Liquid collection device and liquid handling device configured to receive a liquid collection device

Abstract

The present disclosure relates to a liquid collection device, comprising: a capillary collector comprising a capillary tube defining a lumen for collecting liquid by capillary action; and a cap coupled to the capillary collector, wherein the cap is configured to permanently vent the lumen of the capillary tube, and wherein the cap comprises a protrusion extending into the lumen such that when the lumen is filled with liquid, a portion of the liquid is retained between the protrusion and the capillary tube.

Description

[0001] LIQUID COLLECTION DEVICE AND LIQUID HANDLING DEVICE CONFIGURED TO RECEIVE A LIQUID COLLECTION DEVICE

[0002] FIELD

[0003] The present disclosure relates to a liquid collection device and a liquid handling device configured to receive a liquid collection device. In particular, the present disclosure relates to a liquid collection device that is configured to collect a volume of liquid by capillary action.

[0004] BACKGROUND

[0005] Capillary collectors are commonly used for collecting blood or other liquids. For example, a capillary collector may be used for collecting blood from a subject. In their simplest form, capillary collectors are tubes of small lumen cross-section, which define a sample volume. The tubes fill by capillary action when touching a tip of the tube to a surface of a liquid sample such as a droplet of blood. The liquid is drawn into the lumen by capillary action, which is a result of the wetting behaviour of the inner tube surface contacted by the liquid and the lumen geometry and dimensions. Capillary collectors are typically manufactured in a clear material such that the user can observe the filling process. The capillary tubes can also be coated with an anticoagulant on the lumen surface, which hydrates and mixes with the liquid upon liquid filling, and prevents clotting. In recent years, capillary collectors for finger-prick blood samples have become of increasing interest with the rapid growth of point of care diagnostics for near patient testing and self-testing. Advances in microfluidic technology and analytics also allow the use of much smaller sample volumes, rendering capillary sample collection suitable for a wide range of diagnostic applications.

[0006] Where one or more diagnostic tests are to be carried out on the collected liquid, the liquid must be transferred from the capillary collector to a liquid handling device (such as a diagnostic cartridge). Existing solutions for transferring liquid out of a capillary collector are usually dependent on user actions to transfer the liquid from the liquid collection device to the liquid handling device. Handling of small liquid volumes using existing liquid collection devices requires users to have fine motor skills and to be specifically trained in the use of such devices. Therefore, there is an opportunity to simplify the collection and transfer of small sample volumes (in particular, finger-prick blood collection), in order to improve user experience.

[0007] Handling of small volumes of liquid usually requires microfluidic devices, which are highly sensitive to trapped air bubbles and require precise control over the liquid transfer flow rate. Transfer of small volumes of liquid by a user action is likely to introduce air bubbles into the liquid, as there is limited control over the liquid flow rate.

[0008] For liquid handling devices to be used as diagnostic devices, there is also a need to minimise pre-analytical error by controlling the elapsed time between sample transfer to the diagnostic device and commencement of the diagnostic test. When the transfer of a liquid from a liquid collection device to a liquid handling device is carried out by a user, there is no control over this elapsed time. In particular, for finger-prick blood collection associated with point-of-care diagnostic solutions, there is an additional need to automate the step of transferring liquid from the liquid collection device to the liquid handling device, in order to minimise pre-analytical error by requiring the fewest possible actions from the user.

[0009] In addition, there are challenges in transporting capillary collectors that hold a volume of liquid. In particular, movement of the capillary collector can cause ejection of liquid droplets from the end of the capillary collector. This can result in contamination of equipment or users in the vicinity of the capillary collector, in particular where the collected liquid is a subject’s blood. Contamination of users may result in those users becoming cross-contamination vectors. Accordingly, there exists a need for a liquid collection device that better retains a collected liquid, particularly during movement of the liquid collection device, in order to prevent unintentional loss of the collected liquid from the liquid collection device.

[0010] In summary, therefore, there exists a need for an improved liquid collection device that facilitates easier transfer of liquid from the liquid collection device to a liquid handling device, and / or better retains a collected liquid, particularly during handling of the liquid collection device. In addition, there exists a need for a liquid handling device that interfaces with such an improved liquid collection device. SUMMARY

[0011] This summary introduces concepts that are described in more detail in the detailed description. It should not be used to identify essential features of the claimed subject matter, nor to limit the scope of the claimed subject matter.

[0012] According to a first aspect of the present disclosure, there is provided a liquid collection device, comprising: a capillary collector comprising a capillary tube defining a lumen for collecting liquid by capillary action; and a cap coupled to the capillary collector, wherein the cap is configured to permanently vent the lumen of the capillary tube, and wherein the cap comprises a protrusion extending into the lumen such that when the lumen is filled with liquid, a portion of the liquid is retained between the protrusion and the capillary tube.

[0013] By permanently venting the lumen, a differential pressure can be applied (e.g. via a liquid handling device such as a microfluidic cartridge) to transfer liquid out of the lumen. Specifically, a differential pressure can be applied by providing a first pressure at the end of the capillary collector to which the cap is coupled and providing a second pressure at the other end of the capillary collector, wherein the first pressure is higher than the second pressure. For example, liquid may be aspirated out of the lumen by applying a negative pressure to a tip of the capillary tube, while the other end of the capillary tube is vented via the cap. As an alternative example, liquid may be dispensed out of the lumen by venting the tip of the capillary tube while applying a positive pressure to the other end of the capillary tube via the cap. Accordingly, liquid can be easily transferred out of the liquid collection device without requiring, for example, an action done by the user. This simplifies the process of transferring liquid out of the liquid collection device, thereby improving user experience (e.g. by removing the requirement for fine motor skills and / or specialist training in transferring liquid out of the liquid collection device).

[0014] In addition, allowing for transfer of the liquid out of the liquid collection device using a differential pressure increases control over the liquid transfer flow rate, thereby reducing the likelihood of bubble formation in the liquid flow. Moreover, allowing for transfer of the liquid out of the liquid collection device using a differential pressure means that the step of transferring liquid from the liquid collection device can be automated, thereby reducing the number of user actions needed for transfer of a liquid sample, and consequently reducing the potential for pre-analytical error. The permanent venting of the lumen also allows for the passage of air out of the lumen during filling of the capillary tube.

[0015] The portion of liquid retained between the protrusion and the capillary tube provides a high capillary pressure that simplifies handling of the liquid collection device. Specifically, the high capillary pressure provided by the retained portion of liquid means that the liquid collected in the capillary tube is better retained, thereby reducing the potential for unintentional loss of the collected liquid, and consequently reducing the potential for contamination.

[0016] The protrusion may extend into the lumen to a maximum extent. The lumen may be permanently vented when the cap is coupled to the capillary collector such that the protrusion extends into the lumen to its maximum extent. The maximum extent may be defined by abutment of a component of the cap against a component of the capillary collector.

[0017] The protrusion may be formed of a non-porous material. Forming the protrusion of a nonporous material aids in transfer of liquid from the liquid collection device, for at least two reasons. Firstly, porous materials could absorb the liquid sample and reduce the volume to be extracted. Secondly, extracting liquid from an absorbent material requires a higher differential pressure and can easily result in the formation of bubbles.

[0018] The protrusion may extend into a proximal end of the lumen. The cap may comprise one or more openings configured to permit the passage of air into the proximal end of the lumen.

[0019] The protrusion may contact an internal surface of the capillary tube. Having a protrusion that contacts the internal surface of the capillary tube has three main advantages. Firstly, acute wedge shaped regions result from the contact between the protrusion and the internal surface of the capillary tube (particularly, but not exclusively, where the curvature of the protrusion differs from the curvature of the internal surface of the capillary tube at the point of contact between the protrusion and the internal surface of the capillary tube). These wedge shaped regions increase the capillary pressure resulting from the retained portion of liquid, in view of the second dimension of meniscus curvature resulting from the wedge shaped regions at the point of contact between the protrusion and the internal surface of the capillary tube. This higher capillary pressure means that the liquid collection device can retain higher volumes of liquid under more aggressive handling conditions. Secondly, when manufacturing, achieving small gaps reproducibly requires very tight control of each component’s manufacturing tolerances, plus their assembly tolerances. Contacting features are valuable design aids to ensure correct assembly between parts. Thirdly, the wedge shaped regions serve to ‘pin’ the retained liquid. The liquid that is present in the acute wedge shaped regions will typically be retained to some degree during extraction of liquid from the capillary tube. Once the liquid has been extracted from the capillary tube, the liquid in the wedge shaped regions rearranges itself (i.e. equilibrates) so as to minimise the additional surface energy generated when extracting liquid from the capillary tube. The retained liquid in the wedge shaped regions can provide a visual indication to the user that the liquid collection device has already been used and should not be reused. The retained liquid may also act as a liquid plug that reduces the effectiveness of future attempts to fill the capillary tube.

[0020] The cap may be configured to provide a capillary stop for the portion of the liquid retained between the protrusion and the capillary tube. The capillary stop provided by the cap prevents the escape of collected liquid from the capillary collector, thereby preventing contamination of the surrounding environment.

[0021] The cap may comprise a plurality of ribs coupled to a proximal end of the capillary collector. The one or more openings may be defined at least in part by voids between adjacent ones of the plurality of ribs. The voids between the ribs therefore provide for the permanent venting of the lumen. Each of the plurality of ribs may comprise a distally extending finger that is radially spaced apart from the protrusion to define a gap between the finger and the protrusion. The one or more openings may be defined in part by the gaps between the protrusion and each finger that extends from a respective one of the plurality of ribs. The capillary stop may be defined at least in part by the gaps between the protrusion and each finger that extends from a respective one of the plurality of ribs.

[0022] The protrusion may be configured such that one or more capillary channels are defined between an external surface of the protrusion and the capillary tube. Alternatively, the protrusion may be configured such that one or more capillary channels are defined within the protrusion. The portion of the liquid may be retained in the one or more capillary channels. A maximum width of the one or more capillary channels may be between 20 pm and 300 pm, preferably between 75 pm and 300 pm, more preferably between 75 pm and 250 pm, yet more preferably between 75 pm and 200 pm, and most preferably between 75 pm and 150 pm. These ranges provide, with increasing order of preference, a maximum width sufficient to retain collected liquid within the capillary tube under increasingly aggressive handling conditions, while providing a reasonable fill rate of the capillary channels (i.e. a fill rate that is not overly slow).

[0023] Each of the one or more capillary channels may comprise one or more wedge shaped regions. The one or more wedge shaped regions may be defined by one or more points of contact between the external surface of the protrusion and the capillary tube, and / or by one or more acute grooves on the external surface of the protrusion, and / or by one or more acute corners of one or more capillary channels within the protrusion. The one or more capillary channels may be a plurality of capillary channels. The plurality of capillary channels may be defined by multiple points of contact between the protrusion and the internal surface of the capillary tube. Providing multiple points of contact between the protrusion and the internal surface of the capillary tube results in acute wedge shaped regions at the edges of the capillary channels (i.e. adjacent to the points of contact between the protrusion and the internal surface of the capillary tube). The wedge shaped regions may particularly, but not exclusively, be provided where the curvature of the protrusion differs from the curvature of the internal surface of the capillary tube at the point of contact between the protrusion and the internal surface of the capillary tube. The wedge shaped regions provide a second dimension of curvature of the liquid within the capillary channels, thereby increasing the capillary pressure resulting from retention of liquid in the capillary channels. Therefore, the liquid collection device can retain higher volumes of liquid under more aggressive handling conditions. The wedge shaped regions also retain some liquid after extraction of liquid from the capillary tube, thereby providing a visual indication to the user and potentially providing liquid plugs preventing reuse of the liquid collection device, as explained above.

[0024] The protrusion may extend into the lumen to a distance of at least 0.5 mm. This ensures that the meniscus of the portion of liquid is retained between the protrusion and the capillary tube, thereby ensuring that the capillary pressure is generated by the retained portion of liquid. The liquid collection device may be configured to provide a visual indication to a user once the liquid has been collected. Accordingly, a user is capable of determining when a volume of liquid has been collected. Specifically, the capillary tube may be configured to provide the visual indication to the user once the capillary tube has been wetted with liquid. Alternatively (or additionally), the protrusion may be configured to provide the visual indication to the user once the protrusion has been wetted with liquid. This means that a user is capable of determining when a required volume of liquid has been collected, as the capillary tube will be full when the liquid wets the protrusion. The protrusion may comprise a surface configured to disperse light prior to wetting by a liquid, wherein the surface is configured to not disperse light once wetted by the liquid. The protrusion may comprise a material configured to change colour once wetted with liquid.

[0025] The cap may comprise a flat end surface. This allows the liquid collection device to be stably positioned on a flat surface such as a table. For example, after collecting a volume of blood within the lumen, a user may place the flat end surface of the cap on a table, while they attend to a patient or prepare additional equipment. This prevents contact of a tip of the capillary tube with a surface, thereby preventing contamination of the collected sample and any potential wicking of the sample from the tip (that may occur, for example, if the liquid collection device were placed on its side with the tip in contact with the surface).

[0026] According to a second aspect of the present disclosure, there is provided a liquid handling device configured to receive a liquid collection device, the liquid handling device comprising: a plurality of conduits; and an elastomeric member configured to receive a tip of the liquid collection device, wherein the elastomeric member is configured to provide a fluidic connection between the tip of the liquid collection device and one of the plurality of conduits.

[0027] The elastomeric member provides a compliant material that provides a seal around the tip of the liquid collection device. In addition, the compliant nature of the elastomeric member rubs off any residues of sample outside of the liquid collection device, meaning that these residues do not need to be cleaned off.

[0028] The tip of the liquid collection device may be a tip of a capillary tube of the liquid collection device. The elastomeric member may comprise an opening in fluidic communication with the one of the plurality of conduits. The opening may be configured to provide an interference fit for the tip of the capillary tube of the liquid collection device. An interference fit improves the sealing between the tip of the capillary tube and the elastomeric member.

[0029] The liquid handling device may further comprise a pneumatic port in selective fluidic communication with the one of the plurality of conduits. The pneumatic port allows a negative pressure to be applied, meaning that liquid can be aspirated out of the liquid collection device.

[0030] The plurality of conduits may be defined in part by the elastomeric member. Accordingly, a single compliant layer can provide the sealing around the tip of the liquid collection device and the conduits of the liquid handling device, thereby simplifying construction of the liquid handling device.

[0031] The liquid handling device may further comprise one or more guide ribs configured to guide insertion of the tip of the liquid collection device into the elastomeric member. Guiding insertion of the tip of the liquid collection device simplifies the user experience and reduces potential for error when inserting the liquid collection device into the elastomeric member of the liquid handling device. The one or more guide ribs may comprise: one or more first guide ribs configured to restrict movement of the liquid collection device in a first direction; and one or more second guide ribs configured to restrict movement of the liquid collection device in a second direction different to the first direction.

[0032] The one or more first guide ribs may be spatially separated from the one or more second guide ribs in the direction of insertion of the tip of the liquid collection device into the elastomeric member. Spatially separating the first guide ribs from the second guide ribs in the direction of insertion avoids having a complex rib geometry that could result in the liquid collection device becoming stuck or wedged during insertion. The first direction may be orthogonal to the second direction.

[0033] The one or more first guide ribs may be configured to constrain movement of the liquid collection device within a first plane. The one or more second guide ribs may be configured to constrain movement of the liquid collection device within a second plane different to the first plane. The liquid handling device may be configured to receive the liquid collection device of the first aspect. The liquid handling device may be a microfluidic cartridge.

[0034] According to a third aspect of the present disclosure, there is provided a liquid handling assembly, comprising: a liquid collection device according to the first aspect; and a liquid handling device according to the second aspect.

[0035] The tip of the liquid collection device may be a tip of a capillary tube of the liquid collection device. The elastomeric member of the liquid handling device may comprise an opening in fluidic communication with the one of the plurality of conduits of the liquid handling device. The opening may be configured to provide an interference fit for the tip of the capillary tube of the liquid collection device. An interference fit improves the sealing between the tip of the capillary tube and the elastomeric member.

[0036] The cap of the liquid collection device may be configured to interface with the liquid handling device to provide an audible click when the tip of the liquid collection device is fully inserted into the elastomeric member of the liquid handling device. The audible click informs the user that the liquid collection device is properly inserted into the elastomeric member of the liquid handling device, thereby simplifying user handling of the liquid collection device.

[0037] According to a fourth aspect of the present disclosure, there is provided a method of transferring liquid from a capillary tube of a liquid collection device to a liquid handling device, the method comprising: opening a fluidic path between the capillary tube of the liquid collection device and a pneumatic port of the liquid handling device; applying a negative pressure to the pneumatic port of the liquid handling device, to aspirate liquid from the capillary tube of the liquid collection device into one or more conduits of the fluidic path; and closing the fluidic path between the capillary tube of the liquid collection device and the pneumatic port.

[0038] Aspirating liquid out of the capillary tube of the liquid collection device means that liquid can be easily transferred out of the liquid collection device without requiring, for example, an action done by the user. This simplifies the process of transferring liquid out of the liquid collection device, thereby improving user experience. In addition, aspirating liquid out of the liquid collection device increases control over the liquid transfer flow rate, thereby reducing the likelihood of bubble formation in the liquid flow. Moreover, aspirating liquid out of the liquid collection device means that the step of transferring liquid from the liquid collection device can be automated, thereby reducing the number of user actions needed for transfer of a liquid sample, and consequently reducing the potential for pre-analytical error.

[0039] The liquid collection device may be a liquid collection device according to the first aspect. The liquid handling device may be a liquid handling device according to the second aspect. The method may be carried out by an analyser device in which the liquid handling device is received. The analyser device may comprise at least: one or more actuators configured to actuate one or more valves of the liquid handling device; and one or more pneumatic supply conduits configured to provide a negative pressure to one or more pneumatic ports of the liquid handling device.

[0040] The method may be implemented by one or more processors of the analyser device. In particular, the method may be implemented in the form of instructions stored on a transitory or non-transitory computer-readable medium, wherein the instructions are executable by the one or more processors of the analyser device to cause the analyser device to implement the method.

[0041] The method may further comprise detecting whether the capillary tube of the liquid collection device has been coupled to the liquid handling device. The method may comprise opening the fluidic path between the capillary tube of the liquid collection device and the pneumatic port of the liquid handling device in response to detecting that the capillary tube of the liquid collection device has been coupled to the liquid handling device. This may reduce the potential for errors resulting from an incorrectly inserted or missing liquid collection device.

[0042] Opening the fluidic path may comprise opening one or more valves of the liquid handling device. Closing the fluidic path may comprise closing one or more valves of the liquid handling device. The method may further comprise applying a positive or negative pressure to transfer the aspirated liquid from the one or more conduits to a component of the liquid handling device. The component may be a flow cell and / or a chamber of the liquid handling device.

[0043] According to a fifth aspect of the present disclosure, there is provided a computer- readable medium storing instructions that, when executed by one or more processors of an analyser device comprising one or more actuators and one or more pneumatic supply conduits, cause the analyser device to carry out the method of the fifth aspect. According to a sixth aspect of the present disclosure, there is provided a method of transferring liquid out of a liquid collection device of the first aspect, the method comprising applying a pressure differential between a proximal end of a capillary tube of the liquid collection device and a distal end of the capillary tube of the liquid collection device. Applying the pressure differential may comprise providing a pressure at the distal end of the capillary tube that is lower than a pressure provided at the proximal end of the capillary tube. For example, providing the pressure at the distal end of the capillary tube that is lower than a pressure provided at the proximal end of the capillary tube May comprise applying a pressure at the distal end of the capillary tube that is lower than a pressure at the proximal end of the capillary tube.

[0044] Alternatively, providing the pressure at the distal end of the capillary tube that is lower than a pressure provided at the proximal end of the capillary tube may comprise applying a pressure at the proximal end of the capillary tube that is higher than a pressure at the distal end of the capillary tube.

[0045] BRIEF DESCRIPTION OF FIGURES

[0046] Specific embodiments are described below by way of example only and with reference to the accompanying drawings, in which:

[0047] FIG. 1 shows an isometric view of a liquid handling device and a liquid collection device according to a first example, where the liquid collection device is about to be inserted into the liquid handling device.

[0048] FIG. 2 shows an isometric view of the liquid collection device and the liquid handling device shown in FIG. 1 , once the liquid collection device has been inserted into the liquid handling device.

[0049] FIG. 3 shows an isometric exploded view of the liquid collection device shown in FIG. 1.

[0050] FIG. 4 shows a side view of the liquid collection device shown in FIG. 1.

[0051] FIG. 5 shows a section view through line A-A in FIG. 4. FIG. 6 shows a section view through line B-B in FIG. 4.

[0052] FIG. 7 shows a schematic illustration of a section view of a circular cross-section protrusion concentric within a lumen.

[0053] FIG. 8 shows a schematic section view through line C-C in FIG. 7.

[0054] FIG. 9 shows a schematic section view through line D-D in FIG. 8.

[0055] FIG. 10 shows an exploded isometric view of the liquid handling device shown in FIG. 1 , and the liquid collection device of the first example about to be inserted into the liquid handling device.

[0056] FIG. 11 shows a top view of the liquid handling device shown in FIG. 1 once the liquid collection device of the first example has been inserted into the liquid handling device.

[0057] FIG. 12 shows a section view through line E-E in FIG. 11

[0058] FIG. 13 shows a side view of the liquid handling device shown in FIG. 1 once the liquid collection device of the first example has been inserted into the liquid handling device.

[0059] FIG. 14 shows a section view through line F-F in FIG. 13

[0060] FIG. 15 shows an isometric exploded view of a liquid collection device according to a second example.

[0061] FIG. 16 shows a side view of the liquid collection device shown in FIG. 15.

[0062] FIG. 17 shows a section view through line G-G in FIG. 16.

[0063] FIG. 18 shows a section view through line H-H in FIG. 16.

[0064] FIG. 19 shows a schematic illustration of a section view of a circular cross-section protrusion off-centre within a lumen.

[0065] FIG. 20 shows a schematic illustration of a section view of an elliptical cross-section protrusion within a lumen. FIG. 21 shows a schematic section view through line J-J in FIGS. 19 and 20.

[0066] FIG. 22 shows a schematic section view through line K-K in FIG. 21.

[0067] FIG. 23 shows an isometric exploded view of a liquid collection device according to a third example.

[0068] FIG. 24 shows a section view through a protrusion of the liquid collection device shown in FIG. 23.

[0069] FIG. 25 shows an enlarged view of region L in FIG. 24.

[0070] FIG. 26 shows an enlarged view of region M in FIG. 25.

[0071] FIGS. 27A to 27H show section views of alternative protrusion configurations for use with the liquid collection devices of the first to third examples.

[0072] FIG. 28 shows a flowchart of a method of transferring liquid from a liquid collection device to a liquid handling device.

[0073] DETAILED DESCRIPTION

[0074] Implementations of the present disclosure are explained below with particular reference to liquid collection devices that collect a volume of blood. It will be appreciated, however, that the implementations described herein are also applicable to liquid collection devices that are used to collect other types of liquid. In addition, implementations of the present disclosure are explained below with particular reference to transferring a collected volume of liquid to a liquid handling device. It will be appreciated, however, that the implementations of the liquid collection devices described herein are also applicable to other uses besides transfer of a collected sample to a liquid handling device. In particular, liquid collection devices of the present disclosure are not limited to diagnostic applications and may, in principle, be used for collecting, storing and transferring different sample types to other types of analytical devices. FIG. 1 shows an isometric view of a liquid handling device in the form of a microfluidic cartridge 1 and a liquid collection device 101 according to a first example. In the isometric view shown in FIG. 1, the liquid collection device 101 is about to be inserted into a cylinder 11 of the microfluidic cartridge 1 , while FIG. 2 shows a liquid handling assembly 51 provided when the liquid collection device 101 is fully inserted into the microfluidic cartridge 1. As shown in more detail in the exploded isometric view of FIG. 10, the cylinder 11 is formed from an upper part 3 of the microfluidic cartridge 1 and a lower part 5 of the microfluidic cartridge 1.

[0075] As shown in more detail in FIG. 3, the liquid collection device 101 comprises a capillary collector 111 coupled to a cap 131. Returning back to FIG. 1, it can be seen that the cylinder 11 comprises a cylindrical end portion 13 that interfaces with the cap 131 of the liquid collection device 101. Specifically, the cylindrical end portion 13 is housed within a cylindrical holder 133 of the cap 131 when the liquid collection device 101 is fully inserted into the cylinder 11 of the microfluidic cartridge 1, as shown in FIG. 2.

[0076] FIG. 1 also shows that the cylindrical end portion 13 includes an annular collar 15 (also shown in FIG. 14) that projects outwardly from the cylindrical end portion 13. The annular collar 15 interfaces with corresponding features on an interior surface 135 of the cylindrical holder 133 to provide an audible ‘click’ when the cylindrical end portion 13 is fully housed within the cylindrical holder 133 of the cap 131. In one example, the audible ‘click’ is provided by a snap fit interface of the annular collar 15 with a corresponding annular lip 137 (shown in FIG. 5) on the interior surface 135 of the cylindrical holder 133. The audible ‘click’ informs a user that the liquid collection device 101 is fully inserted into the cylinder 11 of the microfluidic cartridge 1. As shown in FIG. 1, a plurality of longitudinal slits 17 in the cylindrical end portion 13 allow for radially inward deflection of the annular collar 15, so that the annular collar 15 can pass over the annular lip 137 of the cylindrical holder 133.

[0077] FIG. 3 is an exploded isometric view of the liquid collection device 101, showing the capillary collector 111 and the cap 131 in greater detail. The capillary collector 111 comprises a capillary tube 113 defining a lumen 115 (shown in FIG. 5). The capillary tube 113 may be formed of glass or a transparent or translucent plastic material, while the cap 131 may be formed of a nonporous material such as plastic (e.g. cellulose acetate, acrylonitrile butadiene styrene (ABS), polycarbonate, cyclo-olefin polymer (COP), cyclic olefin copolymer (COC), etc.). The capillary tube 113 has an internal surface 129 that may be coated with an anticoagulant. When a tip 117 of the capillary tube 113 (i.e. at a distal end 119 of the capillary tube 113) is brought into contact with a liquid, a volume of the liquid is drawn into the lumen 115 of the capillary tube 113 by capillary action. In this example, the lumen 115 is capable of holding 20 pL of liquid. As described below, however, other capacities can be accommodated by varying the length of the capillary tube 113.

[0078] The cap 131 is said to be ‘vented’ because it allows for the passage of air into and out of the lumen 115 of the capillary tube 113 (specifically, via a proximal end 123 of the capillary tube 113). By allowing for the passage of air into the lumen 115, a negative pressure can be applied (e.g. via the microfluidic cartridge 1) to aspirate liquid out of the lumen 115. Accordingly, liquid can be easily transferred out of the liquid collection device 101 without requiring, for example, an action done by the user. The cap 131 also allows for the passage of air out of the lumen 115 during filling of the capillary tube 113.

[0079] As used herein, the term “distal” refers to the direction of the tip 117 of the capillary tube 113 along a longitudinal axis of the liquid handling device 101 (i.e. the axis indicated by line A-A in FIG. 4). Therefore, a component of the liquid collection device 101 that extends “distally” extends towards the tip 117 of the capillary tube 113 along the longitudinal axis of the liquid handling device 101. On the other hand, the term “proximal” refers to the direction opposite to the direction of the tip 117 of the capillary tube 113 along the longitudinal axis of the liquid collection device 101. Therefore, a component of the liquid collection device 101 that extends “proximally” extends away from the tip 117 of the capillary tube 113 along the longitudinal axis of the liquid collection device 101. In addition, as used herein, the term “axial” refers to a dimension along a longitudinal axis of the liquid collection device 101, whereas the term “radial” refers to a dimension that is perpendicular to the longitudinal axis of the liquid collection device 101.

[0080] FIG. 3 also shows that an annular flange 121 joins the proximal end 123 of the capillary tube 113 to a socket 125 of the capillary collector 111. The socket 125 is configured for attachment to the cap 131 (e.g. by interference fit of two or more ribs 139 of the cap 131 within the socket 125 or by using clipping features known in the art of plastic components to provide a snap fit). To facilitate attachment to the cap 131, the socket 125 tapers outwards in the direction of the cap 131 (i.e. away from the distal end 119 of the capillary tube 113). The cap 131 includes a projection 141 that is partially housed within the cylindrical holder 133 of the cap 131. In particular, the projection 141 is joined to the cylindrical holder 133 using a plurality of webs 143 (see FIG. 1) that extend between the projection 141 and the interior surface 135 of the cylindrical holder 133. The webs 143 are disposed proximal to the annular lip 137, such that the webs 143 do not interfere with the snap fit interface between the annular lip 137 of the cap 131 and the annular collar 15 of the cylinder 11. Therefore, an annular volume is provided between the interior surface 135 of the cylindrical holder 133 and the projection 141, so that the cylindrical end portion 13 of the cylinder 11 can be accommodated when the liquid collection device 101 is inserted into the cylinder 11 of the microfluidic cartridge 1.

[0081] The cylindrical holder 133, webs 143 and projection 141 all define a flat proximal end surface of the cap 131, which allows the liquid collection device 101 to be stably positioned on a flat surface such as a table. For example, after collecting a volume of blood within the lumen 115, a user may place the flat proximal end surface of the cap 131 on a table, while they attend to a patient or prepare additional equipment (e.g. picking up the microfluidic cartridge 1). This prevents contact of the tip 117 of the capillary tube 113 with a surface, thereby preventing contamination of the collected sample and any potential wicking of the sample from the tip 117 (that may occur, for example, if the liquid collection device 101 were placed on its side with the tip 117 in contact with the surface).

[0082] The projection 141 includes a plurality of ribs 139 that extend radially outwardly from a central core 145 (see FIG. 5) of the projection 141. In this example, the projection 141 includes four ribs 139. Each rib 139 includes a shoulder 147 located distal to a distal end of the cylindrical holder 133. Each rib 139 also includes a tapered portion 149 configured for interference fit within the socket 125 of the capillary collector 111. The tapered portion 149 of each rib 139 terminates in a distally-extending finger 151. In some examples, the fingers 151 define an extent of axial attachment between the cap 131 and the capillary collector 111 by abutment of the fingers 151 against the annular flange 121 of the capillary collector 111 (e.g. as shown in FIG. 5). In other examples, the extent of axial abutment may be defined by abutment of the shoulders 147 against the annular end surface 127, or by abutment of both the fingers 151 against the annular flange 121 and the shoulders 147 against the annular end surface 127.

[0083] FIG. 3 and FIG. 5 also show that the central core 145 terminates in a protrusion 153 that extends distally from a distal end of the central core 145. The protrusion 153 is integral with the cap 131 and is therefore formed of the same material as the cap 131. As shown in FIG. 5, the protrusion 153 extends partially into the lumen 115 of the capillary collector 111. FIG. 3 and FIG. 5 also show that the fingers 151 that distally extend from the ribs 139 are radially offset from the protrusion 153 that distally extends from the central core 145, such that a gap 155 is provided between the protrusion 153 and each finger 151. Each gap 155 has a radial dimension defined by the radial distance between the protrusion 153 and the corresponding finger 151 , and an axial dimension defined by the axial distance that the corresponding finger 151 extends from its corresponding rib 139.

[0084] As shown in FIG. 3 and in more detail in FIG. 6, the protrusion 153 comprises an external surface 155 that defines, in conjunction with the internal surface 129 of the capillary tube 113, at least one capillary channel. In the example shown in FIG. 3 and FIG. 6, a single, annular capillary channel 157 is defined; however, in alternative examples (described further below), a plurality of capillary channels may be defined.

[0085] When liquid is drawn into the lumen 115 by capillary action, a portion of the liquid is drawn into the capillary channel 157 once the level of liquid reaches the protrusion 153. As shown in FIG. 5, the gaps 155 provide an abrupt change in cross-section at the end of the capillary channel 157, thereby providing a capillary stop at the end of the capillary channel 157 that prevents liquid from being drawn beyond the end of the capillary channel 157. This means that the collected liquid is retained within the lumen 115, and does not flow into the socket 125. The capillary stop provided by the gaps 155 prevents the escape of collected liquid from the capillary collector 111, thereby preventing contamination of the surrounding environment.

[0086] The portion of liquid drawn into the capillary channel 157 results in a high capillary pressure. If the capillary pressure resulting from the portion of liquid drawn into the capillary channel 157 is higher than the pressure due to the weight of the liquid within the lumen 115, flow of the collected liquid from the tip 117 of the capillary tube 113 will be prevented. As explained in the following paragraphs, the capillary pressure needed to prevent flow of liquid from the tip 117 of the capillary tube 113 is dependent on the maximum distance d between the protrusion 153 and the internal surface 129 of the capillary tube 113, as illustrated schematically in FIG. 7.

[0087] The capillary pressure at the free surface of a liquid is given by: (Equation 1)

[0088] Where:

[0089] Pcis the capillary pressure; y is the surface tension of the liquid;

[0090] Ri and R2 are the principal radii of curvature of the free surface, defined by: (Equation 2)

[0091] Where:

[0092] Oi,i is the contact angle between the liquid and the internal surface 129 of the capillary tube 113 and 9 / , 2 is the contact angle between the liquid and the external surface 155 of the protrusion 153 (illustrated schematically in FIG. 8 for Ri , and di is the characteristic length, i.e. the distance between the internal surface 129 of the capillary tube 113 and the external surface 155 of the protrusion 153, as illustrated schematically in FIG. 8 for Ri).

[0093] Where the protrusion 153 is a cylinder that is concentric within the lumen 115 of the capillary tube 113 (e.g. as shown in the example of FIGS.1 to 6), the capillary pressure resulting from the portion of liquid within the capillary channel 157 can be approximated in a number of ways, one of which is by modelling the capillary channel as an infinite trench with R2 =00, as shown schematically in FIG. 9 (meaning that there is only one characteristic length, such that d, can be represented as d). When R2 = °°, Equation 1 becomes:

[0094] (Equation 3)

[0095] Assuming that the pressure due to the weight of supported liquid in the capillary tube 113 can be taken as -pgh, where p is the density of the liquid, g is the acceleration due to gravity (9.81 ms-2) and h is the height of the capillary tube 113, then Equation 1 can be rearranged to give a maximum bound for d:

[0096] (Equation 4) Taking an example where liquid is to be retained in a vertical orientation assuming a surface tension of 7.2 x 10'2Nm-1, a contact angle Qi of 50°, a contact angle O2 of 60°, a density of liquid of 1000 kgrrr3, and a 3 cm height of the capillary tube 113 gives a maximum bound for d of 280 pm.

[0097] It will be appreciated that, in view of variations in liquid density and contact angle, a value of d of 300 pm may be sufficient to retain liquid within a capillary tube having a height of 3 cm (particularly where the contact angles are less than those of the above example). This may be the case, for example, where the walls of the capillary tube 113 and / or the protrusion 153 are formed of or coated with a hydrophilic material. In addition, a value of d of 300 pm may be sufficient to retain liquid within a capillary tube having a height of less than 3 cm, or where the collected liquid has a lower density than that used in the example above. However, it will also be appreciated that in normal operation, the maximum bound given by Equation 2 may not be sufficient to retain the liquid in the capillary tube 113, owing to additional inertial forces imparted on the liquid by physical translation and rotation of the capillary tube 113 from the user. These inertial forces represent an additional pressure that should be compensated for, in order to ensure that liquid is retained within the capillary collector 111 during movement of the liquid collection device 101. To compensate for this additional pressure, a smaller value of d can be implemented.

[0098] In addition, the capillary channel 157 may not be the only source of retention pressure. In some cases, the tip 117 of the capillary tube 113 can also contribute to retaining liquid within the lumen 115. If so, then the pressure required from the capillary channel 157 can be reduced (thereby relaxing the bound on d).

[0099] Moreover, providing contact between the external surface 155 of the protrusion 153 and the internal surface 129 of the capillary tube 113 adds additional retention forces to be considered. These are mainly in the form of a second dimension of curvature, which increases the capillary pressure, as described further below.

[0100] In general, when collecting whole blood, a minimum bound for the capillary channel 157 is 20 pm, in order to prevent obstruction to the flow of individual blood cells into the capillary channel 157. It will be appreciated that a smaller width of the capillary channel 157 will cause the capillary channel 157 to fill more slowly with liquid, as reducing the width of the capillary channel 157 increases the hydraulic resistance of the capillary channel 157.

[0101] Taking into account the above considerations concerning the capillary channel 157, in general, the width of the capillary channel 157 (i.e. the distance d between the protrusion 153 and the internal surface 129 of the capillary tube 113) may be between 20 pm and 300 pm, preferably between 75 pm and 300 pm, more preferably between 75 pm and 250 pm, even more preferably between 75 pm and 200 pm, and most preferably between 75 pm and 150 pm.

[0102] In order for the capillary pressure to be generated by the liquid within the capillary channel 157, the protrusion 153 must extend past the lowest point of the meniscus inside the capillary channel 157, so that the meniscus is contained within the capillary channel 157. To account for this, a protrusion length of at least 0.5 mm is preferred.

[0103] It will also be appreciated that capillary tubes manufactured by injection moulding typically have a shallow draft angle. To compensate for this, the protrusion 153 can also have a draft angle that matches the draft angle of the capillary tube 113, so that the protrusion 153 is parallel to the wall (i.e. internal surface 129) of the capillary tube 113, thereby providing a constant width of the capillary channel 157 along its length. Alternatively, the protrusion 153 can have a draft angle that exceeds the draft angle of the capillary tube 113, to provide a narrowing cross-section at the proximal end of the protrusion 153 (i.e. the end of the protrusion 153 closest to the socket 125, in use), thereby increasing the retaining force at the proximal end of the protrusion 153. As an alternative, the narrow cross-section at the proximal end of the protrusion 153 could be created by localised features on the protrusion 153 or at the proximal end 123 of the capillary tube 113.

[0104] It will be appreciated that the voids between the ribs 139 allow for the passage of ambient air into the socket 125. The gaps 155 provide fluid communication between the end of the capillary channel 157 and the voids between the ribs 139. Therefore, the cap 131 includes openings (i.e. in the form of the voids between the ribs 139 and the gaps 155) that provide for the passage of air into the lumen 115 of the capillary tube 113 via the proximal end 123 of the capillary tube 113. This means that air is displaced from the lumen 115 via the openings of the cap 131 during filling of the capillary tube 113, and that air can be drawn into the lumen 115 during aspiration of liquid from the capillary tube 113. Alternatively, positive pressure can be supplied via the openings of the cap 131 to dispense liquid from the capillary tube 113. Forming the cap 131 (specifically, the protrusion 153) of a nonporous material aids in transfer of liquid from the liquid collection device 101, for at least two reasons. Firstly, porous materials could absorb the liquid sample and reduce the volume to be extracted. Secondly, extracting liquid from an absorbent material requires a higher differential pressure and can easily result in the formation of bubbles.

[0105] As noted above, the capillary tube 113 may be formed of a transparent or translucent material. In addition, the capillary tube 113 may be configured to provide a visual indication to a user once the walls of the capillary tube 113 have been wetted. This can be achieved by forming the capillary tube 113 of a material (e.g. a plastic) with a refractive index similar to that of the liquid that the liquid collection device 101 is intended to collect, and different to the refractive index of air. As an alternative to forming the capillary tube 113 of a material with a refractive index similar to that of the liquid intended for collection but different to that of air, the internal surface 129 of the capillary tube 113 may be coated with a material with a refractive index similar to that of the liquid intended for collection but different to that of air.

[0106] Where the walls of the capillary tube 113 (i.e. the internal surface 129 of the capillary tube 113) and the contained fluid have different refractive indices (e.g. the refractive indices for plastic and air, for an empty capillary tube 113), incident light will be reflected or refracted (as a result of Snell’s law). This distortion of light impairs the user’s ability to see through the liquid collection device 110, and is more significant with the curved internal surface 129 of the capillary tube 113. The impact of the different refractive indices is exacerbated if the interface between the two materials is not smooth, but is instead rough (e.g. by selecting an appropriate SPI (Society of the Plastics Industry) or VDI (Verein Deutscher Ingenieure) surface finish). This results in variable and random incident angles, leading to random angles of refraction and reflection. This random scattering of light typically results in the interface appearing translucent (i.e. being able to pass light but being unable to form a clear image on the far side).

[0107] Where the walls of the capillary tube 113 and the contained fluid have similar refractive indices (e.g. the refractive indices for plastic and the liquid intended to be collected), the distortion of incident light will be reduced, and the user will be able to see more clearly through the liquid collection device 101. That is, the air-filled capillary tube 113 will appear distorted or translucent, whereas the liquid-filled capillary tube 113 will appear transparent.

[0108] Additionally or alternatively, the capillary tube 113 may comprise (e.g. be coated with) a material configured to change colour once wetted with a liquid. For example, the internal surface 129 of the capillary tube 113 may be coated with a pH indicator or a hydrochromic ink.

[0109] Additionally or alternatively, the protrusion 153 may be configured to provide a visual indication to a user once the external surface 155 of the protrusion 153 has been wetted. This can be achieved by forming the protrusion 153 of a material (e.g. a plastic) with a refractive index similar to that of the liquid that the liquid collection device 101 is intended to collect, and different to the refractive index of air. For example, the protrusion 153 may be configured to provide the visual indication in implementations where the capillary tube 113 is formed of a transparent material. The protrusion 153 may alternatively comprise (e.g. be coated with) a material configured to change colour once wetted (e.g. pH indicator or hydrochromic ink).

[0110] FIG. 10 is an exploded view of the microfluidic cartridge 1, showing the upper part 3 and the lower part 5 of the microfluidic cartridge 1. Also shown in FIG. 10 is an elastomeric member 7 (e.g. a thermoplastic elastomer) having an opening 9 that receives the tip 117 of the capillary tube 113. Specifically, the opening 9 is sized to receive the tip 117 of the capillary tube 113, such that an interference fit is provided between the tip 117 and the opening 9. The elastomeric member 7 provides a compliant material that provides a seal around the tip 117 of the capillary tube 113 when inserted into the opening 9. In addition, the compliant nature of the elastomeric member 7 rubs off any residues of sample outside of the capillary tube 113, meaning that these residues do not need to be cleaned off. Examples of microfluidic devices having elastomeric members (which may also be referred to as elastomeric layers) are described in international application no. PCT / EP2022 / 087658, the entire contents of which are herein incorporated by reference in their entirety.

[0111] The elastomeric member 7 provides a fluidic connection to one of a plurality of conduits of the microfluidic cartridge 1. The plurality of conduits are defined in part by the elastomeric member 7. Specifically, the plurality of conduits are defined by channels 19 in upper and lower surfaces of the elastomeric member 7 (only the channels 19 in the upper surface are shown in FIG. 10). The channels 19 in each surface are sealed by respective sealing layers (not shown), to form the conduits of the microfluidic cartridge 1. The opening 9 is in fluidic communication with one of the plurality of conduits of the microfluidic cartridge 1.

[0112] As shown in FIG. 10, the microfluidic cartridge 1 also comprises a plurality of ports 21 that are in selective fluidic communication with the conduits of the microfluidic cartridge 1. The term “selective fluidic communication” indicates that the ports 21 can be placed in communication with the conduits by opening one or more valves 23 of the microfluidic cartridge 1. As such, the communication between the ports 21 and the conduits is dependent on the configuration of the valves 23. The elastomeric member 7 comprises the valves 23 and ports 21 of the microfluidic cartridge 1. By placing one of the ports 21 in fluidic communication with the conduit that is in fluidic communication with the opening 9, a negative pressure can be applied to that port 21 to aspirate liquid from the liquid collection device 101 into the fluidic network defined by the elastomeric member 7. The aspirated liquid can then be routed to flow cells or chambers of the microfluidic cartridge 1 as required, by changing the pneumatic pressures applied to the ports 21 and the configurations of the valves 23.

[0113] FIG. 10 also shows that the lower part 3 includes one or more first guide ribs 25 that are configured to restrict movement of the liquid collection device 101 in a first direction during insertion of the liquid collection device 101 into the cylinder 11 of the microfluidic cartridge 1. In this example, two first guide ribs 25 are shown, although it will be appreciated that a single first guide rib 25 would also serve to restrict movement of the liquid collection device 101 in the first direction. In the example shown in FIG. 10, the direction of insertion of the liquid collection device 101 is indicated as the x-direction, the direction normal to the upper surface of the microfluidic cartridge 1 is indicated as the z-direction, and the direction parallel to the longer edges of the microfluidic cartridge 1 is indicated as the y-direction. The two first guide ribs 25 shown in FIG. 10 restrict movement of the liquid collection device 101 in the y-direction, by providing a tapering channel that gradually constrains movement of the liquid collection device 101 within the xz-plane with increased movement of the liquid collection device 101 in the x-direction towards the opening 9.

[0114] FIG. 11 is a top view of the liquid handling assembly 51 provided by insertion of the liquid collection device 101 into the microfluidic cartridge 1, while FIG. 12 is a section view through line E-E in FIG. 11. As shown in FIG. 12, the microfluidic cartridge 1 includes one or more second guide ribs 27 that are configured to restrict movement of the liquid collection device 101 in a second direction during insertion of the liquid collection device 101 into the cylinder 11 of the microfluidic cartridge 1. Specifically, in the example shown in FIG. 12, the microfluidic cartridge 1 includes two second guide ribs 27 that restrict movement of the liquid collection device 101 in a second direction that is orthogonal to the first direction. Returning to the coordinate system indicated in FIG. 10, the second guide ribs 27 shown in FIG. 12 restrict movement of the liquid collection device 101 in the z-direction, by providing a tapering channel that gradually constrains movement of the liquid collection device 101 within the xy-plane with increased movement of the liquid collection device 101 in the x-direction toward the opening 9. In the example shown in FIG. 12, the upper part 3 comprises one of the second guide ribs 27, while the lower part 5 comprises the other one of the second guide ribs 27.

[0115] By comparing the first guide ribs 25 shown in FIG. 10 with the second guide ribs 27 shown in FIG. 12, it can be seen that the first guide ribs 25 are spatially separated from the second guide ribs 27 in the x-direction. Spatially separating the first guide ribs 25 from the second guide ribs 27 in the x-direction avoids having a complex rib geometry that could result in the liquid collection device 101 becoming stuck or wedged during insertion into the cylinder 11.

[0116] FIG. 13 is a side view of the liquid handling assembly 51 provided by insertion of the liquid collection device 101 into the microfluidic cartridge 1, while FIG. 14 is a section view through line F-F in FIG. 13. FIG. 14 shows the tip 117 of the capillary collector 101 located within the opening 9 of the elastomeric member 7. In addition, FIG. 14 shows the annular collar 15 on the cylindrical end portion 13 of the cylinder 11 having snapped over the annular lip 137 on the interior surface 135 of the cylindrical holder 133, thereby providing the audible ‘click’ to inform the user that the liquid collection device 101 is fully inserted into the cylinder 11 of the microfluidic cartridge 1. As shown in FIG. 14, the cylindrical end portion 13 of the cylinder 11 is housed within the cylindrical holder 133 of the cap 131 when the liquid collection device 101 is fully inserted into the cylinder 11.

[0117] Variations or modifications to the systems and methods described herein are set out in the following paragraphs.

[0118] FIG. 15 is an isometric exploded view of a liquid collection device 201 according to a second example, while FIG. 16 shows a side view of the liquid collection device 201. Components of the liquid collection device 201 of the second example that are identical to those of the liquid collection device 101 of the first example are identified using the same reference signs as used for the liquid collection device 101 of the first example.

[0119] In the example shown in FIG. 15, the liquid collection device 201 comprises a capillary collector 211 and a cap 231. In contrast to the liquid collection device 101 of the first example, the capillary collector 211 has a longer capillary tube 213, meaning that its lumen 215 can accommodate a larger volume of liquid. In this example, the lumen 215 is capable of holding 50 pL of liquid. Other components of the capillary collector 211 are identical to those of the capillary collector 111 of the liquid collection device 101 of the first example.

[0120] The liquid collection device 201 is capable of being inserted into the cylinder 11 of the microfluidic cartridge 1 described with reference to the first example. In order to accommodate the longer capillary tube 213 of the capillary collector 211, the projection 241 of the cap 231 is shorter than the projection 141 of the liquid collection device 101 of the first example. This means that the ribs 239 of the projection 241 are also shorter than the corresponding ribs 139 of the liquid collection device 101.

[0121] In addition to having a different capacity, the liquid collection device 201 also includes a protrusion 253 that has a different cross-section to the protrusion 153 of the liquid collection device 101, and a different length to the protrusion 153 of the liquid collection device 101. The longer length of the protrusion 253 can be seen from FIG. 17, which is a cross-section through line G-G in FIG. 16. In addition, FIG. 17 shows that there are two points of contact between the protrusion 253 and the internal surface 229 of the capillary tube 213. Specifically, and as shown in FIG. 18, the protrusion 253 has an elliptical cross-section, where the maximum width of the ellipse is equal to the diameter of the lumen 215 (or preferably slightly larger than the diameter of the lumen 215, to accommodate manufacturing tolerances). This means that the external surface 255 of the protrusion 253 contacts the internal surface 229 of the capillary tube 213 in two places, thereby defining two capillary channels 257.

[0122] Having a protrusion 253 with an external surface 255 that contacts the internal surface 229 of the capillary tube 213 has three main advantages. Firstly, acute wedge shaped regions 263 result from contact between the curved elliptical cross-section of the protrusion 253 and the cylindrical cross-section of the lumen 215. These wedge shaped regions 263 increase the capillary pressure resulting from the liquid within the capillary channels 257, meaning that the capillary pressure resulting from the retained liquid is higher than in the liquid collection device 101 of the first example. This is because the wedge shaped regions 263 result in a second dimension of meniscus curvature in each of the two capillary channels 257 (as described further below). This higher capillary pressure means that the liquid collection device 201 can retain higher volumes of liquid under more aggressive handling conditions.

[0123] Secondly, when manufacturing, achieving small gaps reproducibly requires very tight control of each component’s manufacturing tolerances, plus their assembly tolerances. Contacting features are valuable design aids to ensure correct assembly between parts.

[0124] Thirdly, the wedge shaped regions 263 serve to ‘pin’ liquid within the capillary channels 257. In use, the liquid collection device 201 requires the collected liquid to be extracted from the end of the capillary tube 213 that is opposite to the capillary channels 257 (i.e. from the tip 117 of the capillary tube 213). The liquid that is present in the acute wedge shaped regions 263 will typically be retained to some degree during extraction of liquid from the capillary tube 213. Once the liquid has been extracted from the capillary tube 213, the liquid in the wedge shaped regions 263 rearranges itself (i.e. equilibrates) so as to minimise the additional surface energy generated when extracting liquid from the capillary tube 213. The retained liquid can provide a visual indication to the user that the liquid collection device 201 has already been used and should not be reused. The retained liquid also acts as a liquid plug that reduces the effectiveness of future attempts to fill the capillary tube 213.

[0125] As described in more detail below, the design of the protrusion can even be optimised so that the full cross-section of the capillary channels is occupied with liquid after extraction of the intended volume of liquid from the capillary tube. This would prevent the tube from being refilled or reused, as there is no escape path for air.

[0126] The effect of the wedge shaped regions arising from contact between the external surface 255 of the protrusion 253 and the internal surface 229 of the capillary tube 213 will now be explained, with reference to the schematic illustrations in FIGS. 19 to 22. FIG. 19 shows an example of a cylindrical protrusion that has a single point of contact with an internal surface of a capillary tube, while FIG. 20 schematically illustrates the capillary channels 257 of the liquid collection device 201 of the second example. In each case, the contact between the protrusion 253 and the internal surface 229 defines two wedge shaped regions 263 on either side of each capillary channel 257 (i.e. a total of four wedge shaped regions 263 for the example shown in FIG. 20). When wetted by liquid, these wedge shaped regions 263 are responsible for an increase in capillary pressure, because they contribute to an increase in curvature of the free surface. In FIGS. 19 to 22, the variable di indicates the maximum width of the capillary channel 257 (i.e. the maximum distance between the protrusion 253 and the internal surface 229 of the capillary tube 213), while the variable c indicates the width of the second dimension of curvature (i.e. the average distance between the wedge shaped regions 263 on either edge of the capillary channel 257).

[0127] Returning to Equation 1 above, the term 1 IR2 is now non-zero because the value of R2 is not infinite (as shown schematically in FIG. 22). This means that the term 1 / F?2 contributes to the capillary pressure, resulting in a higher capillary pressure than for the liquid collection device 101 of the first example. In other words, the presence and geometry of the wedge shaped regions 263 become an important factor in addition to the distance di in order to hold liquid within the capillary tube 213 against gravity or mechanical accelerations and decelerations. As a general rule, the increase in capillary pressure scales inversely with di and the angle defined between the two surfaces at the point of contact (i.e. the angle of the wedge shaped regions 263).

[0128] Specifically, the smaller these are, the higher the capillary pressure and resulting ability to retain liquid.

[0129] It will be appreciated that the features providing the increased capacity of the capillary tube 213 of the liquid collection device 201 of the second example may be implemented without the elliptical cross-section of the protrusion 253. In other words, the increased capillary tube capacity could be provided in combination with the cylindrical protrusion 153 of the liquid collection device 101 of the first example. Likewise, the elliptical cross-section of the protrusion 253 may be implemented without the increased capacity of the capillary tube 213 of the liquid collection device 201 of the second example. That is, the protrusion 253 may be implemented in combination with the lower capacity capillary tube 113 of the liquid collection device 101 of the first example. The elliptical cross-section of the protrusion 253 does, however, provide an advantage when implemented in combination with a higher-capacity capillary tube (such as the capillary tube 213), because the higher capillary pressure resulting from liquid within the capillary channels 257 allows a larger volume of liquid to be held within the capillary tube 213. FIG. 23 is an isometric exploded view of a liquid collection device 301 according to a third example, while FIG. 24 shows a section view through a protrusion 353 of the liquid collection device 301. Components of the liquid collection device 301 of the second example that are identical to those of the liquid collection device 101 of the first example or the liquid collection device 201 of the second example are identified using equivalent reference signs as used for the liquid collection devices 101, 201 of those examples.

[0130] In the example shown in FIG. 23, the liquid collection device 301 comprises a capillary collector 311 and a cap 331. The capillary collector 311 has the same capacity capillary tube 213 as that of the capillary collector 211 of the liquid collection device 201 of the second example (and therefore has the same length projection 241 and ribs 239 as the liquid collection device 201 of the second example). In addition, the cap 331 is the same as the cap 231 of the liquid collection device 201 of the second example, except that the protrusion 353 of the cap 331 has a different cross-section.

[0131] Specifically, as shown in FIG. 24 and in the enlarged views in FIG. 25 and FIG. 26, a plurality of capillary channels 357 are defined by contact between the external surface 355 of the protrusion 353 and the internal surface 229 of the capillary tube 213. In this example, the external surface 355 is corrugated, such that a plurality of axially- extending capillary channels 357 are provided. To provide the corrugated external surface 355, the external surface 355 comprises a plurality of axially-extending convex ridges 359. The plurality of convex ridges 359 are provided on the external surface 355 such that the convex shape of one ridge 359 adjoins the convex shape of its adjacent ridges 359, thereby forming an acute groove 361 between adjacent ridges 359. Such an arrangement provides a ‘scalloped’ perimeter of the external surface 355 of the protrusion 353.

[0132] The increased number of capillary channels 357 provided by contact between the external surface 355 of the protrusion 353 and the internal surface 229 of the capillary tube 213 results in an increased capillary pressure resulting from the liquid within the capillary channels 357, when compared with the liquid collection device 201 of the second example. This is because the additional capillary channels 357 have a lower value of F?2, resulting in a higher value of the term 1 IR2 in Equation 1. In addition, the wedge shaped regions 363 (shown in FIG. 26) of each capillary channel 357 retain a proportion of liquid after liquid is transferred from the capillary tube 213, as explained above. The protrusion 353 provides a clearer visual indication that the liquid collection device 301 has already been used, because it includes an additional wedge shaped region 363 in each capillary channel 357 (i.e. the acute groove 361), when compared with the capillary channels 257 of the liquid collection device 201 of the second example (as illustrated schematically in FIG. 26). In addition, the clearer visual indication is provided by the higher number of capillary channels 357, meaning that the number of liquid-retaining wedge shaped regions 363 is increased. In general, therefore, a capillary channel with an acute groove provides a wedge shaped region at an edge of the capillary channel. This wedge shaped region retains liquid after extraction and therefore provides a visual indication to a user that the liquid collection device has been used.

[0133] In addition, the capillary channels 357 of the liquid collection device 301 of the third example enforce incomplete draining of the capillary tube 213. Liquid is retained as a result of the regions of very high pressure at the interfaces between the convex ridges 359 and the internal surface 229 of the capillary tube 213. Theoretically, these interfaces provide pressure singularities (i.e. two parallel walls spaced infinitesimally apart for infinite capillary pressure), although in a real system, these will not be singularities, but regions of very high pressure. The very high capillary pressures result in the development of liquid plugs within the capillary channels 357 after extraction of the intended volume of liquid from the capillary tube 213. In other words, the full crosssection of the capillary channels 357 is occupied with liquid after extraction, thereby closing the vent path for air to flow out of the lumen 215 and consequently preventing reuse or refill of the liquid collection device 301. The development of liquid plugs is dependent on the minimum cross-section of the capillary channels 357. The minimum cross-section of the capillary channels 357 may be tuned so that liquid plugs develop after extraction of liquid from the capillary tube 213, to prevent reuse of the liquid collection device 301.

[0134] While the liquid collection device 301 is shown as having the same length capillary tube 213, ribs 239 and projection 241 as the corresponding components of the liquid collection device 201 of the second example, it will be appreciated that the liquid collection device 301 may alternatively comprise a capillary tube, ribs and projection having the same length as the corresponding components of the liquid collection device 101 of the first example.

[0135] FIGS. 27A to 27H show additional protrusion cross-sections that may be implemented in the liquid collection devices 101 , 201 , 301 described above. Specifically, FIG. 27A shows a protrusion cross-section defined by the intersection of three ellipses, thereby forming three channels, each having a central groove. FIG. 27B shows a similar example in which the protrusion cross-section is defined by the intersection of four ellipses. FIG. 27C shows an alternative example in which the protrusion cross-section is defined by the intersection of three circles, thereby forming three channels, each having a groove that is more acute than the grooves of the channels in the example shown in FIG. 27A. FIG. 27D shows a further alternative example in which three triangular axial grooves are formed in an external surface of a cylindrical protrusion having a diameter equal to the diameter of the capillary tube. FIG. 27E shows a further example in which twelve triangular grooves are formed in an external surface of a cylindrical protrusion having a diameter equal to that of the capillary tube, while FIG. 27F shows a similar example in which twelve semi-circular grooves are formed in an external surface of a cylindrical protrusion having a diameter equal to that of the capillary tube. FIG. 27G shows a further example in which twelve circular crosssection channels are provided within a cylindrical protrusion having a diameter equal to that of the capillary tube, while FIG. 27H shows a similar example in which twelve elliptical cross-section channels are provided within a cylindrical protrusion having a diameter equal to that of the capillary tube. From the above discussion, it will be appreciated that the above examples provide increased capillary pressure when compared with a protrusion having a circular cross-section that is concentrically located within the capillary tube, while the examples of FIGS. 27A to 27F provide liquidretaining wedge shaped regions that provide a visual indication that a liquid collection device has already been used. Specifically, FIG. 27E is an example where the wedge shaped regions of the capillary channels are provided by the external surface of the protrusion having acute grooves. FIGS. 27G and 27H are examples of capillary channels that are provided within the protrusion itself, and are not, therefore, provided between an external surface of the protrusion and an internal surface of the capillary tube. As an alternative to the example of FIG. 27E, a plurality of triangular crosssection capillary channels may be provided within the protrusion itself. The acute corners of the triangular cross-section capillary channels would define wedge shaped regions that provide a visual indication that a liquid collection device has already been used (e.g. if the protrusion were formed of a transparent or translucent material).

[0136] The present disclosure also relates to a method 501 of transferring liquid from a capillary tube of a liquid collection device (e.g. the capillary tube 113 of the liquid collection device 101 of the first example) to a liquid handling device (e.g. the microfluidic cartridge 1). The method 501 is illustrated schematically in FIG. 28 and may be carried out by an analyser device in which the liquid handling device is received. The analyser device used to carry out the method 501 may comprise at least: one or more actuators configured to actuate one or more valves of the liquid handling device (e.g. the valves 23 of the microfluidic cartridge 1); and one or more pneumatic supply conduits configured to provide a negative pressure to one or more pneumatic ports of the liquid handling device (e.g. the ports 21 of the microfluidic cartridge 1). The method 501 may be implemented by one or more processors of the analyser device. In particular, the method 501 may be implemented in the form of instructions stored on a transitory or non-transitory computer-readable medium, wherein the instructions are executable by the one or more processors of the analyser device to cause the analyser device to implement the method 501. The instructions may be stored in a memory of the analyser device.

[0137] Optionally, the method 501 may firstly comprise detecting whether the capillary tube of the liquid collection device has been coupled to (e.g. inserted into) the liquid handling device. For example, the presence of the liquid collection device may be detected using one or more sensors (e.g. optical sensors and / or proximity sensors) of the analyser device. If no liquid collection device has been inserted, or if the capillary tube has been incorrectly inserted, then the method 501 ends. Otherwise, the method 501 proceeds to 503.

[0138] At 503, a fluidic path is opened between the capillary tube of the liquid collection device and a pneumatic port of the liquid handling device. Opening the fluidic path may comprise opening one or more valves of the liquid handling device.

[0139] At 505, a negative pressure is applied to the pneumatic port of the liquid handling device, to aspirate liquid from the capillary tube of the liquid collection device into one or more conduits of the fluidic path.

[0140] At 507, the fluidic path between the capillary tube of the liquid collection device and the pneumatic port is closed. Closing the fluidic path may comprise closing one or more valves of the liquid handling device. A positive or negative pressure can then be applied to transfer the aspirated liquid from the one or more conduits to a component of the liquid handling device (e.g. a flow cell or chamber of the microfluidic cartridge 1).

[0141] It will be appreciated that a negative pressure is not necessarily needed in order to transfer liquid out of the liquid collection devices described herein. Instead, a pressure differential is required between the ends of the capillary collector. In one example, such a pressure differential may alternatively be provided by applying a centrifugal force to the liquid collection device. In general, therefore, a method of transferring liquid out of the liquid handling devices 101 , 201 , 301 described herein may comprise applying a pressure differential between the proximal end of the capillary tube of the liquid collection device and the distal end of the capillary tube of the liquid collection device (i.e. so that the pressure at the distal end of the capillary tube is lower than the pressure at the proximal end of the capillary tube). For example, as a modification to the method 501 described above, the pneumatic port may be opened to atmospheric pressure at 505 after the fluidic path is opened at 503 (i.e. instead of applying a negative pressure to the pneumatic port at 505). Then, prior to 507, a positive pressure can be applied to a proximal end of the capillary tube (i.e. the end of the capillary tube that is opposite to the end coupled to the liquid handling device), in order to dispense liquid from the capillary tube into the one or more conduits of the fluidic path. For example, where the liquid collection device is one of the liquid collection devices 101, 201, 301 described herein, the positive pressure could be applied via the cap 131 , 231 , 331. Following closure of the fluidic path at 507, a positive or negative pressure can be applied to transfer the dispensed liquid from the one or more conduits to a component of the liquid handling device.

[0142] The described methods may be implemented using computer executable instructions. A computer program product or computer readable medium may comprise or store the computer executable instructions. The computer program product or computer readable medium may comprise a hard disk drive, a flash memory, a read-only memory (ROM), a CD, a DVD, a cache, a random-access memory (RAM) and / or any other storage media in which information is stored for any duration (e.g., for extended time periods, permanently, brief instances, for temporarily buffering, and / or for caching of the information). A computer program may comprise the computer executable instructions. The computer readable medium may be a tangible or non-transitory computer readable medium. The term “computer readable” encompasses “machine readable”.

[0143] The singular terms “a” and “an” should not be taken to mean “one and only one”. Rather, they should be taken to mean “at least one” or “one or more” unless stated otherwise. The word “comprising” and its derivatives including “comprises” and “comprise” include each of the stated features, but does not exclude the inclusion of one or more further features. The above implementations have been described by way of example only, and the described implementations are to be considered in all respects only as illustrative and not restrictive. It will be appreciated that variations of the described implementations may be made without departing from the scope of the invention. It will also be apparent that there are many variations that have not been described, but that fall within the scope of the appended claims.

Claims

CLAIMS:

1. A liquid collection device, comprising: a capillary collector comprising a capillary tube defining a lumen for collecting liquid by capillary action; and a cap coupled to the capillary collector, wherein the cap is configured to permanently vent the lumen of the capillary tube, and wherein the cap comprises a protrusion extending into the lumen such that when the lumen is filled with liquid, a portion of the liquid is retained between the protrusion and the capillary tube.

2. The liquid collection device according to claim 1, wherein the protrusion is formed of a non-porous material.

3. The liquid collection device according to claim 1 or claim 2, wherein the protrusion extends into a proximal end of the lumen, and wherein the cap comprises one or more openings configured to permit the passage of air into the proximal end of the lumen.

4. The liquid collection device according to any of claims 1 to 3, wherein the protrusion contacts an internal surface of the capillary tube.

5. The liquid collection device according to any of claims 1 to 4, wherein the cap is configured to provide a capillary stop for the portion of the liquid retained between the protrusion and the capillary tube.

6. The liquid collection device according to any of claims 1 to 5, wherein the protrusion is configured such that one or more capillary channels are defined between an external surface of the protrusion and the capillary tube.

7. The liquid collection device according to any of claims 1 to 5, wherein the protrusion is configured such that one or more capillary channels are defined within the protrusion.

8. The liquid collection device according to claim 6 or claim 7, wherein the portion of the liquid is retained in the one or more capillary channels.

9. The liquid collection device according to any of claims 6 to 8, wherein a maximum width of the one or more capillary channels is between 20 pm and 300 pm, preferably between 75 pm and 300 pm, more preferably between 75 pm and 250 pm, yet more preferably between 75 pm and 200 pm, and most preferably between 75 pm and 150 pm.

10. The liquid collection device according to any of claims 6 to 9, wherein each of the one or more capillary channels comprises one or more wedge shaped regions.

11. The liquid collection device according to any of claims 1 to 10, wherein the protrusion extends into the lumen to a distance of at least 0.5 mm.

12. The liquid collection device according to any of claims 1 to 11, wherein the liquid collection device is configured to provide a visual indication to a user once the liquid has been collected.

13. The liquid collection device according to claim 12, wherein the capillary tube is configured to provide the visual indication to the user once the capillary tube has been wetted with liquid.

14. The liquid collection device according to claim 12 or claim 13, wherein the protrusion is configured to provide the visual indication to the user once the protrusion has been wetted with liquid.

15. The liquid collection device according to claim 14, wherein the protrusion comprises a surface configured to disperse light prior to wetting by a liquid, wherein the surface is configured to not disperse light once wetted by the liquid.

16. The liquid collection device according to claim 14 or claim 15, wherein the protrusion comprises a material configured to change colour once wetted with liquid.

17. A liquid handling device configured to receive a liquid collection device, the liquid handling device comprising: a plurality of conduits; and an elastomeric member configured to receive a tip of the liquid collection device, wherein the elastomeric member is configured to provide a fluidic connection between the tip of the liquid collection device and one of the plurality of conduits.

18. The liquid handling device of claim 17, wherein the tip of the liquid collection device is a tip of a capillary tube of the liquid collection device, wherein the elastomeric member comprises an opening in fluidic communication with the one of the plurality of conduits, and wherein the opening is configured to provide an interference fit for the tip of the capillary tube of the liquid collection device.

19. The liquid handling device of claim 17 or claim 18, wherein the liquid handling device further comprises a pneumatic port in selective fluidic communication with the one of the plurality of conduits.

20. The liquid handling device of any of claims 17 to 19, wherein the plurality of conduits are defined in part by the elastomeric member.

21. The liquid handling device of any of claims 17 to 20, wherein the liquid handling device further comprises one or more guide ribs configured to guide insertion of the tip of the liquid collection device into the elastomeric member.

22. The liquid handling device of claim 21 , wherein the one or more guide ribs comprise: one or more first guide ribs configured to restrict movement of the liquid collection device in a first direction; and one or more second guide ribs configured to restrict movement of the liquid collection device in a second direction different to the first direction.

23. The liquid handling device according to any of claims 17 to 22, wherein the liquid handling device is configured to receive the liquid collection device of any of claims 1 to 15.

24. A liquid handling assembly, comprising: a liquid collection device according to any of claims 1 to 16; and a liquid handling device according to any of claims 17 to 23.

25. The liquid handling assembly of claim 24, wherein the tip of the liquid collection device is a tip of a capillary tube of the liquid collection device, wherein the elastomeric member of the liquid handling device comprises an opening in fluidic communication with the one of the plurality of conduits of the liquid handling device, and wherein theopening is configured to provide an interference fit for the tip of the capillary tube of the liquid collection device.

26. The liquid handling assembly of claim 24 or claim 25, wherein the cap of the liquid collection device is configured to interface with the liquid handling device to provide an audible click when the tip of the liquid collection device is fully inserted into the elastomeric member of the liquid handling device.

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