment the rate of pressure change for a number of various residual volumes may either be calculated or measured under controlled conditions. When a residual volume is to be determined, the measured rate of pressure change is then compared with the calculated or empirically obtained data, and the calculated or empirically obtained data which mostly resembles the measured rate of pressure change can be identified. It can thereby be determined that the residual volume is identical or nearly identical to the residual volume corresponding to this calculated or empirically obtained data.

The system may further comprise a first valve being fluidly connected between the means for applying a pressure and the primary container. According to this embodiment the fluid connection between the means for applying a pressure and the primary container can be interrupted. Thereby the pressure in the primary container is allowed to adapt to the ambient pressure in a controlled manner and via the flow restrictor as described above. The first valve is preferably open during normal operation and closed during determination of the residual volume.

The system may further comprise a second valve being fluidly connected between the primary container and the flow restrictor. According to this embodiment the fluid connection between the primary container and the exterior position via the flow restrictor can be interrupted. The second valve is preferably closed during normal operation and open during determination of the residual volume. Thereby the container unit is substantially tight during normal operation. As an alternative the second valve may be fluidly connected between the flow restrictor and the exterior position.

The flow restrictor may be or comprise a capillary tube, e.g. made from glass or from a suitable polymer. The capillary tube may have a diameter of between 5 μm and 15 μm, such as between 8 μm and 12 μm, such as approximately 10 μm. As an alternative, the flow restrictor may be of any other suitable kind, as long as it is capable of providing a controlled flow of fluid between the primary container and the exterior of the container unit.

The means for applying a pressure may comprise a pump and/or a compressor.

The system may further comprise means for measuring an ambient pressure of the exterior of the container unit, and the means for determining a residual volume may be adapted to further determine the residual volume based on a measured ambient pressure.

The ambient pressure may advantageously be at or near atmospheric pressure. As an alternatively, the container unit may be arranged in a closed system which is kept at a pressure which is either higher or lower than atmospheric pressure. In any event, the ambient pressure is preferably the pressure at the position exterior of the primary container to which the primary container is fluidly connected via the flow restrictor.

According to this embodiment the residual volume is determined on the basis of a measured rate of pressure change as well as on the basis of a measured ambient pressure.

According to one embodiment the flow restrictor may be fluidly connected between the primary container and a third container. According to this embodiment the fluid which leaves the primary container via the flow restrictor flows into the third container, i.e. the exterior position is the inside of the third container.

The means for applying a pressure inside the primary container may, in this case, comprise means for altering a ratio between a volume of the primary container and a volume of the third container. The means for altering the volume ratio may, e.g., be or comprise a bi-stable actuator, e.g. of a kind having a displaceable wall defining an interface between the primary container and the third container. Thus, displacing the wall causes the volume of the primary container to increase while the volume of the third container decreases, or vice versa. Since a change in volume causes a corresponding change in pressure, at least intermediately, displacing the wall corresponds to applying a pressure to the primary container.

According to this embodiment the system may be operated in the following manner. When it is desired to determine the residual volume the bi-stable actuator is operated in order to displace the wall in a desired direction, thereby altering the ratio of the volume of the primary container and the volume of the third container. As a consequence, a difference in pressure between the primary container and the third container is introduced. The system will seek to eliminate this difference in pressure by allowing fluid to pass via the flow restrictor. During this the pressure in the primary container is monitored and a rate of pressure change is obtained as described above. This may be performed by monitoring the pressure of the primary container as well as the pressure of the third container. Alternatively, only one of these pressures may be monitored. Based on the obtained rate of change of the pressure a residual volume of the container unit can be determined as described above.

According to a second aspect of the invention the above and other objects are fulfilled by providing a method of determining a residual volume of a container unit, the method comprising the steps of:

- providing a container unit comprising at least a primary container,

- applying a pressure to the primary container,

- allowing fluid to leave the primary container via a flow restrictor,

- monitoring at least one pressure of the container unit, thereby obtaining a rate of pressure change while fluid leaves the primary container, and - determining a residual volume of the container unit based on the obtained rate of pressure change.

It should be noted that a skilled person would readily recognise that any feature described in combination with the first aspect of the invention could also be combined with the second aspect of the invention, and vice versa.

The method according to the second aspect of the invention is preferably performed by means of the system according to the first aspect of the invention. The advantages of the method have, accordingly, already been described above.

As described above, the container unit may further comprise at least one secondary container, the primary container and each of the secondary container(s) being separated by at least one movable wall, and the primary container and the secondary container(s) may be arranged relative to each other in such a manner that the sum of the volumes of the primary container and each of the secondary container(s) is substantially constant, and the step of determining a residual volume may comprise determining a residual volume of the secondary container(s). This is also described above.

The step of determining a residual volume may comprise comparing a measured rate of pressure change with empirical or theoretical data.

The method may further comprise the step of disrupting a fluid connection between the primary container and the means for applying a pressure to the primary container, prior to the step of allowing fluid to leave the primary container. According to this embodiment the primary container is first pressurized. Then the fluid connection between the means for applying a pressure and the primary container is disrupted, and the fluid, preferably in gaseous form, is allowed to leave the primary container via the flow restrictor, thereby allowing the pressure of the primary container to adapt to the ambient pressure, while the rate of pressure change of the pressure in the primary container is monitored.

As described above, the method may further comprise the step of measuring an ambient pressure of the exterior of the container unit, and the step of determining a residual volume may further be performed on the basis of the measured ambient pressure.

The step of allowing fluid to leave the primary container may comprise allowing fluid to enter a third volume, and the step of applying a pressure to the primary container may comprise altering a ratio between a volume of the primary container and a volume of the third container.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention will now be described in further detail with reference to the accompanying drawings in which

Fig. 1 is a schematic drawing of a system according to a first embodiment of the invention,

Fig. 2 is a graph illustrating theoretically calculated curves of pressure as a function of time for two different residual volumes, and

Fig. 3 is a schematic view of a system according to a second embodiment of the invention.

DETAILED DESCRIPTION OF THE DRAWINGS

Fig. 1 is a schematic drawing of a system 1 according to a first embodiment of the invention. The system 1 comprises a container unit 2 comprising one primary container 3 and four secondary containers 4, each of the secondary containers 4 containing a liquid. The primary container 3 is separated from each of the secondary containers 4 by a flexible wall 5. Thus, when a pressure is applied to the primary container 3, the flexible wall 5 is pushed towards the secondary containers 4, thereby increasing the volume of the primary container 3 and decreasing the volume of each of the secondary containers 4. Preferably, the secondary containers 4 are in the form of flexible bags, and applying a pressure to the primary container 3 causes the bags to be squeezed. This will be explained in further detail below.

The system 1 further comprises a compressor 6 fluidly connected to the primary container 3 via a valve 7. When the valve 7 is in an open state, the compressor

6 is thereby able to apply a pressure to the primary container 3. Pressure sensor Pi measures the pressure applied to the primary container 3. The valve

7 is open during normal operation. Thus, during normal operation the compressor 6 ensures that a desired pressure level is maintained in the primary container 3. The desired pressure level in the primary container 3 is preferably higher than the ambient pressure, e.g. 0.5-1.0 bar higher. The pressure sensor Pi provides a feedback signal to the compressor 6 via signal line 8, and the operation of the compressor 6 is thereby controlled to maintain the desired pressure level in the primary container 3.

The desired pressure level in the primary container 3 is sufficient to squeeze or push the flexible wall 5 enough to drive liquid from the secondary containers 4 towards a mixing unit 9, via tubes 10. The mixing unit 9 is further fluidly connected to a blood vessel 11 via capillary tube 12. Accordingly, ions are sampled from the blood vessel 11 to the capillary tube 12, preferably via a semipermeable membrane (not shown), and further delivered to the mixing unit 9. In the mixing unit 9 the sampled ions are mixed with the liquids from the secondary containers 4, and the sampled ions can thereby be analysed.

Pressure sensor P ₂ is arranged to measure the ambient pressure, i.e. the pressure outside the container unit 2.

The primary container 3 is fluidly connected to the exterior of the container unit 2, via a valve 13 and a flow restrictor 14 having a known flow resistance. Accordingly, when the valve 13 is in an open state fluid is allowed to leave the primary container 3 via the flow restrictor 14, and the pressure in the primary container 3 will thereby adapt to the ambient pressure. Since the pressure level in the primary container 3 is higher than the ambient pressure this results in a decrease in the pressure level in the primary container 3. Due to the flow restrictor 14 the decrease in pressure takes place in a controlled manner.

The valve 13 is normally in a closed state during normal operation, and in an open state during determination of a residual volume.

During determination of a residual volume the system 1 of Fig. 1 preferably operates in the following manner. Initially valve 7 is closed, thereby interrupting the fluid connection between the compressor 6 and the primary container 3.

Then the valve 13 is opened, thereby allowing fluid to leave the primary container 3 via the flow restrictor 14, and the pressure level in the primary container 3 is thereby adapted to the ambient pressure in a controlled manner as described above. During this the pressure sensor P ₁ monitors the pressure level in the primary container 3 and pressure sensor P ₂ measures the ambient pressure.

Based on the monitored pressure level in the primary container 3 a graph is obtained illustrating pressure level in the primary container 3 as a function of time, and thereby a rate of pressure change of the pressure level in the primary container 3 can be derived. The rate of pressure change during adaptation of the pressure level in the primary container 3 is completely determined by the initial pressure level in the primary container 3, the ambient pressure, the flow resistance of the flow restrictor 14 and the volume of the primary container 3. The smaller the volume of the primary container 3, the faster the pressure level in the primary container 3 adapts to the ambient pressure. Thus, since the initial pressure level in the primary container 3, the ambient pressure and the rate of pressure change is measured, and since the flow resistance of the flow restrictor 14 is known, it is possible to determine the volume of the primary container 3 based on the available information. Since the sum of the volumes of the primary container 3 and each of the secondary containers 4 is substantially constant the sum of the volumes of the secondary containers 4 can easily be derived by subtracting the volume of the primary container 3 from the total volume. Due to the flexible wall 5 the sum of the volumes of the secondary containers 4 is representative for or identical to the remaining amount of liquid in the secondary containers 4. Thereby a residual volume has been determined which indicates the amount of liquid remaining in the secondary containers 4, and it can therefore be determined whether or not the secondary containers 4 need replacement or replenishment, and possibly when a replacement or replenishment is required. Furthermore, this has been obtained without the need for gaining direct access to the container unit 2.

Fig. 2 is a graph illustrating theoretically calculated curves of pressure as a function of time for two different residual volumes. The curves correspond to the system 1 shown in Fig. 1. Both of the curves have been calculated with a flow resistance of the flow restrictor of 0.04 mbar min/μl, an initial pressure in the primary container 3 of 1500 mbar and an ambient pressure of 1000 mbar.

Curve 15 represents a situation where the volume of the primary container 3 is 10,000 μl, and curve 16 represents a situation where the volume of the primary container 3 is 50,000 μl. It is clear that the curve 15, representing the smaller volume, approaches the ambient pressure much faster than the curve 16. Having a plurality of curves similar to curves 15 and 16, each representing a specific volume of the primary container 3, a corresponding measured curve can be compared to the theoretical curves in order to find the theoretical curve which mostly resembles the measured curve. Thereby the volume of the primary container 3 corresponding to the measured curve can be determined.

Fig. 3 is a schematic view of a system 1 according to a second embodiment of the invention. The system 1 of Fig. 3 comprises a container unit 2 with a secondary container 4 having a flexible wall 5 and being arranged inside a primary container 3. The primary container 3 is fluidly connected to a third container 17 via a flow restrictor 14. A pressure sensor P ₁ is arranged to measure the pressure of the primary container 3, and a pressure sensor P ₃ is arranged to measure the pressure of the third container 17. The system 1 further comprises a bi-stable actuator 18 having a wall 19 being displaceable between a first position 20a and a second position 20b. In Fig. 3 the displaceable wall 19 is in the first position 20a. Moving the displaceabie wall 19 from the first position 20a to the second position 20b causes the volume of the primary container 3 to increase and the volume of the third container 17 to decrease. Similarly, moving the displaceable wall from the second position 20b to the first position 20a causes the volume of the primary container 3 to decrease and the volume of the third container 17 to increase.

The system 1 of Fig. 3 may be operated in the following manner. During normal operation the displaceable wall 19 is in the first position 20a. When it is desired to determine the residual volume the bi-stable actuator 18 is operated to cause the displaceable wall 19 to move abruptly to the second position 20b. Thereby the volume of the primary container 3 is abruptly increased and the volume of the third container 17 is abruptly decreased, and a difference in pressure between the primary container 3 and the third container 17 is introduced.

As an alternative, the displaceable wall 19 may initially be in the second position 20b, and it may be moved abruptly into the first position 20a when it is desired to determine the residual volume. In this case the volume of the first container 3 is thereby increased while the volume of the third container is decreased.

A rate of pressure change is now obtained while the pressures of the primary container 3 and the third container 17 adapt to each other. This may be done by monitoring the pressure in the third container 17 by means of pressure sensor P3. Alternatively, it may be done by monitoring the difference in pressure between the pressure inside the primary container 3 and the pressure inside the third container 17. In this case pressure sensor Pi as well as pressure sensor P3 may be used. By means of the obtained rate of pressure change the part of the volume of the primary container 3 which is not occupied by the secondary container 4 can be determined as described above. Subsequently, the volume of the remaining contents of the secondary container 4 can be calculated by subtracting the determined volume from the total volume of the primary container 3, as described above.