Liquid Treatment Equipment

Abstract

Embodiments described herein relate to a liquid treatment device comprising a first rigid layer and a second rigid layer, a fluid layer disposed between the first rigid layer and the second rigid layer, the fluid layer being formed from an elastomer, the fluid layer comprising a network of channels, and a fluid network comprising a plurality of conduits, the plurality of conduits being defined at least in part by the network of channels in the fluid layer.

Description

[Technical field]

[0001] SUMMARY The present disclosure relates to liquid treatment devices, liquid treatment systems, and methods for moving liquid within liquid treatment devices. [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 samples, reagents, buffers, etc.) within the diagnostic device and performs the measurement of biomarkers to perform the diagnostic test. Summary of the Invention [Problem to be solved by the invention]

[0003] Point-of-care detection brings convenient and immediate diagnostic testing to patients, allowing better and faster clinical decisions to be made. However, integrating diagnostic testing into a point-of-care device or system is difficult. Sample preparation for immunoassays may require mixing of multiple solutions and reagents with precise control of volumes and mixing times. Furthermore, the device would ideally be automated to eliminate the need for a medical professional to be present.

[0004] Thus, there is a need for improved liquid handling devices capable of performing liquid handling operations for use in point-of-care diagnostic testing. [Means for solving the problem]

[0005] 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. The inclusion of multiple statements in the same paragraph of the Summary does not imply that a structural or functional relationship exists between such statements.

[0006] According to a first aspect of the present disclosure, there is provided a liquid treatment device comprising a first rigid layer and a second rigid layer, a fluid layer disposed between the first rigid layer and the second rigid layer, the fluid layer being formed from an elastomer, the fluid layer comprising a network of channels, and a fluid network comprising a plurality of conduits, the plurality of conduits being at least partially defined by the network of channels in the fluid layer.

[0007] The use of channels in an elastomer layer improves sealing of the fluid network regardless of the adhesive process (e.g., pressure-sensitive adhesive (PSA) tape, laser welding, etc.) used to seal the network because the elastomer layer acts as a resilient layer when sealed to another layer. Additionally, providing the channels in a flexible elastomer layer allows the channels to be compressed to provide valves in the liquid treatment devices. Thus, the flow of liquid in the liquid treatment devices can be controlled by compressing the channels in the elastomer layer which closes the valves in the liquid treatment devices. The use of a single layer for the network of channels also simplifies the construction of the liquid treatment devices.

[0008] The liquid treatment device may further comprise a plurality of valves, each of which may be configured to close a corresponding one of the plurality of conduits, the valves allowing the flow of liquid within the liquid treatment device to be controlled.

[0009] Each of the plurality of valves may comprise a deformable valve region disposed in the fluidic layer. Each deformable valve region may be deformable to a deformed state in which a corresponding one of the plurality of conduits is blocked. Providing the deformable valve regions in the fluidic layer simplifies construction of the liquid treatment device, as the fluidic layer implements both the conduits of the device and the valves of the device.

[0010] The fluidic layer may comprise a first surface configured to face the first rigid layer and a second surface configured to face the second rigid layer. At least a portion of the network of channels may be provided on the second surface. Each deformable valve region may comprise a depression on the first surface of the fluidic layer. The depression may be aligned with a corresponding channel of at least a portion of the network of channels provided on the second surface. Providing a depression on the first surface of the fluidic layer reduces the volume of material that needs to be deformed to close each valve of the liquid treatment device. This reduces the force required to close each valve.

[0011] A subset of the network of channels may be provided on the first side. Providing channels on both sides of the fluidic layer means that the available area for providing respective adhesive regions around the channels is increased, which is particularly important in view of the limited area available on the fluidic layer due to the small size of the point-of-care device. Providing channels on the first side also allows the channels of the fluidic layer to intersect, meaning that more complex networks of channels can be implemented.

[0012] The first rigid layer may comprise a plurality of openings. Each deformable valve region may be accessible through one of the plurality of openings. Providing openings in the rigid layer means that the liquid treatment device has a rigid housing while still allowing the valves to be actuated by application of an external force (e.g., from an actuator of an analytical device).

[0013] The liquid treatment device may further comprise a plurality of openings extending through at least a portion of the thickness of the fluidic layer. Each of the plurality of openings may be in fluid communication with one of the plurality of conduits. The plurality of openings may include a first plurality of openings and a second plurality of openings. The second plurality of openings may be different from the first plurality of openings. The plurality of openings allows fluid in the fluidic layer (i.e., either liquid or air provided from the pneumatic supply system) to communicate with fluidic components in other layers.

[0014] The liquid treatment device may further comprise a plurality of ports configured to provide a seal against the pneumatic interface. Each of the plurality of ports may comprise a protrusion protruding from a surface of the fluidic layer and a respective one of the first plurality of openings. The respective one of the first plurality of openings may extend through the protrusion. Implementing the ports in an elastomeric fluidic layer allows the ports to form a seal with the pneumatic interface because the fluidic layer acts as a compliant layer when a force is applied to the ports by a pneumatic interface (e.g., a pneumatic actuator of a pneumatic supply system). Providing the ports in the same fluidic layer as the network of channels also simplifies the construction of the liquid treatment device. Fluid communication between the ports and the conduits allows liquid to move within the conduits by applying pneumatic pressure through the ports.

[0015] Each protrusion may have a frusto-conical shape. The frusto-conical shape of the protrusion aids in the formation of a seal between the port and the pneumatic interface because the frusto-conical shape narrows the cross-section of the protrusion as it increases in height above the surface. In other words, the frusto-conical shape provides less material at the top of the protrusion than at the base of the protrusion due to the sloping walls provided by the frusto-conical shape. The reduced cross-section at the top of the protrusion means that less material needs to be deformed by the pneumatic interface to provide a seal around the port. Less material to deform means that a smaller amount of force needs to be applied to compress the port.

[0016] Each of the first plurality of openings may have a diameter that increases with increasing height above the surface of the fluid layer, further reducing the amount of material on top of the protrusion, resulting in less force being required to deform the port.

[0017] Each protrusion may include an annular rim around the open end of the protrusion. The annular rim may define an area of ​​minimum cross-sectional area of ​​the protrusion. The annular rim further reduces the amount of material at the top of the protrusion, which means that less force is required to deform the protrusion.

[0018] One or more of the plurality of ports may further comprise a plurality of support ribs. Each of the plurality of support ribs may extend between the protrusion and a surface of the fluid layer from which the protrusion protrudes. The support ribs help prevent excessive deformation of the port when a force is applied to the port by the pneumatic interface.

[0019] The first rigid layer may comprise a plurality of openings. Each port may be accessible through one of the plurality of openings. Providing openings in the rigid layer means that the liquid handling device has a rigid housing while allowing air pressure to be applied to the ports using an external pneumatic interface (e.g., a pneumatic actuator of an analytical device).

[0020] Each of the multiple ports can be in fluid communication with one of the multiple conduits through a corresponding trough in the second rigid layer. The trough prevents liquid from reaching the port that connects to the pneumatic interface. Thus, the trough prevents liquid from reaching the pneumatic interface, especially during aspiration of liquid. Such liquid could potentially contaminate or damage the pneumatic interface (e.g., in an analytical device). In particular, any liquid drawn from a channel in the fluidic layer between the aspiration pools at the bottom of the trough does not reach the port. Thus, any liquid drawn from the channel is not drawn through the port into the pneumatic interface.

[0021] The liquid treatment device may further include at least one liquid storage capsule disposed over two of the second plurality of openings. Disposing the liquid storage capsule over the openings allows the fluidic network to interface with the liquid storage capsule. This also allows the capsule to be deformed into the openings to form the openings in the capsule.

[0022] The fluidic layer may include one or more chambers, each of which is in fluid communication with one of the conduits. The provision of chambers in the fluidic layer simplifies the construction of liquid handling devices. In particular, the provision of one or more chambers in the fluidic layer expands the functionality of the fluidic layer.

[0023] The fluid layer may comprise a protrusion extending from a surface of the fluid layer. The protrusion may comprise a plurality of cavities. Each of the one or more chambers may be at least partially defined by a corresponding one of the plurality of cavities. Providing a protrusion extending from a surface of the fluid layer means that the volume of the chamber is not limited by the thickness of the fluid layer. Thus, an increased chamber volume may be provided.

[0024] The liquid treatment device may further comprise a sealing film. The plurality of conduits may be defined by a network of channels in the fluidic layer and the sealing film. The flexibility of the elastomeric fluidic layer aids in the channels being sealed by the sealing film.

[0025] Each channel comprises a groove provided in the surface. Each channel therefore has an open cross-section. In other words, the cross-section of each channel is not sealed. Each conduit (i) comprises a channel that is sealed (e.g., by a sealing layer), thereby providing a closed cross-section, or (ii) comprises a hole or tunnel that extends at least partially through the body.

[0026] According to a second aspect of the present disclosure, there is provided a liquid treatment device comprising first and second rigid layers, a fluid network comprising a plurality of conduits, and a fluid layer disposed between the first and second rigid layers, the fluid layer being formed from an elastomer, the fluid layer comprising a plurality of ports configured to provide a seal against a pneumatic interface, each of the plurality of ports comprising a protrusion extending from a surface of the fluid layer and an opening extending through the protrusion and at least a portion of a thickness of the fluid layer, the opening being in fluid communication with one or more of the plurality of conduits.

[0027] Each protrusion may have a frusto-conical shape. The frusto-conical shape of the protrusion aids in the formation of a seal between the port and the pneumatic interface because the frusto-conical shape narrows the cross-section of the protrusion as it increases in height above the surface. In other words, the frusto-conical shape provides less material at the top of the protrusion than at the base of the protrusion due to the sloping walls provided by the frusto-conical shape. The reduced cross-section at the top of the protrusion means that less material needs to be deformed by the pneumatic interface to provide a seal around the port. Less material to deform means that a smaller amount of force needs to be applied to compress the port.

[0028] Each of the first plurality of openings may have a diameter that increases with increasing height above the surface of the fluid layer, further reducing the amount of material on top of the protrusion, resulting in less force being required to deform the port.

[0029] Each protrusion may include an annular rim around the open end of the protrusion. The annular rim may define an area of ​​minimum cross-sectional area of ​​the protrusion. The annular rim further reduces the amount of material at the top of the protrusion, which means that less force is required to deform the protrusion.

[0030] One or more of the plurality of ports may further comprise a plurality of support ribs. Each of the plurality of support ribs may extend between the protrusion and a surface of the fluid layer from which the protrusion protrudes. The support ribs help prevent excessive deformation of the port when a force is applied to the port by the pneumatic interface.

[0031] The first rigid layer may comprise a plurality of openings. Each port may be accessible through one of the plurality of openings. Providing openings in the rigid layer means that the liquid handling device has a rigid housing while allowing air pressure to be applied to the ports using an external pneumatic interface (e.g., a pneumatic actuator of an analytical device).

[0032] Each of the multiple ports can be in fluid communication with one of the multiple conduits through a corresponding trough in the second rigid layer. The trough prevents liquid from reaching the port that connects to the pneumatic interface. Thus, the trough prevents liquid from reaching the pneumatic interface, especially during aspiration of liquid. Such liquid could potentially contaminate or damage the pneumatic interface (e.g., in an analytical device). In particular, any liquid drawn from a channel in the fluidic layer between the aspiration pools at the bottom of the trough does not reach the port. Thus, any liquid drawn from the channel is not drawn through the port into the pneumatic interface.

[0033] The second rigid layer may include a plurality of supports, each of which may be aligned with a corresponding one of the plurality of ports such that each of the plurality of supports prevents deformation of a surface of the fluidic layer when a force is applied to the corresponding one of the plurality of ports, which aids the ports in forming a seal with the pneumatic interface.

[0034] The fluidic layer may comprise a network of channels. Each of the plurality of conduits may be at least partially defined by a network of channels in the fluidic layer. The use of channels in an elastomeric layer improves sealing of the fluidic network regardless of the adhesive process (e.g., pressure-sensitive adhesive (PSA) tape, laser welding, etc.) used to seal the network, since the elastomeric layer acts as an elastic layer when sealed to another layer. Additionally, providing the channels in a flexible elastomeric layer allows the channels to be compressed to provide valves in the liquid treatment device. Thus, the flow of liquid in the liquid treatment device can be controlled by compressing the channels in the elastomeric layer, which closes the valves of the liquid treatment device. The use of a single layer for the network of channels and ports also simplifies the construction of the liquid treatment device.

[0035] The fluid layer of the liquid treatment device according to the first or second embodiment may be formed from a thermoplastic elastomer, optionally a silicone-based thermoplastic elastomer or a styrene-ethylene-butylene-styrene. Such materials should be selected (e.g., by selecting an appropriate grade) to have sufficient hardness to prevent excessive deformation of the fluid layer, and sufficient relaxation time to allow the components of the fluid layer (i.e., ports, channels) to return to their original form when the applied force is removed.

[0036] According to a third aspect of the present disclosure, there is provided a liquid treatment device comprising a rigid layer and a plurality of liquid storage capsules disposed within the liquid treatment device, the rigid layer comprising an actuatable portion actuatable from a first position in which the actuatable portion does not deform the plurality of liquid storage capsules to a second position in which the actuatable portion deforms two or more of the plurality of liquid storage capsules.

[0037] Assuming that a single actuatable portion is capable of deforming two or more of the multiple liquid storage capsules, actuation of the actuatable portion to the second position causes simultaneous deformation of each of the two or more capsules. As a result, multiple capsules in a liquid treatment device can be punctured using a single movement of the actuatable portion. Deforming two or more liquid storage capsules using a single actuatable portion also means that liquid storage capsules of several different configurations can be punctured by the actuatable portion. Thus, the rigid layer and the actuatable portion can be used with a fluid network that implements liquid storage capsules of various configurations.

[0038] The actuatable portion may include a plurality of protrusions. Each of the plurality of protrusions may extend toward one of the plurality of liquid storage capsules. Each of the plurality of protrusions may be configured to apply a force to a corresponding portion of the liquid storage capsule when the actuatable portion is in the second position. The protrusions provide a mechanism for deforming the liquid storage capsule to puncture the liquid storage capsule.

[0039] The plurality of protrusions may be configured to engage two different portions of each of two or more of the plurality of liquid storage capsules when the actuatable portion is in the second position, meaning that two different portions of the capsule can be deformed simultaneously, meaning that two openings (e.g., an inlet and an outlet) can be created in the liquid storage capsule simultaneously.

[0040] The actuatable portion may comprise a plurality of recessed regions. Each of the plurality of recessed regions may be located between two of the plurality of protrusions. Each recessed region may be configured to accommodate a main chamber of a corresponding liquid storage capsule when the actuatable portion is in the second position. This means that the main chamber is not deformed by the actuatable portion when the actuatable portion is in the second position. Thus, the recessed regions maximize the volume of the liquid storage capsule that can be provided.

[0041] The plurality of protrusions may be a first plurality of protrusions. The actuatable portion may further comprise a second plurality of protrusions. Each of the first plurality of protrusions may extend further from the actuatable portion than each of the second plurality of protrusions. Each of the second plurality of protrusions may extend towards one of the plurality of liquid storage capsules. Each of the second plurality of protrusions may be configured to apply a force to a corresponding portion of the liquid storage capsule when the actuatable portion is in a third position. The third position may be beyond the second position. This allows for a two-stage puncture of the liquid storage capsules, which means that liquid can be released from some capsules before other capsules are punctured.

[0042] The rigid layer may comprise one or more elastically deformable members coupled to the actuatable portion. The one or more elastically deformable members may be configured to bias the actuatable portion away from the second position. This means that the elastically deformable members move the actuatable portion out of engagement with the capsule, thereby allowing the actuatable portion to return to its original position and preventing the actuatable portion from impeding the flow of fluid into or out of the capsule.

[0043] Each of the one or more elastically deformable members may be formed from the same material as the rigid layer, which allows for simplified manufacture of the rigid part, including the actuatable portion and the elastically deformable members, (e.g., manufactured by injection molding).

[0044] The rigid layer may comprise two or more elastically deformable members. Providing multiple elastically deformable members allows the actuatable portion to be actuated in a vertical direction, meaning that the actuatable portion is parallel to the base (i.e., the sealing layer) of each liquid storage capsule when the actuatable portion is in the first portion and when the actuatable portion is in the second position. The vertical movement of the actuatable portion allows a consistent force to be applied to the liquid storage capsule (e.g., via a protrusion on the actuatable portion). A first elastically deformable member of the two or more elastically deformable members may be connected to a first edge of the actuatable portion, and a second elastically deformable member of the two or more elastically deformable members may be connected to a second edge of the actuatable portion, the second edge being different from the first edge. The second edge may be opposite the first edge.

[0045] The actuatable portion may comprise a plurality of flat regions disposed on an outer surface of the actuatable portion, the flat surfaces of the actuatable portion allowing the actuatable portion to be easily moved from a first position to a second position (e.g., by an actuator of an analytical device) without requiring a specific shaped actuator to move the actuatable portion.

[0046] The liquid treatment device may further comprise a fluid layer comprising a plurality of openings extending through at least a portion of a thickness of the fluid layer. Each of the plurality of liquid storage capsules may be disposed over a corresponding one of the plurality of openings. For each of the plurality of liquid storage capsules, deformation of the liquid storage capsule by the actuatable portion may cause a portion of the liquid storage capsule to be transformed into the corresponding one of the plurality of openings. Disposing the liquid storage capsule over the opening allows the capsule to be transformed into the opening by the actuatable portion to create an opening in the capsule.

[0047] The rigid layer may be a first rigid layer. The fluid layer may be disposed between the first rigid layer and the second rigid layer. The second rigid layer may comprise a plurality of capsule support regions arranged to contact the fluid layer during actuation of the actuatable portion. Each of the plurality of capsule support regions may be aligned with a corresponding one of the plurality of openings. This means that when a force is applied to the plurality of capsules by the actuatable portion, the fluid layer is prevented from being deformed by the corresponding capsule support region.

[0048] The actuatable portion may be actuatable relative to a plane of the rigid layer. The actuatable portion may be rigid. The actuatable portion may be actuatable in a direction perpendicular to the plane of the rigid layer. The actuatable portion may be parallel to a base of one or more of the plurality of liquid storage capsules when the actuatable portion is in a first position and parallel to a base of one or more of the plurality of liquid storage capsules when the actuatable portion is in a second position.

[0049] According to a fourth aspect of the present disclosure, there is provided a liquid handling system comprising a liquid handling device according to the third aspect of the present disclosure, an actuator configured to actuate an actuatable part of the liquid handling device from a first position to a second position, thereby deforming two or more liquid storage capsules, and an air pressure supply system configured to supply air pressure to at least one of the two or more liquid storage capsules, meaning that a single liquid handling system can be used to puncture the liquid storage capsule and to displace liquid from the liquid storage capsule.

[0050] According to a fifth aspect of the present disclosure, there is provided a liquid treatment device comprising a fluid layer comprising a network of channels, a sealing layer arranged to seal the network of channels to form a plurality of conduits, the sealing layer comprising an opening, and a measurement chamber in fluid communication with at least one of the plurality of conduits, the measurement chamber being defined in part by the opening in the sealing layer.

[0051] By implementing a sealing layer that seals the network of channels and has an opening that partially defines the measurement chamber, the tendency for liquid to remain in the measurement chamber is reduced because there is no constriction between the channel in the fluidic layer and the measurement chamber. Construction of liquid handling equipment is also simplified because the layer used to seal the network of channels is also utilized to provide the measurement chamber.

[0052] The sealing layer may be disposed over the fluidic layer. Covering the fluidic layer increases the bonding area surrounding the network of channels. The sealing layer may be in direct contact with the fluidic layer.

[0053] The thickness of the sealing layer can define the height of the measurement chamber, which allows the volume of the measurement chamber to be defined by the sealing layer and layers on either side of the sealing layer.

[0054] The measurement chamber may include a first end and a second end opposite the first end. A first conduit of the plurality of conduits may be in fluid communication with the first end of the measurement chamber. A second conduit of the plurality of conduits may be in fluid communication with the second end of the measurement chamber. This allows liquid to be transported through the measurement chamber (e.g., to a waste chamber).

[0055] The measurement chamber may include a first tapered section extending between a first end and a central portion of the measurement chamber. The measurement chamber may further include a second tapered section extending between the central portion and a second end. In the first tapered section, an angle between a wall of the measurement chamber and a longitudinal centerline extending through the measurement chamber may be less than 30 degrees. Similarly, in the second tapered section, an angle between a wall of the measurement chamber and a longitudinal centerline extending through the measurement chamber may be less than 30 degrees. A taper angle of less than 30 degrees reduces the tendency for air bubbles to form during filling or emptying the measurement chamber. A taper angle of less than 30 degrees also reduces the tendency for residual liquid to remain in the measurement chamber after emptying the measurement chamber.

[0056] In the first tapered section, the angle between the wall of the measurement chamber and the longitudinal centerline can be between about 15 degrees and about 25 degrees. Similarly, in the second tapered section, the angle between the wall of the measurement chamber and the longitudinal centerline can be between about 15 degrees and about 25 degrees. The taper angle in this region reduces the tendency for air bubbles to form during filling or emptying, and for residual liquid to remain after emptying, while still providing a useful contact area between the interior of the measurement chamber and a sensor surface in fluid communication with the interior of the measurement chamber.

[0057] A second conduit of the plurality of conduits may be aligned with a longitudinal centerline extending through the measurement chamber. Aligning the second conduit of the plurality of conduits with the longitudinal centerline minimizes the volume of liquid remaining in the measurement chamber after the measurement chamber is emptied, while also reducing loss of particles (e.g., blood or functionalized beads) in the flow suspension flowing through the measurement chamber.

[0058] The angle between the second of the plurality of conduits and the longitudinal centerline may be 150 degrees or more, more preferably about 180 degrees. An angle of 150 degrees or more minimizes the volume of liquid remaining in the measurement chamber after emptying the measurement chamber. An angle of 180 degrees keeps the volume of liquid remaining in the measurement chamber low after emptying the measurement chamber, while also reducing the loss of particles (e.g., blood or functional beads) in the flow suspension flowing through the measurement chamber.

[0059] The liquid treatment device may include a plurality of measurement chambers. The sealing layer may include a plurality of openings. Each of the plurality of measurement chambers may be defined in part by a corresponding one of the plurality of openings in the sealing layer.

[0060] According to a sixth aspect of the present disclosure, there is provided a liquid treatment device comprising: a fluidic layer comprising a network of channels; a sealing layer arranged to seal the network of channels to form a plurality of conduits, the sealing layer comprising a plurality of holes; a flow cell layer comprising an opening, the sealing layer being arranged between the fluidic layer and the flow cell layer; and a measurement chamber in fluid communication with at least one of the plurality of conduits via one of the plurality of holes, the measurement chamber being partially defined by the opening in the flow cell layer.

[0061] Each of the plurality of holes may be aligned with one end of a respective one of the networks of channels, meaning that the hole provides a fluid connection between the channel in the fluidic layer and a measurement chamber defined in part by an opening in the flow cell layer.

[0062] The thickness of the flow cell layer can define the height of the measurement chamber, which allows the volume of the measurement chamber to be defined by layers on either side of the flow cell layer and the sealing layer.

[0063] The measurement chamber may include a first end and a second end opposite the first end. A first conduit of the plurality of conduits may be in fluid communication with the first end of the measurement chamber through a first hole of the plurality of holes. A second conduit of the plurality of conduits may be in fluid communication with the second end of the measurement chamber through a second hole of the plurality of holes. This allows liquid to be transported through the measurement chamber (e.g., to a waste chamber).

[0064] The measurement chamber may include a first tapered section extending between a first end and a central portion of the measurement chamber. The measurement chamber may further include a second tapered section extending between the central portion and a second end. In the first tapered section, an angle between a wall of the measurement chamber and a longitudinal centerline extending through the measurement chamber may be less than 30 degrees. Similarly, in the second tapered section, an angle between a wall of the measurement chamber and a longitudinal centerline extending through the measurement chamber may be less than 30 degrees. A taper angle of less than 30 degrees reduces the tendency for air bubbles to form during filling or emptying the measurement chamber. A taper angle of less than 30 degrees also reduces the tendency for residual liquid to remain in the measurement chamber after emptying the measurement chamber.

[0065] In the first tapered section, the angle between the wall of the measurement chamber and the longitudinal centerline can be between about 15 degrees and about 25 degrees. Similarly, in the second tapered section, the angle between the wall of the measurement chamber and the longitudinal centerline can be between about 15 degrees and about 25 degrees. The taper angle in this region reduces the tendency for air bubbles to form during filling or emptying, and for residual liquid to remain after emptying, while still providing a useful contact area between the interior of the measurement chamber and a sensor surface in fluid communication with the interior of the measurement chamber.

[0066] A second conduit of the plurality of conduits may be aligned with a longitudinal centerline extending through the measurement chamber. Aligning the second conduit of the plurality of conduits with the longitudinal centerline minimizes the volume of liquid remaining in the measurement chamber after the measurement chamber is emptied, while also reducing loss of particles (e.g., blood or functionalized beads) in the flow suspension flowing through the measurement chamber.

[0067] The angle between the second conduit of the plurality of conduits and the longitudinal centerline may be 150 degrees or more. An angle of 150 degrees or more minimizes the volume of liquid remaining in the measurement chamber after emptying the measurement chamber. The angle between the second conduit of the plurality of conduits and the longitudinal centerline may be about 180 degrees. An angle of 180 degrees keeps the volume of liquid remaining in the measurement chamber low after emptying the measurement chamber, while also reducing the loss of particles (e.g., blood or functional beads) in the flow suspension flowing through the measurement chamber.

[0068] The first end can be a first rounded end having a first constant curvature. The second end can be a second rounded end having a second constant curvature. A radius of a first hole of the plurality of holes can be equal to the first constant radius of curvature. A radius of a second hole of the plurality of holes can be equal to the second constant radius of curvature. Matching the hole radius to the radius of curvature minimizes the combined volume of liquid remaining in the measurement chamber and the hole after emptying the measurement chamber. Matching the hole radius to the radius of curvature also increases the tolerance to any misalignment during assembly of the layers of the liquid treatment device.

[0069] An origin of a first hole of the plurality of holes may coincide with an origin of the first constant curvature. An origin of a second hole of the plurality of holes may coincide with an origin of the second constant curvature. Aligning the holes and the origin of the curvature minimizes the combined volume of liquid remaining in the measurement chamber and the holes after the measurement chamber is emptied.

[0070] The liquid treatment device may include a plurality of measurement chambers. The flow cell layer may include a plurality of openings. Each of the plurality of measurement chambers may be defined in part by a corresponding one of the plurality of openings in the flow cell layer.

[0071] According to a seventh aspect of the present disclosure, there is provided a liquid treatment device comprising a rigid layer having a first well and a second well, a vent arranged to provide a fluid connection to an outside of the liquid treatment device, the second well being in fluid communication with the vent, and a plurality of grooves extending between the first well and the second well, each of the plurality of grooves providing a fluid connection between the first well and the second well.

[0072] By providing two or more paths for liquid flow between the first and second wells, the possibility of liquid blockage between the first and second wells is reduced. Avoiding liquid blockage between the first and second wells allows the first and second wells to be used as part of a fluid circuit for aspiration of liquid, since air can be drawn from the permanent vent through the second well into the first well during aspiration of liquid from a fluidic component in fluid communication with the first well.

[0073] One or more of the plurality of grooves may be disposed above a base of a first well. The depth of the first well may be greater than a maximum depth of one or more of the plurality of grooves. This means that liquid must flow over a step between the base of the first well and the base of the one or more grooves, which step blocks the flow of liquid into the one or more grooves.

[0074] One or more of the plurality of grooves may be disposed above a base of a second well. The depth of the second well may be greater than the maximum depth of one or more of the plurality of grooves. This means that any liquid in the second well must flow over a step between the base of the second well and the base of the one or more grooves, which step blocks the flow of liquid into the one or more grooves.

[0075] One or more of the plurality of grooves may comprise a first end adjacent to the first well and a second end adjacent to the second well. The second end may be disposed above the first end. The depth of the first end may be greater than the depth of the second end. One or more of the plurality of grooves may comprise a sloped base extending between the first end and the second end. The effect of the sloped base means that even if liquid flows into the one or more grooves, the pressure required to remove liquid from the one or more grooves is reduced. This is because the sloped base of the one or more grooves forces the liquid to flow under gravity towards the first well. In other words, the grooves are more likely to empty when negative pressure is applied to the first well. The sloped shape also serves as a capillary stop, preventing the liquid from proceeding to the second well.

[0076] The liquid treatment device may further comprise a third well in fluid communication with the second well and the vent. The second well may be in fluid communication with the vent through the third well. The liquid treatment device may further comprise a connector channel extending between the second well and the third well. The third well and the connector channel provide an additional fluid component between the second well and the vent, which provides additional resistance to the flow of liquid between the second well and the vent. This reduces the possibility of liquid leaking out of the liquid treatment device through the vent.

[0077] The connector channel may be disposed above a base of the second well. The depth of the second well may be greater than the depth of the connector channel. The connector channel may comprise a plurality of grooves extending between the second well and the third well. Providing the connector channel above the base of the second well means that any liquid in the second well must flow over a step between the base of the second well and the base of the connector channel, which step blocks the flow of liquid into the connector channel. Providing the connector channel in the form of a plurality of grooves provides a plurality of fluid flow paths between the second well and the third well, thereby reducing the possibility of liquid blockage between the second well and the third well.

[0078] The liquid treatment device may further comprise a vent channel extending from the third well. The third well may be in fluid communication with the vent via the vent channel. The vent channel may comprise a first end in fluid communication with the third well and a second end in fluid communication with the vent. The vent may comprise a hole in the rigid layer. The vent channel may extend from the third well in a first direction. The hole may extend in a second direction through the rigid layer to an outer surface of the rigid layer, the second direction being different from the first direction. The second direction may be perpendicular to the first direction.

[0079] The liquid treatment device may further comprise a vent channel extending between the third well and the vent. The vent channel may comprise a first end in fluid communication with the third well and a second end in fluid communication with the vent. The vent may comprise a hole in the rigid layer at the second end of the vent channel.

[0080] The plurality of grooves may be a first plurality of grooves. The liquid treatment device may further comprise a fourth well in fluid communication with the first well and a second plurality of grooves extending between the fourth well and the first well. Each of the second plurality of grooves may provide a fluid connection between the fourth well and the first well. The connector channel may be a first connector channel. The liquid treatment device may further comprise a second connector channel extending between the fourth well and the third well. The second connector channel provides an alternative flow path between the first well and the vent. In the event of a blockage in the first well, air may be drawn through the vent via an unblocked flow path. Similarly, the second connector channel provides an alternative flow path in the event that each of the first plurality of grooves is blocked. The second plurality of grooves provides more than one path for liquid flow between the first well and the fourth well, thereby reducing the possibility of liquid blockage between the first well and the fourth well.

[0081] According to an eighth aspect of the present disclosure, there is provided a liquid treatment device comprising a fluid network comprising a plurality of conduits and a chamber, and a plurality of pneumatic ports, a first pneumatic port of the plurality of pneumatic ports in fluid communication with the chamber, a second pneumatic port of the plurality of pneumatic ports in fluid communication with a conduit of the plurality of conduits, the conduit in fluid communication with the chamber, and the second pneumatic port of the plurality of pneumatic ports configured to receive positive air pressure or negative air pressure while the first pneumatic port of the plurality of pneumatic ports is vented.

[0082] The use of multiple pneumatic ports reduces the need for permanent vents in the liquid treatment device, thus reducing the likelihood of liquid leaking from the liquid treatment device.

[0083] A first pneumatic port of the plurality of pneumatic ports may be further configured to receive positive or negative air pressure while a second pneumatic port of the plurality of pneumatic ports is vented, thereby expanding the range of fluid manipulations that can be performed using the liquid treatment device.

[0084] Each of the first of the plurality of pneumatic ports and the second of the plurality of pneumatic ports may be selectively configured to receive positive or negative pneumatic pressure and to be connected to a vent, further expanding the range of fluid manipulations that may be performed using the liquid treatment device.

[0085] The liquid treatment device may further comprise a fluidic layer disposed between the first and second rigid layers, where in use the second rigid layer is disposed below the fluidic layer. The fluidic layer may comprise a network of channels. The plurality of conduits may be defined at least in part by the network of channels in the fluidic layer. The fluidic layer may comprise a plurality of pneumatic ports. Providing the ports and channels in the same fluidic layer simplifies construction of the liquid treatment device.

[0086] The second rigid layer may include a plurality of troughs. Each of the plurality of pneumatic ports may be in fluid communication with the fluidic network through one of the plurality of troughs in the second rigid layer. The troughs prevent liquid from reaching the pneumatic ports that connect to the pneumatic interface. Thus, the troughs prevent liquid from reaching the pneumatic interface, particularly during aspiration of liquid. Such liquid may potentially contaminate or damage the pneumatic interface (e.g., in an analytical device). In particular, any liquid drawn from the channels in the fluidic layer between the aspiration pools at the bottom of the troughs does not reach the pneumatic ports. Thus, any liquid drawn from the channels is not drawn into the pneumatic interface through the pneumatic ports.

[0087] The chamber may be a waste chamber. Thus, the venting state of the waste chamber may be controlled. The second rigid layer may comprise a waste chamber. Thus, the liquid treatment device allows fluid movements in different layers of the liquid treatment device to be controlled.

[0088] The fluid network may further comprise a measurement chamber in fluid communication with the conduit. The waste chamber may be configured to receive waste fluid from the measurement chamber. Thus, a venting state of the measurement chamber may be controlled.

[0089] The chamber may be a first mixing chamber. Thus, the aeration state of the first mixing chamber may be controlled.

[0090] The fluid layer may comprise a protrusion extending from a surface of the fluid layer. The protrusion may comprise a cavity. The first mixing chamber may be at least partially defined by a cavity in the protrusion. Providing a protrusion extending from a surface of the fluid layer means that the volume of the first mixing chamber is not limited by the thickness of the fluid layer.

[0091] The fluid network may further comprise a second mixing chamber in fluid communication with the conduit and the first mixing chamber. Providing a second mixing chamber means that the solutions can be mixed by transferring the solutions back and forth between the two mixing chambers.

[0092] A third pneumatic port of the plurality of pneumatic ports can be in fluid communication with the fluid network. The third pneumatic port of the plurality of pneumatic ports can be selectively configured to receive positive or negative air pressure and to be connected to a vent. The provision of a third pneumatic port further increases the complexity of the fluid network that can be implemented.

[0093] The liquid treatment device may further comprise a liquid storage capsule. The liquid treatment device may be configured to transmit positive air pressure from one of the plurality of air pressure ports to the liquid storage capsule when the liquid storage capsule is opened.

[0094] The liquid treatment device according to the first, second, third, fifth, sixth, seventh or eighth aspect of the present disclosure may be a diagnostic cartridge. The diagnostic cartridge may be a microfluidic cartridge.

[0095] According to a ninth aspect of the present disclosure, there is provided a liquid treatment device according to the eighth aspect of the present disclosure; and an air pressure supply system comprising a variable pressure source, a first air pressure supply conduit configured to connect a first air pressure port of a plurality of air pressure ports of the liquid treatment device to an air vent in the air pressure supply system, and a second air pressure supply conduit configured to supply positive or negative pressure from the variable pressure source to a second air pressure port of the plurality of air pressure ports of the liquid treatment device while the first air pressure supply conduit connects the first air pressure port of the plurality of air pressure ports to the air vent.

[0096] The second pneumatic supply conduit may be further configured to connect a second pneumatic port of the plurality of pneumatic ports to a vent. The first pneumatic supply conduit may be further configured to supply positive or negative pressure from a variable pressure source to a first pneumatic port of the plurality of pneumatic ports, while the second pneumatic supply conduit connects the second pneumatic port of the plurality of pneumatic ports to a vent. This expands the range of fluid manipulations that can be performed using the liquid treatment device.

[0097] Each of the first and second pneumatic supply conduits may be configured to selectively supply positive or negative pressure from a variable pressure source to its respective pneumatic port and connect its respective pneumatic port to a vent, further expanding the range of fluid manipulations that can be performed using the liquid treatment device.

[0098] The chamber of the liquid treatment device may be a waste chamber. The pneumatic supply system may be configured to supply positive pressure from a variable pressure source to a second pneumatic port of the plurality of pneumatic ports while connecting a first pneumatic port of the plurality of pneumatic ports to a vent to dispense liquid from the conduit to the waste chamber. Thus, the vent state of the waste chamber may be controlled.

[0099] The fluid network of the liquid treatment device may further comprise a measurement chamber in fluid communication with the conduit. A waste chamber of the liquid treatment device may be configured to receive waste liquid from the measurement chamber. The pneumatic supply system may be configured to supply positive pressure from a variable pressure source to a second pneumatic port of the plurality of pneumatic ports while connecting a first pneumatic port of the plurality of pneumatic ports to the vent to dispense liquid from the measurement chamber to the waste chamber. Thus, a venting state of the measurement chamber may be controlled.

[0100] The liquid handling device may include a vented sample inlet chamber in fluid communication with the fluidic network. The pneumatic supply system may be configured to supply negative pressure from a variable pressure source to one of the plurality of pneumatic ports to draw liquid from the sample inlet chamber into the fluidic network.

[0101] The chamber of the liquid treatment device may be a first mixing chamber. The pneumatic supply system may be configured to supply positive pressure from a variable pressure source to a second pneumatic port of the plurality of pneumatic ports while connecting a first pneumatic port of the plurality of pneumatic ports to an air vent to dispense liquid into the first mixing chamber. Thus, the air vent state of the first mixing chamber may be controlled.

[0102] The fluid network of the liquid treatment device may further comprise a second mixing chamber in fluid communication with the conduit and the first mixing chamber. The pneumatic supply system may be configured to provide a positive pressure from a variable pressure source to a second pneumatic port of the plurality of pneumatic ports while connecting a first pneumatic port of the plurality of pneumatic ports to an air vent to dispense liquid from the second mixing chamber to the first mixing chamber, and / or to provide a negative pressure from a variable pressure source to a second pneumatic port of the plurality of pneumatic ports while connecting a first pneumatic port of the plurality of pneumatic ports to an air vent to aspirate liquid from the first mixing chamber to the second mixing chamber. Thus, solutions can be mixed by transferring the solutions back and forth between the two mixing chambers.

[0103] A third pneumatic port of the plurality of pneumatic ports of the liquid treatment device can be in fluid communication with the fluid network. The third pneumatic port of the plurality of pneumatic ports may be selectively configured to receive positive or negative pneumatic pressure and to be connected to a vent. The pneumatic supply system may be configured to supply positive pressure from a variable pressure source to the third pneumatic port of the plurality of pneumatic ports while connecting a first pneumatic port of the plurality of pneumatic ports to the vent, and / or to supply negative pressure from a variable pressure source to the third pneumatic port of the plurality of pneumatic ports while connecting a second pneumatic port of the plurality of pneumatic ports to the vent. Providing a third pneumatic port further increases the complexity of the fluid network that may be implemented.

[0104] The liquid treatment device may further comprise a liquid storage capsule. The liquid treatment device may be configured to transmit positive air pressure from one of the plurality of air pressure ports to the liquid storage capsule when the liquid storage capsule is opened. The liquid treatment device may further comprise an actuatable portion actuatable from a first position in which the actuatable portion does not deform the liquid storage capsule to a second position in which the actuatable portion deforms the liquid storage capsule. The liquid treatment system may be configured to actuate the actuatable portion of the liquid treatment device, thereby deforming the liquid storage capsule.

[0105] According to a tenth aspect of the present disclosure, there is provided a method of moving liquid in a liquid treatment device comprising a fluid network, the fluid network comprising a plurality of conduits and a chamber, the method including venting a first pneumatic port of a plurality of pneumatic ports of the liquid treatment device, the first pneumatic port of the plurality of pneumatic ports being in fluid communication with the chamber, and supplying positive air pressure to a second pneumatic port of the plurality of pneumatic ports of the liquid treatment device while venting the first pneumatic port of the plurality of pneumatic ports, the second pneumatic port of the plurality of pneumatic ports being in fluid communication with a conduit of the plurality of conduits, the conduit being in fluid communication with the chamber, and supplying positive air pressure to a second pneumatic port of the plurality of pneumatic ports while venting the first pneumatic port of the plurality of pneumatic ports dispenses liquid from the conduit to the chamber.

[0106] The method may further include venting a first pneumatic port of the plurality of pneumatic ports, and while venting the first pneumatic port of the plurality of pneumatic ports, supplying negative air pressure to a second pneumatic port of the plurality of pneumatic ports to aspirate liquid from the chamber.

[0107] The chamber can be a waste chamber. The method may further include, while venting the first pneumatic port of the plurality of pneumatic ports, providing positive air pressure to a second pneumatic port of the plurality of pneumatic ports to dispense liquid into the waste chamber.

[0108] The fluidic network may further comprise a measurement chamber. The method may further include, while venting the first pneumatic port of the plurality of pneumatic ports, providing positive air pressure to a second pneumatic port of the plurality of pneumatic ports to dispense liquid from the measurement chamber to a waste chamber.

[0109] The liquid handling device may include a vented sample inlet chamber in fluid communication with the fluidic network. The method may further include applying negative air pressure to one of the plurality of air pressure ports to aspirate liquid from the sample inlet chamber into the fluidic network.

[0110] The chamber can be a mixing chamber. The method may further include, while venting the first pneumatic port of the plurality of pneumatic ports, providing positive air pressure to a second pneumatic port of the plurality of pneumatic ports to dispense liquid from the conduit to the mixing chamber.

[0111] The mixing chamber may be a first mixing chamber. The fluid network may further comprise a second mixing chamber in fluid communication with the conduit and the first mixing chamber. The method may further include, during venting of the first pneumatic port of the plurality of pneumatic ports, providing a positive pressure from a variable pressure source to a second pneumatic port of the plurality of pneumatic ports to dispense liquid from the second mixing chamber to the first mixing chamber.

[0112] The method may further include, while venting a first pneumatic port of the plurality of pneumatic ports, providing a negative pressure from a variable pressure source to a second pneumatic port of the plurality of pneumatic ports to draw liquid from the first mixing chamber to the second mixing chamber.

[0113] The method may further include, while venting the first pneumatic port of the plurality of pneumatic ports, supplying positive pressure from a variable pressure source to a third pneumatic port of the plurality of pneumatic ports in fluid communication with the fluid network.

[0114] The method may further include, while venting the first pneumatic port of the plurality of pneumatic ports, supplying negative pressure from a variable pressure source to a third pneumatic port of the plurality of pneumatic ports in fluid communication with the fluid network.

[0115] The method may further include actuating an actuatable portion of the liquid treatment device to deform a liquid storage capsule contained in the liquid treatment device.

[0116] According to an eleventh aspect of the present disclosure, there is provided a computer readable medium comprising instructions which, when executed by a processor of a pneumatic supply system defined in the ninth aspect, cause the pneumatic supply system to perform the method of the tenth aspect.

[0117] It will be appreciated that features of the above-described embodiments may be combined between different embodiments. As an example, a feature of the liquid treatment device according to any one of the first, second, third, fifth, sixth, seventh, and eighth embodiments may be combined with one or more features described in relation to any other of these embodiments. As another example, a feature of the liquid treatment system according to any one of the fourth and ninth embodiments may be combined with one or more features described in relation to the other embodiments.

[0118] Specific embodiments are now described, by way of example only, and with reference to the accompanying drawings. [Brief description of the drawings]

[0119] [Figure 1] FIG. 1 is an isometric view of a liquid treatment device. [Diagram 2] FIG. 2 is an exploded view showing components of the liquid treatment device of FIG. [Diagram 3]2 is a top cross-sectional view through the liquid treatment device shown in FIG. 1. [Figure 4] 2 is an isometric bottom view of a first rigid layer of the liquid treatment device shown in FIG. 1. [Diagram 5] FIG. 5 is a top view of the first rigid layer shown in FIG. 4. [Figure 6A] FIG. 5 is a bottom view of the first rigid layer shown in FIG. 4. [Figure 6B] FIG. 6B is a cross-sectional view taken along line AA in FIG. 6A. [Figure 7] 5 is a side cross-sectional view illustrating engagement of an actuatable portion of the first rigid layer shown in FIG. 4 with a liquid storage capsule. [Figure 8] 5 is a cross-sectional end view illustrating engagement of an actuatable portion of the first rigid layer shown in FIG. 4 with a liquid-storage capsule. [Figure 9A] 5 is an isometric view of the first rigid layer shown in FIG. 4 showing the actuatable portion in an actuated position. [Figure 9B] 5 is a cross-sectional view through the first rigid layer shown in FIG. 4 showing the actuatable portion in an actuated position. [Figure 10] 2 is an isometric view of a second rigid layer of the liquid treatment device shown in FIG. 1. [Figure 11] FIG. 11 is a top view of the second rigid layer shown in FIG. [Figure 12] 11 is a top view of a portion of the second rigid layer shown in FIG. 10 with an enlarged isometric view of the first and second plurality of grooves of the second rigid layer. FIG. [Figure 13] 2 is an isometric view of a fluid assembly including a fluidic layer of the liquid treatment device shown in FIG. 1 and a sealing layer of the liquid treatment device shown in FIG. 1. [Figure 14A] FIG. 13 illustrates how the volume of liquid remaining in a flow cell of a fluidic assembly in which the flow cell is accessed through a hole in a sealing layer changes as the angle of the exit conduit from the flow cell changes. [Figure 14B] FIG. 13 illustrates how the volume of liquid remaining in a flow cell of a fluidic assembly in which the flow cell is accessed through a hole in a sealing layer varies with misalignment of the hole in the sealing layer and the flow cell. [Figure 14C] 13A-13C show how the volume of liquid remaining in a flow cell of a fluidic assembly in which the flow cell is accessed through a hole in a sealing layer varies with the size of the hole in the sealing layer. [Figure 15] 2 is an isometric view of an alternative fluid assembly comprising a fluidic layer of the liquid treatment device shown in FIG. 1 and an alternative sealing layer. [Figure 16] FIG. 13 shows a simulation of the flow of liquid in a flow cell of a fluidic assembly in which the flow cell is disposed within a sealing layer. [Figure 17A] 2 is a bottom view of the fluid layer of the liquid treatment device shown in FIG. 1. [Figure 17B] 2 is a bottom view of the fluid layer of the liquid treatment device shown in FIG. 1. [Figure 17C] FIG. 17C is a top view of the fluidic layer shown in FIGS. 17A and 17B. [Figure 18A] 2 is a top view of an alternative fluidic layer that may be implemented in the liquid treatment device shown in FIG. 1. [Figure 18B] FIG. 18B is a bottom view of the alternative fluidic layer shown in FIG. 18A. [Figure 19A] FIG. 17D is a cross-sectional view taken along line AA of FIG. 17C. [Figure 19B] FIG. 17D is a cross-sectional view taken along line BB in FIG. 17C. [Figure 19C] FIG. 17D is a cross-sectional view taken along line CC in FIG. 17C. [Figure 19D] FIG. 17D is a cross-sectional view taken along line DD in FIG. 17C. [Figure 19E] FIG. 19E is a cross-sectional view of detail E shown in FIG. 19D. [Figure 20] 17A-17C depict cross-sectional views through chambers of the fluidic layer shown in FIGS. 17A-17C, showing solid reagents within the chambers. FIG. [Figure 21] FIG. 17D is a cross-sectional view through the valve region of the fluidic layer shown in FIGS. 17A-17C, showing the valve region being engaged by an external valve actuator. [Figure 22A]22 is a simulation of engagement of the external valve actuator and valve region shown in FIG. 21, with the external valve actuator in a disengaged position with the valve region. [Figure 22B] 22 is a simulation of the engagement of the external valve actuator and valve region shown in FIG. 21, where the external valve actuator is in a partially engaged position with the valve region. [Figure 22C] 22 is a simulation of the engagement of the external valve actuator and valve region shown in FIG. 21, with the external valve actuator in an engaged position with the valve region. [Figure 23A] FIG. 18 is a cross-sectional view through a pneumatic port and an external pneumatic actuator of the fluidic layer shown in FIGS. 17A-17C. [Figure 23B] 23B is a simulation of the engagement of the external pneumatic actuator and pneumatic port shown in FIG. 23A. [Figure 24A] FIG. 13 is a cross-sectional view through an alternative pneumatic port of the fluidic layer. [Figure 24B] 24B is a simulation of the engagement of the external pneumatic actuator and alternative pneumatic ports shown in FIG. 24A. [Diagram 25] 11A-11C are schematic diagrams illustrating the effect of different pneumatic port geometries on the deformation of the pneumatic port during engagement by an external pneumatic actuator. [Figure 26] FIG. 17C is a schematic diagram of a fluidic circuit that may be implemented using the fluidic layer shown in FIGS. 17A-17C. [Figure 27] FIG. 17C is a schematic diagram of an additional fluidic circuit that can be implemented using the fluidic layer shown in FIGS. 17A-17C. [Figure 28] FIG. 17C is a schematic diagram of a further fluidic circuit that can be implemented using the fluidic layer shown in FIGS. 17A-17C. [Figure 29] 17A-17C are flowcharts of fluidic operations that may be implemented using the fluidic layer shown in FIG. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0120] Implementations of the present disclosure are described below with particular reference to microfluidic cartridges used to perform diagnostic tests. However, it will be appreciated that the implementations described herein are applicable to microfluidic cartridges used for other purposes. It will be further appreciated that the implementations described herein are not limited to microfluidics, but are applicable to liquid handling devices of various sizes used for a variety of purposes.

[0121] 1 is an isometric view of a liquid handling device in the form of a diagnostic cartridge (eg, a microfluidic cartridge) 100. Cartridge 100 comprises several components, as can be seen from the exploded view shown in FIG.

[0122] Specifically, the cartridge 100 comprises a first portion 200 and a second portion 500, each formed from a rigid material. In use (i.e., when the cartridge 100 is in the orientation shown in FIG. 1), the first portion 200 is the upper portion and the second portion 500 is the lower portion. Together, the first portion 200 and the second portion 500 define a housing for the cartridge 100. Specifically, the first portion 200 comprises a rigid surface 250 that defines an upper surface of the cartridge 100. Similarly, the second portion 500 comprises a rigid surface 570 (best shown in FIG. 7) that defines a lower surface of the cartridge 100. Returning to FIG. 2, it can be seen that the first portion 200 further comprises a sidewall 252 joined to the rigid surface 250, and the second portion 500 further comprises a sidewall 572 joined to the rigid surface 570. The side wall 252 of the first portion 200 and the side wall 572 of the second portion 500 cooperate together to define a side wall of the cartridge 100 .

[0123] The cartridge 100 further comprises a fluidic layer 300 arranged within the housing defined by the first part 200 and the second part 500. In particular, the fluidic layer 300 is arranged between the rigid surface 250 of the first part 200 and the rigid surface 570 of the second part 500. The fluidic layer 300 is thus arranged between a first rigid layer in the form of the rigid surface 250 and a second rigid layer in the form of the rigid surface 570. The fluidic layer 300 is formed from a thermoplastic elastomer (TPE), for example an elastomeric material such as a silicone-based TPE or styrene-ethylene-butylene-styrene (SEBS), polydimethylsiloxane (PDMS), or liquid silicone rubber (LSR).

[0124] As described in more detail below, the first surface 308 of the fluidic layer 300 comprises a plurality of valve regions 302 (shown, for example, in FIG. 13). The cartridge 100 is received in an analytical device that includes an actuator 700 that applies a force to the valve regions 302 of the fluidic layer 300 to close one or more conduits 600 (shown in FIG. 21) in the cartridge 100. The properties of the material used for the fluidic layer 300 depend on the available force that can be applied by the actuator 700 to the valve regions 302 of the fluidic layer 300. Two properties that are important are the hardness of the material, and the relaxation time of the material (i.e., the time for the material to return to its original form after deformation). Examples of suitable materials include the elastomeric materials listed above. In some implementations, the fluidic layer 300 can be a medical grade material to prevent reaction of the fluidic layer 300 with reagents used in diagnostic tests or analyses.

[0125] As described in more detail below, the fluidic layer 300 comprises a network of channels 304 (shown in FIG. 17B ) disposed (at least in part) on a second surface 310 of the fluidic layer 300 opposite the first surface 308. The cartridge 100 also comprises a fluidic network comprising a plurality of conduits 600 defined at least in part by the network of channels 304 in the fluidic layer 300. Specifically, the conduits 600 are defined by (i) the network of channels 304 in the fluidic layer 300, (ii) a sealing layer 400 (shown in FIG. 2 ) configured to seal the channels 304 in the second surface 310 of the fluidic layer 300, and optionally (iii) a sealing layer (not shown) configured to seal any channels 304 of the network disposed on the first surface 308.

[0126] Providing the channels 304 in the elastomeric fluid layer 300 improves sealing of the fluid layer regardless of the bonding process (e.g., pressure sensitive adhesive tape, laser welding, etc.) used to seal the network of channels 304. This is because the elastomeric fluid layer 300 acts as a resilient layer when sealed against another layer (e.g., sealing layer 400). In addition, the use of an elastomeric material for the fluid layer 300 means that the channels 304 can be compressed to close the respective conduits 600. This means that a single layer can be utilized to implement the channels 304 and the valves (i.e., valve regions 302), thereby providing a simple cartridge construction.

[0127] Returning to the exploded view shown in FIG. 2, it can be seen that the cartridge 100 further comprises a label 110 arranged to cover at least a portion of the rigid surface 250 of the first part 200, a plurality of liquid storage capsules 120 arranged within the cartridge 100 between the fluidic layer 300 and the first surface 250, and a sealing tape 130 arranged to seal one or more chambers 332 (best shown in FIG. 13) within the fluidic layer 300.

[0128] 2 also shows that cartridge 100 further comprises a flow cell strip 140 comprising a plurality of openings 142, each of which partially defines a corresponding measurement chamber 610 of cartridge 100, a sensor strip 150 comprising a plurality of sensors, each sensor in fluid communication with a respective one of the measurement chambers 610, and a pair of absorbent waste pads 160, each of which is positioned to fit within a corresponding waste chamber 508a, 508b provided in second portion 500. In some implementations (e.g., shown in FIG. 15), flow cell strip 140 is not present and openings 454 that partially define measurement chambers 610 are instead provided in alternative sealing layer 450.

[0129] 1 and 2, the first portion 200 comprises a receptacle in the form of a cylinder 202 configured to receive a portion of a liquid storage container, such as a blood collection tube (e.g., a Vacutainer® blood collection tube manufactured by Becton, Dickinson and Company of Franklin Lakes, NJ, USA). A blood collection tube typically contains a volume of liquid (e.g., blood) and a headspace that contains a volume of gas.

[0130] As shown in the cross-sectional view of FIG. 3, the cartridge 100 further comprises an actuatable liquid extraction mechanism in the form of a piston 204 actuatable within the cylinder 202 from a first liquid extraction mechanism configuration (shown in FIG. 3) to a second liquid extraction mechanism configuration.

[0131] The cylinder 202 comprises a first cylindrical portion 202a defining a first cylindrical interior volume and a second cylindrical portion 202b defining a second cylindrical interior volume. The second cylindrical interior volume extends from the first cylindrical interior volume. The cross-sectional area of ​​the second cylindrical interior volume is smaller than the cross-sectional area of ​​the first cylindrical interior volume, such that the second cylindrical interior volume is narrower than the first cylindrical interior volume. An annular flange 212 is disposed within the cylinder 202 and joins the first cylindrical interior volume to the second cylindrical interior volume. The annular flange 212 serves as an end wall for the first cylindrical interior volume.

[0132] The cylinder 202 also comprises a third cylinder portion 202c disposed within the first cylindrical internal volume. The third cylinder portion 202c defines a third cylindrical internal volume. The cross-sectional area of ​​the third cylindrical internal volume is between the cross-sectional areas of the first cylindrical internal volume and the second cylindrical internal volume. The third cylinder portion 202c protrudes from the annular flange 212 in a direction opposite to the direction in which the second cylinder portion 202b extends. The diameter of the third cylinder portion 202c is smaller than the diameter of the first cylindrical internal volume, which means that there is an annular gap between the first cylinder portion 202a and the third cylinder portion 202c. The height of the third cylinder portion 202c is smaller than the height of the first cylinder portion 202a, which means that the third cylinder portion 202c protrudes halfway into the first cylindrical internal volume.

[0133] The piston 204 includes two sealing elements in the form of first and second annular (e.g., O-ring) seals 210a, 210b. The first O-ring seal 210a is configured to provide a seal between the piston 204 and an inner wall of the third cylinder portion 202c. The second O-ring seal 210b is configured to provide a seal between the piston 204 and an inner wall of the second cylinder portion 202b. The piston 204, the annular flange 212, and the inner walls of the second cylinder portion 202b and the third cylinder portion 202c together define a chamber 214 sealed by the first O-ring seal 210a and the second O-ring seal 210b. The cylinder includes a cylinder outlet 216 configured to allow air to flow around the second O-ring seal 210b when the piston 204 is in the second configuration, thereby compromising the seal provided by the second O-ring seal 210b. Cylinder outlet 216 also allows liquid to be removed from within cylinder 202 once it has been extracted from the blood collection tube. Cylinder outlet 216 is in fluid communication with sample inlet channel 230 (described further below), which provides a connection to a vented fluid arrangement within cartridge 100. Cylinder outlet 216 thereby allows liquid to be transferred from components within cylinder 202 to other fluidic components of cartridge 100.

[0134] The piston 204 comprises a liquid reservoir interface, such as a blood collection tube interface, in the form of a piercing element. The piercing element is shown in FIG. 3 in the form of a needle 206. The needle 206 is configured to provide a fluid connection to a volume of liquid in the liquid reservoir (e.g., a volume of blood in a blood collection tube) when the liquid reservoir is connected to the needle 206. The needle 206 is fixedly attached to the piston 204 such that the needle 206 moves within the cylinder 202 as the piston 204 is actuated from the first liquid extraction mechanism configuration to the second liquid extraction mechanism configuration. The needle 206 comprises a liquid extraction outlet 208 through which liquid extracted from the blood collection tube can flow. The liquid extraction outlet 208 provides a fluid connection between the needle 206 and the cylinder outlet 216 when the piston 204 is in the second configuration.

[0135] In the first liquid extraction mechanism configuration (shown in FIG. 3), the piston 204 is positioned within the cylinder 202 above the cylinder outlet 216 (i.e., a gap exists between the second O-ring seal 210b and the end wall 218 of the cylinder 202).

[0136] After the blood collection tube connects to the needle 206, the volume of the chamber 214 decreases as the piston 204 is actuated from the first liquid extraction mechanism configuration to the second liquid extraction mechanism configuration. The decrease in the volume of the chamber 214 results in an increase in the pressure of the air in the chamber 214 because the chamber 214 is sealed by the O-ring seals 210a, 210b. The increase in air pressure in the chamber 214 forces air through the needle 206 and into the blood collection tube, thereby increasing the pressure of the volume of gas in the blood collection tube. The increase in the pressure of the air in the chamber 214 and the blood collection tube continues as the piston 204 is actuated toward the second configuration.

[0137] When the piston 204 is in the second configuration, the second O-ring seal 210b is aligned with the cylinder outlet 216 and is therefore compromised, meaning that the compressed air in the chamber 214 can flow through the cylinder outlet 216. This reduces the pressure in the liquid extraction outlet 208, which is in fluid communication with the chamber 214, thereby creating a pressure difference between the volume of gas in the collection tube and the liquid extraction outlet 208. This pressure difference forces liquid out of the collection tube through the needle 206 and into the sample inlet channel 230 through the liquid extraction outlet 208, which is aligned with the cylinder outlet 216.

[0138] Cartridge 100 further comprises an actuatable safety mechanism 220 actuatable within cylinder 202 from a first safety mechanism configuration (shown in FIG. 3 ) to a second safety mechanism configuration. Safety mechanism 220 is configured to conceal the liquid reservoir interface (i.e., needle 206) when safety mechanism 220 is in the first safety mechanism configuration and configured to reveal the liquid reservoir interface when safety mechanism 220 is in the second safety mechanism configuration.

[0139] The safety mechanism 220 includes at least one spherical shutoff element 222 (two spherical shutoff elements 222 are shown in FIG. 3). At least one of the shutoff elements 222 prevents actuation of the safety mechanism 220 from a first safety mechanism configuration to a second safety mechanism configuration when the cylinder 202 is in a first orientation (e.g., horizontal). At least one of the shutoff elements 222 also allows actuation of the safety mechanism 220 from the first safety mechanism configuration to the second safety mechanism configuration when the cylinder 202 is in a second orientation (e.g., vertical).

[0140] The cartridge 100 further comprises an elastically deformable element, shown in Fig. 3 in the form of a spring 224. The spring 224 deforms when the safety 220 moves towards the piston 204 (i.e. when the safety 220 is actuated from the first safety configuration to the second safety configuration). The spring 224 is configured to bias the safety 220 away from the piston 204 when the force applied to compress the spring 224 is released. Thus, the spring 224 biases the safety 220 away from the second safety configuration and towards the first safety configuration, which causes the needle 206 to be hidden again after extraction of liquid from the liquid reservoir.

[0141] The cartridge 100 further comprises a sample compatibility control chamber 236 (shown more clearly in FIG. 4 ) that provides a visual indication to a user that a sufficient amount of liquid has been extracted from a liquid reservoir (e.g., a blood collection tube). In particular, the sample compatibility control chamber 236 can provide a visual indication that a sufficient volume of liquid has been extracted for a particular diagnostic test. For example, as shown in FIG. 1 , the sample compatibility control chamber 236 is configured to provide a visual indication through an optically transparent window 238 in an upwardly positioned sidewall of the cartridge 100 when the cylinder 202 is in a vertical orientation (i.e., when the cartridge 100 is used to extract liquid from a liquid reservoir).

[0142] The sample compatibility control chamber 236 shown in FIG. 3 forms part of a first flow path in fluid communication with the sample inlet channel 230. As shown in FIGS. 3 and 4, the cartridge 100 also includes a metering chamber 232 configured to store a specific volume of liquid. For example, the metering chamber 232 can store a volume of liquid required for a specific diagnostic test. The first flow path includes the metering chamber 232, a connector channel 234 providing a fluid connection between the metering chamber 232 and the sample compatibility control chamber 236, the sample compatibility control chamber 236, and a sample waste chamber in fluid communication with the sample compatibility control chamber 236 via a waste outlet 401 in the sealing layer 400 (shown in FIG. 13). The sample waste chamber is provided in the second portion 500 in the form of a first well 504, best shown in FIGS. 10-12. As described in more detail below, the sample waste chamber defined by the first well 504 is vented.

[0143] Cartridge 100 further comprises a second flow path comprising a metering chamber outlet channel 502 (also best shown in FIGS. 10-12 ) extending from an outlet port (not shown) in metering chamber 232. Metering chamber outlet channel 502 is in fluid communication with metering chamber 232 via hole 402 (shown in FIG. 13 ) in sealing layer 400. Metering chamber outlet channel 502 allows liquid to be aspirated into other fluidic components of cartridge 100. Alternative implementations may not include metering chamber 232 or connector channel 234, in which case metering chamber outlet channel 502 extends from an outlet port in a sample compatibility control chamber configured to meter a specific volume of liquid.

[0144] The second flow path (including the metering chamber outlet channel 502) provides a higher hydraulic resistance than the first flow path (including the sample compatibility control chamber 236 and, optionally, the metering chamber 232 and connector channel 234). This means that the flow rate of liquid through the first flow path is higher than the flow rate through the second flow path. The higher flow rate through the first flow path means that liquid flows into the sample compatibility control chamber 236 to provide a visual indication that a sufficient volume of liquid has been received without completely filling the metering chamber outlet channel 502.

[0145] When the cartridge is assembled, the sample inlet channel 230 , the connector channel 234 , and the metering chamber outlet channel 502 each define a corresponding conduit that is sealed by the sealing layer 400 .

[0146] FIG. 3 also illustrates the arrangement of multiple liquid storage capsules 120 within the cartridge 100. In particular, the liquid storage capsules 120 are sealed to the fluidic layer 300 using a sealing tape 180. FIG. 3 illustrates that the sealing tape 180 includes an opening that allows features to protrude above the fluidic layer 300 (i.e., pneumatic port 312 and protrusion 330 defining chamber 332, described in more detail with reference to FIG. 13). As illustrated in FIG. 3, each liquid storage capsule 120 includes an inlet chamber 122, a main chamber 124 for storing a liquid, such as a liquid reagent, and an outlet chamber 126. A sealing layer (e.g., a sealing foil) is used to seal the chambers 122, 124, 126 of each liquid storage capsule 120. The inlet chamber 122 and the outlet chamber 126 each include corresponding recesses 128a, 128b in the upper surface of the chamber (as best shown in FIGS. 7 and 8).

[0147] The liquid storage capsule 120 shown in Figure 3 includes two small liquid storage capsules 120a and two large liquid storage capsules 120b. The small liquid storage capsules 120a are aligned such that the recesses 128a, 128b of the small storage capsules 120a are all in a straight line. Each of the large liquid storage capsules 120b is positioned perpendicular to the corresponding small liquid storage capsule 120a such that the large liquid storage capsules 120b are parallel to each other.

[0148] As will be described in more detail below, each of the liquid storage capsules 120 is disposed over two openings 350 in the fluidic layer 300. Specifically, the inlet chamber 122 of the liquid storage capsule 120 covers a first one of the openings 350, and the outlet chamber 126 of the liquid storage capsule 120 covers a second one of the openings 350. When a force is applied to the recesses 128a, 128b of the liquid storage capsule 120, the material of the liquid storage capsule 120 deforms into each of the openings 350. When sufficient force is applied, the deformation of the liquid storage capsule 120 into the openings 350 causes the rupture of a sealing layer (e.g., foil) used to seal the capsule 120.

[0149] In alternative implementations, the inlet chamber 122 and the outlet chamber 126 may not include the recess 128. Instead, a force may be applied directly to a portion of the inlet chamber 122 and the outlet chamber 126 to deform the liquid storage capsule 120.

[0150] Figure 4 is an isometric bottom view of the first part 200. As shown in Figures 4-6, the first part 200 comprises an actuatable part 240 (e.g., an actuatable platform) that is actuatable from a first position in which the actuatable part 240 does not deform the liquid storage capsule 120 to a second position in which the actuatable part 240 deforms the liquid storage capsule 120. The actuatable part 240 is actuatable relative to a rigid surface 250 of the first part 200 (as best shown in Figures 9A and 9B) and is actuatable in a direction perpendicular to the rigid surface 250 of the first part 200. The actuatable part 240 is rigid.

[0151] The actuatable portion 240 is U-shaped so that it can deform towards each of the liquid storage capsules 120. The U-shape of the actuatable portion 240 also allows the actuatable portion 240 to pass around a protrusion 330 (shown in FIG. 13 ) extending from the first surface 308 of the fluid layer 300.

[0152] As shown in FIG. 4, the lower surface of the actuatable portion 240 includes four pairs of protrusions 242 (shown in cross-section in FIG. 6B). Each pair of protrusions 242 extends toward the liquid storage capsule 120 and is aligned with the recesses 128a, 128b of one of the liquid storage capsules 120. Thus, when the actuatable portion 240 moves to the second position, the protrusions 242 engage with the recesses 128a, 128b of the capsule 120. In an alternative implementation, the liquid storage capsule 120 may not include the recesses 128a, 128b, in which case the protrusions 242 may engage with a portion of the inlet chamber 122 and the outlet chamber 126 of each liquid storage capsule 120 (e.g., a flat or dome-shaped upper surface of the inlet chamber 122 and the outlet chamber 126).

[0153] 6B, the underside of the actuatable portion 240 also includes four recessed areas 244. Each recessed area 244 is located between two of the protrusions 242. Each recessed area 244 is configured to accommodate the main chamber 124 of its corresponding liquid storage capsule 120 when the actuatable portion 240 is in the second position. This means that the main chamber 124 is not deformed by the actuatable portion 240 when the actuatable portion 240 is in the second position.

[0154] Assuming that the protrusions 242 extend from a single actuatable portion 240, actuation of the actuatable portion 242 to the second position causes simultaneous deformation of each of the multiple capsules 120. As a result, all of the capsules 120 in the cartridge 100 can be punctured using a single movement of the actuatable portion 240.

[0155] In an alternative implementation, the actuable portion 240 may include two sets of protrusions 242: a first set of protrusions each extending a first distance toward the recess 128 of the liquid storage capsule 120, and a second set of protrusions each extending a second distance toward the recess 128 of the liquid storage capsule 120, the second distance being smaller than the first distance.

[0156] This alternative implementation allows for the puncturing of the liquid-storage capsules 120 in two stages. The capsules 120 aligned with the first set of protrusions are punctured first when the actuatable portion 240 moves to the second position (as described above). However, to puncture the capsules 120 aligned with the second set of protrusions, the actuatable portion 240 is actuated beyond the second position to a third position (as the second set of protrusions is shorter). Thus, this alternative implementation allows for liquid (e.g., liquid reagent) to be released from some capsules before other capsules are punctured.

[0157] Thus, for example, fluidic workflow steps involving liquid reagents stored in the first and second capsules may be completed prior to releasing liquid reagents from the third and fourth capsules (e.g., if liquid reagents in the third and fourth capsules are required at a later stage in the fluidic workflow). Additional sets of protrusions extending different distances from the actuatable portion 240 may be implemented to further regulate the release of liquid from the capsule 120.

[0158] 5 and 6B, the top surface (i.e., the outer surface) of actuatable portion 240 is flat (or includes a number of flat regions). The flat surface of actuatable portion 240 allows actuatable portion 240 to be easily moved from a first position to a second position without requiring a specific shaped actuator to move actuatable portion 240.

[0159] 4 and 5 also show that the rigid surface 250 includes a plurality of openings 254. The plurality of openings 254 includes an opening 254a aligned with the valve region 302 of the fluidic layer 300, an opening 254b aligned with the first pneumatic port 312a of the fluidic layer 300, and an opening 254c that, together with a protrusion 330 extending from the first surface 308 of the fluidic layer 300, provides an opening for the second pneumatic port 312b and the third pneumatic port 312c of the fluidic layer 300. With reference to FIG. 13, the ports 312 and the protrusion 330 will be described.

[0160] Opening 254a in rigid surface 250 allows valve region 302 of fluidic layer 300 to be accessed by an external valve actuator (e.g., as shown in FIG. 21 ). Similarly, openings 254b and 254c allow pneumatic port 312 of fluidic layer 300 to be accessed by an external pneumatic actuator (e.g., as shown in FIG. 23A ).

[0161] 6B and 7 also show an elastically deformable member 246 coupling the actuatable portion 240 to the first portion 200. The elastically deformable member 246 is configured to bias the actuatable portion 240 away from the second position (i.e., towards the first position). Thus, the elastically deformable member 246 forces the actuatable portion away from engagement with the recesses 128a, 128b of the liquid storage capsule 120.

[0162] Each elastically deformable member 246 has a curved (specifically, U-shaped) profile that allows the elastically deformable member 246 to undergo elastic deformation during movement of the actuatable portion 240 to the second position. Figure 9B illustrates the deformation of the elastically deformable member 246 when the actuatable portion 240 is in the second position, and Figure 9A illustrates the position of the actuatable portion 240 relative to the first portion 200 when the actuatable portion 240 is in the second position.

[0163] The elastically deformable member 246 is formed from the same material as the actuatable portion 240 and the first portion 200. In other words, the elastically deformable member 246 is integral with the first portion 200 and the actuatable portion 240, each provided in the form of an elastic living hinge. This allows the actuatable portion 240 and the first portion 200, including the elastically deformable member 246, to be simplified in manufacture (e.g., manufactured by injection molding).

[0164] As shown in Figures 4-6A, the first portion 200 includes a plurality of elastically deformable members 246 (four elastically deformable members 246 are shown in the example shown in Figures 4-6A). Providing a plurality of elastically deformable members 246 allows the actuatable portion 240 to be actuated in a vertical direction, meaning that the actuatable portion 240 is parallel to the base (i.e., the sealing layer) of each liquid storage capsule 120 when the actuatable portion 240 is in the first portion and when the actuatable portion 240 is in the second position. The vertical movement of the actuatable portion 240 allows the same force to be applied to the recess 128 of a particular liquid storage capsule 120.

[0165] In particular, as shown in FIG. 5, a first one of the elastically deformable members 246 is connected to a first edge 256a of the actuatable portion 240, a second one of the elastically deformable members 246 is connected to a second edge 256b of the actuatable portion 240 opposite the first edge 256a, a third one of the elastically deformable members 246 is also connected to the first edge 256a of the actuatable portion 240 but is spaced from the connection point of the first one of the elastically deformable members 246, and a fourth one of the elastically deformable members 246 is connected to a third edge 256c of the actuatable portion 240 also opposite the first edge 256a.

[0166] 7 and 8 show the alignment of the protrusion 242 with the recesses 128a, 128b of the liquid storage capsule 120 when the actuatable portion 240 is in a first position. It will be appreciated that when a force is applied to the actuatable portion 240 to move the actuatable portion 240 towards its second position, the protrusion 242 engages with the recesses 128a, 128b, causing deformation of the inlet chamber 122 and the outlet chamber 126 of the liquid storage capsule 120. Specifically, the sealing layer below the inlet chamber 122 deforms into a first one of the openings 350, and the sealing layer below the outlet chamber 126 deforms into a second one of the openings 350. The deformation of the inlet chamber 122 and the outlet chamber 126 causes the rupture of the material below the inlet chamber 122 and the outlet chamber 126, meaning that an opening is created in each of the inlet chamber 122 and the outlet chamber 126.

[0167] Rupture of the material underlying the inlet and outlet chambers 122, 126 is achieved by applying a force to the recesses 128a, 128b, which brings the material underlying the inlet and outlet chambers 122, 126 into contact with the recesses 128. This causes the material underlying the inlet and outlet chambers 122, 126 to deform into the openings 350. The top surface of the capsule 120 is formed from a material capable of plastic deformation to allow deformation of the recesses 128.

[0168] FIG. 10 illustrates the second portion 500. As described above, the second portion 500 includes a metering chamber outlet channel 502 that provides a fluid connection between the metering chamber 232 and the fluidic layer 300. The second portion 500 also includes a sample waste chamber defined by a first well 504. The sample waste chamber receives excess sample that overflows from the sample compatibility control chamber 236 in the first portion 200 during receipt of the sample in the cartridge 100. The sample waste chamber is in fluid communication with a permanent vent 506 (best shown in FIG. 12) provided in the form of a hole in the second portion 500. The sample waste chamber and the permanent vent 506 are described in more detail below with reference to FIG. 12.

[0169] The second portion 500 further comprises two further waste chambers, a first waste chamber 508a and a second waste chamber 508b, each of which is provided in the form of two elongated recesses in the inner surface of the rigid surface 570. The two waste chambers 508a, 508b are in fluid communication with each other via a lateral channel 512 extending between the first waste chamber 508a and the second waste chamber 508b.

[0170] The second portion 500 further comprises a first trough 514a in the form of a semi-annular groove on the inner surface of the rigid surface 570, a second trough 514b in the form of an annular groove on the inner surface of the rigid surface 570, and a third trough 514c in the form of an additional semi-annular groove on the inner surface of the rigid surface 570. Each of the troughs 514 provides a fluid connection between a pneumatic port 312 in the fluidic layer 300 and one or more channels 304 of the fluidic layer 300, as described in more detail below. In particular, some of the channels 304 are fluidly connected to the trough 514 via holes in the sealing layer 400, as described with reference to Figures 17A and 17B.

[0171] The second part 500 further comprises a first pneumatic port support 516a at the beginning of the semi-annular groove forming the first trough 514a, a second pneumatic port support 516b at the beginning of the annular groove forming the second trough 514b, and a third pneumatic port support 516c at the beginning of the semi-annular groove forming the third trough 514c. Each of the pneumatic port supports 516 has a truncated cone (or semi-frustum) shape with a flat upper surface. Each of the pneumatic port supports 516 is disposed below a corresponding pneumatic port 312 of the fluidic layer 300 when the cartridge 100 is assembled.

[0172] The first pneumatic port support 516a includes a channel 518a on its flat upper surface. The channel 518a extends from the center of the first pneumatic port support 516a to the first trough 514a. Similarly, the second pneumatic port support 516b includes a channel 518b on its flat upper surface. The channel 518b extends from the center of the second pneumatic port support 516b to the second trough 514b. Similarly, the third pneumatic port support 516c includes a channel 518c on its flat upper surface. The channel 518c extends from the center of the third pneumatic port support 516c to the third trough 514c. When the cartridge 100 is assembled, there is a fluid connection between the opening 316 of each pneumatic port 312 and the channel 518 of the corresponding pneumatic port support 516 (through the sealing layer 400).

[0173] The port support 516 is in contact with the underside of the sealing layer 400, which is used to seal the channel 304 in the second surface 310 of the fluidic layer 300. This means that when a force is applied to the pneumatic port 312 of the fluidic layer 300 (described with reference to FIG. 13 ), the contact between the sealing layer 400 and the port support 516 provides a counter force to the applied force, thereby preventing downward deformation of the sealing layer 400. This helps the pneumatic port 312 form a seal with the pneumatic actuator.

[0174] The trough 514 in the second portion 500 prevents liquid from reaching the pneumatic port 312 that connects to the pneumatic actuator 712 of the analytical device. Thus, the trough 514 prevents liquid from reaching the analytical device, especially during aspiration of liquid. Such liquid could potentially contaminate or damage the analytical device. Air pressure is provided through a channel 518 on the flat upper surface of the port support 516. Assuming that the channel 518 is positioned above the base of the trough 514, any liquid drawn from the channel 304 in the fluidic layer 300 will pool at the bottom of the trough 514 and will not reach the channel 518. Thus, any liquid drawn from the channel 304 in the fluidic layer 300 will not be drawn through the channel 518 to the pneumatic actuator 710 via the pneumatic port 312.

[0175] The second portion 500 further comprises a longitudinal channel 522 extending between the second trough 514b and the lateral channel 512 connecting the two waste chambers 508a, 508b. Thus, the second trough 514b and the channel 518b are in fluid communication with the two waste chambers 508a, 508b via the longitudinal channel 522 and the lateral channel 512.

[0176] The lateral channel 512 and the longitudinal channel 522 allow the two waste chambers 508 to be in fluid communication with the pneumatic port 312 (specifically, the second pneumatic port 312b). The fluid communication is provided by a second trough 514b and a channel 518b in the second port support 516b. The fluid communication between the waste chamber 508 and the second pneumatic port 312b allows the venting state of the waste chamber 508 to be controlled. This is because the second pneumatic port 312b can be vented, as described in more detail below.

[0177] The second portion 500 also comprises a number of valve support regions 524a-l (shown in dashed lines in FIG. 11). In the example shown in FIGS. 10 and 11, twelve valve support regions 524 are shown. Each of the valve support regions 524 is aligned with a corresponding valve region 302 in the fluidic layer 300. Each of the valve support regions 524 is in contact with the underside of the sealing layer 400 that is used to seal the channel 304 in the second surface 310 of the fluidic layer 300. This means that when a force is applied to the valve region 302 of the fluidic layer 300 by an actuator 700 (shown in FIG. 21), the valve region 302 is compressed between the actuator 700 and the corresponding valve support region 524. This means that the waste chambers 508a, 508b do not extend below the valve region 302 of the fluidic layer 300.

[0178] The second portion 500 further comprises a number of capsule support regions 526a-h (also shown in dashed lines in FIG. 11). In the example shown in FIG. 10 and FIG. 11, eight capsule support regions 526 are shown. Each of the capsule support regions 526 is aligned with a corresponding opening 350 in the fluidic layer 300 that is aligned with the inlet chamber 122 or the outlet chamber 126 of one of the plurality of capsules 120. Each of the capsule support regions 526 is in contact with the underside of the sealing layer 400 that is used to seal the channel 304 in the second surface 310 of the fluidic layer 300. This means that when a force is applied to the recess 128 of one of the plurality of capsules 120 by the corresponding protrusion 242 of the actuatable portion 240, the fluidic layer 300 is prevented from being deformed by the corresponding capsule support region 526. This means that the waste chambers 508a, 508b do not extend below the opening 350 in the fluidic layer 300.

[0179] 12, the sample waste chamber is provided in the form of a first well 504 in rigid surface 570 of first portion 500. First well 504 has a depth defined by the distance between a base 530 of first well 504 and a sealing surface 574 of rigid surface 570, which contacts sealing layer 400 when cartridge 100 is assembled.

[0180] The rigid surface 570 also includes a second well 532 having a depth defined by the distance between a base 534 of the second well 532 and a sealing surface 574. As described in more detail below, the second well 532 is in fluid communication with the permanent vent 506. In particular, the second well 532 is disposed between the first well 504 and the permanent vent 506 such that the first well 504 is in fluid communication with the permanent vent 506 via the second well 532.

[0181] Between the first well 504 and the second well 532, a first plurality of grooves 536 (e.g., three grooves 536 as shown in FIG. 12) are provided. Each of the grooves 536 has a sloped base 538. Each groove 536 has a depth defined by the distance between the sloped base 538 and the sealing surface 574. The base 538 of the groove 536 slopes between a maximum depth of the groove 536 at a first end 540a of the groove 536 adjacent to the first well 504 and a minimum depth of the groove 536 at a second end 540b of the groove 536 adjacent to the second well 532. In other words, the second end 540b of each groove 536 is disposed above the first end 540a of each groove 536. This means that the depth of the first end 540a of each groove 536 is greater than the depth of the second end 540b of each groove 536.

[0182] With two or more paths for liquid flow between the first well 504 and the second well 532, the possibility of liquid blockage between the first well 504 and the second well 532 is reduced.

[0183] The angled base 538 of the groove 536 is disposed above the base 530 of the first well 504 and above the base 534 of the second well 532. This means that the depth of the sample waste chamber (defined by the first well 504) is greater than the maximum depth of each groove 536. Similarly, the depth of the second well 532 is also greater than the maximum depth of each groove 536.

[0184] The effect of the sloped base 538 means that even if liquid does flow into one of the grooves 536, the pressure required to remove the liquid from the grooves 536 is reduced. This is because the sloped base 538 of the grooves 536 forces the liquid to flow under gravity towards the first well 504. In other words, the grooves 536 are more likely to empty when negative pressure is applied to the sample waste chamber defined by the first well 504. The sloped shape also acts as a capillary stop, helping to prevent liquid from progressing to the second well 532.

[0185] The second well 532 is in fluid communication with the third well 542 via a first connector channel 544 that extends between the second well 532 and the third well 542. The third well 542 is disposed between the second well 532 and the permanent vent 506. The first connector channel 544 has a depth defined by the distance between a base 546 of the first connector channel 544 and a sealing surface 574. The base 546 of the first connector channel 544 is disposed above the base 534 of the second well 532, meaning that the depth of the second well 532 is greater than the depth of the first connector channel 544.

[0186] 12, the connector channel 544 can be a single channel. In alternative implementations, the connector channel 544 may comprise multiple grooves extending between the second well 532 and the third well 542. The multiple grooves can be in a similar structure to the multiple grooves 536 extending between the first well 504 and the second well 532.

[0187] The third well 542 is in fluid communication with a vent channel 548 extending from the third well 542. The third well 542 is in fluid communication with the permanent vent 506 via the vent channel 548. Specifically, the vent channel 548 extends between the third well 542 and the permanent vent 506. The vent channel 548 has a first end adjacent (i.e., in fluid communication with) the third well 542 and a second end adjacent (i.e., in fluid communication with) the permanent vent 506. As explained above, the permanent vent 506 is provided in the form of a hole in the second portion 500 extending through the rigid surface 570.

[0188] 12 shows that the vent channel 548 extends from the third well 542 in a first direction (i.e., parallel to the sealing surface 574) and the holes extend through the rigid surface 570 in a second direction (i.e., away from, or more specifically perpendicular to, the sealing surface 574, such that the second direction is perpendicular to the first direction). The holes extend to the exterior surface of the rigid surface 570.

[0189] The second portion 500 also includes a fourth well 552. The fourth well 552 is in fluid communication with the first well 504 and is located at an end of the first well 504 opposite the second well 532. The fourth well 552 has a depth defined by the distance between a base 554 of the fourth well 552 and a sealing surface 574. A second plurality of grooves 556 (e.g., two grooves 556 as shown in FIG. 12 ) extend between the first well 504 and the fourth well 552. Similar to the first plurality of grooves 536, each of the second plurality of grooves 556 has a sloped base 558 disposed above the base 530 of the first well 504 and above the base 554 of the fourth well 552. This means that the maximum depth of each groove 556 is less than the depth of the first well 504 and less than the depth of the fourth well 552.

[0190] The fourth well 552 is in fluid communication with the third well 542 via a second connector channel 560 extending from the fourth well 552. The fourth well 552 is in fluid communication with the permanent vent 506 via the second connector channel 560. Specifically, the second connector channel 560 extends between the fourth well 552 and the third well 542. Thus, the fluid circuit is comprised of the first well 504 (defining a sample waste chamber), the first plurality of grooves 536, the second well 532, the first connector channel 544, the third well 542, the second connector channel 560, the fourth well 552, and the second plurality of grooves 556.

[0191] The effect of the first plurality of grooves 536 and the second plurality of grooves 556 on fluid movement will be described in more detail with reference to the fluid circuit shown in FIG.

[0192] 13 is an exploded view showing the fluidic layer 300, sealing layer 400, and flow cell strip 140 in a first implementation of a flow cell (i.e., measurement chamber 610) of cartridge 100. The sealing layer 400 is positioned to seal the channel 304 in the second surface 310 of the fluidic layer 300. For example, the sealing layer 400 may be positioned to cover the second surface 310 of the fluidic layer 300, thereby providing direct contact between the sealing layer 400 and the second surface 310 of the fluidic layer 300.

[0193] 13 shows a number of valve regions 302 of the cartridge, each of which is provided in the form of a recess in the fluidic layer 300. This means that the fluidic layer 300 has a reduced thickness in each of the valve regions 302. By providing an area of ​​reduced thickness that is aligned with a corresponding channel 304, the force required to deform the valve region 302 and close the corresponding channel 304 is reduced.

[0194] Also shown in Fig. 13 is a protrusion 330 extending from the first surface 308 of the fluid layer 300. The protrusion 330 includes cavities that define a number of chambers 332, as will be described in more detail with reference to Fig. 20. Implementing the protrusion 330 extending from the first surface 308 of the fluid layer 300 means that the volume of the chambers 332 defined by the protrusion 330 is not limited by the thickness of the fluid layer 300 between its first surface 308 and second surface 310. The fluid layer 300 further comprises a number of openings 350 extending through the thickness of the fluid layer 300.

[0195] 13, the fluidic layer 300 further includes a plurality of pneumatic ports 312 (e.g., three pneumatic ports 312a, 312b, and 312c shown in FIG. 13). Each pneumatic port 312 includes a protrusion 314 extending from the first surface 308. As described in more detail below, each protrusion 314 has a frusto-conical shape (i.e., a truncated conical shape).

[0196] Each port 312 further comprises an opening 316 that extends through the protrusion 314 and at least a portion of the thickness of the fluidic layer (as best shown in Figures 19D and 19E). In the example shown in Figure 13, the opening 316 extends through the entire thickness of the fluidic layer 300.

[0197] Thus, the fluidic layer 300 comprises two sets of openings: a first plurality of openings 350 located beneath the liquid storage capsule 120 and aligned with the protrusions 242 on the actuatable portion 240, and a second plurality of openings 316, each extending through a corresponding protrusion 314 of the pneumatic port 312. These sets of openings allow communication between the network of channels 304 in the fluidic layer 300 and other fluidic components of the cartridge 100 (e.g., the capsule 120 and the pneumatic port 312).

[0198] Each pneumatic port 312 further includes a plurality of support ribs 318 (e.g., eight support ribs 318 as shown in FIG. 17C). Each support rib 318 extends between the first surface 308 and one of the protrusions 314. The support ribs 318 help prevent excessive deformation of the pneumatic port 312 when a force is applied to the pneumatic port 312 by a pneumatic actuator 710 (e.g., shown in FIGS. 23B and 24B). The pneumatic actuator 710 may be a component of the analyzer in which the cartridge 100 is received.

[0199] Additionally, each projection 314 includes an annular rim 320 (best shown in FIGS. 23A-25) at an open end of projection 314 (i.e., the end of the projection furthest from first surface 308). As described further below, the shape of annular rim 320 determines, in part, whether annular rim 320 deforms inwardly or outwardly when a force is applied to pneumatic port 312 by pneumatic actuator 710 (shown in FIGS. 23B and 24B).

[0200] All of the components of the fluid layer 300 described above are integral with the fluid layer 300, meaning that they are all formed from the same elastomeric material as the fluid layer 300. More specifically, the protrusions 330, the projections 314, the support ribs 318, and the annular rim 320 are all integral with the fluid layer 300 and are formed from the same elastomeric material as the fluid layer 300.

[0201] Each opening 142 of the flow cell strip 140 partially defines a corresponding measurement chamber 610 (schematically shown in FIG. 14A ) of the cartridge 100. In particular, each opening 142 defines an inner wall of the measurement chamber 610. Thus, the height of the measurement chamber 610 is defined by the thickness of the flow cell strip 140. An upper inner surface of each measurement chamber 610 is provided by the sealing layer 400. A lower inner surface of each measurement chamber 610 is provided by a sensor surface comprising one or more electrodes (not shown) and a dielectric layer (not shown) of the sensor strip 150 (shown in FIG. 2 ). Thus, the boundary of each opening 142 provides a perimeter of the corresponding measurement chamber 610, which means that the opening 142 defines the area of ​​the measurement chamber 610.

[0202] 13, each opening 142 of the flow cell strip 140 is accessible from a channel 304 in the fluidic layer 300 (shown in FIG. 17) through a corresponding pair of vias (i.e., holes) 404 in the sealing layer 400. Each of the corresponding pair of vias 404 is aligned with one end of a corresponding channel 304 in the fluidic layer 300. This means that each pair of vias 404 is provided on the upper inner surface of a corresponding measurement chamber 610.

[0203] 13 further shows that the sealing layer 400 comprises a plurality of non-bonded regions 406 (i.e., 12 circles beneath each of the valve regions 302). By providing the non-bonded regions 406 on the top surface of the sealing layer 400 beneath the valve regions 302, the channels 304 do not bond to the sealing layer 400 when a force is applied to the valve regions 302. As a result, the non-bonded regions 406 prevent the valves from remaining closed when the force is removed or from slowly opening when the force is removed.

[0204] It will be appreciated that the sealing layer 400 also includes waste holes (not shown) aligned with the channels 304 of the fluidic layer 300 that provide fluidic connection to the waste chamber 508 in the second portion. For example, with reference to FIG. 17B, the sealing layer 400 may include waste holes aligned with an end of the fifteenth channel 304o and an end of the eighteenth channel 304r.

[0205] 14A-14C show how the amount of liquid remaining after emptying the measurement chamber is varied by (i) changing the angle of the outlet conduit, (ii) the misalignment of the via with the end of the measurement chamber, and (iii) changing the size of the via.

[0206] The measurement chamber 610 of Figures 14A-14C includes three portions, as shown diagrammatically in Figure 14A: a first tapered portion 614a extending from a rounded first end 612a, a second tapered portion 614b tapering toward a rounded second end 612b, and a non-tapered central portion 612c of constant cross-section extending between the first tapered portion 614a and the second tapered portion 614b.

[0207] The first tapered portion 614a has a taper angle defined between the wall of the measurement chamber 610 (i.e., the perimeter of the corresponding opening 142) and a longitudinal centerline through the measurement chamber 610. Similarly, the second tapered portion 614b has a taper angle defined between the wall of the measurement chamber 610 and a longitudinal centerline through the measurement chamber 610. The taper angles of the first tapered portion 614a and the second tapered portion 614b are preferably less than 30 degrees because a larger taper angle will result in air bubbles being formed during filling or emptying the measurement chamber 610 and residual liquid remaining after emptying the measurement chamber 610. A taper angle less than 30 degrees is also preferred because there is no expansion of the flow in the fluid layer 300. As shown in FIG. 14A, the conduit 600 in the fluid layer 300 is of a fixed width, which means there is no expansion of the flow in the fluid layer 300. Instead, the flow of fluid expands outward when the fluid reaches the measurement chamber 610. A taper angle of less than 30 degrees reduces the possibility of air bubbles forming as a result of the expansion of the flow in the measurement chamber 610 (which may occur at higher taper angles, such as, for example, 45 degrees). It will be appreciated that a very small taper angle is undesirable because it reduces the footprint of the measurement chamber 610 (for a given length of the measurement chamber) and reduces the contact area with the electrodes of the sensor strip 150. In light of these considerations, a preferred range of taper angles for the first tapered portion 614a and the second tapered portion 614b is between 15 degrees and 25 degrees. A taper angle of less than 25 degrees further reduces the possibility of air bubbles forming as a result of the expansion of the flow in the measurement chamber 610.

[0208] The rounded ends 612 of the measurement chamber 610 each have a constant curvature. Thus, the curvature of each of the rounded ends 612 can be defined with respect to an origin of curvature and a constant radius of curvature. In other words, each rounded end 612 of the measurement chamber 610 is provided in the form of an arc having a particular radius. In one exemplary implementation, the radius of the first rounded end 612a is 0.5 mm, and the radius of the second rounded end is 0.5 mm.

[0209] 14A also shows diagrammatically inlet conduits 600a and outlet conduits 600b, each defined by a corresponding channel 304 in second surface 310 sealed by sealing layer 400. In addition, FIG. 14A shows diagrammatically pairs of vias 404 that allow liquid to flow into and out of measurement chamber 610. One of each pair of vias 404 is aligned with a rounded first end 612a of measurement chamber 610, and the other of each pair of vias 404 is aligned with a rounded second end 612b of measurement chamber 610. Thus, inlet conduit 600a is in fluid communication with rounded first end 612a, and outlet conduit 600b is in fluid communication with rounded second end 612b. In the example shown in FIG. 14A, the conduit 600 has a smaller width than the via 404 , and the via 404 is aligned with the rounded end 612 of the measurement chamber 610 .

[0210] The outlet conduit angle in FIG. 14A is defined between a centerline through the outlet conduit 600b and a centerline through the measurement chamber 610. FIG. 14A illustrates how changing the outlet angle affects emptying the measurement chamber 610. It is desirable to reduce the volume of liquid remaining in the measurement chamber 610 because any liquid remaining in the measurement chamber 610 may affect measurements performed on liquid subsequently drawn into the measurement chamber 610. For example, the remaining liquid may react with or otherwise contaminate subsequent liquids. In one implementation, air is provided to the measurement chamber 610 (e.g., via a pneumatic actuator 710) to push liquid out of the measurement chamber 610.

[0211] 14A shows five outlet conduit angles: 0 degrees, 45 degrees, 90 degrees, 135 degrees, and 180 degrees. At the 0 degree angle, liquid flows through measurement chamber 610, through corresponding via 404 into outlet conduit 600b, and then flows in a direction opposite to the direction of flow through measurement chamber 610. At the 180 degree angle, liquid flows through measurement chamber 610, through corresponding via 404 into outlet conduit 600b, and then flows in the same direction as the direction of flow through measurement chamber 610.

[0212] At 45, 90, or 135 degree exit conduit angles, the angle of the exit conduit 600b results in a stagnation region (shown in black in FIG. 14A ) where the footprint of the measurement chamber 610 extends beyond the footprint of the exit conduit 600b. The stagnation region results from the small size of the exit conduit 600b compared to the via 404. The stagnation region causes liquid to be trapped within the measurement chamber 610 (i.e., trapped within the flow cell layer 140) since any liquid within the stagnation region cannot be forced out through the exit conduit 600b under pressure. In contrast, at 0 and 180 degree exit conduit angles, the end point of the measurement chamber 610 in the x-direction overlaps with the footprint of the exit conduit 600b. This means that no portion of the measurement chamber 610 extends beyond the footprint of the exit conduit 600b, allowing a larger percentage of liquid to be forced out through the exit conduit 600b under pressure. Thus, of the five exit conduit angles shown in FIG. 14A, the 0 degree and 180 degree exit conduit angles result in the smallest volume of liquid remaining in the measurement chamber 610 after purging the measurement chamber 610 with air.

[0213] Experimental data has been shown to verify improved performance at 0 and 180 degree exit conduit angles, but also indicates that less remaining volume of liquid is achieved at an exit conduit angle of at least 150 degrees. Thus, it is preferred that the exit conduit 600b is aligned with the measurement chamber 610 (i.e., aligned with a longitudinal centerline through the measurement chamber 610). In particular, it is preferred that the exit conduit angle is 150 degrees or greater to minimize the volume of liquid remaining in the measurement chamber 610. More preferably, the exit conduit angle is about 180 degrees to reduce loss of particles in the flow suspension (e.g., blood or functional particles / beads) flowing through the measurement chamber 610. Alternatively, a 0 degree exit conduit angle can be implemented to reduce the volume of liquid remaining in the measurement chamber 610 and via 404.

[0214] 14B illustrates how misalignment of measurement chamber 610 and vias 404 affects the volume of liquid remaining in measurement chamber 610. For the measurement chamber illustrated in FIG. 14B, vias 404 have a diameter of 1 mm and each rounded end 612 has a constant curvature with a diameter of 1 mm (radius of 0.5 mm). The misalignment of vias 404 and rounded ends 612 causes liquid to become trapped within vias 404 (i.e., within sealing layer 400). The liquid remaining in measurement chamber 610 and vias 404 is shown as the solid black areas.

[0215] The top measurement chamber in Figure 14B shows the effect of +0.25 mm misalignment of the vias 404 in each of the x and y directions. The second measurement chamber in Figure 14B shows the effect of -0.25 mm misalignment of the vias 404 in each of the x and y directions. The third measurement chamber in Figure 14B shows the effect of 0.25 mm misalignment of the vias 404 in the x direction outward from the measurement chamber (i.e. -0.25 mm misalignment of the entry via in the x direction, and +0.25 mm misalignment of the exit via in the x direction). The bottom measurement chamber in Figure 14B shows the effect of -0.25 mm misalignment of the vias 404 in the x direction inward toward the measurement chamber (i.e. +0.25 mm misalignment of the entry via in the x direction, and -0.25 mm misalignment of the exit via in the x direction).

[0216] The top measurement chamber in FIG. 14B shows that a stagnation region exists within via 404 (specifically, within the area of ​​via 404 that does not overlap the footprint of measurement chamber 610) as a result of the misalignment of via 404 and rounded end 612 of measurement chamber 610.

[0217] A similar effect is shown in the second measurement chamber of Figure 14B. However, the negative misalignment of the exit via in the x-direction results in an additional stagnation area in measurement chamber 610 (i.e., in flow cell layer 140). This additional stagnation area occurs because the footprint of measurement chamber 610 extends beyond the exit via in the x-direction. As a result of the additional stagnation area, more liquid remains in the second measurement chamber of Figure 14B than in the top measurement chamber of Figure 14B.

[0218] The third measurement chamber of FIG. 14B (like the top measurement chamber of FIG. 14B) introduces a stagnation region within via 404 because via 404 extends beyond the footprint of measurement chamber 610.

[0219] 14B does not result in a stagnation region within via 404 because via 404 falls within the footprint of the measurement chamber. However, as the footprint of the measurement chamber extends beyond both vias 404 in the x-direction, two stagnation regions are formed within measurement chamber 610 (i.e., at either end of measurement chamber 610).

[0220] Each of the hypothetical misalignments shown in FIG. 14B illustrates that any misalignment of via 404 and measurement chamber 610 will result in liquid remaining in measurement chamber 610 and / or via 404 after air is used to clear the flow cell. The misalignments shown in FIG. 14B also result in steps for liquid to exit measurement chamber 610 (i.e., a first step between measurement chamber 610 and the exit via, and a second step between the exit via and exit conduit 600b). The steps can result in liquid run-off when clearing measurement chamber 610, leading to liquid dropping into measurement chamber 610. Any liquid retained at the exit from measurement chamber 610 is problematic because it can result in air bubble formation when measurement chamber 610 (which is now a wetted surface) is subsequently filled with a different liquid. This occurs when the meniscus of the trailing liquid joins the liquid retained in measurement chamber 610 and traps an air bubble. The air bubble can interfere with measurements performed on the solution in measurement chamber 610. For example, if an air bubble is placed at one of the electrodes in measurement chamber 610, the electrochemical measurement may provide an erroneous reading.

[0221] Thus, preferably, one or both of the vias 404 are aligned with the curvature of the corresponding rounded end 612 of the measurement chamber 610 such that there is no misalignment between the via 404 and the measurement chamber 610. In other words, the origin of one or both of the vias 404 preferably coincides with the origin of the curvature of the corresponding rounded end 612.

[0222] Figure 14C illustrates the effect of varying the diameter of vias 404 where the vias 404 have a diameter (or radius) larger than the diameter (or radius) of curvature of the corresponding rounded ends 612 of measurement chambers 610. For the measurement chambers shown in Figure 14C, each rounded end 612 has a constant curvature with a diameter of 1 mm, and the vias 404 have a diameter of 1.3 mm.

[0223] Figure 14C shows that the larger diameter of via 404 creates a stagnation region (shown in black) where via 404 extends beyond the footprint of measurement chamber 610, similar to the effect shown in the third measurement chamber of Figure 14B. It will be appreciated that a stagnation region (within measurement chamber 610) can also result as the diameter of via 404 decreases relative to the curvature of rounded end 612 if the footprint of measurement chamber 610 extends beyond via 404 in the x-direction (i.e., similar to the effect shown in the bottom measurement chamber of Figure 14B).

[0224] 14C , increasing the diameter of the via 404 relative to the diameter of curvature of the rounded end 612 of the measurement chamber 610 increases the volume of liquid remaining in the via 404 (as a result of stagnation areas in the via 404). Reducing the diameter of the via 404 relative to the diameter of curvature of the rounded end 612 of the measurement chamber 610 has a similar effect (as a result of stagnation areas in the measurement chamber 610). Thus, the diameter (or radius) of one of both vias 404 is preferably equal to the diameter (or radius) of curvature of the corresponding rounded end 612 of the measurement chamber 610.

[0225] 15 is an exploded view showing the fluidic layer 300 and the alternative sealing layer 450. The sealing tape 130 that seals the chamber 332 in the fluidic layer 300 can also be seen in FIG.

[0226] Similar to the sealing layer 400 shown in FIG. 13, the sealing layer 450 includes holes 452 that provide fluid communication between the metering chamber 232 (located in the first portion 200) and the metering chamber outlet channel 502 (located in the second portion 500). In addition, the sealing layer 450 includes a waste outlet 451 that provides fluid communication between the sample compatibility control chamber 236 and the first well 504 (defining a waste chamber). The sealing layer 450 also includes a plurality of openings 454, each of which partially defines a corresponding measurement chamber 610 of the cartridge 100. The openings 454 provide the same function as the openings 142 in the sealing strip 140, except that the openings 454 are located in the sealing layer 450. Thus, in the implementation shown in FIG. 15, the sealing layer 450 does not include vias for fluid communication with the measurement chamber 610, and a separate flow cell strip is not required.

[0227] Implementing vias 404 between inlet conduit 600a and outlet conduit 600b and measurement chamber 610 can create a flow impedance in the event of any misalignment between vias 404 and measurement chamber 610. The flow impedance creates a back pressure, which provides an area for residual liquid to remain. As explained above, residual liquid in measurement chamber 610 is undesirable as it can cause contamination.

[0228] The flow impedance provided by the vias is caused by step effects between the measurement chamber 610, the thickness of the sealing layer 400 (in which the vias 404 are located), and the conduits 600a, 600b. These step effects cause the flow to be less smooth, which causes liquid to remain in the measurement chamber 610.

[0229] The implementation of sealing layer 450 without vias reduces the tendency for liquid to remain in measurement chamber 610 by eliminating the constriction provided by vias and reducing the step effect between measurement chamber 610 and conduits 600a, 600b.

[0230] 16 shows a schematic representation of an implementation of a measurement chamber 610 without vias. In this implementation, an inlet conduit 600a (provided by one of the channels 304 in the second surface 310 of the fluidic layer 300 and sealed by the sealing layer 450) overlaps the first end 612a of the measurement chamber 610, and an outlet conduit 600b overlaps the second end 612b of the measurement chamber 610. When an opening 454 is provided in the sealing layer 450, the area of ​​the opening 454 defines an area where the conduits 600a, 600b are not sealed. This means that the inlet conduit 600a and the outlet conduit 600b are in direct fluid communication with the measurement chamber 610.

[0231] FIG. 16 also shows three possible outlet conduit angles: 90 degrees, 135 degrees, and 180 degrees. A preferred configuration of the measurement chamber 610 shown in FIG. 16 is for the inlet conduit 600a and outlet conduit 600b to be aligned with the direction of flow (i.e., an outlet conduit angle of preferably at least 150 degrees, more preferably about 180 degrees). In other words, the inlet conduit 600a and outlet conduit are preferably aligned with a longitudinal centerline through the measurement chamber 610. This reduces the loss of particles in the flow suspension (e.g., blood or functional particles / beads) flowing through the measurement chamber 610.

[0232] 16 additionally shows a first tapered portion 614a, a second tapered portion 614b, and a central portion 614c of the measurement chamber 610. The preferred angles of the tapered portions 614a, 614b are the same as those described with reference to FIG.

[0233] 17A and 17B depict bottom views of the fluidic layer 300 showing the second surface 310 of the fluidic layer 300 opposite the first surface 308. The valve area 302, the pneumatic ports 312 (including the protrusions 314 and the support ribs 318), and the protrusions 330 on the first surface 308 are all shown in dashed lines in FIG. 17A. FIG. 17A also shows the openings 316 and 350 of the ports 312, each of which extends through the thickness of the fluidic layer 300. FIG. 17B identifies certain conduits 304 in the second surface 310 and the junctions 306 between the conduits 304.

[0234] Each of the valve regions 302 allows the flow of fluid through one of the conduits 600 of the cartridge 100 to be controlled. Each valve is defined by one of the valve regions 302 (each of which is disposed over a corresponding channel 304) and a sealing layer 400 that seals the corresponding channel 304. To close a valve, a force is applied to the valve region 302 (e.g., shown in FIG. 21 ) to compress the corresponding channel 304 against the sealing layer 400. Closing the valve prevents fluid flow through the corresponding conduit 600. To open a valve, the force applied to the valve region 302 to close the valve is retracted. Opening the valve allows fluid to flow through the corresponding conduit 600.

[0235] The flow of fluid through the conduit 600 is controlled by applying variable pressure to the pneumatic ports 312. As described in more detail below, each of the pneumatic ports 312 can either (i) receive positive pressure via a corresponding pneumatic actuator 710, (ii) receive negative pressure via a corresponding pneumatic actuator 710, (iii) be vented (i.e., open to atmospheric pressure) via a corresponding pneumatic actuator 710, or (iv) be closed (i.e., not vented), meaning that the pneumatic port 312 is decoupled from the pneumatic actuator 710. In case (iv), there is no air flow through the pneumatic port 312.

[0236] As described below, some channels 304 in the fluid layer extend from a point in the fluid layer that overlies one of the troughs 514 in the second portion 500. This means that positive air pressure is applied to the first pneumatic port 312a, for example, by the pneumatic actuator 710. Pressurized air flows through a corresponding opening 316 in the first pneumatic port 312a, through a corresponding hole in the sealing layer 400, through a channel 518a in the first port support 516a, through the trough 514a, and into one of the channels 304 (specifically, the second channel 304b, the third channel 304c, or the fourth channel 304d, using the channel numbering shown in FIG. 17B). Negative pressure is applied in a similar manner, but with the opposite air flow.

[0237] This arrangement reduces the risk of liquid being drawn into the pneumatic actuator 710 (e.g., during application of negative pressure to aspirate liquid) because any liquid drawn through the channel 304 will fall under gravity to the bottom of the trough 514a. As shown in FIG. 10, the channel 518a is on the flat upper surface of the port support 516a, which means that the channel 518a is disposed above the base of the trough 514a. Thus, any liquid that remains in the trough 514a will not be drawn through the channel 518a and into the pneumatic actuator 710 via the first pneumatic port 312a.

[0238] The fluidic layer 300 includes the following channels 304, which are described in the following paragraphs with reference to Figures 17A and 17B.

[0239] The first channel 304a extends from a point overlying the hole 402 in the sealing layer 400 (or hole 452 in the sealing layer 450). The first channel 304a thus provides a fluid connection to the metering chamber outlet channel 502 in the second portion (via hole 402 / 452). The first channel 304a extends from this point to a point overlying the first measurement chamber. The first channel 304a provides an inlet to the first measurement chamber. The flow of fluid through the first channel 304a is controlled by the third valve region 302c.

[0240] The second channel 304b extends from a point overlying the first trough 514a to a third opening 350c that provides an entrance to the liquid storage capsule 120 that overlies the openings 350c and 350d.

[0241] The third channel 304c extends from a point overlying the first trough 514a to a second opening 350b that provides an entrance to the liquid storage capsule 120 that overlies the openings 350a and 350b.

[0242] The fourth channel 304d extends from a point overlying the first trough 514a to a first junction 306a with the nineteenth channel 304s (described below). Fluid flow through the fourth channel 304d is controlled by the second valve region 302b.

[0243] The fifth channel 304e extends from a point overlying the second trough 514b to a first chamber 332a defined by the protrusion 330. Fluid flow through the fifth channel 304e is controlled by a sixth valve region 302f.

[0244] The sixth channel 304f extends from a point overlying the third trough 514c to the eighth opening 350h. The sixth channel 304f provides an entrance to a liquid storage capsule that overlies the sixth opening 350f and the eighth opening 350h.

[0245] The seventh channel 304g extends from a point overlying the third trough 514c to a fourth chamber 332d defined by the protrusion 330. Fluid flow through the seventh channel 304g is controlled by the eleventh valve region 302k.

[0246] The eighth channel 304h extends from a point overlying the third trough 514c to the seventh opening 350g. The eighth channel 304h provides an entrance to the liquid storage capsule 120 that overlies the fifth opening 350e and the seventh opening 350g.

[0247] The ninth channel 304i extends from the fourth opening 350d to the second junction 306b with the first channel 304a. Liquid released from the liquid storage capsule 120 overlying the openings 350c and 350d flows through a conduit 600 defined by the ninth channel 304i. The flow of fluid through the ninth channel 304i is controlled by the fourth valve region 302d.

[0248] The tenth channel 304j extends from the first opening 350a to a third junction 306c with the sixteenth channel 304p (described below). Liquid released from the liquid storage capsule 120 overlying the openings 350a and 350b flows through a conduit 600 defined by the tenth channel 304j. The flow of fluid through the tenth channel 304j is controlled by the first valve region 302a.

[0249] The eleventh channel 304k extends from the sixth opening 350f to a fourth junction 306d with the fourth channel 304d. Liquid released from the liquid storage capsule 120 overlying the openings 350f and 350h flows through a conduit 600 defined by the eleventh channel 304k. The flow of fluid through the eleventh channel 304k is controlled by the seventh valve region 302g.

[0250] The twelfth channel 304l extends from the fifth opening 350e to a fifth junction 306e with the fourth channel 304d. Liquid released from the liquid storage capsule 120 overlying the openings 350e and 350g flows through a conduit 600 defined by the twelfth channel 304l. The flow of fluid through the twelfth channel 304l is controlled by the fifth valve region 302e.

[0251] The thirteenth channel 304m extends between the second chamber 332b defined by the protrusion 330 and the third chamber 332c defined by the protrusion 330.

[0252] The fourteenth channel 304n extends from a sixth junction 306f with the first channel 304a to a seventh junction 306g with the thirteenth channel 304m. Fluid flow through the fourteenth channel 304n is controlled by an eighth valve region 302h.

[0253] The fifteenth channel 304o extends from a point overlying the first measurement chamber to a point overlying the second waste chamber 508b. The fifteenth channel 304o provides an outlet from the first measurement chamber and an inlet to the second waste chamber 508b. Fluid flow through the fifteenth channel 304o is controlled by the twelfth valve region 302l.

[0254] The sixteenth channel 304p extends from a point overlying the second measurement chamber to an eighth junction 306h with the fifteenth channel 304o. The sixteenth channel 304p provides an outlet from the second measurement chamber.

[0255] Seventeenth channel 304q extends from a point overlying the third measurement chamber to a point overlying the second measurement chamber and provides an outlet from the third measurement chamber and an inlet to the second measurement chamber.

[0256] The eighteenth channel 304r extends from the ninth junction 306i with the seventeenth channel 304q to a point overlying the first waste chamber 508a. The eighteenth channel 304r provides an inlet to the first waste chamber 508a. Fluid flow through the eighteenth channel 304r is controlled by the tenth valve region 302j.

[0257] The nineteenth channel 304s extends from the second chamber 332b defined by the protrusion 330 to a point overlying the third measurement chamber. The nineteenth channel 304s provides an inlet to the third measurement chamber. Fluid flow through the nineteenth channel 304s is controlled by the ninth valve region 302i.

[0258] FIG. 17C is a top view of the fluidic layer 300 showing the first surface 308. FIG. 17C shows the location of the valve region 302, the port 312 (including the protrusion 314, the opening 316, and the support rib 318), the protrusion 330 (including the chambers 332a-332d), and the opening 350. As FIG. 17C shows a top view of the first surface 308 and FIG. 17A shows a bottom view of the second surface 310, it will be appreciated that the lateral order of the valve region 302 and the opening 350 in FIG. 17C is reversed compared to FIG. 17A. As explained above, the opening 350 and the opening 316 extend through the thickness of the fluidic layer 300.

[0259] The junction 306 can provide a known position of the liquid front in the fluidic layer 300. For example, by aspirating liquid into the second waste chamber 508b (via the first channel 304a and the fifteenth channel 304o), a known liquid front exists at the sixth junction 306f. Knowing the liquid front, liquid can be metered (e.g., in one of the chambers 332). For example, a known pressure differential can be implemented via the pneumatic port 312 to meter liquid from the sixth junction 306f to a predetermined fill level in the second chamber 332b or the third chamber 332c. The pressure differential can be calculated based on the desired fill level (i.e., the volume to be metered) and the volume of the conduit 600 defined by the channels 304 between the junction 306 and the chamber (in this example, the volume of the fourteenth channel 304n).

[0260] In the alternative implementation of the fluidic layer shown in Fig. 18A and Fig. 18B, the channels 364 are provided on both the first surface 368 and the second surface 370 of the alternative fluidic layer 360. It is difficult to configure a network of fluidic channels within a limited amount of space. Point-of-care devices are designed to be small, which limits the area available on the fluidic layer 300 for laying the channels with their respective adhesive areas around them (i.e. for adhering to the sealing layer 400). By implementing the channels 364 on both surfaces 368, 370 of the fluidic layer 360, it is possible for example to allow the channels 364 used for transporting air (e.g. for cleaning the measurement chamber or for moving liquid from the liquid storage capsule 120) to move to the first surface 368 without affecting the flow of the liquid. Providing the channels 364 in the first surface 368 also allows the channels 364 of the fluidic layer 360 to intersect, meaning that a more complex network of channels 364 can be implemented.

[0261] In alternative implementations of the fluidic layer 360, a valve region 362 is still provided on a first surface 368 of the fluidic layer 360. Thus, the channels 364 in the first surface 368 are either channels 364 that do not pass under the valve region 362 (e.g., channels 304b, 304c, 304f, 304h in FIG. 17B ) or channels 364 that have a first portion on the first surface 368 and a second portion on the second surface 370. For example, the second portion of the channels 364 can be the portion of the channels 364 that passes under the valve region 362. These two portions of the channels 364 may be connected by a vertical or angled conduit that extends through the thickness of the fluidic layer 360.

[0262] 17B, ​​the second channel 304b, the third channel 304c, the sixth channel 304f, and the eighth channel 304h are all examples of channels 304 that can travel to the second surface 310 of the fluidic layer 300. This is because each of these channels 304 does not pass under the valve region 302 and is used for transporting air. The fifth channel 304e and the seventh channel 304g are both examples of channels that may have a first portion in the first surface 308 and a second portion in the second surface 310. For example, a portion of the fifth channel 304e between a point overlying the second trough 514b and a point downstream of the sixth valve region 302f can be provided in the second surface 310, allowing the flow of fluid through this portion to be controlled by the sixth valve region 302f. The remaining portion of the fifth channel 304e between a point downstream of the sixth valve region 302f and the first chamber 332a may be provided in the first surface 308. Of course, in such an implementation, the fifth channel 304e would include a conduit section through the fluidic layer 300 to connect the two portions of the fifth channel 304e.

[0263] 18A and 18B, various examples of channels 364 having portions on both surfaces 368, 370 are shown. For example, the channel 364a in FIG. 18A and 18B has a first portion 382a on the second surface 370, a second portion 382b on the first surface 368, and a third portion 382c on the second surface 370. The first portion 382a extends between a point overlying the first trough 514a and a first through-hole 384a in the fluidic layer 360. The second portion 382b extends between the first through-hole 384a and the second through-hole 384b in the fluidic layer 360. The third portion 382c extends between the second through-hole 384b and an opening 386 in which the liquid storage capsule 120 may be placed when the cartridge 100 with the fluidic layer 360 is assembled. By providing portions of channel 364a on both surfaces 368, 370, channel 364b can intersect with channel 364a (as shown in FIG. 18B).

[0264] FIG 19A is a cross section through the fluidic layer 300 along line AA in FIG 17C. FIG 19A shows that the valve regions 302 are provided as circular recesses in the first surface 308 of the fluidic layer 300. In other words, the fluidic layer 300 has a reduced thickness at each of the valve regions 302. As shown in FIG 19A, a chamfered annular surface is provided between the thickness of the fluidic layer 300 and the reduced thickness valve regions 302. The protrusion 314 of the first pneumatic port 312a and the support rib 318 can also be seen from FIG 19A.

[0265] As discussed above, the flow of fluid through the conduit 600 defined by the channels 304 is controlled by applying forces to the valve regions 302. To allow the flow of fluid to be controlled, the valve regions 302 are provided directly above the channels 304 for which they control the flow of fluid. Specifically, FIG. 19A shows a fourth valve region 302d provided directly above the ninth channel 304i, a third valve region 302c provided directly above the first channel 304a, a second valve region 302b provided directly above the fourth channel 304d, and a first valve region 302a provided directly above the tenth channel 304j. FIG. 19A also shows a cross section through channels 304b and 304c that are not compressed when forces are applied to the valve regions 302a, 302b, 302c, and 302d.

[0266] Figure 19B is a cross section through fluidic layer 300 along line BB in Figure 17C. Specifically, Figure 19B shows eighth valve region 302h disposed directly above fourteenth channel 304n, seventh valve region 302g disposed directly above eleventh channel 304k, sixth valve region 302f disposed directly above fifth channel 304e, and fifth valve region 302e disposed directly above twelfth channel 304l. Figure 19B also shows a cross section through channels 304a, 304d, and 304j that are not compressed when forces are applied to valve regions 302e, 302f, 302g, and 302h.

[0267] FIG. 19C is a cross section through the fluidic layer 300 along line CC in FIG. 17C. The cross section is through a fourth chamber 332d defined by a protrusion 330 extending from the first surface 308 of the fluidic layer 300. A seventh channel 304g extending between a point on the third trough 514c and the fourth chamber 332d is also visible in FIG. 19C. FIG. 19C also shows a twelfth valve region 302l disposed immediately above the fifteenth channel 304o, an eleventh valve region 302k disposed immediately above the seventh channel 304g, a tenth valve region 302j disposed immediately above the eighteenth channel 304r, and a ninth valve region 302i disposed immediately above the nineteenth channel 304s. Additionally, FIG. 19C shows a cross section through channels 304a, 304f, 304h, and 304j that are not compressed when force is applied to valve regions 302i, 302j, 302k, and 302l.

[0268] FIG. 19D is a cross section through the fluidic layer 300 along line DD in FIG. 17C. FIG. 19E shows the circled portion of the cross section of FIG. 19D in more detail. Specifically, FIG. 19D and FIG. 19E show a cross section through a protrusion 330 extending from a first surface 308 of the fluidic layer 300. FIG. 19D and FIG. 19E also show a cross section through a second pneumatic port 312b and a third pneumatic port 312c. These ports 312 and openings 316 extending through the thickness of the fluidic layer 300 can also be seen in these figures, as specifically shown in FIG. 19E.

[0269] The protrusion 330 defines four chambers 332. Each of the chambers 332 is in fluid communication with a conduit 600 of the cartridge 100, as described in the following paragraphs. The chambers 332 allow for mixing of the fluids that is controlled by applying air pressure to the chambers 332 via the channel 304.

[0270] The first chamber 332a is in selective fluid communication with the second pneumatic port 312b via the fifth channel 304e connecting to the first chamber 332a, the second trough 514b, the second channel 518b in the second port support 516b, and the opening 316 extending through the second pneumatic port 312b. The fluid communication between the first chamber 332a and the second pneumatic port 312b is selective because it is controlled by applying a force to the sixth valve region 302f.

[0271] The second chamber 332b is in selective fluid communication with the third measurement chamber via the nineteenth channel 304s. The fluid communication between the second chamber 332b and the third measurement chamber is selective because it is controlled by applying a force to the ninth valve region 302i. The second chamber 332b is also in selective fluid communication with (i) the first pneumatic port 312a via the fourth channel 304d (controlled by the second valve region 302b), (ii) the fifth opening 350e via the twelfth channel 304l (controlled by the fifth valve region 302e), and (iii) the sixth opening 350f via the eleventh channel 304k (controlled by the seventh valve region 302g).

[0272] The third chamber 332c is in fluid communication with the second chamber 332b via a thirteenth channel 304m that allows liquids to be transported between the second chamber 332b and the third chamber 332c (e.g., to allow mixing of the liquids).

[0273] The fourth chamber 332d is in selective fluid communication with the third pneumatic port 312c via the seventh channel 304g connecting to the fourth chamber 332d, the third trough 514c, the third channel 518c in the third port support 516c, and the opening 316 extending through the third pneumatic port 312c. Fluid communication between the fourth chamber 332d and the third pneumatic port 312c is selective because it is controlled by applying a force to the eleventh valve region 302k.

[0274] The first chamber 332a is in fluid communication with the second chamber 332b through a first opening 334a in the top of a wall 336a separating the first chamber 332a from the second chamber 332b. The fluid communication provided by the first opening 334a allows for fluid to move into the second chamber 332b (e.g., from the third chamber 332c) by, for example, applying negative pressure from the second pneumatic port 312b through the first chamber 332a. Similarly, the fluid communication provided by the first opening 334a allows for fluid to move out of the second chamber 332b (e.g., to the third chamber 332c) by, for example, applying positive pressure from the second pneumatic port 312b through the first chamber 332a. The first opening 334a is located at the top of the wall 336a to maximize the volume of liquid that can be retained within the second chamber 332b, thereby reducing the likelihood of liquid flowing through the first opening 334a into the first chamber 332a.

[0275] Similarly, the fourth chamber 332d is in fluid communication with the third chamber 332c through a second opening 334b ​​in the top of the wall 336b that separates the third chamber 332c from the fourth chamber 332d, allowing fluid to flow into and out of the third chamber 332c by application of a variable pressure from the third pneumatic port 312c through the fourth chamber 332d.

[0276] FIG. 20 is a further cross section through the projection 330 showing the solid reagent 170 disposed within the third chamber 332c. The solid reagent 170 may be a lyophilized reagent. The solid reagent 170 may be suspended within a liquid solution by displacing liquid within the third chamber 332c. Assuming that the outlet from the third chamber 332c (i.e., the thirteenth channel 304m) is provided at the second surface 310 of the fluidic layer 330, the outlet from the third chamber 332c is provided at the base of the third chamber 332c. Providing the outlet from the third chamber 332c at the base of the chamber maximizes the amount of resuspended or dissolved reagent that can be extracted from the third chamber 332c, since any undissolved solid reagent falls under gravity to the base of the third chamber 332c and is subsequently suspended or dissolved. As a result, a significant proportion of the solid reagent 170 (e.g., substantially all of the solid reagent 170) can be utilized. Liquid may be repeatedly transported between the second chamber 332b and the third chamber 332c via the thirteenth channel 304m to resuspend and homogenize the solid reagent 170.

[0277] In other words, by locating the solid reagent 170 in a chamber having an outlet at its base, the likelihood of unsuspended solid reagent becoming trapped within the fluid network and therefore going unused is minimized. Because a high percentage of the solid reagent 170 can be utilized, smaller solid reagents can be utilized as compared to conventional point-of-care devices that incorporate solid reagents.

[0278] Figure 21 is a cross-sectional view through one of the valve regions 302 of the fluidic layer 300. Figure 21 shows the fluidic layer 300, the sealing layer 400 that seals the channel 304 in the second surface 310 of the fluidic layer 300 to form a conduit 600, and the second portion 500 (specifically, the valve support region 524 of the second portion 500).

[0279] 21 shows the valve region 302 with a reduced thickness compared to the thickness of the remainder of the fluid layer 300. One can also see the chamfered annular surface between the thickness of the fluid layer 300 and the reduced thickness valve region 302. The reduced thickness of the fluid layer 300 within the valve region 302 means that the valve region 302 can be more easily compressed to close off a corresponding conduit 600 located below the valve region 302.

[0280] 21 also shows that the distance between the top of the channel 304 and the valve region 302 is defined by a height H. The height H depends on the properties (e.g., hardness) of the material used in the fluidic layer 300 and the available force from the valve actuator 700. In addition, the channel 304 includes a radius R that provides a fillet between the channel 304 and the second surface 310 of the fluidic layer 300. By providing the fillet radius R, the force required to close the valve defined by the valve region 302 is reduced.

[0281] 21, a force is applied to the valve region 302 by the valve actuator 700 to close the conduit 600. The elastomeric properties of the fluidic layer 300 allow for deformation of the fluidic layer 302 within the valve region 302 to close the conduit 600. The elastomeric properties of the fluidic layer 300 also allow the valve region 302 to return to their original shape when the force applied by the valve actuator 700 is removed, thereby allowing the conduit 600 to reopen.

[0282] Figures 22A-C illustrate the process of applying a force to a valve region 302 to close a corresponding conduit 600. As shown in Figure 22A, the valve actuator 700 initially contacts the valve region 302. In the position shown in Figure 22A, the valve actuator 700 is in a disengaged position in which the valve actuator 700 is not applying a force to the valve region 302 to close a corresponding conduit 600. To facilitate deformation of the fluid layer, the valve actuator 700 may have rounded (e.g., hemispherical) ends.

[0283] A force is then applied to the valve region 302 using the valve actuator 700. This compresses the fluid layer 300 at the valve region 302 and deforms the conduit 600 to a partially closed state (Figure 22B). In the position shown in Figure 22B, the conduit 600 is partially closed, which means that the valve actuator 700 is in a partially engaged position.

[0284] Continued application of force to the valve region 302 results in further compression of the fluid layer 300 at the valve region 302, closing the conduit 600 against the sealing layer 400 supported by the corresponding valve support region 524 of the second part 500 (Figure 22C). In the position shown in Figure 22C, the conduit 600 is fully closed, which means that the valve actuator 700 is in the engaged position.

[0285] Assuming that the fluid layer 300 is formed from an elastomeric material, when the force applied by the valve actuator 700 is removed and the valve actuator 700 retracts to the disengaged position shown in FIG. 22A, the valve region 302 returns to the undepressed configuration shown in FIG. 22A.

[0286] 23A and 23B show schematic compression of pneumatic ports 312 by a pneumatic actuator 710. As explained above, the ports 312 are formed from the same material as the fluidic layer 300 (i.e., the elastomeric layer). This means that when a force is applied to the ports 312, deformation of the protrusions 314 and the annular rim 320 occurs. The flexibility of the elastomeric material forms a seal with the pneumatic actuator 710. Thus, each port 312, as a result of being formed from an elastomeric material, is configured to provide a seal with a pneumatic interface (such as a pneumatic actuator). The corresponding port support 516 of the second part 500 is also shown schematic in FIGS. 23A and 23B.

[0287] To improve tolerance stack between cartridge 100 and the analytical device in which cartridge 100 is housed, pneumatic actuator 710 should actuate to a position slightly lower than the expected position of the pneumatic sealing surface, which means that pneumatic port 312 must be compressed to ensure a seal between pneumatic actuator 710 and pneumatic port 312.

[0288] 23A and 23B also show the frusto-conical (frusto-conical) shape of the protrusion 314. The frusto-conical shape of the protrusion 314 aids in the formation of a seal between the pneumatic port 312 and the pneumatic actuator 710. This is because the frusto-conical shape narrows the cross-section of the protrusion 314 as it increases in height above the first surface 308. Stated another way, the frusto-conical shape provides less material at the top of the protrusion 314 than at the base of the protrusion, thanks to the sloping walls provided by the frusto-conical shape. The reduced cross-section at the top of the protrusion 314 means that less material needs to be deformed by the pneumatic actuator 710 to provide a seal around the port 312. Less material to deform means that a lesser amount of force needs to be applied to compress the pneumatic port 312.

[0289] To further reduce the amount of force required to compress pneumatic port 312, opening 316 through port 312 may be provided with a diameter that increases as its height above second surface 310 increases. In other words, the diameter of opening 316 is smallest at second surface 310 and largest at the top of protrusion 314. This further reduces the amount of material above protrusion 314, resulting in less force being required to deform pneumatic port 312.

[0290] Annular rim 320 further reduces the amount of force required to compress pneumatic port 312 because annular rim 320 is defined by an area where the annular cross-section of the projection is smaller. As a result, annular rim 320 further reduces the amount of material on top of projection 314, which means that less force is required to deform projection 314.

[0291] The annular rim 320 has a shape defined by two characteristics: an interior angle between the inside of the annular rim 320 and a vertical line (or a line parallel to the centerline through the opening 316), and an exterior angle between the outside of the annular rim 320 and a vertical line (or a line parallel to the centerline through the opening 316). The cross section of the projection 314 also has a center of gravity. In the example shown in FIG. 23A, the interior angle of the annular rim 320 is greater than the exterior angle of the annular rim 320 (as shown diagrammatically by the dashed line in FIG. 23A). In addition, in the example shown in FIG. 23A, the distance between the center of gravity of the projection 314 and the centerline through the opening 316 is less than the distance between the top of the annular rim 320 and the centerline through the opening 316. In other words, the center of gravity of the projection 314 is closer to the center of the port 312 than the top of the annular rim 320.

[0292] These properties of the annular rim 320 and the protrusions 314 cause the annular rim 320 and the protrusions 314 to bend outward (i.e., away from the centerline through the opening 316) when a force is applied to the annular rim 320 by the pneumatic actuator 710 (as shown in FIG. 23B ). The outward bending of the annular rim 320 increases the contact area between the pneumatic port 312 and the pneumatic actuator 710, which improves the seal between the pneumatic actuator 710 and the pneumatic port 312.

[0293] 24A and 24B show alternative implementations of the pneumatic port 312. In the example shown in FIG. 24A and 24B, the inner angle of the annular rim 320 is smaller than the outer angle of the annular rim 320 (as shown diagrammatically in FIG. 24A by the dashed line). In addition, in the example shown in FIG. 24A, the center of gravity of the cross section of the protrusion 314 is located further away from the centerline through the opening 316 than in the example shown in FIG. 23A and 23B. In practice, this means that less material of the protrusion 314 is inside the boundary defined by the annular rim 320. By reducing the amount of material of the protrusion 314 within the boundary defined by the annular rim 320 and implementing a smaller inner angle, the protrusion 314 and the annular rim 320 bend inward when a force is applied to the annular rim 320 by the pneumatic actuator 710 (as shown in FIG. 24B).

[0294] The inward bending of the annular rim 320 increases the contact area between the pneumatic port 312 and the pneumatic actuator 710 (similar to the example shown in FIGS. 23A and 23B). However, the implementation shown in FIGS. 24A and 24B also reduces the diameter of the annular rim 320 when compressed by the pneumatic actuator 710. This means that even if there is some misalignment between the pneumatic actuator 710 and the pneumatic port 312 (as shown in FIG. 24B), the compressed annular rim 320 can fit within the footprint of the pneumatic actuator 710.

[0295] The effect of the inner and outer angles of the annular rim 320 on the compression of the pneumatic ports 312 is shown diagrammatically in Figure 25. These diagrams ignore the effects associated with the center of gravity of the protruding portion, and instead show the effect of changing the shape of the annular rim 320.

[0296] In the top view of Figure 25, the inner and outer angles of the annular rim 320 are equal. This means that there is equal volume of material on either side of a vertical line 322 (i.e., a line parallel to the direction of the applied force) that passes through the top of the annular rim 320. When a force is applied to the annular rim 320, the equal volume of material on either side of line 322 will cause the annular rim 320 to compress without bending inward or outward.

[0297] In the center view of Figure 25, the inner angle of the annular rim 320 is greater than the outer angle of the annular rim 320. This means that the volume of material inside the line 322 exceeds the volume of material outside the line 322. When a force is applied to the annular rim 320, the smaller volume of material outside the line 322 will cause the annular rim 320 to bend outward (e.g., as in Figure 23B).

[0298] In the bottom diagram of Figure 25, the inner angle of the annular rim 320 is smaller than the outer angle of the annular rim 320. This means that the volume of material outside the line 322 exceeds the volume of material inside the line 322. When a force is applied to the annular rim 320, the smaller volume of material inside the line 322 will cause the annular rim 320 to bend inward (e.g., as in Figure 24B).

[0299] Figures 26-30 show fluidic circuits that may be implemented using the above-described cartridge 100. In the circuits shown in Figures 26-30, rectangles represent chambers, wells, or liquid storage capsules, lines represent conduits or channels, valve regions are indicated using two adjacent triangles, and openings (e.g., ports, vents) in the fluidic circuit are represented by circles.

[0300] FIG. 26 is a first fluidic circuit showing the fluidic components used for the aspiration of a liquid sample from the metering chamber 232 into one of the chambers 332. FIG. 26 shows diagrammatically the first part 200, the second part 500, and the fluidic layer 300. The main fluidic components of the circuit are also shown in FIG. 26. For simplicity, the sealing layer 400 is not diagrammatically shown in FIG. 26. FIG. 26 shows diagrammatically which fluidic components belong to the fluidic layer 300, the first part 200, and the second part 500.

[0301] Negative pressure may be applied to second pneumatic port 312b to aspirate the liquid sample from metering chamber 232 into second chamber 332b in fluidic layer 300 (e.g., for dilution or mixing). The sample is aspirated through channels 304a, 304n, and 304m, which means that valve regions 302c and 302h are not depressed (i.e., not actuated).

[0302] The sample is drawn from the metering chamber 232 in the first portion 200 through the following series of fluidic components: the metering chamber 232, the hole 402 in the sealing layer, the metering chamber outlet channel 502 in the second portion 500, the first channel 304a in the fluidic layer 300 (i.e., the third valve region 302c is not depressed), the fourteenth channel 304n in the fluidic layer 300 (i.e., the eighth valve region 302h is not depressed), the thirteenth channel 304m in the fluidic layer 300, and the second chamber 332b in the fluidic layer 300.

[0303] To aspirate the sample in this manner, negative pressure is applied to the first chamber 332a via the following series of fluidic components: the second pneumatic port 312b, the second channel 518b in the second port support 516b, the second trough 514b in the second portion 500, the fifth channel 304e in the fluidic layer 300 (with the sixth valve area 302f not depressed), the first chamber 332a in the fluidic layer 300, the opening 334a between the first chamber 332a and the second chamber 332b, and the second chamber 332b.

[0304] It will be appreciated that in order for sample to travel downstream from metering chamber 232 to second chamber 332b, there must be a vent upstream of metering chamber 232. This is to prevent the formation of a vacuum as liquid travels downstream from metering chamber 232.

[0305] As mentioned above, the vent is a permanent vent 506 in the second portion 500 in the form of a hole in the second portion 500 (as shown in FIG. 12). Thus, the metering chamber 232 is vented through one of the following series of fluidic components: (i) the permanent vent 506, the vent channel 548, the third well 542, the first connector channel 544, the first plurality of grooves 536, the first well 504 (defining the sample waste chamber), the waste outlet 401 in the sealing layer 400, the sample compatibility control chamber 236, the connector channel 234 in the first portion 200, and the metering chamber 232; or (ii) the permanent vent 506, the vent channel 548, the third well 542, the second connector channel 560, the second plurality of grooves 556, the first well 504, the waste outlet 401, the sample compatibility control chamber 236, the connector channel 234, and the metering chamber 232.

[0306] To prevent contamination, it is important to prevent leakage of the liquid sample from the cartridge 100. Therefore, the liquid sample should be prevented from exiting through the permanent vent 506, even when the cartridge 100 is disturbed or shaken. To reduce the tendency of the liquid sample to exit through the permanent vent 506, a narrow vent channel 548 is used, as shown in FIG. 12. By using a narrow cross section for the vent channel 548, the hydraulic resistance of the vent channel 548 is increased and fluid flow therethrough is prevented.

[0307] A second narrow channel (i.e., first connector channel 544) is also implemented to further block sample flow through permanent vent 506. First connector channel 544 provides fluid communication between third well 542 (to which vent channel 548 connects) and second well 532. Thus, the liquid sample faces two narrow channels in series, each of which contributes to increasing the hydraulic resistance of the flow path to permanent vent 506.

[0308] To reduce the possibility of liquid clogging, multiple grooves 536 are provided between the first well 504 and the second well 532. With more than one path for liquid flow between the first well 504 and the second well 532, the possibility of liquid clogging between the first well 504 and the second well 532 is reduced. For example, if the probability of liquid clogging one of the grooves is 1 / x, then by providing two grooves, the probability of liquid clogging is 1 / x. 2 Furthermore, by providing three grooves, the probability is reduced to 1 / x 3 is reduced to

[0309] Each of the plurality of grooves 536 also includes a sloped base 538 that slopes towards the first well 504. This means that even if liquid does flow into one of the grooves 536, the pressure required to remove the liquid from the groove 536 is reduced because the sloped base 538 of the groove 536 forces the liquid to flow under gravity towards the first well 504.

[0310] The flow of liquid into the plurality of grooves 536 is also prevented as, in use, the base 538 of each groove 536 is located above the base of the first well 504. This means that liquid must flow over a step between the base of the first well 504 and the base of the groove 538. Similarly, the base of the first connector channel 544 is provided above the base of the second well 532 in use, which means that liquid must flow over a step between the second well 532 and the first connector channel 544. A similar step may be provided between the third well 542 and the vent channel 548.

[0311] To minimize the overall volume of the cartridge 100, the first well 504 may be relatively shallow (i.e., have a low depth), resulting in a small cross-sectional area of ​​the sample waste chamber. The low depth of the first well 504 may result in a plug of liquid in the sample waste chamber (i.e., a volume of liquid that fills the cross-sectional area of ​​the sample waste chamber). Such a plug of liquid in the sample waste chamber increases the pressure required to aspirate the liquid sample from the metering chamber 232.

[0312] An optional alternative flow path may be provided between the first well 504 and the permanent vent 506 to reduce the pressure required to aspirate the liquid sample from the metering chamber 232. The components of this optional alternative flow path are shown in dashed lines in Figure 26. Specifically, the optional alternative flow path comprises a second plurality of grooves 556, a fourth well 552, and a second connector channel 560 connecting the fourth well 552 to the third well 542.

[0313] Providing an alternative flow path means that there are two flow paths between the first well 504 and the permanent vent 506: (i) a first flow path through the first plurality of grooves 536, the second well 532, the first connector channel 544, the third well 542, and the vent channel 548, and (ii) a second flow path through the second plurality of grooves 556, the fourth well 552, the second connector channel 560, the third well 542, and the vent channel 548.

[0314] The second flow path provides an alternative flow path when a plug of liquid is present in the sample waste chamber defined by the first well 504 (i.e., between the waste outlet 401 and the first plurality of grooves 536) or when all of the first plurality of grooves 536 are blocked. Similarly, the first flow path also functions as an alternative flow path to the second flow path when a plug of liquid is present between the waste outlet 401 and the second plurality of grooves 556 or when the second plurality of grooves 556 are blocked.

[0315] To prevent the flow of liquid through the permanent vent 506, the second connector channel 560 has a narrow cross-section to increase its hydraulic resistance. As shown in FIG. 12, the second connector channel 560 is longer than the first connector channel 544, which further increases the hydraulic resistance of the second connector channel 560 relative to the first connector channel 544.

[0316] A second plurality of grooves 556 is provided to reduce the likelihood of liquid blockage in the second connector channel 560. Additionally, by providing more than one path for liquid flow between the first well 504 and the fourth well 552, the likelihood of liquid blockage between the first well 504 and the fourth well 552 is reduced. The angled base 558 of the groove 556 also reduces the pressure required to remove liquid from the groove 556 in the event of a blockage, as the angled base 558 facilitates liquid flow under gravity into the first well 504.

[0317] In use, the base 558 of the grooves 556 lies above the base 530 of the first well 504, which means that liquid must overcome a step between the base 530 of the first well 504 and the base 558 of each groove 556 which further blocks the flow of liquid into the grooves 556.

[0318] The fluid circuitry shown in Figures 27 and 28 shows a pump 716 connected to a pump manifold 714. A number of pneumatic supply conduits 712 are connected to the pump manifold 714. The pump 716, pump manifold 714, and pneumatic supply conduits 712 are all components of a pneumatic supply system contained in the analytical device in which the cartridge 100 is housed.

[0319] The pump manifold 714 includes a number of valves that control the application of pressure through the pneumatic supply conduits 712. Specifically, the valves in the manifold 714 allow positive or negative pressure to be applied to each of the pneumatic supply conduits 712, allow each of the pneumatic supply conduits 712 to be open to atmospheric pressure (i.e., vented), or allow each of the pneumatic supply conduits 712 to close (i.e., plug) the corresponding pneumatic port 312. Venting of the pneumatic supply conduits 712 may also be accomplished using vents in the pump manifold 714. The pneumatic supply system may include three pneumatic supply conduits 712 that correspond to the three pneumatic ports 312 of the cartridge 100.

[0320] 27 and 28 show diagrammatically which fluid components belong to the fluid layer 300 and which fluid components belong to the second portion 500. FIG.

[0321] The fluidic circuits shown in Figures 27 and 28 show how the movement of liquids in a fluidic network can be controlled using multiple pneumatic ports. The use of multiple pneumatic ports reduces the need for permanent vents in the cartridge 100 (apart from the permanent vent 506 used for sample aspiration). Thus, the likelihood of liquids leaking from the cartridge 100 is reduced. Specifically, the fluidic circuit may be vented through a waste chamber 508 in the second portion 500 (e.g., as shown in Figure 27) or through a mixing chamber in the fluidic layer 300 (e.g., as shown in Figure 28). In the example shown in Figures 27 and 28, a first one of the pneumatic ports 312 (i.e., first pneumatic port 312a) is in fluid communication with the conduit 600 (e.g., the conduit defined by the first channel 304a) and a second one of the pneumatic ports 312 (i.e., second pneumatic port 312b) is in fluid communication with a chamber (e.g., the measurement chamber 610, or one of the chambers 332 in the protrusion 330).

[0322] 27 is a fluid circuit that illustrates a schematic representation of the dispensing of liquid reagent from the liquid storage capsule 120 to the measurement chamber 610. To dispense liquid reagent into the measurement chamber 610, positive pressure is applied to the first pneumatic port 312a via the first pneumatic supply conduit 712a, and the second pneumatic port 312b is vented using the second pneumatic supply conduit 712b. The positive pressure is applied after the liquid storage capsule 120 is punctured (e.g., using the actuatable portion 240 of the first portion 200).

[0323] Applying positive pressure through the first air pressure port 312a applies positive pressure to the liquid in the liquid storage capsule 120 through the following series of fluid components: a channel 518a in the first port support 516a in the second portion 500, a first trough 514a in the second portion 500, and a second channel 304b in the fluidic layer 300.

[0324] The liquid storage capsule 120 is in fluid communication with the measurement chamber 610 via the following series of fluidic components: the ninth channel 304i in the fluidic layer 300 (with the fourth valve region 302d undepressed), and the first channel 304a in the fluidic layer 300. As mentioned above, the measurement chamber 610 may be defined in part by the opening 142 in the flow cell strip 140 accessed through a via 404 in the sealing layer 400, or may be defined in part by an opening 454 in the alternative sealing layer 450.

[0325] Positive pressure build-up in the fluid circuit is prevented by venting the measurement chamber 610 through the following series of fluid components: the 15th channel 304o in the fluidic layer 300 (with the 12th valve area 302l not depressed), the second waste chamber 508b in the second part 500, the lateral channel 512 in the second part 500, the longitudinal channel 522 in the second part 500, the second trough 514b in the second part, the channel 518b in the second pump support 516b in the second part 500, and the second air pressure port 312b.

[0326] 28 is a fluid circuit that illustrates a schematic representation of the dispensing of a liquid reagent from the liquid storage capsule 120 to a second chamber 332b (e.g., which may be used as a mixing chamber) in the fluidic layer 330. To dispense the liquid reagent into the second chamber 332b, positive pressure is applied to the first pneumatic port 312a via the first pneumatic supply conduit 712a, and the second pneumatic port 312b is vented using the second pneumatic supply conduit 712b. The positive pressure is applied after the liquid storage capsule 120 is punctured (e.g., using the actuatable portion 240 of the first portion 200).

[0327] Applying positive pressure through the first air pressure port 312a applies positive pressure to the liquid in the liquid storage capsule 120 through the following series of fluid components: a channel 518a in the first port support 516a in the second portion 500, a first trough 514a in the second portion 500, and a second channel 304b in the fluidic layer 300.

[0328] The liquid storage capsule 120 is in fluid communication with the second chamber 332b via the following series of fluid components: the ninth channel 304i in the fluid layer 300 (with the fourth valve region 302d not depressed), the first channel 304a in the fluid layer 300, and the thirteenth channel 304m and the fourteenth channel 304n in the fluid layer 300 (with the eighth valve region 302h not depressed).

[0329] Positive pressure build-up in the fluid circuit is prevented by venting the second chamber 332b through the following series of fluid components: opening 334a connecting the first chamber 332a to the second chamber 332b, the first chamber 332a, the fifth channel 304e in the fluidic layer (with the sixth valve area 302f not depressed), the second trough 514b in the second part 500, the channel 518b in the second pump support 516b of the second part 500, and the second air pressure port 312b.

[0330] 27 and 28 both show how multiple pneumatic ports 312 can be used to transfer liquid from the liquid storage capsule 120 to another component of the fluid network. It will be appreciated that the pneumatic ports 312 can be used to transfer liquid from the chamber 332 to other fluid components as well. For example, the port 312 may be used to transfer liquid from one of the chambers 332 to the measurement chamber 610 (e.g., after the liquid has moved from the liquid storage capsule 120 to the second chamber 332b as shown in FIG. 28). As another example, the port 312 may be used to transfer liquid back and forth between the second chamber 332b and the third chamber 332c. This is accomplished by applying positive (or negative) pressure through a first one of the ports 312 and venting another one of the ports 312.

[0331] Specifically, the fluidic layer 300 described above enables at least the fluidic operations described in the following paragraphs to be performed.

[0332] The liquid may be dispensed into a chamber such as waste chamber 508, measurement chamber 610, or mixing chamber 332. This may be achieved by providing positive pressure to a first one of the pneumatic ports 312 (e.g., first pneumatic port 312a or third pneumatic port 312c) while a second one of the pneumatic ports 312 (e.g., second pneumatic port 312b or third pneumatic port 312c) is vented.

[0333] For example, referring to FIG. 17B, the diluent may be dispensed from the liquid storage capsule 120 to the third chamber 332c (used as a mixing chamber in this example). Specifically, positive pressure is applied to the liquid storage capsule 120 located above the openings 350c and 350d by applying positive pressure through the first pneumatic port 312a. The positive pressure is applied through the second channel 304b. With the valve areas 302d, 302h, and 302k undepressed (and all other valve areas 302 are depressed), the diluent flows through the channels 304i, 304a, 304n, and 304m to the third chamber 332c. The third pneumatic port 312c is vented, which means that the third chamber 332c is vented through the openings 334b, the fourth chamber 332d, the seventh channel 304g, and the third pneumatic port 312c.

[0334] As another example, the solution may be dispensed from the third chamber 332c to the measurement chamber 610. Specifically, positive pressure is applied to the liquid in the third chamber 332c by applying positive pressure through the third pneumatic port 312c. The positive pressure is applied through the seventh channel 304g with the eleventh valve region 302k undepressed. With the valve regions 302i, 302j, and 302k undepressed (and all other valve regions 302 are depressed), the solution flows through the thirteenth channel 304m, the second chamber 332b, and the nineteenth channel 304s into the measurement chamber 610 connected to the seventeenth channel 304q and the nineteenth channel 304s. The second pneumatic port 312b is vented, meaning that this measurement chamber 610 is vented via the seventeenth channel 304q, the eighteenth channel 304r, the first waste chamber 508a, channels 512 and 522, and the second pneumatic port 312b. The continued positive pressure pushes solution from the measurement chamber 610 through channels 304q and 304r and into the first waste chamber 508a, which is vented by the second pneumatic port 312b.

[0335] Sample may be aspirated from metering chamber 232 into measurement chamber 610. Specifically, with valve regions 302c and 302l undepressed (and all other valve regions 302 depressed), negative pressure is applied to second pneumatic port 312b. Negative pressure is applied to the sample in metering chamber 232 through the following series of fluidic components: channels 512 and 522 in the second portion, second waste chamber 508b, fifteenth channel 304o, measurement chamber 610 connected to channels 304a and 304o, and first channel 304a. It will be recalled that first channel 304a is in fluid communication with the sample in metering chamber 232, which is in fluid communication with permanent vent 506. Thus, negative pressure applied via second pneumatic port 312b draws the sample into measurement chamber 610, which is in fluid communication with channels 304a and 304o.

[0336] A sample may also be aspirated into the third chamber 332c (e.g., to meter the sample as described in connection with Figures 17A and 17B). Specifically, with valve regions 302c, 302h, and 302k undepressed (and all other valve regions 302 are depressed), negative pressure is applied to the third pneumatic port 312c. Negative pressure is applied to the sample via the seventh channel 304g, the fourth chamber 332d, the opening 334b, the third chamber 332c, and channels 304m, 304n, and 304a. Thus, the negative pressure applied via the third pneumatic port 312c draws the sample from the metering chamber 232 (vented by the permanent vent 506) into the third chamber 332c.

[0337] Additionally, the solution may be mixed between chamber 332b (used as a mixing chamber in this example) and chamber 332c. This may be accomplished by aspirating the solution from the second chamber 332b into the third chamber 332c, and then dispensing the solution from the third chamber 332c into the second chamber 332b. These steps may then be repeated to further mix the solution.

[0338] To draw solution from the second chamber 332b to the third chamber 332c, the second pneumatic port 312b may be vented and negative pressure may be applied to the third pneumatic port 312c with valve areas 302f and 302k not depressed (and all other valve areas depressed). Negative pressure is applied to the solution in the second chamber 332b via the seventh channel 304g, the fourth chamber 332d, the opening 334b, the third chamber 332c, and the thirteenth channel 304m. The second chamber 332b is vented via the fifth channel 304e and the second pneumatic port 312b. To dispense solution from the third chamber 332c to the second chamber 332b, the second pneumatic port 312b may be vented and positive pressure may be applied to the third pneumatic port 312c with the same combination of valve regions 302 depressed.

[0339] Additionally, any solution in the measurement chamber 610 may be removed using air supplied through one of the pneumatic ports 312. Specifically, any solution in the measurement chamber 610 in fluid communication with channels 304q and 304s, and in the measurement chamber 610 in fluid communication with channels 304p and 304q may be removed by applying positive pressure through the first pneumatic port 312a with the second pneumatic port 312b vented. The flow cell is removed with valve regions 302b, 302i, and 302l undepressed (and all other valve regions depressed).

[0340] Specifically, the positive air pressure provides air flow through the fourth channel 304d, the nineteenth channel 304s, the measurement chamber 610 in fluid communication with channels 304s and 304q, the seventeenth channel 304q, the measurement chamber 610 in fluid communication with channels 304p and 304q, the sixteenth channel 304p, the second waste chamber 508b, channels 512 and 522, and the second air pressure port 312b, allowing the two measurement chambers 610 to be cleaned.

[0341] 29 is a flow chart of a method 900 for moving liquid within a liquid treatment device (e.g., cartridge 100) that includes a fluidic network that includes multiple conduits 600 and chambers (e.g., measurement chamber 610, chamber 332, waste chamber 508). The liquid treatment device includes multiple pneumatic ports 312 in fluid communication with the fluidic network.

[0342] Method 900 is applicable to various stages of various fluidic workflows that may be implemented using the fluidic layer 300 described above. Listed below are examples of liquid transfers that may be achieved using the fluidic layer 300 and method 900. It will be appreciated that the steps of the flowcharts described below may be performed in any order (not necessarily in the order described below) depending on the fluidic workflow being implemented.

[0343] At 910, the method may optionally include supplying negative air pressure to one of the plurality of air pressure ports 312 to aspirate liquid from the sample inlet chamber (e.g., metering chamber 232) into the fluidic network.

[0344] For example, negative pressure may be provided to the second pneumatic port 312b, which is in fluid communication with a measurement chamber 610 that is in fluid communication with channels 304a and 304o via channel 304o and fluidic components in the second portion 500 (with the twelfth valve region 302l undepressed). This measurement chamber 610 is in fluid communication with the sample inlet chamber via the first channel 304a with the third valve region 302c undepressed. The negative pressure provided to the second pneumatic port 312b draws liquid into the measurement chamber 610.

[0345] As another example, negative pressure may be supplied to the third pneumatic port 312c, which is in fluid communication with the third chamber 332c via the seventh channel 304g (with the eleventh valve region 302k undepressed). The third chamber 332c is in fluid communication with the sample inlet chamber via channels 304m, 304n, and 304a with the valve regions 302c and 302h undepressed. The negative pressure supplied to the third pneumatic port 312c draws liquid into the third chamber 332c.

[0346] At 920, a first pneumatic port of the plurality of pneumatic ports 312 is vented. The first pneumatic port of the plurality of pneumatic ports 312 is in fluid communication with the chamber.

[0347] At 930, positive pressure is provided to a second pneumatic port of the plurality of pneumatic ports 312 while venting a first pneumatic port of the plurality of pneumatic ports 312. The second pneumatic port of the plurality of pneumatic ports 312 is in fluid communication with a conduit 600, which is in fluid communication with the chamber. Provided with positive pressure to the second pneumatic port of the plurality of pneumatic ports while venting the first pneumatic port of the plurality of pneumatic ports 312 dispenses liquid from the conduit 600 into the chamber.

[0348] For example, the chamber may be the third chamber 332c, the third pneumatic port 312c may be in fluid communication with the third chamber 332c through the undepressed eleventh valve region 302k, and the third pneumatic port 312c may be vented. In this example, the first pneumatic port 312a may be in fluid communication with the conduit 600 defined by the ninth channel 304i through the undepressed fourth valve region 302d, and the ninth channel 304i may be in fluid communication with the third chamber 332c through the undepressed eighth valve region 302h, and a positive pressure may be applied to the first pneumatic port 312a. This causes liquid to be dispensed from the liquid storage capsule 120 into the third chamber 332c.

[0349] As another example, the chamber may be a measurement chamber 610 (i.e., in fluid communication with channels 304q and 304s), the second pneumatic port 312b may be in fluid communication with the measurement chamber 610 via the undepressed tenth valve region 302j and the fluidic components in the second portion 500 (waste chamber 508a, channels 512, 522), and the second pneumatic port 312b may be vented. In this example, the third pneumatic port 312c may be in fluid communication with the conduit 600 defined by the seventh channel 304g via the undepressed eleventh valve region 302k, the seventh channel 304g may be in fluid communication with the measurement chamber 610 via the undepressed ninth valve region 302i, and a positive pressure may be applied to the third pneumatic port 312c. This dispenses liquid from chambers 332b / 332c into measurement chamber 610, which is in fluid communication with channels 304q and 304s. In this example, the method may further include continuing to apply positive pressure to third pneumatic port 312c with second pneumatic port 312b vented to move liquid from measurement chamber 610 to waste chamber 508a.

[0350] As yet a further example, the chamber may be the second chamber 332b, the second pneumatic port 312b may be in fluid communication with the second chamber 332b through the undepressed sixth valve region 302f, and the second pneumatic port 312b may be vented. In this example, the third pneumatic port 312c may be in fluid communication with the conduit 600 defined by the thirteenth channel 304m through the undepressed eleventh valve region 302k, and positive pressure may be provided through the third pneumatic port 312c. This causes liquid to be dispensed from the third chamber 332c through the thirteenth channel 304m to the second chamber 332b. In this example, the second chamber 332b functions as a first mixing chamber, and the third chamber 332c functions as a second mixing chamber. Thus, positive pressure from the third pneumatic port 312c is applied to any liquid in the third chamber 332c, which means that liquid is dispensed from the third chamber 332c to the second chamber 332b. Since the second chamber 332b acts as a first mixing chamber and the third chamber 332c acts as a second mixing chamber, this means that liquid is dispensed from the first mixing chamber to the second mixing chamber.

[0351] At 940, if the chamber is the second chamber 332b used as a mixing chamber, the method may optionally further include, after dispensing liquid from the third chamber 332c to the second chamber 332b, providing negative pressure to a second pneumatic port of the plurality of pneumatic ports 312 while venting a first pneumatic port of the plurality of pneumatic ports 312 to aspirate liquid from the second chamber 332b to the third chamber 332c. Thus, at 940, liquid is aspirated from the first mixing chamber to the second mixing chamber.

[0352] For example, to draw liquid from the second chamber 332b to the third chamber 332c, the second pneumatic port 312b may be vented and negative pressure may be applied to the third pneumatic port 312c with the valve areas 302f and 302k not depressed.

[0353] At 950, the method may optionally further include supplying positive pressure to a third pneumatic port of the plurality of pneumatic ports 312 during venting of the first pneumatic port of the plurality of pneumatic ports 312. Subsequently, or instead, negative pressure may be supplied to the third pneumatic port of the plurality of pneumatic ports 312.

[0354] For example, 920 and 930 may involve using positive pressure from the third pneumatic port 312c with the second pneumatic port 312b vented to move liquid from one of the liquid storage capsules 120b. The liquid from the liquid storage capsule 120b may be moved to the measurement chamber 610 (e.g., via the eleventh channel 304k or the twelfth channel 304l (depending on the capsule 120b), the fourth channel 304d and the nineteenth channel 304s).

[0355] Then, at 950, the method may include clearing the measurement chamber 610 by supplying positive pressure to the first pneumatic port 312a with the second pneumatic port 312b vented, which supplies air to the measurement chamber 610 via the fourth channel 304d to clear the fluid circuit through the measurement chamber.

[0356] As another example, 920 and 930 may include clearing the measurement chamber 610 using positive pressure from the first pneumatic pressure port 312a with the second pneumatic pressure port 312b vented. Liquid from the measurement chamber 610 moves to the waste chamber 508.

[0357] Then, at 950, the method may include dispensing liquid from one of the liquid storage capsules 120b into the measurement chamber 610 by providing positive pressure to the third pneumatic port 312c with the second pneumatic port 312b vented. This pushes liquid from the liquid storage capsule 120b into the measurement chamber 610 (e.g., via the eleventh channel 304k or the twelfth channel 304l (depending on the capsule 120b), the fourth channel 304d, and the nineteenth channel 304s).

[0358] Those skilled in the art will appreciate that the method 900 described above is applicable to additional fluidic workflows beyond those described in the above examples that may be performed using the fluidic layer 300. Thus, the method 900 is not limited to the specific examples described in the above examples.

[0359] The described methods may be implemented using computer-executable instructions. A computer program product or computer-readable medium may include or store computer-executable instructions. A computer program product or computer-readable medium may include 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 medium in which information is stored for any period of time (e.g., long term, permanent, short term, for temporary buffering, and / or for caching information). A computer program may include computer-executable instructions. A computer-readable medium may be a tangible or non-transitory computer-readable medium. The term "computer-readable" encompasses "machine-readable."

[0360] The singular terms "a" and "an" should not be construed to mean "only one." Rather, unless otherwise specified, they should be construed to mean "at least one" or "one or more." The word "comprising" and its derivatives, including "comprises" and "comprise," includes each of the described features but does not exclude the inclusion of one or more additional features.

[0361] The term "channel" as used herein refers to a groove in a surface having an open cross-section (i.e., the cross-section is not sealed). The term "conduit" as used herein refers to (i) a channel that is sealed (e.g., by a sealing layer) thereby providing a closed cross-section, or (ii) a hole or tunnel that extends at least partially through a body.

[0362] 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 modifications of the described implementations can be made 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. a first rigid layer and a second rigid layer; a fluid layer disposed between the first rigid layer and the second rigid layer, the fluid layer is formed from an elastomer; the fluid layer comprising a network of channels; and a fluid network comprising a plurality of conduits, the plurality of conduits being defined at least in part by the network of channels in the fluid layer; and A liquid treatment device comprising:

2. The liquid treatment device of claim 1 , further comprising a plurality of valves, each of the plurality of valves configured to close a corresponding one of the plurality of conduits.

3. 3. The liquid treatment device of claim 2, wherein each of the plurality of valves comprises a deformable valve region disposed within the fluid layer, each deformable valve region being deformable to a deformed state in which the corresponding one of the plurality of conduits is blocked.

4. the fluid layer having a first surface configured to face the first rigid layer and a second surface configured to face the second rigid layer, at least a portion of the network of channels being disposed on the second surface; each deformable valve region comprising a recess in the first surface of the fluidic layer, the recess being aligned with a corresponding channel in at least a portion of the network of channels in the second surface; The liquid treatment device according to claim 3 .

5. 5. A liquid treatment device according to claim 4, wherein a subset of the network of channels is provided on the first surface.

6. 4. The liquid treatment device of claim 3, wherein the first rigid layer comprises a plurality of openings, each deformable valve region being accessible through one of the plurality of openings.

7. a plurality of openings extending through at least a portion of the thickness of the fluid layer, each of the plurality of openings in fluid communication with one of the plurality of conduits; the plurality of openings includes a first plurality of openings and a second plurality of openings, the second plurality of openings being different from the first plurality of openings; The liquid treatment device of claim 1 .

8. The air intake system further comprises a plurality of ports configured to provide a seal for a pneumatic interface, each of the plurality of ports comprising: a protrusion protruding from the surface of the fluid layer; a respective one of the first plurality of openings, the respective one of the first plurality of openings extending through the protrusion; The liquid treatment device of claim 7 comprising:

9. The liquid treatment device of claim 8 , wherein each projection has a frustoconical shape.

10. 9. A liquid treatment device according to claim 8, wherein each projection includes an annular rim around an open end of the projection, the annular rim defining an area of ​​minimum cross-sectional area of ​​the projection.

11. one or more of the plurality of ports: a plurality of support ribs, each of the plurality of support ribs extending between the protrusion and the surface of the fluid layer from which the protrusion projects; The liquid treatment device of claim 8 further comprising:

12. 9. The liquid treatment device of claim 8, wherein the first rigid layer comprises a plurality of openings, each port being accessible through one of the plurality of openings.

13. 9. The liquid treatment device of claim 8, wherein each of the plurality of ports is in fluid communication with one of the plurality of conduits through a corresponding trough in the second rigid layer.

14. 8. The liquid treatment device of claim 7, further comprising at least one liquid storage capsule disposed over two of the second plurality of openings.

15. The liquid treatment device of claim 1 , wherein the fluid layer comprises one or more chambers, each of the one or more chambers being in fluid communication with one of the plurality of conduits.

16. 16. The liquid treatment device of claim 15, wherein the fluid layer comprises a protrusion extending from a surface of the fluid layer, the protrusion comprising a plurality of cavities, and each of the one or more chambers is at least partially defined by a corresponding one of the plurality of cavities.

17. 10. The liquid treatment device of claim 1, further comprising a sealing film, wherein the plurality of conduits are defined by the network of channels in the fluid layer and the sealing film.

18. a first rigid layer and a second rigid layer; a fluid network comprising a plurality of conduits; a fluid layer disposed between the first rigid layer and the second rigid layer, the fluid layer formed from an elastomer, the fluid layer comprising a plurality of ports configured to provide a seal for a pneumatic interface, each of the plurality of ports comprising: a protrusion extending from a surface of the fluid layer; and the fluid layer comprising: an opening extending through the protrusion and at least a portion of the thickness of the fluid layer, the opening being in fluid communication with one or more of the plurality of conduits; and A liquid treatment device comprising:

19. 20. A liquid treatment device according to claim 18, wherein each protrusion has a frustoconical shape.

20. 20. A liquid treatment device according to claim 18, wherein each projection includes an annular rim around an open end of the projection, the annular rim defining an area of ​​minimum cross-sectional area of ​​the projection.

21. one or more of the plurality of ports: a plurality of support ribs, each of the plurality of support ribs extending between the protrusion and the surface of the fluid layer from which the protrusion projects; 20. The liquid treatment device of claim 18, further comprising:

22. 20. The liquid treatment device of claim 18, wherein the first rigid layer comprises a plurality of openings, each port being accessible through one of the plurality of openings.

23. 20. The liquid treatment device of claim 18, wherein each of the plurality of ports is in fluid communication with one of the plurality of conduits through a corresponding trough in the second rigid layer.

24. 20. The liquid treatment device of claim 18, wherein the second rigid layer comprises a plurality of supports, each of the plurality of supports aligned with a corresponding one of the plurality of ports such that when a force is applied to the corresponding one of the plurality of ports, each of the plurality of supports prevents deformation of the surface of the fluid layer.

25. 20. A liquid treatment device according to claim 18, wherein the fluid layer comprises a network of channels, and the plurality of conduits are defined at least in part by the network of channels in the fluid layer.

26. 10. The liquid treatment device of claim 1, wherein the fluid layer is formed from a thermoplastic elastomer, the thermoplastic elastomer optionally being a silicone-based thermoplastic elastomer or a styrene-ethylene-butylene-styrene.

27. 10. The liquid treatment device of claim 1, wherein the liquid treatment device is a diagnostic cartridge.

28. 28. The liquid treatment device of claim 27, wherein the diagnostic cartridge is a microfluidic cartridge.

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