The present invention relates to the field of processing cartridges, more specifically to a processing cartridge for analysis of a sample and an assembly for providing a sample and releasing a processing liquid into the processing cartridge.
Centrifugation as a mean for accelerating sedimentation of cells, particles and precipitates as well as for separation of liquids or cells with different density has long been an integral part of chemical and biochemical protocols. In addition, the use of centrifugation for running chemical reactions and assays in microfluidic circuits arranged in processing cartridges or chips is a well-known technique, see e.g. Tang et al. “A review of biomedical centrifugal microfluidic platforms”, Micromachines 2016, 7, 26.
In most analytical systems using processing cartridges, the direction of the centrifugal force applied to the microfluidic circuit is constant, and centrifuges similar to a compact disc (CD) player, wherein the microfluidic circuit is arranged in a CD-shaped chip or cartridge, are often used. Typical centrifuges for such analytical systems are disclosed in for instance JP 2018-163169 A and US 2018/0003732 A1.
Other analytical systems make use of dual axis centrifuges able to provide a variable centrifugal force as disclosed in for instance U.S. Pat. No. 4,814,282, WO 2011/081531 A1 and WO 2019/091650 A1. A dual axis centrifuge may provide more flexible and faster means of performing processing in a microfluidic circuit.
A common operational feature in processing cartridges is the introduction of a sample to the microfluidic circuit in a reproducible and secure manner. Further, a processing liquid is often required to dissolve, dilute, wash and/or transfer the sample and/or various reactants within the microfluidic circuit of the processing cartridge.
EP 2881743 A1 discloses a processing cartridge wherein a sample is introduced to the cartridge via an insertion type sample cartridge. The sample cartridge features a member which moves a liquid container in the processing cartridge during insertion. The movement releases the liquid in the liquid container simultaneously with the introduction of the sample.
US 2011/0117665 A1 discloses a processing cartridge featuring a pivotably connected arm for keeping a liquid container within the cartridge immobile before use. The arm is pivoted away from the remaining part of the cartridge during use to provide access to a sample collector and release the liquid container. After sampling, the arm is pivoted back towards the cartridge while simultaneously pushing the liquid container towards a spike to release liquid.
It is an object of the present invention to provide a processing cartridge in which a processing liquid may be stored and released in an improved manner A further object of the invention is a processing cartridge providing improved sampling and handling during use.
The present invention is defined by the appended claims and in the following:
In a first aspect, the present invention provides a processing cartridge comprising a main cartridge section and an actuating cartridge section, the main cartridge section comprises a liquid reservoir chamber, a liquid container, a container piercing element and a resilient container holding element, wherein
The dispensing side may comprise any suitable pierceable and fluid tight material, such as an aluminium and/or plastic foil. The dispensing side may also be termed a pierceable sealing cover or pierceable sealing foil.
In other words, the dispensing side faces the container piercing element.
The actuating member may be configured to move the liquid container by direct or indirect interaction with the liquid container. The movement of the liquid container will overcome the force from the resilient container holding element. During the movement of the liquid container, the dispensing side is pushed towards the container piercing element, such that the processing fluid may be released into the liquid reservoir chamber.
In an embodiment of the processing cartridge, the actuating cartridge section may comprise a first end pivotably connected to the main cartridge section, such that the actuating cartridge section may pivot between a non-docking position, in which the liquid container is held in the first position by the container holding element, and a docked position, in which the actuating cartridge section is docked with the main cartridge section and the liquid container is in the second position.
The container holding element may comprise any suitable resilient element able to hold the liquid container in the first position and allow the actuating member to move the liquid container into the second position. The container holding element may be configured to provide an elastic force acting on and holding the liquid container in the first position. Movement of the liquid container from the first position must overcome the elastic force acting on the liquid container. The container holding element may be configured to deflect away from the liquid container during movement of the liquid container towards the second position.
The container holding element may comprise at least one resilient arm in contact with the liquid container. The resilient arm may also be termed a resilient lever.
The resilient arm or lever may be arranged in contact with an edge of the liquid container and arranged to be deflected away from the edge when the actuating member moves the liquid container to the second position. A section of the arm/lever being in contact with the edge of the liquid container may be inclined relative to a direction in which the liquid container is moved by the actuating member. The inclined surface provides a smooth and even movement of the liquid container. The resilient arm/lever may comprise a bend having a first and second opposing sides, wherein the first side is in contact with the liquid container and is pushed towards the second side when the liquid container is moved towards the second position.
In an embodiment of the processing cartridge, the actuating member is configured to enter the liquid reservoir chamber during docking.
In an embodiment of the processing cartridge, the main cartridge section may comprise a cartridge base and a top covering.
In an embodiment of the processing cartridge, the liquid reservoir chamber comprises a sidewall and a base surface. The sidewall and the base surface may be arranged in the cartridge base. The liquid reservoir chamber may further be defined by a top surface. The top surface may be provided by the top covering.
In an embodiment of the processing cartridge, the liquid container may comprise a recess. The actuating member may be configured to interact with an edge of the recess when entering the liquid reservoir chamber during docking. The recess may comprise an edge, by which the actuating member may push or move the liquid container towards the container piercing element, and at least one side surface that may interact with the actuating member to restrict lateral movement of the liquid container. The lateral movement being restricted may be relative to the plane in which the liquid container is pushed or moved, and/or relative to a base surface of the liquid reservoir chamber. The side surface of the recess may be configured such that the actuating member may prevent lateral movement of the liquid container away from the base surface.
The actuating member may be fin-shaped, i.e. be an actuating fin. A portion of the actuating member interacting with the liquid container may have a rounded periphery to obtain a smooth and even interaction with an edge of the recess.
Having the actuating member interacting with a recess in the liquid container provides a stable movement of the liquid container towards the piercing element and prevents lateral movement of the liquid container relative to the actuating member.
In an embodiment, the processing cartridge may comprise a sample collector, the sample collector arranged to be accessible for collection of a sample when the actuating cartridge section is separated from the main cartridge section or is in the non-docking position.
The sample collector may be any element suitable for retrieving a solid, semi-solid, mucous or liquid sample from a subject or object. The sample collector may be a capillary tube for collecting a liquid sample such as whole blood or a swab for collecting a semi-solid/mucous sample.
In an embodiment of the processing cartridge, the sample collector may be arranged on the actuating cartridge section, such that the sample collector is accommodated in a sample receiving cavity in the main cartridge section when the actuating cartridge section is docked with the main cartridge section or is in the docked position.
The actuating cartridge section may be a longitudinal section.
In an embodiment of the processing cartridge, the actuating cartridge section may comprise a second end at which the sample collector is arranged.
In an embodiment of the processing cartridge, the main cartridge section may feature at least one guide rib or recess configured to interact with a corresponding at least one recess or guide rib, respectively, in the actuating cartridge section during docking. The guide rib may feature a tapered edge for insertion into the recess.
The guide rib/recess may be arranged at a peripheral section of the main cartridge section and the corresponding recess/guide rib may be arranged at a side of the actuating cartridge section facing the main cartridge section during docking.
In an embodiment of the processing cartridge, the main cartridge section or the actuating cartridge section may feature a locking rib, having locking recesses arranged on opposite sides thereof, and the corresponding actuating cartridge section or main cartridge section, may feature two opposing resilient hooks, each hook is configured for interaction with a respective locking recess on the locking rib, wherein the locking rib has a tapered edge configured to be inserted between the resilient hooks during docking.
The solution of having two opposing hooks between which the locking rib is inserted allows for a smaller deflection of the hooks, relative to the use of a single hook providing an equally secure locking. The smaller deflection ensures a more even and smooth locking motion. However, in an alternative embodiment, the locking rib may feature a single recess for interaction with a single hook, the single recess may for instance be arranged at an end of the locking rib.
In an embodiment of the processing cartridge, the container piercing element may comprise a base portion, at least one side portion and a sharp portion distal to the base portion. The sharp portion, e.g. a spike, may be arranged towards the dispensing side of the liquid container.
In an embodiment of the processing cartridge, the container piercing element may comprise at least one recess arranged in the side portion. The recess may extend between the base portion and the sharp portion.
In an embodiment of the processing cartridge, the container piercing element and the container holder element constitute parts of a single unit.
In an embodiment of the processing cartridge, the liquid reservoir chamber comprises a sidewall and a base surface featuring a knob, and the single unit is secured within the liquid reservoir chamber by having a section of the single unit arranged between the knob and the sidewall.
In an embodiment of the processing cartridge, the actuating cartridge section may be connected to the main cartridge section by a pivot connection, wherein
In other words, movement of the actuating cartridge section will face a defined resistance when a pivot movement of the actuating cartridge section causes the resilient arm to interact with the third section. The defined resistance may be an even, variable or controllable resistance.
In other words, the third section of the outer periphery has a distance to the centreline of the bore which increases from a distance being equal to the distance of the first section to the distance of the second section.
The bore may have an inner circular periphery arranged to accommodate the pivot knobs. The pivot knobs have an outer periphery of which at least two opposing sections cooperate with the inner circular periphery of the bore. The two opposing sections may be radial or curved sections. When accommodated in the bore, a centreline being common for both pivot knobs coincides with the centreline of the bore. The opposing sections may ensure that the centreline common for both pivot knobs coincides with the centreline of the bore.
In an embodiment of the processing cartridge, the actuating cartridge section may be connected to the main cartridge section by a pivot connection, wherein
The pivot knobs and the recess are dimensioned and configured such that the connector hub may be inserted between the pinch arms, with a minimum deflection of the pinch arms, when each of the pivot knobs are oriented with one of the first sections facing the respective recess.
The first sections may be radial or curved sections, and the second sections may be parallel straight sections.
In an embodiment of the processing cartridge, the main cartridge section may comprise a microfluidic circuit, the microfluidic circuit may be connected to the sample receiving cavity and the liquid reservoir chamber.
In an embodiment of the processing cartridge, the main cartridge section and the actuating cartridge section may define a disc-shaped body when the actuating cartridge section is in the docked position.
In a second aspect, the present invention provides a processing cartridge comprising a main cartridge section and an actuating cartridge section, the main cartridge section comprises a liquid reservoir chamber, a liquid container and a container piercing element, wherein
The second aspect of the invention may comprise any of the features of the embodiments of the first aspect.
In a third aspect, the present invention provides a processing cartridge comprising a main cartridge section and an actuating cartridge section, the main cartridge section comprises a liquid reservoir chamber, a liquid container, a container holding element and a container piercing element, wherein
The third aspect of the invention may comprise any of the features of the embodiments of the first aspect.
The actuating member of the first, second and third aspect may be configured to move the liquid container by direct or indirect interaction with the liquid container.
In a fourth aspect, the present invention provides a method of introducing a sample to a processing cartridge, the processing cartridge comprises a main cartridge section, an actuating cartridge section and a sample collector, the main cartridge section comprises a liquid reservoir chamber, a liquid container, a container piercing element and a resilient container holding element, wherein
In an embodiment of the method, the main cartridge section comprises a sample cavity, and the sample collector is introduced into the sample cavity when the actuating cartridge section is pivoted to the docked position.
In an embodiment of the processing cartridge, an internal volume of the main cartridge section comprises a microfluidic circuit for processing of a sample, e.g. for analysing the sample.
The term “processing cartridge” is intended to mean a chip/cartridge comprising an internal fluid circuit suitable for performing analysis, assays etc. on a suitable sample introduced into the cartridge, as well as performing various types of chemical reactions, such as polymerase chain reaction (PCR) and synthetic chemistry reactions.
Embodiments of the invention will now be described in greater detail by way of example only and with reference to the following drawings:
The object of the present invention is to provide a processing cartridge suitable for use in centrifuge-based analytical system as described in the background section.
An exemplary processing cartridge according to the invention is shown in
The processing cartridge 1 comprises a main cartridge section 2 and a sampler arm 3 (i.e. an actuating cartridge section).
The main cartridge section 2 features an internal fluidic or microfluidic circuit 7. An exemplary fluidic circuit 7 is shown in the cartridges of
In
An exploded view of the processing cartridge 1 is shown in
As described above, the processing cartridge is made up of a main cartridge section 2 and a sampler arm 3.
The main cartridge section 2 features a liquid reservoir chamber 4, a liquid container 5, a spike 6 (i.e. a container piercing element) and a resilient arm 9 (i.e. a resilient container holding element).
The sampler arm 3 has a first end 13 pivotably connected to the main cartridge section. A second end 14 of the sampler arm 3 features a capillary tube 15 (i.e. a sample collector) for collection of a sample. The sampler arm 3 is configured to dock with the main cartridge section 2. An actuating fin 10 (i.e. an actuating member) is arranged on the sampler arm 3 and is configured to enter the liquid reservoir chamber 4 during docking of the sampler arm 3 with the main cartridge section 2.
The liquid container 5, the spike 6 and the resilient arm 9 are arranged in the liquid reservoir chamber 4. The liquid container 5 is filled with a suitable processing liquid and features a pierceable dispensing side 16, see
The spike 6 is arranged to face the dispensing side of the liquid container 5. In this embodiment, see
To obtain a simple way to fasten the spike 6 and the resilient arm 9 within the liquid reservoir chamber 4, the spike 6 and the resilient arm 9 are interconnected by a connecting section 39, i.e. they form parts of a single element or unit, see
During use, the sampler arm is initially arranged in a non-docking position as shown in
To avoid unintended movement of the sampler arm relative to the main cartridge section during sampling, the sampler arm is connected to the main cartridge section by a pivot coupling providing resistance against movement of the sampler arm from the non-docking position. The pivot coupling is obtained by having two opposing pinch arms 30a,30b at the first end 13 of the sampler arm 3 and a resilient arm 29 arranged between the pinch arms 30a,30b, see
During movement of the sampler arm from the non-docked position, the resilient arm 29 will exert a defined resistance against the movement when interacting with the third section of the outer periphery.
To increase the lateral stiffness of the pivot coupling, the bore 33 is defined by a middle section 34a having a circular inner wall, and a first section 34b and a second section 34c arranged on opposite sides of the middle section. Each of the first and second sections comprises a recess 35 extending between the bore 33 and an outer periphery of the connector hub 32. Each pivot knob 31a,31b has an outer periphery comprising two opposing radial sections K1 configured to cooperate with the circular inner wall and two opposing parallel sections K2, wherein a distance between the parallel sections K2 is shorter than a maximum distance between the radial sections K1, and each recess 35 has a width being smaller than the maximum distance between the radial sections K1 and larger than a maximum distance between the parallel sections K2. The dimensions of the pivot knobs 31a,31b and the recesses 35 are configured such that the connector hub 32 may be inserted between the pinch arms 30a,30b by a minimum deflection of the pinch arms, when each of the pivot knobs 31a,31b is oriented with one of the radial sections K1 facing the respective recess 35. Due to the minimal deflection of the pinch arms during connection to the connector hub 32 via the recesses 35, the stiffness of the pinch arms may be increased, and the lateral stiffness of the pivot coupling is optimized.
In other embodiments, the main cartridge section may feature two opposing pinch arms as described above, while a connector hub as described above is arranged on the first end of the sampler arm.
After a sample has been collected by the capillary tube 15, the sampler arm is pivoted from the non-docking position to a docked position, see
When the sampler arm 3 is in the docked position, the liquid container is in a second position. In the second position, the dispensing side 16 of the liquid container has been pierced and liquid may be released into the liquid reservoir chamber 4. The liquid reservoir chamber 4 comprises a liquid outlet 36 through which a processing liquid may be transferred after being released from the liquid container.
During the movement towards the docked position, see
The resilient arm 9 is configured to be deflected away from an edge of the liquid container, when the liquid container 5 is moved towards the spike 6. The deflection may result in an elastic and/or plastic deformation, or even breaking, of the resilient arm. In the exemplary processing cartridge, the resilient arm features a bend 40a and a first 40b and a second 40c opposing sides, wherein the first side 40b is in contact with the liquid container 5 and is pushed towards the second side 40c when the liquid container 5 is moved towards the second position, see
The processing cartridge 1 according to the invention may comprise features for restricting lateral movement of the sampler arm 3 during movement of the sampler arm 3 towards the docked position. That is preventing movement of the sampler arm 3 in a direction perpendicular to the plane of the pivot movement towards the docked position. In this embodiment, the main cartridge section 2 comprises a guide fin 18 and the sampler arm has a guide recess 19 into which the guide fin is introduced during the pivot movement of the sampler arm, see
In the docked position, the sampler arm 3 is connected to the main cartridge section 2 by a locking mechanism. In the exemplary processing cartridge, the main cartridge section 2 features a locking rib 21, having locking recesses 23a,23b arranged on opposite sides thereof, see
In the exemplary processing cartridge, the liquid container is held in the first position by the resilient arm 9. However, other suitable resilient members are envisioned and may have any form provided the member is able to hold the liquid container in the first position, preferably by an elastic force, and allow the actuating fin to move the liquid container towards the second position against a biasing force. In other embodiments, the resilient arm 9 or any other suitable resilient member may be manufactured (e.g. molded) as an integral part of the liquid container 5 or the liquid reservoir chamber 4.
In the exemplary processing cartridge, the spike 6 is molded separate from the cartridge base 2a. In other embodiments, the spike 6 may be manufactured (e.g. molded) as an integral part of the liquid reservoir chamber 4.
The exemplary processing cartridge illustrated and described herein comprises a combination of several highly advantageous features. However, in other embodiments of the invention, an advantageous processing cartridge may comprise any desired combination of the described features.
In the exemplary embodiment, the circumference of the processing cartridge is substantially circular. However, in other embodiments the circumference of the processing cartridge may have any suitable shape, such as rectangular, square or elliptic.
Number | Date | Country | Kind |
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20201413 | Dec 2020 | NO | national |
This application is a U.S. national stage application under 35 U.S.C. § 371 of International Application No. PCT/EP2021/083512, filed Nov. 30, 2021, which claims the priority of Norwegian Application No. 20201413, filed Dec. 21, 2020, the entire contents of each priority application is incorporated herein by reference.
Filing Document | Filing Date | Country | Kind |
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PCT/EP2021/083512 | 11/30/2021 | WO |