Kit

Abstract

An example kit includes a base having a channel configured to receive a fluid, where the fluid includes a test sample to be tested on the kit, and a structure including at least a portion of a fluid conduit. The structure is configured to move relative to the base between a first position and a second position. In the first position, the channel and the fluid conduit are aligned to create a fluid connection between the channel and the fluid conduit, and in the second position, the channel and the fluid conduit are not aligned to block the fluid connection between the channel and the fluid conduit.

Description

Technical Field

[0001] This specification generally relates to exemplary kits and their uses. Background Art

[0002] Diagnostic test systems can use kits to perform tests. A kit includes one or more channels for delivering one or more liquids that can be used during the test process. Summary of the Utility Model

[0003] An exemplary kit includes a base and a structure. The base has a channel configured to receive a fluid, where the fluid includes a test sample to be tested on the kit. The structure includes at least a portion of a fluid conduit. The structure is configured to move relative to the base between a first position and a second position. In the first position, the channel and the fluid conduit are aligned to create a fluid connection between the channel and the fluid conduit. In the second position, the channel and the fluid conduit are misaligned to block the fluid connection between the channel and the fluid conduit. The exemplary kit can include, individually or in combination, one or more of the following features.

[0004] The structure can include a container having a chamber for holding a fluid. The fluid can include at least one of a reagent or a reaction buffer.

[0005] The exemplary kit can include a container having a chamber for holding at least a portion of a fluid. The container can include a fluid conduit. The structure can be between the container and the kit and is configured such that in the first position, the fluid conduit of the container, the fluid conduit of the structure, and the channel are fluidly aligned. The container can be stationary.

[0006] The exemplary kit can include a second channel configured to hold a fluid. The structure can be configured to move relative to the base between a first position, a second position, and a third position. In the third position, the fluid conduit and the second channel can be aligned to create a fluid connection between the second channel and the fluid conduit.

[0007] The structure can include a seal between the structure and the kit. The seal can be liquid-tight. The seal can include at least a portion of the fluid conduit.

[0008] An exemplary kit can include a compression mechanism to apply a force to the structure to push a portion of the structure against the kit. The compression mechanism includes at least one spring.

[0009] The structure can be configured to receive a force and slide between the first position and the second position in response to the force.

[0010] An exemplary kit may include a reservoir for receiving a test sample. At least some test samples may include a first portion of fluid. The channel may include a first section and a second section. The first section may be fluidly connected to the reservoir. In a first position, a fluid conduit is located between the first and second sections of the channel to create a fluid connection such that the second section of the channel can receive the first portion of fluid.

[0011] The structure may include a container having a chamber for holding at least a second portion of fluid. The chamber may include an outlet fluidly connected to the chamber. In a second position, the outlet of the chamber may be fluidly connected to the second section of the channel to enable the second section of the channel to receive at least the second portion of fluid from the chamber.

[0012] The structure may include at least a portion of a second fluid conduit, the channel may be a first channel, and the kit may include a second channel. In a second position, the second fluid conduit may be located between the first and second channels to fluidly connect the first and second channels.

[0013] The shape of the first channel may be serpentine. The serpentine shape may include expansion and contraction geometries. The kit may include a first port connecting the first channel to a first pressure control device and a second port connecting the second channel to a second pressure control device.

[0014] An exemplary kit includes a base having a channel for holding fluid and a structure movable relative to the channel. The structure includes a membrane. In the absence of an applied force, at least a portion of the membrane may be biased to raise relative to the base. At least a portion of the membrane may move between a raised position and a compressed position. The base may include a mesa between two sections of the channel. When the membrane is in the raised position, the two sections of the channel are fluidly connected in a fluid passage between the membrane and the mesa. When the membrane is in the compressed position, the membrane contacts the mesa and blocks the fluid connection between the two sections of the channel.

[0015] Exemplary methods include the following operations: adding a test sample to a channel of a kit; adding a reagent to the channel; identifying the amounts of the test sample and the reagent in the channel; mixing the test sample and the reagent in the channel to produce a mixture composed of the test sample and the reagent; determining whether an anomaly is present in the mixture; and if an anomaly is detected, outputting an alert, or if no anomaly is detected, performing a test based on the mixture. Exemplary methods may individually or in combination include one or more of the following features.

[0016] The amounts of test sample and reagent in the identification channel can include detecting a first edge of a fluid flow in the channel, where the fluid flow includes the test sample and reagent in the channel; detecting a second edge of the fluid flow in the channel; and determining the fluid volume in the channel based on the first edge and the second edge. The value of the first edge can be detected in a plurality of images of the channel, and the value of the second edge can be detected in the plurality of images. The value of the volume of the fluid in the channel can be detected based on the first edge and the second edge detected in each image. The method can include averaging the values of the volume to determine the volume of the fluid in the channel. Determining whether an anomaly exists in the mixture can include analyzing the plurality of images using a machine learning (ML) algorithm.

[0017] In some embodiments, machine learning based on using one or more images can be used to detect one or more fluid objects. In embodiments using one image, additional other images, such as images captured after one image during an assay, can be used to improve detection.

[0018] Any two or more features described in this specification (including the Summary section) can be combined to form embodiments not specifically described herein.

[0019] The systems, processes, devices including kits, and their variations or portions described herein can be implemented or controlled using a computer program product that includes instructions stored on one or more non-transitory machine-readable storage media and executable on one or more processing devices. The systems, processes, devices (including kits), and their variations or portions described herein can be implemented as an apparatus, method, or electronic system, or as a part of an apparatus, method, or electronic system that can include one or more processing devices and a memory to store executable instructions to implement various operations. The systems, processes, operations, devices including kits, and their variations described herein can be configured, for example, by design, configuration, arrangement, composition, placement, programming, operation, activation, deactivation, and / or control.

[0020] Details of one or more embodiments are set forth in the accompanying drawings and the description below. Other features, objects, and advantages will be apparent from the description and drawings, and from the claims. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 and Figure 2 is a block diagram showing a cross-sectional side view of a first exemplary embodiment of a kit. Figure 3 and Figure 4 is a block diagram showing a cross-sectional side view of a second exemplary embodiment of a kit. Figure 5 and Figure 6It is a block diagram showing a cross-sectional side view of a third exemplary embodiment of a kit.

[0022] Figure 7 and Figure 8 It is a block diagram showing a cross-sectional side view of a fourth exemplary embodiment of a kit.

[0023] Fig. 9 、 Fig.10 and Fig.11 It is a block diagram showing a cross-sectional side view and a top view of a fifth exemplary embodiment of a kit. Fig.12 and Fig.13 It is a block diagram showing a cross-sectional side view of a sixth exemplary embodiment of a kit. Fig.14 and Fig.15 It is a block diagram showing a cross-sectional side view of a seventh exemplary embodiment of a kit. Fig.16 It is a perspective partially transparent view of an eighth exemplary embodiment of a kit.

[0024] Fig.17 is Fig.16 exploded perspective view of the kit.

[0025] Fig.18 and Fig.19 are respectively a cross-sectional view and a top view of an exemplary channel included in the kit of Fig.16 the kit. Fig. 20 、 Fig.21 and Fig. 22 respectively show a top view, a bottom view and a perspective view of an exemplary container included in the kit of Fig.16 the kit.

[0026] Fig.23 、 Fig.24 and Fig.25 respectively show a top view, a bottom view and a perspective view of an exemplary seal included in the kit of Fig.16 the kit.

[0027] Fig.26 and Fig. 27 show a bottom view of an exemplary movable structure having a sliding valve function at different positions based on the kit of Fig.16 the kit.

[0028] Fig.28 、 Fig.29 、 Fig.30 、 Fig.31 、 Fig.32 and Fig.33 show a top view of the kit of Fig.16 at different times during an exemplary multi-stage diagnostic test process.

[0029] Fig.34 is included in the use Fig.16 Flowchart of example operations included in an example multi - stage diagnostic test procedure performed by a kit.

[0030] Fig.35 Flowchart of example operations included in an example process for training a model for detecting the edge of a fluid flow.

[0031] Fig.36 Flowchart of example operations included in an example process for detecting the edge of a fluid flow.

[0032] Fig.37 Flowchart of example operations included in an example process for determining the volume of liquid in a kit channel.

[0033] Fig.38 Flowchart of example operations included in an example process for training a model for detecting anomalies in a fluid flow.

[0034] Fig.39 Flowchart of example operations included in an example process for detecting anomalies in a fluid flow.

[0035] Fig.40 Block diagram of an exemplary diagnostic test instrument.

[0036] Fig.41 Bottom perspective view of an example chamber for holding liquid.

[0037] Fig.42 Side view of another example chamber for holding liquid.

[0038] Fig.43 Top view of an exemplary reaction chamber.

[0039] Like reference numerals in different figures represent like elements. Detailed Description

[0040] Examples of kits having one or more fluid channels and / or valve functions are described herein, such as sliding valves or other forms of valves that can perform in a functionally similar manner to these valves. In an example kit of this type (“kit”), the sliding valve is controllable to open a fluid channel (“channel”) of the kit (“kit”) to allow fluid to enter or leave the channel or to close the channel to block fluid from entering or leaving the channel. Using a valve structure of the type described herein can simplify the configuration of the kit and the control of the kit. For example, the valve structure can use a single movable part to create a fluid connection on the kit. This in turn can be simply used by a control mechanism for control to create a fluid connection on the kit.

[0041] Examples of fluids that can be stored on and / or added to the kit include, but are not limited to, test samples such as whole blood or components of whole blood such as plasma, or derivatives of whole blood. Other examples of fluids that can be stored on and / or added to the kit include liquid reagents, liquid reaction buffers, or any other type of liquid sample to be tested or used in testing.

[0042] The kit can also include one or more dry reagents, such as pre-loaded reagents at selected locations, to be mixed with the liquid prior to testing.

[0043] Examples of reagents that can be used include, but are not limited to, colorimetric dyes, enzymes, biological reagents, enzymes, antibodies, and proteins. Examples of dry reagents include latex particles, chromogenic substrates, anti-Xa enzymes deposited in liquid form on the kit and then dried in the channels.

[0044] Examples of tests that can be performed using the kit include, but are not limited to, D-dimer tests (which look for the presence of D-dimers in blood), anti-factor Xa tests (which measure the levels of plasma heparin (unfractionated heparin [UH] and low molecular weight heparin [LMWH]) in the test sample), and hemostasis tests. Other examples of tests that can be performed using the kit include, but are not limited to, agglutination assays, immunoassays, enzyme assays, kinematic assays, and any multi-stage wet chemical assays.

[0045] The following Figures 1 to 15 shows examples of different types of sliding valves that can be used to create fluid connections to and from channels on the kit. Figures 16 to 33 Shows examples of sliding valves for creating fluid connections to and from channels on the kit and for fluid flow through the channels. Fig.34 、 35 、36, 37, 38, and 39 show examples of processes that can be used with any fluid channel, including but not limited to the fluid flow channels on the kit described herein or any other type of kit having one or more channels through which fluid flows.

[0046] Figure 1 and Figure 2 Shows an example kit 100 having a structure 111 that includes a groove 120 aligned with fluid inlets / outlets ("I / O") 104, 107, thereby creating a fluid connection between the fluid I / Os via the groove. One of the I / Os can be connected to the exterior of the kit, and the other I / O can be connected to a channel in the kit. The exterior of the kit can include, for example, a reservoir for holding a test sample, a liquid reagent, or both. The fluid connection enables fluid to flow between the exterior of the kit (e.g., the reservoir) and the channel.

[0047] The kit 100 includes a base 101, a movable structure 111, an optional housing 130, and its associated components. Figure 1 and Figure 2 One or more actuators 122 that interact with the kit 100 in the manner described below are also shown.

[0048] The base 101 can be made of plastic, polymer, glass, acrylic, or any other deformation-resistant material. In some embodiments, all or at least a portion of the base 101 can be made of a transparent or translucent material to enable optical testing using the kit. The base 101 includes an I / O 107 and a channel 102 (which includes an I / O 104). The I / O 107, I / O 104, and channel 102 are all examples of fluid conduits ("conduits") because each of these structures is configured for fluid to flow therethrough.

[0049] In some embodiments, the channel 102 can be a microchannel that is configured to receive a test sample and / or a reagent to mix the test sample and the reagent, and / or to enable testing of the resulting mixture. In some embodiments, the channel 102 can have a hydraulic diameter of less than 1 millimeter (1 mm); however, the channel 102 is not limited to this size. When viewed in the direction of arrow 103, the channel 102 can be linear, curved, serpentine, meandering, zigzag, or have any other shape. The cross-section of the channel 102 in a direction perpendicular to the flow direction within the channel can be circular or non-circular, such as rectangular or square.

[0050] The I / O 104 is fluidly connected to the channel 102 to allow fluid to enter the channel 102. The I / O 104 is thus referred to as the channel I / O. For example, as Figure 2 shown, fluid can flow into the channel I / O 104 in the direction of arrow 106 or flow out of the channel I / O 104 in the direction opposite to arrow 106.

[0051] The I / O 107 can be fluidly connected to a fluid reservoir (not shown) external to the storage kit 100 to allow fluid to enter the storage kit 100 or to receive fluid from the storage kit 100. For example, as Figure 2 shown, fluid can flow from the fluid reservoir into the kit I / O 107 in the direction of arrow 109, or flow out of the kit I / O 107 in the direction opposite to arrow 109. For example, a test sample and / or a reagent can flow from a source into the kit I / O 107. For example, a mixture of a test sample and a reagent can flow out of the kit I / O 107. The I / O 107 is referred to as the kit I / O.

[0052] The kit 100 includes a movable structure 110. The structure 110 is movable in the direction of arrow 117 and includes a groove that fluidly connects I / O 104 and I / O 107. In this example, the structure 110 includes a block 111 and a fluid seal ("seal") 112. The block 111 can be hollow or solid; it can be a rectangular prism, a rectangular cuboid, or any other shape. The block 111 can be made of plastic, acrylic, metal, or other materials that resist or at least partially resist deformation.

[0053] The seal 112 can be made of an elastomer, rubber, silicone, or any other type of elastic material that is deformable and capable of forming a fluid seal with the surface 115 of the base 101. The fluid-impermeable seal reduces the chance of inadvertent fluid leakage from the I / O and channels 102 during fluid movement. The seal 112 and the base 101 can be made of materials that together produce a sufficiently low coefficient of friction (e.g., from 0.05 to 0.2) to allow the structure 110 to slide across the surface 115 of the base 101 in the direction of arrows 117 and / or 118. This sliding enables the creation of a fluid connection between I / O 104, I / O 107, and the groove 120.

[0054] The structure 110 also includes a groove 120. The groove 120 is a notch or depression within a portion of the structure 110 that creates an open space between the structure 110 and the base 101 through which fluid can flow. In this example, the groove is entirely within the seal 112; however, in other embodiments, the groove can extend into the block 111.

[0055] The kit can be used with one or more actuators (e.g., actuator 122) to move the structure 110. The actuator may or may not be considered part of the kit. The actuator 122 can be an electromechanical linear actuator. For example, the actuator 122 can be a solenoid-driven actuator. Examples of linear actuators that can be used include, but are not limited to, a plunger or a slider body operated by a stepper motor.

[0056] The actuator 122 is configured and controlled by a control system such as Fig.40 the electronic control system 2201 (described below) to drive to the structure 110. For example, the actuator 122 can be electronically controlled to move in the direction of arrows 117 and / or 118. In the example, when moving in the direction of arrow 117, the actuator contacts the structure 110. A continuous force applied to the actuator 122 in the direction of arrow 117 causes the structure 110 to move in the direction of arrow 117.

[0057] Kit 100 may optionally include a housing 125 and a compression mechanism 128. In some embodiments, these components may be omitted from the kit 100. The housing 125 may surround the structure 110 and is used to restrict its movement in the directions of arrows 117, 118. The compression mechanism may force the structure 110 against the seal 112 to create a liquid-tight fit therebetween.

[0058] The housing 125 may be made of plastic, acrylic, metal, or other materials that resist deformation. The housing 125 may be connected (e.g., fixed) to the base 101 to prevent relative movement between the housing 125 and the base 101 when the structure 110 moves. The housing 125 may partially surround the structure 110, but is large enough to allow the structure 110 to move relative to the housing. The housing 125 may also include one or more openings 127 to allow one or more actuators (such as actuator 122) to move into, out of, and through the housing.

[0059] The compression mechanism 128 is configured to apply a downward force on the structure 110 in the direction of arrow 103 to push the seal 112 against the surface 115 of the base 101 to facilitate a liquid-tight seal between the seal 112 and the base 101 without preventing the structure 110 from moving on the surface of the base 101. The compression mechanism 128 may be or include one or more high-density polyethylene (HDPE) spacers or springs to apply the force. The force may be controlled by spring force or simply by distance control as a spacer. The HDPE material may be used to limit friction when the subassembly moves. The compression mechanism 128 may be fixed (e.g., connected) to the block 111 but not to the housing 125 to allow the compression mechanism to move within the housing together with the block 111 when the housing is present.

[0060] The structure 110 is configured to operate as a sliding valve to control the flow of fluid into or out of the channel 102. More specifically, the actuator 122 is controlled by a control system to move the structure 110 between Figure 1 a "closed" position and Figure 2 an "open" position. In the closed position, the structure 110 (seal 112 in this example) covers the kit I / O 107 and the channel I / O 104 and forms a fluid seal over the kit I / O 107 and the channel I / O 104. Thus, the structure 110 blocks the kit I / O 107 and the channel I / O 104 (i.e., the kit I / O and the channel I / O are not aligned with the groove 120), thereby blocking the flow of fluid therethrough. This position may be used during storage and transportation of the storage kit, for example, before a test performed using the storage kit. In Figure 2In the open position, the groove 120 is aligned with the kit I / O 107 and the channel I / O 104. This alignment creates a fluid connection between the kit I / O 107, the groove 120, the channel I / O 104, and the channel 102, which allows fluid to flow into the channel 102 from outside the kit and allows fluid to flow from the channel 102 to the outside of the kit. This position can be used during testing with the kit, for example, to introduce a test sample, reagent, and / or other liquid into the kit.

[0061] In this example, to move from the Figure 1 closed position to the Figure 2 open position, the actuator 122 is controlled to move in the direction of arrow 118, thereby causing the structure 110 to also move in the direction of arrow 118. The amount of movement is sufficient to align the groove 120 with the kit I / O 107 and the channel I / O 104. The resulting fluid connection allows fluid to flow from the kit I / O 107 through the groove 120 in the direction of arrow 109, through the channel I / O 104 in the direction of arrow 109, and into the channel 102, or in the opposite direction. Positive or negative pressure applied by one or more pressure control devices (not shown) and / or capillary action and / or other mechanisms can be used to control fluid flow. The fluid can be, for example, a test sample or a liquid reagent. In some embodiments, the channel 102 can include a dry reagent that is mixed with the test sample and / or liquid reagent to enable a test to be performed, such as the test described below with respect to Figures 28 to 34 the test.

[0062] In Figure 1 and Figure 2 the example, the kit 100 is biased closed. This means that, in the absence of an applied force, the kit 100 is in the Figure 1 configuration. In some embodiments, the kit 100 can be biased open. This means that, in the absence of an applied force, the kit 100 is in the Figure 2 configuration. A force can be applied to the structure 110 by one or more actuators in the direction of arrow 117 to move the structure 110 to the Figure 1 closed position. In cases where contents such as a dry reagent are pre-stored in the channel 102 of the kit, a biased closed configuration can be used, while in cases where no contents are pre-stored in the kit, a biased open configuration can be used.

[0063] In some embodiments, the actuator 122 can be physically connected to the structure 110 to pull the structure 110 from the open position to the closed position. In some embodiments, the actuator 122 can be located on the side 130 of the kit 100 to push the structure 110 from the open position to the closed position. In some embodiments, there can be two actuators - one on each of the sides 130 and 131 of the kit 100 - which are configured and controlled by a control system to move the structure 110 between the open and closed positions.

[0064] Figure 3 and Figure 4 is a block diagram of another example kit 200 having a base 101 similar to Figure 1 and Figure 2 and a movable structure. The movable structure has a chamber that can contain a pre-stored liquid and I / O to the chamber, which is different from the structure 111 of Figure 1 and Figure 2 in that the structure 111 of Figure 1 and Figure 2 does not contain a pre-stored liquid. The structure is movable to align the I / O of the chamber with the I / O of the kit channel, thereby creating a fluid connection between the channel and the chamber. Such a configuration can be used to move or release a liquid (e.g., a reagent) from the chamber to the channel. A test sample can be provided directly (e.g., by pipetting) or through another inlet (not shown) to the channel for mixing with the liquid from the container.

[0065] Kit 200 includes a base 201, a movable structure 210, an optional housing 230, and its associated components. Figure 3 and Figure 4 One or more actuators 222 that interact with the storage kit 100 in the manner described below are also shown.

[0066] Base 201 includes a channel 202 and a channel I / O 204, which can be similar or identical to the channel 102 and the channel I / O 104 of Figure 1 and Figure 2 . The composition of the base 201 can be similar or identical to the composition of the base 101 of Figure 1 and Figure 2 .

[0067] In Figure 3 and Figure 4In the example, structure 210 includes a container 211 having a fluid - sealed chamber 235 configured to hold fluid, as described above. The internal volume of the container can be designed based on the volume requirements of the assay to be used in the kit. In some examples, container 211 serves as a storage container for storing reagents, reaction buffers, or other materials required to perform tests on test samples. For example, the container can include a liquid (e.g., a reagent) required for a particular assay. The container enables such materials to be pre - measured and pre - packaged, thus facilitating the testing process, e.g., by eliminating the need for the system or user performing the test to measure the materials.

[0068] Container 211 can be made of plastic, acrylic, metal, or other materials that resist deformation. Container 211 also includes I / O 236, which is fluidly connected to the interior of chamber 235.

[0069] Structure 210 includes a seal 212 between the surface 215 of container 212 and base 201. Seal 212 can be the same type of seal as Figure 1 and Figure 2 seal 112. In this example, container I / O 236 extends completely through seal 212 into chamber 235. Structure 210 abuts against surface 215 of base 201 to form a liquid - tight seal against the base.

[0070] Housing 225 can be the same type of housing as Figure 1 and Figure 2 housing 125, except that housing 225 does not need to include compression mechanism 128. In this example, the top plate 238 of housing 225 is configured and arranged to abut against the top of structure 210 such that structure 210 is forced against surface 215 with sufficient force to create a fluid - tight seal, but not with enough force to prevent structure 210 from sliding across surface 215.

[0071] Actuator 222 can be the same type of actuator as Figure 1 and Figure 2 actuator 122. Actuator 222 is controlled by a control system to move structure 210 between Figure 3 the open position of Figure 4move between the closed positions. In the open position, the container I / O 236 is aligned with the channel I / O 204 and opens the fluid connection between the channel and the container. That is, this alignment creates a fluid connection between the chamber 235, the container I / O 236, the channel I / O 204, and the channel 202, allowing fluid to flow between the chamber 235 and the channel 202. In the closed position, the structure 210 (in this example, the seal 212) covers the channel I / O 204 and forms a fluid seal over the channel I / O 204 (the channel I / O 204 and the container I / O 236 are also misaligned), closing the channel to the contents of the container. Thus, the structure 210 blocks the channel I / O 214, blocking the fluid between the chamber 235 and the channel 202

[0072] The actuator 222 is controlled by a control system to move in the direction of arrow 218, moving the structure 210 from the open position to the closed position. In Figure 3 and Figure 4 example, the kit 200 is biased open. In some embodiments, the kit 200 can be biased closed. The kit can be biased closed when it is desired to prevent the contents of the container from entering the channel before testing. To move from the closed position to the open position, a force can be applied to the structure 210 in the direction of arrow 217 by one or more actuators to move the structure 210 to the open position. This force can be applied by one or more actuators, as described above with respect to Figure 1 and Figure 2 using one or more actuators on one or both sides of the kit 200.

[0073] Figure 5 and Figure 6 is a block diagram of another example kit 200 having a base and a movable structure similar to the base 101 of Figure 1 and Figure 2 . The movable structure has a chamber that can contain a pre-stored liquid and an I / O to the chamber. The structure is movable to align the I / O of the chamber with the I / O of the kit channel, creating a fluid connection between the channel and the chamber. Such a configuration can be used to move a liquid (e.g., a reagent) from the chamber to the channel. A test sample can be provided directly (e.g., by pipetting) or through another inlet (not shown) to the channel for mixing with the liquid from the container.

[0074] In this example, the base 301 can have Figure 3 and Figure 4 all the properties of the base 201 of Figure 2 including the channel 302 and the channel inlet 304. The structure 310 can have Figure 3 and Figure 4 All properties of the actuator 222. The housing 325 may have Figure 3 and Figure 4 All properties of the housing 225 of Figure 1 and Figure 2 except that in this example, the compression mechanism 328 can be used to apply downward pressure to create a fluid seal between the seal 312 of the structure 310 and the base 301 while still allowing movement of the structure controlled by the actuator 322. The compression mechanism 328 can have the same structure and function as the compression mechanism 128 of

[0075] As with the kit 200, the kit 300 is biased to open but can also be biased to close, and its structure 310 can be moved by moving one or more actuators on one or both sides of the kit 300. The actuator 322 is controlled by a control system to move the structure 310 between Figure 5 the open position of Figure 6 and

[0076] Figure 7 and Figure 8 are block diagrams of the kit 400, which is a variant of the kits of Figure 5 and Figure 6 The movable structure in the kit 300 contains multiple (e.g., two) chambers, each of which can contain a pre-stored liquid, such as two different reagents. The I / O of each chamber can be individually aligned with the I / O of the kit channel to create a fluid connection between the corresponding chamber and the channel. Such a configuration can be used to move liquids (e.g., reagents) from multiple chambers to the channel in a predefined order (which can be specified by the control system). The test sample can be provided directly (e.g., by pipetting) or through another inlet (not shown) to the channel for mixing with the liquid (e.g., reagent) from the container.

[0077] In this example, the base 401 may have Figure 5 and Figure 6 All attributes of the base 301, including channels 402 and channel I / O 404. The actuator 422 may have Figure 5 and Figure 6 All attributes of the actuator 322. The housing 425 may have Figure 5 and Figure 6 All attributes of the housing 325. The compression mechanism 428 may have Figure 5 and Figure 6 All attributes of the compression mechanism 328.

[0078] The structure 410 includes a container 411 having two chambers 440 and 441. In some embodiments, there may be more than two chambers (e.g., three, four, five, etc. chambers). Chambers 440 and 441 are fluidly isolated from each other.

[0079] Each chamber 440, 441 may be empty or hold a fluid, such as those described herein. The fluids in different chambers may be different, e.g., different reagents, different reaction buffers, etc. Each chamber 440, 441 includes a corresponding container I / O 444, 445. Each container I / O 444 and 445 may be a fluid conduit of the type described herein. Each container I / O extends through a seal 412 and through the container 411 into its corresponding chamber.

[0080] The structure 410 may move along the surface 415 of the base 401 to align one of the container I / O 444 or 445 with the channel I / O 404, thereby creating a fluid connection between the corresponding chamber and the channel 402. For example, when the container I / O 445 is aligned with the channel I / O 404 ( Figure 7 ), a fluid connection is created between the chamber 441, the container I / O 445, the channel I / O 404, and the channel 402, thereby allowing fluid to flow between the chamber 441 and the channel 402. For example, when the container I / O 444 is aligned with the channel I / O 404 ( Figure 8 ), a fluid connection is created between the chamber 440, the container I / O 444, the channel I / O 404, and the channel 402, thereby creating a fluid connection between the chamber 440 and the channel 402.

[0081] Similar to the case of kit 300, the movement of structure 410 can be controlled by moving one or more actuators on one or both sides of kit 400. In the example, actuator 422 can be configured and controlled by a control system to move structure 410 to align container I / O 444 or 445 with channel I / O 404. This movement can be based on the order of outputting different liquids into channel 402. For example, the liquid from container 440 can be output first, and then the liquid from container 441. This information can be programmed into the control system and used to control the operation of the actuator. Actuator 422 can also be controlled to move structure 410 such that neither container I / O 444 nor 445 is aligned with channel I / O 404 (i.e., channel I / O 404 is not aligned with either container I / O). In this configuration, seal 412 is aligned with channel I / O 404, thereby blocking the fluid connection.

[0082] Figure 9-11 FIG. is a block diagram of another example kit 500. In this example, the movable structure includes a chamber that is empty or holds pre-stored liquid. The I / O of the chamber can be aligned with the I / O of one of the multiple channels on the kit, thereby creating a fluid connection between the chamber and one of the channels on the kit. The structure is also movable to align the I / O of the chamber with the I / O of different channels in sequence, for example. Such a configuration can be used to move a liquid (such as a reagent) from a single chamber to one or more channels on the kit. The test sample can be provided directly (e.g., by pipetting) or through another inlet (not shown) to the channel for mixing with the liquid from the chamber.

[0083] Structure 510 can have Figure 3 and Figure 4 all the properties of structure 210. Actuator 522 can have Figure 3 and Figure 4 all the properties of actuator 222. Housing 525 can have Figure 3 and Figure 4 all the properties of housing 225. Compression mechanism 528 can have Figure 5 and Figure 6 all the properties of compression mechanism 328 to create a fluid-tight seal between seal 512 and base 501 while still allowing the movement of structure 510.

[0084] Also refer to Fig.11 which is a downward view along Fig. 9 arrow 550. In this example, base 501 includes a plurality (three in this example) of channels 550a, 551a, and 552a having corresponding channel I / Os 550, 551, and 552. Although the channels are shown in Fig.11is linear, but the channels can have any shape, such as serpentine, meandering, zigzag, or irregular shapes. In Fig. 9 and Fig.10 the channels are shown in a transverse (widthwise) cross-section (i.e., the channels extend into and / or out of the page), while in Figures 1 to 8 the channels are shown in a longitudinal (lengthwise cross-section). Although Figure 9-11 shows three channels, any number of channels, such as two, four, five, six, or more channels, each having a corresponding channel I / O, can be included on the base 501. The three channels can be fluidly isolated, or two or more of them can be fluidly connected downstream of the structure 510.

[0085] Similar to the case of the kit 300 with respect to Figure 5 and Figure 6 the movement of the structure 510 can be controlled by moving one or more actuators on either or both sides of the kit 500. In this example, the actuator 522 is controlled by a control system to move the structure 510 such that the container I / O 536 is aligned with one of the channel I / Os 550, 551, or 552, thereby creating a fluid connection between the chamber 535, the container I / O 536, one of the channel I / Os 550, 551, or 552, and a corresponding channel 550a, 551a, or 552a connected to the channel I / O 550, 551, or 552. The actuator 522 can be controlled by the control system to move the structure 510 such that the container outlet 536 is aligned with different channels at different times.

[0086] Fig. 9 shows a situation where the actuator 522 has moved the container I / O 536 from alignment with the channel I / O 550 to alignment with the channel I / O 551. Fig.10 shows a situation where the actuator 522 has moved the container I / O 536 from alignment with the channel I / O 551 to alignment with the channel I / O 552. As described above, the movement can be based on the order of outputting different liquids (e.g., reagents) to the channels. This information can be programmed into the control system and used to control the operation of the actuator. The actuator 522 can also be controlled to move the structure 510 such that no channel I / O is aligned with the container I / O 536 (i.e., each channel I / O is misaligned with the container I / O 536). In this configuration, the seal 512 is aligned with each channel I / O 550, 552, and 552, thereby preventing fluid connection with any channel.

[0087] In some embodiments, Figure 7 and Figure 8 the structure 410 can replace Figure 9-11Structure 510 in. In such an implementation, the actuator 522 can be controlled to move to align different container I / Os with different channel I / Os. The alignment can be programmed into the control system and used to control the operation of the actuator. For example, in the presence of two containers, the actuator 522 can be moved to align the I / O of one container with one of the I / Os 550, 551, or 552, and the other I / O of the other container with a different one of the I / Os 550, 551, or 552.

[0088] Fig.12 and Fig.13 is a block diagram of another example kit 600. In this example, the kit includes a container of the type described herein, which has a chamber that is empty or contains a pre-stored liquid. The kit also includes a base. Both the container 611 and the base 601 include aligned I / Os 636 and 634, respectively. There is an intermediate structure between the container and the base. The intermediate structure contains I / Os and is movable relative to the container and the base. When the I / O of the intermediate structure is aligned with the I / Os of the container and the base, a fluid connection is created between the container and the base. When the I / O of the intermediate structure is not aligned with the I / Os of the container and the base, no fluid connection is created between the container and the base. This configuration may be advantageous because it does not require the movement of the container. For example, the movable structure can be smaller than the container and lighter than the container. Therefore, compared to the container, the movable structure may require less force and thus a smaller actuator to move.

[0089] The container 611 can have Figure 5 and Figure 6 all the properties of the container 311, including the container I / O 636. The seal 612 can have Figure 5 and Figure 6 all the properties of the seal 312. The actuator 622 can have Figure 5 and Figure 6 all the properties of the actuator 322. The base 601 can have Figure 5 and Figure 6 all the properties of the base 301, including the channel 602 and the channel I / O 604. The base also includes a seal 650 on its surface or at least partially embedded therein, which is separate from the seal 612. The seal 650 can have all the properties of the seal 612. The channel I / O 604 can be partially within the seal 650 and pass through the seal 650, as shown. The channel I / O 604 and the container I / O 636 are vertically aligned.

[0090] In this example, there is a structure 610 between the container 611 and the base 601. Specifically, the structure 610 is sandwiched between the container seal 612 and the base seal 650. The structure 610 can be made of the same material as the container 611 or a different material, such as plastic, polymer, glass, acrylic. The structure 601 can be substantially planar on its upper and lower surfaces so as to enable a liquid-tight seal to be produced for each of the container seal 612 and the kit seal 650 while maintaining a low coefficient of friction so that the structure can move. The structure 610 can also include an I / O 651 extending between its upper and lower surfaces through which fluid can flow.

[0091] In this example, the container 611 is stationary (and the base 601 is also stationary), and the structure 650 is configured to move relative to the container 611 and the base 601 in the directions of arrows 617 and / or 618. As in the case of the structure 111, the movement of the structure 601 can be controlled by moving one or more actuators on one or both sides of the kit 600. In Fig.12 the example, the structure 601 is in the open position, in which the chamber 635, the container I / O 636, the structure I / O 651, the channel I / O 604, and the channel 602 are in fluid communication. In Fig.13 the example, the actuator 622 is controlled by a control system to move the structure 601 to the closed position, in which the structure I / O 651 is misaligned with the container I / O 636 and the channel I / O 604 and is blocked by the seals 612 and 650. Alternatively, more than one actuator can be controlled by the control system to move the structure from the closed position to the open position, as described above.

[0092] Fig.14 and Fig.15 is a block diagram of another example kit 700. In this example, the membrane or foil is controllable to open or close the fluid connection between two channels on the kit or between two sections of the same channel. For example, the structure can be movable to raise the membrane to create a fluid connection between the channels or compress the membrane to close the fluid connection between the channels. The liquid in the channel can be, for example, a test sample or a combination of a reagent and a test sample introduced at a location not shown in Fig.14 and Fig.15 into the kit.

[0093] The kit 700 includes a base 701, a flexible membrane ("membrane") 704, and a structure 720. The base 701 can have the same composition as the other bases described herein. The base 701 includes channels 709 and 710 separated by a bench 712.

[0094] A flexible membrane (“membrane”) 704 covers at least a portion of the base, including channels 709, 710, and the mesa 712. The membrane 705 can be made of an elastic material, rubber, silicone, or other types of flexible materials.

[0095] In Fig.14 the configuration (open position), at the position of the mesa 702, the membrane 704 is biased to rise relative to the mesa 712. That is, in the absence of a downward force (arrow 715) on the membrane 704, the membrane remains above the mesa 712, leaving a space 717 between the membrane 704 and the mesa 712. This space 717 defines a conduit that constitutes a fluid connection between the first channel 709 and the second channel 710.

[0096] The structure 720 can move in the direction of arrows 722 and / or 723. The structure 720 can be a solid structure made of, for example, plastic, acrylic, metal, or other materials resistant to deformation. The structure 720 and the membrane 704 can be made of materials that together produce a sufficiently low coefficient of friction (e.g., 0.05 to 0.2) to allow the structure 720 to slide over the membrane 704 in response to a force applied to the structure 720 in the direction of arrows 722 and / or 723. The structure 720 also includes a notch 731 or indentation that is wider than the mesa 712.

[0097] The force against the structure 720 can be applied by an actuator 730. The actuator 730 can have Figure 3 and Figure 4 all the properties of the actuator 222.

[0098] In Fig.14 the exemplary configuration, the structure is positioned such that the notch 731 is aligned with the mesa 712, thereby allowing a fluid connection between the first channel 709 and the second channel of the channel 710. Because the notch 731 is wider than the mesa, the membrane remains elevated to achieve a fluid path between the channels. More specifically, the fluid 733 in the channel 709 can flow into the channel 710 in the direction of arrow 734, and vice versa. The actuator 730 can be controlled by a control system to produce this alignment, or the kit 700 can be biased by this alignment. The actuator 730 can be controlled by the control system to move in the direction of arrow 722 to move the notch 731 out of alignment with the mesa 712. This movement causes the bottom surface 740 of the structure 720 to flatten the membrane 704, thereby forcing the membrane 704 against the mesa 712, as Fig.15 shown. The membrane and the mesa form a fluid seal that fluidly isolates the first channel 709 from the second channel 710, thereby blocking fluid flow between the two channels.

[0099] Alternatively, one or more actuators on one or both sides of the structure 720 can be controlled by a control system to move the structure 720 from the closed channel position ( Fig.15 ) to the open channel position ( Fig.14 ) in the manner described above.

[0100] Figures 16 to 27 FIG. is a diagram showing components of another exemplary kit 800 including the function of a valve (e.g., a sliding valve). The kit 800 can have the advantage that both a test sample and a reagent can be introduced into a channel of the kit using a single slidable structure, and (one or more) parts of the channel can be a place where a reaction or a test occurs. The sliding action can also use a single slidable structure to enable waste from the kit to move into a waste channel different from the test channel.

[0101] The kit 800 can be used in a diagnostic test instrument that performs a multi-stage assay test. The multi-stage test includes mixing a test sample with a first reagent to produce a first mixture, and then mixing the first mixture with a second reagent to produce a second mixture, and so on. Examples of multi-stage assay tests include, but are not limited to, D-dimer tests (which look for the presence of D-dimers in blood), anti-factor Xa tests (which measure the level of plasma heparin (unfractionated heparin [UH] and low molecular weight heparin [LMWH]) in a test sample), and hemostasis tests.

[0102] Specifically referring to FIGS. 168 and 17, the exemplary kit 800 includes a base 801, a structure 820, a container 821, a compression mechanism 846, and a housing 845.

[0103] All or part of the base 801 can be made of a transparent material, such as poly(methyl methacrylate), acrylic (PMMA), or the materials used for other exemplary kits described above. The base 801 includes a reservoir 802. The reservoir 802 is a chamber for receiving a test sample, which can be a fluid, such as whole blood, a blood-based fluid, a body fluid, or any other testable fluid. The test sample can be manually input into the reservoir 802 from a vial, or automatically input using a robot, such as a robotic pipette that inputs the test sample into the reservoir 802. In some embodiments, the reservoir 802 includes one or more membrane filters or one or more different types of plasma separation filters (not shown). These filters are used to separate plasma from whole blood. As described below, the plasma moves through the filter and into the reaction channel of the kit, leaving other components of the blood in the reservoir.

[0104] In some embodiments, reservoir 802 may further include one or more reagents to be mixed with the test sample. For example, the reagents may be pre-loaded into the kit during manufacturing. The reagents may be dry, such as lyophilized or beaded, or liquid. In some cases, the reagents may not be present in reservoir 802.

[0105] Also refer to Fig.18 and Fig.19 , base 801 includes fluid channels 804, and fluid channels 804 include channels 805, 806, and 807 ( Fig.18 ). For ease of description, channel 805 is referred to as input channel 805, channel 807 is referred to as reaction channel 807, and channel 806 is referred to as waste channel 806. Channels 805, 806, and 807 can be controlled to be fluidly isolated from each other and can be controlled to be selectively fluidly connected, as described below. The fluid connection between channels 805 and 807 allows the test sample to move from reservoir 802 to channel 807; and the fluid connection between channels 806 and 807 allows waste to move into channel 806.

[0106] In this example, input channel 805 is linear and includes an inlet 805a fluidly connected to reservoir 802 and an outlet 805b that can be fluidly connected to reaction channel 807. In this example, waste channel 806 is substantially linear and includes an inlet 806a that enables fluid connection to a portion of reaction channel 807. Waste channel 806 also includes a port 806b at its end. Port 806b enables a fluid connection between waste channel 806 and a pressure control device, such as a vacuum pump, that introduces a negative pressure (suction) into the channel to move materials into the channel. In this example, the shape of reaction channel 807 is serpentine. Reaction channel 807 includes a first inlet 807a that can be fluidly connected to input channel 805. The reaction channel also includes a port 807b at its end. Port 807b enables a fluid connection between reaction channel 807 and a pressure control device, such as a pump that provides positive and negative pressures (e.g., vacuum or suction) to reaction channel 807. A portion of reaction channel 807 also includes a second outlet 807c that can be fluidly connected to waste channel 806.

[0107] In some examples, the same or different pressure control devices can be connected to both ports 807b and 806b to effect pressure changes in reaction channel 807 and waste channel 806. In some embodiments, the two pressure control devices can be isolated from each other and connected to each of ports 806b and 807b. The pressure control device connected to reaction channel 807 can be programmed or controlled to perform mixing by aspirating (e.g., pulling with negative pressure) samples and reagents upstream along the reaction channel towards the pressure control device and by applying positive pressure to force the samples and reagents to return downstream along the reaction channel away from the pressure control device. The positive and negative pressures can be applied alternately multiple times to allow the samples and reagents to move multiple times within a selected section of channel 807 to produce a uniform mixture.

[0108] The serpentine shape can be advantageous as it enables a longer channel to be present on a kit of a limited size suitable for use with test devices than other shapes. The long channel can provide a good opportunity for mixing the sample with the reagents on the kit. However, channels of different shapes can be used. For example, in some embodiments, the reaction channel can be zigzag or linear.

[0109] Optionally, reaction channel 807 can store one or more reagents in different regions. For example, one or more dry reagents of the type described above can be stored at region 810 of the reaction channel or at any other location. One or more dry reagents can also be stored in other regions of the reaction channel. The location (if any) for storing the dry reagents will depend on the test to be performed using the kit. In some embodiments, the dry reagents can be stored within the channel itself rather than in separate chambers or cavities along the channel. Reaction channel 807 also includes a test region 811 where the mixture of the test sample and reagents is part of the diagnostic testing process. If any reagents are present in the reaction channel, the test region is typically downstream of the reagents in the reaction channel.

[0110] Additionally or alternatively, reaction channel 807 can alternately include constriction and dilation geometries along its length. For example, as Fig.18As shown, portions 807d, 807e of reaction channel 807 and portions 807f, 807g have the same generally cylindrical shape, but portions 807d, 807e are narrower than portions 807f, 807g of reaction channel 807. Thus, portions 807d, 807e can hold a smaller volume of liquid than portions 807f, 807g of equivalent length. In other words, taking portions 807d and 807f as an example, portion 807d can hold a smaller volume of liquid than the portion of 807f having a length equal to the length of portion 807d. The lengths of portions 807d and 807f can be measured along the path between inlet 807a and port 807b. For example, the lengths of portions 807d and 807f can be measured along axis 815. In some embodiments, the larger and smaller volume portions of reaction channel 807 can have different shapes - for example, portions 807d, 807e can be cylindrical and portions 807f, 807g can be rectangular parallelepipeds. The constricting and expanding geometries along the length of reaction channel 807 create a pressure gradient within the reaction channel, which can assist in causing mixing to occur within the reaction channel, as described below.

[0111] The test area 811 can be or include a reaction chamber. The reaction chamber can have an elliptical cross-sectional shape having a wide center and tapered ends. An example of such a reaction chamber 2701 is shown in Fig.43 . In other examples, the reaction chamber can have a cross-sectional shape different from the cross-sectional shapes of channels 806, 807, such as a circular or rectangular cross-sectional shape.

[0112] When the test sample and the reagent begin to contact each other and continue to mix, a chemical reaction begins and continues. A uniformly mixed test sample and reagent can be a mixture of materials from which neither the unmixed test sample nor the unmixed reagent can be identified. For example, (a) in an anti-factor Xa colorimetric assay, free Xa enzyme reacts with a chromogenic substrate to enable quantification of unfractionated heparin (UFH), and (b) in a sample containing D-dimer mixed with a latex reagent, its reaction buffer causes agglutination, where the turbidity change depends on the amount of D-dimer.

[0113] Returning to reference Fig.16 and Fig.17 , kit 800 further includes a movable structure 820. Structure 820 is assembled on top of base 801 and is configured to move in the direction of arrow 847 ( Figure 5 and Figure 6 ) like movable structure 310. As described below, this structure is movable to create a fluid path through the channels on base 801. Fig.17 )).

[0114] In this example, structure 820 includes seal 832 , container 821 , and compression mechanism 846 , all of which are movable within a stationary housing 845 .

[0115] Container 821 includes a chamber that holds a liquid (e.g., one or more liquid reagents or reaction buffers). The container can also hold dry (or "solid") reagents. The container can be made of polyethylene terephthalate glycol (PETG) or HDPE, and in some embodiments, the internal volume of the chamber is designed based on the volume requirements of the reagents used in the assays performed on the kit. The chamber can include more liquid (e.g., reagents) than is required for a particular assay. Fig. 20 , Fig.21 and Fig. 22 8 and 9 respectively show a top view, a bottom view and a perspective view of the container 821. Fig. 20 and 22 A container 821 having a chamber 828 is shown, and as Fig. 20 and 21 As shown, container 821 includes a container outlet 830 of the type described above, through which fluid is output from the chamber to the channel on the reagent kit. A vent port 831 is also included to vent air from the chamber. The top of chamber 828 can be sealed using, for example, a plastic cover or membrane. Figure 20-22 In the example of FIG. 8 , chamber 828 is a rectangular cuboid. In other examples, chamber 828 can have a different shape. For example, the chamber can have Fig.41 Cylindrical shape 2501 or Fig.42 A combination of cylindrical and pyramidal shapes 2601.

[0116] like Figure 17-19 As shown, the structure 820 also includes an exemplary seal 832. The seal 832 can be made of silicone or Figures 3 to 13 Any other material described herein that is capable of forming a fluid-tight connection between the seal and the top surface 835 of the base 801. Fig.23 , Fig.24 and Fig.25 , respectively, show a top view, a bottom view, and a perspective view of the seal 832. Fig.24 and 25 As shown, seal 832 includes two channels 836 and 837 formed by notches or depressions in the bottom of seal 832 that do not extend all the way through the seal. Channels 836 and 837 form fluid connections on the reagent cartridge, as described below.

[0117] The seal 832 also includes a conduit 840 that, when the seal 832 and the container 821 cooperate to form the structure 820, Fig.16 and Fig.17As shown, the container outlet 830 and the conduit 840 are aligned to create a fluid communication path from the chamber 828. Additionally, the conduit 840 is disposed on the seal 832 such that when the structure 820 is placed on the base 801, the conduit 840 can be aligned with the inlet 807a of the reaction channel 807. The seal 832 also includes a vent conduit 841 that is aligned with the conduit 831 to equalize the pressure inside the container with the external pressure, thereby facilitating the output of the contents from the container. In some embodiments, the seal 832 includes a membrane above the conduit 840. The membrane peels in response to lateral movement, thereby creating a fluid path from the chamber 828 through the container outlet 830, the conduit 840, and into the channel.

[0118] Fig.26 and Fig. 27 shows a front view of the seal 832 (as part of the structure 820) at different positions placed on the base 801. Referring Figure 23-26 to, the channel 836 of the seal 832 has a sufficient length to span the distance between the outlet 805b of the input channel 805 and the inlet 807a of the reaction channel 807, thereby fluidly connecting the input channel 805 and the reaction channel 807. Referring Figure 23-25 and Fig. 27 to, the channel 837 of the seal 832 has a sufficient length to span the distance between the outlet 807c of a portion of the reaction channel 807 and the inlet 806a of the waste channel 806, thereby fluidly connecting the waste channel 806 and a portion of the reaction channel 807. Additionally, at the Fig. 27 position of the structure 820 shown, the conduit 840 is aligned with the inlet 807a of the reaction channel 807, thereby creating a fluid connection between the interior of the chamber 828 of the container 821 and the reaction channel 807 such that the contents of the chamber 828 can be drawn into the reaction channel 807.

[0119] The channel 837 is connected to the waste channel 806 such that residual / additional liquid can be aspirated from the container 821 to prevent the liquid from reaching the reaction channel. The sample flow side channel 807b ( Fig. 27 ) can limit bubble formation in the remainder of the reaction channel 807. More specifically, during the aspiration of a test sample (e.g., to separate plasma from other blood components), there is a possibility of bubble formation in the reaction channel 807. The channel 807b is an alternative path for the test sample to flow, but with minimal flow. This occurs by capillary action when the operation of the pressure control device 2206a terminates. When the pressure control device 2206a is reactivated, to complete the aspiration of the test sample for metering, the air aspirated into the reaction channel 807 can be reduced due to the plasma in the channel 807b.

[0120] In some embodiments, a separate channel different from channels 837 and 836 in seal 832 can connect port 806a and port 807c. In this example, seal 832 may not include channel 837.

[0121] Kit 800 also includes a compression mechanism 846 similar to that described with respect to Figure 1 and Figure 2 , Figure 5-11 for example, to push structure 820 downward against base 801 while still allowing structure 820 to move through surface 835 of base 801 in one or both directions of arrow 847. In some embodiments, this movement is substantially perpendicular to the direction of the force applied by compression mechanism 846. The compression mechanism can be an HDPE spacer or a spring, but spacers or springs made of other plastics or metals can be used.

[0122] Housing 845 is similar to the housings described herein to at least partially enclose structure 820 while allowing access to the actuator. In some embodiments, housing 845 can be made of aluminum or high density polyethylene (HDPE), similar to the housings described above with respect to Figures 3 to 13 . For example, housing 845 can be attached to base 801 by screws, snap fits, or plastic welding.

[0123] Kit 800 can be used with one or more actuators (such as a linear actuator). The actuator can be controlled by a control system to contact structure 820 and move structure 820 across surface 835 of base 801 in one or both directions of arrow 847 ( Fig.16 ). The use of silicone in seal 832 enables structure 820 to move in the presence of compression.

[0124] Fig.40is a block diagram of an exemplary diagnostic test instrument 2200 on which tests (such as multi-stage tests) can be performed using a kit (such as kit 800). The diagnostic test instrument 2200 includes a control system 2201, one or more actuators 2202 of the type described herein, an optical test system 2203, an input port 2204 for receiving the kit 800, an optional robot 2205 (such as a robotic pipette for providing test samples), and one or more pressure control devices 2206 of the type described herein. The control system 2201 includes a machine-readable memory 2210 storing instructions 2211 that can be executed by one or more processing devices 2212 to control the movement of the actuator 2202 as described herein, control the operation of the pressure control device 2206 as described herein, control the robot 2205, and control the test via the optical test system 2203 based on a mixture of samples and reagents in the kit. Specifically, the control system executes instructions to perform all or part of the operations included in the Fig.34 process 2000, Fig.36 process 2101, Fig.37 process 2220, and Fig.39 process 2301. The diagnostic test instrument 2200 may also include a thermal subsystem 2220. The thermal subsystem can be controlled by the control system and can be used to monitor the temperature of the kit and heat the kit when required for a particular test. For example, for some tests, the kit can be heated to 37 °C. Although Fig.40 the control system is shown as being inside the diagnostic test instrument, all or part of the control system can be external to the diagnostic test instrument. For example, all or part of the control system can be implemented on a computing system external to the diagnostic test instrument.

[0125] Examples of diagnostic test instruments on which the kits described herein can be used include, but are not limited to, the GEM 100 instrument from S.A., the analyzer from A.G., and the instrument from Abbott .

[0126] Fig.34 shows the operations included in an exemplary test process 2000 that can be performed using a kit such as kit 800. Also referring to Fig.28 , process 2000 includes moving (2000a) the structure 820 to the Fig.28 position shown. For example, the control system 2201 can control the actuator 860 to move the structure to this position. Alternatively, the structure can be loaded into this position in the kit before the test and no movement may be required. In Fig.28 In the position shown, the channel 836 in the seal 832 of the structure 820 is aligned with the outlet of the input channel 805 and the inlet of the reaction channel 807 to fluidly connect the input channel 805 to the reaction channel 807. This alignment is described above with respect to Fig.26 and defines a fluid conduit between the input channel 805 and the reaction channel 807.

[0127] Process 2000 includes adding (2000b) a test sample to the reservoir 802. For example, the control system can control a robotic pipette to provide the test sample to the reservoir 802. In an example, the test sample can be whole blood, and a plurality (e.g., two) of membrane filters or plasma separation filters in the reservoir 802 can separate the plasma from the whole blood within the reservoir 802. The plasma can be the liquid that moves into the channels of the kit for testing. Alternatively, whole blood or other types of processed whole blood (such as serum, blood derivatives, or a premix of blood and one or more reagents) can be one or more samples that are moved into the channels of the kit 800 for testing.

[0128] Then, the control system 2201 can control a pressure control device 2206a (which can be one of the pressure control devices 2206) connected to the port 807b of the reaction channel to apply a negative pressure (e.g., suction or vacuum pressure) to the reaction channel 807. This negative pressure draws (2000c) a sample 864 such as plasma from the reservoir 802 through the input channel 805 and through the conduit formed by the channel 836 in the seal 832 and into the reaction channel 807.

[0129] The pressure control device 2206a continues to apply the negative pressure until the amount of the sample reaches a predetermined amount required for an assay implemented as part of the test procedure. This predetermined amount of the test sample can be programmed into the control system. For example, the predetermined amount can be based on the amount of time of applying the negative suction and the flow rate, e.g., based on the size of the channel and the amount of pressure applied. After the predetermined amount of the test sample has entered the reaction channel 807, the control system 2201 controls the actuator 860 to move the structure 820 from Fig.28 the position shown to Fig.29 the position shown.

[0130] As Fig.29 shown, the structure 820 is moved such that the channel 836 in the seal 832 is misaligned. In this configuration, as Fig. 27 shown, the channel 837 in the seal 832 is aligned with the inlet 806a of the waste channel 806 and the outlet 807c of the side channel 807b of the reaction channel to fluidly connect the waste channel 806 to the reaction channel 807, enabling the removal of unused contents from the container, as described below with respect to Fig.31 As described above. This alignment creates a fluid path between the reaction channel 807 and the waste channel 806. In Fig.29 the configuration shown, the container outlet 831 / conduit 840 of the structure 820 is aligned with the inlet 807a of the reaction channel 807. This alignment creates a fluid connection between the chamber 828 in the container containing liquid, the container outlet, the inlet of the reaction channel 807, and the reaction channel itself, as described above. Fig. 27 and creates a fluid connection between the chamber 828 in the container containing liquid, the container outlet, the inlet of the reaction channel 807, and the reaction channel itself.

[0131] Next, as shown in Fig.30 the control system controls the pressure control device 2206a to apply a negative pressure to the reaction channel 807. This negative pressure sucks (2000e) a predetermined amount of liquid (e.g., reagent) 866 from the chamber 828 through the container outlet and through the inlet of the reaction channel 807 and into the reaction channel 807. The amounts of sample and reagent in the channel can be determined using an edge detection process, examples of which are described below in Fig.35 and Fig.36 or the amounts of sample and reagent can be based on the amount of time negative suction is applied. The amounts of sample and reagent in the channel can also be determined by monitoring pixel characteristics of an image or optical data from the channel and comparing these characteristics to one or more thresholds, and / or performing machine learning-based edge detection and tracking over time. Combinations of one or more of these techniques can also be used.

[0132] After the sample and reagent have entered the reaction channel 807, the control system 2201 stops the operation of the pressure control device 2206a, thereby stopping additional liquid from entering the reaction channel.

[0133] The control system detects (2000f) the correct volume of liquid 866 (such as a combination of a test sample and an optional liquid reagent from the container 821) in the reaction channel 807 for measurement. For example, the correct volume can be determined using edge detection according to the process 2220 in Fig.37 . Next, the control system controls the pressure control device 2206b to pass through along elements 807a, 807c, and 837 ( Fig. 27)The resulting fluid path aspirates (2000g) any unwanted remaining liquid from chamber 828 and into waste channel 806. Control pressure control device 2206a to provide aspiration in reaction channel 807 while controlling pressure control device 2206b to provide aspiration in waste channel 806. When pressure control device 2206a terminates at 807b, channel 807 is blocked by a plunger within the syringe kit of the pressure control device. This creates a strong resistance to the aspiration from pressure control device 2206b at port 806a. Thus, when pressure control device 2206b at port 806b is activated for aspiration, pressure control device 2206b aspirates liquid from the reagent reservoir rather than from reaction channel 807.

[0134] Assume the reaction channel contains the correct volume of liquid (e.g., the correct volume of test sample and (if needed) liquid reagent), as Fig.31 shown, the control system controls pressure control device 2206a to alternately apply negative and positive pressure to reaction channel 807b to move the combination 868 of test sample and optional liquid reagent back and forth (2000h) in the reaction channel in the direction of arrow 866. This oscillatory motion mixes the test sample and liquid within the reaction channel to produce a uniform mixture. For example, the sample and liquid can be mixed in the serpentine portion of the reaction channel, and the pressure required to perform the mixing and the number of back-and-forth movements of the combination of test sample and liquid can be programmed into the control system in some embodiments and can be based on, for example, the type of reagent and sample used. As previously described, the expanding and contracting geometry of reaction channel 807 creates a pressure gradient within the reaction channel that aids in mixing.

[0135] After mixing the liquids, as Fig.32 shown, the control system controls pressure control device 2206a to apply negative pressure to move (2000i) the resulting liquid mixture to position 870 where one or more dry reagents are located in reaction channel 807. The one or more positions of the dry reagent in the reaction channel will depend on, for example, the type of test being performed using the kit and the ease of dissolving the dry reagent. The control system controls (2000j) pressure control device 2206a to alternately apply negative and positive pressure to reaction channel 807 to move the liquid mixture and dry reagent back and forth around position 870 in the direction of arrow 873 within the reaction channel. This oscillatory motion dissolves the dry reagent in the liquid mixture, thereby mixing the two into a uniform mixture. In some embodiments, the pressure required to perform the mixing and the number of back-and-forth movements of the combination of test sample and liquid can be programmed into the control system and can be based on, for example, the type of reagent and sample used. As previously described, the expanding and contracting geometry of reaction channel 807 creates a pressure gradient within the reaction channel that aids in mixing.

[0136] In embodiments where dry reagents are present at more than one location within reaction channel 807, operations 2000i and 2000j may or may not be repeated for each location. The dry reagents at different locations may be the same or may be different reagents. In some embodiments, no dry reagents may be present in the reaction channel, and thus, operations 2000i and 2000j may be omitted.

[0137] The amount of mixing performed may be based on the test to be performed. For example, for a D-dimer dried latex mix, 10 to 30 (e.g., 20) mixing cycles (e.g., back and forth) may be performed. For a factor Xa assay, 10 to 30 (e.g., 20) cycles are used to mix with the substrate in the first part of the serpentine channel, and then 2 to 10 (e.g., 5) cycles are used to mix the dried enzyme in the second downstream part of the serpentine channel.

[0138] After all dry reagents are mixed with the liquid in the reaction channel, as Fig.33 shown, the control system controls pressure control device 2206a to apply a negative pressure to move (2000k) the resulting liquid mixture to test location 871 in reaction channel 807. The negative pressure is downstream of the liquid mixture so that the mixture can be moved in the desired direction. In embodiments where pressure is applied upstream of the direction of movement of the liquid mixture, the pressure should be a positive pressure. At test location 871, optical test system 2203 performs an optical test (2000l) on the liquid mixture. For example, optical detection techniques such as absorbance measurement, scatter measurement, or fluorescence signal measurement may be used to monitor reactions in the liquid mixture. Physical parameters that may be measured include, but are not limited to, optical absorbance, optical fluorescence, color, degree of agglutination of D-dimer, colorimetric intensity of anti-Xa, and fibrin clot formation. The control system may report the test results as data to a computing system (2000m), or display the results as text and / or graphics on the user interface of the diagnostic test instrument.

[0139] In some embodiments, kit 800 may be disposable. Thus, after the test as described above, the kit may be discarded.

[0140] Return reference Figure 1 and Figure 2 channel 102 may have the same as with respect to Figures 16 to 34The reaction channel 807 described above or a variation thereof having the same structure, function, and contents as described herein may be connected to a pressure control device 2206a to move a test sample and / or reagent through the channel 102 in the manner described in operations 2000h to 2000k above, and may have an optical testing system 2203 positioned relative to the channel 102 to perform a test on a mixture of the test sample and reagent, as described with respect to operations 2000l and 2000m above. Figure 1 and Figure 2 In this example, the test sample and / or optional liquid reagents can enter channel 102 via I / O 107 and I / O 104. Alternatively, the test sample can be passed through Figure 1 and Figure 2 A fluid connection (not shown) enters channel 102, or a test sample can be deposited into channel 102 manually or automatically.

[0141] Return to reference Figure 3 and Figure 4 , channel 202 may have Figures 16 to 34 The reaction channel 807 described above or a variation thereof having the same structure, function and contents as described herein may be connected to a pressure control device 2206a to move a test sample and / or reagent through the channel 202 in the manner described in operations 2000h to 2000k above, and may have an optical testing system 2203 positioned relative to the channel 202 to perform a test on a mixture of the test sample and reagent, as described with respect to operations 2000l and 2000m above. Figure 3 and Figure 4 In this example, liquids such as test samples and / or reagents enter channel 202 from chamber 235. For example, test samples and / or reagents can be added to chamber 235 via one or more inlets (not shown). Alternatively, reagents only enter channel 202 from chamber 235, and test samples are passed through chamber 235. Figure 3 and Figure 4 A fluid connection (not shown) enters channel 202, or a test sample can be deposited into channel 202 manually or automatically.

[0142] Return to reference Figure 5 and Figure 6 , channel 302 may have Figures 16 to 34 The reaction channel 807 described above or a variation thereof having the same structure, function, and contents as described herein may be connected to a pressure control device 2206a to move a test sample and / or reagent through the channel 302 in the manner described in operations 2000h to 2000k above, and may have an optical testing system 2203 positioned relative to the channel 302 to perform a test on a mixture of the test sample and reagent, as described with respect to operations 2000l and 2000m above. Figure 5 and Figure 6 In this example of Figure 6 , a liquid such as a test sample and / or a reagent enters channel 302 from chamber 335. For example, the test sample and / or the reagent may be added to chamber 335 via one or more inlets (not shown). Alternatively, only the reagent enters channel 302 from chamber 335, and the test sample enters channel 302 through Figure 5 and Figure 6 a fluid connection not shown in Figure 6 , or the test sample may be manually or automatically deposited into channel 302.

[0143] Return reference Figure 7 and Figure 8 , channel 402 may have the same structure, function, and contents as the reaction channel 807 described with respect to Figures 16 to 34 or a variant thereof described herein, may be connected to a pressure control device 2206a to move the test sample and / or the reagent through channel 402 in the manner described in operations 2000h to 2000K above, and may have an optical test system 2203 positioned with respect to channel 402 to perform tests on the mixture of the test sample and the reagent, as described in operations 2000l and 2000m above. In Figure 7 and Figure 8 this example of Figure 8 , a first liquid such as a test sample and / or a first reagent enters channel 402 from chamber 440. In Figure 7 and Figure 8 this example of Figure 8 , a second liquid such as a test sample and / or a second reagent, the same as or different from the first reagent, enters channel 402 from chamber 440. For example, the test sample and / or the reagent may be added to chambers 440, 4401 via one or more inlets (not shown) entering each chamber. Alternatively, only the reagent enters channel 402 from chambers 440 and 441, and the test sample may enter channel 402 through Figure 7 and Figure 8 a fluid connection not shown in Figure 8 , or the test sample may be manually or automatically deposited into channel 402.

[0144] Return reference Figure 9-11 , one or more or each of channels 550a, 551a, and 552a ( Fig.11 ) may be provided with a structure having the same as that with respect to Figures 16 to 34A channel having the same structure, function, and contents as the described reaction channel 807, or a variant thereof described herein, may be substituted. One or more such channels may be connected to corresponding pressure control devices 2206a to move test samples and / or reagents through each channel in the manner described in operations 2000h to 2000K above, and may have an optical test system 2203 positioned relative to the channel to perform tests on mixtures of test samples and reagents, as described above with respect to operations 2000l and 2000m. In Figure 9-11 In this example, a liquid such as a test sample and / or reagent enters one or more of channels 550a, 551a, and 552a from chamber 535. For example, a test sample and / or reagent may be added to chamber 535 via one or more inlets (not shown). Alternatively, the reagent alone enters one or more of channels 550a, 551a, and 552a from chamber 535, and the test sample enters one or more of channels 550a, 551a, and 552a through Figure 9-11 one or more fluid connections not shown in

[0145] Return reference Fig.12 and 13 Referring back to Figures 16 to 34 and Fig.12 and Fig.13 In this example, a liquid such as a test sample and / or reagent enters channel 602 from chamber 635. For example, a test sample and / or reagent may be added to chamber 635 via one or more inlets (not shown). Alternatively, the reagent alone enters channel 602 from chamber 635, and the test sample enters channel 602 through Fig.12 and Fig.13 fluid connections not shown in

[0146] Return reference Fig.14 and Fig.15 Referring back to Figures 16 to 34The described reaction channel 807 or a structure and function identical to a variant thereof described herein can be connected to a pressure control device 2206a to move a test sample and / or reagent through channel 702 in the manner described in operations 2000h to 2000K above, and can have an optical test system 2203 positioned relative to channel 710 to perform tests on a mixture of the test sample and reagent, as described with respect to operations 2000l and 2000m above. In Fig.14 and Fig.15 this example, the test sample and / or optional liquid reagent can enter channel 710 from channel 709 via space 717. Alternatively, the test sample enters channel 710 through a fluid connection not shown in Fig.14 and Fig.15 , or the test sample can be deposited manually or automatically into channel 710.

[0147] Fig.35 Operations included in an example process 2100 for obtaining a machine learning (ML) model for detecting the edge of a fluid flow are shown. Process 2100 can be executed by a computing system separate from the diagnostic test instrument and can be executed at a time prior to the test.

[0148] Process 2100 includes training (2100a) one or more machine learning models to identify and / or track edges in a fluid flow. The one or more machine learning models can include machine learning processes that perform classification, regression, localization, detection, tracking, and / or segmentation in one or more images or over time. The one or more machine learning models can include, but are not limited to, convolutional neural networks, fully connected neural networks, models based on convolutional networks, transformers, and models based on transformers. The one or more machine learning models can include one or more classifiers and / or regressors, each of which can be used for specific object detection or tracking. The one or more machine learning models can include object detection and tracking models that track multiple objects simultaneously.

[0149] The machine learning model can be part of an ensemble model with complementary algorithms that analyze image pixel intensity or color as input features and / or signals from additional device sensors, such as supervised learning techniques, which include but are not limited to logistic regression, multiple regression, decision trees, random forests, support vector machines (SVMs), gradient boosting, or neural networks.

[0150] Supervised machine learning techniques can build a model by examining examples and trying to find a model that minimizes the loss; this process is called empirical risk minimization. If the model's predictions are accurate, the loss is close to zero; otherwise, the loss is greater, which results in a higher penalty during training. The goal of training the model is to find a set of weights and biases that on average have a low loss across all examples, in order to achieve process robustness and generalization.

[0151] In some embodiments, data including the plasma flow can be used to train a machine learning model, where the plasma flow is near clear and thus may be more difficult to detect than fluid flows with distinct colors.

[0152] To enhance fluid object detection and tracking robustness, the trained model can be integrated into an ensemble with complementary inference algorithms and / or attention mechanisms. The complementary inference algorithms analyze the pixel characteristics of the image at one or more specified fluid channel locations. The attention mechanism can include, but is not limited to, weighting up pixels or features adjacent to the detected objects in the previous image, and weighting down or removing pixels or features far from the detected objects in the previous image. The amounts constituting adjacent or distant pixels or features can be pre-programmed into the model. The upper and lower weights can enable the detection process to focus on the area bordering the detected object.

[0153] Example inference algorithms apply logical rules to a knowledge base to evaluate and analyze new information. During the training phase, intelligence is developed by recording, storing, and labeling information. Images of the edge flow can be fed into the machine learning process. In the inference phase, the process uses the intelligence collected and stored in phase one to understand new data. In this phase, the process uses inference to recognize and classify new images as edges.

[0154] The inference algorithm can analyze the pixel characteristics at one or more locations of an image of the kit, and can combine and analyze inputs from one or more sensors (such as the sensors in the optical test system 2203). These models can be threshold-based classification algorithms or machine learning models that make inferences based on multiple features.

[0155] Process 2100 stores (2100b) one or more such machine learning models and / or inference algorithms in the memory 2210 of a diagnostic test instrument that uses the kit ( Fig.40 )

[0156] Fig.36Shows operations in an exemplary process 2100 for detecting the edge of a fluid flow in a channel, such as reaction channel 807. Process 2101 may be performed by processing device 2212 using a stored machine learning model and / or inference algorithm and by executing some instructions 2211 stored in memory 2210 of control system 2201. Each of the foregoing machine learning processes and inference algorithms may be used individually, in parallel, or altogether to improve detection robustness and redundancy.

[0157] Process 2101 receives (2100c) image data representing the fluid flow. For example, a camera may capture one or more images of reaction channel 807. The camera may be included in a test instrument into which a test kit is inserted and is located above reaction channel 807. In some embodiments, the camera may capture 10 to 20 images per second while the fluid is flowing in the channel or while the fluid is stationary in the channel. In embodiments where one image may be captured and used for detection as described below, additional other images, such as images captured after one image, may be used for improvement during detection.

[0158] These images constitute the received image data input into the stored model. Process 2101 uses the model, either alone or integrated with a complementary inference algorithm, to detect (2100d) the leading edge of the fluid flow (both the liquid reagent and the test sample in this example) and the position of the leading edge within reaction channel 807. For example, referring to Fig.30 , the model may analyze the image data to detect leading edge 880 of the fluid flow within reaction channel 807. The leading edge may be determined by identifying differences in the composition of the image data. For example, the fluid in the channel may have a different color or shade from the regions of the channel that do not include fluid. Regions of the channel may be imaged, and the resulting imaging data may be used to identify regions with different colors or shades. For example, the imaging data may be compared to a color or shade threshold that may be preset based on experimental data. Adjacent regions that exceed their respective thresholds may be identified as edges in the fluid. The position of the edge may be detected in the reaction channel.

[0159] The position of the edge detected in operation 2100 within the reaction channel is compared to a predetermined position within the reaction channel to determine (2100e) whether the fluid flow has reached the predetermined position. The predetermined position may be programmed into the control system and may be based on the volume of fluid required for a particular test to be performed in the reaction channel. For example, the predetermined position may be set such that the reaction channel is filled with enough liquid to perform a particular test. After determining that the fluid flow has reached the predetermined position, process 2000 may continue (2100e) the test process.

[0160] In all the required fluid 866 ( Fig.30 )After entering the reaction channel, process 2100 can be repeated to detect the trailing edge of the fluid flow in the reaction channel, for example, simultaneously with detecting the leading edge. In some embodiments, the trailing edge detection can be a secondary detection for confirming the position of the front fluid edge and the progress of the workflow.

[0161] Reference Fig.37 , process 2220 can be used to determine that the correct volume of liquid for the current assay is in the reaction channel 807. Process 2220 can be executed by a processing device 2212 that executes some instructions 2211 stored in the memory 2210 of the control system 2201.

[0162] Process 2220 includes using process 2100 to detect (2220a) the leading edge of the fluid flow along the fluid flow direction in the reaction channel 807. Process 2220 includes using process 2100 to detect (2220b) the trailing edge of the fluid flow in the reaction channel 807. The detections 2220a, 2220b can be performed simultaneously at the same frequency or at different frequencies, for example, at 5 to 20 or more images per second or greater, or using occasional or on-demand inference in combination with Fig.36 the operations described. The positions of the leading edge and the trailing edge can be used to determine the volume of liquid (e.g., reagent and test sample) in the reaction channel. That is, the geometry of the reaction channel is stored in the memory. Given the geometry and positions of the liquid leading edge and the liquid trailing edge, the control system can determine the volume of liquid in the reaction channel.

[0163] The liquid volume can be determined a predetermined number of times. For example, the camera captures image data of the leading edge and the trailing edge multiple times per second, for example, 5 to 20 or more images per second, or using occasional or on-demand inference. For each such image, process 2220 determines the volume, and the resulting volumes can be averaged (2220c). The averaging can be a weighted average considering the certainty of the machine learning process and can be combined with the removal of values outside a predetermined value range. This method can reduce the chance of error in volume estimation because it does not emphasize abnormal measurements. Based on known data correlating error reduction with the number of average volumes, the number of volumes to be averaged can be programmed into the control system.

[0164] Thereafter, the average volume of the liquid is compared with a predetermined volume of the liquid required for the current measurement. If the volume is correct (2220d), i.e., the average volume is equal to the predefined volume or within an acceptable variance (e.g., 1%, 2%, or 3%) of the predefined volume, the test process continues (2220e). If the volume is incorrect (2220d), the process notifies (2220f) the operator that an incorrect amount of liquid has been metered. This notification can be visual, such as by displaying on the user interface of the diagnostic test instrument, or audio, such as by emitting an alarm. In some embodiments, unless the operator intervenes to restart the test process, the test process can be automatically stopped in the case of an incorrect volume.

[0165] By using process 2220 to measure the volume based on edge detection of the fluid flow, the test liquid can be metered without using a valve or sensor inside the channel of the kit. This can simplify the configuration of the kit.

[0166] In some embodiments of operations 2220a to 2220c, the average value may not be used. For example, the edge can be tracked over time without using the average value. In some embodiments of operations 2220a and 2220b, the separate running average may not be used. For example, when determining the average value, the edge measurements that fall outside one standard deviation, two standard deviations, etc. of a set of edge measurements can be ignored. The averaging of the measured distances between the edges can be combined with the additional techniques described herein to increase the estimation accuracy over time, such as the weighted average using model certainty and attention mechanisms, which reduces the influence of image features that are greater than a predefined distance from the detected object position in the previous image.

[0167] In some cases, anomalies in the liquid in the reaction channel 807 may adversely affect the test. Examples of such anomalies are bubbles in the sample or the sample - reagent mixture; however, foreign particles, debris, or unmixed dry reagents at region 871 in the reaction channel may also affect the test. Process 2301 can be used to detect such anomalies. Process 2301 can be performed at any point in the test process 2000 (34) after the liquid enters the reaction channel, and the result of process 2301 can cause the test to stop. Process 2301 can be executed by a processing device 2212 that executes some instructions 2211 stored in the memory 2210 of the control system 2201( Fig.40 )

[0168] Fig.38Illustrates operations included in an exemplary process 2300 for obtaining a machine learning model used in a process 2301 for detecting anomalies (including transparency anomalies) in a fluid flow. Process 2300 can be executed by a computing system separate from a diagnostic test instrument and can be executed at a time prior to testing. Process 2300 includes training (2300a) a machine learning model to identify anomalies in a fluid flow. Any machine learning process can be used, including those described herein. In a particular non-limiting example, the EfficientNet or MobileNet convolutional neural network algorithm is used to perform anomaly detection, and all or its top layers of the algorithm are extended with additional layers, or customized and trained to detect anomalies and fluid edges. In some embodiments, a portion rather than the entire convolutional neural network algorithm can be trained to perform the detection.

[0169] Similar to edge detection, a customized fully connected neural network or a transformer-based object detection model can be used to perform anomaly detection and tracking. Similar to edge detection, to enhance the robustness of anomaly object detection and tracking, the trained model can be integrated in an ensemble with a complementary inference algorithm that analyzes the pixel characteristics of an image at one or more specified fluid channel locations, and / or integrated in an ensemble with an attention mechanism that can be, but is not limited to, up-weighting pixels or features adjacent to object detection and down-weighting or removing pixels or features far from the object in one or more previous images.

[0170] The inference algorithm can analyze the pixel characteristics at one or more locations of a frame or kit and can combine and analyze inputs from one or more sensors, such as sensors in the optical test system 2203. These inference algorithms can include, for example, a threshold-based classification algorithm or a machine learning model that makes inferences based on multiple features.

[0171] The machine learning model and / or inference algorithm (such as those described above) can be trained to detect anomalies and / or edges in fluid flow in fluid platforms other than kits (such as tubes). Cross-platform (e.g., channels and tubes) training can improve the detection accuracy of each of the machine learning model and / or inference algorithm.

[0172] In the above example, the machine learning model and / or inference algorithm can be deployed on and executed on a tensor processing unit (TPU) or alternatively a graphics processing unit (GPU) 2240, and the tensor processing unit (TPU) or graphics processing unit (GPU) 2240 can be Fig.40Part of the control system 2201. These devices are battery - efficient when typically quantizing machine - learning models using TFLite or TensorRT, which are libraries for machine - learning models or for deploying machine - learning models to devices. The reduction of layers in the above - mentioned machine - learning models can further improve the battery efficiency of these devices.

[0173] Fig.39 Shows operations in an example process 2301 for detecting anomalies in a fluid flow (such as, but not limited to, a fluid flow in a channel (such as reaction channel 807)). In this example, the anomalies can include bubbles or solid particles, such as debris in the channel, which reflect or refract light and are located at positions other than the positions where known dry reagents (if any) are deposited in the channel. Process 2301 can also detect the leading and trailing edges of the fluid flow.

[0174] In this example, process 2301 can be executed by the TPU or GPU 2240 and a processing device 2212 that executes some of the instructions 2211 stored in the memory 2210 of the control system 2201.

[0175] Process 2301 selects (2300a) a region of interest of the kit, such as a portion of the reaction channel 807. The region of interest can include one or more or all of the channels and can include all or part of each selected channel.

[0176] Process 2301 controls (2300b) a camera, which can be part of a test instrument into which the kit is inserted and is located above the kit. The camera can be configured to capture images of one or more or all of the channels. The captured images can represent the content of the channels based on the intensity of the pixels in the captured images. The camera can be movable to point at all or part of the kit and can include a zoom lens (e.g., 2x zoom, 5x zoom, 10x zoom) to capture magnified images.

[0177] Process 2301 guides the camera to the region of interest and controls the camera to capture one or more images of the region of interest. In some embodiments, multiple images can be captured. For example, 5 to 10 or more images of the region of interest can be captured. Images can be captured while the fluid is flowing through the channels in the region of interest or when the fluid is static in the channels.

[0178] Process 2301 receives (2300c) image data representing the region of interest from the camera. Process 2301 pre - processes (2300d) the image data to enhance the contrast between the background of the image and the objects in the image, which can enhance the depiction of potential anomalies in the region.

[0179] Process 2301 uses a trained machine learning model and possibly an inference algorithm to detect (2300e) one or more anomalies and / or edges of fluid flow in a region of interest in any channel based on image data. Multiple machine learning processes and inference algorithms can be used individually, in parallel, or as a whole to improve detection robustness and redundancy.

[0180] The location of the identified anomalies and / or edges can be fed back to the used machine learning process(es) and / or inference algorithm(s). The machine learning process(es) and / or inference algorithm(s) can use this information to guide the camera along the channel to track the anomalies and / or edges as they travel through the channel. By using the initial location of the anomalies and / or edges, the camera can focus on a narrower region of the channel while tracking the travel of the anomalies and / or edges. In some embodiments, the machine learning process(es) and / or inference algorithm(s) can know the flow rate of the fluid passing through the channel and take this information into account when guiding the camera to perform the tracking. Guiding the camera can be done by, but not limited to, cropping the location of interest or through an attention mechanism, which can be, but not limited to, up-weighting pixels or features adjacent to the detected object in the previous image and down-weighting or removing pixels or features far from the detected object in the previous image.

[0181] In the case where an edge of the fluid flow is detected, the detected edge can be used to determine the fluid volume in the channel according to the above process 2220. In the case of an anomaly, the machine learning model can continue to track the anomaly as it moves through the channel. In some cases, anomalies such as bubbles may dissipate, in which case no action needs to be taken on these anomalies.

[0182] The detection process 2300e can continue to track the anomalies and fluid edges until they are included in region 871, where optical detection is performed.

[0183] In some embodiments, process 2301 can be performed using data captured by the optical detection system 2203 ( Fig.33 ) instead of the image data captured by the camera. In some embodiments, process 2301 can be performed using both data captured by the optical detection system 2203 ( Fig.33 ) and the image data captured by the camera.

[0184] Other techniques can also be used to detect (2300e) anomalies at region 871. For example, each assay performed using kit 800 can be associated with an expected diagnostic curve. The expected diagnostic curve for each assay can be stored in the memory 2210 of the control system 2201 ( Fig.40)。The optical test system 2203 at region 871 of the kit 800( Fig.33 ) can generate a measured diagnostic curve based on the optical detection performed by the optical test system. Process 2300 can retrieve the expected diagnostic curve of the subject assay from the memory 2210 and attempt to fit the expected diagnostic curve to the generated diagnostic curve. After curve fitting, the results are analyzed to identify the locations where there are deviations between the expected diagnostic curve and the generated diagnostic curve. These locations can be identified as abnormal locations in the channel content. For example, the generated diagnostic curve may contain noise, which is represented by spikes in the curve and does not exist in the expected diagnostic curve.

[0185] Process 2301 can also detect anomalies in the region of interest based on analyzing the derivative peaks in the generated diagnostic curve. For example, the start of the expected diagnostic curve for the assay can be flat. The generated diagnostic curve for the assay; however, may contain noise, which indicates an anomaly in the channel. Process 2301 can generate the derivative of the curve containing the noise, such as the second derivative and / or the third derivative of the portion of the curve containing the noise. The positions of the second derivative peaks and / or the third derivative peaks correspond to the positions where the diagnostic curve approaches the baseline, which is the point where there are no longer any anomalies. In some embodiments, the positions of the second derivative peaks and / or the third derivative peaks having a width above or below a predetermined threshold correspond to the positions where the diagnostic curve approaches the baseline.

[0186] In some embodiments, all three of the above techniques, namely machine learning, curve fitting, and peak detection, can be used at region 871 to identify anomalies. In some embodiments, the three techniques can be complementary because the three techniques can be used to verify each other's results. In some embodiments, if one or more of these techniques, or two or more of these techniques, or all of these techniques detect an anomaly at region 871, the control system provides an output (2300f) to the operator, and then the operator can indicate to re-run the assay or indicate to continue the assay. The output can be presented on a graphical display device, which can be part of a diagnostic test instrument, such as those described herein. The output can include the identification of the anomaly and the location of the anomaly in the channel. For example, a depiction of the channel and the location and identity of the anomaly can be provided. Then, the user can make a decision to continue with the assay or re-run the assay based on the detected anomaly. In some embodiments, if one or more of these techniques, two or more of these techniques, or all of these techniques detect an anomaly at region 871, the control system can automatically re-run the assay without user input.

[0187] The previously described inference algorithms can be used to analyze pixel characteristics at one or more locations in an image of a kit in order to perform anomaly detection in operation 2300e. Examples of inference algorithms that can be used were described above and include, but are not limited to, threshold-based classification algorithms and machine learning models that make inferences based on multiple features.

[0188] Each of the techniques for detecting anomalies described herein can be used alone or in combination with one or more of the other techniques.

[0189] In some embodiments, recovery can be made from an anomaly or fluid edge detected at region 871. Generally, if an anomaly or fluid edge is detected at the detection location by system 2203 at region 871, the fluid in channel 807 can be moved so that the anomaly or fluid edge is not at that location. For example, control system 2201 can be programmed to control pressure control device 2206a to introduce a positive or negative pressure into reaction channel 807 to move the anomaly or fluid edge away from location 871. The amount of movement can range from a single millimeter to a single centimeter, depending on the sensitivity of optical test system 2203, the area covered by the system, the size of the anomaly (if any), and the amount of fluid in the channel.

[0190] In some embodiments, recovery from an anomaly at region 871 can be made by processing the generated diagnostic curve using measurements from optical test system 2203. For example, in the curve fitting example above, the expected curve can be fit to the generated curve, and the generated curve can be extrapolated to cover the location where the expected diagnostic curve and the generated diagnostic curve deviate on the curve (i.e., to remove the noise representing the anomaly).

[0191] In some embodiments, positions where a second derivative peak and / or a third derivative peak are present adjacent to the expected starting point on the generated curve can be identified. All positions before these positions contain noise and thus contain anomalies. Therefore, the portion of the diagnostic curve before those positions can be ignored, and the starting point of the diagnostic curve can be designated as the position where the second derivative peak and / or the third derivative peak reaches zero or some other predetermined constant.

[0192] In some embodiments, denoising techniques such as filtering or mean smoothing can be used to remove noise caused by artifacts in the diagnostic curve. In an example, mean averaging smoothing smooths portions of the curve over a moving average in order to remove spikes in the curve.

[0193] In some embodiments, diagnostic waveforms or portions of diagnostic waveforms can be analyzed by an artificial intelligence (AI) or machine learning process during and / or after data collection. The AI or machine learning process can provide qualitative or quantitative indications, including but not limited to the type of waveform and whether the waveform contains anomalies.

[0194] The processes described herein can be implemented using any computing system or any other suitable computing device. The system and processes can be implemented, at least in part, using one or more computer program products, e.g., one or more computer programs tangibly embodied in one or more information carriers such as one or more non-transitory machine-readable media, for execution or control of the operations of one or more data processing devices (e.g., programmable processors, computers, multiple computers, and / or programmable logic components).

[0195] A computer program can be written in any form of programming language, including compiled or interpreted languages, and it can be deployed in any form, including as a stand-alone program or as a module, component, subroutine, or other unit suitable for use in a computing environment. A computer program can be deployed to execute on one computer or on one site or on multiple computers interconnected by a network and located at multiple sites.

[0196] The actions associated with implementing all or part of the processes can be performed by one or more programmable processors executing one or more computer programs to perform the functions described herein. All or part of the processes can be implemented using special purpose logic circuitry (e.g., FPGAs (Field Programmable Gate Arrays) and / or ASICs (Application Specific Integrated Circuits)).

[0197] As an example, processors suitable for executing a computer program include both general and special purpose microprocessors, as well as any one or more processors of any type of digital computer. Generally, a processor will receive instructions and data from a read-only storage area or a random access storage area or both. Elements of a computer (including a server) include one or more processors for executing instructions and one or more storage area devices for storing instructions and data. Generally, a computer will also include one or more machine-readable storage media, or be operatively coupled to receive data from and transfer data to one or more machine-readable storage media, such as mass storage devices for storing data, e.g., magnetic disks, magneto-optical disks, or optical disks. Machine-readable storage media suitable for embodying computer program instructions and data include all forms of non-volatile storage area, including, for example, semiconductor storage area devices, such as EPROM, EEPROM, and flash storage area devices; magnetic disks, such as internal hard disks or removable disks; magneto-optical disks; and CD-ROM and DVD-ROM disks.

[0198] The elements of the different embodiments described herein can be combined to form other embodiments not specifically set forth above. An element can be omitted from the structures described herein without adversely affecting their operation. Where appropriate, the operations in the flowcharts can be performed in an order different from that shown. The various individual elements can be combined into one or more separate elements to perform the functions described herein.

Claims

1. A kit, characterized in that, Comprising: A base including a channel configured to receive a fluid, the fluid including a test sample to be tested on the kit; And A structure including at least a portion of a fluid conduit, the structure being configured to move between a first position and a second position relative to the base; Wherein, in the first position, the channel and the fluid conduit are aligned to create a fluid connection between the channel and the fluid conduit, and in the second position, the channel and the fluid conduit are misaligned to block the fluid connection between the channel and the fluid conduit.

2. The kit according to claim 1, wherein The structure includes a container, the container including a chamber for holding a fluid.

3. The kit according to claim 2, wherein The fluid includes at least one of a reagent or a reaction buffer.

4. The kit according to claim 2, wherein Further comprising: A container including a chamber for holding at least a portion of the fluid, the container including a fluid conduit; Wherein the structure is located between the container and the kit and is configured such that in the first position, the fluid conduit of the container, the fluid conduit of the structure, and the channel are fluidly aligned; And Wherein the container is fixed.

5. The kit according to claim 1, characterized in that, The kit includes a second channel configured to hold a fluid; Wherein the structure is configured to move between the first position, the second position, and a third position relative to the base; Wherein, in the third position, the fluid conduit and the second channel are aligned to create a fluid connection between the second channel and the fluid conduit.

6. The kit according to claim 1, wherein The structure includes a seal between the structure and the kit, the seal being liquid-tight, and the seal including at least a portion of the fluid conduit.

7. The kit according to claim 1, wherein Further comprising: A compression mechanism for applying a force to the structure to push a portion of the structure against the kit.

8. The kit according to claim 7, characterized in that, The compression mechanism includes at least one spring.

9. The kit according to claim 1, characterized in that, The structure is configured to receive a force and slide between the first position and the second position in response to the force.

10. The kit according to claim 1, wherein The kit includes a reservoir for receiving a test sample, at least some of the test sample including a first portion of the fluid; Wherein the channel includes a first section and a second section, the first section being fluidly connected to the reservoir; And Wherein, in the first position, the fluid conduit is located between the first section and the second section of the channel to create a fluid connection such that the second section of the channel can receive the first portion of the fluid.

11. The kit according to claim 10, characterized in that, The structure includes a container, the container including a chamber for holding at least a second portion of the fluid, the chamber including an outlet fluidly connected to the chamber; And Wherein, in the second position, the outlet of the chamber is fluidly connected to the second section of the channel to enable the second section of the channel to receive at least the second portion of the fluid from the chamber.

12. The kit according to claim 11, wherein The structure includes at least a portion of a second fluid conduit, the channel being a first channel, and the kit including a second channel; and Wherein, in the second position, the second fluid conduit is located between the first channel and the second channel to fluidly connect the first channel and the second channel.

13. The kit according to claim 12, wherein The shape of the first channel is serpentine, and the serpentine shape includes geometries of expansion and contraction; and wherein the kit includes a first port connecting the first channel to a first pressure control device and a second port connecting the second channel to a second pressure control device.

14. The kit according to claim 12, characterized in that, The shape of the first channel is serpentine, and the serpentine shape includes geometries of expansion and contraction.

15. A kit, characterized in that, Comprising: a base including a channel for holding a fluid; and a structure capable of moving relative to the channel; wherein the structure includes a membrane, at least a portion of which is biased to rise relative to the base in the absence of an applied force, and at least a portion of the membrane is capable of moving between a raised position and a compressed position; wherein the base includes a mesa between two sections of the channel; wherein, when the membrane is in the raised position, the two sections of the channel are fluidly connected in a fluid channel between the membrane and the mesa; and wherein when the membrane is in the compressed position, the membrane contacts the mesa and blocks the fluid connection between the two sections of the channel.

Images