WO2022024011A1

WO2022024011A1 - A fluid measurement chamber

Info

Publication number: WO2022024011A1
Application number: PCT/IB2021/056886
Authority: WO
Inventors: Keyu Chen; Luke English; Xiaoke Yi; Mengwei Yuan
Original assignee: AusMed Global Limited
Priority date: 2020-07-29
Filing date: 2021-07-29
Publication date: 2022-02-03

Abstract

A fluid measurement chamber (10) comprising: a fluid inlet (12) for receiving an inflow of fluid (13) into the fluid measurement chamber (10) and a fluid outlet (14) for discharging an outflow of fluid (15) from the fluid measurement chamber (10); a first flow control unit (16) in fluid communication with the fluid inlet (12); a fluid storage chamber (18) in fluid communication with the first flow control unit (16); a second flow control unit (20) in fluid communication between the fluid storage chamber (18), the first flow control unit (16), and the fluid outlet (14); and a fluid sensing unit (22) operatively associated with the fluid storage chamber (18) to detect and measure a concentration of an analyte in a fluid that circulates around a fluid circulation path (24) between the first control unit (16), the fluid storage chamber (18), and the second flow control unit (20).

Description

A FLUID MEASUREMENT CHAMBER

FIELD

[0001] The present invention relates to fluid measurement chambers, systems, apparatus and methods of operating the same.

[0002] The invention has particular application to the measurement of analyte concentration in gas, and it will be convenient to describe the invention herein in this exemplary context. It will be appreciated, however, that the invention is not necessarily limited to this particular application, but may also be employed in other applications involving trace gas measurement and analysis in the fields of biotechnology, clinical applications, diagnostic, instrumentation, and medical devices.

BACKGROUND

[0003] Trace gas analysis is widely used in a variety of medical, chemical and industrial systems, and typically performed as an application of mass spectrometry or ion-mobility spectrometry using heavy and expensive equipment. In recent times, trace gas analysis has been increasingly used in the medical and healthcare fields. For example, measurement of breath acetone can provide a plethora of important information for medical diagnosis and disease monitoring. However, there are inherent difficulties in detecting and measuring target biomarker analytes at parts per million concentrations in small volume gas.

[0004] In conventional gas analysis systems, input gas is passed through a measurement apparatus to react with a sensor or reaction material, following which the concentration of an analyte in the input gas may be measured. Depending on the reaction type within the apparatus, such systems typically require a large volume of gas to be input in order to obtain a highly sensitive gas measurement. Large volumes of gas are not always readily available in some applications, which may either render the gas measurement unfeasible or otherwise inaccurate. There are therefore limitations to the detection of target biomarker analytes in small volume gases, particularly for medical and healthcare applications. SUMMARY

[0005] There is disclosed herein a fluid measurement chamber comprising: a fluid inlet for receiving an inflow of fluid into the fluid measurement chamber and a fluid outlet for discharging an outflow of fluid from the fluid measurement chamber; a first flow control unit in fluid communication with the fluid inlet; a fluid storage chamber in fluid communication with the first flow control unit; and a second flow control unit in fluid communication between the fluid storage chamber, the first flow control unit and the fluid outlet; and a fluid sensing unit operatively associated with the fluid storage chamber to detect and measure a concentration of an analyte in a fluid that circulates around a fluid circulation path between the first control unit, the fluid storage chamber, and the second flow control unit.

[0006] The first flow control unit may include a first valve to control the inflow of fluid from the fluid inlet to the fluid storage chamber, the first valve being actuatable between an open state to permit the inflow of fluid and a closed state to prevent the inflow of fluid.

[0007] The second flow control unit may include a second valve to control the outflow of fluid from the fluid storage chamber to the fluid outlet, the second valve being actuatable between an open state to permit the outflow of fluid and a closed state to prevent the outflow of fluid.

[0008] Either one or both of the first and second flow control units may include a micropump configured to circulate the flow of fluid around the fluid circulation path between the first flow control unit, the fluid storage chamber, and the second flow control unit.

[0009] The fluid measurement chamber may further include a temperature sensor to monitor a temperature of the fluid within the fluid measurement chamber.

[0010] The fluid measurement chamber may further include a pressure sensor to detect leaks in the fluid circulation path.

[0011] The fluid measurement chamber may be contained within a hermetically sealed housing to isolate the fluid measurement chamber from an external environment. [0012] The fluid measurement chamber may further include a fluid dilution unit in fluid communication between the first flow control unit and the fluid storage chamber, the fluid dilution unit being configured to introduce a reference fluid of a known analyte concentration to the fluid that is being circulated along the fluid circulation path.

[0013] There is also disclosed herein a method of measuring analyte concentration in fluid using a fluid measurement chamber, the method comprising the steps of: receiving an inflow of fluid into a fluid measurement chamber through a fluid inlet, and discharging an outflow of fluid from the fluid measurement chamber through a fluid outlet, wherein the fluid measurement chamber comprises: a first flow control unit in fluid communication with the fluid inlet; a fluid storage chamber in fluid communication with the first flow control unit; a second flow control unit in fluid communication between the fluid storage chamber, the first flow control unit, and the fluid outlet; and a fluid sensing unit operatively associated with the fluid storage chamber; actuating the first and second flow control units to prevent the inflow and outflow of fluid to and from the fluid measurement chamber; circulating a flow of fluid around a fluid circulation path between the first flow control unit, the fluid storage chamber, and the second flow control unit, such that the flow of fluid interacts with the fluid sensing unit more than once; and detecting and measuring a concentration of an analyte in the flow of fluid being circulated around the fluid circulation path.

[0014] The flow of fluid between the first flow control unit, the fluid storage chamber, and the second flow control unit may be circulated using a micropump associated with either one or both of the first and second flow control units.

[0015] The fluid measurement chamber may further include a fluid dilution unit in fluid communication between the first flow control unit and the fluid storage chamber, and the method may further comprise the step of: introducing, using the fluid dilution unit, a reference fluid of a known concentration to the flow of fluid that is being circulated along the fluid circulation path so as to dilute the flow of fluid. [0016] The method may further comprise the step of: determining the concentration of the analyte in the inflow of fluid by applying a known dilution factor to a measured concentration of the diluted flow of fluid.

[0017] The method may further comprise the step of: actuating the first and second flow control units to permit the inflow and outflow of fluid to and from the fluid measurement chamber; and flushing the fluid measurement chamber.

[0018] There is also disclosed herein a fluid measurement system comprising: a fluid measurement chamber including: a fluid inlet for receiving an inflow of fluid into the fluid measurement chamber and a fluid outlet for discharging an outflow of fluid from the fluid measurement chamber; a first flow control unit in fluid communication with the fluid inlet; a reaction chamber in fluid communication with the first flow control unit; and a second flow control unit in fluid communication between the reaction chamber and the first flow control unit; and a fluid sensing unit operatively associated with the reaction chamber to detect and measure a concentration of an analyte in a fluid that circulates around a fluid circulation path between the first control unit, the reaction chamber, and the second flow control unit; and a fluid storage chamber including: a fluid storage chamber inlet for receiving an inflow of fluid into the fluid storage chamber and a fluid storage chamber outlet for discharging an outflow of fluid from the fluid storage chamber and into the fluid measurement chamber via an intermediate fluid conduit.

[0019] The fluid measurement system may further comprise a flow generator located along the intermediate fluid conduit to pump a flow of fluid from the fluid storage chamber into the fluid measurement chamber.

[0020] The fluid storage chamber may further include a pressure sensor to detect and measure a pressure of fluid within the fluid storage chamber. [0021] The fluid storage chamber may include a movable partition operable to adjust a volume of fluid within the fluid storage chamber.

[0022] The fluid storage chamber may be housed separately from the fluid measurement chamber.

[0023] There is also disclosed herein a method of measuring fluid using a fluid measurement system, the method comprising the steps of: receiving an inflow of fluid into a fluid storage chamber; storing the inflow of fluid in the fluid storage chamber until the fluid reaches a predetermined pressure; discharging the stored fluid from the fluid storage chamber into a fluid measurement chamber, wherein the fluid measurement chamber is separate from the fluid storage chamber and comprises: a first flow control unit in fluid communication with a fluid inlet; a reaction chamber in fluid communication with the first flow control unit; a second flow control unit in fluid communication between the fluid reaction chamber, the first flow control unit, and a fluid outlet; and a fluid sensing unit operatively associated with the fluid reaction chamber; actuating the first and second flow control units to close the fluid inlet and the fluid outlet; circulating a flow of fluid around a fluid circulation path between the first flow control unit, the fluid reaction chamber, and the second flow control unit, such that the flow of fluid interacts with the fluid sensing unit more than once; and detecting and measuring a concentration of an analyte in the flow of fluid being circulated around the fluid circulation path.

[0024] There is also disclosed herein an apparatus for measuring analyte concentration in a fluid, the apparatus comprising: a housing surrounding an internal chamber and including a fluid inlet to receive an inflow of fluid into the internal chamber and a fluid outlet to discharge an outflow of fluid from the internal chamber; a flow control unit located within the internal chamber and in fluid communication with the fluid inlet; a reaction chamber located in fluid communication with the filter and the fluid outlet, the reaction chamber including: a light source; a slide positionable below the light source; a reaction material locatable on the slide; and a photodetector located below the slide and at a base of the reaction chamber.

[0025] There is also disclosed herein a method of operating the apparatus described above, the method including the steps of: loading the reaction material on the slide; passing light from the light source through the reaction material to the photodetector, and obtaining a baseline measurement of an optical characteristic of the reaction material; receiving a fluid sample into the reaction chamber via the fluid inlet and flow control unit; circulating the fluid sample through the reaction chamber so as to allow the fluid sample to chemically react with the reaction material; passing light from the light source through the reaction material to the photodetector, and obtaining a post-reaction measurement of the optical characteristic of the reaction material; and obtaining a concentration of the analyte in the fluid sample by calculating a change in the optical characteristic of the reaction material between the post-reaction measurement and the baseline measurement.

BRIEF DESCRIPTION OF THE DRAWINGS

[0026] For a more complete understanding of the present invention, exemplary embodiments of the invention are explained in more detail in the following description with reference to the accompanying drawing figures, in which like reference signs designate like parts and in which:

[0027] Figure l is a schematic perspective view of a fluid measurement chamber according to one embodiment;

[0028] Figure 2 is a schematic view of an exemplary calibration curve for a sensor of a fluid measurement chamber; [0029] Figure 3 is a schematic perspective view of a fluid measurement chamber according to another embodiment;

[0030] Figure 4 is a schematic perspective view of a fluid measurement system according to another embodiment;

[0031] Figure 5 is a schematic perspective view of a fluid measurement apparatus according to another embodiment;

[0032] Figure 6 is a flow diagram showing an operation of the fluid measurement apparatus of Figure 5; and

[0033] Figure 7 is a schematic view of a plot showing measurement results at different acetone concentrations.

DETAILED DESCRIPTION OF EMBODIMENTS

[0034] In Figure 1 of the accompanying drawings, there is schematically depicted an embodiment of a fluid measurement chamber 10 having a fluid inlet 12 for receiving an inflow of fluid 13 into the fluid measurement chamber 10 and a fluid outlet 14 for discharging an outflow of fluid 15 from the fluid measurement chamber 10. It will be understood that the fluid may be in the form of a gas, such as air that is expelled from a person’s mouth during ventilation. The fluid may alternatively be in the form of a liquid.

[0035] The fluid measurement chamber 10 further includes a first flow control unit 16 that is in fluid communication with the fluid inlet 12, and a fluid storage chamber 18 that is in fluid communication with the first flow control unit 16. In the depicted embodiment, a first conduit 17 provides the fluid communication between the first flow control unit 16 and the fluid storage chamber 18.

[0036] The fluid measurement chamber 10 further includes a second flow control unit 20 that is in fluid communication with the fluid storage chamber 18. The second flow control unit 20 is also in fluid communication with the fluid outlet 14 and the first flow control unit 16. In the depicted embodiment, the second flow control unit 20 is disposed in fluid communication between the fluid storage chamber 18, the first flow control unit 16, and the fluid outlet 14.

Also shown in the depicted embodiment is a second conduit 19 that provides the fluid communication between the fluid storage chamber 18 and the second flow control unit 20, and a third conduit 21 that provides the fluid communication between the second flow control unit 20 and the first flow control unit 16. It will thus be appreciated that the first flow control unit 16, the fluid storage chamber 18, and the second flow control unit 20 are arranged to be fluidically interconnected so as to form a circuit through which a fluid may circulate.

[0037] The fluid measurement chamber 10 further includes a fluid sensing unit 22 that is operatively associated with the fluid storage chamber 18. In the depicted embodiment, the fluid sensing unit 22 is provided inside the fluid storage chamber 18, and is arranged to detect and measure a concentration of an analyte in a fluid that circulates around a fluid circulation path 24 between the first flow control unit 16, the fluid storage chamber 18, and the second flow control unit 20. It will be understood that in the depicted embodiment, the fluid storage chamber 18 also provides a reaction chamber in which the fluid is able to interact with the fluid sensing unit 22. The fluid sensing unit 22 may comprise a chemical interactant having optical characteristics that change in response to a chemical reaction with the target analyte. Details of the sensing arrangement are described in detail in the Applicant’s earlier International Publication No. WO 2020/047606, filed on 6 September 2019. In the interest of brevity, the entire content of this International Publication is incorporated herein by cross-reference.

[0038] In the depicted embodiment, the fluid circulation path 24 extends from the first control unit 16 to the fluid storage chamber 18 along the first conduit 17, to the second flow control unit

20 along the second conduit 19, and back to the first flow control unit 16 along the third conduit

21 in a counter-clockwise direction. However, it will be understood that the fluid circulation path 24 does not necessarily need to follow the counter-clockwise direction as depicted, and may instead follow a reverse (i.e. clockwise) direction, depending on how the various components are configured and positioned in relation to each another.

[0039] It is envisaged that the first flow control unit 16 may include a valve (not shown) and/or a tube (not shown) to control the inflow of fluid 13 from the fluid inlet 12 to the fluid storage chamber 18. The valve of the first flow control unit 16 may be actuatable between an open state to permit the inflow of fluid 13 from the fluid inlet 12 to the fluid storage chamber 18, and a closed state to prevent the inflow of fluid 13 from the fluid inlet 12 to the fluid storage chamber 18.

[0040] The second flow control unit 20 may also include a valve (not shown) and/or a tube (not shown) to control the outflow of fluid 15 from the fluid storage chamber 18 to the fluid outlet 14. The valve of the second flow control unit 20 is actuatable between an open state to permit the outflow of fluid 15 from the fluid storage chamber 18 to the fluid outlet 14, and a closed state to prevent the outflow of fluid 15 from the fluid storage chamber 18 to the fluid outlet 14.

[0041] It will be appreciated that the valves of the first and second flow control units 16 and 20 may each be one-way valves. For example, the valve of the first flow control unit 16 may be adapted to only permit the inflow of fluid 13 from the fluid inlet 12 to the fluid storage chamber 18, and prevent the reverse flow of fluid from the fluid storage chamber 18 to the fluid inlet 12.

[0042] The first and second flow control units 16, 20 may each include a micropump (also not shown) to circulate the fluid around the fluid circulation path 24 between the first flow control unit 16, the fluid storage chamber 18, the second flow control unit 20, back to the first flow control unit 16, and so on. It is envisaged that in some embodiments, only one of the first or second flow control units 16, 20 may include the micropump, and in other embodiments, both of the first and second flow control units 16, 20 may include the micropump. The micropump of each of the first and second flow control units 16, 20 may propel or circulate the fluid around the fluid circulation path 24 at a set flow rate.

[0043] The fluid measurement chamber 10 may further include a temperature sensor (not shown) to detect and monitor a temperature of the fluid within the fluid measurement chamber 10. The temperature sensor may be located and operatively associated with any one or more of the aforementioned components of the fluid measurement chamber 10. For example, the temperature sensor may be located within the fluid storage chamber 18 to provide an indication of the temperature of the fluid that enters the fluid storage chamber 18, and that subsequently circulates around the fluid circulation path 24.

[0044] The fluid measurement chamber 10 may further include a pressure sensor (not shown) to detect and monitor a pressure of the fluid that circulates around the fluid circulation path 24.

The pressure sensor may be located and operatively associated with any one or more of the aforementioned components of the fluid measurement chamber 10, for example to detect leaks in the fluid circulation path 24.

[0045] In preferred forms, the fluid measurement chamber 10 is contained within a hermetically sealed housing (not shown) to isolate the fluid measurement chamber 10 from an external environment surrounding the chamber 10, which may prevent fluid leakage and contamination during fluid measurement. It will be appreciated that the hermetically sealed housing may be in any shape or form suitable for containment and measurement of fluid.

[0046] The operation of the fluid measurement chamber 10 will now be described.

[0047] Prior to operation, the valves of the first and second flow control units 16 and 20 are actuated or set to their open states. An inflow of fluid 13 (e.g. a gas containing a target analyte) then enters the fluid measurement chamber 10 through the fluid inlet 12, whereby the inflow of fluid 13 passes through the first flow control unit 16 and the fluid storage chamber 18, and is then discharged from the fluid measurement chamber 10 when the outflow of fluid 15 passes through the second flow control unit 20. Once a sufficient volume of fluid has entered the fluid measurement chamber 10, the valves of the first and second flow control units 16 and 20 are actuated or set to their closed states, which in turn opens the fluid circulation path 24 inside the chamber 10.

[0048] The fluid is then pumped (by way of the micropump of the first and/or second flow control units 16 and 20, for example) around the fluid circulation path 24 at a set flow rate. The fluid in the fluid circulation path 24 is allowed to circulate more than once, so as to allow successive passes of the fluid through the fluid storage chamber 18. Accordingly, the fluid in the fluid circulation path 24 may interact with the fluid sensing unit 22 more than once. Once the fluid in the fluid circulation path 24 has passed through the fluid storage chamber 18 a sufficient number of times, the fluid sensing unit 22 is enabled to detect and measure a concentration of an analyte in the fluid being circulated around the fluid circulation path 24.

[0049] Once the measurement of the analyte concentration in the fluid has concluded, the valves of the first and second flow control units 16 and 20 are returned to their open states. The fluid in the fluid measurement chamber 10 is then flushed by passing a fluid from the fluid inlet 12, through the storage chamber 18, and out through the fluid outlet 14. [0050] It is understood that in chemical analysis, a sensor’s response to a target analyte will typically have a “dynamic range of linearity”, after which the reaction becomes saturated and the slope approaches flat, for example as shown in the exemplary calibration curve of a chemical analysis system in Figure 2.

[0051] In Figure 2, point A indicates the measured sensor response, point B indicates the actual analyte concentration, and point C indicates the boundary of the linear range. It is thus understood that the saturation of the reaction can limit the measurement range and as such, it is understood to be beneficial to extend the measurement range in some applications.

[0052] Referring to Figure 3 of the accompanying drawings, there is schematically depicted an alternative embodiment of a fluid measurement chamber 50, which operates in generally the same manner as the fluid measurement chamber 10 described above, with like reference numerals being used to indicate like features. In this embodiment, however, the fluid measurement chamber 50 includes a fluid dilution unit 52 to facilitate dilution of the fluid that circulates around the fluid circulation path 24, thereby allowing the measurement range of the sensor (i.e. the fluid sensing unit 22) to be extended whilst maintaining accuracy.

[0053] The fluid dilution unit 52 is disposed in fluid communication between the first flow control unit 16 and the fluid storage chamber 18. A fourth conduit 54 provides the fluid communication between the first flow control unit 16 and fluid dilution unit 52, whilst a fifth conduit 56 provides the fluid communication between the fluid dilution unit 52 and the fluid storage chamber 18. The fluid dilution unit 52 is configured to introduce a reference fluid of a known analyte concentration to the fluid that is being circulated along the fluid circulation path 24. In a preferred form, it is envisaged that the reference fluid has a known zero concentration of the target analyte, and the sensor has a zero response to the reference fluid. This exemplary approach may at least simplify the dilution factor. For example, nitrogen (N2) gas may be used as the reference fluid in an acetone sensing experiment.

[0054] In the depicted embodiment, the fluid dilution unit 52 introduces the reference fluid into the fluid storage chamber 18 via the fifth conduit 56, along a first dilution path 58. The fluid in the fluid circulation path 24 is mixed with the reference fluid that enters the fluid storage chamber 18 via the first dilution path 58. The resulting (diluted) fluid mixture may travel from the fluid storage chamber 18 and into the first flow control unit 16 via the first conduit 17, back into the fluid dilution unit 52 via the fourth conduit 54 along a second dilution path 59, and back into the fluid storage chamber 18 via the fifth conduit 56 along the first dilution path 58. The resulting (diluted) fluid mixture may also travel around the fluid circulation path 24 and interact with the fluid sensing unit 22 more than once.

[0055] The operation of the fluid measurement chamber 50 is generally the same as the operation of the fluid measurement chamber 10 described above, with the additional passing of the fluid through the fluid dilution unit 52. Once the circulation path 24 is open, the fluid dilution unit 52 is enabled to introduce the reference fluid into the fluid storage chamber 18.

The reference fluid then mixes with the fluid in the fluid storage chamber 18 (i.e. the inflow of fluid 13 that enter the fluid measurement chamber 10 via the fluid inlet 12), and the resulting (diluted) fluid mixture is then circulated around the fluid circulation path 24 multiple times as discussed above. Once the resulting (diluted) fluid mixture in the fluid circulation path 24 has passed through the fluid storage chamber 18 a sufficient number of times, the fluid sensing unit 22 is enabled to detect and measure a concentration of an analyte in the diluted fluid mixture that is being circulated around the fluid circulation path 24. The concentration of the analyte in the inflow of fluid 13 may then be calculated by applying a known dilution factor to the concentration of the analyte in the diluted fluid mixture.

[0056] The concentration of an analyte within a fluid after dilution (CAI) is given by:

where CAI is the concentration of analyte A in the input fluid (i.e. the inflow of fluid 13), q input is the volume flow of the input fluid, CAI is the concentration of analyte A in the dilution fluid (i.e. the diluted fluid mixture) and qda is the volume flow of dilution fluid (i.e. the reference fluid).

[0057] After measurement of the concentration of the diluted fluid mixture within the fluid storage chamber 18, the concentration CAI of analyte A in the input fluid (i.e. the inflow of fluid 13) may be determined by rearranging the above formula expressed as: [0058] Ideally, the concentration CA2 of the analyte A in the dilution fluid (i.e. the reference fluid) is zero, thereby simplifying the above equation.

[0059] It will therefore be appreciated from the above that the fluid dilution unit 52 may allow for an accurate measurement of the target analyte at a greater range of concentration, simply by applying the corresponding dilution so as to bring the concentration’s magnitude into the dynamic range of linearity as discussed above.

[0060] Turning to Figure 4 of the accompanying drawings, there is schematically depicted an embodiment of a fluid measurement system 100, which includes a fluid measurement chamber 110 that operates in generally the same manner as the fluid measurement chamber 10 described above, with like reference numerals being used to indicate like features. However, in this embodiment, the fluid measurement chamber 110 includes a fluid reaction chamber 118 which operates in a like manner to the fluid storage chamber 18 described above, and the fluid measurement system 100 further includes a designated fluid storage chamber 160 that is located separately from the fluid measurement chamber 110.

[0061] The components of the fluid measurement chamber 110 (which generally correspond to the components of the fluid measurement chamber 10 described above) will be described below for completeness.

[0062] The fluid measurement chamber 110 includes a fluid inlet 112 for receiving an inflow of fluid 113 into the fluid measurement chamber 110 and a fluid outlet 114 for discharging an outflow of fluid (not shown) from the fluid measurement chamber 110.

[0063] The fluid measurement chamber 110 further includes a first flow control unit 116 that is in fluid communication with the fluid inlet 112 and the fluid reaction chamber 118. In the depicted embodiment, a first conduit 117 provides the fluid communication between the first flow control unit 116 and the fluid reaction chamber 118. [0064] The fluid measurement chamber 110 further includes a second flow control unit 120 that is in fluid communication with the fluid outlet 114. The second flow control unit 120 is also in fluid communication between the fluid reaction chamber 118 and the first flow control unit 116. In the depicted embodiment, the second flow control unit 120 is disposed in fluid communication between the fluid storage chamber 118, the first flow control unit 116, and the fluid outlet 114. A second conduit (not shown) provides the fluid communication between the fluid reaction chamber 118 and the second flow control unit 120, and a third conduit 121 provides the fluid communication between the second flow control unit 120 and the first flow control unit 116.

[0065] The fluid measurement chamber 110 further includes a fluid sensing unit 122 that is operatively associated with the fluid reaction chamber 118. In the depicted embodiment, the fluid sensing unit 122 is provided within the fluid reaction chamber 118, and is arranged to detect and measure a concentration of an analyte in a fluid that circulates around a fluid circulation path 124 between the first flow control unit 116, the fluid reaction chamber 118, and the second flow control unit 120.

[0066] The first flow control unit 116 may include a valve (not shown) to control the inflow of fluid 113 from the fluid inlet 112 to the fluid reaction chamber 118. The valve of the first flow control unit 116 is actuatable between an open state to permit the inflow of fluid 113, and a closed state to prevent the inflow of fluid 113. The second flow control unit 120 may also include a valve (not shown) to control the outflow of fluid from the fluid reaction chamber 118 to the fluid outlet 114. The valve of the second flow control unit 120 is actuatable between an open state to permit the outflow of fluid, and a closed state to prevent the outflow of fluid.

[0067] Turning to the fluid storage chamber 160, it will be appreciated that the fluid storage chamber 160 includes a fluid storage chamber inlet 162 for receiving an inflow of fluid 163 (e.g. from an external fluid source) into the fluid storage chamber 160, and a fluid storage chamber outlet 164 for discharging an outflow of fluid from the fluid storage chamber 160. In the depicted embodiment, the outflow of fluid that is discharged from the fluid storage chamber outlet 154 travels along an intermediate fluid conduit 166, and becomes the inflow of fluid 113 that enters the fluid measurement chamber 110. [0068] The fluid measurement system 100 may further include a flow generator 168 located along the intermediate fluid conduit 166 and configured to pump or direct the outflow of fluid from the fluid storage chamber 160 into the fluid measurement chamber 110. In the depicted embodiment, the flow generator 168 is installed in the intermediate fluid conduit 166 to facilitate and regulate the flow of fluid from the fluid storage chamber 160 into the fluid measurement chamber 110.

[0069] The separation of the fluid storage chamber 160 and the fluid measurement chamber 110 in this embodiment may thus allow for the fluid collection/storage and measurement/sensing to be conducted separately, which may be important for analyte detection where a continuous fluid sample input is difficult to obtain. For example, breath sampling from a comatose patient may be difficult due to the limited volume and flow of air that is expelled from their lungs. By firstly collecting and storing breath samples from the comatose patient in the fluid storage chamber 160, a sufficient volume of breath may be obtained and subsequently discharged to the fluid measurement chamber 110 for detection of analyte concentration in said breath.

[0070] In the depicted embodiment, the fluid storage chamber 160 further includes a pressure sensor 170 to detect and measure a pressure of fluid within the fluid storage chamber 160. The pressure sensor 170 may at least facilitate the monitoring of the pressure of fluid within the fluid storage chamber 160, for example, to ensure that the fluid storage chamber 160 contains sufficient fluid at an appropriate volume before said fluid is transferred to the fluid measurement chamber 110.

[0071] The fluid storage chamber 160 may also include a partition 172 that separates the fluid storage chamber 160 into a first sub-chamber 174 and a second sub-chamber 176. The partition 172 is movable within the fluid storage chamber 160 to adjust the respective volumes of the first and second sub-chambers 174 and 176. In the depicted embodiment, movement of the partition 172 is facilitated by support structures 180 that extend between the partition 172 and a floor 182 of the fluid storage chamber 160. The support structures 180 may be in the form of pneumatic cylinders which move between the partition 172 and the floor 182, which in turn moves the partition 172 within the fluid storage chamber 160. In the depicted embodiment, movement of the partition 172 towards the top of the fluid storage chamber 160 decreases the volume of the first sub-chamber 174, whilst at the same time increases the volume of the second sub-chamber 176. Conversely, movement of the partition 172 towards the bottom of the fluid storage chamber 160 (i.e. towards the floor 182) increases the volume of the first sub-chamber 174, whilst at the same time decreases the volume of the second sub-chamber 176. Accordingly, the respective volumes of the first and second sub-chambers 174 and 176 may be adjusted as required. The inflow of fluid 163 that enters the fluid storage chamber 160 may thus be stored within the first sub-chamber 174 at a set volume prior to being discharged into the fluid measurement chamber 110. It will be appreciated that the edges of the partition 172 may be sealed against the sidewalls of the fluid storage chamber 160 to prevent fluid from leaking from the first sub-chamber 174 (in which the volume is set) to the second sub-chamber 176.

[0072] The operation of the fluid measurement system 100 will now be described.

[0073] The inflow of fluid 163 firstly enters the fluid storage chamber 160 through the fluid inlet 162, whereby the fluid is stored within the first sub-chamber 174. The pressure sensor 170 may be enabled to monitor the pressure of the fluid within the first sub-chamber 174. Once a sufficient fluid pressure has been reached, the flow generator 168 is enabled to pump the fluid from the fluid storage chamber 160, through the intermediate fluid conduit 166, and into the fluid measurement chamber 110. As discussed above in relation to the fluid measurement chamber 10, the inflow of fluid 113 enters the fluid measurement chamber 110 through the fluid inlet 112, whereby the inflow of fluid 113 passes through the first flow control unit 116, and is then discharged from the fluid measurement chamber 110 when the outflow of fluid passes through the second flow control unit 120. Once a sufficient volume or flow of fluid has entered the fluid measurement chamber 110, the valves of the first and second flow control units 116 and 120 are actuated or set to their closed states, which in turn opens the fluid circulation path 124.

[0074] The fluid is then pumped (by way of micropumps in the first and/or second flow control units 116 and 120, for example) around the circulation path 124 at a set flow rate. The fluid in the fluid circulation path 124 is allowed to circulate more than once, so as to allow successive passes of the fluid through the fluid reaction chamber 118. Accordingly, the fluid in the fluid circulation path 124 may interact with the fluid sensing unit 122 more than once. Once the fluid in the fluid circulation path 124 has passed through the fluid reaction chamber 118 a sufficient number of times, the fluid sensing unit 122 is enabled to detect and measure a concentration of an analyte in the fluid being circulated around the fluid circulation path 124. [0075] Once the measurement of the analyte concentration has concluded, the valves of the first and second flow control units 116 and 120 are returned to their open states. The fluid in the measurement chamber 110 is then flushed.

[0076] It will be appreciated that in other embodiments (not shown), the fluid measurement chamber 110 may be replaced by the embodiment of the fluid measurement chamber 50 discussed above, whereby the fluid dilution unit 52 is added to allow the fluid measurement range to be extended.

[0077] The methods of operating the fluid measurement chamber and systems described above may be used for applications involving measurement of breath acetone concentration, for example. It is understood be that breath acetone is a key biomarker for medical diagnosis and disease monitoring. Individuals suffering from diabetes may monitor their breath acetone concentration levels to monitor progression of diabetic ketoacidosis.

[0078] In the embodiment of Figure 5, there is depicted a fluid measurement apparatus 200 which incorporates various elements of the fluid measurement chamber 10 and fluid measurement system 100 described above. The fluid measurement apparatus 200 may be in the form of a breath acetone monitoring device, for example. In this embodiment, the fluid measurement apparatus 200 includes a housing 202 having a fluid inlet 204 and a fluid outlet 206. The fluid inlet 204 includes a fluid inlet valve 208, and likewise, the fluid outlet 206 includes a fluid outlet valve 210. The fluid inlet and outlet valves 208, 210 may each be in the form of electric valves, for example. The fluid inlet 204 may be provided with a disposable mouthpiece (not shown) for hygiene and ease of contact with the patient’s mouth.

[0079] The fluid measurement apparatus 200 further includes a flow control unit in the form of a micropump 212 that is in fluid communication with the fluid inlet 204. Similar to the micropumps of the flow control units described earlier, the micropump 212 is adapted to generate and regulate fluid flow through the fluid measurement apparatus 200. The fluid measurement apparatus 200 also further includes a replaceable filter 214 that is in fluid communication with the micropump 212 and located downstream therefrom. In a preferred form, the filter 214 is a passive chemical filter adapted to remove unwanted components in the fluid sample (for example, water vapour in the patient’s breath). [0080] The filter 214 is in fluid communication with a reaction chamber 218, which includes one or more light sources 220, a slide 222 located below the light sources 220, a reaction material 224 locatable on the slide 222, one or more photodetectors 226 located below the slide 222, and pressure and temperature sensor(s) 228. The reaction chamber 218 is also in fluid communication with the fluid outlet 206, which is in turn in fluid communication with the fluid inlet 204 via a fluid conduit 229.

[0081] Within the housing 202, there is also provided a power unit 230 and a control unit 232 to operate and control the various components of the fluid measurement apparatus 200.

[0082] The operation of the fluid measurement apparatus 200 will now be described with reference to the accompanying flow diagram of Figure 6.

[0083] The reaction material 224 is firstly loaded on the slide 222, which is in turn placed in the reaction chamber 218. The reaction material 224 is preferably a single-use material such as a paper strip that has been soaked with Hydroxylamine Hydrochloride and the pH indicator Bromophenol Blue. This exemplary arrangement is tuned to acetone sensing. Further examples of reaction materials are again described in detail in the Applicant’s earlier International Publication No. WO 2020/047606.

[0084] At step 300, the light sources 220 and photodetectors 226 are enabled so that a baseline measurement of the optical characteristics of the reaction material 224 may be obtained. In particular, light from the light sources 220 is passed through the reaction material 224 to the photodetectors 226 located at the bottom of the reaction chamber 218, and the baseline measurement of the optical characteristics of the reaction material 224 is taken.

[0085] At step 302, a fluid sample (for example, breath expelled from a patient) is input into the fluid inlet 204, whereby the fluid sample passes through the fluid inlet valve 208 and into the micropump 212. The fluid sample is then pumped through the filter 214 and into the reaction chamber 218.

[0086] At step 304, the fluid sample circulates through the reaction chamber 218, along the fluid conduit 229, back to the fluid inlet 204, again through the micropump 212 and the filter 214, and back into the reaction chamber 218. Accordingly, the fluid sample circulates along a fluid circulation path 233. The fluid sample chemically reacts with the reaction material 224 in the reaction chamber 218, which produces a colorimetric change in the optical characteristics of the reaction material 224, whereby the change is enhanced by the circulation of the fluid sample. In the exemplary arrangement as described above whereby the reaction material 224 is in the form of a paper strip that has been soaked with Hydroxylamine Hydrochloride and the pH indicator Bromophenol Blue, it will be understood that when acetone (for example) in the fluid sample comes in contact with the strip, the acetone reacts with the Hydroxylamine Hydrochloride to form Acetoxime, Hydrochloride and water. This reaction changes the pH of the strip and the Bromophenol Blue’s transmittance spectra correspondingly changes, which can then be measured by the light source 220 and photodetector 226 arrangement as discussed below.

[0087] At step 306, a post-reaction measurement of the optical characteristics of the reaction material 224 is obtained. As discussed above in relation to step 300, light from the light sources 220 is passed through the reaction material 224 to the photodetectors 226 located at the bottom of the reaction chamber 218, and the post-reaction measurement of the optical characteristics of the reaction material 224 is taken.

[0088] Finally, at step 308, the acetone concentration in the fluid sample is obtained by calculating the change in the optical characteristics of the reaction material 224 between post reaction measurement (step 306) and baseline measurement (step 300).

[0089] Once the measurement has been concluded, the fluid measurement apparatus may be flushed by passing a fluid through a pass-through path 234, which extends from the fluid inlet 204, through the micropump 212 and filter 214, into the reaction chamber 218, and to the fluid outlet 206.

[0090] The circulation method described above in relation to the fluid measurement apparatus 200 may at least reduce the required volume of input breath for detection. The minimisation of this breath volume may important for patients in respiratory distress, or the breathing impaired, as they may not be able to provide the amount of breath sample necessary for analysis. The circulation method may also improve the accuracy and precision of acetone concentration measurement through the complete reaction between the acetone and the interactant (i.e. the redaction material 224). [0091] As will be discussed in further detail below, the apparatus has been experimentally verified to have a measurement resolution of 10 parts per million with coefficient of variation of less than 10%.

Experimental data

[0092] Figure 7 shows the result of an experimental study conducted on an exemplary fluid measurement apparatus, which incorporated a reaction chamber having an inner volume of about 40 milliliters. This chamber volume is understood to be very small in comparison with the normal human breath volume of 6 liters. The temperature and pressure sensors were utilised used in the reaction chamber to monitor the internal temperature, and to check the hermetic sealing of the device, respectively.

[0093] In the experiment, hydroxylamine hydrochloride solution was added on the testing strip before the pumping of gas, which is a mixture of air and acetone. The reaction of hydroxylamine hydrochloride with acetone introduced color change that was detected by the photodetectors. Acetone gas with various concentrations from 0 ppm to 50 ppm in an increment of 10 ppm were used in the testing.

[0094] The experimental study was carried out in a room temperature of 21 degrees Celsius.

The acetone gas was input into the apparatus for 7 seconds to flush the residual gas and fill out the chamber, and then the input gas was circulated within the reaction chamber for 18 seconds.

[0095] Figure 7 shows the performance of the measurement, where three measurements were taken at each acetone concentration. The R-squared value is close to 1, which indicates a strong correlation between the sensor response and the target concentration.

[0096] The study also calculated a coefficient of variation (CV) at all concentrations. The results are shown in Table 1 below, where the CV is under 10%, indicating the apparatus has the capability to measure acetone concentration in a small volume of gas, with good repeatability and high accuracy.

Table 1: CV at different acetone concentrations

[0097] Various forms of the fluid measurement chambers, systems and apparatus described above may have one or more of the following advantages. By recirculating fluid (gas) through a reaction chamber multiple times, it may be possible to enhance the total reaction of a target analyte with an interactant or sensor in the chamber, thus greatly reducing the volume of fluid (gas) required whilst at the same time, improving the sensitivity and accuracy in the detection of the target analyte. Additionally, recirculation of the fluid (gas) may at least allow for a patient’s breath to be analysed under a normal breath condition, thereby improving usability by breathing-impaired patients. By enabling a reduction in input fluid volume, and by placing all the components in one device or apparatus, a smaller form factor may be obtained. The incorporation of pressure sensors in the fluid measurement chamber may also enable continuous condition monitoring for hermetic sealing, which may at least minimise the risk of fluid (gas) leakage and contamination, and improve the accuracy of the analyte measurement. The addition of the fluid dilution unit may additionally allow for dilution of high concentration gas samples so as to enable measurement of a large concentration range. The addition of replaceable filters in the fluid passageway may also improve the accuracy of the fluid measurement and reduce power consumption. The fluid measurement chambers, systems and apparatus are also non- invasive and do not require any direct contact with a patient. The fluid measurement chambers, systems and apparatus are also reusable to improve cost efficiency and reduce waste.

[0098] As discussed earlier, the various forms of the fluid measurement chambers, systems and apparatus described above may be useful applications involving trace gas measurement and analysis in the fields of biotechnology, clinical applications, diagnostic, instrumentation, and medical devices. Possible commercial application may include portable breath ketone detectors, acetone alarm systems, other biomarker detection (e.g. ammonia measurement in breath), early stage lung cancer detection, and gas leakage detection.

[0099] Although specific embodiments of the invention are illustrated and described herein, it will be appreciated by those of ordinary skill in the art that a variety of alternative and/or equivalent implementations exist. It should be appreciated that the exemplary embodiment or exemplary embodiments are examples only and are not intended to limit the scope, applicability, or configuration in any way. Rather, the foregoing summary and detailed description will provide those skilled in the art with a convenient road map for implementing at least one exemplary embodiment, it being understood that various changes may be made in the function and arrangement of elements described in an exemplary embodiment without departing from the scope as set forth in the appended claims and their legal equivalents. Generally, this application is intended to cover any adaptations or variations of the specific embodiments discussed herein.

[0100] It will also be appreciated that in this document the terms "comprise", "comprising", "include", "including", "contain", "containing", "have", "having", and any variations thereof, are intended to be understood in an inclusive (i.e. non-exclusive) sense, such that the process, method, device, apparatus or system described herein is not limited to those features or parts or elements or steps recited but may include other elements, features, parts or steps not expressly listed or inherent to such process, method, article, or apparatus. Furthermore, the terms "a" and "an" used herein are intended to be understood as meaning one or more unless explicitly stated otherwise. Moreover, the terms "first", "second", etc. are used merely as labels, and are not intended to impose numerical requirements on or to establish a certain ranking of importance of their objects.

Claims

1. A fluid measurement chamber comprising: a fluid inlet for receiving an inflow of fluid into the fluid measurement chamber and a fluid outlet for discharging an outflow of fluid from the fluid measurement chamber; a first flow control unit in fluid communication with the fluid inlet; a fluid storage chamber in fluid communication with the first flow control unit; and a second flow control unit in fluid communication between the fluid storage chamber, the first flow control unit and the fluid outlet; and a fluid sensing unit operatively associated with the fluid storage chamber to detect and measure a concentration of an analyte in a fluid that circulates around a fluid circulation path between the first control unit, the fluid storage chamber, and the second flow control unit.

2. The fluid measurement chamber of claim 1, wherein the first flow control unit includes a first valve to control the inflow of fluid from the fluid inlet to the fluid storage chamber, the first valve being actuatable between an open state to permit the inflow of fluid and a closed state to prevent the inflow of fluid.

3. The fluid measurement chamber of claim 1 or 2, wherein the second flow control unit includes a second valve to control the outflow of fluid from the fluid storage chamber to the fluid outlet, the second valve being actuatable between an open state to permit the outflow of fluid and a closed state to prevent the outflow of fluid.

4. The fluid measurement chamber of any one of claims 1 to 3, wherein either one or both of the first and second flow control units includes a micropump configured to circulate the flow of fluid around the fluid circulation path between the first flow control unit, the fluid storage chamber, and the second flow control unit.

5. The fluid measurement chamber of any one of claims 1 to 4, further including a temperature sensor to monitor a temperature of the fluid within the fluid measurement chamber.

6. The fluid measurement chamber of any one of claims 1 to 5, further including a pressure sensor to detect leaks in the fluid circulation path.

7. The fluid measurement chamber of any one of claims 1 to 6, wherein the fluid measurement chamber is contained within a hermetically sealed housing to isolate the fluid measurement chamber from an external environment.

8. The fluid measurement chamber of any one of claims 1 to 7, further including a fluid dilution unit in fluid communication between the first flow control unit and the fluid storage chamber, the fluid dilution unit being configured to introduce a reference fluid of a known analyte concentration to the fluid that is being circulated along the fluid circulation path.

9. A method of measuring analyte concentration in fluid using a fluid measurement chamber, the method comprising the steps of: receiving an inflow of fluid into a fluid measurement chamber through a fluid inlet, and discharging an outflow of fluid from the fluid measurement chamber through a fluid outlet, wherein the fluid measurement chamber comprises: a first flow control unit in fluid communication with the fluid inlet; a fluid storage chamber in fluid communication with the first flow control unit; a second flow control unit in fluid communication between the fluid storage chamber, the first flow control unit, and the fluid outlet; and a fluid sensing unit operatively associated with the fluid storage chamber; actuating the first and second flow control units to prevent the inflow and outflow of fluid to and from the fluid measurement chamber; circulating a flow of fluid around a fluid circulation path between the first flow control unit, the fluid storage chamber, and the second flow control unit, such that the flow of fluid interacts with the fluid sensing unit more than once; and detecting and measuring a concentration of an analyte in the flow of fluid being circulated around the fluid circulation path.

10. The method of claim 9, wherein the flow of fluid between the first flow control unit, the fluid storage chamber, and the second flow control unit is circulated using a micropump associated with either one or both of the first and second flow control units.

11. The method of claim 9 or 10, wherein the fluid measurement chamber further includes a fluid dilution unit in fluid communication between the first flow control unit and the fluid storage chamber, the method further comprising the step of: introducing, using the fluid dilution unit, a reference fluid of a known concentration to the flow of fluid that is being circulated along the fluid circulation path so as to dilute the flow of fluid.

12. The method of claim 11, further comprising the step of: determining the concentration of the analyte in the inflow of fluid by applying a known dilution factor to a measured concentration of the diluted flow of fluid.

13. The method of any one of claims 9 to 12, further comprising the step of: actuating the first and second flow control units to permit the inflow and outflow of fluid to and from the fluid measurement chamber; and flushing the fluid measurement chamber.

14. A fluid measurement system comprising: a fluid measurement chamber including: a fluid inlet for receiving an inflow of fluid into the fluid measurement chamber and a fluid outlet for discharging an outflow of fluid from the fluid measurement chamber; a first flow control unit in fluid communication with the fluid inlet; a reaction chamber in fluid communication with the first flow control unit; and a second flow control unit in fluid communication between the reaction chamber and the first flow control unit; and a fluid sensing unit operatively associated with the reaction chamber to detect and measure a concentration of an analyte in a fluid that circulates around a fluid circulation path between the first control unit, the reaction chamber, and the second flow control unit; and a fluid storage chamber including: a fluid storage chamber inlet for receiving an inflow of fluid into the fluid storage chamber and a fluid storage chamber outlet for discharging an outflow of fluid from the fluid storage chamber and into the fluid measurement chamber via an intermediate fluid conduit.

15. The fluid measurement system of claim 14, further comprising a flow generator located along the intermediate fluid conduit to pump a flow of fluid from the fluid storage chamber into the fluid measurement chamber.

16. The fluid measurement system of claim 14 or 15, wherein the fluid storage chamber further includes a pressure sensor to detect and measure a pressure of fluid within the fluid storage chamber.

17. The fluid measurement system of any one of claims 14 to 16, wherein the fluid storage chamber includes a movable partition operable to adjust a volume of fluid within the fluid storage chamber.

18. The fluid measurement system of any one of claims 14 to 17, wherein the fluid storage chamber is housed separately from the fluid measurement chamber.

19. A method of measuring fluid using a fluid measurement system, the method comprising the steps of: receiving an inflow of fluid into a fluid storage chamber; storing the inflow of fluid in the fluid storage chamber until the fluid reaches a predetermined pressure; discharging the stored fluid from the fluid storage chamber into a fluid measurement chamber, wherein the fluid measurement chamber is separate from the fluid storage chamber and comprises: a first flow control unit in fluid communication with a fluid inlet; a reaction chamber in fluid communication with the first flow control unit; a second flow control unit in fluid communication between the fluid reaction chamber, the first flow control unit, and a fluid outlet; and a fluid sensing unit operatively associated with the fluid reaction chamber; actuating the first and second flow control units to close the fluid inlet and the fluid outlet; circulating a flow of fluid around a fluid circulation path between the first flow control unit, the fluid reaction chamber, and the second flow control unit, such that the flow of fluid interacts with the fluid sensing unit more than once; and detecting and measuring a concentration of an analyte in the flow of fluid being circulated around the fluid circulation path.

20. An apparatus for measuring analyte concentration in a fluid, the apparatus comprising: a housing surrounding an internal chamber and including a fluid inlet to receive an inflow of fluid into the internal chamber and a fluid outlet to discharge an outflow of fluid from the internal chamber; a flow control unit located within the internal chamber and in fluid communication with the fluid inlet; a reaction chamber located in fluid communication with the filter and the fluid outlet, the reaction chamber including: a light source; a slide positionable below the light source; a reaction material locatable on the slide; and a photodetector located below the slide and at a base of the reaction chamber.

21. A method of operating the apparatus of claim 20, the method including the steps of: loading the reaction material on the slide; passing light from the light source through the reaction material to the photodetector, and obtaining a baseline measurement of an optical characteristic of the reaction material; receiving a fluid sample into the reaction chamber via the fluid inlet and flow control unit; circulating the fluid sample through the reaction chamber so as to allow the fluid sample to chemically react with the reaction material; passing light from the light source through the reaction material to the photodetector, and obtaining a post-reaction measurement of the optical characteristic of the reaction material; and obtaining a concentration of the analyte in the fluid sample by calculating a change in the optical characteristic of the reaction material between the post-reaction measurement and the baseline measurement.