Liquid treatment device capable of determining the presence or absence of a volume of liquid - Patent application

Abstract

Embodiments described herein relate to a liquid treatment device comprising an inlet conduit configured to receive a liquid sample, a first flow path in fluid communication with the inlet conduit and including a sample adequacy control chamber configured to enable the sample adequacy control chamber to determine the presence or absence of a volume of liquid within the sample adequacy control chamber, and a second flow path in fluid communication with the inlet conduit and configured to provide a higher hydraulic resistance than the first flow path.

Description

[Technical field]

[0001] The present disclosure relates to a liquid treatment device that is capable of determining the presence or absence of a volume of liquid. [Background technology]

[0002] Point-of-care diagnostic devices are typically used to perform diagnostic tests, such as immunoassays, on biological samples (such as whole blood, serum, or plasma). To perform such diagnostic tests, the biological sample must be transferred to the diagnostic device. The diagnostic device is then inserted into an analytical device (or instrument) that controls the movement of fluids (e.g., biological sample, reagents, buffers, etc.) within the diagnostic device and performs the measurement of biomarkers to perform the diagnostic test.

[0003] A biological sample, such as whole blood or plasma, is typically received into a point-of-care diagnostic device. Existing devices include an observation window that allows a user to see that liquid has been received into the device. However, when a user looks at the observation window, the user may not know if a sufficient volume of liquid has been received. This means that if liquid is received into the device by some form of user action, the user does not know when they can stop that action.

[0004] Additionally, filling of the observation window may result in unintended liquid flow into other fluidic components of the device. Summary of the Invention [Problem to be solved by the invention]

[0005] Therefore, there is a need for a device that allows for determining the presence or absence of a volume of liquid that improves user ease of use and minimizes unintended liquid flow into other fluid components of the device.

[0006] overview This summary introduces concepts that are described in more detail in the detailed description. It is not intended to identify essential features of the claimed subject matter, nor should it be used to limit the scope of the claimed subject matter. [Means for solving the problem]

[0007] According to one aspect of the present disclosure, a liquid treatment device is provided comprising an inlet conduit configured to receive a liquid sample, a first flow path in fluid communication with the inlet conduit and including a sample sufficiency control chamber, the first flow path being configured to enable the sample sufficiency control chamber to determine the presence or absence of a volume of liquid within the sample sufficiency control chamber, and a second flow path in fluid communication with the inlet conduit, the second flow path being configured to provide a higher hydraulic resistance than the first flow path.

[0008] The sample adequacy control chamber allows a user to determine whether a particular volume of liquid has been received into the liquid treatment device. For example, a user may be able to determine whether a sufficient volume of liquid has been received to allow a diagnostic test to be performed. A higher hydraulic resistance in the second flow path means that liquid will fill the sample adequacy control chamber in the first flow path in preference to the second flow path. This means that a visual indication can be provided to the user without (or with minimal) fluid flow to other fluidic components of the liquid treatment device (e.g., other chambers of a diagnostic cartridge).

[0009] The liquid treatment device may include an indicator area where the sample adequacy control chamber is visible so that the user can determine the presence or absence of a volume of liquid in the sample adequacy control chamber. This means that the user knows when sufficient liquid has been received into the liquid treatment device. If the user's action is to cause liquid to be received into the inlet conduit, the indication to the user means that the user knows when such action can be stopped. Furthermore, if liquid is received into the liquid treatment device by the user applying force to a liquid extraction mechanism that extracts liquid from a liquid storage container, the indication to the user means that the user knows when the user can remove the liquid storage container from the liquid extraction mechanism before proceeding with the diagnostic test.

[0010] The indicator area through which the sample adequacy control chamber is visible may be downstream of the sample adequacy control chamber inlet port in the first flow path. For example, when liquid is received by the liquid treatment device by a user applying force to a liquid extraction mechanism that extracts liquid from a liquid storage container, the force is applied from above the liquid treatment device (e.g., when a diagnostic cartridge is on its side). By providing an indicator area located downstream of the sample adequacy control chamber inlet port, the user can easily see a visual indication from above the device when applying force to the liquid extraction mechanism. The indicator area may be provided in a wall of the liquid treatment device. The indicator area may comprise an observation window in the wall of the liquid treatment device. Providing an indicator area located downstream of the sample adequacy control chamber inlet port also ensures that a visual indication to the user is provided after liquid begins to fill the sample adequacy control chamber.

[0011] The second flow path may include an outlet conduit. The outlet conduit may have a smaller cross-sectional area than the inlet conduit. This increases the hydraulic resistance of the second flow path to facilitate the flow of liquid through the first flow path and into the sample adequacy control chamber. The outlet conduit may be in fluid communication with the inlet conduit through the sample adequacy control chamber.

[0012] The sample validity control chamber may comprise a sample validity control chamber inlet port configured to receive liquid from the inlet conduit and a sample validity control chamber outlet port fluidly connected to the second flow path. The distance between the sample validity control chamber outlet port and the indicator region may be less than the distance between the sample validity control chamber inlet port and the indicator region. By positioning the sample validity control chamber outlet port to be closer to the indicator region than the sample validity control chamber inlet port, the head pressure on the sample validity control chamber outlet port when the liquid treatment device is in use is reduced (i.e., when the indicator region is oriented upward, it means that the indicator region is higher than the inlet conduit). The reduced head pressure in this orientation impedes the flow of liquid through the sample validity control chamber outlet port (i.e., into the second flow path).

[0013] The first flow path may further comprise a metering chamber configured to store a specific volume of liquid, the metering chamber comprising a metering chamber inlet port configured to receive the liquid from the inlet conduit and a metering chamber outlet port in fluid communication with the second flow path, the metering chamber holds a specific volume of liquid such that the specific volume is less likely to be displaced if the liquid treatment device is moved or shaken.

[0014] The first flow path may include a connector conduit providing a fluid connection between the metering chamber and the sample adequacy control chamber. The cross-sectional area of ​​the connector conduit may be smaller than the cross-sectional area of ​​the metering chamber to minimize the volume of the metering chamber visible through the sample adequacy control chamber. Minimizing the volume of the metering chamber visible through the sample adequacy control chamber reduces the likelihood of a false positive indication that the sample adequacy control chamber contains a volume of liquid.

[0015] The second flow path may include an outlet conduit. A cross-sectional area of ​​the connector conduit may be equal to or greater than a cross-sectional area of ​​the outlet conduit. This increases the hydraulic resistance of the second flow path, thereby facilitating the flow of liquid through the first flow path and into the sample adequacy control chamber.

[0016] The sample adequacy control chamber may be downstream of the metering chamber. Locating the sample adequacy control chamber downstream of the metering chamber ensures that the metering chamber is filled before the sample adequacy control chamber, thereby ensuring that a sufficient volume of liquid is received by the liquid treatment device.

[0017] The distance between the metering chamber outlet port and the indicator area may be less than the distance between the metering chamber inlet port and the indicator area. By positioning the metering chamber outlet port so that it is closer to the indicator area than the metering chamber inlet port, the head pressure on the metering chamber outlet port is reduced when the liquid treatment device is in use (i.e., when the indicator area is facing upward, it means that the indicator area is higher than the inlet conduit). The reduced head pressure in this orientation prevents the flow of liquid into the second flow path through the metering chamber outlet port.

[0018] The second flow path may comprise an outlet conduit section extending in the direction of the indicator area. The extension of the outlet conduit section in the direction of the indicator area increases the potential pressure head in the outlet conduit when the liquid treatment device is in use (i.e., if the indicator area is oriented upwards, it means that the indicator area is higher than the inlet conduit). This increase in the potential pressure head in the outlet conduit reduces the tendency of liquid to flow through the second flow path. The second flow path may further comprise an additional outlet conduit section in fluid communication with the outlet conduit section, the additional outlet conduit section extending in a direction opposite to the extension direction of the outlet conduit section.

[0019] The first flow path may include a vent waste chamber in fluid communication with the sample adequacy control chamber. The use of a vent waste chamber provides an outlet for any excess liquid so that such excess liquid does not fill the second flow path.

[0020] The sample adequacy control chamber may comprise a waste outlet providing a fluid connection to a waste chamber, the waste outlet being located between an upper end and a lower end of the sample adequacy control chamber, the distance between the upper end of the sample adequacy control chamber and the indicator region being less than the distance between the lower end of the sample adequacy control chamber and the indicator region. By arranging the waste outlet in this manner, the sample adequacy control chamber may be used to meter a specific volume of liquid, thereby avoiding the need for a separate metering chamber.

[0021] The liquid treatment device may further comprise a pad of porous material, the pad configured to contact the liquid in the sample validity control chamber. The use of a pad of porous material provides an indication that the sample validity control chamber contains a volume of liquid as the liquid flows through the porous material, but occludes the contents of the sample validity control chamber before filling the sample validity control chamber to the required level. This reduces the possibility of a false positive indication that the sample validity control chamber contains the required volume of liquid.

[0022] Alternatively, the liquid handling device may comprise a pad of absorbent material configured to absorb liquid within the sample adequacy control chamber. The use of a pad of absorbent material provides a persistent indication that the sample adequacy control chamber contains a volume of liquid, thereby allowing a user to easily determine that the sample adequacy control chamber contains a volume of liquid.

[0023] The liquid treatment device may further comprise an occluding material disposed on a wall of the liquid treatment device through which the sample adequacy control chamber is visible, the occluding material configured to occlude at least a portion of the sample adequacy control chamber until the occluding material comes into contact with a volume of liquid. The occluding material reduces the likelihood of a false positive indication that the sample adequacy control chamber contains a volume of liquid because a user cannot see the contents of the sample adequacy control chamber until the occluding material becomes more optically transparent.

[0024] The liquid treatment device may further comprise a liquid reservoir interface configured to provide a fluid connection to a volume of liquid in the puncturable liquid reservoir, the liquid reservoir interface comprising a liquid extraction outlet configured to allow liquid to be extracted from the liquid reservoir, the liquid extraction outlet being in fluid communication with the inlet conduit such that liquid extracted from the liquid reservoir is received in the inlet conduit. Thus, the liquid treatment device may be used to extract liquid from the liquid reservoir and to determine the presence or absence of a volume of liquid extracted from the liquid reservoir.

[0025] The liquid treatment device may further comprise a liquid extraction mechanism actuable from a first configuration to a second configuration, the liquid extraction mechanism configured to provide a pressure differential between the volume of gas in the liquid storage container and the liquid extraction outlet when the liquid extraction mechanism is actuated from the first configuration to the second configuration. Thus, the liquid treatment device may be used to extract liquid from the liquid storage container using a force applied by a user and provide an indication of the presence or absence of a volume of liquid extracted from the liquid storage container, such that a user may stop applying the force used to extract liquid from the liquid storage container.

[0026] The indicator region may enable an external device to determine the presence or absence of a volume of liquid in the sample validity control chamber using a sensor (e.g., an optical sensor, or an electrochemical sensor). Thus, a liquid handling system may comprise a liquid handling device according to any one of the previous paragraphs and an external device comprising a sensor (e.g., via the indicator region) configured to determine the presence or absence of a volume of liquid in the sample validity control chamber. The liquid handling device may be contained within an analytical device that controls the flow of fluid in the liquid handling device according to a diagnostic protocol, for example, to perform a diagnostic test. In such an example, the presence or absence of a volume of liquid may be detected using an optical sensor located within the analytical device. If the optical sensor detects the absence of a volume of liquid in the sample validity control chamber, the diagnostic test may be stopped immediately. This is advantageous in time-critical diagnostic tests, as it means that the user does not have to wait for the diagnostic test to be performed and an error message to be output, but can retry the diagnostic test using another liquid handling device.

[0027] Specific embodiments are now described, by way of example only, and with reference to the accompanying drawings. [Brief description of the drawings]

[0028] [Figure 1] FIG. 2 is a schematic diagram of a first liquid extraction device in fluid communication with the cartridge. [Figure 2A] FIG. 2 is a schematic diagram of the attachment of a first liquid extraction device to a cartridge. [Figure 2B] FIG. 13 is a schematic diagram of the attachment of a second liquid extraction device to a cartridge. [Diagram 3] FIG. 1 is an isometric view of a liquid handling device with a sample adequacy control chamber. [Figure 4] 4 is a front view of the first and second molded parts of the liquid treatment device shown in FIG. 3. [Diagram 5] FIG. 4 shows an assembly of the liquid treatment device shown in FIG. 3. [Figure 6]FIG. 4 is a front view of the liquid treatment device of FIG. 3 in an orientation used to determine the presence or absence of a volume of liquid, with some components shown partially transparent. [Figure 7] FIG. 13 is an isometric view of an alternative liquid handling device including a sample adequacy control chamber. [Figure 8] 8 is a front view of the first and second molded parts of the liquid treatment device shown in FIG. 7. [Figure 9] FIG. 8 shows an assembly of the liquid treatment device shown in FIG. 7. [Figure 10] FIG. 8 is a front view of the liquid treatment device of FIG. 7 in an orientation used to determine the presence or absence of a volume of liquid, with some components shown partially transparent. [Figure 11] FIG. 13 is an isometric view of a further alternative liquid handling device comprising a sample adequacy control chamber. [Figure 12] 12 is a front view of the first and second molded parts of the liquid treatment device shown in FIG. [Figure 13] FIG. 12 illustrates an assembly of the liquid treatment device shown in FIG. [Figure 14] FIG. 12 is a front view of the liquid treatment device of FIG. 11 in an orientation for use in determining the presence or absence of a volume of liquid, with some components shown partially transparent. [Figure 15] FIG. 1 shows a blood collection tube being inserted vertically into a liquid extraction device. [Figure 16A] FIG. 1 is a schematic diagram of the fluidic configuration of a liquid handling device including a sample adequacy control chamber. [Figure 16B] FIG. 16B is a schematic diagram of an equivalent circuit to the fluidic configuration shown in FIG. 16A. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0029] Embodiments of the present disclosure are described below with particular reference to liquid handling devices that include a sample adequacy indicator that indicates whether the volume of a sample received within the device is sufficient to perform a diagnostic test on the sample, however, it will be understood that the embodiments described herein may also be used to indicate the sufficiency of a liquid sample used in other contexts.

[0030] FIGURE 1 is a schematic diagram illustrating a first liquid extraction device 200 in fluid communication with a liquid treatment device in the form of a cartridge 100. As shown in FIGURE 1, the cartridge 100 includes a number of chambers in fluid communication via a number of conduits 102. Specifically, the multiple chambers include a main chamber 104, a reagent chamber 106, a mixing chamber 108, a waste chamber 110, and a measurement chamber 112. The cartridge 100 also includes a number of valves 114, each of which controls the flow of fluid through a respective conduit 102. A sensor 116 is used to perform a measurement (e.g., an electrochemical measurement) on the solution in the measurement chamber 112.

[0031] Fluid flow between the chambers is controlled by an external pump 120 configured to apply positive or negative pressure to the main chamber 104 via pump conduit 122. The positive or negative pressure either dispenses or aspirates fluid from one chamber to another depending on which of the valves 114 is open. For example, when aspirating a reagent from the reagent chamber 106 to the main chamber 104 (e.g., to mix with a sample), the valve 114 between the reagent chamber 106 and the main chamber 104 is opened and a negative pressure is applied to the main chamber 104 by the pump 120.

[0032] The liquid extraction device 200 is in fluid communication with the cartridge 100 via the inlet conduit 14. As described in more detail below, the liquid extraction device 200 is configured to extract a liquid sample (e.g., blood) from a puncturable liquid storage container (e.g., a blood collection tube, not shown in FIG. 1). Once the liquid sample is extracted from the liquid storage container, it is transferred under pressure via the inlet conduit 14 to the metering chamber 16. The liquid sample can then be drawn from the metering chamber 16 through the outlet conduit 43 and into the main chamber 104 by applying negative pressure using the pump 120.

[0033] The sample may then be combined with one or more reagents in the main chamber 104 by aspirating the reagents from the reagent chamber 106 into the main chamber 104. The solution may be repeatedly transferred between the main chamber 104 and the mixing chamber 108 to mix the sample and reagents. The solution may then be dispensed into the measurement chamber 112, where an electrochemical measurement is made on the solution using the sensor 116. Any effluent from the main chamber 104 or the measurement chamber 112 may be transferred to the waste chamber 110.

[0034] The liquid extraction apparatus 200 comprises a receptacle in the form of a cylinder 202 (or tube) in which a puncturable liquid storage container, such as a blood collection tube, is received. The liquid extraction apparatus 200 also includes an actuatable liquid extraction mechanism in the form of a piston 204 that is actuatable within the cylinder 202 from a first liquid extraction mechanism configuration to a second liquid extraction mechanism configuration. In FIG. 1, the piston 204 is shown in the second liquid extraction mechanism configuration.

[0035] Piston 204 includes a sealing element in the form of an O-ring seal 210 configured to provide a seal between piston 204 and cylinder 202. Cylinder 202 includes a recess 212 configured to compromise O-ring seal 210 by allowing air to flow around O-ring seal 210 when piston 204 is in the second configuration shown in FIG.

[0036] The liquid extraction device 200 includes a liquid reservoir interface (e.g., a blood collection tube interface) in the form of a needle 206 fixedly attached to a piston 204. The needle 206 is configured to puncture the liquid reservoir (e.g., by puncturing a septum of a blood collection tube). The needle 206 includes a liquid extraction outlet 208 through which liquid extracted from the blood collection tube can flow.

[0037] The cylinder 202 also includes an outlet 216 that allows for the removal of liquid from the liquid extraction device 200 after it has been extracted from the blood collection tube. The outlet 216 is in fluid communication with the inlet conduit 14, thereby allowing the liquid to be transferred from the liquid extraction device 200 to the cartridge 100.

[0038] In the first liquid extraction mechanism, the piston 204 is located above the outlet 216 in the cylinder 202 (ie, further from the end wall 218 of the cylinder 202 than shown in FIG. 1).

[0039] The piston 204 and the cylinder 202 together define a chamber. After connecting a blood collection tube to the needle 206, as the piston 204 is actuated from the first liquid extraction mechanism configuration to the second liquid extraction mechanism configuration, the volume of the chamber decreases. As the piston 204 is actuated past the outlet 216, the decrease in the volume of the chamber results in an increase in the pressure of the air in the chamber, since the chamber is sealed by the O-ring seal 210. The increase in air pressure in the chamber forces air into the blood collection tube through the needle 206, increasing the pressure of the volume of gas in the blood collection tube. The increase in pressure of the air in the chamber and the blood collection tube continues as the piston 204 is actuated toward the second configuration.

[0040] When the piston 204 is in the second configuration, the O-ring seal 210 is aligned with the recess 212 and is therefore compromised, meaning that the pressurized air in the chamber can flow around the O-ring seal 210. This reduces the pressure at the liquid extraction outlet 208, which is in fluid communication with the chamber, thereby creating a pressure differential between the volume of gas in the blood collection tube and the liquid extraction outlet 208. This pressure differential forces liquid out of the blood collection tube, through the needle 206, around the O-ring seal 210, and out of the liquid extraction device 200 via the outlet 216.

[0041] The liquid extraction apparatus 200 includes a safety mechanism 250 that is actuable from a first safety configuration (as shown in FIG. 1 ), in which the safety mechanism 250 conceals the needle 206, to a second safety configuration, in which the safety mechanism 250 exposes the needle 206. The safety mechanism 250 further includes a blocking element (not shown) that prevents actuation of the safety mechanism 250 from the first safety configuration to the second safety configuration when the liquid extraction apparatus 200 is in a first orientation (e.g., horizontal), but allows actuation of the safety mechanism 250 from the first safety configuration to the second safety configuration when the liquid extraction apparatus 200 is in a second orientation (e.g., vertical).

[0042] The cartridge 100 further comprises a sample adequacy control chamber 24 that provides a visual indication to a user that a sufficient amount of liquid has been extracted from a liquid storage container (e.g., a blood collection tube). In particular, the sample adequacy control chamber 24 may provide a visual indication that a sufficient volume of liquid has been extracted for a particular diagnostic test. For example, as shown in FIG. 15, the sample adequacy control chamber 24 is configured to provide a visual indication through an optically transparent window 130 in an upwardly disposed sidewall of the cartridge 100 when the liquid extraction device is in a vertical orientation (i.e., when the liquid extraction device is used to extract liquid from a liquid storage container).

[0043] The sample adequacy control chamber 24 forms part of a first flow path in fluid communication with the inlet conduit 14 (which receives fluid extracted using the liquid extraction device 200). The cartridge 100 also includes a metering chamber 16 configured to store a specific volume of liquid. The first flow path includes the metering chamber 16, a connector conduit 22 that provides a fluid connection between the metering chamber 16 and the sample adequacy control chamber 24, the sample adequacy control chamber 24, and a vent waste chamber 44 in fluid communication with the sample adequacy control chamber 24. The cartridge 100 further includes a second flow path comprising an outlet conduit 43 extending from an outlet port in the metering chamber 16. The outlet conduit 43 allows liquid to be aspirated into the main chamber 104 of the cartridge 100. As described in more detail below, alternative embodiments may not include a metering chamber 16 or a connector conduit 22, in which case the outlet conduit 43 extends from an outlet port in the sample adequacy control chamber configured to meter a specific volume of liquid.

[0044] The second flow path (including the outlet conduit 43) provides a higher hydraulic resistance than the first flow path (including the sample adequacy control chamber 24 and, optionally, the metering chamber 16 and connector conduit 22). This means that the flow rate of liquid through the first flow path is greater than the flow rate through the second flow path. The higher flow rate through the first flow path means that liquid can flow into the sample adequacy control chamber 24 without filling the outlet conduit 43, providing a visual indication that a sufficient volume of liquid has been received.

[0045] An embodiment of a liquid handling device including a sample adequacy control chamber will now be described in more detail with reference to Figures 3-16B.

[0046] The outlet 216 of the liquid extractor 200 shown in Figure 1 is provided in a side wall of the cylinder 202. Figure 2A shows the attachment between the first liquid extractor 200 and the cartridge 100 in more detail. When the outlet 216 is provided in the side wall of the cylinder 202, fluid communication between the liquid extractor 200 and the cartridge 100 may be provided by aligning the outlet 216 with a hole or via in the cartridge 100 that allows the passage of fluid into the inlet conduit 14. The alignment of the outlet 216 with the hole or via may be provided by attaching the liquid extractor 200 to the cartridge 100 using a layer of adhesive (e.g., pressure sensitive adhesive).

[0047] 2B illustrates an alternative attachment of a liquid extraction device to a cartridge, in which a second liquid extraction device 300 is attached to the cartridge (e.g., cartridge 100). Similar to the liquid extraction device 200 illustrated in FIG 2A, the liquid extraction device 300 includes a cylinder 302 in which a puncturable liquid storage container, such as a blood collection tube, is housed.

[0048] The liquid extraction device 300 also includes a piston 304 movable from a first configuration to a second configuration within the cylinder 302. Attached to the piston 304 is a liquid reservoir interface (e.g., a needle 306) that provides a path for air to enter the liquid reservoir and a path for liquid (e.g., blood) to exit the liquid reservoir.

[0049] However, in contrast to the liquid extractor 200 shown in Figure 2A, the cylinder 302 includes an outlet 316 provided in an end wall 318 of the cylinder 302. As shown in Figure 2B, the outlet 316 in the cylinder 302 may be in fluid communication with a connector 322 protruding from a base of the cylinder 302. The connector 322 allows the liquid extractor 300 to be attached to a cartridge by a push-fit attachment (e.g., by inserting the connector 322 into a corresponding hole or aperture in a cartridge), or by using a luer lock, or by any other suitable type of fluid connector.

[0050] It will be understood that these attachment mechanisms are not specific to the location of the outlet in the cylinder of the liquid extractor. In particular, the liquid extractor 300 shown in FIG. 2B may be attached to the cartridge using adhesive, and the liquid extractor 200 shown in FIG. 2A may include a connector protruding from the side wall of the cylinder 202, allowing it to be attached to the cartridge 100 using a push-fit or luer lock mechanism, or any other suitable type of fluid connector. Alternatively, the liquid extractors 200, 300 shown in FIGS. 2A and 2B may be integrated into the cartridge. For example, the cylinders 202, 302 may be molded (or otherwise manufactured) together with the cartridge 100.

[0051] Below, embodiments of liquid treatment devices are described that include a sample adequacy control chamber that allows for determining the presence or absence of a volume of liquid. Each of the embodiments of liquid treatment devices described below includes an inlet conduit configured to receive a liquid sample. The inlet conduit may be in fluid communication with an outlet from a liquid extraction device (e.g., as described above with reference to Figures 1, 2A and 2B) for extracting liquid from a liquid storage container, such that the liquid sample is extracted from the liquid storage container and transferred to the inlet conduit of the liquid treatment device. The liquid extraction device may be part of the same liquid treatment device as the liquid treatment device that includes the sample adequacy control chamber (e.g., part of a cartridge such as a microfluidic cartridge used to perform diagnostic tests on the liquid sample). Alternatively, the inlet conduit may receive the liquid sample from a syringe or pipette, in which case the liquid treatment device may not include a liquid extraction device.

[0052] The embodiments of the liquid handling device described herein comprise two flow paths in fluid communication with an inlet conduit. The first flow path comprises a sample adequacy control chamber, while the second flow path comprises an outlet conduit that allows liquid to be aspirated, for example, into other fluidic components of the cartridge. The second flow path is configured to provide a higher hydraulic resistance than the first flow path. This means that liquid will flow through the first flow path (and consequently into the sample adequacy control chamber) in preference to the second flow path.

[0053] The hydraulic resistance of the system (R h ) can be categorized into two components: frictional resistance and local (separation) resistance. Frictional resistance arises from momentum transfer to the surrounding walls and can be calculated using the Darcy-Weisbach empirical equation. Local resistance is caused by the dissipation of mechanical energy when the flow direction changes due to the formation of vortices. Local resistance can be caused by inlet and outlet features, bends and flow adaptors along the fluid flow path. Such local resistance can be calculated using theories for pipe constrictions or orifice discharges to atmosphere.

[0054] The total hydraulic resistance along a particular flow path can be calculated by summing the frictional resistance and the local resistance.

[0055]

number

[0056] In a network of conduits, the series sum can be used to calculate the equivalent resistance. Thus, for channels in series,

[0057]

number

[0058] From the above, it will be appreciated that the hydraulic resistance of a particular flow path may be tailored by adjusting the frictional or local resistance of fluid components along the flow path. In embodiments of liquid treatment devices described herein, the second flow path is configured to provide a higher hydraulic resistance than the first flow path.

[0059] 3-6 show a liquid treatment device 400 comprising a sample validity control chamber 424. The liquid treatment device 400 allows for determining the presence or absence of a volume of liquid in the sample validity control chamber 424. As best shown in FIG. 5, the liquid treatment device 400 comprises a first molded part 410, a second molded part 440, a first sealing layer 460 configured to seal one or more fluidic features in the first molded part 410, and a second sealing layer 480 configured to seal one or more fluidic features in the second molded part 440. Alternatively, the first sealing layer 460 and the second sealing layer 480 may be provided as a single sealing layer that seals the fluidic features of both the first molded part 460 and the second molded part 440. One or more of the first molded part 410 and the second molded part 440 may be formed from polycarbonate or polypropylene, for example. The components of liquid treatment device 400 are assembled using an adhesive, such as, for example, a pressure sensitive adhesive. First molded part 410 and second molded part 440 may define the fluidic components within a cartridge that is used to perform a diagnostic test (i.e., when liquid treatment device 400 is incorporated into such a cartridge). Alternatively, liquid treatment device 400 may be a stand-alone module that can be fluidly coupled to such a cartridge using a push-fit attachment, a luer lock, or any other suitable type of fluidic connector.

[0060] Returning to Figure 3, it can be seen that liquid treatment device 400 comprises a cylinder 412 defined by a first molded part 410. Cylinder 412 may be the cylinder of one of the liquid extraction devices 200, 300 described above with reference to Figures 1, 2A and 2B. That is, cylinder 412 may comprise a component of liquid extraction device 200, 300 used to extract liquid from a liquid storage container.

[0061] The liquid treatment device 400 further comprises an inlet conduit 414 that provides a fluid connection to the cylinder 412. The inlet conduit 414 is defined by the first molded part 410 and the first sealing layer 460.

[0062] Inlet conduit 414 is in fluid communication with a metering chamber 416, which is also defined by first molded part 410 and first seal layer 460. Metering chamber 416 is configured to store a specific volume of liquid and includes a metering chamber inlet port 418 (see FIG. 4) that provides a fluid connection to inlet conduit 414. Metering chamber 416 includes a first metering chamber outlet port, shown in FIG. 5 in the form of a hole 462 in first seal layer 460 and a corresponding hole 482 in second seal layer 480.

[0063] The first metering chamber outlet port provides a fluid connection between metering chamber 416 and a U-shaped outlet conduit 442 (shown in FIG. 4) defined by second molded part 440 and second seal layer 480. Outlet conduit 442 is vented to allow liquid to be aspirated from metering chamber 416 into another fluidic component of liquid treatment device 400. For example, if liquid treatment device 400 is incorporated into a cartridge (e.g., cartridge 100 shown in FIG. 1), outlet conduit 442 may allow liquid to be aspirated into a chamber of the cartridge (e.g., main chamber 104 in FIG. 1). Outlet conduit 442 is described in further detail below with reference to FIG. 4.

[0064] Returning to FIG. 3, it can be seen that the metering chamber 416 further comprises a second metering chamber outlet port 420 that provides a fluid connection to a connector conduit 422. The connector conduit 422 is defined by the first molded part 410 and the first seal layer 460. The connector conduit 422 provides a fluid connection between the metering chamber 416 and the sample adequacy control chamber 424 that is defined by the first molded part 410 and the first seal layer 460. The connector conduit 422 has a smaller cross-sectional area than the metering chamber 416 and the sample adequacy control chamber 424, which means that the connector conduit 422 defines a constriction between the metering chamber 416 and the sample adequacy control chamber 424. The constriction defined by the connector conduit 422 reduces the volume of the metering chamber 416 that is visible through the sample adequacy control chamber 424.

[0065] 4, the sample adequacy control chamber 424 has a conical shape with a wider upper end 426 and a narrower lower end 428 that provide a fluid connection to the connector conduit 422. The lower end 428 thus provides a sample adequacy control chamber inlet port to the sample adequacy control chamber 424. When the liquid treatment device 400 is used such that it can determine the presence or absence of a volume of liquid in the sample adequacy control chamber 424, the liquid treatment device 400 is in the orientation shown in FIG. 6. In this orientation, the sample adequacy control chamber 424 is located above the metering chamber 416, which means that the sample adequacy control chamber 424 is downstream of the metering chamber 416.

[0066] The sample validity control chamber 424 allows for the determination of the presence or absence of a volume of liquid within the sample validity control chamber 424. In the example shown in Figures 3-6, the liquid treatment device 400 includes an indicator area in the form of a transparent or translucent observation window 430 (shown in Figure 3) provided in a wall 402 of the liquid treatment device 400. The wall 402 is defined by a first molded part 410. The sample validity control chamber 424 is viewable through the indicator area within the liquid treatment device 400 (i.e., through the observation window 430).

[0067] When the liquid treatment device 400 is in use (i.e., to determine the presence or absence of a volume of liquid in the sample adequacy control chamber 424), the observation window 430 is positioned above the sample adequacy control chamber 424, as shown in Figure 6. In other words, the indicator region is downstream of the sample adequacy control chamber inlet port (i.e., the bottom end 428 of the sample adequacy control chamber 424).

[0068] 6, the top end 426 of the sample adequacy control chamber 424 is disposed above the bottom end 428 of the sample adequacy control chamber 424. Furthermore, the second metering chamber exit port 420 is disposed above the first metering chamber exit port, which is disposed above the metering chamber inlet port 418. In other words, the distance between the top end 426 of the sample adequacy control chamber 424 and the indicator region is less than the distance between the bottom end 428 of the sample adequacy control chamber 424. Also, the distance between the second metering chamber exit port 420 and the indicator region (observation window 430) is less than the distance between the first metering chamber exit port and the indicator region, which is less than the distance between the metering chamber inlet port 418 and the indicator region.

[0069] The sample validity control chamber 424 further comprises a waste outlet 432 (shown in FIG. 4) that provides a fluid connection to a waste chamber 444 defined by the second molded part 440 and the second sealing layer 480. The waste outlet 432 is provided between an upper end 426 of the sample validity control chamber 424 and a lower end 428 of the sample validity control chamber 424. The waste outlet 432 is provided in the form of an overflow from the sample validity control chamber 424, meaning that when the liquid level in the sample validity control chamber 424 reaches the level of the waste outlet 432, any additional liquid will overflow via the waste outlet 432 into the waste chamber 444. The fluid connection between the waste outlet 432 and the waste chamber 444 is provided by an opening 464 (shown in FIG. 5) in the first sealing layer 460 and a corresponding opening (not shown) in the second sealing layer 480.

[0070] As best shown in Figure 6, the waste chamber 444 is vented through a waste chamber vent 434 located in the second sealing layer 480. Fluid connection between the waste chamber 444 and the waste chamber vent 434 is provided by a vent hole 466 (shown in Figure 5) in the first sealing layer 460 and a corresponding opening (not shown) in the second sealing layer 480. The waste chamber vent 434 prevents pressurization of fluid in the waste chamber 444.

[0071] As best shown in Figure 4, the U-shaped outlet conduit 442 comprises a first outlet conduit section 446 that extends from the first metering chamber outlet port in a direction towards the sample adequacy control chamber 424. In other words, the first outlet conduit section 446 extends from the first metering chamber outlet port towards the indicator region (i.e., towards the wall 402 in which the observation window 430 is provided). As shown in Figure 6, which shows the orientation in which the liquid treatment device 400 is used, the first outlet conduit section 446 extends vertically from the first metering chamber outlet port towards the wall 402 (i.e., in the direction of the indicator region) in use.

[0072] The outlet conduit 442 further comprises a U-shaped bend 448 connecting the first outlet conduit section 446 to a second outlet conduit section 450 that extends parallel to the first outlet conduit section 446 and then curves away from the first outlet conduit section 446 to extend perpendicular to the first outlet conduit section 446. After extending perpendicular to the first outlet conduit section 446, the second outlet conduit section 450 terminates at an end 452 of the outlet conduit 442.

[0073] Liquid treatment device 400 thus comprises two flow paths, each in fluid communication with inlet conduit 414. The first flow path comprises a portion of metering chamber 416 downstream of first metering chamber outlet port, second metering chamber outlet port 420, connector conduit 422, sample adequacy control chamber 424, waste outlet 432, and waste chamber 444. The second flow path comprises first metering chamber outlet port and outlet conduit 442. The junction between the two flow paths is within metering chamber 416. Thus, the first metering chamber outlet port provides an inlet to the second flow path.

[0074] The second flow path provides a higher hydraulic resistance than the first flow path. To provide the higher hydraulic resistance of the second flow path, the outlet conduit 442 is narrower (i.e., has a smaller cross-sectional area) than each of the inlet conduit 414 and the metering chamber 416, and has a cross-sectional area equal to or less than the cross-sectional area of ​​the connector conduit 422. The smaller cross-sectional area of ​​the outlet conduit 442 provides an increased hydraulic resistance than the inlet conduit 414, the metering chamber 416, and the connector conduit 422. In addition, the outlet conduit 442 is longer than the connector conduit 422, which also serves to increase its hydraulic resistance. Furthermore, as liquid is forced into the first outlet conduit section 446, a column of liquid is formed in the first outlet conduit section 446. This column of liquid increases the hydraulic resistance to further liquid flow into the second flow path. The hydraulic resistance of the second flow path is also higher than the hydraulic resistance of the sample adequacy control chamber 424.

[0075] In use, liquid treatment device 400 is initially oriented in the orientation shown in Figure 6. In this orientation, liquid may be extracted from a liquid reservoir using a liquid extraction mechanism disposed within cylinder 412 (e.g., as described with reference to Figure 1), resulting in liquid flowing under pressure into inlet conduit 414. As mentioned above, inlet conduit 414 may alternatively receive a flow of liquid from, for example, a pipette or syringe.

[0076] The pressurized liquid flows through inlet conduit 414 and into metering chamber 416, filling metering chamber 416. At the same time, some liquid is forced into the second flow path (i.e., through the first metering chamber outlet port and into outlet conduit 442). However, as a result of the higher hydraulic resistance of the second flow path, liquid has a tendency to flow through the first flow path, thereby filling metering chamber 416, meaning that only a small amount of liquid is forced into outlet conduit 442. The flow of liquid into the second flow path is further slowed by the pressure head of any liquid in first outlet conduit section 446 when liquid treatment device 400 is in the orientation shown in FIG. 6 (i.e., when observation window 430 is facing upwards, meaning that observation window 430 is higher than inlet conduit 414). Additionally, the flow of liquid through the first metering chamber outlet port (i.e., the inlet to the second flow path provided by holes 462, 482) creates a pressure drop in the liquid, further reducing the tendency for liquid to flow into the second flow path.

[0077] During filling of the metering chamber 416, the percentage of the metering chamber 416 that is visible through the observation window 430 in the sample adequacy control chamber 424 is minimized by the smaller cross-sectional area of ​​the connector conduit 422 acting as a visual constriction. The constriction provided by the connector conduit 422 reduces the risk that a user will misidentify the liquid in the metering chamber 416 as a volume of liquid in the sample adequacy control chamber 424. After the metering chamber 416 is filled, the constriction provided by the connector conduit 422 also helps prevent air bubbles from entering the metering chamber 416 (e.g., if the liquid treatment device 400 is moved or shaken).

[0078] Once the metering chamber 416 is filled, the pressurized liquid continues to flow through the first flow path. In particular, the pressurized liquid flows through the constriction provided by the connector conduit 422 and begins to fill the sample adequacy control chamber 424. At this point, the user can view the volume of liquid in the sample adequacy control chamber 424 through the observation window 430 in the wall 402 of the liquid handling device 400. The conical shape of the sample adequacy control chamber 424 means that the diameter of the visual indicator of the volume of liquid increases as the sample adequacy control chamber 424 fills. When the user determines that there is a volume of liquid in the sample adequacy control chamber 424, the flow of liquid into the inlet conduit 414 can be stopped. For example, the user can stop applying force to the blood collection tube from which liquid is being extracted using the liquid extraction mechanism disposed in the cylinder 412. This is because the user knows that for liquid to be present in the sample adequacy control chamber 424, the metering chamber 416 must be filled. As a result, the user knows that a sufficient volume of liquid required for a particular diagnostic test (i.e., the volume of metering chamber 416) has been received into the liquid treatment device 400. The user also knows that the blood collection tube can be removed from cylinder 412 and that the diagnostic test can be performed.

[0079] When the liquid level in the sample adequacy control chamber 424 reaches the waste outlet 432, any additional liquid introduced into the sample adequacy control chamber 424 flows over the overflow provided by the waste outlet 432 and subsequently into the vented waste chamber 444.

[0080] The higher relative hydraulic resistance provided by the second flow path encourages the flow of liquid through the first flow path and into the sample adequacy control chamber 424 rather than into the outlet conduit 442. This means, for example, that a user can determine that a sufficient volume of liquid has been received into the liquid treatment device 400 for a particular diagnostic test without the unintended flow of liquid into other fluidic components of the cartridge.

[0081] To increase the hydraulic resistance provided by the second flow path, the extent of the first outlet conduit section 446 in the direction of the indicator area (i.e., the observation window 430) is maximized. For example, the first outlet conduit section 446 may extend to the same height as the bottom end 428 of the sample adequacy control chamber 424 (when viewed from the orientation shown in FIG. 6). Alternatively, the first outlet conduit section 446 may extend further than the bottom end 428 or further than the waste outlet 432 to further impede the flow of liquid into the outlet conduit 442 by maximizing the potential pressure head provided by the liquid in the first outlet conduit section 446 when the liquid treatment device 400 is in the orientation shown in FIG. 6. This reduces the tendency for liquid to flow past the U-shaped bend 448 in the outlet conduit 442, thereby reducing unintended aspiration of liquid (e.g., into the cartridge).

[0082] It should be noted that instead of the user determining the presence or absence of a volume of liquid, a sensor (e.g., an optical sensor) of an external device may be used to determine the presence or absence of a volume of liquid. For example, the liquid treatment device 400 may be implemented in a cartridge used to perform diagnostic tests. The cartridge may be housed in an analytical device that controls the flow of fluid in the cartridge according to a diagnostic protocol to perform the diagnostic test. In such an example, the presence or absence of a volume of liquid may be detected using an optical sensor located in the analytical device. If the optical sensor detects that the volume of liquid in the sample validity control chamber 424 is not present, the diagnostic test may be stopped immediately. This is advantageous in time-critical diagnostic tests, as it means that the user does not have to wait for the diagnostic test to be performed and an error message output, and the user can retry the diagnostic test using a different cartridge. Instead of using an optical sensor, the analytical device may include an alternative detection means (e.g., an electrochemical detection means) to detect the presence or absence of a volume of liquid in the sample validity control chamber 424.

[0083] Figures 7-10 show an alternative liquid treatment device 500 which includes a sample adequacy control chamber 524. In contrast to the liquid treatment device 400 shown in Figures 3-6, the metering functionality of the liquid treatment device 500 is provided by the sample adequacy control chamber 524, meaning that there is no separate metering chamber.

[0084] Liquid treatment device 500 comprises a first molded part 510, a second molded part 540, a first sealing layer 560, and a second sealing layer 580 (optionally combined into a single sealing layer), each of which has the same function as the corresponding features of liquid treatment device 400 shown in Figures 3-6, except for the differences described below.

[0085] The liquid treatment device 500 further comprises an inlet conduit 514 providing a fluid connection to the cylinder 512. The inlet conduit 514 is in fluid communication with a sample validity control chamber 524. The sample validity control chamber 524 comprises a sample validity control chamber outlet port shown in FIG. 9 in the form of a hole 562 provided in the first sealing layer 560 and a corresponding hole 582 provided in the second sealing layer 580. The sample validity control chamber outlet port provides a fluid connection between the sample validity control chamber 524 and an outlet conduit 542 that allows liquid to be aspirated from the sample validity control chamber 524 to another fluidic component of the liquid treatment device 500. The outlet conduit 542 has the same structure as the outlet conduit 442 of the liquid treatment device 400 shown in FIGS. 3-6.

[0086] Returning to Figure 8, it can be seen that the sample validity control chamber 524 has a conical shape with a wider upper end 526 and a narrower lower end 528. The lower end 528 provides a sample validity control chamber inlet port to the sample validity control chamber 524. The sample validity control chamber inlet port provides a fluid connection to the inlet conduit 514.

[0087] The sample adequacy control chamber 524 of the liquid treatment device 500 includes a pad 590 of porous or absorbent material that is exposed to the liquid in the sample adequacy control chamber 524. The pad 590 is visible through an indicator area of ​​the liquid treatment device 500. Specifically, in the example shown in Figures 7-10, the pad 590 is visible through a transparent or semi-transparent observation window 530 provided in the wall 502 of the liquid treatment device 500. The pad 590 provides a visual indicator when liquid contacts the pad 590. For example, a user may be able to see the liquid as it passes through the pad of porous material or as it is absorbed by the pad of absorbent material. As another example, the pad 590 may change color as it absorbs liquid.

[0088] When the liquid treatment device 500 is in use (i.e., to enable the presence or absence of a volume of liquid in the sample adequacy control chamber 524 to be determined), the liquid treatment device 500 is in the orientation shown in Figure 10. In this orientation, the sample adequacy control chamber outlet port is located above the sample adequacy control chamber inlet port (i.e., bottom end 528). In other words, the distance between the sample adequacy control chamber outlet port and the indicator region (e.g., observation window 530) is less than the distance between the sample adequacy control chamber inlet port and the indicator region.

[0089] In liquid treatment device 500, second molded part 540 is extended (relative to second molded part 440 of liquid treatment device 400) so that it overlaps with the top end of sample adequacy control chamber 524 (when viewed in the orientation shown in FIG. 10 ). This means that second molded part 540 occludes liquid in inlet conduit 514 such that the liquid in inlet conduit 514 is not visible through wall 502 of liquid treatment device 500.

[0090] 8, the sample adequacy control chamber 524 includes a waste outlet 532 that provides a fluid connection to the waste chamber 544, which is vented via a waste chamber vent 534. The waste outlet 532 is provided between an upper end 526 of the sample adequacy control chamber 524 and a lower end 528 of the sample adequacy control chamber 524. In particular, the waste outlet 532 is provided above a fill level of a specific volume of liquid required for a diagnostic test. The waste outlet 532 is provided in the form of an overflow from the sample adequacy control chamber 524, meaning that once the sample adequacy control chamber 524 contains a specific volume of liquid required for a diagnostic test, any additional liquid will overflow via the waste outlet 532 into the waste chamber 544.

[0091] The sample adequacy control chamber 524 further comprises an overflow subchamber 536 in fluid communication with the waste outlet 532 and an opening 564 in the first sealing layer 560 (and a corresponding opening 584 in the second sealing layer 580) providing a fluid connection to the waste chamber 544.

[0092] The waste outlet 532 provides a narrowed flow path to the overflow subchamber 536. A pad 590 of porous or absorbent material is disposed above the waste outlet 532. This means that liquid passing through the narrowed flow path provided by the waste outlet 532 passes over the pad 590 of porous or absorbent material. Once the liquid passes through the waste outlet 532, it flows into the overflow subchamber 536 and subsequently through the openings 564, 584 into the waste chamber 544.

[0093] Thus, liquid treatment device 500 comprises two flow paths, each in fluid communication with inlet conduit 514. The first flow path comprises the portion of sample validity control chamber 524 downstream of the sample validity control chamber outlet port, waste outlet 532, overflow subchamber 536, and waste chamber 544. The second flow path comprises the sample validity control chamber outlet port and outlet conduit 542. The junction between the flow paths is within sample validity control chamber 524, meaning that the sample validity control chamber outlet port provides an inlet to the second flow path. Similar to liquid treatment device 400 described above, the second flow path of liquid treatment device 500 provides a higher hydraulic resistance than the first flow path.

[0094] In use, the liquid treatment device 500 is initially oriented in the orientation shown in Figure 10. The inlet conduit 514 receives a flow of pressurized liquid in this orientation. The pressurized liquid flows through the inlet conduit 514 into the sample adequacy control chamber 524. The liquid flows into the first flow path as a result of its low hydraulic resistance, thereby filling the sample adequacy control chamber 524 to the level of the waste outlet 532. This means that the sample adequacy control chamber 524 contains the volume of liquid required for the diagnostic test.

[0095] At the same time, some liquid is forced through the sample adequacy control chamber outlet port into the second flow path and into the outlet conduit 542. However, as a result of the higher hydraulic resistance of the second flow path, liquid has a tendency to flow through the first flow path, thereby filling the sample adequacy control chamber 524, which means that only a small amount of liquid is forced into the outlet conduit 542.

[0096] While the sample adequacy control chamber 524 is filling, the liquid within the sample adequacy control chamber 524 is not visible through the walls 502 of the liquid treatment device 500. When the liquid fills the sample adequacy control chamber 524 to the level of the waste outlet 532, the liquid flows through the waste outlet 532 and over a pad 590 of porous or absorbent material, which is visible through the observation window 530. When the liquid contacts the pad 590, the user can determine the presence of a volume of liquid within the sample adequacy control chamber 524. In particular, the user determines that a sufficient volume of liquid required for a particular diagnostic test has been received by the liquid treatment device 500.

[0097] Liquid flowing through waste outlet 532 enters overflow subchamber 536 under gravity and then flows into vent waste chamber 544 .

[0098] The lack of a separate metering chamber and connector conduit means that there is no constriction at the inlet to the sample adequacy control chamber 524 of fluid treatment device 500. This means that there is a lower backpressure on the outlet conduit 442 compared to the backpressure on the outlet conduit 542 of fluid treatment device 400 shown in Figures 3-6. Additionally, by using the sample adequacy control chamber 524 to meter a specific volume of fluid, a lower volume of blood is required to indicate the presence or absence of a sufficient volume of fluid compared to fluid treatment device 400. As a result, fluid treatment device 500 requires a reduced volume of sample to perform a diagnostic test compared to fluid treatment device 400.

[0099] The constriction provided by waste outlet 532 prevents air bubbles from entering sample adequacy control chamber 524 after sample adequacy control chamber 524 fills (eg, when the liquid handling device is moved or shaken).

[0100] As a modification of the liquid treatment device 500 described above, the pad of porous or absorbent material 590 may not be used. In this case, a visual indication of the presence of liquid in the sample adequacy control chamber 524 is provided by the flow of liquid through the waste outlet 532, which is visible through the observation window 530.

[0101] Figures 11-14 show a further alternative liquid treatment device 600 that includes a sample adequacy control chamber 624. In contrast to liquid treatment device 500 shown in Figures 7-10, the waste outlet from sample adequacy control chamber 624 of liquid treatment device 600 flows directly into the waste chamber without flowing through a constricted flow path.

[0102] The liquid treatment device comprises a first molded part 610, a second molded part 640, a first sealing layer 660, and a second sealing layer 680 (optionally combined into a single sealing layer), each having the same functionality as the corresponding features of liquid treatment device 400 shown in Figures 3-6, except for the differences described below.

[0103] Similar to the liquid treatment device 500 shown in Figures 7-10, the liquid treatment device 600 shown in Figures 11-14 includes an inlet conduit 614 that provides a fluid connection to the cylinder 612. The inlet conduit 614 is in fluid communication with a sample validity control chamber 624. The sample validity control chamber 624 includes a sample validity control chamber outlet port, shown in Figure 13 in the form of a hole 662 in the first sealing layer 660 and a corresponding hole 682 in the second sealing layer 680. The sample validity control chamber outlet port provides a fluid connection between the sample validity control chamber 624 and an outlet conduit 642 that allows liquid to be drawn from the sample validity control chamber 624 to another fluidic component of the liquid treatment device 600. The outlet conduit 642 has the same structure as the outlet conduit 442 of the liquid treatment device 400 shown in Figures 3-6.

[0104] 12, it can be seen that the sample validity control chamber 624 has a conical shape with a wider upper end 626 and a narrower lower end 628. The lower end 628 provides a sample validity control chamber inlet port to the sample validity control chamber 624. The sample validity control chamber inlet port provides a fluid connection to the inlet conduit 614.

[0105] The sample validity control chamber 624 of the liquid treatment device 600 includes a pad 690 of porous or absorbent material that is exposed to the liquid in the sample validity control chamber 624. The pad 690 is visible through an indicator area of ​​the liquid treatment device 600. Specifically, in the example shown in Figures 11-14, the pad 690 is visible through a transparent or semi-transparent observation window 630 provided in the wall 602 of the liquid treatment device 600. The pad 690 provides a visual indicator when liquid contacts the pad 690. For example, a user may be able to see the liquid as it passes through the pad of porous material or as it is absorbed by the pad of absorbent material. As another example, the pad 690 may change color when it absorbs liquid.

[0106] When the liquid treatment device 600 is in use (i.e., to enable the presence or absence of a volume of liquid in the sample adequacy control chamber 624 to be determined), the liquid treatment device 600 is in the orientation shown in Figure 14. In this orientation, the sample adequacy control chamber outlet port is located above the sample adequacy control chamber inlet port (i.e., bottom end 628). In other words, the distance between the sample adequacy control chamber outlet port and the indicator region (e.g., observation window 630) is less than the distance between the sample adequacy control chamber inlet port and the indicator region.

[0107] The sample adequacy control chamber 624 comprises a waste outlet that provides a fluid connection to a waste chamber 644 having the same structure as the waste chamber 444 of the liquid treatment device 400. The waste chamber 644 is vented via a waste chamber vent (not shown). The waste outlet is provided in the form of an opening 664 in the first sealing layer 660 and a corresponding opening 684 in the second sealing layer 680. The waste outlet is provided between an upper end 626 of the sample adequacy control chamber 624 and a lower end 628 of the sample adequacy control chamber 624. In particular, the waste outlet is provided above the fill level of a specific volume of liquid required for a diagnostic test. The waste outlet (i.e., openings 664, 684) is provided in the form of an overflow from the sample adequacy control chamber 624, meaning that once the sample adequacy control chamber 624 contains a specific volume of liquid required for a diagnostic test, any additional liquid will overflow into the waste chamber 644 via the waste outlet.

[0108] A pad 690 of porous or absorbent material is positioned such that the flow of liquid from the sample adequacy control chamber 624 through the waste outlet flows over the pad 690 .

[0109] Thus, liquid treatment device 600 comprises two flow paths, each in fluid communication with inlet conduit 614. The first flow path comprises the portion of sample validity control chamber 624 downstream of the sample validity control chamber outlet port, a waste outlet from sample validity control chamber 624, and waste chamber 644. The second flow path comprises the sample validity control chamber outlet port and outlet conduit 642. The junction between the flow paths is within sample validity control chamber 624, meaning that the sample validity control chamber outlet port provides an inlet to the second flow path. Similar to liquid treatment device 400 described above, the second flow path of liquid treatment device 600 provides a higher hydraulic resistance than the first flow path.

[0110] In use (ie, in the orientation shown in FIG. 14), operation of liquid treatment device 600 is the same as operation of liquid treatment device 500 described above, with the following exceptions.

[0111] Before the fill level of the sample adequacy control chamber 624 reaches the level of the waste outlet, the pad 690 of porous or absorbent material acts as an occluding material that occludes the contents of the sample adequacy control chamber 624. When liquid fills the sample adequacy control chamber 624 to the level of the waste outlet, the liquid flows through the waste outlet (i.e., openings 664, 684) and over the pad 690 of porous or absorbent material, which can be seen through the observation window 630. When liquid contacts the pad 690, the user can determine the presence of a volume of liquid in the sample adequacy control chamber 624. In particular, the user determines that a sufficient volume of liquid required for a particular diagnostic test has been received by the liquid treatment device 600.

[0112] Liquid flowing through the waste outlet subsequently flows into vented waste chamber 644 . The lack of a constriction in the waste outlet from sample adequacy control chamber 624 of fluid treatment device 600 means that the backpressure on outlet conduit 642 is lower compared to the backpressure on outlet conduit 542 of fluid treatment device 500 and outlet conduit 442 of fluid treatment device 400. Additionally, the use of sample adequacy control chamber 624 to meter a specific volume of fluid reduces the amount of blood required to indicate the presence or absence of a sufficient volume of fluid compared to fluid treatment device 400. As a result, fluid treatment device 600 requires a reduced sample volume to perform a diagnostic test compared to fluid treatment device 400.

[0113] The pad of porous or absorbent material 690 may be configured to provide a visual indication when in contact with a number of different types of liquid sample (e.g., serum, blood, plasma), meaning that a cartridge comprising the liquid handling device 600 may be used for a wide variety of diagnostic tests involving different liquid sample types.

[0114] FIG. 15 shows a blood collection tube 11 being inserted into the cylinder of the liquid extraction device 200. In this example, the liquid extraction device 200 is integral with a cartridge 100 that includes the functionality of the liquid treatment device 400 described above. As described above with reference to FIGS. 1, 2A and 2B, the liquid extraction device comprises a liquid reservoir interface (e.g., a needle) configured to provide a fluid connection to the blood collection tube 11. The liquid reservoir interface comprises a liquid extraction outlet configured to allow liquid to be extracted from the blood collection tube 11. The liquid extraction outlet is in fluid communication with an inlet conduit in the cartridge (e.g., inlet conduit 414 of the liquid treatment device 400) such that liquid extracted from the blood collection tube 11 is received in the inlet conduit.

[0115] Again, as described above with reference to Figures 1, 2A and 2B, the liquid extraction apparatus 200 further comprises a liquid extraction mechanism operable from a first configuration to a second configuration, the liquid extraction mechanism configured to provide a pressure differential between the volume of gas in the liquid storage container and the liquid extraction outlet when the liquid extraction mechanism is actuated from the first configuration to the second configuration.

[0116] The blood collection tube 11 is shown inserted into the cylinder when the cartridge 100 is in a vertical orientation. Figure 15 also shows an indicator area in the form of an optically transparent observation window 130 in the side wall of the cartridge 100. The sample adequacy control chamber (and / or pad of porous or absorbent material) is visible through the window 130. The window 130 may be provided, for example, in the form of an observation window 430 in the liquid treatment device 400.

[0117] 16A is a schematic diagram of a fluidic configuration of a liquid treatment device including a sample adequacy control chamber 24. The fluidic configuration is described with reference to the fluidic components shown in FIG. 1. In particular, the inlet to inlet conduit 14 (e.g., an outlet from the liquid extraction device) is shown as point (1), the metering chamber inlet port is shown as point (2), a first metering chamber outlet port providing a fluid connection to outlet conduit 43 is shown as point (3), the end of outlet conduit 43 is shown as point (4), a second metering chamber outlet port providing a fluid connection to connector conduit 22 is shown as point (5), and a waste outlet from sample adequacy control chamber 24 providing a fluid connection to waste chamber 44 is shown as point (6).

[0118] Figure 16B is a schematic diagram of a circuit equivalent to the fluid configuration shown in Figure 16A. As shown in Figure 16B, each of points (1)-(6) provides a respective local resistance RhL1-RhL6. Additionally, a frictional resistance Rh1 / 2 is provided between points (1) and (2) (i.e., inlet conduit 14), a frictional resistance Rh3 / 4 is provided between points (3) and (4) (i.e., outlet conduit 43), a frictional resistance Rh2 / 5 is provided between points (2) and (5) (i.e., metering chamber 16), and a frictional resistance Rh5 / 6 is provided between points (5) and (6) (i.e., connector conduit 22 and sample adequacy control chamber 24).

[0119] The pressure at point (1) is P1, which is greater than atmospheric pressure (P0), meaning that pressurized fluid is provided to the liquid treatment device. The pressure at point (6) is the sum of atmospheric pressure P0 and a gravitational pressure component (i.e., ρgh6) resulting from the elevation of point (6) above point (1). The pressure at point (4) is the sum of atmospheric pressure P0 and a gravitational pressure component (i.e., ρgh4) resulting from the elevation of point (4) above point (1).

[0120] As shown in Figures 16A and 16B, two flow paths are in fluid communication with the inlet conduit 14. A first flow path is provided along points (2), (5), and (6). A second flow path is provided between points (3) and (4). The liquid flow rate through the inlet conduit 14 is QA and the liquid flow rate through the second flow path is Q B and the liquid flow rate through the first flow path is represented as Q C It is represented by Q A =Q B +Q C It will be understood that.

[0121] To prevent liquid from entering the cartridge through the second flow path (i.e., (3)-(4)), Q B Q C much smaller than Q B ≪Q C It must be.

[0122] The resistance along a circular pipe assuming turbulent flow can be calculated using the Darcy-Weisbach empirical formula and a circular cross section.

[0123]

number

[0124] During the ceremony, Δp is the pressure drop between two points in the pipe, f D is the Darcy friction coefficient calculated from an approximation such as the Colebrook equation or the Churchill equation, L is the length of the pipe between the two points, g=9.81m / s 2 , D is the diameter of the pipe K i is the hydraulic resistance coefficient of the pipe, Q is the flow rate.

[0125] Using Equation 3, the frictional components of the hydraulic resistance provided by the conduits / channels shown in Figures 16A and 16B (i.e., Rh1 / 2, Rh3 / 4, Rh2 / 5 and Rh5 / 6) can be calculated. As can be seen from Equation 3, the hydraulic resistance is inversely proportional to the square of the flow rate.

[0126] The local resistance offered by an orifice or via (e.g., point (3)) can be derived using the theory of flow through an orifice plate and the Bernoulli equation, which is an approximation of the through point (3).

[0127]

number

[0128] During the ceremony, C d is the discharge coefficient, typically 0.65 to 0.7 for a via or orifice.

[0129] d is the diameter of the via or orifice, D is the diameter of the pipe (i.e., upstream of the via or orifice), P 上流 is the pressure upstream of the via or orifice, P 下流 is the pressure downstream of the via or orifice, ρ is the density of the liquid.

[0130] From equation 4, we get:

[0131]

number

[0132] During the ceremony, Δp is the pressure drop between points upstream and downstream of the via or orifice; K3 is the hydraulic resistance coefficient of the orifice or via (eg, at point (3)).

[0133] As can be seen from Equation 5, here too the hydraulic resistance is inversely proportional to the square of the flow rate. The local resistance provided by the constriction at point (5) (i.e., the constriction provided by the connector conduit 22) can be derived using expansion and contraction flow theory. The local resistance depends on the angle of the constriction. The local resistance is given by:

[0134]

number

[0135] During the ceremony, Δp is the pressure difference between points upstream and downstream of the constriction; K5 is the hydraulic resistance coefficient of the constriction (e.g., at point (5)); Q is the flow rate.

[0136] The formula for K5 depends on the angle of the constriction (i.e., the angle of the constriction between the wider upstream pipe and the narrower downstream pipe; a step constriction has θ=90°). Specifically, for θ≦45°:

[0137]

number

[0138] During the ceremony, θ is the angle of the constriction, d is the diameter of the pipe downstream of the constriction, D is the diameter of the pipe upstream of the constriction.

[0139] For θ>45°:

[0140]

number

[0141] As can be seen from Equation 6, here too, the hydraulic resistance is inversely proportional to the square of the flow rate.

[0142] The total hydraulic resistance of the first flow path (points (2)-(5)-(6)) is given by:

[0143]

number

[0144] The total hydraulic resistance of the second flow path (points (3) to (4)) is given by:

[0145]

number

[0146] From the above equation, it can be seen that the total hydraulic resistance of the first and second flow paths, ignoring the height variation between points (4) and (6), is inversely proportional to the square of the flow rate through each path.

[0147]

number

[0148] In the formula, K i is the hydraulic resistance coefficient of the flow path. Equation 11 This means that:

[0149]

number

[0150] As mentioned above, the ends of the first and second flow paths are at atmospheric pressure, which means that the pressure drop across the first flow path is the same as the pressure drop across the second flow path, ignoring the height variations between points (4) and (6).

[0151] This means that: K C ×Q C 2 =K B ×Q B 2 , which is KB / K C =Q C 2 / Q B 2 means.

[0152] To provide a lower flow rate through the second flow path, the flow rate Q through the first flow path is C is the flow rate Q through the second flow path B N times higher than, i.e.,

[0153]

number

[0154] Q B N times higher flow rate Q C To provide a hydraulic resistance of N2 greater than the hydraulic resistance of the first flow path, as shown in Equation 14, 2 It needs to be twice as big.

[0155]

number

[0156] As one specific example of adjusting the hydraulic resistance of the second flow path, the target time to extract liquid from the blood collection tube and visually indicate that a sufficient volume of liquid (approximately 300 μL or less) has been extracted is 10 to 30 seconds. In this specific example, the expected flow rate Q through the first flow path is adjusted to ensure that the outlet conduit does not completely fill during extraction of liquid. C is 5-30 μL / s, and the preferred flow rate Q through the second flow path B is 0.1 to 1 μL / s.

[0157] In this embodiment, preferred values ​​of N are 5, 20 and 50. From Equation 14, to provide a value of N=5, the hydraulic resistance of the second flow path must be N times greater than the hydraulic resistance of the first flow path. 2 = 25 times higher, that is, the hydraulic resistance of the second flow path must be N = 25 times higher than the hydraulic resistance of the first flow path to provide a value of N = 20. 2= 400 times higher, and to provide a value of N = 50, the hydraulic resistance of the second flow path must be N = 400 times higher than the hydraulic resistance of the first flow path. 2 It can be seen that the required value is 2500 times higher.

[0158] Further variations or modifications to the systems and methods described herein are described in the following paragraphs.

[0159] The indicator region of the liquid treatment device described above may further comprise an occluding material on a wall of the device through which the sample adequacy control chamber is visible. The occluding material may be provided in the form of roughness introduced into the molded wall forming the top of the sample adequacy control chamber, the roughness configured to appear hazy when dry and transparent when wet. In this case, the occluding material is the same material as the material of the first or second molded parts. The occluding material may be configured to occlude at least a portion of the sample adequacy control chamber until the occluding material comes into contact with a quantity of liquid.

[0160] For example, the liquid treatment device 400 may include an occluding material that occludes the liquid in the metering chamber 416 until the liquid reaches a certain fill level in the sample adequacy control chamber 424. As another example, the liquid treatment device 500 may include an occluding material instead of extending the second molded part 540 to cover the top of the sample adequacy control chamber 524. In the liquid treatment device 500, 600, the occluding material may be provided on the pad 590, 690 of porous or absorbent material, or may be incorporated into the pad 590, 690 such that the pad 590, 690 is only visible when the occluding material comes into contact with a volume of liquid. As a further example, the liquid treatment device 600 may incorporate an occluding material instead of the pad 690 of porous or absorbent material such that the interior of the sample adequacy control chamber 624 can be viewed when the occluding material comes into contact with a volume of liquid. The occluding material may be a material that becomes optically more transparent when in contact with a volume of liquid (e.g., using the optical coupling effect).

[0161] Although the above embodiments have been described with respect to extracting liquid from blood collection tubes such as Vacutainers (RTM), it will be appreciated that the above embodiments are also suitable for extracting liquid from other forms of puncturable liquid storage containers that may differ in size and / or shape from blood collection tubes. In such cases, the dimensions of the cylinder may be adapted to the size and shape of the liquid storage container from which liquid is to be extracted.

[0162] Additionally, although the above embodiments use a liquid reservoir interface (e.g., a blood collection tube interface) in the form of one or more needles, other liquid reservoir interfaces may be implemented as long as they are capable of providing a fluid connection to a volume of liquid in a liquid reservoir (e.g., to a volume of liquid in a blood collection tube 11).

[0163] The term "needle" in the above embodiments is not intended to be limited to metal needles, but is intended to encompass other piercing elements configured to pierce the septum of a blood collection tube, such as a piercing element integral with a piston.

[0164] Finally, although the above embodiments are described with respect to a force applied by a user to activate the liquid extraction mechanism, it will be appreciated that the liquid extraction mechanism may alternatively be activated without requiring user input (e.g., under the control of a motor).

[0165] As a general point, although the above embodiments have been described with respect to extracting liquid for use in diagnostic tests performed using the cartridge, it will be appreciated that the liquid handling device described above is suitable for enabling the presence or absence of a volume of liquid in a sample adequacy control chamber to be determined for a wide range of other purposes.

[0166] The term "chamber" as used herein is not intended to convey a particular shape or dimension of the chamber. Furthermore, use of the term "chamber" does not imply that there is a gradual change in cross-sectional area at the interface between the "conduit" and the "chamber." In particular, the chambers described herein may be implemented using a continuous conduit having a wider cross-section in the region of the chamber.

[0167] The term "conduit," as used herein, is intended to mean any form of enclosed passage through which a fluid can flow, and may alternatively be referred to as a passage, channel, pipe, or duct.

[0168] The term "port" as used herein is intended to mean an opening that provides a fluid entry or exit point in a conduit, and may alternatively be referred to as an opening, via, orifice, hole, or aperture.

[0169] The singular terms "a" and "an" should not be construed to mean "one and only one." Rather, they should be construed to mean "at least one" or "one or more," unless otherwise specified. The word "comprising" and its derivatives, including "comprises" and "comprises," includes each of the described features but does not exclude the inclusion of one or more additional features.

[0170] The above-described embodiments have been described by way of example only, and the described embodiments are to be considered in all respects only as illustrative and not restrictive. It will be understood that modifications may be made to the described embodiments without departing from the scope of the invention. It will also be apparent that there are many variations which have not been described but which are within the scope of the appended claims.

Claims

1. an inlet conduit configured to receive a liquid sample; a first flow path in fluid communication with the inlet conduit, the first flow path including a sample adequacy control chamber configured to enable determining the presence or absence of a volume of liquid within the sample adequacy control chamber; a second flow path in fluid communication with the inlet conduit, the second flow path configured to provide a higher hydraulic resistance than the first flow path; A liquid treatment device comprising:

2. 10. The liquid treatment device of claim 1, wherein the sample adequacy control chamber comprises a visible indicator area to enable a user to determine the presence or absence of the volume of liquid in the sample adequacy control chamber.

3. 3. The liquid treatment device of claim 2, wherein the indicator area through which the sample adequacy control chamber is visible is downstream of a sample adequacy control chamber inlet port in the first flow path.

4. 10. The liquid treatment device of claim 1, wherein the second flow path comprises an outlet conduit, the outlet conduit having a smaller cross-sectional area than the inlet conduit.

5. the sample adequacy control chamber comprising: a sample adequacy control chamber inlet port configured to receive liquid from the inlet conduit; a sample adequacy control chamber outlet port in fluid communication with the second flow path; Equipped with 3. The liquid treatment device of claim 2, wherein the distance between the sample adequacy control chamber outlet port and the indicator area is less than the distance between the sample adequacy control chamber inlet port and the indicator area.

6. The first flow path further comprises a metering chamber configured to store a specific volume of liquid, the metering chamber comprising: a metering chamber inlet port configured to receive liquid from the inlet conduit; a metering chamber outlet port in fluid communication with the second flow path; The liquid treatment device according to claim 1 or 2, comprising:

7. 7. The liquid treatment device of claim 6, wherein the first flow path comprises a connector conduit providing a fluid connection between the metering chamber and the sample adequacy control chamber.

8. The liquid treatment device of claim 7 , wherein the cross-sectional area of the connector conduit is smaller than the cross-sectional area of the metering chamber.

9. 8. A liquid treatment device according to claim 7, wherein the second flow path comprises an outlet conduit, and wherein the cross-sectional area of the connector conduit is equal to or greater than the cross-sectional area of the outlet conduit.

10. 7. The liquid treatment device of claim 6, wherein the sample adequacy control chamber is downstream of the metering chamber.

11. 7. The liquid treatment device of claim 6 when dependent on claim 2, wherein the distance between the metering chamber outlet port and the indicator area is less than the distance between the metering chamber inlet port and the indicator area.

12. 3. The liquid treatment device of claim 2, wherein the second flow path comprises an outlet conduit section extending toward the indicator area.

13. 10. The liquid treatment device of claim 1, wherein the first flow path comprises a vented waste chamber in fluid communication with the sample adequacy control chamber.

14. 14. The liquid treatment device of claim 13, wherein the sample adequacy control chamber comprises a waste outlet providing a fluid connection to the waste chamber, the waste outlet being located between an upper end and a lower end of the sample adequacy control chamber, and the distance between the upper end of the sample adequacy control chamber and an indicator region is less than the distance between the lower end of the sample adequacy control chamber and the indicator region.

15. 10. The liquid treatment device of claim 1, further comprising a pad of porous material, said pad configured to contact liquid within said sample adequacy control chamber.

16. 10. The liquid treatment device of claim 1, further comprising a pad of absorbent material, said pad configured to absorb liquid within said sample adequacy control chamber.

17. 10. The liquid treatment device of claim 1, further comprising an occluding material disposed on a wall of the liquid treatment device through which the sample adequacy control chamber is visible, the occluding material configured to occlude at least a portion of the sample adequacy control chamber until the occluding material contacts a quantity of liquid.

18. a liquid reservoir interface configured to provide a fluid connection to a volume of liquid in a puncturable liquid reservoir, the liquid reservoir interface comprising a liquid extraction outlet configured to allow extraction of liquid from the liquid reservoir; the liquid extraction outlet is in fluid communication with the inlet conduit such that liquid extracted from the liquid storage vessel is received by the inlet conduit; The liquid treatment device of claim 1 .

19. 20. A liquid treatment device as described in claim 18, further comprising a liquid extraction mechanism actuatable from a first configuration to a second configuration, the liquid extraction mechanism configured to provide a pressure differential between a volume of gas in the liquid storage vessel and the liquid extraction outlet when the liquid extraction mechanism is actuated from the first configuration to the second configuration.

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