Devices for analysis of a biological sample and manufacturing methods thereof, and methods of anaylsis of a biological sample

Abstract

A device for analysis of a biological sample, the device comprising an inflatable vessel for containing a biological sample, the vessel being gas-impermeable and / or liquid-impermeable one or more sensors disposed on an internal surface of the vessel, and an electronic component disposed on an external surface of the vessel, wherein the electronic component is configured to communicate with the one or more sensors.

Description

[0001] DEVICES FOR ANALYSIS OF A BIOLOGICAL SAMPLE AND MANUFACTURING METHODS THEREOF, AND METHODS OF ANAYLSIS OF A BIOLOGICAL SAMPLE

[0002] BACKGROUND TO THE INVENTION

[0003] The present invention relates to a device for analysis of a biological sample and manufacturing methods thereof, and a method of analysis of a biological sample.

[0004] Devices which are used to analyse biological samples are well known. For example, such devices may be used to analyse a sample of breath, a sample of urine, a sample of blood, a sample of saliva, a sample of sweat, or a sample of any other biological substance.

[0005] In some known arrangements, the sample is analysed immediately after collection. For example, in devices for analysis of a sample of breath, the user may blow into the device, and the exhaled breath sample may be immediately analysed by an electronic apparatus. Similar devices are known for analysis of other biological samples such as those set out above. However, such devices may be expensive and / or complex to manufacture, and may be bulky.

[0006] In other known arrangements, a biological sample may be placed into a vessel (such as a bag) by a user, and sent to a laboratory for analysis. However, in such arrangements, there may be a significant delay before the results of the analysis are obtained, due to the need to send the collected sample to a laboratory. Further, the sample may degrade and / or become contaminated during the transport process.

[0007] It is an aim of the present invention to at least partially address the problems noted above.

[0008] SUMMARY OF THE INVENTION

[0009] According to a first aspect, there is provided a device for analysis of a biological sample, the device comprising an inflatable vessel for containing a biological sample, the vessel being gas-impermeable and / or liquid-impermeable, one or more sensors disposed on an internal surface of the vessel, and an electronic component disposed on an external surface of the vessel, wherein the electronic component is configured to communicate with the one or more sensors.

[0010] Optionally, at least one sensor of the one or more sensors comprises one or more of an electrochemical sensor, a graphene sensor, an immunosensor, a field effect transistor, a gas phase biosensor, and a molecular assay.

[0011] Optionally, at least one sensor of the one or more sensors comprises a molecular assay, wherein the molecular assay is a recombinase polymerase amplification assay.

[0012] Optionally, at least one sensor of the one or more sensors is configured to detect a species contained within an aerosol exhaled by the subject.

[0013] Optionally, at least one sensor of the one or more sensors is configured to detect a species in said aerosol which has been enhanced due to an ingestible consumed by the subject.

[0014] Optionally, at least one sensor of the one or more sensors is configured to detect one or more of nitric oxide, oxygen, carbon dioxide, tetrahydrocannabinol (THC) or a derivative thereof, volatile organics, methane, hydrogen sulphide, and hydrogen.

[0015] Optionally, the at least one sensor is configured to detect volatile organics used in determination of cancer.

[0016] Optionally, the at least one sensor is configured to detect volatile organics used in determination of at least one of colorectal cancer, oesophageal cancer, lung cancer, gastric cancer, and breast cancer.

[0017] Optionally, at least one of the one or more sensors is configured to determine sample sufficiency.

[0018] Optionally, the device further comprises a collection portion for collection of the biological sample, the collection portion being in fluidic communication with the interior of the vessel. Optionally, the collection portion is a mouthpiece.

[0019] Optionally, the device further comprises a collar for interfacing the collection portion to the vessel.

[0020] Optionally, the collar includes one or more additional sensors.

[0021] Optionally, the one or more additional sensors include one or more of a heart rate sensor, a heart rate variability sensor, a temperature sensor, and a 3D accelerometer.

[0022] Optionally, the electronic component is reusable and / or detachable from the vessel.

[0023] Optionally, the electronic component includes a battery.

[0024] Optionally, the electronic component includes a plurality of battery subassemblies configured to combine to provide a battery.

[0025] Optionally, the electronic component includes an electronic display.

[0026] Optionally, the electronic component includes a printed circuit.

[0027] Optionally, the electronic component includes a near field communication (NFC) module.

[0028] Optionally, the electronic component includes a microprocessor.

[0029] Optionally, the microprocessor is an application specific integrated circuit (ASIC).

[0030] Optionally, the ASIC comprises a near field communication (NFC) module.

[0031] Optionally, the device further comprises a biometric identification element on an external surface of the vessel and / or on the electronic component. Optionally, the biometric identification element can be integrated with an electronic patient record.

[0032] Optionally, the volumetric capacity of the vessel is between 250ml and 2000ml.

[0033] Optionally, the device is configured to concentrate a species in the sample.

[0034] Optionally, the device further comprises a valve configured to allow release of the biological sample.

[0035] Optionally, the device is configured to determine the volume of sample released through the valve.

[0036] Optionally, the device is for analysis of a sample of one or more of breath, urine, blood, saliva and sweat.

[0037] According to a second aspect, there is provided a method of manufacturing a device for analysis of a biological sample, the method comprising providing an inflatable vessel for containing a biological sample, the vessel being gas-impermeable and / or liquid-impermeable, disposing one or more sensors on an internal surface of the vessel, and disposing an electronic component on an external surface of the vessel, wherein the electronic component is configured to communicate with the one or more sensors.

[0038] Optionally, the one or more sensors are disposed on the internal surface of the vessel by printing.

[0039] Optionally, the electronic component is disposed on the external surface of the vessel by printing.

[0040] Optionally, the inflatable vessel is provided by providing a substantially flat template, folding the template, and sealing one or more portions of the template. According to a third aspect, there is provided a method of analysing a biological sample from a subject, the method comprising providing an inflatable vessel for containing a biological sample, the vessel being gas-impermeable and / or liquid-impermeable, collecting the sample in the vessel, analysing the sample using one or more sensors disposed on an internal surface of the vessel, and providing a measurement result from the one or more sensors to an electronic component disposed on an external surface of the vessel.

[0041] Optionally, the method further comprises transmitting the measurement result via a wireless communication to an external device.

[0042] Optionally, the external device is a smart phone, a computer or a cloud server.

[0043] Optionally, the method further comprises sealing the sample within the vessel.,

[0044] Optionally, the method further comprises analysing the sample using a laboratory instrument.

[0045] Optionally, the method further comprises acquiring one or more biometric measurements from the subject.

[0046] Optionally, the method further comprises obtaining a biometric identification using said one or more biometric measurements to associate the measurement result with an electronic patient record.

[0047] Optionally, the method further comprises determining a condition of the subject based on the measurement result.

[0048] BRIEF DESCRIPTION OF THE DRAWINGS

[0049] The present invention will now be described, by way of non-limitative example only, with reference to the accompanying drawings, in which: Figure 1 shows a schematic external view of a device according to the present invention;

[0050] Figure 2 shows a schematic internal view of the device of figure 1 ;

[0051] Figure 3 shows a schematic external view a further example of a device according to the present invention

[0052] Figure 4 shows a perspective view of a further arrangement of device according to the invention;

[0053] Figure 5 shows a cutaway view of the device of figure 4; and Figure 6 shows an exploded view of the device of figure 4.

[0054] DETAILED DESCRIPTION

[0055] The present invention relates to a device for analysis of a biological sample. The device may also have the function of collecting (i.e. acquiring) the biological sample. The biological sample may be, for example, a sample of breath (e.g. exhaled breath), urine, blood, saliva, sweat, or any other biological substance.

[0056] A first arrangement of device of the present invention is depicted schematically in figures 1 and 2. The device comprises a vessel 101 for containing the sample, one or more sensors 102 disposed on an internal surface of the vessel; and an electronic component 103 disposed on an external surface of the vessel 101, wherein the electronic component 103 is configured to communicate with the one or more sensors 102.

[0057] The vessel 101 may be an inflatable vessel. That is, the volume of the vessel may be able to change so as to accommodate the sample and / or a volume of other liquid or gas. It will be understood that the term “inflatable” may be used to indicate any suitable arrangement where volume of the vessel can change, including vessels made of a flexible material. Such flexibility may allow the vessel to inflate (i.e. for the volume of the vessel to change). The vessel may also have folds in the surface thereof and / or be formed of a material with elasticity such that the volume of the vessel can change. The vessel 101 has an internal surface and an external surface. In other words, the vessel 101 forms an enclosed cavity bounded by the wall of the vessel, with the wall of the vessel having an inner surface and an outer surface.

[0058] The vessel 101 is gas impermeable and / or liquid impermeable. This may allow the sample to be contained without the sample leaking, escaping or otherwise exiting the vessel, and without other substances (e.g. contamination from the atmosphere) entering the vessel.

[0059] The vessel may comprise and / or be formed of any suitable material. The material may be a polymeric material. For example, the material may be a laminate of polyethylene terephthalate (PET) / Aluminium foil / low density polyethylene (LDPE); a laminate of metallised oriented polypropylene (OPP) / OPP; a laminate of PET / LDPE; a laminate of OPP / OPP, or any combination thereof. The material layers may have thicknesses of between 10pm and 100pm. PET may be about 12pm thick; LDPE may be about 50pm - 75um thick; aluminium foil may be about 12pm thick; OPP may be about 18pm - 25pm thick. Other materials that may be used include biaxially oriented polypropylene (BOPP). Preferred laminates include Aluminium / polypropylene (AL / PP) and PP / A1 / PP. The total thickness of the laminate film may be up to 250pm. In general, the term “foil” or “plastic-laminated foil” is used to describe a thin layer of metal and a thin layer of metal laminated with a layer (or layers) of polymer-based material(s) on one or either side of the metal.

[0060] One or more sensors 102 are disposed on an internal surface of the vessel. In the description below of example sensors, it will be understood that “the sensor” may refer to a single sensor present in the device, to one of a plurality of sensors present in the device, or more than one sensor present in the device. The one or more sensors may be any suitable sensor for detecting a property of the biological sample (i.e. sensitive to a substance contained in the sample). Further details of suitable sensors will be described below.

[0061] At least one electronic component 103 is disposed on the external surface of the vessel. The electronic component 103 (on the external surface of the vessel) is configured to communicate with the one or more sensors 102 on the internal surface of the vessel. Thus, the sensors can sense data relating to the biological sample, and communicate the data to the electronic component.

[0062] The electronic component 103 may be any suitable electronic component or combination of electronic components. The electronic component may be configured to receive an output (i.e. a reading, result or detection value) from the one or more sensors. The communication between the electronic component and the sensors may be by an electrical coupling.

[0063] In some arrangements, the electronic component may also be configured to transmit the sensor output to an external device, or to indicate the sensor output (or a result derived therefrom) to a user.

[0064] In some arrangements, such as that depicted in figures 1 and 2, the device may comprise a collection portion 104 for collection of the biological sample. The collection portion 104 may be in fluidic communication with the interior of the vessel. That is, the collection portion 104 may serve to allow the biological sample to be disposed inside the vessel 101.

[0065] In an arrangement where the biological sample is a sample of breath, the collection portion

[0066] 104 may be a mouthpiece. In such arrangements, the user may blow through the mouthpiece such that the sample enters the vessel 101.

[0067] Although a collection portion is depicted in figures 1 and 2, it will be understood arrangements are also possible in which the collection portion is omitted, and the sample is provided to the interior of the vessel by other means.

[0068] The device of figures 1 and 2 further includes a valve 105 configured to allow release of the biological sample from the vessel 101. This may be used to remove excess sample from the vessel, and / or to exhaust the vessel (and restart the collection process) when too little sample has been collected (which may be detected by a sensor in the interior of the vessel). The valve

[0069] 105 may also be operated to void (i.e. vent) the first portion of exhaled breath to atmosphere and thereafter switch (i.e. close) to collect a later portion of breath into the vessel. In the arrangement shown in figures 1 and 2, the valve 105 is provided on the collection portion 104. However, it will be appreciated that a valve may also be provided in other locations, such as on the vessel 101 itself. It will also be appreciated that other arrangements are possible in which no valve is present.

[0070] Further, the device may also be configured to determine the volume of sample released through the valve. This may be implemented by the valve itself, or by another component of the device (e.g. a flow meter mounted adjacent the valve).

[0071] Figure 3 depicts a further example arrangement of analysis device, with similar features to the arrangement of figure 1 (description of which is not repeated, and is the same other than the differences described below). However, in the arrangement of figure 3, the electronic component 103 includes a battery 103 a, an application specific integrated circuit (ASIC) 103b, a display 103c, and printed circuitry 103d connecting the battery 103a and ASIC 103b to the display 103c. It will be understood that this arrangement of subcomponents making up the electronic component 103 is merely exemplary, and that any other suitable combination of electronic components may be used.

[0072] Figures 4-6 depict a further arrangement of device in accordance with the present invention.

[0073] A further arrangement of device of the present invention is depicted schematically in figures 4-6. The device comprises a vessel 201 for containing the sample, one or more sensors 202 disposed on an internal surface of the vessel (which may be at the position labelled 202 in figure 6, but on the inside of the vessel 201); and an electronic component 203 disposed on an external surface of the vessel 201, wherein the electronic component 203 is configured to communicate with the one or more sensors 202.

[0074] The vessel 201 may be an inflatable vessel. That is, the volume of the vessel may be able to change so as to accommodate the sample and / or a volume of other liquid or gas. It will be understood that the term “inflatable” may be used to indicate any suitable arrangement where volume of the vessel can change, including vessels made of a flexible material. Such flexibility may allow the vessel to inflate (i.e. for the volume of the vessel to change). The vessel may also have folds in the surface thereof and / or be formed of a material with elasticity such that the volume of the vessel can change.

[0075] The vessel 201 has an internal surface and an external surface. In other words, the vessel 201 forms an enclosed cavity 207 bounded by the wall of the vessel, with the wall of the vessel having an inner surface and an outer surface.

[0076] The vessel 201 is gas impermeable and / or liquid impermeable. This may allow the sample to be contained without the sample leaking, escaping or otherwise exiting the vessel, and without other substances (e.g. contamination from the atmosphere) entering the vessel.

[0077] The vessel may comprise and / or be formed of any suitable material. The material may be a polymeric material. For example, the material may be a laminate of polyethylene terephthalate (PET) / Aluminium foil / low density polyethylene (LDPE); a laminate of metallised oriented polypropylene (OPP) / OPP; a laminate of PET / LDPE; a laminate of OPP / OPP, or any combination thereof. The material layers may have thicknesses of between 10pm and 100pm. PET may be about 12um thick; LDPE may be about 50pm - 75pm thick; aluminium foil may be about 12um thick; OPP may be about 18pm - 25pm thick. Other materials that may be used include biaxially oriented polypropylene (BOPP). Preferred laminates include Aluminium / polypropylene (AL / PP) and PP / A1 / PP. The total thickness of the laminate film may be up to 250pm. In general, the term “foil” or “plastic-laminated foil” is used to describe a thin layer of metal and a thin layer of metal laminated with a layer (or layers) of polymer-based material(s) on one or either side of the metal.

[0078] One or more sensors are disposed on an internal surface of the vessel. In the description below of example sensors, it will be understood that “the sensor” may refer to a single sensor present in the device, to one of a plurality of sensors present in the device, or more than one sensor present in the device. The one or more sensors may be any suitable sensor for detecting a property of the biological sample (i.e. sensitive to a substance contained in the sample). Further details of suitable sensors will be described below. At least one electronic component 203 is disposed on the external surface of the vessel. The electronic component 203 (on the external surface of the vessel) is configured to communicate with the one or more sensors 202 on the internal surface of the vessel. Thus, the sensors can sense data relating to the biological sample, and communicate the data to the electronic component.

[0079] The electronic component 203 may be any suitable electronic component or combination of electronic components. The electronic component may be configured to receive an output (i.e. a reading, result or detection value) from the one or more sensors. The communication between the electronic component and the sensors may be by an electrical coupling.

[0080] In some arrangements, the electronic component may also be configured to transmit the sensor output to an external device, or to indicate the sensor output (or a result derived therefrom) to a user.

[0081] In some arrangements, such as that depicted in figures 4-6, the device may comprise a collection portion 204 for collection of the biological sample. The collection portion 204 may be in fluidic communication with the interior of the vessel. That is, the collection portion 204 may serve to allow the biological sample to be disposed inside the vessel 201. The collection portion 204 may be reusable, but is preferably single-use so as to avoid contamination of the sample.

[0082] In arrangement where the biological sample is a sample of breath, the collection portion 204 may be a mouthpiece. In such arrangements, the user may blow through the mouthpiece such that the sample enters the vessel 201.

[0083] Although a collection portion is depicted in figures 4-6, it will be understood arrangements are also possible in which the collection portion is omitted, and the sample is provided to the interior of the vessel by other means.

[0084] The device of figures 4-6 further includes a valve 205 configured to allow release of the biological sample from the vessel 201. This may be used to remove excess sample from the vessel, and / or to exhaust the vessel (and restart the collection process) when too little sample has been collected (which may be detected by a sensor in the interior of the vessel).

[0085] In the arrangement shown in figures 4-6, the valve 205 is provided on the collection portion 204. However, it will be appreciated that a valve may also be provided in other locations, such as on the vessel 201 itself. The valve may be a one-way valve allowing substances to enter but not exit the vessel 201 (which may provide simplicity of manufacture and operation), or may be a two-way valve (which may allow air or other substances to be selectively exhausted from the valve). It will also be appreciated that other arrangements are possible in which a no valve is present.

[0086] Further, the device may also be configured to determine the volume of sample released through the valve. This may be implemented by the valve itself, or by another component of the device (e.g. a flow meter mounted adjacent the valve).

[0087] The device shown in figures 4-6 also includes a collar 206. The collar may be used to interface between the collection portion 204 and the vessel 201. That is, the collar 206 may be interposed between the collection portion 204 and the vessel 201. The collection portion 204 may be removable from the collar 206. Once the sample has been collected, the collection portion 204 may be removed from the vessel 201, which may be sealed by the valve 205. In arrangements with a two-way valve, the valve may be closed after collection of the sample to seal the vessel 201. In other words, the valve may act as a stopcock.

[0088] The collar 206 may also include further features. For example, the collar may include one or more additional sensors (i.e. in addition to those provided on the internal surface of the vessel 201). For example, the additional sensors may include or more of a heart rate sensor, a heart rate variability sensor, a temperature sensor, a 3D accelerometer, or any combination thereof. This may allow additional data to be collected whilst the device is in use. For example, biological or biometric signals related to the patient which are not evident from (or cannot be determined and / or directly measured from) the sample itself, such as heart rate or temperature, may be acquired by the additional sensor or sensors. An example of such a sensor is a plethysmography sensor, which may be worn on the wrist, applied to the upper arm or applied via a chest strap. This information may also be provided to the electronic component, and in some arrangements may be processed by the electronic component (e.g. combined with the data from the sensors on the internal surface of the vessel). The combined data package may be transmitted by a wireless communication element, for example near field communication (NFC) or Bluetooth low energy (BLE) to an electronic patient record, for example.

[0089] The following paragraphs describe various features which can be applied to devices disclosed herein. It will be understood that any of the features below, and any combination or subcombination thereof, may be applied to any of the devices described herein (including but not limited to those depicted in figures 1-5 and described above).

[0090] The sensor may be an electrochemical sensor, a graphene sensor, an immunosensor, a field effect transistor, a gas phase biosensor, and a molecular assay, or any combination thereof. The field effect transistor may be an organic field effect transistor (O-FET), an organic electrochemical transistor or a graphene field effect transistor (GFET). An exemplary GFET is described in US12,372,541 (the contents of which are incorporated herein by reference).

[0091] In arrangements where the sensor includes a molecular assay, the molecular assay may be recombinase polymerase amplification assay. Examples of suitable reagents are described in according to a reagent described in, for example, US11,807,899, or GB2410287.3, the disclosures of which are incorporated herein by reference in their entireties.

[0092] The sensor may be configured to detect (i.e. be sensitive to) a species contained within an aerosol exhaled by a subject. That is, where the device is configured to receive a sample of breath, the sensor may be sensitive to a substance suspended in droplets of moisture in exhaled breath.

[0093] Prior to the exhalation of the sample, the subject may consume an ingestible which enhances (e.g. increases the concentration of) a particular substance (such as a marker) in the sample. One example ingestible (for a sample of breath) is an ingestible developed under the “Platform Optimising SynBio for Early Intervention and Detection in Oncology (POSEIDON)” program funded by Advanced Research Projects Agency for Health (ARPA- H) and Health Science Futures Office (HSF). The sensor may be configured so as to detect (i.e. be sensitive to) a substance enhanced by or produced as a metabolite of, or in response to chemical conversion of such an ingestible by a cellular process within the body of the subject.

[0094] The sensor may be configured to configured to detect (i.e. be sensitive to) one or more of nitric oxide, oxygen, carbon dioxide, tetrahydrocannabinol (THC) (or a derivative thereof), volatile organics, methane, hydrogen sulphide, acetone, isoprene, ammonia, ethanol, aldehyde, and hydrogen, or any combination thereof.

[0095] Where the sensor is configured to detect volatile organics, the sensor may be in particular configured to detect volatile organics used in determination (i.e. detection or diagnosis) of cancer. For example, the sensor may detect volatile organics indicative of one or more of colorectal cancer, oesophageal cancer, lung cancer, gastric cancer, and breast cancer.

[0096] The sensor may also be configured to detect that sufficient sample has been collected for analysis. For example, in one exemplary arrangement, there may be two or more sensors present, wherein one sensor detects that a certain volume or concentration of sample is present, and the sample may be further analysed (e.g. to detect one or more of the substances set out above) by an additional sensor or sensors. In some embodiments the vessel may include external markings to provide a visual indicator to the user of the volume of breath introduced to the vessel.

[0097] The electronic component may be detachable from the vessel. This may allow a single electronic component to be reused with multiple vessels (which may be single use).

[0098] The electronic component may include a power source. The power source may be (or include) a battery. It will be appreciated that any suitable type of battery may be used in the device, depending on the application of the device. Alternatively, in other arrangements, the power source may be (or may include) a plurality of battery sub-assemblies configured to combine to provide a battery. That is, rather than an assembled battery being provided on the substrate, two or more parts which, when brought together, form a battery may be provided. Merely as an example, the battery sub-assemblies may include an anodic component and a cathodic component, which when pressed together (or combined in any other suitable way) form a battery. In arrangements where an anodic component and a cathodic component are provided, an electrolyte may either be separately provided between the anodic and cathodic components, or an electrolyte may be provided on one of the anodic or cathodic materials in a suitable form, such that when the respective components are pressed together electron flow between the terminals of the battery is initiated. Arrangements which use a plurality of battery sub-assemblies may provide the advantage of ease of transport, because safety precautions associated with transporting a fully assembled or intact battery may not apply where a plurality of battery sub-assemblies is instead provided.

[0099] The electronic component may be (or include) an electronic display. This may allow a sensor output (or a result derived therefrom) to be presented to a user. For example, the display may be used to indicate the result of a test, the presence or absence of a substance, or a numerical value measured by the sensor. The display may also be configured to provide an instruction, such as when to perform a certain action, to a user. Alternatively, another indicator (such as an LED) may be used to convey information (such as the detection of a substance) to the user.

[0100] The electronic component may include a printed circuit. The printed circuit may be used to link other (sub)components within the electronic component together, and / or to process data provided by the sensor.

[0101] The electronic component may include a communication module. Such a communication module may be configured to supply data (which may be received from the sensor) to an external device. In some arrangements, the communication module may be a short-range wireless communication module, such as a near field communication (NFC) coil or module. However, it will be understood that other communication modules may be used, including (but not limited to) a Bluetooth module, a Bluetooth Low Energy (BLE) module, a low-power Wi-Fi module, a Zigbee (registered trade mark) module, an ANT+ (registered trade mark) module, or any combination thereof. The electronic component may include a microprocessor, such as an application specific integrated circuit (ASIC). In arrangements where an NFC module is present, the NFC module may be part of the ASIC.

[0102] The device may include a biometric identification element. This may allow the sample to be associated with a particular user. Such a biometric element may be usable with, or associated with, or integrated with, an electronic patient record. This may allow chain of custody of the sample to be preserved (i.e. for the sample to be correctly associated with a user). Such a biometric element may be located in any suitable location on the device. For example, a biometric element may be located on the vessel (e.g. on an external surface thereof) and / or on the electronic component.

[0103] The volume of the vessel may be between 250ml and 2000ml. It will be understood that the volume may be defined as the volume of the vessel when empty, or when inflated. For vessels which are formed of an elastic material, the volume may vary within this range. In some arrangements, the volume of the vessel may be selected from the group comprising 250ml, 500ml, 750ml, 1000ml, 1500ml and 2000ml.

[0104] The device may be configured to concentrate a species in the sample (or to concentrate a portion of the sample). For example, a species of interest may collect in a certain portion of the vessel (e.g. as condensation from a sample of exhaled breath). In such a situation, an unwanted portion of the sample may be expelled from the vessel (e.g. through a valve as described above), which may provide a more concentrated sample of the specifies of interest. Alternatively, the inside surface of the vessel may be treated with a hydrophobic membrane or coating, while the sensor surface is treated with a hydrophilic coating. Upon exhalation of breath into the vessel the moisture vapour may condense on the inner surface of the vessel and the liquid be selectively directed to the sensor surface. Instructions for use of such a vessel would include ensuring that the sensor portion is oriented downwards with respect to gravity, such that breath condensate is directed to the sensor surface.

[0105] Additionally, the internal features of the vessel, such as joints or seams, may be formed such that breath condensate is guided to the sensor surface by capillary forces, which may be sufficient to overcome the effects of gravity should a user orient the vessel otherwise as instructed.

[0106] As described above, the device may be for analysis of a sample of breath (e.g. exhaled breath), urine, blood, saliva, sweat, or any other biological substance. The device may additionally be used in acquiring (i.e. obtain) such a sample. In some arrangements (e.g. for collection and analysis of breath), the subject may directly supply the sample to the vessel (e.g. by blowing into the device). In other arrangements, the sample may be obtained by other means (e.g. by way of a blood test, or a urine sample) and subsequently introduced into the vessel.

[0107] The devices disclosed herein may be manufactured by any suitable method. However, a nonlimiting example method for manufacturing a device for analysis of a biological sample will be set out below.

[0108] In particular, the method comprises providing an inflatable vessel for containing a biological sample, the vessel being gas-impermeable and / or liquid-impermeable. The vessel has an internal surface and an external surface.

[0109] The method also includes disposing one or more sensors on an internal surface of the vessel. In some methods, the one or more sensors may be disposed (i.e. positioned and / or attached) to the internal surface by a printing process, such as flexographic printing.

[0110] The method further includes disposing an electronic component on an external surface of the vessel. In some methods, the one or more sensors may be disposed (i.e. positioned and / or attached) to the external surface by a printing process, such as flexographic printing.

[0111] The method described above may be used to produce an arrangement in which the electronic component is configured to communicate with the one or more sensors. This may be implemented by, for example, forming conductive tracks between the electronic component and the one or more sensors. In some methods, the inflatable vessel is provided by providing a substantially flat template, folding the template, and sealing one or more portions of the template so as to form the vessel (and a cavity therein). In such methods, the components may be applied to the parts of the template which will form the internal and external surfaces of the vessel prior to the folding process, which may provide improved speed and / or ease of manufacture.

[0112] The devices as disclosed herein may be used in methods of analysing a biological sample from a subject. Such a method may comprise providing an inflatable vessel for containing a biological sample, the vessel being gas-impermeable and / or liquid-impermeable, collecting the sample in the vessel, analysing the sample using one or more sensors disposed on an internal surface of the vessel, and providing a measurement result from the one or more sensors to an electronic component disposed on an external surface of the vessel. The measurement result may correspond to a positive / negative indication, a numerical reading, or any other result derived from the sensors. The measurement result may be directly obtained by the sensors, or may be obtained by the electronic component processing the sensor output.

[0113] The method may further comprise transmitting the measurement result via a wireless communication to an external device. This may allow the data to be used elsewhere, such as for further analysis or for logging / storage in an electronic patient record. The external device may be, for example, a smart phone, a computer or a cloud server.

[0114] The method may further comprise sealing the sample within the vessel. This may allow the sample to be stored within the vessel, which may (for example) allow the vessel to be transported to a laboratory, as explained below. The sealing may be provided by a one-way valve in the vessel, or by sealing an opening in the vessel by any other suitable arrangement.

[0115] In some methods, the sample may be further analysed using a laboratory instrument. For example, after the measurement result has been displayed to the user, the vessel may be transported / sent to a laboratory. This may allow further analysis or testing to be performed beyond the capabilities of the sensor provided in the vessel, or to provide a confirmation of the result obtained by the sensor. The method may further comprise acquiring one or more biometric measurements from the subject. These measurements may be acquired by a sensor, such as the additional sensors described above. The biometric measurement may be used to obtain a biometric identification, to associate the measurement result with an electronic patient record.

[0116] In some arrangements, the measurement result may not relate to a particular clinical picture, but may merely be a measurement of a particular substance in the biological sample.

[0117] However, in other arrangements, a condition of the subject may be determined based on the measurement result.

[0118] It should be understood by those skilled in the art that while the present invention has been described with reference to exemplary embodiments, it is not limited to the disclosed exemplary embodiments. Various modifications, combinations, sub-combinations and alterations may occur depending on design requirements and other factors insofar as they are within the scope of the appended claims or the equivalents thereof. Features from any example or embodiment of the present disclosure can be combined with features from any other example or embodiment of the present disclosure.

Claims

CLAIMS1. A device for analysis of a biological sample, the device comprising: an inflatable vessel for containing a biological sample, the vessel being gas- impermeable and / or liquid-impermeable; one or more sensors disposed on an internal surface of the vessel; and an electronic component disposed on an external surface of the vessel, wherein the electronic component is configured to communicate with the one or more sensors.

2. The device of claim 1, wherein at least one sensor of the one or more sensors comprises one or more of an electrochemical sensor, a graphene sensor, an immunosensor, a field effect transistor, a gas phase biosensor, and a molecular assay.

3. The device of claim 1 or 2, wherein at least one sensor of the one or more sensors comprises a molecular assay, wherein the molecular assay is a recombinase polymerase amplification assay.

4. The device of claim 1, 2 or 3, wherein at least one sensor of the one or more sensors is configured to detect a species contained within an aerosol exhaled by the subject.

5. The device of claim 4, wherein at least one sensor of the one or more sensors is configured to detect a species in said aerosol which has been enhanced due to an ingestible consumed by the subject.

6. The device of any preceding claim, wherein at least one sensor of the one or more sensors is configured to detect one or more of nitric oxide, oxygen, carbon dioxide, tetrahydrocannabinol (THC) or a derivative thereof, volatile organics, methane, hydrogen sulphide, and hydrogen.

7. The device of claim 6, wherein the at least one sensor is configured to detect volatile organics used in determination of cancer.

8. The device of claim 7, wherein the at least one sensor is configured to detect volatile organics used in determination of at least one of colorectal cancer, oesophageal cancer, lung cancer, gastric cancer, and breast cancer.

9. The device of any preceding claim, wherein at least one of the one or more sensors is configured to determine sample sufficiency.

10. The device of any preceding claim, further comprising a collection portion for collection of the biological sample, the collection portion being in fluidic communication with the interior of the vessel.

11. The device of claim 10, wherein the collection portion is a mouthpiece.

12. The device of claim 10 or 11, further comprising a collar for interfacing the collection portion to the vessel.

13. The device of claim 12, wherein the collar includes one or more additional sensors.

14. The device of claim 13, wherein the one or more additional sensors include one or more of a heart rate sensor, a heart rate variability sensor, a temperature sensor, and a 3D accelerometer.

15. The device of any preceding claim, wherein the electronic component is reusable and / or detachable from the vessel.

16. The device of any preceding claim, wherein the electronic component includes a battery.

17. The device of any preceding claim, wherein the electronic component includes a plurality of battery subassemblies configured to combine to provide a battery.

18. The device of any preceding claim, wherein the electronic component includes an electronic display.

19. The device of any preceding claim, wherein the electronic component includes a printed circuit.

20. The device of any preceding claim, wherein the electronic component includes a near field communication (NFC) module.

21. The device of any preceding claim, wherein the electronic component includes a microprocessor.

22. The device of claim 21, wherein the microprocessor is an application specific integrated circuit (ASIC).

23. The device of claim 22, wherein the ASIC comprises a near field communication (NFC) module.

24. The device of any preceding claim, further comprising a biometric identification element on an external surface of the vessel and / or on the electronic component.

25. The device of claim 24, wherein the biometric identification element can be integrated with an electronic patient record.

26. The device of any preceding claim, wherein the volumetric capacity of the vessel is between 250ml and 2000ml.

27. The device of any preceding claim, wherein the device is configured to concentrate a species in the sample.

28. The device of any preceding claim, further comprising a valve configured to allow release of the biological sample.

29. The device of claim 28, wherein the device is configured to determine the volume of sample released through the valve.

30. The device of any preceding claim, wherein the device is for analysis of a sample of one or more of breath, urine, blood, saliva and sweat.

31. A method of manufacturing a device for analysis of a biological sample, the method comprising: providing an inflatable vessel for containing a biological sample, the vessel being gas- impermeable and / or liquid-impermeable; disposing one or more sensors on an internal surface of the vessel; and disposing an electronic component on an external surface of the vessel, wherein the electronic component is configured to communicate with the one or more sensors.

32. The method of claim 31, wherein the one or more sensors are disposed on the internal surface of the vessel by printing.

33. The method of claim 31 or 32, wherein the electronic component is disposed on the external surface of the vessel by printing.

34. The method of any of claims 31, 32 or 33, wherein the inflatable vessel is provided by providing a substantially flat template, folding the template, and sealing one or more portions of the template.

35. A method of analysing a biological sample from a subject, the method comprising: providing an inflatable vessel for containing a biological sample, the vessel being gas-impermeable and / or liquid-impermeable;collecting the sample in the vessel; analysing the sample using one or more sensors disposed on an internal surface of the vessel; and providing a measurement result from the one or more sensors to an electronic component disposed on an external surface of the vessel.

36. The method of claim 35, further comprising transmitting the measurement result via a wireless communication to an external device.

37. The method of claim 36, wherein the external device is a smart phone, a computer or a cloud server.

38. The method of any of claims 35-37, further comprising sealing the sample within the vessel.,39. The method of any of claims 35-38, further comprising analysing the sample using a laboratory instrument.

40. The method of any of claims 35-39, further comprising acquiring one or more biometric measurements from the subject.

41. The method of claim 40, further comprising obtaining a biometric identification using said one or more biometric measurements to associate the measurement result with an electronic patient record.

42. The method of any of claims 35-41, further comprising determining a condition of the subject based on the measurement result.

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