Analysis devices

Abstract

The present invention provides an analysis device, the device comprising: a sample reception zone; a fluid storage in fluid communication with the sample reception zone; an analysis zone in fluid communication with the sample reception zone; and a drive arrangement which, when activated, is configured to drive fluid stored in the fluid storage so that it passes through the sample reception zone to the analysis zone.

Description

[0001] ANALYSIS DEVICES

[0002] This project has been funded in whole or in part with Federal funds from the NHLBI, National Institutes of Health, Department of Health and Human Services, under Contract No. 75N92023D00001.

[0003] The present invention relates to analysis devices. The invention is of particular, but not exclusive, relevance to analysis devices which are arranged to receive a sample and analyse it.

[0004] Devices which are able to receive a sample from a user, process that sample and analyse it have particular use in personal diagnostics. Such devices can be used for many diagnostic purposes

[0005] In order to process and analyse the sample, the devices need to move fluids through the device to perform various functions such as removing the sample from the medium on which it is introduced into the device (such as a swab), rehydrating reagents, mixing the sample with reagents, lysis and separating the sample into wells for separate analysis.

[0006] On smaller scales, analysis devices can use capillary flow to conduct liquids through the device. In other arrangements, diffusion can be used to transport molecules of interest which are suspended in a fluid. However, where larger volumes of fluids are required, for example in order to perform multiple analyses, or because the reactions to perform the analysis require larger volumes, a mechanism for driving fluid through the device is required. Alternatively or additionally, capillary action can have flow rate limitations; for some applications a flow rate which is faster than is enabled by capillary action may be needed to enable desired functional steps such as mixing, splitting and rehydrating reagents.

[0007] Several devices are known which make use of an external driver to cause flow of fluid through the device. This is particularly relevant where liquid is to be moved through a device by mechanisms other than capillary action. Such devices therefore need to be interfaced with a base unit such as a reader or other instrument in order for the analysis to be performed. In one known arrangement a channel is formed in the rigid substrate of the device and covered with an elastomeric membrane. When the device is inserted into a base unit an actuator engages with the membrane, applying pressure to the channel and movement of the actuator is therefore able to drive fluid in the channel, and thus through the device as a whole by volume-based displacement (e.g. peristalsis).

[0008] However, the need for an external driver means that such devices cannot be used remotely from their associated base unit. This means that users either need to have a base unit as well as the disposable device, or they need to take their device and sample to a central location in order for the analysis to be completed.

[0009] It is an aim of the present invention to overcome one or more of these limitations.

[0010] It is an aim of the present invention to provide an analysis device which is self-contained such that it does not need to interact with another device or base unit in order to complete the analysis.

[0011] At their broadest, aspects of the present invention provide analysis devices which have a drive mechanism which is configured to drive fluid through the analysis device.

[0012] A first aspect of the present invention provides an analysis device, the device comprising: a sample reception zone; a fluid storage in fluid communication with the sample reception zone; an analysis zone in fluid communication with the sample reception zone; and a drive arrangement which, when activated, is configured to drive fluid stored in the fluid storage so that it passes through the sample reception zone to the analysis zone.

[0013] Preferably the provision of the drive arrangement means that the analysis device is operable to analyse a sample provided in the sample reception zone without input from an external device.

[0014] The analysis device may be self-contained and can thus be used in locations which are remote from healthcare settings. This can allow for rapid testing to be performed at the location where the sample is obtained, without any need to transport or maintain the viability of the sample.

[0015] The devices also may not require complex and / or expensive cooperating equipment such as base units, readers or other instruments to operate and perform the analysis. The analysis device may further comprise one or more control elements which are configured to control the flow of fluid through the device.

[0016] For example, in certain embodiments, the device may include a control element between the fluid storage and the sample reception zone, the control element being configured to prevent flow of fluid from the fluid storage to the sample reception zone until activated.

[0017] Alternatively or additionally one or more control elements may be arranged between the sample reception zone and the analysis zone.

[0018] In certain embodiments the control elements are seals which can be ruptured when it is desired to permit fluid flow. For example, a seal formed of a meltable plastic layer or a heat-shrinking plastic layer may be used as the control element.

[0019] In other embodiments one or more of the control elements may include a microfluidic control gate.

[0020] The drive arrangement may be configured to be activated by insertion of a sample into the sample reception zone. This may result from detecting the presence of a sample in the sample reception zone, for example by the breaking of a light beam by the sample, or by a contact switch. In certain configurations the drive arrangement may be configured to only be activated when a sample has been inserted into the sample reception zone and the opening through which the sample is inserted has been fully closed or sealed.

[0021] In certain embodiments the drive arrangement uses the motion of the insertion of the sample into the sample reception zone to drive the fluid. In these embodiments the device may be configured to store pressure arising from the motion and to use that pressure to drive the fluid.

[0022] For example, the device may further include a sample carrier which is configured to be inserted into the sample reception zone, wherein the analysis device has an opening into which the sample carrier can be introduced and wherein the sample carrier has a seal which is configured to engage with the opening such that insertion of the sample carrier into the analysis device causes a displacement of gas from the sample reception zone, the displacement of gas driving fluid from the fluid storage to the sample reception zone. The device may further include a gas storage chamber, wherein the displacement of gas causes gas to move into the gas storage chamber, thereby increasing the pressure in the gas storage chamber, wherein the pressure in the gas storage chamber is used to drive fluid from the fluid storage to the sample reception zone.

[0023] In certain embodiments the drive arrangement includes an energy storage element which stores energy and, when the drive arrangement is activated, releases said energy so as to drive fluid stored in the fluid storage to the sample reception zone.

[0024] For example the energy storage element may be a pre-compressed or pre-tensioned elastic element such as a spring. The elastic element may be used to drive a plunger or other mechanical element so as to either directly drive fluid through the device, or to generate pressure which is used to drive fluid.

[0025] In certain embodiments the drive arrangement includes a reactive element and activation of the drive arrangement causes the reactive element to react so as to generate a gas, wherein the generated gas drives fluid stored in the fluid storage to the sample reception zone. For example generated gas may produce an over-pressure in part of the device which can be used to drive the fluid.

[0026] The drive arrangement may further include a stored reactive fluid and wherein activation of the drive arrangement causes the stored reactive fluid to contact the reactive element and thereby cause a reaction between the reactive fluid and the reactive element to generate the gas. For example, an acid and a carbonate may be used to generate carbon dioxide. The volume of gas generated is typically greater than the volume of the reactive fluid and the reactive element and therefore can produce an over-pressure in part of the device.

[0027] In certain embodiments the drive arrangement includes a storage chamber and a heater which is configured to heat a stored fluid in said storage chamber so as to increase pressure within the storage chamber, wherein the increased pressure is used to drive fluid stored in the fluid storage through the device. For example, a liquid stored in the storage chamber may be heated so that it vaporises, forming a gas, which leads to increased pressure in the storage chamber. Alternatively, a gas in the storage chamber may be heated, increasing the pressure. The device may further include a manual activation element which allows a user to activate the drive arrangement by moving the manual activation element. This can allow a user to initiate the operation of the device after inserting a sample, for example by pulling on a tag or ring- pull.

[0028] In certain embodiments the sample reception zone has an opening into which the sample can be introduced and the device can be configured to seal the opening when a sample is introduced. The sealing may, for example, be by way of a cap or bung, or may be through interaction of a specifically-configured sample collection device, such as a swab, with the opening so as to seal the swab to the device. Such an interaction may take the form of one or more sealing elements, such as O-rings, or a screw thread in the opening which engages with a corresponding thread on the sample collection device. In certain embodiments a Luer lock or a Luer taper connection may be used to seal the opening.

[0029] The device may alternatively or additionally have a cover or seal for sealing the opening prior to use of the device. This can prevent contaminants from entering the sample reception zone prior to use of the device. In certain embodiments where the device has a sample collection device which is configured to interact with the opening, this may provide this seal.

[0030] The analysis chambers preferably contain all the necessary elements to perform the desired analysis of the sample. This may include one or more reagents (which may be, for example, in dried form and activated when fluid containing the sample enters the analysis chamber), a heater, one or more electrodes, etc..

[0031] In embodiments of the invention, one or more of the assays in the analysis chambers may be configured to detect the presence or absence of one or more respiratory viral infections, including influenza A, influenza B, respiratory syncytial virus (RSV), or COVID-19. The assays could also be configured to detect sexual health infections, including HIV, chlamydia, and / or gonorrhoea. The device may also be configured to detect the presence or absence of hospital acquired infections, such as methicillin resistant S. Aureus (MRSA), C. Difficile, etc.. It will be appreciated that these are merely examples of the uses to which the device can be put and that embodiments of the invention cover devices irrespective of the purpose and function of the analysis chambers. In certain embodiments the analysis zone further comprises a plurality of analysis chambers. The plurality of analysis chambers may be configured to analyse the sample in different ways and / or for the presence of different analytes. The plurality of analysis chambers may also include a control chamber which can be used to confirm the correct operation of the device.

[0032] The plurality of analysis chambers may be arranged in parallel. Arrangement of the analysis chambers in parallel can cause equal distribution of a sample between the analysis chambers as fluid arriving from the sample reception zone can be distributed equally between the analysis chambers.

[0033] Preferably the device is configured to divide sample contained in fluid arriving in the analysis zone equally (or approximately equally) between the plurality of analysis chambers.

[0034] Equal sample distribution is important for the tests performed in different analysis chambers to achieve consistent sensitivity; if the sample is distributed unequally, there is an increased risk of false negatives.

[0035] Preferably the device is configured to fill the plurality of analysis chambers in parallel (or simultaneously) when fluid arrives from the sample reception zone.

[0036] Preferably the device is configured to split fluid arriving from the sample reception zone equally (or approximately equally) between the plurality of analysis chambers.

[0037] In certain embodiments the geometry of the analysis chambers and / or of fluid passages leading to the analysis chambers is configured to cause equal split of fluid arriving from the sample reception zone between the plurality of analysis chambers. For example, the analysis chambers may be substantially identical in volume and configuration.

[0038] Preferably the device is also configured to cause mixing of the fluid (e.g. chaotic mixing) as it passes between the sample reception zone and the analysis zone. This may be achieved by the configuration of the flow path between the sample reception zone and the analysis zone.

[0039] Mixing of the fluid can help to ensure that the distribution of sample eluted from the sample reception zone is homogenous (or at least more homogenous) throughout the fluid. This can help to ensure equal (or approximately equal) distribution of the sample between different analysis chambers as an equal distribution of a fluid with the sample well-mixed can be considered to result in equal distribution of the sample.

[0040] Often, neither mixing nor equal splitting of the fluid is completely effective in ensuring a homogenous sample distribution between analysis chambers. However, a combination of mixing and equal splitting has been found by the inventors to measurably improve the desired outcome of evenly distributing the sample between the analysis chambers.

[0041] Each of the plurality of analysis chambers may include a vent which permits gas in the analysis device to exit the device as fluid is driven through the analysis device from the fluid storage. This can allow gas present in the analysis chambers to exit the chamber when fluid arrives from the fluid storage. This can prevent the build-up of back pressure which could otherwise resist the driving of fluid through the analysis device.

[0042] In certain embodiments the vents are configured to provide equal resistances to the exiting of gas such that liquid arriving from the sample reception zone divides equally between the plurality of analysis chambers. This can help to cause the equal splitting and division of fluid between the analysis chambers in parallel.

[0043] The vents may have a gas-permeable membrane through which the gas can exit the analysis device whilst liquid is retained in the device. This can ensure that all liquids containing the sample and reagents are retained within the device and therefore the risk of any contaminants being released from the device into the surrounding atmosphere is reduced or eliminated. The membrane may also be hydrophobic so as to reduce or eliminate the possibility of liquid exiting the analysis device through the membrane.

[0044] The membrane may also be configured to filter gas which exits therethrough. The filter may help to remove contaminants or reaction products and retain these within the device such that the risk of any contaminants being released from the device into the surrounding atmosphere is reduced or eliminated.

[0045] In certain embodiments the device is configured to prevent liquid from exiting the analysis chambers after it has entered one of the analysis chambers. This can help to prevent crosscontamination between the analysis chambers and the reagents present therein. In certain embodiments the analysis device is configured to process the analysis of a sample following insertion of a sample into the sample reception zone without user intervention.

[0046] Thus, the device can be effectively self-contained in performing all of the physical and chemical processes required for completing the analysis once the user has provided the sample.

[0047] The device may contain a processor, for example an ASIC, which is configured to control the operation of one or more electrical or electronic components in the device. The electrical or electronic components may include a battery, one or more fluid flow control elements, one or more heaters, one or more analysis components.

[0048] The device of the above aspect may include some, all or none of the above-described optional and preferred features in any combination.

[0049] Unless indicated otherwise, any of the features (including the optional or preferred features) described in relation to one of the above aspects are equally applicable in combination with the devices, systems and methods of any of the other above-described aspects.

[0050] Embodiments of the invention are described below, by way of example, with reference to the accompanying figures in which:

[0051] Figures la and lb show, respectively, top and bottom views of an analysis device according to an embodiment of the present invention;

[0052] Figures 2a and 2b show, respectively, the insertion of a sample collection device into an analysis device according to an embodiment of the present invention and the sample collection device itself;

[0053] Figure 3 shows a close-up view of the analysis section of an analysis device according to an embodiment of the present invention;

[0054] Figures 4a and 4b show views of a portion of a mechanism for causing a fluid to be driven through an analysis device according to an embodiment of the present invention; Figure 5 shows a driving mechanism forming part of an analysis device according to an embodiment of the present invention;

[0055] Figure 6 shows a driving mechanism forming part of an analysis device according to an embodiment of the present invention;

[0056] Figure 7 shows a valve and pressure storage forming part of an analysis device according to an embodiment of the present invention;

[0057] Figures 8a and 8b show a driving mechanism forming part of an analysis device according to an embodiment of the present invention; and

[0058] Figure 9 shows an arrangement for sensing the presence of a sample collection device in an analysis device according to an embodiment of the present invention.

[0059] Embodiments of the present invention will be set out below. First a general description of an embodiment of an analysis device will be provided. Then variations to certain components in the device will be described. Unless otherwise indicated, these variations can be combined with the other features of the device, and with variations of other components in any combination.

[0060] Figure 1 shows, in outline, an analysis device 10 according to an embodiment of the present invention. Figure la shows one side of the device 10 and Figure lb shows the opposite side of the device 10. The device 10 is formed of a substantially planar substrate 100 in which a plurality of fluidic channels 110 are formed, along with further components as discussed below. The substrate is typically a rigid plastics material. The substrate 100 and fluidic channels 110 may be formed by any known methods of manufacture such as thermoforming or injection moulding. As shown in Figures la and lb, the fluidic channels 110 may be formed on both sides of the substrate 100 and may alternate between sides. Such alternation may be provided in order to induce chaotic flow and thus enhance the mixing of fluids passing through the channels 110.

[0061] The device 10 has a fluid storage 120 which contains a fluid (a liquid in this embodiment) which is used during the analysis. This liquid may be, for example, a lysis buffer and / or may contain reagents which are used in the analysis performed on the device. The fluid storage 120 has an exit port 122 through which liquid can exit the fluid storage for passage through the fluidic channels to other parts of the device 10. The fluid storage 120 will generally be described as being at the “upstream” end of the device and portions of the fluidics on the device which are further from the fluid storage will be referred to as being “downstream”.

[0062] The exit port 122, or the fluidic channel downstream of the exit port 122, is preferably sealed to prevent liquid from leaving the fluid storage until the device 10 is used. The sealing of exit port 122 may be by way of a seal 123, such as a membrane, across the port, or across the fluidic channel, which is configured to be ruptured on activation of the device.

[0063] In certain embodiments the seal has a resistive wire passing through it such that passing a current through the resistive wire causes the seal to melt and allow liquid to flow through the exit port 122. In other embodiments a surface mount resistor may be placed below a seal, which when a voltage is passed therethrough generates sufficient heat to melt the material from which the seal is formed. Examples of the material for the seal include HPB900, EVA or polystyrene, which when heated tend to melt and subsequently contract in response to application of heat, producing a hole through which the liquid can flow. Flow of the liquid may be caused by a force being exerted upstream of the seal, and / or pressure differential being present across the port.

[0064] Other seals or “gates” may be provided to control the flow of liquid through the device 10 and / or to cause liquid to remain in certain portions of the device for periods of time, or whilst another action, such as mixing or heating, is performed on liquid upstream of the gate. These gates may have similar configurations to the seal of the exit port 122 described above.

[0065] The device 10 may be configured to control the flow of liquid through the device by controlling the timing of the breaking of these gates. This can allow the device to control the length of time that liquid spends in a particular portion of the device which may be important, for example, to control elution and / or mixing of the sample with the working liquid, or to control the flow of liquid into analysis chambers.

[0066] The activation of the liquid flow may be performed by a microprocessor, such as an ASIC, or by circuitry which is designed to activate certain components after certain predetermined periods of time have elapsed since an earlier event or trigger (such as the insertion of a sample into the device).

[0067] In the device 10 shown in Figure 1, downstream of the exit port 122 of the fluid storage 120 is a sample reception zone 130. The sample reception zone 130 is configured to receive the sample from the user.

[0068] In the embodiment shown in Figure 1 the sample reception zone 130 is configured to receive a sample collection device 133, such as that shown in Figure 2, which a user has used to obtain a sample through an opening 138. Figure 2a shows the device 10 with the sample collection device 133 inserted. Figure 2b shows the sample collection device 133 separate from the device 10.

[0069] The sample collection device 133 has a swab 134 (which may be flocked) and an elongate arm 132. The arm 132 has one or more sealing elements, such as O-ring 139, which engage with the opening 138 of the sample reception zone in order to create a fluidic seal such that neither liquid or gas in the sample reception zone can exit the device 10. The sample collection device 133 may also have a locking mechanism to secure it into the opening 138, such as a screw thread or a twist-lock mechanism.

[0070] The sample reception zone 130 has an exit port 131 which allows fluid to pass from the sample reception zone to the downstream elements of the device. The exit port 131 may have a seal or gate which may be configured as described above for the seal of the exit port 122 of the fluid storage 120.

[0071] From the exit port 131, liquid passes through an elongate and convoluted channel 140 which is designed to facilitate enhanced mixing of the liquid both longitudinally (along the liquid column) and latitudinally (across the width of the channel) and the sample which has been eluted in the liquid from the contact of liquid with the sample in the sample reception zone.

[0072] The convoluted channel 140 terminates in an intermediate reservoir 142 which has a sealed exit port 144. An air vent 143 is provided within intermediate reservoir 142 to ensure the chamber completely fills with liquid before onward flow through the device. The intermediate reservoir 142 allows collection of the liquid that has liberated and suspended sample from sampling device 133 and which has passed through the device prior to passing to the subsequent analysis section of the device.

[0073] From the intermediate reservoir 142, liquid passes to the analysis section 150. This section contains a distribution hub 152 which is connected to each of a plurality of analysis chambers 160a-160d, a flow-dependent temporary air spring 156 with an air vent 157 at its downstream end (also referred to as an overflow). An optional permanent air spring 154 is also depicted in Fig. la, which when present serves to maintain a backpressure on distribution hub 152. However, the permanent air spring 154 is not a requirement for normal operation of the device. Figure 3 is an expanded view of the analysis section 150 with the components illustrated in Figures 1 and 2 given the same references.

[0074] The analysis chambers 160a-160d are configured so that they have comparable volumes (ideally identical, or as close to identical as possible within manufacturing tolerances) and comparable dimensions (again, ideally identical, or as close to identical as possible within manufacturing tolerances) of entry channels. This, along with the flow rate of liquid at the distribution hub, and the flow-dependent air spring that vents to atmosphere, helps to ensure that liquid entering the distribution hub 152 is equally distributed between the analysis chambers in parallel.

[0075] The analysis chambers 160a-160d in this embodiment each have a narrow entrance passage 162 connected to the distribution hub 152 and an analysis well 164. An air vent 166 is connected to the analysis well 164 at a position distal from the entrance passage 162. The air vent 166 allows air in the analysis chamber to be displaced to the exterior of the device 10 as liquid from the upstream components fills the analysis chamber.

[0076] The air vents 166 are formed with a hydrophobic gas-permeable membrane. The air vent 157 on the temporary air spring 156 also has a hydrophobic gas-permeable membrane. These membranes allow gas initially present in the analysis well 164 or temporary air spring 156 (and in the remainder of the fluidic channels) prior to activation of the device to be expelled from the device by the movement of liquid through the device, whilst all liquids and particulates are retained in the device. Thus, the gas exiting the membrane is effectively free of any airborne products as a result of the analysis that could contaminate the user environment, and compromise the performance of future tests. The membranes may be configured to embody a flow dependent air spring that vents to atmosphere. This leads to a back pressure that is generated in the analysis chambers 160 as liquid displaces air out of the channels and analysis chambers which at least partially resists the entry into the analysis chambers of liquid from the distribution hub 152. This back pressure increases with the flow rate of liquid, and can help to ensure that there is equal partitioning of liquid from the distribution hub 152 into each of the analysis chambers 160. If more liquid from the distribution hub 152 enters one of the analysis chambers 160, then the back pressure in that chamber generated by the membrane will be greater than the back pressure in the other chambers, as the flow rate in this channel is greater than the flow rate in channels with less liquid. Therefore, the flow rate in the fuller analysis chamber will decrease relative to the less full analysis chamber. This will mean that liquid in the distribution hub will more preferentially enter the less full analysis chamber(s) as the back pressure in those chambers will be lower and so there will be less resistance to liquid entering those chambers.

[0077] The respective hydrophobic membranes in the vents 166 of each analysis chambers 160 and the vent 157 of the temporary air spring 156 provide a resistance and thus back pressure until the liquid touches the respective membranes, at which point the pressure drops to zero. The temporary air springs thus generated are physically separate and disconnected and so operate in parallel with each other.

[0078] The vent 157 on the temporary air spring 156 may be configured to generate a back-pressure such that the air spring 156 is less-preferentially filled compared to analysis chambers 160. This can ensure that the analysis chambers 160 are the first to be filled with fluid arriving at the distribution hub 152.

[0079] Overflow section 156 provides a true (or permanent) air spring; the air pocket trapped at the end of this channel will relax only once all of the analysis chambers 160 have filled, thus providing a means of mitigating back-flow out of the filled chambers, by way of the excess portion of liquid that was present within the overflow section 156.

[0080] The membranes may also serve to filter the gases exiting the device such that larger, more complex molecules, including reaction products from the analysis reaction, are retained in the device. This can help to ensure that no contaminants exit the device to the surrounding environment.

[0081] The distribution hub 152 and / or entrance passages 162 and / or analysis chambers 160 may also be configured so as to prevent liquid which has entered one of the analysis chambers 160 from exiting that chamber and re-entering the distribution hub 152. This prevents any mixing of reactants between the analysis chambers, thus preventing the possibility of false results arising from cross-contamination between respective analysis chambers 160.

[0082] This prevention of mixing can be achieved in a number of ways. In certain embodiments valves, such as duck-bill valves, may be provided in the entrance passages 162, or at the join between the entrance passages and either the analysis wells 164 or the distribution hub 152.

[0083] In other embodiments, an expandable filler compound, such as a hydrogel, may be positioned in the entrance passages 162 or at one end of entrance passages. The filler compound is configured to expand on contact with a liquid so as to form a solid barrier across entrance passage 162 once liquid has been in contact with the filler for a pre-determined period of time. Thus, the filler may be configured to seal the entrance passage at a point when the analysis well 164 has filled with liquid.

[0084] In a variation on this embodiment, the analysis section 150 includes an overflow section 156 connected to the distribution hub 152. Excess liquid from the fluid storage / sample chamber which is not required in the analysis chambers 160 flows into the overflow section 156. Alternatively or additionally, the connection between the overflow section 156 and the distribution hub 152 may be initially sealed with a seal or gate, such as those described above, and the device is configured to break the seal after a predetermined time when it is assumed that sufficient liquid will have entered the distribution hub to fill the analysis chambers. This ensures that the drive pressure within the system is reduced to zero once the operation of the device is complete.

[0085] Devices according to embodiments of the present invention have one or more mechanisms which drive fluid flow through the device from the fluid storage to the analysis chambers. In order for the devices to operate without external source of driving force or power, these mechanisms store energy which is used to selectively increase the pressure in one or more portions of the fluid path on the device. The fluid path can be constructed so as to allow the build-up of the pressure in sections of the device, prior to releasing the fluid to flow through subsequent sections of the fluid path. This can be accomplished by gates or seals such as those described in relation to the embodiment above, or by valves or other known fluid flow control mechanisms.

[0086] Several examples of drive mechanism will be set out below. It will be appreciated that any of these examples could be used in a device according to an embodiment of the present invention, including any or all of the optional features of such a device, and that these mechanisms could, if desired, be combined. It will also be appreciated that these examples are not limiting and devices containing other mechanisms are also encompassed by the present invention.

[0087] In the embodiment shown in Figure 1, the drive mechanism 200 takes the form of a spring- loaded plunger 210. The plunger 210 has a seal 211, which contacts with the walls of the fluid storage 120. A compression spring 212 urges the plunger towards the exit port 122. However, in the stored position, the plunger is held in place by a locking mechanism 213. On actuation of the drive mechanism 200 which, in the embodiment shown in Figure 1 is achieved by pulling on ring-pull 214, the locking mechanism 213 is released and the spring 212 urges the plunger 210 towards the exit port 122, which compresses the liquid in the fluid storage 120. The spring 212 can be chosen such that the compression achieved is sufficient to drive fluid form the fluid storage 120 through the remainder of the device 10. However, in embodiments of the invention, the pressure is retained in the fluid storage 120 until the actual flow of fluid through the remainder of the device can be controlled by the seal on the exit port 122 as described above.

[0088] Figure 4 shows the configuration of the spring 212 and locking mechanism 213 in more detail. Figure 4a shows the spring 212 and locking mechanism 213 together, whilst Figure 4b shows the locking mechanism 213 without the spring. In this embodiment the locking mechanism is connected to a pull bar 214’ which is used to actuate the drive mechanism. The pull bar 214’ is also connected to a cap 215 which is configured to cover and close off the opening 138 to the sample chamber 130 prior to the device being used. This can prevent dirt or other contaminants entering the sample chamber 130 prior to use, as well as preventing the user from prematurely inserting the swab. As shown in Figure 4b, the locking mechanism 213 contains a plurality (in this embodiment, three) of locking pins 216 arranged around a central channel 217. The locking pins are generally hook-shaped, and are connected to the body 218 of the locking mechanism in a pivotable fashion and biased into a retracted configuration as shown in Figure 4b. Insertion of the pin 219 through the central channel 217 urges the locking pins to pivot such that the hooked tip is urged radially outward, beyond the outer circumference of the body 218. With the compressed spring 212 in place, this causes the hooks on the locking pins to prevent expansion of the spring 212 (in the upward direction shown in Figure 4).

[0089] Removal of the pin 219 releases the locking pins 216 which pivot inward to the now unoccupied central channel thus releasing the spring 212 which can drive the plunger 210.

[0090] Another embodiment of the drive mechanism 200 is shown in Figure 5. In this embodiment the drive mechanism 200 is a chemically-based mechanism. In this mechanism, two reactive substances are provided on the device but maintained separately prior to activation of the device. On activation the substances are allowed to combine, or forced into contact, and react. The reaction causes an expansion in a restricted volume, leading to an increase in pressure which is used to drive fluid through the device. For example, the reaction may produce a gas, such as carbon dioxide, from a combination of two liquids, or a solid and a liquid. The gas produced naturally occupies a much larger volume than the reactants and therefore causes an increase in pressure.

[0091] In particular embodiments the reaction involves the combination of a solid carbonate, such as sodium bicarbonate, with an acid, such as acetic acid; or other similar effervescent reaction between a liquid and a solid. This reaction produces carbon dioxide. The reagents needed to produce this reaction are inexpensive, commonly available and very stable.

[0092] An embodiment of such a drive mechanism 200 is shown in Figure 5. In this embodiment there are two containers 230, 231 which are joined by a passage 235 formed in the substrate of the device.

[0093] The first container 230 holds a liquid 232. The first container 230 has a rigid outer wall and a flexible inner wall, which may be formed from an elastomeric material. When first container 230 is filled with a liquid (e.g. an acid) 232, the inner wall of the container 230 is in tension. A membrane 233 seals the liquid 232 into the container 230. The membrane may be as described above in relation to the gates used elsewhere in embodiments of the device to control fluid flow. Breaking the membrane 233 (for example by passing current through a resistive heating element in contact with the membrane 233) releases the liquid 232 which flows along passage 235 towards the second container 231, as shown by the arrows in Figure 5. Where the elastomeric inner wall is in tension, this further urges the liquid out of the container 230 and along passage 235.

[0094] The second container 231 holds the working fluid 236 for the device, such as a lysis buffer. A gas-permeable hydrophobic membrane 234 is arranged at the entrance from the passage 235 to the second container 231.

[0095] Close to the entrance to the second container 231, a quantity of solid reactant (e.g. a carbonate) 231 is positioned, for example in an aperture formed in the lower portion of the substrate below the membrane 234 so as to provide a small well below the entrance to the second container. The reaction between the liquid 232 and the carbonate produces carbon dioxide which passes through the membrane 234 and collects in a gas bubble 237 above the liquid 236 in the second container 231. In certain embodiments, heat from a resistive heating element can be used to accelerate this reaction.

[0096] The membrane 234 allows the gas from the reaction to pass through and into the second container 231, but prevents the working fluid 236 from exiting the second container 231 and any liquid 232 from the first container entering the second container 231 and mixing with the working fluid 236.

[0097] The carbon dioxide formed from the reaction between the liquid and the carbonate would naturally occupy a larger volume than the reactants that produced it and so results in increased pressure in container 231.

[0098] When the pressure of the gas in the bubble 237 (and within the second container 231) reaches a desired level, a meltable membrane 238, for example as described above in relation to the gates used elsewhere in embodiments of the device to control fluid flow, is broken, for example by heating by a resistor 239 positioned below the membrane 238 and in contact with the lower side of the membrane. This allows the pressure of the gas in the bubble 237 to drive the working fluid 236 through the melted membrane and onwards through the device through channel 233.

[0099] Another embodiment of a drive mechanism 200 is shown in Figure 6. The drive mechanism 200 has a container 220 which contains a volume of liquid working fluid (such as a lysis buffer) 222. A membrane 226 seals the exit from the container 220. The membrane 226 is meltable, for example as described above in relation to the gates used elsewhere in embodiments of the device to control fluid flow. A resistor 228 is positioned below the membrane 226 and in contact with the lower side of the membrane.

[0100] On activation of the device, a current is passed through the resistor 228, causing it to heat the membrane 226 which ruptures. This allows working fluid 222 from the container 220 to contact the hot resistor 228 which vaporises some of the working fluid. The gaseous form of the working fluid permeates back through the liquid layer of working fluid 222 and builds up in a gas bubble 225 at the top of the container 220. This gas forces more working fluid 222 to contact the resistor 228, thus continuing the vaporisation process. The presence of the gas 225 in the container 220 increases the pressure in the container, thus generating a force which can be used to drive fluid around the device. Other membranes or gates, such as described elsewhere, may be used to control the flow of the working fluid 222 and / or to retain the working fluid 222 in the container 220 until a desired pressure has accumulated.

[0101] Figure 7 shows an arrangement of a one-way valve which may be used to store pressurised gas in the device prior to its use to drive working fluid through the device. The configuration of the valve is similar to the containers described above and illustrated in Figures 5 and 6.

[0102] The valve 240 has a container 242 which holds a working fluid 244 which is to be used in the analysis device (e.g. a lysis buffer). A gas-permeable hydrophobic membrane 243 is arranged at the entrance from a passage 241 from the drive mechanism which generates pressurised gas (such as one of the drive mechanisms described above). The gas-permeable hydrophobic membrane 243 allows the pressurised gas to pass through into the container 242, but prevents the working fluid 244 from exiting the container 242. The gas builds up as a bubble 245 above the working fluid 244. The pressurised gas from the drive mechanism is stored in the bubble 245. When the gas in the bubble reaches a desired pressure (which may be measured, or may be predicted in advance as being a certain time period after the drive mechanism is activated), a meltable membrane 246, for example as described above in relation to the gates used elsewhere in embodiments of the device to control fluid flow, is broken, for example by heating by a resistor 247 positioned below the membrane 246 and in contact with the lower side of the membrane. This allows the pressure of the gas in the bubble 245 to drive the working fluid 244 through the melted membrane and onwards through fluidic channel 248 to the other parts of the device.

[0103] Another embodiment of the drive mechanism 200 is shown in Figure 8. In this embodiment the drive mechanism uses energy from the action of the user in inserting the sample collection device 133 into the sample chamber 130. Figure 8a shows the sample collection device 133 starting to be inserted and Figure 8b shows the sample collection device when fully inserted.

[0104] In addition to the swab 134 which contains the sample to be tested, the sample collection device 133 has three elongate sections, being a distal section 135 a middle section 136 and a proximal section 137. These sections are substantially cylindrical elements of differing cross-section. In the embodiment shown in Figure 8, the sections are substantially cylindrical, but could be other shapes. The cross-sections of the sections 135, 136, 137 narrows from the proximal section 137 to the distal section 135. These changes in cross-section can involve tapered or non-tapered changes. Some of the changes in cross-section are substantially identical to changes in the cross-section of the sample chamber 130, as shown in Figure 8b where the sample collection device 133 is fully inserted into the sample chamber 130, leaving a small gap between the proximal section 137 and the middle section 136 and their respective portions of the sample chamber 130.

[0105] Two O-ring seals 252, 253 are located at the points at which the cross-sections of the sample collection device 133 change. These seals engage with the internal walls of the sample chamber 130 as the user inserts the sample collection device 133. As shown in Figure 8a, when the sample collection device 133 is inserted, the seals 252, 253 engage with the internal walls of the sample chamber at the same point. This traps a fixed volume of air 255 between the seals 252, 253. Further insertion of the sample collection device 133 into the sample chamber reduces this volume, as shown in Figure 8b. The trapped air 255 is forced out of the sample chamber through port 254 and the pressure generated by this motion can be used to drive the flow of fluid through the device.

[0106] As shown in Figure 8b, the swab 134 remains in a reduced portion of the sample chamber 130 which remains around the distal section 135 of the sample collection device 133. Fluid from the fluid storage chamber can pass around the swab 134 in this portion of the chamber and exit to the remainder of the device through exit port 131.

[0107] Figure 9 shows an arrangement which may be used to detect the insertion of the sample collection device into the sample chamber 130. Figure 9 shows a portion of a device 1 such as that shown in Figures 1 and 2 with salient components given the same references.

[0108] A light-emitting diode (LED) 170 is arranged adjacent to the sample chamber 130. The LED 170 is configured to shine through a portion of the sample chamber 130, distal from the opening 138, towards a photo-diode 171. Complete insertion of a sample collection device into the sample chamber breaks the beam between the LED 170 and the photo-diode 171. The breaking of this beam can be used to actuate other components in the device 1, such as a drive mechanism 200 and / or gates which prevent / permit fluid flow through portions of the device. The actuation of the device may be performed by a microprocessor, for example an ASIC, which controls the actuation of components such as the drive mechanism and / or gates. The actuation of the components may be arranged to be performed in a pre-determined sequence or at predetermined time intervals after the insertion of the sample collection device, in order to control the fluid flow through the device and / or mixing of the fluid with the sample.

[0109] In other embodiments, alternative approaches may be used to detect insertion of a sample collection device into the sample chamber, for example using a contact switch arranged at or near the opening 138 which is closed by the action of inserting the sample collection device into the sample chamber 130.

[0110] The above configurations ensure that actuation of the device only occurs once a sample collection device has been properly inserted into the sample chamber and therefore the device is ready for actuation. However, in further embodiments, the actuation of the device may be triggered by alternative approaches. For example, where the actuation of the drive mechanism 200 arises from user interaction (for example by the pulling of the pull ring 214 in the embodiment shown in Figures 1 and 2), this actuation may be detected and used to initiate and / or control other parts of the actuation and / or operation of the device. In yet further embodiments, the actuation of the device may be triggered by a specific user interaction, such as the pressing of a button which closes a switch or other electrical contact.

[0111] The forgoing description is exemplary in nature only, and the skilled person will understand that changes and variations on the disclosed embodiments are possible within the scope of the claims. The claims define the invention.

Claims

CLAIMS1. An analysis device, the device comprising: a sample reception zone; a fluid storage in fluid communication with the sample reception zone; an analysis zone in fluid communication with the sample reception zone; and a drive arrangement which, when activated, is configured to drive fluid stored in the fluid storage so that it passes through the sample reception zone to the analysis zone.

2. The analysis device of claim 1 further comprising a control element between the fluid storage and the sample reception zone, the control element being configured to prevent flow of fluid from the fluid storage to the sample reception zone until activated.

3. The analysis device of claim 1 or claim 2 wherein the drive arrangement is configured to be activated by insertion of a sample into the sample reception zone.

4. The analysis device of claim 3 wherein the drive arrangement uses the motion of the insertion of the sample into the sample reception zone to drive the fluid.

5. The analysis device of claim 4 further including a sample carrier which is configured to be inserted into the sample reception zone, wherein the analysis device has an opening into which the sample carrier can be introduced and wherein the sample carrier has a seal which is configured to engage with the opening such that insertion of the sample carrier into the analysis device causes a displacement of gas from the sample reception zone, the displacement of gas driving fluid from the fluid storage to the sample reception zone.

6. The analysis device of claim 5 further including a gas storage chamber, wherein the displacement of gas causes gas to move into the gas storage chamber, thereby increasing the pressure in the gas storage chamber, wherein the pressure in the gas storage chamber is used to drive fluid from the fluid storage to the sample reception zone.

7. The analysis device of any one of the preceding claims wherein the drive arrangement includes an energy storage element which stores energy and, when the drivearrangement is activated, releases said energy so as to drive fluid stored in the fluid storage to the sample reception zone.

8. The analysis device of claim 7 wherein the energy storage element is a pre-compressed or pre-tensioned elastic element.

9. The analysis device of any one of the preceding claims wherein the drive arrangement includes a reactive element and activation of the drive arrangement causes the reactive element to react so as to generate a gas, wherein the generated gas drives fluid stored in the fluid storage to the sample reception zone.

10. The analysis device of claim 9 wherein the drive arrangement further includes a stored reactive fluid and wherein activation of the drive arrangement causes the stored reactive fluid to contact the reactive element and thereby cause a reaction between the reactive fluid and the reactive element to generate the gas.

11. The analysis device of any one of the preceding claims wherein the drive arrangement includes a storage chamber and a heater which is configured to heat a stored fluid in said storage chamber so as to increase pressure within the storage chamber, wherein the increased pressure is used to drive fluid stored in the fluid storage through the device.

12. The analysis device of any one of the preceding claims further including a manual activation element which allows a user to activate the drive arrangement by moving the manual activation element.

13. The analysis device of any one of the preceding claims wherein the sample reception zone has an opening into which the sample can be introduced and is configured to seal the opening when a sample is introduced.

14. The analysis device of any one of the preceding claims further including a fluid pathway between the sample collection zone and the analysis zone, wherein the fluid pathway is configured to mix sample contained in fluid passing through the fluid pathway with the fluid.

15. The analysis device of any one of the preceding claims wherein the analysis zone further comprises a plurality of analysis chambers.

16. The analysis device of claim 15 wherein the plurality of analysis chambers are arranged in parallel.

17. The analysis device of claim 16 wherein the device is configured to divide sample contained in fluid arriving in the analysis zone equally between the plurality of analysis chambers.

18. The analysis device of claim 17 wherein the device is configured to split fluid arriving from the sample reception zone equally between the plurality of analysis chambers.

19. The analysis device of claim 18 wherein the geometry of the analysis chambers and / or of fluid passages leading to the analysis chambers is configured to cause equal split of fluid arriving from the sample reception zone between the plurality of analysis chambers.

20. The analysis device of any one of claims 15-19 wherein each of the plurality of analysis chambers includes a vent which permits gas in the analysis device to exit the device as fluid is driven through the analysis device from the fluid storage.

21. The analysis device of claim 20 wherein the vents are configured to provide equal resistances to the exiting of gas such that liquid arriving from the sample reception zone divides equally between the plurality of analysis chambers.

22. The analysis device of claim 20 or claim 21 wherein the vents have a gas-permeable membrane through which the gas can exit the analysis device whilst liquid is retained in the device.

23. The analysis device of claim 22 wherein the membrane is configured to filter gas which exits therethrough.

24. The analysis device of any one of claims 15-23 wherein the device is configured to prevent liquid from exiting the analysis chambers after it has entered one of the analysis chambers.

5. The analysis device of any preceding claim wherein the device is configured to process the analysis of a sample following insertion of a sample into the sample reception zone without user intervention.

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