Liquid processing equipment
The liquid processing apparatus addresses integration challenges in point-of-care diagnostic devices by using a fluid and rigid layer system with actuated projections for automated and precise fluid control, enhancing diagnostic test efficiency and reducing professional dependency.
Patent Information
- Authority / Receiving Office
- JP · JP
- Patent Type
- Applications
- Current Assignee / Owner
- OLSER DIAGNOSTICS LTD
- Filing Date
- 2024-06-26
- Publication Date
- 2026-07-07
Smart Images

Figure 2026522477000001_ABST
Abstract
Description
Technical Field
[0001] Field The present disclosure relates to a liquid processing apparatus, a liquid processing system, and a method for moving a liquid within a liquid processing apparatus.
Background Art
[0002] Background 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, it is necessary to transfer the biological sample to the diagnostic device. Thereafter, the diagnostic device controls the movement of fluids (such as biological samples, reagents, buffers, etc.) within the diagnostic device and is inserted into an analyzer (or instrument) that measures biomarkers to perform the diagnostic test.
[0003] Point-of-care detection enables diagnostic tests to be easily and immediately provided to patients, allowing for better and more rapid clinical decision-making. However, integrating diagnostic tests into point-of-care devices or systems is difficult. Sample preparation for immunoassays may require the mixing of multiple solutions and reagents with precise control of volume and mixing time. Furthermore, the device is ideally automated to eliminate the need for the presence of medical professionals.
Summary of the Invention
Problems to be Solved by the Invention
[0004] Therefore, there is a need for an improved liquid processing apparatus capable of performing liquid processing operations for use in point-of-care diagnostic tests.
Means for Solving the Problems
[0005] Summary This summary introduces concepts that will be explained in more detail in the detailed description. It should not be used to identify essential features of the claimed subject matter, nor should it be used to limit the scope of the claimed subject matter. Including multiple descriptions in the same paragraph of the summary does not imply any structural or functional relationship between such descriptions.
[0006] According to a first aspect of the present disclosure, a liquid apparatus is provided, the liquid apparatus comprising: a fluid layer comprising a plurality of channels and openings in the surface of the fluid layer, extending through at least a portion of the thickness of the fluid layer to one of the plurality of channels; a rigid layer comprising an actuated portion; and a liquid storage capsule positioned between the fluid layer and the actuated portion, the liquid storage capsule comprising a body defining a volume in which a liquid is stored, the body comprising a first deformable portion, a main liquid storage portion, and a limiting portion connecting the first deformable portion to the main liquid storage portion; and a sealing layer configured to seal the volume, the liquid storage capsule being positioned above the opening such that a portion of the sealing layer covers the opening, the actuated portion comprising a projection extending toward the liquid storage capsule, the actuated portion being actuated from a first position in which the projection does not deform the first deformable portion to a second position in which the projection deforms the first deformable portion and brings into contact with a portion of the sealing layer, causing the portion of the sealing layer to rupture, and when the actuated portion is in the second position, the projection does not deform the limiting portion.
[0007] The protruding part does not need to be able to pass through the opening. The liquid storage capsule may be positioned above the opening such that the first deformable portion and limiting portion are at least partially positioned above the opening. The opening may have an oval shape.
[0008] The first deformable portion may comprise a first region and a second region, and the first distance between the first region and the sealing layer is greater than the second distance between the second region and the sealing layer. The first region and the second region may be concentric such that the first region surrounds the second region.
[0009] The width of the opening may be smaller than the width of the protruding part. The projection may have an end that engages with the first deformable portion of the liquid storage capsule. The end of the projection may be flat. The end of the projection may have a cross-section having a main sector shape.
[0010] The protrusion may have a groove that defines the cross-section of the end of the protrusion. The groove may be aligned with the limiting portion of the liquid storage capsule. The groove may define the main sector shape of the cross-section of the end of the protrusion.
[0011] The cross-section of the end of the protruding portion may include one or more outwardly extending protruding ribs. The one or more outwardly extending protruding ribs may extend from the curved portion of the main sector shape.
[0012] The projection may be a first projection, and the actuariable portion may have a second projection extending toward the liquid storage capsule. The body of the liquid storage capsule may have a second deformable portion. The opening may be a first opening, and the fluid layer may have a second opening extending through at least a portion of the thickness of the fluid layer to one of a plurality of channels. The sealing layer portion may be a first portion of the sealing layer, and the liquid storage capsule may be positioned above the second opening such that the second portion of the sealing layer covers the second opening. In the first position, the second projection may not deform the second deformable portion. In the second position, the second projection may deform the second deformable portion to contact the second portion of the sealing layer and cause the second portion of the sealing layer to rupture.
[0013] The liquid storage capsule may be a first liquid storage capsule, and the liquid processing apparatus may include a second liquid storage capsule. The second liquid storage capsule may comprise a body that defines a volume in which liquid is stored, and comprising a body having a first deformable portion and a second deformable portion, and a sealing layer configured to seal the volume. The operable portion may comprise a third projection extending toward the first deformable portion of the second liquid storage capsule and a fourth projection extending toward the second deformable portion of the second liquid storage capsule. The fluid layer may comprise a third opening extending through at least a portion of the thickness of the fluid layer to one of a plurality of channels, and a fourth opening extending through at least a portion of the thickness of the fluid layer to one of a plurality of channels. The second liquid storage capsule may be positioned over the third and fourth openings such that a first portion of the sealing layer of the second liquid storage capsule covers the third opening and a second portion of the sealing layer of the second liquid storage capsule covers the fourth opening. In the first position, the third projection does not have to deform the first deformable portion of the body of the second liquid storage capsule, and the fourth projection does not have to deform the second deformable portion of the body of the second liquid storage capsule. In the second position, the third projection may deform the first deformable portion of the body of the second liquid storage capsule and come into contact with the first portion of the sealing layer of the second liquid storage capsule, causing the first portion of the sealing layer of the second liquid storage capsule to rupture. In the second position, the fourth projection may deform the second deformable portion of the body of the second liquid storage capsule and come into contact with the second portion of the sealing layer of the second liquid storage capsule, causing the second portion of the sealing layer of the second liquid storage capsule to rupture.
[0014] A second aspect of the present disclosure provides a liquid apparatus comprising: a fluid layer comprising a plurality of channels and an opening in the surface of the fluid layer, extending through at least a portion of the thickness of the fluid layer to one of the plurality of channels; a rigid layer comprising an actuated portion; and a liquid storage capsule positioned between the fluid layer and the actuated portion, the liquid storage capsule comprising a body defining a volume in which a liquid is stored and a sealing layer configured to seal the volume, the liquid storage capsule being positioned above the opening such that a portion of the sealing layer covers the opening, the actuated portion comprising a projection extending toward the liquid storage capsule, the actuated portion being actuated from a first position in which the projection does not deform the body to a second position in which the projection deforms the body and comes into contact with a portion of the sealing layer, causing the portion of the sealing layer to rupture, the projection cannot pass through the opening.
[0015] The opening may have an oval shape. The body of the liquid storage capsule may include a first deformable portion configured to be deformable by a projection when the operable portion is in a second position. The body may further include a main liquid storage portion and a limiting portion connecting the first deformable portion to the main liquid storage portion, and the liquid storage capsule is positioned over the opening such that the first deformable portion and the limiting portion are at least partially positioned over the opening.
[0016] The first deformable portion may comprise a first region and a second region, and the first distance between the first region and the sealing layer is greater than the second distance between the second region and the sealing layer. The first region and the second region are concentric such that the first region surrounds the second region.
[0017] The width of the opening may be smaller than the width of the protruding part. The projection may have an end that engages with the first deformable portion of the liquid storage capsule. The end of the projection may be flat. The end of the projection may have a cross-section having a main sector shape.
[0018] The protrusion may have a groove that defines the cross-section of the end of the protrusion. The groove may be aligned with the limiting portion of the liquid storage capsule. The groove may define the main sector shape of the cross-section of the end of the protrusion.
[0019] The cross-section of the end of the protruding portion may include one or more outwardly extending protruding ribs. The one or more outwardly extending protruding ribs may extend from the curved portion of the main sector shape.
[0020] The projection may be a first projection, and the operable portion may have a second projection extending toward the liquid storage capsule. The opening may be a first opening, and the fluid layer may have a second opening extending through at least a portion of the thickness of the fluid layer to one of a plurality of channels. The sealing layer portion may be a first portion of the sealing layer, and the liquid storage capsule may be positioned above the second opening such that the second portion of the sealing layer covers the second opening. In the first position, the second projection may not deform the body of the liquid storage capsule. In the second position, the second projection may deform the body and come into contact with the second portion of the sealing layer, causing the second portion of the sealing layer to rupture.
[0021] The liquid storage capsule may be a first liquid storage capsule, and the liquid processing apparatus may include a second liquid storage capsule, the second liquid storage capsule comprising a body defining a volume in which liquid is stored, and a sealing layer configured to seal the volume. The operable portion may include a third projection extending toward the second liquid storage capsule and a fourth projection extending toward the second liquid storage capsule. The fluid layer may include a third opening extending through at least a portion of the thickness of the fluid layer to one of a plurality of channels, and a fourth opening extending through at least a portion of the thickness of the fluid layer to one of a plurality of channels. The second liquid storage capsule may be positioned above the third and fourth openings such that a first portion of the sealing layer of the second liquid storage capsule covers the third opening and a second portion of the sealing layer of the second liquid storage capsule covers the fourth opening. In the first position, the third projection does not have to deform the body of the second liquid storage capsule, and the fourth projection does not have to deform the body of the second liquid storage capsule. In the second position, the third projection may deform the body of the second liquid storage capsule and come into contact with the first portion of the sealing layer of the second liquid storage capsule, causing the first portion of the sealing layer of the second liquid storage capsule to rupture. In the second position, the fourth projection may deform the body of the second liquid storage capsule and come into contact with the second portion of the sealing layer of the second liquid storage capsule, causing the second portion of the sealing layer of the second liquid storage capsule to rupture.
[0022] A third aspect of the present disclosure provides a liquid apparatus comprising a fluid layer having a chamber, the chamber comprising a fluid layer having an opening at the upper end of the chamber, and a sealing layer configured to seal the opening of the chamber, the chamber comprising one or more protrusions, each of which extends from the inner wall of the chamber, and when a reagent ball is contained in the chamber, the one or more protrusions prevent the reagent ball from coming into contact with the sealing layer.
[0023] The opening may be configured to allow the reagent ball to be inserted into the chamber.
[0024] One or more protrusions may be elastically deformable. The fluid layer is formed from a thermoplastic elastomer.
[0025] Each of the one or more protrusions may extend from the inner wall of the chamber at the upper end of the chamber. The opening may be partially defined by each of the one or more protrusions.
[0026] The fluid layer may include protrusions extending from the upper surface of the fluid layer, and the protrusions partially define the chamber.
[0027] The chamber may further include a fluid inlet disposed below the one or more protrusions and an air outlet disposed on the inner wall, and a first maximum distance between the air outlet and the upper end base is less than or equal to a second maximum distance between the one or more protrusions and the upper end.
[0028] Each of the one or more protrusions may include a first protruding portion extending from the inner wall of the chamber and a second protruding portion extending from the distal end of the first protruding portion, and the second protruding portion extends away from the upper end of the chamber.
[0029] A fourth aspect of the present disclosure provides a liquid processing apparatus comprising a first liquid storage container and a second liquid storage container, each of which is configured to be opened by creating an inlet and an outlet within the liquid storage container; and a fluid layer comprising a fluid layer comprising a network of channels and a pneumatic port configured to receive positive pressure, the network of channels comprising a first liquid storage container inlet channel configured to provide a fluid connection between the pneumatic port and an inlet within the first liquid storage container when the first liquid storage container is opened, and a second liquid storage container inlet channel configured to provide a fluid connection between the pneumatic port and an inlet within the second liquid storage container when the second liquid storage container is opened.
[0030] The liquid processing apparatus may further include a first liquid storage container valve configured to control the flow of liquid from the outlet of a first liquid storage container, and a second liquid storage container valve configured to control the flow of liquid from the outlet of a second liquid storage container.
[0031] The network of channels further comprises a first liquid storage container outlet channel configured to be in fluid communication with an outlet in the first liquid storage container when the first liquid storage container is opened, and a first liquid storage container valve located in the first liquid storage container outlet channel.
[0032] The channel network further comprises a second liquid storage container outlet channel configured to communicate fluidly with an outlet in the second liquid storage container when the second liquid storage container is opened, and a second liquid storage container valve located in the second liquid storage container outlet channel.
[0033] The liquid processing apparatus may further include wells, which are at least partially defined by openings extending through at least a portion of the thickness of the fluid layer, and the wells are in fluid communication with a pneumatic port, a first liquid storage container inlet channel, and a second liquid storage container inlet channel.
[0034] The opening, the first liquid storage container inlet channel, and the second liquid storage container inlet channel may be provided on the upper surface of the fluid layer, respectively. The depth of the opening may be greater than the depth of the first and second liquid storage container inlet channels.
[0035] The liquid processing apparatus may further comprise a lower section, the lower section having a trough on its upper surface. The fluid layer may be positioned above the lower section. The well may be at least partially defined by an opening in the fluid layer and a trough in the lower section.
[0036] The openings within the fluid layer may extend through the thickness of the fluid layer. The pneumatic ports may extend through the thickness of the fluid layer, and the pneumatic ports may communicate with the trough via connector channels in the lower part.
[0037] The well may be equipped with absorbent material. Each of the first liquid storage container inlet channel and the second liquid storage container inlet channel may include one or more first channel regions and a second channel region wherein the first depth of the one or more first channel regions is less than the second depth of the second channel region.
[0038] The second depth may be equal to the thickness of the fluid layer. The first width of one or more first channel regions may be less than the second width of the second channel region.
[0039] The liquid processing apparatus may further comprise a third liquid storage container, the third liquid storage container being configured to open by creating an inlet and an outlet within the liquid storage container, and the network of channels further comprises a third liquid storage container inlet channel configured to provide a fluid connection between a pneumatic port and an inlet within the third liquid storage container when the third liquid storage container is opened.
[0040] The pneumatic port may be a first pneumatic port. The liquid processing device may further include a second pneumatic port configured to communicate with an outlet in a first liquid storage container.
[0041] The second pneumatic port may be configured to communicate fluidly with an outlet in the second liquid storage container.
[0042] The liquid processing device may further include a third pneumatic port configured to communicate with an outlet in a second liquid storage container.
[0043] A fifth aspect of the present disclosure provides a method for controlling the flow of liquid in a liquid processing apparatus, the method comprising: creating an inlet and outlet in a first liquid storage container of the liquid processing apparatus to create a fluid connection between a pneumatic port of the liquid processing apparatus and an inlet in a first liquid storage container; creating an inlet and outlet in a second liquid storage container of the liquid processing apparatus to form a fluid connection between a pneumatic port and an inlet in a second liquid storage container; dispensing liquid from the outlet in the first liquid storage container by applying positive pressure through the pneumatic port; and dispensing liquid from the outlet in the second liquid storage container by applying positive pressure through the pneumatic port.
[0044] Dispensing liquid from the outlet in the first liquid storage container may include opening a first liquid storage container valve configured to control the flow of liquid from the outlet in the first liquid storage container.
[0045] Dispensing liquid from the outlet in the second liquid storage container may include opening a second liquid storage container valve configured to control the flow of liquid from the outlet in the second liquid storage container.
[0046] The method may further include creating an inlet and an outlet in the third liquid storage container of the liquid processing apparatus to create a fluid connection between the pneumatic port and the inlet in the third liquid storage container, and dispensing the liquid from the outlet in the third liquid storage container by applying positive pressure through the pneumatic port.
[0047] The pneumatic port may be a first pneumatic port. The liquid processing device may also have a second pneumatic port. Dispensing liquid from the outlet in the first liquid storage container may include opening one or more valves of the liquid processing device to create a fluid connection between the outlet in the first liquid storage container and the second pneumatic port, and venting the second pneumatic port while applying positive pressure through the first pneumatic port.
[0048] Dispensing liquid from the outlet in the second liquid storage container may include opening one or more valves of the liquid processing device to create a fluid connection between the outlet in the second liquid storage container and the second pneumatic port, and venting the second pneumatic port while applying positive pressure through the first pneumatic port.
[0049] The liquid processing apparatus may include a third pneumatic port. Dispensing liquid from the outlet in the second liquid storage container may include opening one or more valves of the liquid processing apparatus to create a fluid connection between the outlet in the second liquid storage container and the third pneumatic port, and venting the third pneumatic port while applying positive pressure through the first pneumatic port.
[0050] A sixth aspect of the present disclosure provides a liquid apparatus comprising: a first chamber fluid-communicating with a second chamber; a first pneumatic port fluid-communicating with either the first chamber or the second chamber; a second pneumatic port fluid-communicating with the other chamber; a chamber inlet conduit configured to allow liquid to flow into the first chamber; a chamber outlet conduit configured to allow liquid to flow out of the second chamber; and a third pneumatic port fluid-communicating with a first liquid reagent capsule, wherein when the first liquid reagent capsule is opened, the first liquid reagent capsule selectively fluid-communicates with either the first chamber or the second chamber.
[0051] As used herein, the term “selective fluid communication” between A and B means that A can be fluidly connected to B by opening one or more valves in order to provide a fluid connection between A and B through components of a fluid network.
[0052] The flow of liquid through the chamber inlet conduit may be controlled using a chamber inlet valve. The flow of liquid through the chamber outlet conduit may be controlled using a chamber outlet valve. The flow of liquid from the first liquid reagent capsule may be controlled using a first liquid reagent capsule valve.
[0053] The first pneumatic port may be permanently in fluid communication with the first chamber. The second pneumatic port may be permanently in fluid communication with the second chamber.
[0054] The liquid processing apparatus may further include a first flow cell that is in fluid communication with a second chamber via a chamber outlet conduit, a second flow cell that is in fluid communication with the first flow cell, and a bypass conduit configured to allow the liquid to bypass the second flow cell after flowing through the first flow cell. The flow of liquid through the bypass conduit may be controlled using a bypass conduit valve.
[0055] The first flow cell is in fluid communication with the waste chamber via the first flow cell outlet conduit. The flow of liquid to the waste chamber via the first flow cell outlet conduit may be controlled using a bypass conduit valve.
[0056] The waste chamber may be permanently ventilated. A second flow cell may be in fluid communication with the waste chamber via a second flow cell outlet conduit. The flow of liquid into the waste chamber via the second flow cell outlet conduit may be controlled using a second flow cell outlet valve.
[0057] A third pneumatic port may be in fluid communication with the second liquid reagent capsule. The flow of liquid from the second liquid reagent capsule may be controlled using a second liquid reagent capsule valve. When the second liquid reagent capsule is opened, it may be selectively in fluid communication with the second flow cell.
[0058] When the second liquid reagent capsule is opened, the second liquid reagent capsule may be in fluid communication with the second flow cell via the second flow cell outlet conduit.
[0059] A third pneumatic port may be in fluid communication with a third liquid reagent capsule. The flow of liquid from the third liquid reagent capsule may be controlled using a third liquid reagent capsule valve. When the third liquid reagent capsule is opened, it may be selectively in fluid communication with the first chamber. Additionally or alternatively, when the third liquid reagent capsule is opened, it may be selectively in fluid communication with the first flow cell.
[0060] The liquid processing apparatus may further include a sample inlet chamber that is in fluid communication with a chamber inlet conduit. The flow of liquid from the sample inlet chamber may be controlled using a sample inlet valve. The sample inlet chamber may be permanently ventilated.
[0061] The liquid processing apparatus may further include a sample flow cell that is in fluid communication with the sample inlet chamber via a sample flow cell inlet conduit. The flow of liquid into the sample flow cell may be controlled using a sample flow cell valve.
[0062] The sample flow cell may be fluidly connected to the sample flow cell waste chamber via a sample flow cell outlet conduit. The flow of liquid to the sample flow cell waste chamber may be controlled using a sample flow cell valve. The sample flow cell waste chamber may be fluidly connected to a second pneumatic port.
[0063] The liquid processing apparatus may further include a third chamber, the third chamber being in fluid communication with a first pneumatic port. The first pneumatic port may be permanently in fluid communication with the third chamber. The flow of liquid into the third chamber may be controlled using a third chamber valve. The third chamber may be in fluid communication with a first liquid reagent capsule. The third chamber may contain a dry reagent.
[0064] The first liquid reagent capsule may be fluidly connected to the first chamber via a priming conduit. The flow of liquid through the priming conduit may be controlled using a priming conduit valve. The priming conduit may be fluidly connected to the sample flow cell inlet conduit via a priming conduit valve.
[0065] A third pneumatic port may be in fluid communication with an air / cleaning fluid supply conduit. The airflow through the air / cleaning fluid supply conduit may be controlled using an air supply valve. The air / cleaning fluid supply conduit may be in fluid communication with a chamber outlet conduit.
[0066] One or more of the first and second chambers may contain dried reagents.
[0067] A seventh aspect of the present disclosure provides a method for metering a liquid in a channel of a liquid processing apparatus, the method comprising: applying a first pressure to move a first liquid out of a first chamber through a first fluid path including two joints; and applying a second pressure to move the fluid through a second fluid path including a portion of the first fluid path between the two joints such that the fluid displaces the volume of the first liquid between the two joints.
[0068] The first pressure may be applied using a first pneumatic port of the liquid processing device, which selectively communicates with the first chamber. The second pressure may be applied using a second pneumatic port of the liquid processing device, which selectively communicates with the second chamber.
[0069] A second pressure may be applied to dispense the fluid and the first liquid into the third chamber.
[0070] A first pressure may be applied to draw a first liquid from a first chamber through a first fluid path. The first chamber may be permanently ventilated. Alternatively, a first pressure may be applied to dispense a first liquid from a first chamber through a first fluid path.
[0071] The fluid may be a second liquid. A second pressure may be applied to dispense the second liquid from the second chamber through the second fluid path.
[0072] Alternatively, the fluid may be air. A second pressure may be applied to supply air to the second fluid path via an air supply conduit.
[0073] The method may further include measuring multiple volumes of a first liquid by repeating one or more times the following steps: applying a first pressure to move the first liquid from a first chamber through a first fluid path including two joints, and applying a second pressure to move the fluid through a second fluid path including a portion of the first fluid path between the two joints, such that the fluid displaces the volume of the first liquid between the two joints.
[0074] An eighth aspect of the present disclosure provides a method for priming a fluid circuit of a liquid processing apparatus, the method comprising: applying a first pressure to move a liquid from a chamber into a first channel; continuing to apply the first pressure to move the liquid until the liquid front of the liquid moves over a joint on the first channel, the joint connecting the first channel to a second channel; and applying a second pressure to move the liquid from the chamber through the first channel and the joint to the second channel.
[0075] Applying the first pressure may include applying negative pressure to move the liquid. The chamber may be permanently ventilated.
[0076] Applying a second pressure may include applying negative pressure to move the liquid.
[0077] Applying the first pressure may include applying negative pressure to the first pneumatic port of the liquid processing device. Applying the second pressure may include applying negative pressure to the second pneumatic port of the liquid processing device.
[0078] Applying the first pressure may include applying positive pressure to move the liquid. Applying the first pressure may include applying positive pressure to the first pneumatic port of the liquid processing apparatus while venting the second pneumatic port of the liquid processing apparatus.
[0079] Applying a second pressure may include applying positive pressure to move the liquid. Applying a second pressure may include applying positive pressure to the first pneumatic port of the liquid processing device. Applying a second pressure may include applying positive pressure to the first pneumatic port of the liquid processing device while venting the third pneumatic port of the liquid processing device.
[0080] A ninth aspect of the present disclosure provides a method for diluting a sample using a liquid apparatus, the method comprising: applying negative pressure to draw a certain volume of a first liquid into a first flow cell of the liquid apparatus; applying negative pressure to draw a certain volume of the first liquid into a first chamber of the liquid apparatus; applying positive pressure to dispense a certain volume of a second liquid into the first chamber; applying positive pressure to dispense the first and second liquids from the first chamber into a second chamber; and repeating the process of applying negative pressure to draw the first and second liquids from the second chamber into the first chamber one or more times; and applying positive pressure to move a mixture containing the first and second liquids from the first chamber or the second chamber into a second flow cell.
[0081] The method may further include measuring the detection signal in a first flow cell. The method may further include measuring the detection signal in a second flow cell.
[0082] The volume of the first liquid drawn into the first chamber may be the measured volume of the first liquid. The volume of the second liquid dispensed into the first chamber may be the measured volume of the second liquid.
[0083] A tenth aspect of the present disclosure provides a method for resuspending a dry reagent using a liquid processing apparatus, the method comprising: applying a first pressure to transfer a metered volume of a first liquid into a first chamber to resuspend one or more first dry reagents, wherein resuspending one or more first dry reagents forms the first reagents; applying a second pressure to transfer a metered volume of a first liquid into a second chamber to resuspend one or more second dry reagents, wherein resuspending one or more second dry reagents forms the second reagents; applying a third pressure to move the first reagents through at least one flow cell; applying a fourth pressure to move the second reagents through at least one flow cell; and measuring a detection signal in at least one flow cell.
[0084] The volume of the first liquid transferred into the first chamber may be the measured volume of the first liquid. The volume of the first liquid transferred into the second chamber may be the measured volume of the first liquid.
[0085] The advantages related to the features of the above embodiments are described in the following detailed description. Brief explanation of the drawing Specific embodiments are described below, by reference only to the accompanying drawings. [Brief explanation of the drawing]
[0086] [Figure 1] This is an isometric view of a liquid processing device. [Figure 2] Figure 1 is an isometric view of the liquid processing apparatus with the label removed. [Figure 3] Figure 1 is an exploded view showing the components of the liquid processing apparatus. [Figure 4] This is an exploded view of the components shown in Figure 3, assembled during the first assembly stage. [Figure 5] This is an exploded view of the components shown in Figure 3, assembled during the second assembly stage. [Figure 6] This is an exploded view of the components shown in Figure 3, assembled during the third assembly stage. [Figure 7] Figure 1 is a top view of the liquid processing apparatus with the label removed. [Figure 8] Figure 1 is a top view showing a liquid storage capsule attached to the fluid layer of the liquid processing apparatus shown in Figure 1. [Figure 9A] This is an exploded view showing the components of the liquid storage capsule shown in Figure 8, according to the first example. [Figure 9B] This is an exploded view showing the components of the liquid storage capsule shown in Figure 8, according to the second example. [Figure 10] Figure 1 is an isometric view of the first component of the liquid processing apparatus. [Figure 11] Figure 10 is a top view of the first component. [Figure 12] Figure 10 is a bottom view of the first component. [Figure 13] This is a cross-sectional view along line AA in Figure 12. [Figure 14] Figure 1 is a top view of the liquid processing apparatus shown. [Figure 15] Figure 14 is a cross-sectional view along the PP line. [Figure 16] Figure 14 is a cross-sectional view along the QQ line. [Figure 17] Figure 15 is an enlarged cross-sectional view of region R. [Figure 18] Figure 1 is a top view showing the liquid storage capsule and fluid layer of the liquid processing apparatus, with the liquid storage capsule and fluid layer shown as partially transparent. [Figure 19] Figure 10 is a top view showing the protruding part of the operable portion of the first component superimposed on Figure 18. [Figure 20] Figure 7 is a cross-sectional view along the HH line. [Figure 21] This is an enlarged cross-sectional view of region S shown in Figure 20. [Figure 22] This is a schematic diagram showing the protrusions, the deformable portion of the liquid storage capsule, and the opening within the fluid layer. [Figure 23]Figure 1 is an isometric view of the second component of the liquid processing apparatus. [Figure 24] Figure 23 is a top view of the second component. [Figure 25] Figure 3 is an exploded view of a specific component shown. [Figure 26] Figure 1 is a top view of the fluid layer of the liquid processing apparatus shown in Figure 1. [Figure 27] Figure 26 is a bottom view of the fluid layer. [Figure 28] These are schematic diagrams of the fluid network defined by channels within the fluid layer, as shown in Figures 26 and 27. [Figure 29] Figure 28 is a further schematic diagram of the fluid network. [Figure 30] Figure 26 is a side view of the fluid layer shown. [Figure 31] This is a cross-sectional view passing through the fluid layer shown in Figure 26. [Figure 32] This is a top view of the components shown in Figure 25 when assembled. [Figure 33] Figure 32 is a cross-sectional view along the ZZ line. [Figure 34] Figure 33 is an enlarged cross-sectional view of region T. [Figure 35] This is a flowchart showing how to control the flow of liquid within a liquid processing device. [Figure 36] This is a flowchart showing a method for measuring liquid in a channel of a liquid processing device. [Figure 37] This is a flowchart showing a method for priming the fluid circuit of a liquid processing device. [Figure 38] This is a flowchart showing a method for diluting a sample using a liquid processing device. [Figure 39] This is a flowchart showing a method for resuspending a dried reagent using a liquid processing device. [Figure 40-1] This is a flowchart of the method for performing the first assay using the liquid processing apparatus shown in Figure 1. [Figure 40-2] This is a flowchart of the method for performing the first assay using the liquid processing apparatus shown in Figure 1. [Figure 41] This is a flowchart showing how to perform the second assay using the liquid processing apparatus shown in Figure 1. [Figure 42] This is a flowchart of the method for performing the third assay using the liquid processing apparatus shown in Figure 1. [Figure 43-1] This is a flowchart showing the method for performing the fourth assay using the liquid processing apparatus shown in Figure 1. [Figure 43-2] This is a flowchart showing the method for performing the fourth assay using the liquid processing apparatus shown in Figure 1. [Modes for carrying out the invention]
[0087] Detailed explanation Embodiments of this disclosure are described below with particular reference to microfluidic cartridges used for performing diagnostic tests. However, it will be understood that the embodiments described herein are applicable to microfluidic cartridges used for other purposes. Where used herein, the term “microfluidic cartridge” is intended to refer to a device having conduits having a width or depth of less than 1 mm. It will be further understood that the embodiments described herein are not limited to microfluidics and are applicable to liquid processing devices of various sizes used for various purposes.
[0088] Figure 1 is an isometric view of a liquid processing device in the form of a diagnostic cartridge 100 (e.g., a microfluidic cartridge), and Figure 2 shows an isometric view of the cartridge 100 with the label 110 removed. The cartridge 100 comprises several components, as can be seen from the exploded view shown in Figure 3.
[0089] Specifically, the cartridge 100 comprises a first part 200 and a second part 500, each formed of a rigid material. When in use (i.e., when the cartridge 100 is in the orientation shown in Figure 1), the first part 200 is the top and the second part 500 is the bottom. Together, the first part 200 and the second part 500 define the housing of the cartridge 100. Specifically, the first part 200 comprises a rigid surface 250 defining the top surface of the cartridge 100. Similarly, the second part 500 comprises a rigid surface 570 (as shown, for example, in Figure 15) defining the bottom surface of the cartridge 100. Returning to Figure 3, it can be seen that the first part 200 further comprises a side wall 252 joined to the rigid surface 250, and the second part 500 further comprises a side wall 572 joined to the rigid surface 570. Together, the side wall 252 of the first part 200 and the side wall 572 of the second part 500 work together to define the side wall of the cartridge 100.
[0090] The cartridge 100 further comprises a fluid layer 300 disposed within a housing defined by a first component 200 and a second component 500. Specifically, the fluid layer 300 is disposed between the rigid surface 250 of the first component 200 and the rigid surface 570 of the second component 500. Thus, the fluid layer 300 is disposed between the first rigid layer in the form of the rigid surface 250 and the second rigid layer in the form of the rigid surface 570. The fluid layer 300 is formed of an elastomer material such as thermoplastic elastomer (TPE), for example, silicon-based TPE or styrene-ethylene-butylene-styrene (SEBS), polydimethylsiloxane (PDMS), or liquid silicone rubber (LSR).
[0091] As will be described in more detail below, the first surface 308 of the fluid layer 300 comprises a plurality of valve regions 302 (for example, shown in Figures 25 and 26). The cartridge 100 is received by an analyzer equipped with an actuator that applies force to the valve regions 302 of the fluid layer 300 to close one or more conduits 600 (best shown in Figures 16 and 21) within the cartridge 100. The properties of the material used for the fluid layer 300 depend on the available force that can be applied to the valve regions 302 of the fluid layer 300 by the actuator. Two important properties are the hardness of the material and the relaxation time of the material (i.e., the time it takes for the material to return to its original shape after deformation). Examples of suitable materials include the elastomer materials listed above. In some embodiments, the fluid layer 300 may be made of medical-grade material to prevent reaction between the fluid layer 300 and reagents used in diagnostic tests or assays.
[0092] As will be described in more detail below, the fluid layer 300 comprises a network of channels 304 (shown in Figures 26 and 27), some of which are located on the first surface 308 and others on the second surface 310 of the fluid layer 300 opposite the first surface 308. The cartridge 100 also comprises a fluid network comprising a plurality of conduits 600, which are at least partially defined by the network of channels 304 in the fluid layer 300. Specifically, the conduits 600 are defined by (i) the network of channels 304 in the fluid layer 300, (ii) a first sealing layer 400 (shown in Figure 3) configured to seal the channels 304 in the second surface 310 of the fluid layer 300, and (iii) a second sealing layer 410 configured to seal the channels 304 in the first surface 308 of the fluid layer.
[0093] Providing channels 304 in the elastomer fluid layer 300 provides improved 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 elastomer fluid layer 300 acts as an elastic layer when sealed to another layer (e.g., sealing layer 400). Furthermore, using an elastomer material for the fluid layer 300 means that the channels 304 can be compressed to close each conduit 600. This means that a single layer can be utilized to implement the channels 304 and valves (i.e., valve regions 302), thereby providing a simple cartridge structure.
[0094] Returning to the exploded view shown in Figure 3, the cartridge 100 comprises a label 110 arranged to cover at least a portion of the rigid surface 250 of the first component 200, a plurality of liquid storage capsules 120 disposed within the cartridge 100 between the fluid layer 300 and the first surface 250, sealing tapes 130a and 130b arranged to seal the chamber 332 in the fluid layer (the chamber 332 is best shown in Figure 25), and sealing tape 180 for attaching the liquid storage capsules 120 to the second sealing layer 410, and It can be seen that the sensor strip 150 comprises several sensors, each sensor being in fluid communication with a measuring chamber 610 defined by a corresponding opening 454 of a first sealing layer 400, and further comprises a plurality of absorbent waste pads 160, respectively, arranged to fit into corresponding waste chambers 508a, 508b or troughs 514a, 514b provided in a second component 500 (waste chambers 508 and trough 514 are best shown in Figure 24).
[0095] As shown in Figures 1 and 2, the first component 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 (RTM) blood collection tube manufactured by Becton, Dickinson and Company, Franklin Lakes, New Jersey, USA). The blood collection tube typically contains a headspace containing a certain volume of liquid (e.g., blood) and a certain volume of gas. The cylinder 202 may be as described in PCT / EP2022 / 087658, the whole of which is incorporated herein by reference, and the cartridge may further comprise an operable liquid extraction mechanism, the whole of which is incorporated herein by reference. Alternatively, the operable liquid extraction mechanism may be any of the operable liquid extraction mechanisms described in PCT / EP2022 / 071433, the whole of which is incorporated herein by reference.
[0096] Figure 3 also shows an arrangement of multiple liquid storage capsules 120 within the cartridge 100. In particular, the liquid storage capsules 120 are sealed to the fluid layer 300 using sealing tape 180. As shown in Figures 8 and 9, each liquid storage capsule 120 comprises an inlet chamber 122, a main chamber 124 (also referred to herein as the “liquid storage chamber”) for storing a liquid such as a liquid reagent, and an outlet chamber 126. A sealing layer 136 (e.g., sealing foil) is used to seal the chambers 122, 124, and 126 of each liquid storage capsule 120. The capsule 120 also includes a first restriction 123 between the inlet chamber 122 and the liquid storage chamber 124, and a second restriction 125 between the liquid storage chamber 124 and the outlet chamber 126. Each of the first and second restriction 123, 125 is provided in the form of a neck (or narrow region) between the liquid storage chamber 124 and the inlet / outlet chamber. The inlet chamber 122 is in fluid communication with the liquid storage chamber 124 via a first restriction 123. The outlet chamber 126 is in fluid communication with the liquid storage chamber 124 via a second restriction 125. The liquid storage capsule 120 may be as described in PCT / EP2022 / 058804, the entire contents thereof are incorporated herein by reference.
[0097] The liquid storage capsule 120 shown in Figure 3 comprises one large liquid storage capsule (i.e., the first liquid storage capsule 120a) and two smaller liquid storage capsules (i.e., the second liquid storage capsule 120b and the third liquid storage capsule 120c). Each of the smaller liquid storage capsules 120b and 120c is positioned perpendicular to the larger liquid storage capsule 120a such that the smaller liquid storage capsules 120b and 120c are parallel to each other.
[0098] As will be described in more detail below, each of the liquid storage capsules 120 is positioned above two openings 350 in the fluid layer 300. When force is applied to the inlet chamber 122 and outlet chamber 126 of the liquid storage capsule 120, the material of the liquid storage capsule 120 is deformed into each opening 350. When sufficient force is applied, the deformation of the liquid storage capsule 120 into the openings 350 causes the sealing layer (e.g., foil) used to seal the capsule 120 to rupture.
[0099] Figure 4 shows the first assembly stage of the cartridge 100. First, the absorbent waste pad 160 is placed in the waste chamber 508 and trough 514 provided in the second part 500. Next, the sensor strip 150 is positioned at one end of the second part 500. Then, the fluid layer assembly (comprising the fluid layer 300, the first sealing layer 400, and the second sealing layer 410) is positioned within the second part 500. Figure 5 shows the second assembly stage in which the liquid reagent capsule 120 and sealing tape 180 are attached to the fluid layer assembly so that the liquid reagent capsule 120 is positioned over the opening 350 of the fluid layer 300. Figure 6 shows the third assembly stage in which the first part 200 is coupled to the second part 500 to form the cartridge housing.
[0100] Figure 7 is a top view of the cartridge 100 with the label 110 removed. As shown in Figure 7, the first component 200 includes an actuated portion 240 (e.g., an actuated platform). The actuated portion 240 is positioned on the liquid storage capsule 120. The actuated portion 240 is actuated from a first position in which the actuated portion 240 does not deform the liquid storage capsule 120 to a second position in which the actuated portion 240 deforms the liquid storage capsule 120. The actuated portion 240 is actuated with respect to the rigid surface 250 of the first component 200 and is actuated in a direction perpendicular to the rigid surface 250 of the first component 200. The actuated portion 240 is rigid. As shown in Figure 7, the actuated portion 240 is U-shaped so that it can be deformed toward each of the liquid storage capsules 120. The U-shape of the movable portion 240 also allows the movable portion 240 to pass around the projection 330 (also shown in Figure 25) extending from the first surface 308 of the fluid layer 300 and the pneumatic port 312 within the fluid layer 300. As shown in Figure 8, the sealing tape 180 also includes a recess 182 that allows the chamber 332 and the pneumatic port 312 to protrude through the sealing tape 180.
[0101] Figure 9A shows the liquid storage capsule 120 in more detail. As shown in Figure 9A, each liquid storage capsule 120 includes a liquid storage chamber 124, an inlet chamber 122, an outlet chamber 126, and a capsule body 134 that defines the shape of the first and second limiting sections 123, 125. The capsule body 134 includes an opening through which the capsule 120 is filled, as is best shown in Figure 9B.
[0102] The capsule 120 further comprises a sealing layer 136 that seals the opening, as shown in Figure 9B. The sealing layer 136 is attached to a sealing tape 180. As shown in Figure 9A, the sealing tape 180 includes a first set of openings 184 having the same size and shape as the opening 350 in the fluid layer 300 on which the liquid storage capsule 120 is positioned. The size and shape of these openings 350 (and the corresponding first set of openings 184 in the sealing tape 180) will be described further below. Figure 9A also shows that the sealing tape 180 includes a second set of openings 186 that allow access to the valve region 302 defined by the fluid layer 300.
[0103] As best illustrated in Figure 17, the inlet chamber 122 and the outlet chamber 126 each provide a first region 127a, 127b and a second region 128a, 128b (also referred to herein as “recesses”) on the upper surface of the chambers 122, 126, respectively. For each chamber 122, 126, the first region 127 and the second region 128 are concentric such that the first region 127 surrounds the second region 128. The distance between the first region 127 and the sealing layer 136 is greater than the distance between the second region 128 and the sealing layer 136. In other words, the second region 128 provides a recess on the upper surface of the chambers 122, 126, which is surrounded by the first region 127 of the chambers 122, 126.
[0104] Figure 9B shows an alternative structure for a liquid storage capsule, in which a single component 134a defines the capsule body 134 of all three liquid storage capsules 120. In this alternative example, the openings within the liquid storage capsule 120 are sealed using a single sealing layer 136a. The single sealing layer 136a includes an opening 138 that allows access to the valve region 302 defined by the fluid layer 300.
[0105] Figure 10 is an isometric top view of the first part 200. As shown in Figure 10, the top surface (i.e., outer surface) of the movable part 240 is flat (or includes multiple flat areas). The flat surface of the movable part 240 allows the movable part 240 to be easily moved from a first position to a second position without requiring an actuator of a specific shape to move the movable part 240.
[0106] As shown in Figures 10 and 11, the first component 200 includes a plurality of elastically deformable members 246 (in the example shown in Figures 10 and 11, four elastically deformable members 246 are shown). Providing a plurality of elastically deformable members 246 allows the actuarial portion 240 to be actuated vertically, meaning that when the actuarial portion 240 is in the first position and when the actuarial portion 240 is in the second position, the actuarial portion 240 is parallel to the base (i.e., the sealing layer) of each liquid storage capsule 120. The vertical movement of the actuarial portion 240 allows substantially the same force to be applied to the recess 128 of a particular liquid storage capsule 120.
[0107] In particular, as shown in Figure 11, the first elastically deformable member 246 is connected to the first edge 256a of the operable portion 240, the second elastically deformable member 246 is connected to the second edge 256b of the operable portion 240 opposite to the first edge 256a, the third elastically deformable member 246 is also connected to the first edge 256a of the operable portion 240 but spaced apart from the connection point of the first elastically deformable member 246, and the fourth elastically deformable member 246 is similarly connected to the third edge 256c of the operable portion 240 opposite to the first edge 256a.
[0108] As shown in Figure 12, the lower surface of the operable portion 240 is provided with three pairs of projections 242 (shown in the cross-sectional view in Figure 13). Each pair of projections 242 extends toward the liquid storage capsule 120 and aligns with one of the inlet chambers 122 and outlet chamber 126 of the liquid storage capsule 120.
[0109] When the movable part 240 is moved to the second position, one of each pair of projections 242 deforms the inlet chamber 122, and the other projection deforms the outlet chamber 126. Specifically, when the movable part is moved from the first position to the second position, the deformation of the inlet chamber 122 and the outlet chamber 126 by the projections 242 brings the recess 128 (defined by the capsule body 134) into contact with the sealing layer 136. When the movable part 240 reaches the second position, the force applied to the sealing layer 136 by the recess 128 is high enough to cause the sealing layer 136 to rupture. The rupture of the sealing layer 136 provides an inlet (inside the sealing layer 136) to the inlet chamber 122 and an outlet (inside the sealing layer 136) from the outlet chamber 126. By providing an inlet and outlet within the liquid storage capsule 120, air can be supplied to the inlet (through the fluid layer 300) and the liquid can be pushed out through the outlet (into the fluid layer 300). In an alternative embodiment, the liquid storage capsule 120 does not have to include the recess 128, in which case the protrusion 242 may deform a portion of the inlet and outlet chambers 122, 126 of each liquid storage capsule 120 (for example, the flat or domed upper surface of the inlet and outlet chambers 122, 126) so that a portion of the capsule body 134 is in contact with the sealing layer 136.
[0110] There are three potential challenges when creating an opening in the liquid storage capsule 120 in this manner. First, there is a risk that displacement of recess 128a could block the opening in the fluid layer 300 through which air is intended to be supplied, or that displacement of recess 128b could block the opening in the fluid layer 300 through which liquid from the capsule 120 is intended to flow. Second, there is a risk that if excessive force is applied by an external actuator that operates the actuatable portion 240, one or more of the protrusions 242 could be pushed through both the capsule body 134 and the sealing layer 136. Third, there is a risk that the protrusions 242 could deform the restrictors 123, 125, obstructing the passage of air into the liquid storage chamber 124 or obstructing the passage of liquid from the liquid storage chamber 124. If these challenges are not addressed, precise actuator control will be required to ensure that the opening is not blocked and that the capsule body 134 does not rupture.
[0111] As will be explained in more detail below, the projection 242 is sized and shaped in such a way that it cannot enter the opening 350 of the fluid layer covered by the liquid storage capsule 120. This means that the downward displacement of the projection 242 is limited by the second sealing layer 410 and the first surface 308 of the fluid layer 300. This prevents the projection 242 from penetrating both the capsule body 134 and the sealing layer 136.
[0112] Separately, as will be described in more detail below, the opening 350 covered by the liquid storage capsule 120 is positioned at least partially above the opening 350 containing the inlet chamber 122 and limiter 123 of the liquid storage capsule 120, and at least partially above the outlet chamber 126 and limiter 125 of the other opening 350. As will be described below, the projection 242 deforms the inlet chamber 122 and outlet chamber 126, but not the limiters 123, 125. Thus, even if the recess 128 is pushed into the opening 350, a portion of the opening remains unobstructed because it is positioned below one of the limiters 123, 125. Partially positioning each limiter 123, 125 above one of the openings 350 also means that the fluid layer 300 provides a smaller reaction force when a force is applied to the top of the limiters 123, 125, reducing the likelihood of the limiters 123, 125 being crushed during the operation of the actuated portion 240.
[0113] Furthermore, the protrusion 242 and the liquid storage capsule 120 are sized and positioned relative to each other so that the protrusion 242 does not deform the restricting portions 123 and 125 when the operable portion 240 is in the second position. This reduces the risk of blockage inside the liquid storage capsule 120.
[0114] As shown in Figure 19, each of the projections 242 is provided with a groove 243 that defines the cross-section of the end of the projection 242. The groove 243 of each projection 242 is aligned with the corresponding limiting portions 123, 125 of the liquid storage capsule 120. Figure 19 shows that four of the projections 242 have end cross-sections with a main sector shape, while the other two projections 242 have end cross-sections with a trapezoidal shape, with grooves 243 on the longer, parallel edges of the trapezoid. Providing grooves 243 in the end cross-section of each projection 242 reduces the risk that the projections 242 will deform the limiting portions 123, 125 of the liquid storage capsule 120 when the inlet chamber 122 and outlet chamber 126 are deformed.
[0115] In the case of a projection 242 having an end cross section with a main fan shape, the end cross section also includes a plurality of outwardly extending projection ribs 245 extending from the curved portion of the main fan shape. The outwardly extending projection ribs 245 function to maximize the overall width of the projection 242 (therefore, the larger the area of the end of the projection 242, the greater the force required to deform the capsule body 134), while minimizing the overall cross-sectional area of the end of the projection 242 (therefore, the greater the force required to deform the capsule body 134). In the case of a projection 242 having a trapezoidal end cross section, the perimeter of the trapezoid prevents the projection 242 from entering the opening 350. In an alternative example, a trapezoidal projection 242 may also be provided with outwardly extending projection ribs 245.
[0116] Figure 13 is a cross-sectional view through the first part 200, showing the elastically deformable member 246 in more detail. As shown in Figure 13, the lower side of the actuarial portion 240 also includes concave regions 244. Specifically, the actuarial portion 240 includes three concave regions, which can be seen in Figures 16 and 17. Each concave region 244 is located between two protrusions 242. Each concave region 244 is configured to accommodate the main chamber 124 of its corresponding liquid storage capsule 120 when the actuarial portion 240 is in a second position. This means that when the actuarial portion 240 is in a second position, the main chamber 124 is not deformed by the actuarial portion 240.
[0117] Since the projection 242 extends from a single actuating portion 240, the actuation of the actuating portion 240 to a second position causes simultaneous deformation of each of the multiple capsules 120. As a result, all capsules 120 within the cartridge 100 can be opened using a single movement of the actuating portion 240.
[0118] Figure 13 also shows an elastically deformable member 246 that connects the actuariable portion 240 to the first part 200. The elastically deformable member 246 is configured to bias the actuariable portion 240 away from the second position (i.e., toward the first position). Thus, the elastically deformable member 246 forces the actuariable portion away from engagement with the inlet and outlet chambers 122, 126 of the liquid storage capsule 120.
[0119] Each elastically deformable member 246 has a curved (specifically, U-shaped) contour that allows the elastically deformable member 246 to undergo elastic deformation during movement of the actuarial portion 240 to a second position. The elastically deformable members 246 are formed from the same material as the actuarial portion 240 and the first part 200. In other words, the elastically deformable members 246 are integral with the first part 200 and the actuarial portion 240, each provided in the form of an elastic, integral hinge. This allows for the simplification of the manufacturing of the first part 200, including the actuarial portion 240 and the elastically deformable members 246 (e.g., by injection molding).
[0120] Figures 11 and 12 also show that the rigid surface 250 includes a plurality of openings 254. The plurality of openings 254 include an opening 254a aligned with the valve region 302 of the fluid layer 300, an opening 254b aligned with the first pneumatic port 312a of the fluid layer 300, and an opening 254c that provides openings for the second pneumatic port 312b and the third pneumatic port 312c of the fluid layer 300, along with a projection 330 extending from the first surface 308 of the fluid layer 300 (as shown, for example, in Figure 25). The ports 312 and projection 330 will be described with reference to Figure 30.
[0121] The opening 254a in the rigid surface 250 allows the valve region 302 of the fluid layer 300 to be accessed by an external valve actuator. Similarly, the openings 254b and 254c allow the pneumatic port 312 of the fluid layer 300 to be accessed by an external pneumatic actuator.
[0122] Figures 15 to 17 show the alignment of the projection 242 with the inlet and outlet chambers 122 and 126 of the liquid storage capsule 120 when the movable part 240 is in a first position. When a force is applied to the movable part 240 to move it toward its second position, it will be understood that the projection 242 engages with the inlet and outlet chambers 122 and 126, causing deformation of the inlet and outlet chambers 122 and 126 of the liquid storage capsule 120, bringing the recess 128 into contact with the sealing layer 136. Specifically, the portion of the sealing layer 136 below the inlet chamber 122 is deformed into a first of the openings 350, and the portion of the sealing layer 136 below the outlet chamber 126 is deformed into a second of the openings 350. The deformation of the inlet chamber 122 and outlet chamber 126 causes the material to rupture on the underside of the inlet chamber 122 and outlet chamber 126, which means that an opening is formed in each of the inlet chamber 122 and outlet chamber 126. The upper surface of the capsule 120 is formed of a plastically deformable material to allow deformation of the recess 128.
[0123] Figures 15 and 17 show one of the recessed regions 244 that house the main chamber 124 of the second liquid storage capsule 120b. Figures 15 and 17 also show that the second liquid storage capsule 120b and the opening 350 it covers are sized and positioned relative to each other such that the inlet chamber 122 and limiter 123 of the second liquid storage capsule 120b are partially positioned over one of the openings 350, and the outlet chamber 126 and limiter 125 are partially positioned over another of the openings 350. Figure 16 shows the recessed region 244 that house the main chamber 124 of the first liquid storage capsule 120a, which can also be seen in Figure 15. Figure 16 also shows that the first liquid storage capsule 120a and the opening 350 it covers are sized and positioned relative to each other such that the inlet chamber 122 and limiter 123 of the first liquid storage capsule 120a are partially positioned over one of the openings 350, and the outlet chamber 126 and limiter 125 are partially positioned over another of the openings 350.
[0124] Figure 18 shows a partially perforated view of the positioning of the liquid storage capsules 120 relative to the openings 350 of the fluid layer 300. As shown in Figure 18, the openings 350 and the liquid storage capsules 120 are sized and positioned relative to each other such that each opening 350 partially extends below one of the restrictors 123, 125 of the liquid storage capsule 120. In other words, for each liquid storage capsule 120, the openings 350 and the liquid storage capsules 120 are sized and positioned relative to each other such that the inlet chamber 122 and restrictor 123 of the liquid storage capsule 120 are partially positioned above the first opening 350 covered by the liquid storage capsule 120, and the outlet chamber 126 and restrictor 125 of each liquid storage capsule 120 are partially positioned above the second opening 350 covered by the liquid storage capsule 120. Figure 18 also shows that each opening 350 is oval-shaped. The oval shape minimizes the width of the opening 350 while allowing it to extend beneath the inlet or outlet chambers 122, 126 and adjacent restricting sections 123, 125. For comparison, a circular opening extending beneath the inlet or outlet chamber and adjacent restricting sections would be large enough to prevent the opening from being blocked by the capsule body 134 (specifically, the recess 128), but it might not prevent the projection 242 from puncturing both the capsule body 134 and the sealing layer 136 of the liquid storage capsule 120.
[0125] In Figure 19, the cross-section of the end of the projection 242 is superimposed on Figure 18. Figure 19 shows that the width of each opening 350 (i.e., the width of the oval) is smaller than the width of the corresponding projection 242 aligned with the opening 350. In other words, the footprint of each projection 242 extends outside the footprint of the corresponding opening 350 to which it is aligned. To put it another way, the periphery of each projection 242 extends outside the periphery of the corresponding opening 350 to which it is aligned. This means that, as shown in Figure 19, each projection 242 cannot pass through the corresponding opening 350 to which it is aligned. Figure 19 also shows the alignment of the groove 243 of each projection 242 with the limiting portions 123, 125 that partially cover the opening 350 to which the projection 242 is aligned. In other words, the groove 243 of each projection 242 is aligned with (i) the recess 128 of the inlet or outlet chamber 122, 126 in which the projection 242 is aligned, and (ii) the centerline passing through the limiting portions 123, 125 adjacent to the inlet or outlet chamber 122, 126 in which the projection 242 is aligned.
[0126] Figure 20 is a cross-sectional view through the respective inlet chambers 124 of the smaller liquid storage capsules 120b and 120c. As shown in the enlarged views in Figures 20 and 21, the width of each projection 242 is greater than the width of the corresponding opening 350 into which it is aligned, meaning that no portion of the projection 242 can pass through the corresponding opening 350 into which it is aligned. Figures 20 and 21 also show that the ends of each projection 242 are flat. Providing flat ends on each projection 242 means that no portion of the projection 242 can pass through the opening 350 into which it is aligned. The flat ends of the projections 242 also reduce the risk of puncturing the capsule body 134 when deforming the inlet and outlet chambers 122 and 126 of the liquid storage capsule 120.
[0127] Figure 22 schematically shows the projection 242, the inlet or outlet chambers 122, 126 of the liquid storage chamber 120, and the opening 350 from the same position as shown in Figures 20 and 21 (i.e., viewed through the width of the opening 350). Three distances are shown in Figure 22. The first distance, indicated as "C", is the clearance between the inlet or outlet chambers 122, 126 (specifically, the first region 127 of the inlet or outlet chambers 122, 126) and the end of the projection 242. The second distance, indicated as "D1", is the displacement of the capsule body 134 (specifically, the recess 128 of the inlet or outlet chambers 122, 126) after the projection has contacted the first region 127 of the inlet or outlet chambers 122, 126 and has not punctured the sealing layer 126. The third distance, indicated as "D2," is the displacement of the capsule body 134 (specifically, the recess 128 of the inlet or outlet chambers 122 and 126) during puncture of the sealing layer 126. From Figure 22, it can be seen that D2 is limited by the inability of the protrusion 242 to pass into the opening 350, thereby reducing the risk of the protrusion 242 puncturing the capsule body 134.
[0128] Distances C and D1 are implemented to prevent premature puncture of the liquid storage capsule 120 during manufacturing and processing. The width of the projection 242 is also greater than the width of the second portion 128 (or recess), thereby reducing the possibility of the projection 242 passing through the recess 128, and thereby reducing the possibility of the projection 242 puncturing both the capsule body 134 and the sealing layer 136.
[0129] Figure 23 shows an isometric view of the second part 500, and Figure 24 shows a top view of the second part 500. The second part 500 includes a sample waste chamber defined by a first well 504 on the top surface of the second part 500. The sample waste chamber receives excess sample during sample receiving in the cartridge 100. The sample waste chamber is in fluid communication with a permanent vent 506 provided in the second part 500 in the form of a hole. Thus, the sample inlet chamber 236 of the first part 200 (shown in Figure 12), which receives the sample, is permanently ventilated through the permanent vent 506.
[0130] The second component 500 further comprises two additional waste chambers (a first waste chamber 508a and a second waste chamber 508b), each of which is provided in the form of two recesses on the inner surface of the rigid surface 570. The first waste chamber 508 is in fluid communication with a first trough 514a on the inner surface of the rigid surface 570. The second waste chamber is in fluid communication with the first well 504 and is therefore permanently ventilated through the permanent vent 506.
[0131] The second component 500 further comprises a first trough 514a in the form of a circular recess on the inner surface of the rigid surface 570, a second trough 514b in the form of a circular recess on the inner surface of the rigid surface 570, and a third trough 514c in the form of a circular recess having integral fingers 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 fluid layer 300 and one or more channels 304 in the fluid layer 300, as will be described in more detail below. Specifically, as will be described with reference to Figure 26, some channels 304 are fluidly connected to the troughs 514 through holes in the sealing layer 400.
[0132] The second component 500 further comprises a first pneumatic port support area 516a adjacent to the first trough 514a, a second pneumatic port support area 516b adjacent to the second trough 514b, and a third pneumatic port support area 516c adjacent to the third trough 514c. Each of the pneumatic port support areas 516 is positioned below the corresponding pneumatic port 312 of the fluid layer 300 when the cartridge 100 is assembled.
[0133] The first pneumatic port support region 516a includes a connector channel 518a that connects the first pneumatic port 312a to the first trough 514a. Similarly, the second pneumatic port support region 516b includes a connector channel 518b that connects the second pneumatic port 312b to the second trough 514b. Furthermore, the third pneumatic port support region 516c includes a connector channel 518c that connects the third pneumatic port 312c to the third trough 514c. When the cartridge 100 is assembled, a fluid connection exists (through the sealing layer 400) between the opening 316 of each pneumatic port 312 and the corresponding connector channel 518 of the pneumatic port support region 516.
[0134] The port support region 516 is in contact with the underside of the sealing layer 400, which is used to seal the channel 304 within the second surface 310 of the fluid layer 300. This means that when a force is applied to the pneumatic port 312 of the fluid layer 300, the contact between the sealing layer 400 and the port support region 516 provides a reaction 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.
[0135] The trough 514 of the second component 500 prevents liquid from reaching the pneumatic port 312, which is connected to the pneumatic actuator of the analyzer. Thus, the trough 514 prevents liquid from reaching the analyzer, especially during liquid aspiration. Such liquid could contaminate or damage the analyzer. Air pressure is supplied through the connector channel 518 of the port support 516. The connector channel 518 is positioned above the base of the trough 514, which means that liquid drawn from the channel 304 of the fluid layer 300 accumulates at the bottom of the trough 514 and does not reach the connector channel 518. Thus, liquid drawn from the channel 304 in the fluid layer 300 is not drawn into the analyzer through the connector channel 518 and the pneumatic port 312.
[0136] Fluid communication between the first waste chamber 508a and the first trough 514a allows control of the ventilation state of the waste chamber 508 via the first pneumatic port 312a (i.e., by either venting or not venting the first pneumatic port 312a using the analyzer containing the cartridge 100).
[0137] The second component 500 also comprises a plurality of valve support regions 524 (shown as dashed circles in Figure 24). In the example shown in Figures 23 and 24, twelve valve support regions 524 are shown. Each of the valve support regions 524 is aligned with a corresponding valve region 302 in the fluid layer 300. Each of the valve support regions 524 is in contact with the underside of the sealing layer 400 used to seal the channel 304 in the second surface 310 of the fluid layer 300. This means that when a force is applied to the valve region 302 of the fluid layer 300 by the analyzer's actuator, the valve region 302 is compressed between the actuator and the corresponding valve support region 524. Thus, the waste chambers 508a, 508b do not extend below the valve region 302 of the fluid layer 300.
[0138] The second component 500 further comprises a plurality of capsule support regions 526 (also shown as dashed rectangles in Figure 24). In the example shown in Figures 23 and 27, six capsule support regions 526 are shown. Each of the capsule support regions 526 is aligned with a corresponding opening 350 in the fluid layer 300 that is aligned with an inlet chamber 122 or outlet chamber 126 of the plurality of capsules 120. Each of the capsule support regions 526 is in contact with the underside of the sealing layer 400 used to seal the channel 304 in the second surface 310 of the fluid layer 300. This means that when a force is applied to one of the inlet or outlet chambers 122, 126 of the plurality of capsules 120 by the corresponding projection 242 of the operable portion 240, the second surface 410 of the fluid layer 300 is prevented from being displaced downward by the corresponding capsule support region 526. Thus, the waste chambers 508a, 508b do not extend below the opening 350 in the fluid layer 300.
[0139] Figure 25 is an exploded view showing the fluid layer 300, the first sealing layer 400, and the second sealing layer 410. The first sealing layer 400 is arranged to seal the channels 304 in the second surface 310 of the fluid layer 300, and the second sealing layer 410 is arranged to seal the channels 304 in the first surface 308 of the fluid layer 300.
[0140] Figure 25 shows multiple valve regions 302 of the cartridge, each of which is provided in the form of a recess within the fluid layer 300. This means that the fluid layer 300 has a reduced thickness in each of the valve regions 302. By providing a thin region that aligns with the corresponding channel 304, the valve region 302 is deformed, and the force required to close the corresponding channel 304 is reduced.
[0141] Figure 25 also shows a projection 330 extending from the first surface 308 of the fluid layer 300. The projection 330 includes openings defining a plurality of chambers 332, as will be described in more detail with reference to Figures 25 and 26. Implementing the projection 330 extending from the first surface 308 of the fluid layer 300 means that the volume of the chambers 332 defined by the projection 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 plurality of openings 350 extending through the thickness of the fluid layer 300.
[0142] As shown in Figure 25, the fluid layer 300 further comprises a plurality of pneumatic ports 312 (for example, three pneumatic ports 312a, 312b, and 312c as shown in Figure 26). Each pneumatic port 312 comprises a projection 314 extending from the first surface 308.
[0143] Each port 312 further comprises a projection 314 and an opening 316 that extends through at least a portion of the thickness of the fluid layer. In the example shown in Figures 26 and 27, the opening 316 extends through the entire thickness of the fluid layer 300.
[0144] Accordingly, the fluid layer 300 is located directly beneath the liquid storage capsule 120 and comprises two sets of openings: a first set of multiple openings 350 aligned with the projections 242 on the operable portion 240, and a second set of multiple openings 316, each extending through the corresponding projections 314 of the pneumatic port 312. These sets of openings enable communication between the network of channels 304 within the fluid layer 300 and other fluid components of the cartridge 100 (e.g., the capsule 120 and the pneumatic port 312).
[0145] All components of the fluid layer 300 described above are integral to the fluid layer 300, meaning that they are all formed from the same elastomer material as the fluid layer 300. More specifically, the protrusions 330 and projections 314 are all integral to the fluid layer 300 and are formed from the same elastomer material as the fluid layer 300.
[0146] The first sealing layer 400 includes a plurality of openings 454, each of which partially defines the corresponding measuring chamber 610 of the cartridge 100 and is accessed through two channels 304 in the fluid layer 300, which provide an inlet and an outlet to the measuring chamber 610.
[0147] Figure 26 shows a top view of the fluid layer 300 showing the first surface 308. Figure 26 shows the locations of the valve region 302, the port 312, the projection 330 (including the chambers 332a-332c shown in Figure 27), and the opening 350. As described above, the openings 350 and 316 extend through the thickness of the fluid layer 300.
[0148] Each valve region 302 allows control of the fluid flow through one of the conduits 600 of the cartridge 100. Each valve is defined by one of the valve regions 302 (each positioned above the corresponding channel 304) and a sealing layer 400 that seals the corresponding channel 304. To close the valve, a force is applied to the valve region 302 to compress the corresponding channel 304 against the sealing layer 400. Closing the valve prevents the fluid flow through the corresponding conduit 600. To open the valve, the force applied to the valve region 302 to close the valve is canceled. Opening the valve allows the fluid flow through the corresponding conduit 600.
[0149] The fluid flow through the conduit 600 is controlled by applying a variable pressure to the pneumatic ports 312. As will be described in more detail below, each of the pneumatic ports 312 can be (i) receive positive pressure via the corresponding pneumatic actuator, (ii) receive negative pressure via the corresponding pneumatic actuator, (iii) be ventilated (i.e., open to atmospheric pressure) via the corresponding pneumatic actuator, or (iv) be closed (i.e., not ventilated), i.e., the pneumatic port 312 is disconnected from the pneumatic actuator. In case (iv), there is no airflow through the pneumatic port 312.
[0150] Several channels 304 within the fluid layer extend from a point in the fluid layer that covers one of the troughs 514 in the second component 500. This means, for example, that when positive air pressure is applied to the first pneumatic port 312a, the pressurized air flows through the corresponding opening 316 of the first pneumatic port 312a, through the corresponding hole in the sealing layer 400, through the channel 518a of the first port support region 516a, through the trough 514a, and into one of the channels 304. Negative pressure is applied similarly, but with the opposite airflow.
[0151] This arrangement reduces the risk of liquid being drawn into the pneumatic actuator (for example, while applying negative pressure to draw in liquid). This is because any liquid drawn in through channel 304 falls to the bottom of trough 514a under gravity. As shown in Figures 23 and 24, channel 518a is located on the flat upper surface of port support region 516a, which means that channel 518a is positioned above the base of trough 514a. Therefore, any liquid accumulated in trough 514a is not drawn into the pneumatic actuator through channel 518a via the first pneumatic port 312a.
[0152] As shown in Figures 25 and 26, two projections 330 extend from the first surface 308 of the fluid layer 300. The first projection 330a includes a hole that partially defines the first chamber 332a and the second chamber 332b. The second projection 330b includes a hole that partially defines the third chamber 332c. Specifically, the holes in the first and second projections 330 define the inner wall of the chamber 332 and thus define the height of the chamber 332. The holes defined by the projections 330 extend through the entire thickness of the fluid layer 300 in the region of the projections 330 (as shown, for example, in the bottom view of the fluid layer 300 shown in Figure 27). This means that the base of each chamber 332 is defined by a first sealing layer 400 (as shown, for example, in Figure 25), and the upper part of each chamber 332 is defined by a sealing tape 130 (specifically, the first sealing tape 130a seals the first chamber 332a and the second chamber 332b defined by a first projection 330a, and the second sealing tape 130b seals the third chamber 332c defined by a second projection 330b). Figures 26 and 27 also show that each chamber 332 includes a projection 338 extending from the inner wall 340 of the chamber 332 (see Figure 31), as will be described in more detail below with reference to Figures 31 to 34.
[0153] According to the examples described herein, a liquid processing apparatus (such as a microfluidic cartridge 100) comprises a first liquid storage container (e.g., a first of the liquid storage capsules 120) and a second liquid storage container (e.g., a second of the liquid storage capsules 120), each of which is configured to open by creating an inlet and an outlet within the liquid storage container, and a fluid layer (e.g., a fluid layer 300), the fluid layer comprising a network of channels (e.g., a channel 304) and pneumatic ports (e.g., pneumatic ports) configured to receive positive pressure. 312b) comprising a fluid layer comprising a network of channels including a first liquid storage container inlet channel (e.g., a first of the liquid storage capsule inlet channels 360, 362, 364 described below) configured to provide a fluid connection between a pneumatic port and an inlet in the first liquid storage container when the first liquid storage container is opened, and a second liquid storage container inlet channel (e.g., a second of the liquid storage capsule inlet channels 360, 362, 364 described below) configured to provide a fluid connection between a pneumatic port and an inlet in the second liquid storage container when the second liquid storage container is opened. Such an arrangement is not limited to a liquid processing apparatus including a liquid storage capsule 120 having a particular structure of those described herein (i.e., having chambers 122, 124, 126 and restrictors 123, 125), but may be implemented in any liquid storage container configured to be opened by creating an inlet and an outlet within the liquid storage container.
[0154] Figure 26 shows the channels 304 within the first surface 308 of the fluid layer 300. The channels 304 within the first surface of the fluid layer include a first liquid storage container inlet channel 360 (also referred herein as the first liquid storage capsule inlet channel 360), a second liquid storage container inlet channel 362 (also referred herein as the second liquid storage capsule inlet channel 362), and a third liquid storage container inlet channel 364 (also referred herein as the third liquid storage capsule inlet channel 364). The first liquid storage capsule inlet channel 360 provides a fluid connection between the inlet chamber 122a (see Figure 8) of the first liquid storage capsule 120a and the second pneumatic port 312b. The second liquid storage capsule inlet channel 362 provides a fluid connection between the inlet chamber 122b of the second liquid storage capsule 120b and the second pneumatic port 312b. The third liquid storage capsule inlet channel 364 provides a fluid connection between the inlet chamber 122c of the third liquid storage capsule 120c and the second pneumatic port 312b.
[0155] Cartridge 100 also includes a well 602, which is partially defined by an opening 324 in the fluid layer 300. In the example shown in Figure 26, the opening 324 extends through the entire thickness of the fluid layer 300 (as can be seen from the bottom view in Figure 27). In this example, the well 602 is defined by the opening 324 and a second trough 514b (also called a “cavity”) in the second part 500. Referring back to Figure 4, we can see that the second trough 514b contains one of the absorbent waste pads 160, which means that the well 602 is equipped with absorbent material. As described above, the second pneumatic port 312b is in fluid communication with the second trough 514b via a connector channel 518b in the second pneumatic port support area 516b, which means that the second pneumatic port 312b is in fluid communication with the well 602. Each of the liquid storage capsule inlet channels 360, 362, and 364 is connected to the opening 324, which means that each of the liquid storage capsule inlet channels 360, 362, and 364 is in fluid communication with the well 602. Thus, each of the liquid storage capsule inlet channels 360, 362, and 364 is in fluid communication with the second pneumatic port 312b via the well 602.
[0156] Each liquid storage capsule inlet channel 360, 362, 364 includes a plurality of regions in the form of one or more first channel regions 366a and one or more second channel regions 366b. Each first channel region 366a is provided on the first surface 308 of the fluid layer 300 and has a depth that is part of the thickness of the fluid layer 300. Each second channel region 366b is provided on the first surface 308 of the fluid layer 300 and has a depth greater than the depth of the first channel region 366a and a width greater than the width of the first channel region 366a. In the example shown in Figures 25 to 27, each liquid storage container inlet channel 360, 362, 364 includes two first channel regions 366a and two second channel regions 366b. Furthermore, in this example, the second channel region 366b has a depth equal to the thickness of the fluid layer 300 and is provided in the form of a circular hole extending through the fluid layer 300 (as can be seen from Figure 27). Thus, the second channel region 366b is sealed using the first sealing layer 400 and the second sealing layer 410.
[0157] While the liquid storage capsule 120 is open, some of the liquid from the liquid storage capsule 120 may flow towards the second pneumatic port 312b through the respective liquid storage capsule inlet channels 360, 362, and 364. Providing the first and second channel regions 366 of the liquid storage capsule inlet channels 360, 362, and 364 and the well 602 prevents the liquid from flowing into the second pneumatic port 312b and thus prevents the liquid from reaching the analyzer that applies pneumatic pressure through the second pneumatic port 312b. The depth of the second channel region 366b and the well 602 means that liquid accumulates in the second channel region 366b and the well 602, while the absorbent material in the well 602 absorbs the liquid in the well 602. The lower depth of the first channel region 366a compared to the second channel region 366b provides a barrier to the movement of liquid from the second channel region 366b to the first channel region 366a. Therefore, the arrangement of the liquid storage capsule inlet channels 360, 362, 364 and well 602 reduces the risk of liquid reaching the analyzer, which applies pressure through the second pneumatic port 312b.
[0158] The bottom view of the fluid layer 300 shown in Figure 27 shows the channel 304 within the second surface 310 of the fluid layer 300, which will be described in more detail with reference to Figure 28. Figure 27 also shows the opening 350 on which the liquid storage capsule 120 is positioned, the opening 316 for the pneumatic port 312, the second channel region 366b, and the opening 324 that partially defines the well 602, each as described above.
[0159] Figure 28 is a schematic diagram of the fluid network defined by channels 304 within the fluid layer 300. In Figure 28, channels 304 within the first surface 308 are shown by multiple lines (similar to Figure 26), and channels 304 within the second surface 310 are shown by a single line. Dotted lines indicate fluid connections (i.e., connector channels 518) through the second component 500. Figure 29 is a schematic diagram of the fluid network shown in Figure 28.
[0160] The fluid network includes a first pneumatic port 312a (P1), a second pneumatic port 312b (P2), and a third pneumatic port 312c (P3). The fluid network also includes a first chamber 332a (M1), a second chamber 332b (M2), and a third chamber 332c (M3). One or more of the first chamber 332a (M1), the second chamber 332b (M2), and the third chamber 332c (M3) may contain a dry reagent, for example, a lyophilized reagent provided in the form of a reagent ball.
[0161] Having a third chamber 332c that can be used to store reagents allows cartridge 100 to perform more complex assay methods (e.g., methods 1500 and 1800 described later) that require additional reagents not mixed with the sample in the first reaction. Furthermore, having a chamber 332 configured to store dry reagents is advantageous because (i) dry reagents are generally more stable for long-term storage, and (ii) different dry reagents can be stored in different chambers and resuspended in the same liquid buffer, thereby forming different liquid reagents during operation of cartridge 100.
[0162] One or more of the first chamber 332a (M1), the second chamber 332b (M2), and the third chamber 332c (M3) may be used as a mixing chamber for mixing a sample with a liquid (e.g., a reagent, a diluent), or as a mixing chamber for mixing a liquid used to resuspend a dry reagent with a dry reagent.
[0163] Furthermore, the fluid network includes the liquid reagent capsule inlet channels 360, 362, and 364 described above, in addition to the three measurement chambers 610 in the form of a first flow cell 610a (F1), a second flow cell 610b (F2), and a sample flow cell 610c (F3). Furthermore, the fluid network includes first and second waste chambers 508a and 508b. The ventilation state of the first waste chamber 508a is controlled using the first pneumatic port 312a, as described above. The first waste chamber 508a (also called the sample flow cell waste chamber) is accessed via the first waste chamber port 358a (W1) in the fluid layer 300, and the second waste chamber 508b (also called the flow cell waste chamber) is accessed via the second and third waste chamber ports 358b (W2) and 358c (W3) in the fluid layer 300. As described above, the second waste chamber 508b is permanently ventilated. Permanently ventilating the second waste chamber 508b frees up the pneumatic port 312 for other operations. In other words, fewer pneumatic ports 312 are required.
[0164] The sample inlet channel 367 provides a fluid connection to the permanently ventilated sample inlet chamber 236 (S1). The flow through the sample inlet channel 367 is controlled using the sample inlet valve region 302a (V2). The sample inlet channel 367 provides a fluid connection to the first joint 306a. As will be described later, two other channels are connected to the first joint 306a.
[0165] The chamber inlet channel 368 provides a fluid connection between the first joint 306a and the second chamber 332b(M2) (also referred to herein as the “mixing chamber”). The flow through the chamber inlet channel 368 is controlled using the chamber inlet valve 302b(V6). The second chamber 332b(M2) is in permanent fluid communication with the third pneumatic port 312c(P3), meaning there is no valve between the second chamber 332b(M2) and the third pneumatic port 312c(P3).
[0166] The sample flow channel 370 provides a fluid connection between the first joint 306a and the second joint 306b. Furthermore, the sample flow cell inlet channel 372 provides a fluid connection between the second joint 306b and the sample flow cell 610c(F3), and the sample flow cell outlet channel 374 provides a fluid connection between the sample flow cell 610c(F3) and the first waste chamber 508a. The flow through the sample flow cell inlet channel 372, the sample flow cell 610c(F3), and the sample flow cell outlet channel 374 is controlled using the sample flow cell valve 302c(V9).
[0167] Implementing a sample flow cell (F3) that can be filled with samples allows for additional measurements to be performed directly on the sample (without dilution). This makes it possible to measure additional biomarkers in the same cartridge (e.g., hematocrit).
[0168] The second chamber 332b(M2) and the first chamber 332a(M1) are fluidly connected using a mixing channel 376. Furthermore, a chamber outlet channel 378 provides a fluid connection between the first chamber 332a(M1) and the third joint 306c. The flow through the chamber outlet channel 378 is controlled using a chamber outlet valve 302d(V12). The first chamber 332a(M1) is permanently in fluid communication with the first pneumatic port 312a(P1), meaning there is no valve between the first chamber 332a(M1) and the first pneumatic port 312a(P1).
[0169] Having two chambers 332a, 332b (M1, M2) that are permanently in fluid communication with separate pneumatic ports 312a, 312c (P1, P3), respectively, allows for mixing by moving the liquid back and forth between the two chambers 332a, 332b (M1, M2). This can be achieved, for example, by venting one of the pneumatic ports 312a, 312c (P1, P3) that is permanently in fluid communication with one chamber 332a, 332b (M1, M2), and applying positive and negative pressure cycles through the other pneumatic port 312a, 312c (P1, P3) that is permanently in fluid communication with the other chamber 332a, 332b (M1, M2).
[0170] The first flow cell inlet channel 380 provides a fluid connection between the third joint 306c and the first flow cell 610a(F1). Thus, the first flow cell 610a(F1) is in fluid communication with the first chamber 332a(M1) via the chamber outlet channel 378 and the first flow cell inlet channel 380. Connecting the first flow cell 610a(F1) to the first chamber 332a(M1) in this way (i.e., by providing a direct connection between the first flow cell 610a(F1) and the first chamber 332a(M1)) makes it possible to minimize the length of the fluid path for moving the diluted sample into the first flow cell 610a(F1), thereby reducing the loss of analytes or reagents along the fluid path. In comparison, some existing liquid processing devices have coatings on the surface of the channel to avoid the loss of analytes or reagents due to adsorption to the surface of the channel walls. This method requires a complex manufacturing process and therefore increases the cost of such liquid processing equipment.
[0171] Furthermore, the first flow cell 610a(F1) is connected to the second flow cell 610b(F2) using a flow cell connection channel 382. The bypass channel 384 fluidly connects a fourth joint 306d on the flow cell connection channel 382 to the second waste chamber 508b via a third waste chamber port 358c(W3). The bypass channel 384 allows the liquid to bypass the second flow cell 610b(F2) after flowing through the first flow cell 610a(F1). The flow through the bypass channel 384 is controlled using a bypass valve 302e(V11). Thus, the bypass valve 302e(V11) controls the flow of liquid from the first flow cell 610a(F1) into the second waste chamber 508b.
[0172] The bypass channel 384 provides the option to select which liquids move through only the first flow cell 610a(F1) and which liquids move through both the first flow cell 610a(F1) and the second flow cell 610b(F2). Another advantage relates to the use of magnetic beads in assays performed using cartridge 100. The configuration of the bypass channel 384 allows the first flow cell 610a(F1) to be used as an off-sensor wash cell, and allows the beads to be transferred to the measurement flow cell (e.g., the second flow cell 610b(F2)) only after they have reacted with the detection solution.
[0173] The second flow cell outlet channel 386 fluidly connects the second flow cell 610b(F2) to the second waste chamber 508b via the second waste chamber port 358b(W2). The flow through the second flow cell outlet channel 386 is controlled using the second flow cell outlet valve 302f(V10). Thus, the flow circuit including the second flow cell 610b(F2) can be connected to a permanently ventilated waste chamber (i.e., the second waste chamber 508b) using the valve (i.e., the second flow cell outlet valve 302f(V10)) without requiring the use of the pneumatic port 312.
[0174] The second pneumatic port 312b (P2) is permanently in fluid communication with the first liquid storage capsule 120a (B1), the second liquid storage capsule 120b (B2), and the third liquid storage capsule 120c (B3), meaning there are no valves between the second pneumatic port 312b and each of the liquid storage capsules 120. The second pneumatic port 312b is permanently in fluid communication with the first liquid storage capsule 120a (B1), the second liquid storage capsule 120b (B2), and the third liquid storage capsule 120c (B3) via the first liquid storage capsule inlet channel 360, the second liquid storage capsule inlet channel 362, and the third liquid storage capsule inlet channel 364, respectively.
[0175] Controlling the liquid storage capsule 120 by the second pneumatic port 312b (P2) while the first and third pneumatic ports 312a, 312c (P1, P3) are in permanent fluid communication with the first and second chambers 332a, 332b (M1, M2), respectively, allows for the movement of liquid from the liquid storage capsule 120 to the first and / or second chambers 332a, 332b, while still allowing mixing between the two chambers 332a, 332b.
[0176] A permanent fluid connection between port 312 and the fluid network mechanism (chamber 332, liquid storage capsule 120) frees up valves used to control other functions (i.e., fewer valves are needed).
[0177] The first liquid storage capsule outlet channel 388 (also referred to herein as the first liquid storage container outlet channel) provides an outlet from the first liquid storage capsule 120a(B1). The flow through the first liquid storage capsule outlet channel 388 is controlled using the first liquid storage capsule valve 302g(V4) (also referred to herein as the first liquid storage container valve). Thus, the first liquid storage capsule 120a(B1) can be fluidly communicated with the first flow cell 610a(F1) via the first flow cell inlet channel 380 using the first liquid storage capsule valve 302g(V4).
[0178] The second liquid storage capsule 120b(B2) is in fluid communication with the fifth joint 306e on the second flow cell outlet channel 386 via the second liquid storage capsule outlet channel 390 (also referred herein as the second liquid storage container outlet channel). The flow through the second liquid storage capsule outlet channel 390 is controlled using the second liquid storage capsule valve 302h(V5) (also referred herein as the second liquid storage container valve). Thus, the second liquid storage capsule 120b(B2) can be in fluid communication with the second flow cell 610b via the second flow cell outlet channel 386 using the second liquid storage capsule valve 302h(V5).
[0179] A third liquid storage capsule outlet channel 392 (also referred to herein as the third liquid storage container outlet channel) provides an outlet from the third liquid storage capsule 120c(B3). The flow through the third liquid storage capsule outlet channel 392 is controlled using a third liquid storage capsule valve 302i(V7) (also referred to herein as the third liquid storage container valve).
[0180] The third liquid storage capsule outlet channel 392 and the first liquid storage capsule outlet channel 388 are in fluid communication with the third chamber inlet channel 394, which provides fluid connection to the third chamber 332c(M3). The flow through the third chamber inlet channel 394 is controlled using the third chamber inlet valve 302j(V8), and thus controls the flow into the third chamber 332c(M3). The third chamber 332c(M3) is in permanent fluid communication with the third pneumatic port 312c(P3), meaning there is no valve between the third pneumatic port 312c and the third chamber 332c(M3).
[0181] The third liquid storage capsule outlet channel 392 and the first liquid storage capsule outlet channel 388 are also in fluid communication with the priming channel 396, respectively. The priming channel 396 provides a fluid connection between the second joint 306b and the sixth joint 306f on the air / cleaning fluid supply channel 398. The flow through the priming channel 396 is controlled using the priming channel valve 302k(V1). This means that the third liquid storage capsule 120c(B3) and the first liquid storage capsule 120a(B1) can be in fluid communication with the second chamber 332b(M2) by opening the first or third liquid storage capsule valves 302g, 302i(V4, V7), the priming channel valve 302k(V1), and the chamber inlet valve 302b(V6). The air / cleaning fluid supply channel 398 provides a fluid connection between the second pneumatic port 312b and the third joint 306c. The airflow through the air / cleaning fluid supply channel 398 is controlled using the air supply valve 302l(V3), and the flow of liquid (e.g., cleaning fluid) through the air / cleaning fluid supply channel 398 is controlled using the first liquid storage capsule valve 302g(V4).
[0182] Having an air / cleaning fluid supply channel 398 connected to the fluid circuit allows any remaining liquid to be moved (swept) out of the channel between operations, thereby avoiding mixing or contamination between different liquids.
[0183] Each of the channels 304 within the fluid layer 300 described above is sealed using the first sealing layer 400 and / or the second sealing layer 410. Once sealed, a conduit is formed. For example, the sample inlet channel 367 is sealed by the first sealing layer 400 to form a sample inlet conduit. Thus, a reference to a “conduit” in the fluid network refers to a channel 304 in the fluid network that has been sealed using the first sealing layer 400 and / or the second sealing layer 410.
[0184] Figure 30 is a side view of the fluid layer 300, showing a projection 330 extending from the first surface 308 of the fluid layer 300. The projection 314 of the pneumatic port 312 can also be seen in the side view shown in Figure 30. Figure 31 is a cross-sectional view through the fluid layer 300, showing a cross-section through one of the chambers 332. As shown in Figure 31, the chamber 332 includes a plurality of projections 338 extending from the inner wall 340 of the chamber 332. When the chamber 332 is used to house reagent balls 344 (for example, as shown in Figures 33 and 34), the projections 338 prevent the reagent balls 344 from coming into contact with the sealing layer (i.e., sealing tape 130) that seals the chamber 332.
[0185] The projection 330 defining the chamber 332 extends from the first surface 308 of the fluid layer 300 and is therefore integral with the fluid layer 300. Similarly, the protrusion 338 extends from the inner wall 340 of the chamber 332 and is therefore integral with the projection 330. As a result, since the material of the fluid layer 300 is an elastomer (e.g., a thermoplastic elastomer), the protrusion 338 is elastically deformable. This allows the reagent ball 344 to be inserted into the chamber 332 through the protrusion 338 when a force is applied to the reagent ball 344. The reagent ball 344 can be inserted through the protrusion 338 before sealing the chamber 332 using, for example, a sealing tape 130.
[0186] Figure 32 is a top view of a fluid layer assembly comprising a fluid layer 300 to which a sealing layer 410 is attached, and Figure 33 is a cross-sectional view along the line ZZ passing through the fluid layer assembly shown in Figure 32. Figure 34 is an enlarged view of region T in Figure 33.
[0187] As shown in Figures 33 and 34, each chamber 332 includes an opening 342 at its upper end 343 (i.e., adjacent to the sealing tape 130 when the cartridge 100 is assembled). The opening 342 provides an entry point into a hole defined by the projection 330, meaning that the opening 342 allows the reagent ball 344 to be inserted into the chamber 332. The sealing tape 130 is configured to seal the opening 342 of the chamber 332. Handling dry reagents is difficult given the low humidity conditions (typically less than 10%) required to handle such reagents. The use of strictly controlled humidity limits the time workers can spend handling dry reagents, as excessive exposure to low humidity conditions is detrimental to human health. While reagent handling can be automated, strictly controlled humidity is still required, adding cost and complexity to the reagent handling process. The elastically deformable protrusion 338 allows the reagent ball 344 to be inserted into the chamber 332, and holding the reagent ball 344 in place during the application of the sealing tape 130 reduces the time required to process the reagent ball 344. As a result, these features also reduce human exposure to low humidity conditions and lower the cost and complexity of the manufacturing process.
[0188] Each of the projections 338 extends from the inner wall 340 at the upper end 343 of the chamber 332. In other words, each of the projections 338 extends from the inner wall 340 adjacent to the opening 342. As shown in Figures 32 to 34, the projections 338 define the perimeter of the opening 342, so the opening 342 is effectively defined by the projections 338. This allows the sealing tape 130 to contact the projections 338 when attached to the projections 330, thereby sealing the chamber 332.
[0189] Each of the projections 338 comprises a first projection 339a extending from the inner wall 340 of the chamber 332 and a second projection 339b extending from the distal end of the first projection 339a. The second projection 339b extends away from the upper end 343 of the chamber 332, thereby giving the projection 338 a "claw" shape. The use of the second projection 339b minimizes the amount of material that comes into contact with the reagent ball 344. This means that the reagent ball 344 can be resuspended without wetting the projection 338 (since it is necessary to wet about half to two-thirds of the reagent ball 344 in order to resuspend the reagent).
[0190] The inner wall 340 of each chamber 332 also includes at least one liquid flow orifice 346 that allows liquid to flow in and out of the chamber 332. For the first chamber 332a, one liquid flow orifice 346 allows liquid to flow from the first chamber 332a into the chamber outlet channel 378 and from the chamber outlet channel 378 into the first chamber 332a, and another liquid flow orifice 346 allows liquid to flow from the first chamber 332a into the mixing channel 376 and from the mixing channel 376 into the first chamber 332a. For the second chamber 332b, one liquid flow orifice 346 allows liquid to flow from the second chamber 332b into the chamber inlet channel 368 and from the chamber inlet channel 368 into the second chamber 332b, and another liquid flow orifice 346 allows liquid to flow from the second chamber 332b into the mixing channel 376 and from the mixing channel 376 into the second chamber 332b. For the third chamber 332c, the liquid flow orifice 346 allows liquid to flow from the third chamber 332c into the third chamber inlet channel 394 and from the third chamber inlet channel 394 into the third chamber 332c.
[0191] Figures 33 and 34 show one liquid flow orifice 346 in each of the first chamber 332a and the second chamber 332b, in the form of a liquid flow orifice 346 that allows liquid to flow from chambers 332a and 332b into the mixing channel 376 and from the mixing channel 376 into chambers 332a and 332b. Since each of the channels 304 connected to chamber 332 is coplanar, all liquid flow orifices 346 are provided at the same height (relative to the height of chamber 332) as shown in Figures 33 and 34. As shown in Figures 33 and 34, each liquid flow orifice 346 is positioned below the projection 338 such that the distance between the upper end 343 and the liquid flow orifice 346 is greater than the distance between the upper end 343 and the distal end of the second projection 339b.
[0192] Each chamber 332 also includes an air orifice 348, which is also located in the inner wall 340. The air orifice 348 provides a fluid connection to a pneumatic connection conduit 349 that extends perpendicularly between the air orifice 348 and the second surface 310 of the fluid layer 300 (as shown in Figures 26-28), and provides a fluid connection to a pneumatic port 312 to which the chamber 332 is connected (i.e., via the corresponding trough 514 of the second component 500). As shown in Figures 33 and 34, the first maximum distance between the air orifice 348 and the upper end 343 of the chamber 332 (measured perpendicular to the first surface 308) is less than or equal to the second maximum distance between the projection 338 (specifically, the second projection 339b) and the upper end 343 (measured perpendicular to the first surface 308). In other words, the projection 338 extends away from the upper end 343 such that the distal end of the second projection 339b is positioned below the height of the air orifice 348. As a result, the liquid does not flow into the air orifice 348 during the resuspension of the reagent ball 344.
[0193] Figure 35 is a flowchart of method 1000 for controlling the flow of liquid in a liquid processing apparatus (e.g., the microfluidic cartridge 100 described above). In 1002, an inlet and outlet are created in the first liquid storage container (e.g., liquid storage capsule 120) of the liquid processing apparatus to create a fluid connection between the pneumatic port (e.g., 312b) of the liquid processing apparatus and the inlet in the first liquid storage container.
[0194] In 1004, an inlet and outlet are created in the second liquid storage container (e.g., liquid storage capsule 120) of the liquid processing device in order to create a fluid connection between the pneumatic port 312b of the liquid processing device and the inlet in the second liquid storage container.
[0195] Optionally, in 1006, an inlet and outlet are created in the third liquid storage container (e.g., liquid storage capsule 120) of the liquid processing apparatus to create a fluid connection between the pneumatic port 312b of the liquid processing apparatus and the inlet in the third liquid storage container.
[0196] In 1008, liquid is dispensed from the outlet in the first liquid storage container by applying positive pressure through the pneumatic port 312b. Dispensing liquid from the outlet in the first liquid storage container may include opening a valve in the first liquid storage container configured to control the flow of liquid from the outlet in the first liquid storage container. Dispensing liquid from the outlet in the first liquid storage container may also include opening one or more valves of the liquid processing device to create a fluid connection between the outlet in the first liquid storage container and a second pneumatic port (e.g., 312a) of the liquid processing device, and venting the second pneumatic port while applying positive pressure through the (first) pneumatic port 312b.
[0197] In 1010, liquid is dispensed from the outlet in the second liquid storage container by applying positive pressure through the pneumatic port 312b. Dispensing liquid from the outlet in the second liquid storage container may include opening a second liquid storage container valve configured to control the flow of liquid from the outlet in the second liquid storage container. Dispensing liquid from the outlet in the second liquid storage container may include opening one or more valves of the liquid processing device to create a fluid connection between the outlet in the second liquid storage container and a second pneumatic port (e.g., 312a) of the liquid processing device, and venting the second pneumatic port while applying positive pressure through the (first) pneumatic port 312b.
[0198] Optionally, in 1012 (if 1006 is performed), liquid may be dispensed from the outlet in the third liquid storage container by applying positive pressure through the pneumatic port 312b. Dispensing liquid from the outlet in the third liquid storage container may include opening a third liquid storage container valve configured to control the flow of liquid from the outlet in the third liquid storage container. Dispensing liquid from the outlet in the third liquid storage container may include opening one or more valves of the liquid processing device to create a fluid connection between the outlet in the third liquid storage container and a third pneumatic port (e.g., 312c) of the liquid processing device, and venting the third pneumatic port while applying positive pressure through the (first) pneumatic port 312b.
[0199] Figure 36 is a flowchart of method 1100 for metering a liquid in a channel. In 1102, a first pressure is applied to move a first liquid from a first chamber through a first fluid path including two joints. The first pressure may be applied (i.e., using negative pressure) to draw the first liquid from a chamber (e.g., an aerated sample chamber) through the first fluid path. Alternatively, the first pressure may be applied (i.e., using positive pressure) to dispense the first liquid from a chamber such as a liquid reagent capsule.
[0200] In 1104, a second pressure is applied to move the fluid through a second fluid path, which includes a portion of the first fluid path between the two joints, such that the fluid displaces the volume of the first liquid between the two joints. The fluid may be a second liquid that can be dispensed from a second chamber (such as a liquid reagent capsule). Alternatively, the fluid may be air, which may be supplied via an air supply conduit communicating with the fluid through a pneumatic port.
[0201] The fluid may displace the volume of the first liquid by moving the volume of the first liquid into the chamber. Displacing the volume of the first liquid using the second fluid means that a precisely measured volume of liquid can be moved into the chamber. This precise volume is the volume of liquid between two junctions of the fluid network shown in Figure 28 (e.g., junctions 306a and 306b). Steps 1102 and 1104 may be repeated to measure a specific volume of the first liquid that is a multiple of the volume of the first fluid path between the two junctions. For example, if the volume of the first fluid path between the two junctions is 5 μL, steps 1102 and 1104 may be performed to move a volume of 20 μL of the first liquid into the chamber.
[0202] Figure 37 is a flowchart of method 1200 for priming a fluid circuit. At 1202, a first pressure is applied to move the liquid from the chamber to the first channel. At 1204, the first pressure continues to be applied to move the liquid until it fills the first channel by passing over a joint on the first channel, and the joint connects the first channel to the second channel. At 1206, a second pressure is applied to move the liquid from the chamber to the second channel through the first channel and the joint.
[0203] Figure 38 is a flowchart of method 1300 for diluting a sample. At 1302, negative pressure is applied to draw a certain volume of a first liquid into a first flow cell. Optionally, at 1304, a detection signal is measured in the first flow cell. At 1306, negative pressure is applied to draw a certain volume (e.g., a measured volume) of the first liquid into a first chamber. At 1308, positive pressure is applied to dispense a certain volume (e.g., a measured volume) of a second liquid into the first chamber. At 1310, positive pressure is applied to dispense the first and second liquids from the first chamber to the second chamber. At 1312, negative pressure is applied to draw the first and second liquids from the second chamber to the first chamber. At 1314, steps 1310 and 1312 are repeated once or more times. At 1316, positive pressure is applied to move the mixture from the first or second chamber to the second flow cell. Optionally, at 1318, a detection signal is measured in the second flow cell.
[0204] Figure 39 is a flowchart of method 1400 for resuspending a dried reagent. At 1402, a first pressure is applied to transfer a metered volume of a first liquid into a first chamber to resuspend one or more first dried reagents, and resuspending one or more first dried reagents in the first liquid forms the first reagent. At 1404, a second pressure is applied to transfer a metered volume of the first liquid into a second chamber to resuspend one or more second dried reagents, and resuspending one or more second dried reagents in the first liquid forms the second reagent. At 1406, a third pressure is applied to move the first reagent through at least one flow cell. At 1408, a fourth pressure is applied to move the second reagent through at least one flow cell. At 1410, a detection signal is measured in at least one flow cell.
[0205] Methods 1000, 1100, 1200, 1300, and 1400, as described with reference to Figures 35 to 39, may be performed using the cartridge 100 having the fluid circuit described with reference to Figures 26 to 28. It will be understood that the steps of these methods may be performed in a different order than those described above. That is, the specific order of the steps of the methods described above is not intended to be limiting, but rather optional. Figures 40 to 43 illustrate examples of assays that may be performed using the cartridge 100 having the fluid circuit described with reference to Figures 26 to 28. The assays described below may include one or more of the above methods 1000, 1100, 1200, 1300, and 1400. Thus, methods 1000, 1100, 1200, 1300, and 1400 may further include one or more steps of the exemplary assays described with reference to Figures 40 to 43.
[0206] Figure 40 is a flowchart of method 1500 for performing the first assay. At 1502, with valves 302a (V2) and 302c (V9) open, the sample is flowed from the permanently ventilated sample inlet chamber 236 (S1) to the first waste chamber port 358a (W1) and negative pressure is applied to the first pneumatic port 312a (P1) to fill the sample flow cell 610c (F3). At 1504, a detection signal is measured from the sample present in the sample flow cell 610c (F3).
[0207] At 1506, valves 302k(V1), 302i(V7), and 302c(V9) are opened, and with the first pneumatic port 312a(P1) vented, positive pressure is applied to the second pneumatic port 312b(P2) to allow the diluent to flow from the outlet of the third liquid storage capsule 120c(B3B) to the first waste chamber port 358a(W1). Since the ventilation state of the first waste chamber 508a is controlled via the first pneumatic port 312a(P1), the first pneumatic port 312a(P1) needs to be vented to allow flow to the first waste chamber port 358a(W1). At 1508, valves 302k(V1), 302b(V6), and 302i(V7) are opened, and with the third pneumatic port 312c(P3) vented, positive pressure is applied to the second pneumatic port 312b(P2) to transfer a metered volume of diluent from the outlet of the third liquid storage capsule 120c(B3B) to the second chamber 332b(M2). In this example, the second chamber 332b(M2) contains the dried reagent in the form of two Riobeads: one having magnetic beads coated with a scavenging agent, and another Riobead having a sample treatment reagent. During this step, the two Riobeads are hydrated.
[0208] At 1510, with valves 302i (V7) and 302j (V8) open and the third pneumatic port 312c (P3) vented, positive pressure is applied to the second pneumatic port 312b (P2) to transfer a metered volume of diluent from the outlet of the third liquid storage capsule 120c (B3B) to the third chamber 332c (M3). In this example, the third chamber 332c (M3) contains a dried reagent in the form of a single rio bead having a secondary antibody and enzyme label. During this step, this rio bead is hydrated.
[0209] At 1512, with valves 302a(V2) and 302b(V6) open, negative pressure is applied to the third pneumatic port 312c(P3) to flow a metered volume of sample from the permanently ventilated sample inlet chamber 236(S1) into the second chamber 332b(M2). At 1514, with the first pneumatic port 312a(P1) open, positive and negative pressure cycles are applied to the third pneumatic port 312c(P3) to mix the sample with the diluent by moving the liquid back and forth between the first chamber 332a(M1) and the second chamber 332b(M2) and to resuspend the dried reagent stored in the first chamber 332a(M1) and / or the second chamber 332b(M2). Step 1514 may also be applied by applying positive and negative pressure cycles to the first pneumatic port 312a(P1) while the third pneumatic port 312c(P3) is open.
[0210] In 1516, with valves 302e(V11) and 302d(V12) open and the magnet operating on the first flow cell 610a(F1), positive pressure is applied to the third pneumatic port 312c(P3) to flow the mixture from the first chamber 332a(M1) or the second chamber 332b(M2) through the first flow cell 610a(F1) to the third waste chamber port 358c(W3). The magnet may be actuated by an analyzer that receives cartridge 100 and uses cartridge 100 to perform method 1500 of the first assay. The magnet can be actuated by the analyzer to apply a local magnetic field to the first flow cell 610a(F1). The magnet may be a movable permanent magnet or a stationary electromagnet. At 1518, valves 302k(V1), 302g(V4), and 302c(V9) are opened, and with the first pneumatic port 312a(P1) open, positive pressure is applied to the second pneumatic port 312b(P2) to allow the cleaning solution to flow from the outlet of the first liquid storage capsule 120a(B1B) to the first waste chamber port 358a(W1).
[0211] At 1520, with valves 302g(V4) and 302e(V11) open and the magnet operating on the first flow cell 610a(F1), positive pressure is applied to the second pneumatic port 312b(P2) to allow the cleaning solution to flow from the outlet of the first liquid storage capsule 120a(B1B) through the first flow cell 610a(F1) to the third waste chamber port 358c(W3). At 1522, with valves 302l(V3) and 302e(V11) open and the magnet operating on the first flow cell 610a(F1), positive pressure is applied to the second pneumatic port 312b(P2) to allow air to flow through the first flow cell 610a(F1) to the third waste chamber port 358c(W3).
[0212] In step 1524, with valves 302j (V8) and 302e (V11) open and the magnet operating on the first flow cell 610a (F1), positive pressure is applied to the third pneumatic port 312c (P3) to flow the detection solution from the third chamber 332c (M3) through the first flow cell 610a (F1) to the third waste chamber port 358c (W3). In this example, the detection solution is prepared in step 1510 from a diluted solution and detection beads in the third chamber 332c (M3). At 1526, with valves 302g(V4) and 302e(V11) open and the magnet operating on the first flow cell 610a(F1), positive pressure is applied to the second pneumatic port 312b(P2) to allow the cleaning solution to flow from the outlet of the first liquid storage capsule 120a(B1B) through the first flow cell 610a(F1) to the third waste chamber port 358c(W3). At 1528, with valves 302l(V3) and 302e(V11) open and the magnet operating on the first flow cell 610a(F1), positive pressure is applied to the second pneumatic port 312b(P2) to allow air to flow through the first flow cell 610a(F1) to the third waste chamber port 358c(W3).
[0213] At 1530, with valves 302g(V4) and 302f(V10) open and the magnet operating on the second flow cell 610b(F2), positive pressure is applied to the second pneumatic port 312b(P2) to flow the cleaning solution from the outlet of the first liquid storage capsule 120a(B1B) through the first flow cell 610a(F1) and the second flow cell 610b(F2) to the second waste chamber port 358b(W2). This step transfers the magnetic beads from the first flow cell 610a(F1) to the second flow cell 610b(F2). At 1532, with valves 302l(V3) and 302f(V10) open and the magnet operating on the second flow cell 610b(F2), positive pressure is applied to the second pneumatic port 312b(P2) to allow air to flow through the first flow cell 610a(F1) and the second flow cell 610b(F2) to the second waste chamber port 358b(W2).
[0214] In 1534, with valves 302h (V5) and 302f (V10) open, positive pressure is applied to the second pneumatic port 312b (P2) to flow the signal solution from the outlet of the second liquid storage capsule 120b (B2B) to the second waste chamber port 358b (W2). At 1536, with valves 302k(V1), 302h(V5), and 302c(V9) open, the first pneumatic port 312a(P1) vented, and the magnet operating on the second flow cell 610b(F2), positive pressure is applied to the second pneumatic port 312b(P2) to flow the signal solution from the outlet of the second liquid storage capsule 120b(B2B) through the first flow cell 610a(F1) and the second flow cell 610b(F2) to the first waste chamber port 358a(W1). At 1538, the detection signal is measured in the flow cells 610a(F1) and / or 610b(F2).
[0215] Figure 41 is a flowchart of method 1600 for performing the second assay. In 1602, with valves 302a (V2) and 302c (V9) open, the sample is flowed from the permanently ventilated sample inlet chamber 236 (S1) to the first waste chamber port 358a (W1), and negative pressure is applied to the first pneumatic port 312a (P1) to fill the sample flow cell 610c (F3). In 1604, a detection signal is measured from the sample present in the sample flow cell 610c (F3).
[0216] At 1606, valves 302k(V1), 302i(V7), and 302c(V9) are opened, and with the first pneumatic port 312a(P1) open, positive pressure is applied to the second pneumatic port 312b(P2) to flow the diluent from the outlet of the third liquid storage capsule 120c(B3B) to the first waste chamber port 358a(W1). At 1608, valves 302k(V1), 302b(V6), and 302i(V7) are opened, and with the third pneumatic port 312c(P3) open, positive pressure is applied to the second pneumatic port 312b(P2) to transfer the metered volume of diluent from the outlet of the third liquid storage capsule 120c(B3B) to the second chamber 332b(M2). The diluent moves a portion of the metered and held sample within the U-shaped channel between valves 302k(V1), 302a(V2), and 302b(V6).
[0217] In step 1610, a positive and negative pressure cycle is applied to the third pneumatic port 312c(P3) with the first pneumatic port 312a(P1) open, in order to mix the sample with the diluent by moving the liquid back and forth between the first chamber 332a(M1) and the second chamber 332b(M2) and to resuspend the dried reagent stored in the first chamber 332a(M1) and / or the second chamber 332b(M2). Step 1610 may also be applied by applying a positive and negative pressure cycle to the first pneumatic port 312a(P1) with the third pneumatic port 312c(P3) open.
[0218] At 1612, with valves 302e(V11) and 302d(V12) open and the magnet operating on the first flow cell 610a(F1), positive pressure is applied to the third pneumatic port 312c(P3) to flow the mixture from the first chamber 332a(M1) or the second chamber 332b(M2) through the first flow cell 610a(F1) to the third waste chamber port 358c(W3). At 1614, valves 302k(V1), 302g(V4), and 302c(V9) are opened, and with the first pneumatic port 312a(P1) vented, positive pressure is applied to the second pneumatic port 312b(P2) to flow the washing solution from the outlet of the first liquid storage capsule 120a(B1B) to the first waste chamber port 358a(W1). Following this step, priming of the washing buffer can now be performed.
[0219] At 1616, with valves 302g(V4) and 302e(V11) open and the magnet operating on the first flow cell 610a(F1), positive pressure is applied to the second pneumatic port 312b(P2) to allow the cleaning solution to flow from the outlet of the first liquid storage capsule 120a(B1B) through the first flow cell 610a(F1) to the third waste chamber port 358c(W3). At 1618, with valves 302l(V3) and 302e(V11) open and the magnet operating on the first flow cell 610a(F1), positive pressure is applied to the second pneumatic port 312b(P2) to allow air to flow through the first flow cell 610a(F1) to the third waste chamber port 358c(W3).
[0220] At 1620, with valves 302g(V4) and 302f(V10) open and the magnet operating on the second flow cell 610b(F2), positive pressure is applied to the second pneumatic port 312b(P2) to flow the cleaning solution from the outlet of the first liquid storage capsule 120a(B1B) through the first flow cell 610a(F1) and the second flow cell 610b(F2) to the second waste chamber port 358b(W2). This step transfers the magnetic beads from the first flow cell 610a(F1) to the second flow cell 610b(F2). At 1622, with valves 302l(V3) and 302f(V10) open and the magnet operating on the second flow cell 610b(F2), positive pressure is applied to the second pneumatic port 312b(P2) to allow air to flow through the first flow cell 610a(F1) and the second flow cell 610b(F2) to the second waste chamber port 358b(W2).
[0221] At 1624, with valves 302h (V5) and 302f (V10) open, positive pressure is applied to the second pneumatic port 312b (P2) to flow the signal solution from the outlet of the second liquid storage capsule 120b (B2B) to the second waste chamber port 358b (W2). At 1626, with valves 302h (V5) and 302j (V8) open, the third pneumatic port 312c (P3) is vented, and the magnet is operating on the second flow cell 610b (F2), positive pressure is applied to the second pneumatic port 312b (P2) to flow the signal solution from the outlet of the second liquid storage capsule 120b (B2B) through the first flow cell 610a (F1) and the second flow cell 610b (F2) to the third chamber 332c (M3). At 1628, the detection signal is measured in the first flow cell 610a (F1) and the second flow cell 610b (F2).
[0222] Figure 42 is a flowchart of method 1700 for performing the third assay. In 1702, with valves 302a (V2) and 302c (V9) open, the sample is flowed from the permanently ventilated sample inlet chamber 236 (S1) to the first waste chamber port 358a (W1) and negative pressure is applied to the first pneumatic port 312a (P1) to fill the sample flow cell 610c (F3). In 1704, a detection signal is measured from the sample present in the flow cell sample flow cell 610c (F3).
[0223] At 1706, valves 302k(V1), 302i(V7), and 302c(V9) are opened, and with the first pneumatic port 312a(P1) open, positive pressure is applied to the second pneumatic port 312b(P2) to flow the diluent from the outlet of the third liquid storage capsule 120c(B3B) to the first waste chamber port 358a(W1). At 1708, valves 302k(V1), 302b(V6), and 302i(V7) are opened, and with the third pneumatic port 312c(P3) open, positive pressure is applied to the second pneumatic port 312b(P2) to transfer the metered volume of diluent from the outlet of the third liquid storage capsule 120c(B3B) to the second chamber 332b(M2). At 1710, positive and negative pressure cycles are applied to the third pneumatic port 312c (P3) with the first pneumatic port 312a (P1) open, in order to mix the sample with the diluent by moving the liquid back and forth between the first chamber 332a (M1) and the second chamber 332b (M2), and to resuspend the dried reagent stored in the first chamber 332a (M1) and / or the second chamber 332b (M2).
[0224] At 1712, with valves 302f(V10) and 302e(V11) open, positive pressure is applied to the third pneumatic port 312c(P3) to flow the mixture from the first chamber 332a(M1) or the second chamber 332b(M2) through the first flow cell 610a(F1) and the second flow cell 610b(F2) to the second waste chamber port 358b(W2). At 1714, with valves 302k(V1), 302g(V4) and 302c(V9) open and the first pneumatic port 312a(P1) vented, positive pressure is applied to the second pneumatic port 312b(P2) to flow the cleaning solution from the first liquid storage capsule 120a(B1B) to the first waste chamber port 358a(W1). At 1716, with valves 302g(V4) and 302f(V10) open, positive pressure is applied to the second pneumatic port 312b(P2) to allow the cleaning solution to flow from the first liquid storage capsule 120a(B1B) through the first flow cell 610a(F1) and the second flow cell 610b(F2) to the second waste chamber port 358b(W2). At 1718, with valves 302l(V3) and 302f(V10) open, positive pressure is applied to the second pneumatic port 312b(P2) to allow air to flow through the first flow cell 610a(F1) and the second flow cell 610b(F2) to the second waste chamber port 358b(W2).
[0225] At 1720, with valves 302h (V5) and 302f (V10) open, positive pressure is applied to the second pneumatic port 312b (P2) to flow the signal solution from the outlet of the second liquid storage capsule 120b (B2B) to the second waste chamber port 358b (W2). At 1722, with valves 302h (V5) and 302j (V8) open and the third pneumatic port 312c (P3) vented, positive pressure is applied to the second pneumatic port 312b (P2) to flow the signal solution from the outlet of the second liquid storage capsule 120b (B2B) through the first flow cell 610a (F1) and the second flow cell 610b (F2) to the third chamber 332c (M3). At 1724, the detection signal is measured in the first flow cell 610a (F1) and the second flow cell 610b (F2).
[0226] Figure 43 is a flowchart of method 1800 for performing the fourth assay. In 1802, with valves 302a (V2) and 302c (V9) open, the sample is flowed from the permanently ventilated sample inlet chamber 236 (S1) to the first waste chamber port 358a (W1) and negative pressure is applied to the first pneumatic port 312a (P1) to fill the sample flow cell 610c (F3). In 1804, a detection signal is measured from the sample present in the sample flow cell 610c (F3).
[0227] At 1806, valves 302k(V1), 302i(V7), and 302c(V9) are opened, and with the first pneumatic port 312a(P1) open, positive pressure is applied to the second pneumatic port 312b(P2) to flow the diluent from the outlet of the third liquid storage capsule 120c(B3B) to the first waste chamber port 358a(W1). At 1808, valves 302k(V1), 302b(V6), and 302i(V7) are opened, and with the third pneumatic port 312c(P3) open, positive pressure is applied to the second pneumatic port 312b(P2) to transfer the metered volume of diluent from the outlet of the third liquid storage capsule 120c(B3B) to the second chamber 332b(M2). At 1810, with valves 302i (V7) and 302j (V8) open and the third pneumatic port 312c (P3) vented, positive pressure is applied to the second pneumatic port 312b (P2) to transfer a metered volume of diluent from the outlet of the third liquid storage capsule 120c (B3B) to the third chamber 332c (M3).
[0228] At 1812, with valves 302a(V2) and 302b(V6) open, negative pressure is applied to the third pneumatic port 312c(P3) to flow a metered volume of sample from the permanently ventilated sample inlet chamber 236(S1) into the second chamber 332b(M2). At 1814, with the first pneumatic port 312a(P1) open, positive and negative pressure cycles are applied to the third pneumatic port 312c(P3) to mix the sample with the diluent by moving the liquid back and forth between the first chamber 332a(M1) and the second chamber 332b(M2) and to resuspend the dried reagent stored in the first chamber 332a(M1) and / or the second chamber 332b(M2).
[0229] At 1816, with valves 302f(V10) and 302e(V11) open, positive pressure is applied to the third pneumatic port 312c(P3) to flow the mixture from the first chamber 332a(M1) or the second chamber 332b(M2) through the first flow cell 610a(F1) and the second flow cell 610b(F2) to the second waste chamber port 358b(W2). At 1818, with valves 302k(V1), 302g(V4) and 302c(V9) open and the first pneumatic port 312a(P1) vented, positive pressure is applied to the second pneumatic port 312b(P2) to flow the cleaning solution from the outlet of the first liquid storage capsule 120a(B1B) to the first waste chamber port 358a(W1).
[0230] At 1820, with valves 302g(V4) and 302f(V10) open, positive pressure is applied to the second pneumatic port 312b(P2) to allow the cleaning solution to flow from the outlet of the first liquid storage capsule 120a(B1B) through the first flow cell 610a(F1) and the second flow cell 610b(F2) to the second waste chamber port 358b(W2). At 1822, with valves 302l(V3) and 302f(V10) open, positive pressure is applied to the second pneumatic port 312b(P2) to allow air to flow through the first flow cell 610a(F1) and the second flow cell 610b(F2) to the second waste chamber port 358b(W2).
[0231] At 1824, with valves 302j(V8) and 302f(V10) open, positive pressure is applied to the third pneumatic port 312c(P3) to flow the detection solution from the third chamber 332c(M3) through the first flow cell 610a(F1) and the second flow cell 610b(F2) to the second waste chamber port 358b(W2). At 1826, with valves 302g(V4) and 302f(V10) open, positive pressure is applied to the second pneumatic port 312b(P2) to flow the cleaning solution from the outlet of the first liquid storage capsule 120a(B1B) through the first flow cell 610a(F1) and the second flow cell 610b(F2) to the second waste chamber port 358b(W2). At 1828, with valves 302l(V3) and 302f(V10) open, positive pressure is applied to the second pneumatic port 312b(P2) to allow air to flow through the first flow cell 610a(F1) and the second flow cell 610b(F2) to the second waste chamber port 358b(W2).
[0232] At 1830, with valves 302h (V5) and 302f (V10) open, positive pressure is applied to the second pneumatic port 312b (P2) to flow the signal solution from the outlet of the second liquid storage capsule 120b (B2B) to the second waste chamber port 358b (W2). At 1832, with valves 302k (V1), 302h (V5) and 302c (V9) open and the first pneumatic port 312a (P1) open, positive pressure is applied to the second pneumatic port 312b (P2) to flow the signal solution from the outlet of the second liquid storage capsule 120b (B2B) through the first flow cell 610a (F1) and the second flow cell 610b (F2) to the first waste chamber port 358a (W1). At 1834, the detection signal is measured in the first flow cell 610a (F1) and the second flow cell 610b (F2).
[0233] Methods 1500, 1600, 1700, and 1800 can each be carried out using the fluid circuit of the cartridge 100 described above. Thus, the cartridge 100 can perform several different assay protocols. Depending on the sensor configuration, the same assay method can be used for single detection (one biomarker) or multiple detection (two or more biomarkers). Methods 1500 and 1600 are designed to allow a liquid-phase reaction between the sample and a capture agent (e.g., antibody or antigen) coated on the magnetic beads. Methods 1700 and 1800 are designed to allow a solid-phase reaction between the sample and a capture agent (e.g., antibody or antigen) coated on the sensor surface. The sensor and flow cell can be configured for different types of detection, such as electrochemical detection (as shown in Figure 3) or optical detection (e.g., photometry or surface plasma resonance). It will be understood that the steps of Methods 1500, 1600, 1700, and 1800 may be carried out in a different order than described above. In other words, the specific order of the method steps described above is not intended to be restrictive, but rather optional.
[0234] Embodiments described herein also include an analyzer configured to accept cartridge 100. The analyzer may be configured to operate cartridge 100 to perform one or more of the methods described with reference to Figures 35 to 43. Thus, the analyzer may include a computer-readable medium that stores computer-executable instructions, which, when executed by the analyzer's processor, cause the analyzer to perform one or more of the methods described with reference to Figures 35 to 43. The analyzer may comprise one or more of the following hardware components: one or more valve actuators configured to deform the valve region 302 of the cartridge 100 to close the valve of the cartridge 100; one or more capsule actuators configured to actuate the actuated portion 240 of the first part 200 of the cartridge 100 to create an inlet and outlet for each of the one or more liquid storage capsules 120; one or more pneumatic actuators configured to supply positive or negative pressure to each of the pneumatic ports 312 of the cartridge 100, to vent the pneumatic ports 312 of the cartridge 100, and / or to close the pneumatic ports 312 of the cartridge 100; one or more magnets (e.g., movable permanent magnets or electromagnets) that can be actuated to apply a local magnetic field to one or more of the flow cells 610 of the cartridge 100 (e.g., to hold magnetic beads in one or more flow cells 610); and a detection module for measuring detection signals in one or more of the flow cells 610 of the cartridge 100. The specific hardware requirements of the analytical instrument depend on which of the above methods the instrument is used to perform, and will be understood by those skilled in the art from the steps of the above method.
[0235] The methods described may be carried out using computer-executable instructions. Computer program products or computer-readable media may contain or store computer-executable instructions. Computer program products or computer-readable media may include hard disk drives, flash memory, read-only memory (ROM), CDs, DVDs, caches, random-access memory (RAM), and / or any other storage media on which information is stored for any period of time (e.g., long-term, permanent, short-term, temporary buffering, and / or information caching). Computer programs may contain computer-executable instructions. Computer-readable media may be tangible or non-temporary computer-readable media. The term "computer-readable" includes "machine-readable."
[0236] The singular terms “a” and “an” should not be interpreted as meaning “only.” Rather, unless otherwise specified, they should be interpreted as meaning “at least one” or “one or more.” The words “comprising,” and their derivatives including “comprises,” include each of the listed features, but do not exclude the inclusion of one or more further features.
[0237] As used herein, the term “channel” means a groove provided on a surface having an open cross-section (i.e., the cross-section is not sealed). As used herein, the term “conduit” means (i) a channel that is sealed (e.g., by a sealing layer) and thereby provides a closed cross-section, or (ii) a hole or tunnel that extends at least partially through the body.
[0238] The embodiments described above are for illustrative purposes only, and the embodiments described should be considered in all respects as illustrative only and not limiting. It will be understood that modifications of the embodiments described can be made without departing from the scope of the invention. It will also be apparent that there are many modifications that are not described but fall within the scope of the appended claims.
[0239] This disclosure also includes the following numbered clauses that describe combinations of features useful for understanding this disclosure.
[0240] A1. A liquid processing apparatus, wherein the liquid processing apparatus is A fluid layer, Multiple channels, An opening in the surface of a fluid layer, which extends through at least a portion of the thickness of the fluid layer to one of a plurality of channels, and A fluid layer comprising, A rigid layer with an operable part, The liquid storage capsule comprises a fluid layer and a liquid storage capsule positioned between the fluid layer and the operable part, A body that defines the volume in which a liquid is stored, the body comprising a first deformable portion, a main liquid storage portion, and a limiting portion connecting the first deformable portion to the main liquid storage portion, A sealing layer configured to seal the volume and The liquid storage capsule is positioned above the opening such that the sealing layer portion covers the opening. Liquid processing apparatus, wherein the movable part comprises a projection extending toward a liquid storage capsule, the movable part being movable from a first position in which the projection does not deform a first deformable part to a second position in which the projection deforms the first deformable part and comes into contact with a portion of the sealing layer, causing the portion of the sealing layer to rupture, and when the movable part is in the second position, the projection does not deform a limiting part.
[0241] A2. The liquid processing apparatus described in clause A1, wherein the protruding part cannot pass through the opening. A3, The liquid storage capsule is positioned above the opening such that the first deformable portion and limiting portion are at least partially positioned above the opening, as described in Clause A1 or Clause A2.
[0242] A4. A liquid processing apparatus according to any one of clauses A1 to A3, wherein the opening is oval in shape.
[0243] A5. The liquid processing apparatus according to any one of the clauses A1 to A4, wherein the first deformable portion comprises a first region and a second region, and the first distance between the first region and the sealing layer is greater than the second distance between the second region and the sealing layer.
[0244] A6. The liquid apparatus according to Clause A5, wherein the first and second regions are concentric such that the first region surrounds the second region.
[0245] A7. A liquid processing apparatus as described in any one of clauses A1 to A6, wherein the width of the opening is less than the width of the protrusion.
[0246] A8. The liquid processing apparatus according to any one of the clauses A1 to A7, wherein the projection has an end that engages with a first deformable portion of the liquid storage capsule.
[0247] A9. The end of the protrusion is flat, as described in clause A6 of the liquid processing apparatus. A10. The liquid processing apparatus according to clause A8 or A9, wherein the end of the protruding portion has a cross-section having a main sector shape.
[0248] A11. A liquid processing apparatus according to any one of clauses A8 to A10, wherein the projection is provided with a groove defining the cross-section of the end of the projection.
[0249] A12. The liquid processing apparatus according to clause A11, wherein the groove is aligned with the limiting portion of the liquid storage capsule.
[0250] A13. The groove is the liquid treatment device according to clause A11 or clause A12, which is subordinate to clause A10 and defines the main fan-shaped cross-section at the end of the protrusion.
[0251] A14. The cross-section at the end of the protrusion includes one or more outwardly extending protruding ribs, and the liquid treatment device according to any one of clauses A8 - A13.
[0252] A15. The one or more outwardly extending protruding ribs extend from the curved portion of the main fan-shaped cross-section, and the liquid treatment device according to clause A14, which is subordinate to clause A10.
[0253] A16. The protrusion is the first protrusion, and the operable part includes a second protrusion extending towards the liquid storage capsule. The body of the liquid storage capsule includes a second deformable part. The opening is the first opening, and the fluid layer includes a second opening extending to one of the plurality of channels through at least a part of the thickness of the fluid layer. The part of the sealing layer is the first part of the sealing layer, and the liquid storage capsule is positioned above the second opening such that the second part of the sealing layer covers the second opening. In the first position, the second protrusion does not deform the second deformable part. In the second position, the second protrusion deforms the second deformable part to contact the second part of the sealing layer and cause the rupture of the second part of the sealing layer, and the liquid treatment device according to any one of clauses A1 - A15.
[0254] A17. The liquid storage capsule is the first liquid storage capsule, and the liquid treatment device includes a second liquid storage capsule, and the second liquid storage capsule has a body that defines a volume for storing liquid, the body includes a first deformable part and a second deformable part, and a sealing layer configured to seal the volume and the operable part includes a third protrusion extending towards the first deformable part of the second liquid storage capsule. a fourth protrusion extending toward a second deformable portion of the second liquid storage capsule, and comprising, the fluid layer is a third opening extending through at least a portion of the thickness of the fluid layer to one of a plurality of channels, and a fourth opening extending through at least a portion of the thickness of the fluid layer to one of a plurality of channels comprising The second liquid storage capsule is positioned over the third opening and the fourth opening such that a first portion of the sealing layer of the second liquid storage capsule covers the third opening and a second portion of the sealing layer of the second liquid storage capsule covers the fourth opening. In the first position, the third protrusion does not deform the first deformable portion of the body of the second liquid storage capsule, and the fourth protrusion does not deform the second deformable portion of the body of the second liquid storage capsule. In the second position, the third protrusion deforms the first deformable portion of the body of the second liquid storage capsule and contacts the first portion of the sealing layer of the second liquid storage capsule to cause rupture of the first portion of the sealing layer of the second liquid storage capsule. In the second position, the fourth protrusion deforms the second deformable portion of the body of the second liquid storage capsule and contacts the second portion of the sealing layer of the second liquid storage capsule to cause rupture of the second portion of the sealing layer of the second liquid storage capsule. The liquid processing apparatus according to any one of clauses A1 to A16.
[0255] B1. A liquid processing apparatus, the liquid processing apparatus comprising a fluid layer, comprising a plurality of channels, and an opening in the surface of the fluid layer, the opening extending through at least a portion of the thickness of the fluid layer to one of a plurality of channels comprising, the fluid layer a rigid layer having an operable portion, and a liquid storage capsule positioned between the fluid layer and the operable portion comprising, the liquid storage capsule is A main body that defines the volume in which the liquid is stored, A sealing layer configured to seal the volume and The liquid storage capsule is positioned above the opening such that the sealing layer portion covers the opening. The movable part comprises a projection extending toward the liquid storage capsule, and the movable part is movable from a first position in which the projection does not deform the main body to a second position in which the projection deforms the main body and comes into contact with a portion of the sealing layer, causing the portion of the sealing layer to rupture. A liquid processing device in which protruding parts cannot pass through the opening.
[0256] B2. The liquid processing apparatus according to clause B1, wherein the opening is oval in shape. B3. The liquid processing apparatus according to clause B1 or B2, wherein the body of the liquid storage capsule comprises a first deformable portion configured to be deformed by a projection when the operable portion is in a second position.
[0257] B4. The liquid processing apparatus according to clause B3, wherein the main body further comprises a main liquid storage section and a limiting section connecting a first deformable section to the main liquid storage section, and the liquid storage capsule is positioned above the opening such that the first deformable section and the limiting section are at least partially positioned above the opening.
[0258] B5. The liquid apparatus according to clause B3 or B4, wherein the first deformable portion comprises a first region and a second region, and the first distance between the first region and the sealing layer is greater than the second distance between the second region and the sealing layer.
[0259] B6. The liquid apparatus according to Clause B5, wherein the first and second regions are concentric such that the first region surrounds the second region.
[0260] B7. A liquid processing apparatus according to any one of the clauses B1 to B6, wherein the width of the opening is less than the width of the protrusion.
[0261] B8. A liquid processing apparatus according to any one of the clauses B1 to B7, wherein the protrusion has an end that engages with the body of the liquid storage capsule.
[0262] B9. The end of the protrusion is flat, as described in clause B8 of the liquid processing apparatus. B10. The liquid processing apparatus according to clause B8 or B9, wherein the end of the protruding portion has a cross-section having a main sector shape.
[0263] B11. A liquid processing apparatus according to any one of the clauses B8 to B10, wherein the projection is provided with a groove defining the cross-section of the end of the projection.
[0264] B12. The liquid processing apparatus according to clause B11, wherein the groove is aligned with the limiting portion of the liquid storage capsule.
[0265] B13. A liquid apparatus according to clause B11 or B12, which is subordinate to clause B10, wherein the groove defines the main sector shape of the cross-section of the end of the protruding portion.
[0266] B14. The liquid processing apparatus according to any one of the clauses B8 to B13, wherein the cross section of the end of the protrusion includes one or more outwardly extending protruding ribs.
[0267] B15. A liquid apparatus according to clause B14, which is dependent on clause B10, wherein one or more outwardly extending protruding ribs extend from the curved portion of the main sector shape.
[0268] B16. The projection is a first projection, and the operable portion comprises a second projection extending toward the liquid storage capsule. The opening is a first opening, and the fluid layer has a second opening that extends through at least a portion of the thickness of the fluid layer to one of a plurality of channels. The sealing layer portion is the first portion of the sealing layer, and the liquid storage capsule is positioned above the second opening such that the second portion of the sealing layer covers the second opening. In the first position, the second projection does not deform the body of the liquid storage capsule. In the second position, the second protrusion causes deformation of the main body to contact the second part of the sealing layer to cause rupture of the second part of the sealing layer, the liquid treatment apparatus according to any one of clauses B1 to B15.
[0269] B17. The liquid storage capsule is the first liquid storage capsule, the liquid treatment apparatus includes a second liquid storage capsule, and the second liquid storage capsule a main body that defines a volume in which a liquid is stored, a sealing layer configured to seal the volume and includes, and the actuating part a third protrusion extending towards the second liquid storage capsule, a fourth protrusion extending towards the second liquid storage capsule and includes, and the fluid layer a third opening extending through at least a part of the thickness of the fluid layer to one of the plurality of channels, a fourth opening extending through at least a part of the thickness of the fluid layer to one of the plurality of channels and includes, The second liquid storage capsule is positioned above the third opening and the fourth opening such that the first part of the sealing layer of the second liquid storage capsule covers the third opening and the second part of the sealing layer of the second liquid storage capsule covers the fourth opening, In the first position, the third protrusion does not deform the main body of the second liquid storage capsule, and the fourth protrusion does not deform the main body of the second liquid storage capsule, In the second position, the third protrusion deforms the main body of the second liquid storage capsule to contact the first part of the sealing layer of the second liquid storage capsule to cause rupture of the first part of the sealing layer of the second liquid storage capsule, In the second position, the fourth protrusion deforms the main body of the second liquid storage capsule to contact the second part of the sealing layer of the second liquid storage capsule to cause rupture of the second part of the sealing layer of the second liquid storage capsule, the liquid treatment apparatus according to any one of clauses B1 to B16.
[0270] C1. A liquid processing apparatus, wherein the liquid processing apparatus is A fluid layer comprising a chamber, the chamber is Opening at the upper end of the chamber A fluid layer comprising, A sealing layer configured to seal the opening of the chamber Equipped with, The chamber comprises one or more projections, each of which extends from the inner wall of the chamber. A liquid processing apparatus in which, once a reagent ball is placed in a chamber, one or more protrusions prevent the reagent ball from coming into contact with a sealing layer.
[0271] C2. The liquid apparatus according to clause C1, wherein the opening is configured to allow a reagent ball to be inserted into the chamber.
[0272] C3. A liquid processing apparatus according to clause C1 or C2, wherein one or more protrusions are elastically deformable.
[0273] C4. A liquid apparatus according to any one of the clauses C1 to C3, wherein the fluid layer is formed from a thermoplastic elastomer.
[0274] C5. A liquid processing apparatus according to any one of the C1 to C4, wherein each of the one or more protrusions extends from the inner wall of the chamber at the upper end of the chamber.
[0275] C6. The liquid apparatus according to clause C5, wherein the opening is partially defined by each of one or more protrusions.
[0276] C7. The liquid apparatus according to any one of the clauses C1 to C6, wherein the fluid layer comprises projections extending from the upper surface of the fluid layer, the projections partially defining the chamber.
[0277] C8. Chamber is A fluid inlet located below one or more protrusions, Air outlets located on the inner wall and Furthermore, A liquid processing apparatus according to any one of the clauses C1 to C7, wherein the first maximum distance between the air outlet and the upper end base is less than or equal to the second maximum distance between one or more protrusions and the upper end.
[0278] C9. Each of the one or more protrusions is: A first protruding portion extending from the inner wall of the chamber, A second projection extends from the distal end of the first projection, the second projection extending away from the upper end of the chamber and A liquid processing apparatus as described in any one of clauses C1 to C8, comprising:
[0279] D1. A liquid processing apparatus, wherein the liquid processing apparatus is A first liquid storage container and a second liquid storage container, each of the first and second liquid storage containers being configured to open by creating an inlet and an outlet within the liquid storage container, A fluid layer, and the fluid layer is The channel network and A pneumatic port configured to receive positive pressure and The network of channels is equipped with A first liquid storage container inlet channel is configured to provide a fluid connection between a pneumatic port and an inlet inside the first liquid storage container when the first liquid storage container is opened, A second liquid storage container inlet channel is configured to provide a fluid connection between the pneumatic port and the inlet inside the second liquid storage container when the second liquid storage container is opened. A fluid layer comprising A liquid processing apparatus equipped with the following features.
[0280] D2. Liquid processing equipment is, A first liquid storage container valve configured to control the flow of liquid from the outlet of the first liquid storage container, A second liquid storage container valve configured to control the flow of liquid from the outlet of the second liquid storage container, The liquid processing apparatus described in Clause D1, further comprising:
[0281] The D3 channel network is A first liquid storage container outlet channel configured to communicate fluidly with an outlet in the first liquid storage container when the first liquid storage container is opened, wherein a first liquid storage container valve is located in the first liquid storage container outlet channel. The liquid processing apparatus described in Clause D2 further comprises the following:
[0282] The D4 channel network is A second liquid storage container outlet channel configured to communicate fluidly with an outlet in the second liquid storage container when the second liquid storage container is opened, wherein a second liquid storage container valve is located in the second liquid storage container outlet channel. A liquid apparatus according to clause D2 or clause D3, further comprising:
[0283] D5. The liquid processing apparatus according to any one of the clauses D1 to D4, further comprising a well, the well being at least partially defined by an opening extending through at least a portion of the thickness of the fluid layer, the well being in fluid communication with a pneumatic port, a first liquid storage container inlet channel, and a second liquid storage container inlet channel.
[0284] D6. The liquid processing apparatus according to Clause D5, wherein the opening, the first liquid storage container inlet channel and the second liquid storage container inlet channel are provided on the upper surface of the fluid layer, and the depth of the opening is greater than the depth of the first and second liquid storage container inlet channels.
[0285] D7. The liquid processing apparatus further comprises a lower section, the lower section having a trough on the upper surface of the lower section. The fluid layer is positioned above the bottom, A liquid apparatus according to clause D5 or clause D6, wherein the well is at least partially defined by an opening in the fluid layer and a trough in the lower part.
[0286] D8. The liquid apparatus according to clause D7, wherein the opening in the fluid layer extends through the thickness of the fluid layer.
[0287] D9. A liquid apparatus according to clause D7 or D8, wherein the pneumatic port extends through the thickness of the fluid layer, and the pneumatic port communicates with the trough via a connector channel in the lower part.
[0288] D10. A liquid processing apparatus as described in any one of clauses D5 to D9, wherein the well contains an absorbent material.
[0289] D11. Each of the first liquid storage container inlet channel and the second liquid storage container inlet channel is: One or more first channel regions, A second channel region, wherein the first depth of one or more first channel regions is less than the second depth of the second channel region. A liquid processing apparatus comprising any one of clauses D1 to D10.
[0290] D12. The liquid apparatus described in clause D11, wherein the second depth is equal to the thickness of the fluid layer. D13. The liquid processing apparatus according to clause D11 or D12, wherein the first width of one or more first channel regions is less than the second width of the second channel region.
[0291] D14. A liquid processing apparatus according to any one of the clauses D1 to D13, further comprising a third liquid storage container, the third liquid storage container being configured to open by creating an inlet and an outlet within the liquid storage container, and a network of channels further comprising a third liquid storage container inlet channel configured to provide a fluid connection between a pneumatic port and an inlet within the third liquid storage container when the third liquid storage container is opened.
[0292] D15. The liquid processing apparatus according to any one of the clauses D1 to D14, wherein the pneumatic port is a first pneumatic port, and the liquid processing apparatus further comprises a second pneumatic port configured to be in fluid communication with an outlet in a first liquid storage container.
[0293] D16. The liquid processing apparatus according to clause D15, wherein the second pneumatic port is configured to communicate fluidly with an outlet in the second liquid storage container.
[0294] D17. The liquid processing apparatus according to clause D15 or clause D16, further comprising a third pneumatic port configured to communicate with a fluid outlet in a second liquid storage container.
[0295] E1. A method for controlling the flow of liquid in a liquid processing apparatus, wherein the method is: Creating an inlet and outlet within the first liquid storage container of the liquid processing device in order to create a fluid connection between the pneumatic port of the liquid processing device and the inlet within the first liquid storage container, Creating an inlet and outlet within the second liquid storage container of the liquid processing device in order to form a fluid connection between the pneumatic port and the inlet within the second liquid storage container, Dispensing liquid from the outlet in the first liquid storage container by applying positive pressure through the pneumatic port, By applying positive pressure through the pneumatic port, liquid is dispensed from the outlet in the second liquid storage container. Methods that include...
[0296] E2. The method according to clause E1, wherein dispensing liquid from an outlet in a first liquid storage container includes opening a first liquid storage container valve configured to control the flow of liquid from an outlet in the first liquid storage container.
[0297] E3. The method according to clause E1 or clause E2, wherein dispensing liquid from an outlet in a second liquid storage container includes opening a second liquid storage container valve configured to control the flow of liquid from an outlet in the second liquid storage container.
[0298] E4. Creating an inlet and outlet in the third liquid storage container of the liquid processing device in order to create a fluid connection between the pneumatic port and the inlet in the third liquid storage container, By applying positive pressure through the pneumatic port, liquid is dispensed from the outlet in the third liquid storage container. The method described in any one of the clauses E1 to E3, further including the method described in any one of the clauses E1 to E3.
[0299] E5. The pneumatic port is the first pneumatic port, and the liquid processing apparatus is equipped with a second pneumatic port, and the liquid is dispensed from the outlet in the first liquid storage container. Opening one or more valves of the liquid processing device to create a fluid connection between the outlet in the first liquid storage container and the second pneumatic port, Applying positive pressure through the first air pressure port while venting through the second air pressure port The method described in any one of the clauses E1 to E4, including the method described in any one of the clauses E1 to E4.
[0300] E6. Dispensing liquid from the outlet in the second liquid storage container is Opening one or more valves of the liquid processing device to create a fluid connection between the outlet in the second liquid storage container and the second pneumatic port, Applying positive pressure through the first air pressure port while venting through the second air pressure port The method described in clause E5, including the method described in clause E5.
[0301] E7. The liquid processing apparatus is equipped with a third pneumatic port, and dispenses liquid from the outlet in the second liquid storage container. Opening one or more valves of the liquid processing device to create a fluid connection between the outlet in the second liquid storage container and the third pneumatic port, Applying positive pressure through the first air pressure port while venting through the third air pressure port The method described in clause E5 or E6, including the method described in clause E5 or E6.
[0302] F1. A liquid processing apparatus, wherein the liquid processing apparatus is A first chamber that is in fluid communication with a second chamber, A first pneumatic port that is in fluid communication with either the first chamber or the second chamber, A second pneumatic port that is in fluid communication with the other of the first and second chambers, A chamber inlet conduit configured to allow liquid to flow into the first chamber, A chamber outlet conduit configured to allow liquid to flow out of the second chamber, A third pneumatic port that communicates with the first liquid reagent capsule and fluid A liquid processing apparatus comprising a first liquid reagent capsule, wherein when the first liquid reagent capsule is opened, the first liquid reagent capsule selectively enters fluid communication with a first chamber or a second chamber.
[0303] F2. The liquid apparatus according to clause F1, wherein the flow of liquid through the chamber inlet conduit is controlled using a chamber inlet valve.
[0304] F3. The liquid apparatus according to clause F1 or clause F2, wherein the flow of liquid through the chamber outlet conduit is controlled using a chamber outlet valve.
[0305] F4. A liquid processing apparatus according to any one of clauses F1 to F3, wherein the flow of liquid from the first liquid reagent capsule is controlled using the first liquid reagent capsule valve.
[0306] F5. A liquid processing apparatus according to any one of the clauses F1 to F4, wherein the first pneumatic port is in permanent fluid communication with the first chamber.
[0307] F6. A liquid processing apparatus according to any one of the clauses F1 to F5, wherein the second pneumatic port is in permanent fluid communication with the second chamber.
[0308] F7. A first flow cell that is in fluid communication with the second chamber via a chamber outlet conduit, A second flow cell that is in fluid communication with the first flow cell, A bypass conduit configured to allow the liquid to bypass the second flow cell after flowing through the first flow cell, A liquid processing apparatus according to any one of clauses F1 to F6, further comprising:
[0309] F8. The liquid processing apparatus described in clause F7, wherein the flow of liquid through the bypass conduit is controlled using a bypass conduit valve.
[0310] F9. The liquid processing apparatus according to clause F7 or clause F8, wherein the first flow cell is in fluid communication with the waste chamber via the first flow cell outlet conduit.
[0311] F10. The liquid apparatus according to clause F9, which is dependent on clause F8, wherein the flow of liquid to the waste chamber via the first flow cell outlet conduit is controlled using a bypass conduit valve.
[0312] F11. The waste chamber is permanently ventilated, as described in Clause F9 or Clause F10 of the liquid treatment apparatus.
[0313] F12. A liquid processing apparatus according to any one of the clauses F7 to F11, wherein the second flow cell is in fluid communication with the waste chamber via the second flow cell outlet conduit.
[0314] F13. The liquid flow to the waste chamber via the second flow cell outlet conduit is controlled using the second flow cell outlet valve, as described in Clause F12.
[0315] F14. A liquid processing apparatus according to any one of clauses F1 to F13, wherein the third pneumatic port is in fluid communication with the second liquid reagent capsule.
[0316] F15. The liquid processing apparatus according to clause F14, wherein the flow of liquid from the second liquid reagent capsule is controlled using the second liquid reagent capsule valve.
[0317] F16. When the second liquid reagent capsule is opened, the second liquid reagent capsule selectively enters fluid communication with the second flow cell, as described in clause F14 or F15, which is dependent on clause F7.
[0318] F17. When the second liquid reagent capsule is opened, the second liquid reagent capsule is in fluid communication with the second flow cell via the second flow cell outlet conduit, as described in clause F16, which is dependent on clause F12.
[0319] F18. A liquid processing apparatus according to any one of clauses F14 to F17, wherein the third pneumatic port is in fluid communication with the third liquid reagent capsule.
[0320] F19. The liquid processing apparatus according to clause F18, wherein the flow of liquid from the third liquid reagent capsule is controlled using a third liquid reagent capsule valve.
[0321] F20. The liquid apparatus according to clause F18 or clause F19, wherein when the third liquid reagent capsule is opened, the third liquid reagent capsule selectively enters fluid communication with the first chamber.
[0322] F21. When the third liquid reagent capsule is opened, the third liquid reagent capsule selectively enters fluid communication with the first flow cell, as described in any one of clauses F18 to F20.
[0323] F22. A liquid processing apparatus according to any one of the clauses F1 to F21, further comprising a sample inlet chamber having fluid communication with a chamber inlet conduit.
[0324] F23. The liquid processing apparatus described in clause F22, wherein the flow of liquid from the sample inlet chamber is controlled using a sample inlet valve.
[0325] F24. The sample inlet chamber is permanently ventilated, as described in clause F22 or clause F23 of the liquid processing apparatus.
[0326] F25. A liquid processing apparatus according to any one of the clauses F22 to F24, further comprising a sample flow cell that is in fluid communication with a sample inlet chamber via a sample flow cell inlet conduit.
[0327] F26. The liquid processing apparatus according to clause F25, wherein the flow of liquid into the sample flow cell is controlled using a sample flow cell valve.
[0328] F27. The liquid processing apparatus according to clause F25 or clause F26, wherein the sample flow cell is in fluid communication with the sample flow cell waste chamber via the sample flow cell outlet conduit.
[0329] F28. A liquid processing apparatus according to clause F27, which is subject to clause F26, wherein the flow of liquid into the sample flow cell waste chamber is controlled using a sample flow cell valve.
[0330] F29. The sample flow cell waste chamber is in fluid communication with a second pneumatic port, as described in the liquid processing apparatus according to clause F27 or F28.
[0331] F30. A liquid apparatus according to any one of the clauses F1 to F29, further comprising a third chamber, the third chamber being in fluid communication with a first pneumatic port.
[0332] F31. The liquid apparatus according to clause F30, wherein the first pneumatic port is in permanent fluid communication with the third chamber.
[0333] F32. The liquid apparatus according to clause F30 or clause F31, wherein the flow of liquid into the third chamber is controlled using a third chamber valve.
[0334] F33. A liquid processing apparatus according to any one of the clauses F30 to F32, wherein the third chamber is in fluid communication with the first liquid reagent capsule.
[0335] F34. A liquid processing apparatus according to any one of the clauses F30 to F33, wherein the third chamber contains a dry reagent.
[0336] F35. A liquid processing apparatus according to any one of the clauses F1 to F34, wherein the first liquid reagent capsule is in fluid communication with the first chamber via a priming conduit.
[0337] F36. The liquid processing apparatus described in Clause F35, wherein the flow of liquid through a priming conduit is controlled using a priming conduit valve.
[0338] F37. A liquid processing apparatus according to clause F35 or F36, which is dependent on clause F25, wherein the priming conduit is in fluid communication with the sample flow cell inlet conduit via a priming conduit valve.
[0339] F38. A third pneumatic port is in fluid communication with an air / cleaning fluid supply conduit, as described in any one of clauses F1 to F37.
[0340] F39. The flow of air through the air / cleaning fluid supply conduit is controlled using an air supply valve, as described in Clause F38 of the liquid processing apparatus.
[0341] F40. The liquid processing apparatus according to clause F38 or F39, wherein the air / cleaning fluid supply conduit is in fluid communication with the chamber outlet conduit.
[0342] F41. A liquid processing apparatus according to any one of the first and second chambers, wherein one or more chambers contain a dry reagent, as described in any one of the F1 to F40 clauses.
[0343] G1. A method for measuring liquid in a channel of a liquid processing apparatus, wherein the method is: Applying a first pressure to move a first liquid from a first chamber through a first fluid path including two joints, Applying a second pressure to move the fluid through a second fluid path, which includes a portion of the first fluid path between two joints, such that the fluid displaces the volume of the first liquid between the two joints. Methods that include...
[0344] G2. The method according to clause G1, wherein the first pressure is applied using a first pneumatic port of the liquid processing apparatus, and the first pneumatic port is selectively in fluid communication with a first chamber.
[0345] G3. The method according to clause G1 or clause G2, wherein the second pressure is applied using a second pneumatic port of the liquid processing apparatus, and the second pneumatic port is in fluid communication with a second chamber.
[0346] G4. The method according to any one of the clauses G1 to G3, wherein a second pressure is applied to dispense the fluid and the first liquid into the third chamber.
[0347] G5. The method according to any one of the clauses G1 to G4, wherein a first pressure is applied to draw a first liquid from a first chamber through a first fluid path.
[0348] G6. The first chamber is permanently ventilated, as described in Clause G5. G6. The method according to any one of the clauses G1 to G4, wherein a first pressure is applied to dispense a first liquid from a first chamber through a first fluid path.
[0349] G7. The fluid is a second liquid, as described in any one of the clauses G1 to G6. G8. The method according to clause G7, wherein a second pressure is applied to dispense the second liquid from the second chamber through a second fluid path.
[0350] G9. The fluid is air, as described in any one of the clauses G1 to G6. G10. The method according to clause G9, wherein a second pressure is applied to supply air to a second fluid path via an air supply conduit.
[0351] G11. Applying a first pressure to move the first liquid from the first chamber through a first fluid path including two joints, Applying a second pressure to move the fluid through a second fluid path, which includes a portion of the first fluid path between two joints, such that the fluid displaces the volume of the first liquid between the two joints. The method according to any one of the clauses G1 to G10, further comprising measuring multiple volumes of a first liquid by repeating the process once or more times.
[0352] H1. A method for priming a fluid circuit of a liquid processing apparatus, wherein the method is: Applying a first pressure to move the liquid from the chamber to the first channel, The process involves continuously applying a first pressure to move the liquid until the liquid front surface moves beyond the junction on the first channel, the junction connecting the first channel to the second channel, and continuing to apply pressure. Applying a second pressure to move liquid from the chamber through the first channel and joint to the second channel, Methods that include...
[0353] H2. The method according to clause H1, wherein applying a first pressure includes applying a negative pressure to move a liquid.
[0354] H3. The chamber is permanently ventilated, as described in clause H2. H4. The method described in any one of the clauses H1 to H3, wherein applying a second pressure includes applying negative pressure to move a liquid.
[0355] H5. The method according to clause H4, which is dependent on clause H2, wherein applying a first pressure includes applying negative pressure to a first pneumatic port of the liquid processing apparatus, and applying a second pressure includes applying negative pressure to a second pneumatic port of the liquid processing apparatus.
[0356] H6. The method according to clause H1, wherein applying a first pressure includes applying a positive pressure to move a liquid.
[0357] H7. The method according to clause H6, wherein applying a first pressure includes applying a positive pressure to the first pneumatic port of the liquid processing apparatus while venting the second pneumatic port of the liquid processing apparatus.
[0358] H8. The method of Clause H6 or Clause H7, which includes applying a second pressure, which includes applying a positive pressure to move a liquid.
[0359] H9. The method of clause H8, which is dependent on clause H7, wherein applying a second pressure includes applying positive pressure to the first pneumatic port of the liquid processing apparatus.
[0360] H10. The method according to clause H9, wherein applying a second pressure includes applying positive pressure to the first pneumatic port of the liquid processing apparatus while venting the third pneumatic port of the liquid processing apparatus.
[0361] I1. A method for diluting a sample using a liquid processing apparatus, wherein the method is: Applying negative pressure to draw a certain volume of a first liquid into a first flow cell of a liquid processing device, Applying negative pressure to draw a certain volume of a first liquid into a first chamber of a liquid processing device, Applying positive pressure to dispense a certain volume of a second liquid into the first chamber, Applying positive pressure to dispense the first liquid and the second liquid from the first chamber to the second chamber, and Applying negative pressure to draw the first liquid and the second liquid from the second chamber to the first chamber. Repeating this once or multiple times, Applying positive pressure to move a mixture containing the first liquid and the second liquid from the first chamber or the second chamber to the second flow cell. Methods that include...
[0362] I2. The method according to clause I1, further comprising measuring the detection signal within a first flow cell.
[0363] I3. The method of clause I1 or clause I2, further comprising measuring the detection signal in a second flow cell.
[0364] I4. The method according to any one of the clauses I1 to I3, wherein the volume of the first liquid drawn into the first chamber is the measured volume of the first liquid.
[0365] I5. The method according to any one of the clauses I1 to I4, wherein the volume of the second liquid dispensed into the first chamber is the measured volume of the second liquid.
[0366] J1. A method for resuspending a dried reagent using a liquid processing apparatus, wherein the method is: Applying a first pressure to transfer a measured volume of a first liquid into a first chamber in order to resuspend one or more first dry reagents, wherein resuspending one or more first dry reagents forms the first reagent, and applying pressure Applying a second pressure to transfer a measured volume of a first liquid into a second chamber in order to resuspend one or more second dry reagents, wherein resuspending one or more second dry reagents forms the second reagents, and applying pressure Applying a third pressure to move the first reagent through at least one flow cell, Applying a fourth pressure to move the second reagent through at least one flow cell, Measure the detection signal within at least one flow cell and Methods that include...
[0367] J2. The method according to clause J1, wherein the volume of the first liquid transferred into the first chamber is the measured volume of the first liquid.
[0368] J3. The method according to clause J1 or clause J2, wherein the volume of the first liquid transferred into the second chamber is the measured volume of the first liquid.
Claims
1. A liquid processing apparatus, wherein the liquid processing apparatus is A first chamber that is in fluid communication with a second chamber, A first pneumatic port that is in fluid communication with one of the first chamber and the second chamber, A second pneumatic port that is in fluid communication with the other of the first chamber and the second chamber, A chamber inlet conduit configured to allow liquid to flow into the first chamber, A chamber outlet conduit configured to allow liquid to flow out of the second chamber, A third pneumatic port that communicates with the first liquid reagent capsule and fluid A liquid processing apparatus comprising, wherein when the first liquid reagent capsule is opened, the first liquid reagent capsule selectively enters fluid communication with the first chamber or the second chamber.
2. The liquid processing apparatus according to claim 1, wherein the first pneumatic port is in permanent fluid communication with the first chamber.
3. The liquid processing apparatus according to claim 1 or 2, wherein the second pneumatic port is in permanent fluid communication with the second chamber.
4. A first flow cell that is in fluid communication with the second chamber via the chamber outlet conduit, A second flow cell that is in fluid communication with the first flow cell, A bypass conduit configured to allow the liquid to bypass the second flow cell after flowing through the first flow cell, A liquid processing apparatus according to any one of claims 1 to 3, further comprising:
5. The liquid processing apparatus according to claim 4, wherein the first flow cell is in fluid communication with a waste chamber via a first flow cell outlet conduit.
6. The liquid processing apparatus according to claim 5, wherein the waste chamber is permanently ventilated.
7. The liquid processing apparatus according to any one of claims 4 to 6, wherein the second flow cell is in fluid communication with the waste chamber via a second flow cell outlet conduit.
8. The liquid processing apparatus according to any one of claims 1 to 7, wherein the third pneumatic port is in fluid communication with the second liquid reagent capsule.
9. A liquid apparatus according to claim 8, dependent on claim 4, wherein when the second liquid reagent capsule is opened, the second liquid reagent capsule selectively enters fluid communication with the second flow cell.
10. The liquid processing apparatus according to claim 8 or 9, wherein the third pneumatic port is in fluid communication with the third liquid reagent capsule.
11. The liquid processing apparatus according to claim 10, wherein when the third liquid reagent capsule is opened, the third liquid reagent capsule selectively enters fluid communication with the first flow cell.
12. The liquid processing apparatus according to any one of claims 1 to 11, further comprising a sample inlet chamber that is in fluid communication with the chamber inlet conduit.
13. The liquid processing apparatus according to claim 12, further comprising a sample flow cell that is in fluid communication with the sample inlet chamber via a sample flow cell inlet conduit.
14. The liquid processing apparatus according to claim 13, wherein the sample flow cell is in fluid communication with the sample flow cell waste chamber via the sample flow cell outlet conduit.
15. The liquid processing apparatus according to claim 13 or 14, wherein the sample flow cell waste chamber is in fluid communication with the second pneumatic port.
16. The liquid processing apparatus according to any one of claims 1 to 15, further comprising a third chamber, the third chamber being in fluid communication with the first pneumatic port.
17. The liquid processing apparatus according to claim 16, wherein the third chamber is in fluid communication with the first liquid reagent capsule.
18. The liquid processing apparatus according to any one of claims 1 to 17, wherein the third pneumatic port is in fluid communication with an air / cleaning fluid supply conduit and is configured to supply air through the air / cleaning fluid supply conduit.
19. The liquid processing apparatus according to any one of claims 1 to 18, wherein one or more of the first chamber, the second chamber, and the third chamber contain a dry reagent.
20. A liquid processing apparatus, wherein the liquid processing apparatus is A fluid layer comprising a chamber, the chamber is The opening at the upper end of the chamber A fluid layer comprising, A sealing layer configured to seal the opening of the chamber and Equipped with, The chamber comprises one or more protrusions, each of which extends from the inner wall of the chamber. A liquid processing apparatus wherein, when a reagent ball is housed in the chamber, one or more protrusions prevent the reagent ball from coming into contact with the sealing layer.
21. The liquid apparatus according to claim 20, wherein the opening is configured to allow the reagent ball to be inserted into the chamber.
22. The liquid processing apparatus according to claim 20 or 21, wherein one or more of the protruding portions are elastically deformable.
23. The liquid processing apparatus according to any one of claims 20 to 22, wherein each of the one or more protrusions extends from the inner wall of the chamber at the upper end of the chamber.
24. The liquid processing apparatus according to claim 23, wherein the opening is partially defined by each of the one or more protrusions.
25. The aforementioned chamber is A fluid inlet located below one or more of the aforementioned protrusions, An air outlet located in the inner wall and Furthermore, The liquid processing apparatus according to any one of claims 20 to 24, wherein the first maximum distance between the air outlet and the upper end base is less than or equal to the second maximum distance between the one or more protruding portions and the upper end.
26. Each of the one or more protrusions is, A first protruding portion extending from the inner wall of the chamber, A second protruding portion extending from the distal end of the first protruding portion, wherein the second protruding portion extends away from the upper end of the chamber and A liquid processing apparatus according to any one of claims 20 to 25, comprising: