WO1997047728A1 - Monitoring the contents of sealed containers - Google Patents
Monitoring the contents of sealed containers Download PDFInfo
- Publication number
- WO1997047728A1 WO1997047728A1 PCT/GB1997/001530 GB9701530W WO9747728A1 WO 1997047728 A1 WO1997047728 A1 WO 1997047728A1 GB 9701530 W GB9701530 W GB 9701530W WO 9747728 A1 WO9747728 A1 WO 9747728A1
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- WO
- WIPO (PCT)
- Prior art keywords
- sensing unit
- container
- pressure
- sensing
- property
- Prior art date
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Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01L—MEASURING FORCE, STRESS, TORQUE, WORK, MECHANICAL POWER, MECHANICAL EFFICIENCY, OR FLUID PRESSURE
- G01L19/00—Details of, or accessories for, apparatus for measuring steady or quasi-steady pressure of a fluent medium insofar as such details or accessories are not special to particular types of pressure gauges
- G01L19/14—Housings
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
- C12M41/00—Means for regulation, monitoring, measurement or control, e.g. flow regulation
- C12M41/30—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration
- C12M41/36—Means for regulation, monitoring, measurement or control, e.g. flow regulation of concentration of biomass, e.g. colony counters or by turbidity measurements
Definitions
- This invention relates to a sensing unit for monitoring variations of a property associated with the headspace in a sealed container partially filled with a liquid, and also to a method of monitoring for the same purpose.
- WO 93/03178 is known a method of monitoring the growth of microorganisms in a liquid culture in which pressure variations in the headspace of a bottle containing the liquid culture are sensed, wherein the bottle is provided with a sealed top incorporating a flexible diaphragm or septum and deflections of the diaphragm due to pressure variations within the bottle headspace are detected by a distance-measuring means, more especially a laser.
- the laser repetitively scans a plurality of bottles mounted in a carrier in both x and y directions, and movements of the diaphragm are fed to a remote signal processing unit in conjunction with simultaneously detected codes on the bottle tops which relate the detected movements to particular bottles.
- the sensing unit for determination of biological oxygen demand (BOD) in water or waste water.
- the sensing unit which includes microelectronics including a pressure sensor, micro-controller, timer and LED display, screws to the top of an open or opened bottle containing the liquid to be tested.
- the complete system is therefore not a sealed system, because even if the bottle is sealed beforehand, the seal has to be broken when the sensing unit is fined, exposing the liquid contents of the bottle to atmosphere.
- the sensing unit monitors decreasing pressure only, and displays measurements on a daily basis.
- European Specification No. 0592728A1 concerns a method of monitoring the growth of microorganisms in a liquid culture in which pressure variations in the headspace of a bottle containing the liquid culture are sensed, and discloses an electronic sensing unit which fits to the sealed top of a bottle containing the liquid to be tested.
- the sensing unit includes a hollow needle for puncturing a rubber septum responsible for sealing the top of the bottle, whereby communication is established between the bottle interior and a pressure sensor contained in the sensing unit.
- the pressure sensor may be connected to remote electronics.
- a sensing unit for monitoring the contents of a sealed container partially filled with a liquid which can give rise to variations of a property associated with the container headspace above the liquid, comprising a housing having means enabling its connection to a closure at the top of the container through which the container headspace is placed in communication with the housing, the connection enabling means effecting said commumcation without at any time exposing the liquid contents of the container to atmosphere, and the housing incorporating a transducer responsive to the sensed property of the headspace and providing electrical outputs proportional to variations in the property, data processing means receiving the signal outputs of the transducer and including a signal processor storing a data processing algorithm, and indicating means receiving the output of the data processor to enable the sensed property to be visually monitored at the sensing unit.
- the sensing unit is especially useful for monitoring the growth of microorganisms in a liquid culture partially filling a culture bottle. This is made possible only by the fact that the sensing unit connects to bottle without compromising the sterile conditions under which the bottle was initially sealed and subsequently primed without risk of atmospheric contamination.
- a culture bottle is normally totally sealed at the top by a closure fitting and, in a preferred arrangement in accordance with the invention, the sensing unit connects by linear displacement towards and into engagement with this closure fitting to form a total seal therewith before displacement is completed to place the interior of the bottle in communication with the sensing unit without breaking the said total seal between the sensing unit and the closure fitting.
- the properties of which variations may be detected by the transducer are gas pressure in the container headspace, one or more constituent contents of the container headspace such as oxygen and/or carbon dioxide content, and the pH value of the gas in the container headspace.
- monitoring of the contents of sealed containers such as liquid culture bottles has hitherto been a centralised process in which large numbers of bottles are monitored simultaneously with the aid of a remote signal processor and an indicator which is required to indicate any abnormal variation in container contents coupled with bottle identification.
- the present invention enables monitoring to be carried out in a decentralised manner, because connection to additional equipment is not necessary .
- the only further requirement is for an incubator in which to stand the culture bottle or bottles.
- the sensing unit of the invention is a stand alone unit, it may for convenience optionally include an infra-red signal generator for optically transmitting signals to a remote location. However, there remains no requirement to make physical connections to the sensing unit to enable monitoring to be carried out.
- the sensing unit preferably carries a code stored in the data processing means for identification of the container to which the unit is attached. This can enable the unit to transmit an alarm signal to a remote display in the event of detection of a property change (positive or negative) in the bottle headspace in excess of predetermined values, most preferably in conjunction with the identification code.
- the container and the sensing unit may also be given the same visible codes, and the code transmitted by the unit will preferably correspond to its visible code.
- a further feature of the invention concerns the combination of the sensing unit with a rubber seal normally sealing the top of the container, said rubber seal having a formation adapted to receive and locate an attachment boss on the base of the housing of the sensing unit.
- a preferred formation on the rubber seal is a chimney in which the attachment boss on the base of the sensing unit housing is tightly received, thus ensuring a very effective pneumatic seal.
- Splining or the like may be provided on the chimney interior and/or boss to ensure that the sensing unit is only connectable to the rubber seal on the bottle in one orientation.
- the formation on the rubber seal accommodates a device which punctures the rubber seal when the sensing unit is located in the formation, thereby to allow communication between the container headspace and the sensing unit, but without exposing the container contents to the atmosphere and thus compromising any initial sterile conditions under which the container was initially sealed.
- One convenient puncturing device is a hollow needle through which communication is established between the container headspace and the sensing unit.
- the puncturing device preferably includes a sterility barrier which allows communication but prevents risk of contamination of the sensing unit from the container contents. The sensing unit is thereby repeatedly re-usable.
- the puncturing device establishes pressure communication with the sensing unit, which in this incorporates the pressure transducer.
- the sensing unit or the puncturing device then preferably incorporates a pressure relief device, which may operate automatically or on demand.
- a method of monitoring a property of the headspace of a sealed container partially filled with liquid according to which the container is provided with a closure having a formation to which is attached a sensing unit and through which communication is established between the container headspace and the sensing unit, the sensing unit incorporating a data processing means which receives signals representative of the property to be sensed in the container headspace when the sensing unit is attached to the closure formation, and the property representative signals are processed and a visual indication given on the sensing unit at least when any abnormal variation in the property is detected.
- a temperature sensor may be provided to provide direct correction of data within the sensing unit.
- the closure includes a rubber seal puncmred by a puncturing device housed in the closure formation when the sensing unit is attached, and property-representative signals are transmitted to the sensing unit via the puncturing device.
- the puncturing device preferably establishes pressure communication with the sensing unit which in this case incorporates a pressure sensor generating electrical signals fed to the data processing means.
- the rubber seal is thick enough to prevent the influence of barometric pressure variations on the pressure-representative signals.
- the data processing means in the sensing unit may transmit to a remote location an infra-red signal containing an identification code when a significant property change, exceeding a predetermined value, is detected in the container.
- Figure 1 shows stages in the fitting of a sensing unit to a sealed culture bottle
- Figure 2 again shows the sensing unit fitted to a sealed culture bottle, but with the housing of the sensing unit removed;
- Figure 3 is a block circuit diagram of the electronics incorporated in the sensing unit
- Figure 4 is state transition diagram appertaining to use of the sensing unit; and Figure 5 is a user flow diagram appertaining to use of the sensing unit.
- the culture bottle comprises a cylindrical glass bottle of circular cross section with a gently tapering broad neck closed by a crimped metal seal, typically made from aluminium. Other sealing methods, such as threaded caps, can be used.
- a crimped metal seal typically made from aluminium.
- Other sealing methods such as threaded caps, can be used.
- Such bottles are normally supplied to the end user in sealed form containing an appropriate liquid growth medium.
- the crimped seal has a central aperture which is closed by a rubber septum.
- the septum may be of chlor-butyl rubber, as disclosed in Patent Specification No. WO 94/19453.
- a sample such as a sample of blood or other body fluid, can be injected directly into the culture bottle through the septum by use of a syringe, and the septum seals itself when the needle of the injecting syringe is withdrawn from the bottle.
- a typical culturing unit may conveniently comprise an incubator having a plurality of drawers each of which holds a plurality of culture bottles.
- Each drawer may comprise a plurality of side-by-side bottle supports in the form of apertured aluminium blocks in which the bottles are seated.
- the bottles are maintained at an appropriate culturing temperature, typically 37 °C.
- the bottles may be monitored during culturing by sensing pressure changes within the headspaces above the liquid in the bottles.
- Patent Specification No. WO 94/19698 describes a monitoring method which relies for monitoring on the detection of deflections of the rubber septum as pressure changes occur in a bottle headspace. These deflections are measured by a laser distance measuring device which is mounted above each drawer in the culturing housing and is driven in x and y coordinate directions to scan each bottle top in turn. Information representative of pressure variation is transmitted in conjunction with a bottle top code also detected by the laser, thereby to relate the pressure- representative information to the x, y coordinate position of the bottle in the drawer.
- the present invention differs from the prior art in a number of ways.
- the culture bottle 10 as supplied has a modified chlor-butyl rubber septum 12 which is substantially thicker than that conventionally used. However, as previously, it is held in place by a crimped aluminium seal 14.
- the relatively thick septum 12 is susceptible to a minimum extent to deformation due to changes in barometric pressure. It is thus apparent, however, that its deflections are relatively minimal due to pressure variations within the bottle headspace 16.
- the present invention in one practical embodiment, thus provides for monitoring the bottle headspace pressure more directly.
- the rubber septum is integrally moulded with an upstanding tube or chimney 18, in which is located a septum puncturing device 20.
- the rest position of this puncturing device 20 is shown (for the bottle 10 on the left-hand side of Figure 1).
- the culture bottle is supplied with the chimneyed rubber septum 12 containing puncturing device 20 in place and protected at the top of the chimney 18 by a removable cover plug 22.
- the culture can be primed in the conventional manner by injection with a syringe and, as in the prior art, the chlor-butyl rubber septum re-seals itself as the syringe is withdrawn.
- the most important aspect of the present invention resides in the provision of an individual pressure sensing unit 24, including data processing means, for each bottle.
- the unit 24 is shown, prior to fitting, above the centre bottle 10 in Figure 1.
- the cover plug 22 at the top of the chimney of die rubber septum 12 of this bottle has been removed ready for fitting of the unit. It will be noted that the lateral dimensions of the unit 24 do not exceed those of the bottle footprint.
- the unit 24 which is battery powered, comprises a miniature pressure transducer, an analogue-to-digital converter, a processor storing a data interpretation algorithm, and a display device 26. These are contained within a housing which has an underside boss 28 which can be sealingly engaged in the chimney 18 of the septum of the bottle 10. This arrangement of chimney and boss fitting closely therein ensures a very effective pneumatic seal. As the bottle is held in registration in known manner by its seating in the support in the culturing unit, it may be convenient for the pressure sensing unit 24 to be angularly aligned by means of a vertical tongue/slot or spline arrangement provided on the boss 28 and the interior of the chimney 18.
- the housing of the pressure sensing unit 24 may also have an infra-red port 29 through which processed data output from the processor may be signalled to a remote location, i.e. a remote display supervised by an operator.
- the data fed to the remote display will preferably include a signal for activating an alarm at the remote location if any bottle being monitored develops a significant pressure change, exceeding a predetermined value.
- the unit 24 of the present invention is a stand alone device which enables monitoring of the culture bottle without the need for any additional equipment other than a simple incubator in which to stand the bottle.
- the right-hand bottle 10 is shown with the pressure sensing unit 24 in fitted condition. It can be seen that, when the boss 28 on the bottom of the housing is inserted into the top of the chimney 18, the puncturing device 20, which includes a hollow needle 30, penetrates the septum 12, which has a small area 32 of reduced thickness aligned with the needle at the bottom of the chimney 18, thereby to open pressure communication through the needle to the miniature pressure transducer in the sensing unit 24. This communication is established without in any way exposing the contents of the bottle to atmosphere. Thus, a total seal is established between the boss 28 and the chimney 18, which seal is maintained during completion of the insertion step to cause the needle to penetrate die septum 12.
- a sterility barrier 34 forming pan of the puncturing device 20 not only to avoid contamination of the pressure sensing unit and ensure that it is re-usable, but also to ensure that the bottie contents are not contaminated from the pressure transducer. It is also important that the sepmm 18 reseals around the needle 30 after puncturing, and to ensure this the sepmm is most preferably made of chlor-butyl rubber, as noted above.
- the miniamre pressure transducer outputs pressure-representative electrical signals to the analogue to digital convener, and thence to the processor within the sensing unit 24.
- each bottle is monitored individually, it is nevenheless useful to retain a coding system for the bottle and the sensing unit fitted to it, especially if information is to be transmitted to a remote location.
- the pressure sensing unit 24 will bear a visible bar code and a corresponding stored code which can be transmitted to the remote location, in conjunction with pressure-representative signals, on demand.
- This code may also be displayed on the on-board display, conveniently an integral LCD, of the sensing unit 24.
- This LCD display will show at least the pressure stams, i.e. positive or negative, together with the pressure value and elapsed time.
- the bottle is maintained at the appropriate culturing temperature, and the sensing unit conveniently acts as a heat insulative top to the bottle.
- the data link with a remote location is performed using modulated infra-red signals, at least to trigger an alarm if pressure in a bottle exceeds a predetermined value.
- a venting device in the pressure sensing unit 24, i.e. a valve which opens to atmosphere. This may operate automatically or on demand.
- Figure 2 again shows the sensing unit 24, but with its cover removed.
- the puncturing device is shown in its rest position 20 and its position 20A in which the sepmm 12 has been puncmred.
- Figure 2 otherwise uses the same references as in Figure 1 for corresponding pans.
- Figure 2 shows a two pan pressure manifold 36 via which internal bottle pressure is transmitted to a pressure transducer 38, which outputs pressure representative signals to a printed circuit board 39 carrying the electronics of the sensing unit. This board outputs signals to an integral LCD device 40.
- the pressure transducer 38 and also a temperature transducer 42, output signals dirough signal conditioning and/or amplifying means 44, 46 to an A/D convener 48 which supplies digitised signals to a CPU 50 which incorporates a clock 52, a main memory 54 storing a signal processing algorithm, and a supplementary memory 56 for temporary data storage.
- An on-bottle switch 58 and a reset switch 60 provide user interrupts, and a non ⁇ volatile memory 62 provides for calibration and entry of non-transient data.
- Power control circuitry is indicated at 64, 66.
- the processed data is fed to the LCD device 40 and, in the event of an overpressure, an output is supplied to a solenoid 68 controlling the pressure relief or venting valve.
- Figure 4 shows the functions performed by the sensing unit, with possible unit interrupts in the event of any kind of detected operational error or initial stand-by test error and other interrupts, automatic or user, due to failures during monitoring.
- Figure 5 is user flow diagram showing the functions performed during normal operation. It will be noted that the sensing unit remains uncontaminated and is therefore re-usable, and also that it is therefore possible for the user to extract a sub-culture and then reconnect me sensing unit to the bottle for further monitoring.
Abstract
A stand-alone sensing unit (24) for fitting to a sealed container (10) which is partially filled with a liquid which gives rise to variations of a given property of the container headspace (16), comprising a housing (24) containing a transducer responsive to the given property and a data processor, and having a boss (28) which engages in the top of a chimney (18) of a rubber septum (12) which seals the container, thereby to cause the septum to be punctured and open communication between the container headspace and the transducer, which delivers signals to the data processor, in turn feeding signals to a visual indicating means (26) forming part of the sensing unit.
Description
Title: Monitoring the Contents of Sealed Containers
Field of the invention
This invention relates to a sensing unit for monitoring variations of a property associated with the headspace in a sealed container partially filled with a liquid, and also to a method of monitoring for the same purpose.
Prior art
From prior published Patent Specification No. WO 93/03178 is known a method of monitoring the growth of microorganisms in a liquid culture in which pressure variations in the headspace of a bottle containing the liquid culture are sensed, wherein the bottle is provided with a sealed top incorporating a flexible diaphragm or septum and deflections of the diaphragm due to pressure variations within the bottle headspace are detected by a distance-measuring means, more especially a laser. In practice the laser repetitively scans a plurality of bottles mounted in a carrier in both x and y directions, and movements of the diaphragm are fed to a remote signal processing unit in conjunction with simultaneously detected codes on the bottle tops which relate the detected movements to particular bottles.
Also known from the prior art is a sensing unit for determination of biological oxygen demand (BOD) in water or waste water. The sensing unit, which includes microelectronics including a pressure sensor, micro-controller, timer and LED display, screws to the top of an open or opened bottle containing the liquid to be tested. The complete system is therefore not a sealed system, because even if the bottle is sealed beforehand, the seal has to be broken when the sensing unit is fined, exposing the liquid contents of the bottle to atmosphere. In use, the sensing unit monitors decreasing pressure only, and displays measurements on a daily basis.
European Specification No. 0592728A1 concerns a method of monitoring the growth of microorganisms in a liquid culture in which pressure variations in the headspace of a bottle
containing the liquid culture are sensed, and discloses an electronic sensing unit which fits to the sealed top of a bottle containing the liquid to be tested. The sensing unit includes a hollow needle for puncturing a rubber septum responsible for sealing the top of the bottle, whereby communication is established between the bottle interior and a pressure sensor contained in the sensing unit. The pressure sensor may be connected to remote electronics.
The invention
According to one aspect of the present invention, there is provided a sensing unit for monitoring the contents of a sealed container partially filled with a liquid which can give rise to variations of a property associated with the container headspace above the liquid, comprising a housing having means enabling its connection to a closure at the top of the container through which the container headspace is placed in communication with the housing, the connection enabling means effecting said commumcation without at any time exposing the liquid contents of the container to atmosphere, and the housing incorporating a transducer responsive to the sensed property of the headspace and providing electrical outputs proportional to variations in the property, data processing means receiving the signal outputs of the transducer and including a signal processor storing a data processing algorithm, and indicating means receiving the output of the data processor to enable the sensed property to be visually monitored at the sensing unit.
The sensing unit is especially useful for monitoring the growth of microorganisms in a liquid culture partially filling a culture bottle. This is made possible only by the fact that the sensing unit connects to bottle without compromising the sterile conditions under which the bottle was initially sealed and subsequently primed without risk of atmospheric contamination. Thus, such a culture bottle is normally totally sealed at the top by a closure fitting and, in a preferred arrangement in accordance with the invention, the sensing unit connects by linear displacement towards and into engagement with this closure fitting to form a total seal therewith before displacement is completed to place the interior of the bottle in communication with the sensing unit without breaking the said total seal between the sensing unit and the closure fitting.
Amongst the properties of which variations may be detected by the transducer are gas pressure in the container headspace, one or more constituent contents of the container headspace such as oxygen and/or carbon dioxide content, and the pH value of the gas in the container headspace.
In practice, monitoring of the contents of sealed containers such as liquid culture bottles has hitherto been a centralised process in which large numbers of bottles are monitored simultaneously with the aid of a remote signal processor and an indicator which is required to indicate any abnormal variation in container contents coupled with bottle identification. The present invention enables monitoring to be carried out in a decentralised manner, because connection to additional equipment is not necessary . In the monitoring of liquid cultures, for example, the only further requirement is for an incubator in which to stand the culture bottle or bottles.
While the sensing unit of the invention is a stand alone unit, it may for convenience optionally include an infra-red signal generator for optically transmitting signals to a remote location. However, there remains no requirement to make physical connections to the sensing unit to enable monitoring to be carried out.
If a facility for infra-red data transmission is provided in the sensing unit, the sensing unit preferably carries a code stored in the data processing means for identification of the container to which the unit is attached. This can enable the unit to transmit an alarm signal to a remote display in the event of detection of a property change (positive or negative) in the bottle headspace in excess of predetermined values, most preferably in conjunction with the identification code.
Conveniently, the container and the sensing unit may also be given the same visible codes, and the code transmitted by the unit will preferably correspond to its visible code.
A further feature of the invention concerns the combination of the sensing unit with a rubber seal normally sealing the top of the container, said rubber seal having a formation adapted to receive and locate an attachment boss on the base of the housing of the sensing
unit. A preferred formation on the rubber seal is a chimney in which the attachment boss on the base of the sensing unit housing is tightly received, thus ensuring a very effective pneumatic seal. Splining or the like may be provided on the chimney interior and/or boss to ensure that the sensing unit is only connectable to the rubber seal on the bottle in one orientation.
Preferably, the formation on the rubber seal accommodates a device which punctures the rubber seal when the sensing unit is located in the formation, thereby to allow communication between the container headspace and the sensing unit, but without exposing the container contents to the atmosphere and thus compromising any initial sterile conditions under which the container was initially sealed. One convenient puncturing device is a hollow needle through which communication is established between the container headspace and the sensing unit. In this case, the puncturing device preferably includes a sterility barrier which allows communication but prevents risk of contamination of the sensing unit from the container contents. The sensing unit is thereby repeatedly re-usable.
In one practical construction, the puncturing device establishes pressure communication with the sensing unit, which in this incorporates the pressure transducer. Either the sensing unit or the puncturing device then preferably incorporates a pressure relief device, which may operate automatically or on demand.
According to another aspect of the invention, there is provided a method of monitoring a property of the headspace of a sealed container partially filled with liquid, according to which the container is provided with a closure having a formation to which is attached a sensing unit and through which communication is established between the container headspace and the sensing unit, the sensing unit incorporating a data processing means which receives signals representative of the property to be sensed in the container headspace when the sensing unit is attached to the closure formation, and the property representative signals are processed and a visual indication given on the sensing unit at least when any abnormal variation in the property is detected.
A temperature sensor may be provided to provide direct correction of data within the sensing unit.
In a practical method and as hitherto mentioned, the closure includes a rubber seal puncmred by a puncturing device housed in the closure formation when the sensing unit is attached, and property-representative signals are transmitted to the sensing unit via the puncturing device. Thus, in this practical method, the puncturing device preferably establishes pressure communication with the sensing unit which in this case incorporates a pressure sensor generating electrical signals fed to the data processing means.
Most preferably, the rubber seal is thick enough to prevent the influence of barometric pressure variations on the pressure-representative signals.
Optionally, the data processing means in the sensing unit may transmit to a remote location an infra-red signal containing an identification code when a significant property change, exceeding a predetermined value, is detected in the container. This enables bottle identification in a system for monitoring bottles containing liquid cultures such as blood samples, more especially when a plurality of such bottles are located in a single incubator.
Description of embodiment
A sensing unit and method of monitoring in accordance with the invention will now be described in more detail, by way of illustration, with reference to the accompanying drawings, in which:
Figure 1 shows stages in the fitting of a sensing unit to a sealed culture bottle;
Figure 2 again shows the sensing unit fitted to a sealed culture bottle, but with the housing of the sensing unit removed;
Figure 3 is a block circuit diagram of the electronics incorporated in the sensing unit;
Figure 4 is state transition diagram appertaining to use of the sensing unit; and
Figure 5 is a user flow diagram appertaining to use of the sensing unit.
Detailed Description of the Drawings
First, there will be briefly described a standard commercially available culture bottle as is widely used in laboratories and hospitals in the culturing of samples, such as blood samples, to detect the presence of microorganisms. The culture bottle comprises a cylindrical glass bottle of circular cross section with a gently tapering broad neck closed by a crimped metal seal, typically made from aluminium. Other sealing methods, such as threaded caps, can be used. Such bottles are normally supplied to the end user in sealed form containing an appropriate liquid growth medium. The crimped seal has a central aperture which is closed by a rubber septum. The septum may be of chlor-butyl rubber, as disclosed in Patent Specification No. WO 94/19453. A sample, such as a sample of blood or other body fluid, can be injected directly into the culture bottle through the septum by use of a syringe, and the septum seals itself when the needle of the injecting syringe is withdrawn from the bottle.
Under normal circumstances there will always be a volume of gas in the headspace because the liquid growth medium and injected sample will only occupy part of the bottle capacity. Changes in the internal pressure can result from temperature changes, e.g. warming of the bottle to normal culturing conditions. In general, culture is conducted at elevated temperature, e.g. 37°C. If microorganisms are present in the injected sample, they will grow in the medium and many species produce gas during growth, which increases the internal pressure. Other species may cause a net reduction in the gas content of the bottle, and this leads to a drop in internal pressure.
Next, reference will be briefly made to a typical culturing unit. This may conveniently comprise an incubator having a plurality of drawers each of which holds a plurality of culture bottles. Each drawer may comprise a plurality of side-by-side bottle supports in the form of apertured aluminium blocks in which the bottles are seated. In use, the bottles are maintained at an appropriate culturing temperature, typically 37 °C.
The bottles may be monitored during culturing by sensing pressure changes within the
headspaces above the liquid in the bottles. Patent Specification No. WO 94/19698 describes a monitoring method which relies for monitoring on the detection of deflections of the rubber septum as pressure changes occur in a bottle headspace. These deflections are measured by a laser distance measuring device which is mounted above each drawer in the culturing housing and is driven in x and y coordinate directions to scan each bottle top in turn. Information representative of pressure variation is transmitted in conjunction with a bottle top code also detected by the laser, thereby to relate the pressure- representative information to the x, y coordinate position of the bottle in the drawer.
The present invention differs from the prior art in a number of ways.
First, referring to die left-hand side of Figure 1 , the culture bottle 10 as supplied has a modified chlor-butyl rubber septum 12 which is substantially thicker than that conventionally used. However, as previously, it is held in place by a crimped aluminium seal 14. The relatively thick septum 12 is susceptible to a minimum extent to deformation due to changes in barometric pressure. It is thus apparent, however, that its deflections are relatively minimal due to pressure variations within the bottle headspace 16. The present invention, in one practical embodiment, thus provides for monitoring the bottle headspace pressure more directly.
To this end, the rubber septum is integrally moulded with an upstanding tube or chimney 18, in which is located a septum puncturing device 20. The rest position of this puncturing device 20 is shown (for the bottle 10 on the left-hand side of Figure 1). The culture bottle is supplied with the chimneyed rubber septum 12 containing puncturing device 20 in place and protected at the top of the chimney 18 by a removable cover plug 22. The culture can be primed in the conventional manner by injection with a syringe and, as in the prior art, the chlor-butyl rubber septum re-seals itself as the syringe is withdrawn.
However, the most important aspect of the present invention resides in the provision of an individual pressure sensing unit 24, including data processing means, for each bottle.
The unit 24 is shown, prior to fitting, above the centre bottle 10 in Figure 1. The cover plug 22 at the top of the chimney of die rubber septum 12 of this bottle has been removed ready for fitting of the unit. It will be noted that the lateral dimensions of the unit 24 do not exceed those of the bottle footprint.
The unit 24, which is battery powered, comprises a miniature pressure transducer, an analogue-to-digital converter, a processor storing a data interpretation algorithm, and a display device 26. These are contained within a housing which has an underside boss 28 which can be sealingly engaged in the chimney 18 of the septum of the bottle 10. This arrangement of chimney and boss fitting closely therein ensures a very effective pneumatic seal. As the bottle is held in registration in known manner by its seating in the support in the culturing unit, it may be convenient for the pressure sensing unit 24 to be angularly aligned by means of a vertical tongue/slot or spline arrangement provided on the boss 28 and the interior of the chimney 18. Optionally, the housing of the pressure sensing unit 24 may also have an infra-red port 29 through which processed data output from the processor may be signalled to a remote location, i.e. a remote display supervised by an operator. The data fed to the remote display will preferably include a signal for activating an alarm at the remote location if any bottle being monitored develops a significant pressure change, exceeding a predetermined value. However, the unit 24 of the present invention is a stand alone device which enables monitoring of the culture bottle without the need for any additional equipment other than a simple incubator in which to stand the bottle.
Referring again to Figure 1 , the right-hand bottle 10 is shown with the pressure sensing unit 24 in fitted condition. It can be seen that, when the boss 28 on the bottom of the housing is inserted into the top of the chimney 18, the puncturing device 20, which includes a hollow needle 30, penetrates the septum 12, which has a small area 32 of reduced thickness aligned with the needle at the bottom of the chimney 18, thereby to open pressure communication through the needle to the miniature pressure transducer in the sensing unit 24. This communication is established without in any way exposing the contents of the bottle to atmosphere. Thus, a total seal is established between the boss 28 and the chimney 18, which seal is maintained during completion of the insertion step to
cause the needle to penetrate die septum 12. Moreover, communication is established via a sterility barrier 34 forming pan of the puncturing device 20, not only to avoid contamination of the pressure sensing unit and ensure that it is re-usable, but also to ensure that the bottie contents are not contaminated from the pressure transducer. It is also important that the sepmm 18 reseals around the needle 30 after puncturing, and to ensure this the sepmm is most preferably made of chlor-butyl rubber, as noted above. The miniamre pressure transducer outputs pressure-representative electrical signals to the analogue to digital convener, and thence to the processor within the sensing unit 24.
Although each bottle is monitored individually, it is nevenheless useful to retain a coding system for the bottle and the sensing unit fitted to it, especially if information is to be transmitted to a remote location. Thus, not only will the bottle 18 bear a unique bar code for bottle identification, but also the pressure sensing unit 24 will bear a visible bar code and a corresponding stored code which can be transmitted to the remote location, in conjunction with pressure-representative signals, on demand. This code may also be displayed on the on-board display, conveniently an integral LCD, of the sensing unit 24. This LCD display will show at least the pressure stams, i.e. positive or negative, together with the pressure value and elapsed time.
As previously mentioned, in use the bottle is maintained at the appropriate culturing temperature, and the sensing unit conveniently acts as a heat insulative top to the bottle.
The data link with a remote location is performed using modulated infra-red signals, at least to trigger an alarm if pressure in a bottle exceeds a predetermined value.
Additionally, it is appropriate to incorporate a venting device in the pressure sensing unit 24, i.e. a valve which opens to atmosphere. This may operate automatically or on demand.
It is also possible to include an environment temperature measuring device in the sensing unit, supplying environmental temperature information to the sensing unit 24 so that direction correction of data with respect to temperature is carried out.
Figure 2 again shows the sensing unit 24, but with its cover removed. The puncturing device is shown in its rest position 20 and its position 20A in which the sepmm 12 has been puncmred. Figure 2 otherwise uses the same references as in Figure 1 for corresponding pans. Additionally, however, Figure 2 shows a two pan pressure manifold 36 via which internal bottle pressure is transmitted to a pressure transducer 38, which outputs pressure representative signals to a printed circuit board 39 carrying the electronics of the sensing unit. This board outputs signals to an integral LCD device 40.
Details of the electronics carried by the printed circuit board are shown in Figure 3.
The pressure transducer 38, and also a temperature transducer 42, output signals dirough signal conditioning and/or amplifying means 44, 46 to an A/D convener 48 which supplies digitised signals to a CPU 50 which incorporates a clock 52, a main memory 54 storing a signal processing algorithm, and a supplementary memory 56 for temporary data storage. An on-bottle switch 58 and a reset switch 60 provide user interrupts, and a non¬ volatile memory 62 provides for calibration and entry of non-transient data. Power control circuitry is indicated at 64, 66. The processed data is fed to the LCD device 40 and, in the event of an overpressure, an output is supplied to a solenoid 68 controlling the pressure relief or venting valve.
Figure 4 shows the functions performed by the sensing unit, with possible unit interrupts in the event of any kind of detected operational error or initial stand-by test error and other interrupts, automatic or user, due to failures during monitoring.
Figure 5 is user flow diagram showing the functions performed during normal operation. It will be noted that the sensing unit remains uncontaminated and is therefore re-usable, and also that it is therefore possible for the user to extract a sub-culture and then reconnect me sensing unit to the bottle for further monitoring.
Claims
1. A sensing unit for monitoring the contents of a sealed container partially filled with a liquid which can give rise to variations of a property associated with the container headspace above the liquid, comprising a housing having means enabling its connection to a closure at the top of the container through which the container headspace is placed in communication with the housing, the connection enabling means effecting said communication without at any time exposing the liquid contents of the container to atmosphere, and the housing incorporating a transducer responsive to the sensed property of the headspace and providing electrical outputs proportional to variations in the property, data processing means receiving the signal outputs of the transducer and including a signal processor storing a data processing algorithm, and indicating means receiving die output of the data processor to enable the sensed property to be visually monitored at the sensing unit.
2. A sensing unit according to claim 1 , for a container which is totally sealed at the top by a closure fitting, wherein the sensing unit housing connects by displacement towards and into engagement with the closure fitting to form a total seal therewith before displacement is completed to place the interior of the bottle in communication with the housing without breaking the said total seal between the housing and the closure fitting.
3. A sensing unit according to claim 1 or 2, when applied to the monitoring of the growth of microorganisms in a liquid culture partially filling the container.
4. A sensing unit according to claim 1 , 2 or 3, in which the sensing unit carries a code stored in the data processing means for identification of the container to which the unit is attached.
5. A sensing unit according to claim 4, in which the sensing unit is able to transmit an infra-red alarm signal to a remote location in the event of detection of a property variation in the container headspace in excess of a predetermined value, the alarm signal being transmitted in conjunction with the identification code.
6. A sensing umt according to any one of claims 1 to 5, in which the umt includes an environmental temperamre measurement device for providing data correction signals to the processing means.
7. A sensing umt according to any one of claims 1 to 6, in combination with a rubber seal normally sealing the top of the container, said rubber seal having a formation adapted to receive and sealingly locate an attachment boss on the base of die housing of the pressure sensing umt.
8. The combination according to claim 7, in which the formation on the rubber seal accommodates a device which punctures the rubber seal when the pressure sensing umt is located in the formation, thereby to allow commumcation between the container headspace and the sensing umt.
9 The combination according to claim 8, m which the puncturing device is a hollow needle through which commumcation is established between the container headspace and the sensing unit.
10. The combination according to claim 8 or 9, m which the puncturing device includes a sterility barrier which allows pressure commumcation but prevents πsk of contamination of the sensing umt from the container contents.
11 The combination according to any one of claims 8 to 10, in which the puncturing device establishes a pressure communications link with the pressure sensing umt, which incorporates a pressure transducer
12. The combination according to any one of claims 8 to 11, in which the sensing umt or the puncturing device incorporates a pressure relief device
13. A method of monitoring a property of the headspace of a sealed container partially filled with liquid, accordmg to which the container is provided with a closure having a formation to which is attached a sensing umt and through which commumcation is established between the container headspace and the sensing unit, the sensing unit incorporating a data processing means which receives signals representative of the property to be sensed in the container headspace when the sensing unit is attached to the closure formation, and the property representative signals are processed and a visual indication given on the sensing unit at least when any abnormal variation in the property is detected.
14. A method according to claim 13, according to which the closure includes a rubber seal puncmred by a puncmring device housed in the closure formation when the sensing unit is attached, and property representative signals are transmitted to the sensing unit via the puncmring device.
15. A method according to claim 14, according to which the puncmring device establishes a pressure communications link with the sensing unit, which incorporates a pressure sensor generating electrical signals fed to the data processing means.
16. A method according to any one of claims 13 to 15. according to which the rubber seal is thick enough to prevent the influence of barometric pressure variations on the property representative signals.
17. A method according to any one of claims 13 to 16, according to which the data processing means transmits to a remote display an infra-red signal containing an identification code when an overpressure is detected in the container.
18. A method according to any one of claims 13 to 17, applied to a container partially filled with a liquid culture, in order to monitor the growth of microorganisms.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP96304359.1 | 1996-06-11 | ||
EP96304359 | 1996-06-11 |
Publications (1)
Publication Number | Publication Date |
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WO1997047728A1 true WO1997047728A1 (en) | 1997-12-18 |
Family
ID=8224976
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
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PCT/GB1997/001530 WO1997047728A1 (en) | 1996-06-11 | 1997-06-09 | Monitoring the contents of sealed containers |
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WO (1) | WO1997047728A1 (en) |
Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
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US4059017A (en) * | 1976-07-02 | 1977-11-22 | General Cable Corporation | Detecting apparatus with excess pressure protectors |
GB2159282A (en) * | 1984-05-21 | 1985-11-27 | Nat Nuclear Corp Ltd | Monitoring pressure within a vessel |
DE9003081U1 (en) * | 1990-03-14 | 1990-06-07 | Scherer, Paul A., Prof. Dr., 8042 Oberschleissheim, De | |
US5060108A (en) * | 1990-01-25 | 1991-10-22 | Texas Instruments Incorporated | Packaging and sealing for pressure transducer |
US5120313A (en) * | 1986-03-28 | 1992-06-09 | Nancy W. Elftman | Method for measuring blood pressure in an animal or human using a percutaneous access port |
EP0592728A1 (en) * | 1992-04-16 | 1994-04-20 | Difco Laboratories Incorporated | Detecting microbiological growth |
WO1994019451A1 (en) * | 1993-02-17 | 1994-09-01 | Unipath Limited | Venting device |
-
1997
- 1997-06-09 WO PCT/GB1997/001530 patent/WO1997047728A1/en active Application Filing
Patent Citations (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US4059017A (en) * | 1976-07-02 | 1977-11-22 | General Cable Corporation | Detecting apparatus with excess pressure protectors |
GB2159282A (en) * | 1984-05-21 | 1985-11-27 | Nat Nuclear Corp Ltd | Monitoring pressure within a vessel |
US5120313A (en) * | 1986-03-28 | 1992-06-09 | Nancy W. Elftman | Method for measuring blood pressure in an animal or human using a percutaneous access port |
US5060108A (en) * | 1990-01-25 | 1991-10-22 | Texas Instruments Incorporated | Packaging and sealing for pressure transducer |
DE9003081U1 (en) * | 1990-03-14 | 1990-06-07 | Scherer, Paul A., Prof. Dr., 8042 Oberschleissheim, De | |
EP0592728A1 (en) * | 1992-04-16 | 1994-04-20 | Difco Laboratories Incorporated | Detecting microbiological growth |
WO1994019451A1 (en) * | 1993-02-17 | 1994-09-01 | Unipath Limited | Venting device |
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