WO2016037234A1

WO2016037234A1 - Reservoir unit for a biological sample test device

Info

Publication number: WO2016037234A1
Application number: PCT/AU2015/050530
Authority: WO
Inventors: Richard Francis Day; Thomas Stephen Collings; Sean Andrew Parsons
Original assignee: Ellume Pty Ltd
Priority date: 2014-09-08
Filing date: 2015-09-08
Publication date: 2016-03-17

Abstract

A reservoir unit for supplying liquid to a sampling portion of a biological sample test device is disclosed. The reservoir unit includes a pouch having a first chamber comprising liquid, a second chamber connected to the first chamber, and a releasable seal between the first chamber and the second chamber. Upon release of the seal, a liquid flow path is created between the first chamber and the second chamber. Liquid flowing into the second chamber can be transferred from the second chamber to a sampling portion of the test device, via a liquid transfer element. The first chamber and second chamber can be configured in an elongated arrangement and can be integrally formed.

Description

Reservoir unit for a biological sample test device Cross-Reference to Related Applications

[0001] The present application claims priority from Australian provisional patent application no. 2014903560 filed on 8 September 2014, the content of which is incorporated herein by reference.

Technical Field

[0002] The present disclosure relates to devices for testing biological samples. Background

[0003] Devices for testing biological samples routinely employ liquid transfer elements, such as lateral flow mediums, to transfer all or part of a sample through the devices as part of a testing process.

[0004] For example, a test device such as an immunoassay can employ a lateral flow medium when testing for the presence or absence of an antigen in a biological sample. The sample, such as urine, blood or mucus, is supplied to a sampling portion of the lateral flow medium and flows by capillary action through the test device.

[0005] It can be desirable to increase the fluidity of a biological sample to improve flow of the sample through the test device. Increasing fluidity may be particularly important where the sample is relatively viscous in its natural form. To increase fluidity, a liquid such as a buffer solution may be combined with the sample.

[0006] It can also be desirable to control the flow of sample through a capillary path by providing liquid which acts on and ameliorates capillary forces to facilitate flow of sample and fluid in a desired direction.

[0007] The liquid may be introduced from an external source by placing the liquid onto the test device, e.g., using a dropper such as a pipette, etc. The liquid may be combined with the sample prior to, or after, placement of the sample onto the test device. As an alternative to dropping the liquid onto the test device, a liquid reservoir can be included with the test device that is releasable to allow liquid contained in the reservoir to combine with the sample. [0008] Any discussion of documents, acts, materials, devices, articles or the like which has been included in the present specification is not to be taken as an admission that any or all of these matters form part of the prior art base or were common general knowledge in the field relevant to the present disclosure as it existed before the priority date of each claim of this application.

Summary

[0009] In one aspect, the present disclosure provides a reservoir unit for supplying liquid to a sampling portion of a biological sample test device, the reservoir unit comprising: a pouch comprising

a first chamber comprising liquid;

a second chamber connected to the first chamber; and

a releasable seal between the first chamber and the second chamber, wherein, upon release of the seal, a liquid flow path is created between the first chamber and the second chamber.

[0010] The first chamber can provide a storage area for the liquid. Liquid may be held in the first chamber immediately after manufacture of the reservoir unit and prior to any assembling in and subsequent use of the reservoir unit in the test device. The test device may comprise a sampling portion to receive a biological sample and a test portion to test the biological sample.

[0011] In one aspect, the present disclosure provides a biological sample test device comprising:

a reservoir unit, the reservoir unit comprising:

a pouch comprising:

a first chamber comprising liquid;

a second chamber connected to the first chamber; and

a releasable seal between the first chamber and the second chamber, wherein, upon release of the seal, a liquid flow path is created between the first chamber and the second chamber;

a sampling portion to receive a biological sample; and

a test portion to test the biological sample;

wherein at least the sampling portion is fluidly connected to the second chamber.

[0012] In any of the above aspects, the reservoir unit may comprise a liquid transfer element. The liquid transfer element may have a first portion located in the second chamber and a second portion external to the second chamber and the first chamber. The sampling portion may be liquidly connected to the second chamber via the liquid transfer element.

[0013] Upon establishment of the liquid flow path between the first and second chambers, liquid may flow from the first chamber into the second chamber, where it may transfer out of the second chamber via the liquid transfer element. The liquid transfer element may transfer liquid out of the second chamber using capillary action. The liquid transfer element may be a lateral flow medium, e.g., a wick, and liquid in the second chamber may be drawn into the lateral flow medium by capillary action.

[0014] The provision of the second chamber in addition to the first chamber can provide for controlled release of liquid to the liquid transfer element, preventing flooding of the test device or other undesirable outcomes. The second chamber can create a 'buffer zone' where liquid originally present in the first chamber can be temporarily stored in a process of being drawn into the liquid transfer element at a rate compatible with a holding capacity of the liquid transfer element.

[0015] Nevertheless, liquid may be transferred out of the second chamber by alternative means. For example, instead of using a liquid transfer element such as a wick, liquid may flow out of the second chamber under the effect of gravity, or by virtue of a wiping or squeezing action caused by an actuator.

[0016] By providing the first and second chambers in a pouch, the second chamber may be manufactured in combination with the first chamber in a relatively straightforward and cost-efficient manner and use of the reservoir unit in conjunction with a sampling portion of a test device may be enhanced. Further, the releasable seal may be formed in a reliable and easily reproducible manner between the first and second chambers. These and other advantages will be evident from discussions below.

[0017] The test portion may include or form part of a lateral flow test strip (lateral flow assay). The test portion may be adapted to test for the presence or absence of a biological entity in a sample using immunochromatography or other techniques.

[0018] The sampling portion may be adapted to receive a biological sample, e.g., on a surface thereof. Where a lateral flow test strip is present, the sampling portion may form part of the lateral flow test strip or may be a separate from the lateral flow test strip. The device may be configured such that liquid is transferred by the liquid transfer element from the second chamber to the sampling portion where it combines with the received sample and increase the fluidity of the sample. The liquid may be a buffer solution. The combination of the liquid and the received sample may then be transferred to the test portion for further processing. A further liquid transfer element, e.g., lateral flow medium, may be provided to transfer the combination from the sampling portion to the test portion. Thus, transfer between the reservoir unit and the sampling portion, and between the sampling portion and the test portion, may be by virtue of capillary action.

[0019] The releasable seal may be a burstable seal. The releasable seal may be configured to release by bursting upon application of pressure to the seal. Pressure may be applied to the seal by pressurising liquid comprised in the first chamber. The pressurised liquid may press against the seal with sufficient force to cause release of the seal.

[0020] The pouch may be formed partially or entirely of flexible material. Thus, the pouch may be flexible in its entirety or may include portions that are rigid in addition to portions that are flexible.

[0021] The pouch may comprise one or more flexible walls that define the first chamber and the second chamber. The pouch may comprise at least one flexible wall that extends across both the first and second chambers. The at least one flexible wall extending across both the first and second chambers may be a unitary element.

[0022] In some embodiments, the pouch may comprise two opposing walls that extend across both the first and second chambers, the first and second chambers being located between the first and second walls, each of the opposing walls being flexible. As one alternative, one of the opposing walls may be flexible and the other may be rigid.

[0023] Upon application of a controlled compressive force to one or more flexible walls of the pouch defining the first chamber, liquid in the first chamber may be pressurised.

[0024] In some embodiments, the first chamber may comprise a gas (e.g., air) in addition to the liquid. Upon application of a controlled compressive force to the flexible walls, gas in the first chamber may be pressurised. Thus, in addition to or as an alternative to pressurised liquid, pressurised gas may press against the seal with sufficient force to cause release of the seal.

[0025] The second chamber may be substantially empty of liquid and adapted to at least partially fill with liquid from the first chamber upon release of the releasable seal. [0026] One or more flexible walls defining the second chamber may deform upon filling of the second chamber with liquid. The second chamber may be take a substantially collapsed configuration prior to release of the seal and may expand upon filling by liquid after release of the seal. Additionally or alternatively, the second chamber may have a fixed volume prior to release of the seal. The second chamber may be filled with air or other gas, for example.

[0027] To facilitate transfer of liquid from the first chamber to the second chamber, and transfer of liquid out of the second chamber via the liquid transfer element, one or more vents may be provided. The one or more vents may comprise perforations in one or more walls of the pouch. The one or more vents may be dimensioned to allow gas to pass through the vents but substantially not allow liquid to pass through the vents. Gas passing through the vents may be released to the atmosphere.

[0028] In one embodiment, one or more walls that define the second chamber comprise the one or more vents. The one or more vents may allow gas present in the second chamber to be vented when liquid is transferred from the first chamber to the second chamber. Gas may be present in the second chamber prior to release of the seal between the first and second chambers. By enabling venting of the gas from the second chamber, a substantial increase in pressure in the second chamber may be avoided as liquid flows from the first chamber to the second chamber, thus making transfer of the liquid between the two chambers more straightforward. Moreover, the liquid may replace some or all of the gas in the second chamber.

[0029] In general, transfer of gas through the one or more vents may enable pressure in the second chamber to be controlled, e.g. at or close to atmospheric pressure. While the vents may allow gas to escape the second chamber when the second chamber fills with liquid and pressure in the second chamber increases, the vents may also allow entry of gas to the second chamber as liquid is transferred out of the second chamber via the liquid transfer element and pressure in the second chamber decreases. Entry of gas to the second chamber via the one or more vents may therefore prevent a reduction of pressure occurring in the second chamber that might otherwise impede transfer of liquid out of the second chamber via the liquid transfer element.

[0030] The reservoir unit may be elongated along an axis of elongation. The first chamber, second chamber and releasable seal may each be located along the axis of elongation of the reservoir unit. [0031] The first and second chambers may each be elongate. The first and second chambers may each be elongate along the axis of elongation of the reservoir unit. The liquid transfer element may be elongate. The liquid transfer element may be elongate along the axis of elongation of the reservoir unit.

[0032] The first and second chambers may be integrally formed with each other. For example, the first and second chambers may be formed from a flexible sheet of material that is folded, bent, crimped, glued, welded (e.g., ultrasonic ally welded) and/or heat-sealed to form the first and second chambers.

[0033] The releasable seal may also be integrally formed with the first and second chambers. For example, the releasable seal may be formed from a flexible sheet of material that is folded, bent, crimped, glued, welded and/or heat-sealed to form the releasable seal in addition to the first and second chambers. In one embodiment, the releasable seal is formed by non-permanently heat sealing or welding together portions of inner surfaces of the sheet material, at a location between the first and second chambers.

[0034] The pouch may be elongate and may have a substantially tubular configuration, for example. The releasable seal may be provided by releasable engagement between opposing inner surfaces of walls of the pouch at a position between the first and second chambers. The opposing inner surfaces may be releasably engaged by heat sealing or welding. In one embodiment, the releasable seal may be approximately midway along the pouch. The first and second chambers may have substantially the same maximum fill volumes. Alternatively, the first and second chambers may have different fill volumes. For example, the second chamber may have a larger fill volume than the first chamber so that it may more easily accommodate a surge of liquid from the first chamber into the second chamber upon release of the releasable seal.

[0035] The pouch may comprise first and second opposite ends along the axis of elongation of the reservoir unit. The first chamber and the second chamber may be located adjacent the first end and second end of the pouch, respectively. The first end of the pouch may be permanently closed (e.g., permanently sealed closed) to provide a closed outer end of the first chamber. The second end of the pouch may be permanently closed (e.g., permanently sealed closed) to provide a closed outer end of the second chamber. Each of the first and second chambers may have releasably closed inner ends, which are adjacent to one another and provided by the releasable seal. [0036] The liquid transfer element may extend out of the second chamber via the second end of the pouch. The second end of the pouch may therefore be permanently closed around the liquid transfer element, as the liquid transfer element transitions out of the second chamber.

[0037] The pouch and/or flexible walls forming the first and/or second chambers may be formed from a variety of different materials, which materials may be capable of heat sealing or otherwise. For example, a heat sealable laminate of polyester - aluminium - nylon - LDPE may be employed.

[0038] The test device may comprise a housing, e.g., a substantially rigid housing, in which the reservoir unit is partially or fully enclosed. The housing may also partially or fully enclose other parts of the test device, such as the test portion. The housing may protect the reservoir unit and other parts of the test device from damage. The housing may be elongate. The housing may be elongate along the axis of elongation of the reservoir unit, when the reservoir unit is enclosed in the housing.

[0039] The test device may comprise an actuator that is operable to apply compressive force to the flexible walls of the first chamber. The compressive force may cause squeezing of the first chamber. Through the application of the compressive force, liquid in the first chamber (and optionally any gas in the first chamber) may be pressurised to a level that causes release (e.g., bursting) of the releasable seal.

[0040] The actuator may comprise a slider that is slidable relative to the reservoir unit. When the reservoir unit is at least partially enclosed in the housing, the slider may be slidably mounted to the housing and may slide in a direction that is parallel to the axis of elongation of the reservoir unit.

[0041] Compressive forces applied to flexible walls at the first chamber by the slider may cause both release of the seal and urging of liquid in the first chamber towards the second chamber. The urging may be by virtue of a wiping or squeezing effect provided by the slider. The slider may have an engagement surface that engages and compresses one more walls of the first chamber as it slides. Prior to release of the seal, in a plane perpendicular to the axis of elongation of the reservoir unit, the engagement surface may extend across an area that is substantially aligned with, and substantially the same as or greater than, the area across which the first chamber extends. Accordingly, the engagement surface of the slider may push through substantially the entire cross-section area of the first chamber, forcing substantially all of the liquid held in the first chamber to be urged toward the second chamber.

[0042] The slider may comprise a push element that includes the engagement surface. To enable urging in a progressive, controlled manner, the push element may configured as a ramp, the engagement surface being provided by an inclined surface of the ramp. The inclined surface may be neither parallel to nor perpendicular to the axis of elongation of the reservoir unit. The slider may comprise a grip portion, e.g., a thumb grip, which is engageable by a user to cause sliding of the slider. The grip portion may be external to the housing and the push element may be internal to the housing. One or more connectors may extend between the grip portion and the push element. The one or more connectors may locate through one or more openings in one or more walls of the housing. The one or more openings may comprise one or more slots that extend in a direction parallel to the axis of elongation of the reservoir unit. The one or more slots may guide movement of the slider in a direction parallel to the axis of elongation of the reservoir unit.

[0043] The test device may comprise an anchor portion to fix the position of the reservoir unit in the housing, preventing gross movement of the reservoir unit upon application of force thereto by the actuator. As an example, the anchor portion may comprise one or more openings in the reservoir unit, e.g. punched holes, and one or more anchor projections that are received in the holes to effect the fixing. The anchor projections may project from an inner surface of the housing of the test device, for example. Where the actuator is a slider, for example, the anchor portion may be positioned at an end of the reservoir unit that is located at or adjacent the slider prior to operation of the slider. The anchor portion may therefore counteract tension forces applied to the reservoir unit by the slider as the slider moves.

[0044] The sampling portion may be adjustably conformable to a part of a human or animal body for receiving a biological sample directly from the body. In this regard, except for the configuration and operation of the reservoir unit, the test device may be configured substantially in accordance with a test device as disclosed in PCT publication no. WO 2011/091473 Al, the content of which is incorporated herein by reference.

[0045] The sampling portion may comprise flexible material that is sufficiently supple to bend or fold freely or repeatedly in order to conform to a variety of different shapes of body parts to receive a biological sample. The flexible material may be bent or folded repeatedly without being substantially damaged, cosmetically and/or and functionally. In one embodiment, the device may take, generally, a butterfly configuration. The test device may comprise two flexible wings at least partially forming the sampling portion, and the housing that at least partially encloses the reservoir unit may be located centrally between the two wings and the housing may therefore be considered to provide a spine of the test device. The wings may be relatively pivotable or flexible about the housing. Nevertheless, the test device may take a variety of other configurations.

[0046] The test device, including the test portion thereof, may detect the presence or absence of one or more specific biological entities, such as antigens. The antigens may be found in common respiratory viruses including but not limited to Influenza A (including the H1N1 virus subtype), Influenza B, Respiratory Synctial Virus, parainfluenza viruses, adenoviruses, rhinoviruses, coronaviruses, coxsackie viruses, HIV viruses and/or enteroviruses. The test device may also detect specific biological antigens found in bacteria, fungi, protozoa, Helminths, Mycoplasma and prions. The test device may also be capable of detecting specific proteins produced by the human or animal body, including but not limited to immunoglobulin, hormone molecules, inflammatory or malignant proteins. The test portion of the test device may comprise a plurality of different test zones so that the presence or absence of different biological entities such as antigens can be tested simultaneously.

[0047] In addition to the reservoir, the housing may at least partially enclose the test portion and/or other elements of the device, such as optional electronic componentry.

When the housing at least partially encloses the test portion, the housing may include one or more openings or transparent portions to permit observation of indicia related to the results of testing.

[0048] As indicated, the test device may comprise one or more lateral flow test strips, e.g., in the form of relatively rigid elongate layered strips of the type commonly used for pregnancy testing, etc. The lateral flow test strips may comprise the test portion. The sampling portion may be integrated into the test strip or may be provided separately from the test strip and connected to the test strip by a liquid transfer portion.

[0049] The test portion of the device may be provided with antigens or antibodies to allow testing for the presence of one or more biological entities using existing principles of lateral flow immunochromatography. One or more label-holding areas, e.g. coloured label-holding areas containing specific antibodies bound to light visible molecules, may be provided in the test portion. The label-holding areas may be located at the edge or adjacent the edge of a test zone,. The sample received by the sampling portion may travel via capillary action through the sampling portion and into the test portion where it mixes with the label-holding areas and may form antigen-antibody (labelled) complexes. The test zones may comprise stripes (lines), crosses, squares or other shaped regions of the test portion that have been impregnated with antibodies or antigens. Depending upon the biological antigens present in the sample, and the antibodies or antigens at the label-holding areas and the test zones, the sample may become bound at one or more of the test zones, causing a colour change at the test zones. The change in colour may be observable by a user and indicative of the presence or absence of a specific biological entity in the sample, such as, but not limited to, influenza A or influenza B. In alternative embodiments, however, an electronic reader may be provided to analyse changes at the test portion and results of testing may be presented to the user through an electronic display, e.g. an LCD or LED display, etc.

[0050] Although the device may use principles of immunochromatography, it is conceived, however, that alternative means of testing could be incorporated into the device and make use of liquid from the reservoir unit. As one example, the reservoir unit may be incorporated in a microfluidic device, e.g., a microfluidic lab on a chip (LOC) device. Further, while the liquid in the reservoir unit can have a function of increasing fluidity of a sample as described above, it may have additional or alternative functions within the test device. For example, liquid comprised in the reservoir unit may be a reagent, catalyst or solvent that is provided to bring about or take part in a chemical reaction at the sampling portion and/or test portion.

[0051] The test device may provide a rapid diagnosis test device, permitting testing in less than one hour, less than 30 minutes, less than 10 minutes, less than 5 minutes, or less than 2 minutes, for example. The test device, including the reservoir unit, may be disposable, configured for single-use only. The test device may be provided in sterile packaging prior to use. The test device may provide a means for entirely non-invasive testing for the presence or absence of one or more biological entities. The test device may be used for testing in the veterinary field as well as in the field of human medicine. The test device may provide a home use or point-of-care test device.

[0052] In one aspect, the present disclosure provides a reservoir unit for supplying liquid to a sampling portion of a biological sample test device, the reservoir unit comprising: a first chamber comprising liquid;

a second chamber connected to the first chamber; and

a releasable seal between the first chamber and the second chamber,

wherein, upon release of the seal, a liquid flow path is created between the first chamber and the second chamber; and

wherein the first and second chambers are integrally formed with each other.

[0053] The reservoir unit may comprise a liquid transfer element having a first portion located in the second chamber and a second portion external to the first chamber and the second chamber. The reservoir unit may be configured in accordance with the reservoir unit of preceding aspects. The reservoir unit may form part of a test device as described with respect to preceding aspects.

[0054] The first and second chambers may be formed from a flexible sheet of material that is folded, bent, crimped, glued, welded and/or heat-sealed to form the first and second chambers.

[0055] The releasable seal may also be integrally formed with the first and second chambers. For example, the releasable seal may be formed from a flexible sheet of material that is folded, bent, crimped, glued, welded and/or heat-sealed to form the releasable seal in addition to the first and second chambers. In one embodiment, the releasable seal is formed by non-permanently heat sealing or welding together portions of inner surfaces of the sheet material, between the first and second chambers.

[0056] As indicated, the reservoir unit may be elongated along an axis of elongation, and the first chamber, second chamber and releasable seal may each be located along the axis of elongation.

[0057] In one aspect, the present disclosure provides a reservoir unit for supplying liquid to a sampling portion of a biological sample test device, the reservoir unit comprising: a first chamber comprising liquid;

a second chamber connected to the first chamber; and

wherein the reservoir unit is elongated along an axis of elongation and the first chamber, second chamber and releasable seal are each located along the axis of elongation.

[0058] The first and second chambers may each be elongate. The first and second chambers may each be elongate along the axis of elongation of the reservoir unit. The liquid transfer element may be elongate. The liquid transfer element may be elongate along the axis of elongation of the reservoir unit. [0059] In any of the preceding aspects, by providing the first chamber, second chamber and releasable seal along the axis of elongation of the reservoir, significant advantages may be achieved. For example, the release of the seal may be easily controlled, manufacture of the reservoir may be straightforward, transfer of liquid from the first chamber to the second chamber may be effective and reliable, and the reservoir unit may be appropriately shaped for locating, e.g., discreetly locating, in the test device.

[0060] While reservoir units described with respect to preceding aspects have or may have the first chamber, second chamber and releasable seal each located along the axis of elongation of the reservoir unit, alternatively, one or more of the first chamber, second chamber and releasable seal may be located off the axis of elongation of the reservoir unit, or the reservoir unit may not be elongated at all. For example, the first and second chambers may be positioned side -by-side.

[0061] Throughout this specification the word "comprise", or variations such as

"comprises" or "comprising", will be understood to imply the inclusion of a stated element, integer or step, or group of elements, integers or steps, but not the exclusion of any other element, integer or step, or group of elements, integers or steps.

Brief Description of Drawings

[0062] By way of example only, embodiments of the present disclosure are described below with reference to the accompanying Figures, in which:

[0063] Fig. 1 shows an oblique view of a reservoir unit according to an embodiment of the present disclosure;

[0064] Figs. 2a and 2b show cross-sectional views of the reservoir unit of Fig. 1 , in combination with a push element, with the push element in an initial and actuated position, respectively;

[0065] Fig. 3a shows a top view of a test device, including the reservoir unit of Fig. 1 , according to an embodiment of the present disclosure, and Fig. 3b shows a cross-sectional view of the test device along line A— A of Fig. 3a;

[0066] Fig. 4a to 4h show steps in the manufacture of a reservoir unit according to an embodiment of the present disclosure; [0067] Fig. 5 shows the test device of Fig. 3a brought adjacent a nose for receipt of a nasal sample;

[0068] Fig. 6a shows a top view of a reservoir unit according to another embodiment of the present disclosure, and Fig. 6b shows a cross-sectional end view of the reservoir unit along line B— B of Fig. 6a; and

[0069] Fig. 7 shows an oblique view of a reservoir unit according to another embodiment of the present disclosure.

Description of Embodiments

[0070] A reservoir unit 10 according to an embodiment of the present disclosure is shown in Fig. 1. The reservoir unit 10 is designed to be assembled into a biological sample test device. A biological sample test device 20 according to an embodiment of the present disclosure, into which the reservoir unit 10 can be assembled, is represented in Fig. 3a and 3b. The test device 20 is configured to test a nasal sample in this embodiment, but may be adapted to test a variety of different biological samples.

[0071] The reservoir unit 10 includes a pouch 11 and a liquid transfer element 12 partially located in the pouch.

[0072] Referring to Fig. 2a, which shows a cross-sectional view of the pouch 11, the pouch 11 includes first and second chambers 111, 112. In an initial, pre -use configuration as represented in Fig. 2a, the first chamber 111 contains liquid 113, in particular buffer solution in this embodiment, and the second chamber 112 is absent of any liquid. The first chamber 111 is therefore in a substantially full, expanded configuration and the second chamber 112 is in a substantially empty, collapsed configuration, although in some embodiments a fixed volume of gas may be provided in the second chamber 112. The first and second chambers 111, 112 are separated internally in the pouch 11 by a releasable seal 114. Upon release of the seal 114, a liquid flow path is established between the first chamber 111 and the second chamber 112.

[0073] Upon establishment of the liquid flow path between the first and second chambers 111, 112, liquid flows from the first chamber 111 into the second chamber 112, where it can subsequently transfer out of second chamber 112 via the liquid transfer element 12. In this embodiment, the liquid transfer element 12 is en elongate lateral flow medium, e.g., a wick, and liquid in the second chamber 112 is drawn into and along the liquid transfer element by capillary action. [0074] The reservoir unit 10, and the pouch 11 included in the reservoir unit 10, are elongated. The axis of elongation of the reservoir unit and pouch is identified by broken line 100 in the Figures. The first chamber 111, second chamber 112 and releasable seal 114 are each located along the axis of elongation 100 of the reservoir unit 10. The liquid transfer element 12 is also located along the axis of elongation 100 and is elongated along the axis of elongation 100.

[0075] The pouch 11 includes first and second opposing walls 115a, 115b. The pouch 11 also includes first and second lateral edges 116a, 116b, located at opposite sides of each wall 115a, 115b and extending parallel to the axis of elongation 100. The pouch also includes first and second end ends 117a, 117b, located at opposite ends of each wall 115a, 115b and extending in a direction perpendicular to the axis of elongation 100.

[0076] The pouch 11 is formed from a sheet of flexible material that is folded over along the first lateral edge 116a to form the first and second opposing walls 115a, 115b. The first and second walls 115a, 115b each extend across both the first and second chambers 111, 112 and are each of a unitary construction as they extend across both the first and second chambers 111, 112. In addition to the folding, seals are provided between the first and second walls 115a, 115b to form the first and second chambers 111, 112. In particular, the first and second walls 115a, 115b are permanently sealed together at the second lateral edge 116b and at the first and second ends 117a, 117b of the pouch 11. Further, the first and second walls 115a, 115b (particularly inner surfaces of the first and second walls) are releasably sealed together at an intermediate portion 118 of the pouch 11 , approximately midway between the first and second ends 117a, 117b of the pouch 11. The releasable sealing together of the walls 115a, 115b at the intermediate portion 118 provides a division between the first and second chambers 111, 112 and forms the releasable seal 114. In this embodiment, the first and second chambers 111, 112 have approximately the same maximum liquid-fill volume. However, in alternative embodiments, the second chamber may have a larger fill volume than the first chamber so that it may more easily

accommodate a surge of liquid from the first chamber into the second chamber upon release of the releasable seal.

[0077] By providing the first and second chambers in a pouch, the second chamber may be manufactured in combination with the first chamber in a relatively straightforward and cost-efficient manner and use of the reservoir unit may be enhanced. Further, the releasable seal may be formed in a reliable and easily reproducible manner between the first and second chambers. Reliability can be enhanced by the provision of the flexible walls 115a, 115b that are unitary in nature at least as they extend between the first and second chamber and define the releasable seal at an intermediate portion thereof. Nevertheless, alternative embodiments may employ one or more walls that are formed in multiple parts that are connected together.

[0078] In this embodiment, the pouch 11 is formed from a heat sealable laminate of polyester - aluminium - nylon - LDPE. However, other or additional materials may be employed.

[0079] The test device 20 in which the reservoir unit 10 is employed comprises an actuator, in particular a slider 21, that is operable to apply compressive force to the flexible walls of the first chamber 111 of the reservoir unit 10. Figs. 3a and 3b show the reservoir unit 10 assembled in the test device 20 according to an embodiment of the present disclosure. The reservoir unit 10 is enclosed discreetly in a housing 22 of the test device 20. The housing 22 is elongated along the axis of elongation 100 of the reservoir unit 10. The slider 21 is slidably mounted to the housing 22 and operable to slide relative to the housing 22 in an actuation direction 101 from the first chamber 111 to the second chamber 112, the actuation direction 101 being parallel to the axis of elongation 100.

[0080] The slider 21 includes a push element 211, including a reservoir unit engagement surface 212, and a grip portion 213, e.g., a thumb grip, the grip portion 213 being engageable by a user to cause movement of the slider 21, including the push element 211, in the actuation direction 101. The push element 211 is internal to the housing 22 and the grip portion 213 is external to the housing. To transfer forces between the grip portion 213 and the push element 211, the slider 21 comprises connection elements that extend between the grip portion and the push element via slots in the housing 20. The slots (not shown) extend in a direction parallel to the axis of elongation 100 of the reservoir unit 10 and the housing 22. The one or more slots guide movement of the slider 21, including the push element 211, in the actuation direction 101.

[0081] Positioning of the push element 211 before and after movement in the actuation direction 101 is illustrated in Figs. 2a and 2b, respectively. As the push element 211 moves in the actuation direction 101, its engagement surface 212 presses against the outer surface of first wall 115a of the pouch 11 adjacent the first chamber 111, causing

squeezing/compression of the first chamber 111, resulting in liquid 113 inside the first chamber 11 becoming increasingly pressurised. As it reaches a threshold pressure, the liquid 113 forces open or 'bursts' the releasable seal 114 such that engagement between the inner surfaces of the first and second walls 115a, 115b at the intermediate portion 118 of the pouch ceases and the first and second walls 115a, 115b move apart. A gap is therefore created between the first and second walls 115a, 115b at the intermediate portion 118 of the pouch, as identifiable in Fig. 2b, which gap provides the liquid flow path along which liquid can transfer from the first chamber 111 to the second chamber 112.

[0082] Transfer of the liquid from the first chamber 111 to the second chamber 112 is assisted by the push element 211. The push element 211 is configured to urge any recalcitrant liquid in the first chamber 111 to the second chamber 112 by virtue of a wiping or squeezing effect. As the slider moves forward in the actuation direction 101, it progressively flattens the first chamber in the actuation direction 101, forcing liquid to move into the second chamber. To achieve this flattening effect, the engagement surface 112 extends across an area, in a plane perpendicular to the axis of elongation 100 of the reservoir unit 10, that is substantially aligned with, and substantially the same as or greater than, the area across which the first chamber 111 extends in a plane perpendicular to the axis of elongation 100 of the reservoir unit 10. Accordingly, the engagement surface 112 of the slider 21 substantially pushes through the entire cross-sectional area of the first chamber 111 as it moves in the actuation direction 101.

[0083] To enable urging in a progressive, controlled manner, the push element 211 is configured as a ramp in this embodiment, with the engagement surface 212 being provided by an inclined surface of the ramp. The inclined surface is neither parallel to nor perpendicular to the axis of elongation 100 of the reservoir unit.

[0084] The reservoir unit 10 includes an anchor portion. The anchor portion is provided to help locate and engage the reservoir unit 10 at an appropriate position in the housing 22 of the test device 20 when the reservoir unit 10 is assembled in the test device 20.

Moreover, the anchor portion can prevent gross movement of the reservoir unit 10 in the housing 22 during use, particularly when forces are applied thereto by the push element 211. The anchor portion includes one or more anchor openings or slots 119 at the first end 117a of the pouch 11 that are adapted to receive respective anchor projections 221 that project from an inner surface of the housing 22. The anchor projections 221 can be stakes and the stakes can be fixed within the slots 119 by virtue of a heat staking process or otherwise. In a heat staking process, distal ends of the stakes will spread through melting, causing trapping of the first end 117a of the pouch 11 between the distal ends of the stakes and the inner surface of the housing 22. Other means of fixing the reservoir unit 10 in the housing 22 may be used, however, including adhesive, clips, fasteners or otherwise. [0085] A method of manufacturing a reservoir unit (e.g., the reservoir unit 10 as described above) according to an embodiment of the present disclosure is now described with reference to Figs. 4a to 4h. In a first step, a sheet of flexible material 31 is folded into a tubular shape (Fig. 4a). Next, a permanent heat seal is applied along a seam 32 opposite to the fold (Fig. 4b). Another permanent heat seal is then applied to a first end 33 of the tubular shaped material to create a pouch 34 (Fig. 4c). Subsequently, with the first end 33 oriented downwards, a 'dose' of liquid 35, e.g., 1ml of buffer solution, is inserted into the pouch 34 via an open second end 37 (Fig. 4d). Next, a releasable heat seal is applied at an intermediate section 36 of the pouch 34, forming a first chamber at the bottom of the pouch 34 in which all of the liquid is contained and an empty second chamber with the open second end 37 (Fig. 4e). A liquid transfer element 38 (e.g., a wick) is then inserted into the second chamber via the open second end 37 (Fig. 4f). The open second end 37 is then permanently heat sealed closed around the liquid transfer element 38 (Fig. 4g). Finally, anchor slots 39 are formed at the bottom end 33 of the pouch 34, e.g., by a hole punching process (Fig. 4h).

[0086] Alternative methods of manufacturing the reservoir unit 10 may be employed. As one example, rather than folding a single sheet of material, two sheets of flexible material may be brought together and sealed at both lateral edges to form the tubular shape.

[0087] Permanent and releasable seals have been described above. In general, in the present disclosure, a permanent seal is a seal that is not intended to be released. Any attempted release of a permanent seal can be expected to cause significant damage to and/or impair normal function of the reservoir unit. On the other hand, a releasable seal in the present disclosure is intended to be released. Release of a releasable seal at an appropriate time will not cause any substantial damage or substantially impair the function and integrity of the reservoir unit. Where a permanent seal and a releasable seal are formed by the same process, e.g., heat sealing, the permanent seal may be a stronger seal than the releasable seal. A permanent heat seal may be formed through application of heat for a longer period of time and/or at a higher temperature than for a releasable heat seal, for example.

[0088] Referring again to Figs. 3a and 3b, the test device 20 includes a sampling portion (indicated generally as item 23) and a test portion (indicated generally as item 24). In this embodiment, the test portion 24 is provided by a lateral flow test strip (lateral flow assay) located in the housing 22. The lateral flow test strip is adapted to test for the presence or absence of a biological entity in a sample using immunochromatography. [0089] In this embodiment, the sampling portion 23 comprises absorbent material adapted to receive a nasal sample (nasal mucus) from a body via a nose-blowing technique. As better seen in Fig. 5, the sampling portion 23 is formed from two flexible wing elements 231 , 232 that are relatively moveable about the housing 22 and which are locatable either side of a nose 3 to receive nasal mucus therefrom.

[0090] The test device 20 is configured such that liquid is transferred by virtue of capillary action through the liquid transfer element 12 from the second chamber 112 to the sampling portion 23 where it combines with the received sample at the sampling portion 23 and increases the fluidity of the sample. The combination of the liquid and the received sample is then transferred from the sampling portion 23 via one or more additional liquid transfer elements to the test portion 24 in the housing 22.

[0001] Except for the configuration and operation of the reservoir unit, the test device 20 may be configured substantially in accordance with a test device discussed in PCT publication no. WO 2011/091473 Al (particularly with reference to Figs. 8 to 13c thereof), the content of which is incorporated herein by reference.

[0091] The test device 20, including the test portion thereof, may detect the presence or absence of one or more specific biological entities, such as antigens. The antigens may be found in common respiratory viruses including but not limited to Influenza A (including the H1N1 virus subtype), Influenza B, Respiratory Synctial Virus, parainfluenza viruses, adenoviruses, rhinoviruses, coronaviruses, coxsackie viruses, HIV viruses and/or enteroviruses. The test device may also detect specific biological antigens found in bacteria, fungi, protozoa, Helminths, Mycoplasma and prions. The test device may also be capable of detecting specific proteins produced by the human or animal body, including but not limited to immunoglobulin, hormone molecules, inflammatory or malignant proteins. The test portion 24 of the test device may comprise a plurality of different test zones so that the presence or absence of different biological entities such as antigens can be tested simultaneously.

[0092] The housing 24 can include one or more openings or transparent portions to permit observation of indicia related to the results of testing at the test portion 24.

[0093] The test portion 24 of the device 20 may be provided with antigens or antibodies to allow testing for the presence of one or more biological entities using existing principles of lateral flow immunochromatography. One or more label-holding areas, e.g. coloured label-holding areas containing specific antibodies bound to light visible molecules, may be provided in the test portion. The sample received by the sampling portion may travel via capillary action through the sampling portion and into the test portion where it mixes with the label-holding areas and may form antigen-antibody (labelled) complexes. Test zones may be provided in the test portion that comprise stripes (lines), crosses, squares or other shaped regions of the test portion that have been impregnated with antibodies or antigens. Depending upon the biological antigens present in the sample, and the antibodies or antigens at the label-holding areas and the test zones, the sample may become bound at one or more of the test zones, causing a colour change at the test zones. The change in colour may be observable by a user and indicative of the presence or absence of a specific biological entity in the sample, such as, but not limited to, influenza A or influenza B. In alternative embodiments, however, an electronic reader may be provided to analyse changes at the test portion and results of testing may be presented to the user through an electronic display, e.g. an LCD or LED display, etc.

[0094] Although the device 20 may use principles of immunochromatography, it is conceived, however, that alternative means of testing can be incorporated into the device 20 while making use of liquid from the reservoir unit 10. Further, while the liquid in the reservoir unit 10 can have a function of increasing fluidity of a sample as described above, it may have additional or alternative functions within the test device. For example, liquid comprised in the reservoir unit may be a reagent, catalyst or solvent that is provided to bring about or take part in a chemical reaction at the sampling portion and/or test portion.

[0095] While embodiments have been described above in which the first chamber 111, second chamber 112, and releasable seal 114 are each located along the same axis of elongation 100 of the reservoir unit 10, in alternative embodiments a different configuration may be provided while still achieving one or more advantages of the present disclosure. For example, with reference to Figs. 6a and 6b, a reservoir unit 4 in one embodiment includes a first chamber 41 and second chamber 42, the first and second chamber 41, 42 being integrally formed side-by-side in a pouch 40. A releasable seal 43 is formed between adjacent ends of the first and second chambers 41, 42. Again, transfer of liquid from the first chamber 41 to the second chamber 42 is assisted by a push element that wipes and squeezes along an axis of elongation of the first chamber 41 in a direction a generally indicated by arrow 44. The squeezing causes pressurising of the liquid and ultimately bursting of the seal 43. However, in this embodiment, liquid is forced into the second chamber 42 in a direction, generally as indicated by arrow 45, which is substantially opposite to the direction 44 in which the liquid moves through the first chamber 41. [0096] In this embodiment, the first and second chambers are again defined by first and second opposing walls 46a, 46b. However, in this embodiment, only one of the walls 46a is flexible, the other wall 46b being substantially rigid. The actuator presses against the flexible wall 46a only.

[0097] A reservoir unit 50 according to another embodiment of the present disclosure is illustrated in Fig. 7. The reservoir unit 50 is configured substantially identically to the reservoir unit 10 described above with reference to Fig. 1, for example, and includes a pouch 51 with first and second chambers 511, 512 separated by a releasable seal 514, and a liquid transfer element 52. However, unlike the embodiment illustrated in Fig. 1 , vents are provided in the first and second opposing walls 515a, 515b that define the second chamber 512. In particular, the vents are provided by perforations 501 in the walls 515a, 515b. The perforations 501 are dimensioned to allow gas to pass therethrough but substantially not allow liquid to pass therethrough. Gas passing through the perforations 501 can be released to atmosphere.

[0098] Gas, such as air, can be present in the second chamber 512 prior to release of the seal 514 between the first and second chambers 511, 512. The perforations 501 allow gas present in the second chamber 512 to be vented when liquid is transferred from the first chamber 511 to the second chamber 512 after release of the seal 514. By enabling venting of the gas from the second chamber 512, a substantial increase in pressure in the second chamber 512 can be avoided as liquid flows from the first chamber 511 to the second chamber 512, thus making transfer of the liquid more straightforward. Moreover, the liquid may replace some or all of the gas in the second chamber 512.

[0099] In general, transfer of gas through the perforations 501 may enable pressure in the second chamber 512 to be controlled, e.g. at or close to atmospheric pressure. While the perforations 501 can allow gas to escape the second chamber 512 when the second chamber 512 fills with liquid and pressure in the second chamber increases 512, the perforations 501 can also allow entry of gas to the second chamber 512 as liquid is transferred out of the second chamber 512 via the liquid transfer element 52 and pressure in the second chamber 512 decreases. Entry of gas to the second chamber 512 via the perforations 501 can therefore prevent a reduction of pressure in the second chamber 512 occurring that might otherwise impede transfer of liquid out of the second chamber 512 via the liquid transfer element 52.

[0100] In any of the embodiments, the test device 20 may provide a rapid diagnosis test device, permitting testing in less than one hour, less than 30 minutes, less than 10 minutes, less than 5 minutes, or less than 2 minutes, for example. The test device 20, including the reservoir unit 10, may be disposable, configured for single -use only. The test device 20 may be provided in sterile packaging prior to use. The test device 20 may provide a means for entirely non-invasive testing for the presence or absence of one or more biological entities. The test device 20 may be used for testing in the veterinary field as well as in the field of human medicine. The test device 20 may provide a home use or point-of-care test device.

[0101] It will be appreciated by persons skilled in the art that numerous variations and/or modifications may be made to the above-described embodiments, without departing from the broad general scope of the present disclosure. The present embodiments are, therefore, to be considered in all respects as illustrative and not restrictive.

Claims

Claims:

1. A reservoir unit for supplying liquid to a sampling portion of a biological sample test device, the reservoir unit comprising:

a pouch comprising:

a first chamber comprising liquid;

a second chamber connected to the first chamber; and

2. The reservoir unit of claim 1, wherein the releasable seal is configured to release by bursting upon application of pressure to the seal.

3. The reservoir unit of claim 1 or 2, comprising one or more flexible walls defining the first and second chambers.

4. The reservoir unit of claim 3, wherein at least one flexible wall extends across both the first and second chambers.

5. The reservoir unit of claim 4, wherein the at least one flexible wall is a unitary element that extends across both the first and second chambers.

6. The reservoir unit of claim 3, 4 or 5, comprising two opposing flexible walls defining the first and second chambers.

7. The reservoir unit of any one of claims 3 to 5, wherein the pouch comprises one or more vents that allow gas to pass through the vents but substantially do not allow liquid to pass through the vents.

8. The reservoir unit of claim 7, wherein the one or more vents are perforations.

9. The reservoir unit of claim 7 or 8, wherein the one or more vents are provided in walls of the pouch that define the second chamber.

10. The reservoir unit of any one of the preceding claims, wherein the first chamber is configured for pressurisation of liquid in the first chamber.

11. The reservoir unit of claim 10, wherein the releasable seal is adapted to release upon application of pressure to the releasable seal applied by pressurised liquid in the first chamber.

12. The reservoir unit of any one of the preceding claims, wherein the second chamber is substantially empty of liquid and adapted to at least partially fill with liquid from the first chamber upon release of the releasable seal.

13. The reservoir unit of claim 12, wherein the second chamber is configured to deform upon filling of the second chamber with liquid.

14. The reservoir unit of any one of the preceding claims, wherein the reservoir unit is elongated along an axis of elongation, and the first chamber, second chamber and releasable seal are each located along the axis of elongation.

15. The reservoir unit of claim 14, wherein the first and second chambers are each elongate along the axis of elongation of the reservoir unit.

16. The reservoir unit of any one of the preceding claims comprising a liquid transfer element having a first portion located in the second chamber and a second portion external to the first chamber and the second chamber.

17. The reservoir unit of claim 16, wherein the liquid transfer element comprises a lateral flow medium.

18. The reservoir unit of claim 16 or 17 when dependent on claim 14, wherein the liquid transfer element is elongate along the axis of elongation of the reservoir unit.

19. The reservoir unit of any one of the preceding claims, wherein the first and second chambers are integrally formed with each other.

20. The reservoir unit of any one of the preceding claims, wherein the first and second chambers are formed from a flexible sheet of material that is folded, bent, crimped, glued, welded and/or heat-sealed to form the first and second chambers.

21. The reservoir unit of any one of the preceding claims, wherein the releasable seal is integrally formed with the first and second chambers.

22. The reservoir unit of any one of claim 20 or 21, wherein the releasable seal is provided by a non-permanent sealing together of inner surfaces of the sheet material between the first and second chambers.

23. The reservoir unit of any one of the preceding claims, wherein the pouch comprises first and second opposite ends, the first chamber and the second chamber being located adjacent the first end and second end of the pouch, respectively.

24. The reservoir unit of claim 23 when dependent on claim 16, wherein the liquid transfer element extends out of the second chamber via the second end of the pouch, and wherein the second end of the pouch is sealed around an intermediate portion of the liquid transfer element.

25. The reservoir unit of any one of any one of the preceding claims, wherein the releasable seal is positioned substantially midway along the pouch.

26. The reservoir unit of any one of the preceding claims, wherein the first and second chambers have substantially the same maximum fill volumes or the second chamber has a larger fill volume than the first chamber.

27. A biological sample test device comprising:

a reservoir unit according to any one of the preceding claims;

a sampling portion to receive a biological sample; and

a test portion to test the biological sample;

wherein at least the sampling portion is liquidly connected to the second chamber.

28. The test device of claim 27, wherein the test device comprises a housing, wherein the reservoir unit is at least partially enclosed in the housing.

29. The test device of claim 28, wherein the housing is elongate along the axis of elongation of the reservoir unit.

30. The test device of claim 28 or 29, wherein the test portion is at least partially enclosed in the housing.

31. The test device of any one of claims 27 to 30, wherein the sampling portion is at least partially external to the housing.

32. The test device of any one of claims 27 to 31 , wherein the sampling portion is adjustably conformable to a part of a human or animal body for receiving a biological sample directly from the body.

33. The test device of any one of claims 27 to 32, wherein the test device is configured such that liquid that has flowed from the first chamber to the second chamber transfers out of the second chamber and to the sampling portion to combine with a biological sample received by the sampling portion.

34. The test device of claim 33, wherein the liquid is a buffer solution.

35. The test device of claim 33 or 34, comprising a second liquid transfer element configured to transfer a combination of the biological sample and the liquid from the sampling portion to the test portion.

36. The test device of claim 35, wherein the second liquid transfer element comprises a lateral flow medium.

37. The test device of any one of claims 27 to 36, wherein the test portion includes or forms part of a lateral flow test strip.

38. The test device of any one of claims 27 to 37 comprising an actuator operable to apply compressive force to flexible walls of the first chamber.

39. The test device of claim 38, wherein the actuator comprises a slider that is slidable relative to the reservoir unit.

40. The test device of claim 38 or 39, wherein the actuator is adapted to slide in an actuation direction that is parallel to an axis of elongation of the reservoir unit.

41. The test device of claim 38, 39 or 40, wherein the actuator is operable to urge liquid in the first chamber towards the second chamber.

42. The test device of claim 41, wherein the actuator urges liquid to the second chamber by virtue of a wiping effect.

43. The test device of any one of claims 38 to 42, wherein the actuator comprises a portion configured as a ramp.

44. The test device of any one of claims 27 to 43 comprising an anchor portion to anchor the position of the reservoir unit in the test device.

45. The test device of claim 44, wherein the anchor portion comprise one or more openings in the reservoir unit that are adapted to receive one or more projections.

46. A reservoir unit for supplying a liquid to a sampling portion of a biological sample test device, the reservoir unit comprising:

a first chamber comprising liquid;

a second chamber connected to the first chamber;

a releasable seal between the first chamber and the second chamber, wherein, upon release of the seal, a liquid flow path is created between the first chamber and the second chamber; and

47. The reservoir unit of claim 46, wherein the first and second chambers are each elongate along the axis of elongation of the reservoir unit.

48. The reservoir unit of claim 46 or 47 comprising a liquid transfer element having a first portion located in the second chamber and a second portion external to the first chamber and the second chamber.

49. The reservoir unit of claim 48, wherein the liquid transfer element is elongate along the axis of elongation of the reservoir unit.

50. A reservoir unit for supplying liquid to a sampling portion of a biological sample test device, the reservoir unit comprising:

a first chamber comprising liquid;

a second chamber connected to the first chamber; and

a releasable seal between the first chamber and the second chamber,

wherein the first and second chambers are integrally formed with each other.

51. The reservoir unit of claim 50, wherein the first and second chambers are formed from a flexible sheet of material that is folded, bent, crimped, glued, welded and/or heat- sealed to form the first and second chambers.

52. The reservoir unit of claim 50 or 51 , wherein the releasable seal is integrally formed with the first and second chambers.

53. The reservoir unit of any one of claims 50 to 52, wherein the releasable seal is provided by a non-permanent sealing together of inner surfaces of the sheet material between the first and second chambers.