Method and apparatus for the non-invasive monitoring of gas exchange by biological material

Abstract

The invention provides an indirect pressure sensing system for non-invasive measurement of primary pressure in a sealed container, which communicates primary pressure changes from within the container, via a flexible diaphragm, to a secondary chamber wherein there is a defined relationship between the primary and secondary pressures, which enables a pressure sensor in the secondary chamber to generate a signal representing primary pressure in the sealed container, but to remain isolated from the contents of the sealed container. The pressure sensor can provide electrical outputs representing the pressure detected, and the outputs are fed to data processing means capable of producing a measurement of primary pressure. The system can have a liquid culture of cellular material (eg. micro organisms, plant tissue cells, animal cells etc.) partially filling the container, whereby the metabolism and/or growth of cellular material causes gas exchanges between liquid and headspace, which can result in primary pressure changes.

1 . An indirect pressure sensing system for non-invasive measurement of primary pressure in a sealed container, which communicates primary pressure changes from within the container, via a flexible diaphragm, to a secondary chamber wherein there is a defined relationship between the primary and secondary pressures, which enables a pressure sensor in the secondary chamber to generate a signal representing primary pressure in the sealed container, but to remain isolated from the contents of the sealed container.  
     
     
         2 . A pressure sensing system as in  claim 1  in which the pressure sensor provides electrical outputs representing the pressure detected, and the outputs are fed to data processing means capable of producing a measurement of primary pressure.  
     
     
         3 . A pressure sensing system according to  claim 1 , having a sealed container partially filled with liquid, wherein pressure variations arise in the gaseous phase of the headspace of the container are due to biological activity within the liquid.  
     
     
         4 . A pressure sensing system according to  claim 1  having a liquid culture of cellular material partially filling the container.  
     
     
         5 . A pressure sensing system according to  claim 4 , wherein metabolism and/or growth of the cellular material causes gas exchanges between liquid and headspace, which result in primary pressure changes.  
     
     
         6 . A pressure sensing system according to  claim 1 , wherein the container includes a mixing means to promote gas exchange between the liquid phase and gaseous phase.  
     
     
         7 . The pressure sensing system of  claim 6 , wherein the mixing means is a rotating component which includes features to enhance gas exchange by increasing interfacial areas between liquid and gas phases.  
     
     
         8 . The pressure sensing system of  claim 7 , wherein the mixing means is either wholly or partially submerged in the liquid phase, such that the surface interface boundary is disturbed continuously.  
     
     
         9 . The pressure sensing system of  claim 6 , wherein the mixing means is operated with variable speed, changes of direction and/or variable run/stop intervals.  
     
     
         10 . The system of  claim 6 , wherein the mixing means includes as part of the assembly an ‘axle’ which experiences moving liquid contact but low shear forces.  
     
     
         11 . The system according to  claim 1 , wherein the container, with associated components, contents, and pressure transfer diaphragm are provided as a single-use, disposable item.  
     
     
         12 . The system according to  claim 11  including a secondary chamber and a seal having a formation adapted to receive a connection to an electronic pressure transducer.  
     
     
         13 . The system according to  claim 11  including a second diaphragm, attached to the first to follow movements in an identical way, whereby the second diaphragm transfers pressure changes to a non-electronic pressure indicator.  
     
     
         14 . The system according to  claim 11  including as an enabling feature the addition of a frangible seal (e.g. foil) to be broken by a hollow component pushed into place via indirect pressure on a flexible covering, creating an irreversible valve action.  
     
     
         15 . The system according to  claim 11  with a first opening to the headspace and a second opening to the external atmosphere such that a connection is made on the application/removal of the pressure, exerted indirectly via flexible covering, whereby this feature allows the container contents to assume atmospheric pressure as and when necessary (e.g. addition of sample), and whereby this can be operated at any time (repeatedly if necessary) on demand.  
     
     
         16 . The system according to  claim 11 , wherein either a second route to one filter or a separate filter to provide a venting port, which is activated if the container headspace becomes either significantly positive or negative in pressure and which, in addition, as a safety measure, also prevents build up of substantial internal pressures.  
     
     
         17 . The system according to  claim 11  in which a fluid transfer septum is provided for addition or removal of the contents of the sealed chamber using a hypodermic syringe and needle.  
     
     
         18 . The system according to  claim 11 , which generates electrical signals fed to a data processing means where interpretation can take place.  
     
     
         19 . The system according to  claim 18  wherein the data processing means can process and display pressure representative signals, examined by reference to an algorithm, and signal any significant events via an LED or other prominent display device.  
     
     
         20 . The system according to  claim 18  wherein the signals include identity codes for identification of the container, pressure sensing unit and data processing means.  
     
     
         21 . The system according to  claim 11 , wherein the single use disposable item carries batch and application specific data in the form of a bar code label.  
     
     
         22 . The system according to  claim 11  includes color coding of the top or other prominent region of the container to rapidly identify the formulation of the fluid contents.  
     
     
         23 . The system according to  claim 17  which also includes, first, a tamper-evident closure for the point of access to the container, and second, a physical formation which extends above the septum so that the latter is at the base of a recess, so as to limit the possibility of a needle-stick injury to an operator using the system.  
     
     
         24 . The system according to  claim 11  which is made from materials selected for effective and environmentally sound disposal.  
     
     
         25 . A system according to  claim 11 , having means to stabilize temperature, whereby the entire disposable is located in a close fitting ‘silo’ which is temperature controlled.  
     
     
         26 . The system according to  claim 25 , wherein the ‘silo’, and optionally other external surfaces, are insulated, thereby minimizing heat losses.  
     
     
         27 . The system according to  claim 25 , wherein the system has precise temperature control using a small, low wattage heater pad bonded to the external surface of the silo, linked to a safety thermostat and subject to constant monitoring.  
     
     
         28 . The system according to  claim 25 , wherein the silo is a leak proof vessel, which is of adequate volume to totally contain the disposable container and all fluids present, and optionally the ‘silo’ includes electrodes to detect and signal any leakage.  
     
     
         29 . The system according to  claim 28 , whereby in the event of a leak being detected the entire unopened silo can be extracted for safe disposal.  
     
     
         30 . A single test unit for use in a system according to  claim 1 , comprises a temperature controlled silo, a magnet drive rotor attached to a motor, a pressure sensor assembly and a micro processor which controls and monitors pressure, wherein processor can also optionally apply a predetermined algorithm to make interpretations, plus display status and outcomes to human operators.  
     
     
         31 . A test unit for use in a system according to  claim 1 , comprises two ‘silos’, two sensor systems and one double ended motor carrying two magnetic drive rotors and a micro processor dealing with data, whereby two tests, usually from one sample, can be run simultaneously.  
     
     
         32 . The test units according to  claim 30 , in which groups of the single test unit/dual test unit form a compact array so as to provide a small, space efficient test facility which can be scaled up in a cost effective modular way.  
     
     
         33 . A test unit for use in a system according to  claim 1 , wherein the unit provides monitoring of a plurality of test containers, wherein each single or dual arrangement is serviced by its own pressure sensing system and wherein each system reports its findings and conclusions to a centralized and/or remote location, in conjunction with an ID code which denotes the locations of the system/test combinations.  
     
     
         34 . The pressure sensing system according to  claim 4 , wherein the cellular material is microorganisms, plant tissue cells, or animal cells.  
     
     
         35 . The pressure sensing system according to  claim 6 , wherein the mixing means is driven indirectly.  
     
     
         36 . The pressure sensing system according to  claim 35 , wherein the mixing means is driven indirectly by magnetic coupling.  
     
     
         37 . The pressure sensing system of  claim 7 , wherein the rotating component includes paddles, hollow paddles, perforated paddles, or cylindrical forms with pockets, recesses or holes.  
     
     
         38 . The system according to  claim 13 , wherein the pressure indicator is a manometer.  
     
     
         39 . The system according to  claim 15  wherein the second opening to the external atmosphere is via filter.