CN110371435B - Liquid reagent storage box for centrifugal flow control and microfluidic chip structure - Google Patents
Liquid reagent storage box for centrifugal flow control and microfluidic chip structure Download PDFInfo
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Abstract
The application relates to a liquid reagent storage box and a microfluidic chip structure, wherein the storage box comprises a kit main body, a reagent box bottom plate and a sealing plug; the reagent box bottom plate is matched with the reagent box main body and forms a storage cavity together; the storage box is provided with an outlet far away from the rotation center of the storage box, and the outlet is positioned at the adjacent position of the kit bottom plate and the kit main body; the storage cavity is communicated with the outlet and is used for being communicated with the outside through the outlet; the reagent box bottom plate is also provided with an outflow structure at the outlet, and the outflow structure and other structures of the reagent box bottom plate adjacent to the outflow structure form a height difference. On one hand, the liquid reagent storage box is beneficial to conveniently and effectively storing the liquid reagent required by centrifugal microfluidics through the design of the storage cavity; on the other hand, the design of the height difference of the outflow structure at the outlet is favorable for ensuring that liquid can completely flow out in the centrifugal process, so that reagent waste or shortage is avoided, the cost is saved, and the reaction effect of centrifugal microfluidics is ensured.
Description
Technical Field
The present application relates to the field of centrifugal fluidics, and in particular to a liquid reagent storage cartridge and a microfluidic chip structure for centrifugal fluidics, and more particularly to a liquid reagent storage cartridge and a microfluidic chip structure for centrifugal microfluidics.
Background
Centrifugal fluidics refers to the manipulation of liquids on a sub-millimeter scale, i.e., centrifugal liquid flow control. It integrates the basic operation units related to the biological and chemical fields, even the functions of the whole laboratory, including sampling, diluting, reacting, separating, detecting, etc. on a small Chip, so it is also called Lab-on-a-Chip. The chip generally comprises various liquid storage tanks and a micro-channel network which is connected with each other, can greatly shorten the sample processing time, and realizes the maximum utilization efficiency of reagent consumables by precisely controlling the liquid flow. The micro-fluidic provides a very wide prospect for the application in numerous fields such as biomedical research, drug synthesis screening, environmental monitoring and protection, health quarantine, judicial identification, biological reagent detection and the like.
For microfluidic-based point-of-care diagnostic (POCT) devices, "sample-to-answer" (sample-to-answer) is an important goal of such devices. To achieve "sample in and out", a pre-storage of reagents is made. This is because there are often more than one reagent involved in a POCT apparatus, and if these reagents are added manually, the ease of use of the apparatus is greatly compromised. The reagent pre-storage of the microfluidic chip is generally divided into the pre-storage of dry powder and liquid reagent forms. The pre-stored release of the dry powder reagent typically requires the use of a diluent, which may be the added liquid sample itself. Of course, in many cases, the diluent is pre-stored in liquid form inside the chip separately. In addition, for some reagents that are not well suited to pre-storage in dry powder form, it is also contemplated to pre-store them directly inside the microfluidic chip in liquid form. At the same time, it is also necessary to ensure that the pre-stored liquid reagent is effectively released when required. Pre-storage and release of liquid reagents is critical in centrifugal microfluidics.
Disclosure of Invention
Therefore, it is necessary to provide a liquid reagent storage box and a microfluidic chip structure, which mainly solve the problem of pre-storing and releasing liquid reagents in centrifugal microfluidics.
A liquid reagent storage cassette comprising a reagent cartridge, the reagent cartridge comprising a reagent cartridge body and a reagent cartridge floor;
the reagent box bottom plate is matched with the reagent box main body and forms a storage cavity together;
the liquid reagent storage box is provided with an outlet far away from the rotation center of the liquid reagent storage box, and the outlet is positioned at the adjacent position of the kit bottom plate and the kit main body;
the storage cavity is communicated with the outlet and is used for being communicated with the outside through the outlet;
the reagent box bottom plate is also provided with an outflow structure at the outlet, and the outflow structure and other structures of the reagent box bottom plate adjacent to the outflow structure form a height difference.
On one hand, the liquid reagent storage box is beneficial to conveniently and effectively storing the liquid reagent required by centrifugal microfluidics through the design of the storage cavity; on the other hand, the design of the height difference of the outflow structure at the outlet is favorable for ensuring that liquid can completely flow out in the centrifugal process, so that reagent waste or shortage is avoided, the cost is saved, and the reaction effect of centrifugal microfluidics is ensured.
In one embodiment, the cartridge body has an arcuate surface on a side thereof away from the center of rotation, and the outlet is provided at a position where the arcuate surface is at a maximum distance from the center of rotation.
In one embodiment, the reagent box main body or the reagent box bottom plate is further extended with a protruding structure.
In one embodiment, the protruding structure is provided with a through hole; and/or the projection structure and the outlet are respectively positioned at two opposite sides of the kit body, and the projection structure is closer to the rotation center of the liquid reagent storage box than the outlet.
In one embodiment, the end of the cassette base plate at the position away from the center of rotation of the liquid reagent storage cassette is provided with the outflow structure in an extending manner;
the outflow structure and the rest of the adjacent reagent box bottom plate form a step shape, or the outflow structure and the rest of the adjacent reagent box bottom plate form a slope shape;
the kit main body is provided with a matching structure at the end part close to the outflow structure, the matching structure and other adjacent structures of the kit main body form a height difference, and the matching structure is used for matching with the outflow structure to jointly install a sealing plug;
the kit main body and the kit bottom plate are integrally arranged;
the kit main body and the kit bottom plate are made of hard aluminum foil, metal plates or low-permeability thermoplastic plastics.
In one embodiment, the liquid reagent storage cartridge further comprises a closure disposed at the outlet to close the storage chamber.
In one embodiment, the closure plug has a hot melt structure to open the storage chamber by hot melt.
In one embodiment, the closure plug is removably disposed in the outlet to centrifugally open the storage chamber.
In one embodiment, the sealing plug is made of an elastic material and closes the storage chamber in an elastically deformable manner, or the sealing plug has a rigid structure and an adhesive layer and closes the storage chamber in an adhesive manner.
In one embodiment, the end of the cassette base plate at the position away from the center of rotation of the liquid reagent storage cassette is provided with the outflow structure in an extending manner;
the outflow structure and the rest of the adjacent reagent box bottom plate form a step shape, or the outflow structure and the rest of the adjacent reagent box bottom plate form a slope shape;
the kit main body is provided with a matching structure at the end part close to the outflow structure, the matching structure and other adjacent structures of the kit main body form a height difference, and the matching structure is used for matching with the outflow structure to jointly install the sealing plug;
the shape of the sealing plug is matched with the shape of the outermost side of the outlet, or the shape of the sealing plug is matched with the outlet and/or the outflow structure, and/or the sealing plug has a T-shaped section;
the kit main body and the kit bottom plate are integrally arranged;
the kit main body and the kit bottom plate are made of hard aluminum foil, metal plates or low-permeability thermoplastic plastics.
A microfluidic chip structure comprising any one of the liquid reagent storage cartridges.
In one embodiment, the microfluidic chip structure is further provided with a holding groove for holding the liquid reagent storage box and a positioning member for fixing the liquid reagent storage box.
Drawings
Fig. 1 is a schematic structural diagram of an external shape of a liquid reagent storage cassette according to an embodiment of the present application.
Fig. 2a is another schematic view of the embodiment shown in fig. 1.
Fig. 2b is another schematic view of the embodiment shown in fig. 1.
FIG. 2c is a schematic cross-sectional view taken along the line A-A of the embodiment shown in FIG. 2 a.
Fig. 3a is a partially enlarged schematic view of the embodiment shown in fig. 2c and a structural schematic view of a sealing plug B-B of the embodiment shown in fig. 3B in a direction cross-sectional view.
Fig. 3b is a schematic structural diagram of a sealing plug according to an embodiment of the present application.
Fig. 3c is a schematic view of the closure side of the embodiment shown in fig. 3 b.
Fig. 4 is a schematic cross-sectional view of a part of a microfluidic chip structure according to an embodiment of the present application.
Fig. 4a is a schematic diagram of another embodiment of a microfluidic chip structure according to the present application.
FIG. 4b is another schematic view of the embodiment shown in FIG. 4 a.
FIG. 4c is another schematic view of the embodiment shown in FIG. 4 a.
Fig. 5a is a schematic diagram of another embodiment of a microfluidic chip structure according to the present application.
FIG. 5b is another schematic view of the embodiment shown in FIG. 5 a.
FIG. 5c is another schematic view of the embodiment shown in FIG. 5 a.
FIG. 6a is a schematic view of a portion of a liquid reagent storage cassette according to an embodiment of the present application.
Fig. 6b is a schematic view of the shape of the closure plug of the embodiment shown in fig. 6 a.
Fig. 7a is a partial schematic structural view of a liquid reagent storage box with a sealing plug removed according to another embodiment of the present application.
Fig. 7b is a schematic view of the closure plug of the embodiment shown in fig. 7 a.
Fig. 8a is a partial schematic structural view of a liquid reagent storage box with a sealing plug removed according to another embodiment of the present application.
Fig. 8b is a schematic view of the closure plug of the embodiment shown in fig. 8 a.
Fig. 9a is a partial schematic structural view of a liquid reagent storage box with a sealing plug removed according to another embodiment of the present application.
Fig. 9b is a schematic view of the closure plug of the embodiment of fig. 9 a.
Detailed Description
In order to make the aforementioned objects, features and advantages of the present application more comprehensible, embodiments accompanying the present application are described in detail below with reference to the accompanying drawings. In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present application. This application is capable of embodiments in many different forms than those described herein and that modifications may be made by one skilled in the art without departing from the spirit and scope of the application and it is therefore not intended to be limited to the specific embodiments disclosed below. It will be understood that when an element is referred to as being "secured to" or "disposed on" another element, it can be directly on the other element or intervening elements may also be present. When an element is referred to as being "connected" to another element, it can be directly connected to the other element or intervening elements may also be present. The terms "vertical," "horizontal," "left," "right," and the like as used herein are for illustrative purposes only and do not represent the only embodiments.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application belongs. The terminology used herein in the description of the present application is for the purpose of describing particular embodiments only and is not intended to be limiting of the application. As used herein, the term "and/or" includes any and all combinations of one or more of the associated listed items.
The device related to the scheme comprises a liquid reagent storage box and a corresponding centrifugal microfluidic platform for carrying a reagent kit, and the core of the scheme lies in a reagent sealing and controlled release method and different installation methods of the reagent kit, and the detailed description is as follows. In one embodiment of the present application, a liquid reagent storage cassette comprises a reagent cassette comprising a reagent cassette main body and a reagent cassette bottom plate; the reagent box bottom plate is matched with the reagent box main body and forms a storage cavity together; the liquid reagent storage box is provided with an outlet far away from the rotation center of the liquid reagent storage box, and the outlet is positioned at the adjacent position of the kit bottom plate and the kit main body; the storage cavity is communicated with the outlet and is used for being communicated with the outside through the outlet; the reagent box bottom plate is also provided with an outflow structure at the outlet, and the outflow structure and other structures of the reagent box bottom plate adjacent to the outflow structure form a height difference. On one hand, the liquid reagent storage box is beneficial to conveniently and effectively storing the liquid reagent required by centrifugal microfluidics through the design of the storage cavity; on the other hand, the design of the height difference of the outflow structure at the outlet is favorable for ensuring that liquid can completely flow out in the centrifugal process, so that reagent waste or shortage is avoided, the cost is saved, and the reaction effect of centrifugal microfluidics is ensured.
In one embodiment, a liquid reagent storage cassette for centrifugal fluidic, comprising part or all of the structure of the following embodiments; that is, the liquid reagent storage cassette includes some or all of the following technical features. In one embodiment, a liquid reagent storage cassette for centrifugal fluidic comprising a kit; the kit comprises a kit bottom plate and a kit main body. In one embodiment, the liquid reagent storage box is used for being fixed in the containing groove of the microfluidic chip structure. In one embodiment, the receiving groove has an output channel communicating with the reaction chamber, the accumulation chamber or the other chamber. In one embodiment, a liquid reagent storage cassette for centrifugal fluidic control includes a reagent cartridge and a closure.
In one embodiment, the kit main body and the kit bottom plate are integrally arranged; such a design facilitates the manufacturing of the liquid reagent storage cassette. In one embodiment, the materials of the kit body and the kit bottom plate are both hard aluminum foil, metal plate or low-permeability thermoplastic. The design is not only beneficial to the production and manufacture of the liquid reagent storage box, but also beneficial to the storage of liquid reagents required by the structure of the microfluidic chip.
In one embodiment, the reagent kit bottom plate and the reagent kit main body are matched and form a storage cavity together; the storage cavity is used for storing liquid reagents required by centrifugal microfluidics. The shape of the storage cavity is determined by the matching of the reagent box bottom plate and the reagent box main body, and can be a cuboid, a sphere, an ellipsoid and the like. Further, in one embodiment, the storage chamber has an extreme position therein that is further from the center of rotation of the liquid reagent storage cartridge than other positions of the storage chamber; further, in one embodiment, the reagent cassette base plate is adapted to contact the bottom of the receiving well, the extreme position being located adjacent to the reagent cassette base plate. Further, in one embodiment, the extreme position has the greatest centrifugal moment than the other positions of the storage chamber. Further, in one embodiment, a side of the cartridge body away from the rotation center has an arc surface, and the extreme position is located at a position where the arc surface is the largest distance from the rotation center. The design is such that the liquid reagent storage cassette has an extreme position which, in cooperation with the outlet of the other embodiments, facilitates full flow of the liquid reagent out of the storage chamber.
In one embodiment, the liquid reagent storage box is provided with an outlet away from the rotation center of the liquid reagent storage box, and the outlet is positioned at the position of the adjacent position of the kit bottom plate and the kit main body; further, in one of the embodiments, the outlet is located at the extreme position. In one embodiment, the cartridge body has an arcuate surface on a side thereof away from the center of rotation, and the outlet is provided at a position where the arcuate surface is at a maximum distance from the center of rotation. The design skillfully utilizes the centrifugal force of the centrifugal flow control, thereby not only being beneficial to conveniently and effectively storing the liquid reagent required by the centrifugal flow control, but also being beneficial to further ensuring that the liquid can completely flow out in the centrifugal process, avoiding the waste or the deficiency of the reagent, saving the cost and ensuring the reaction effect of the centrifugal flow control.
In one embodiment, the storage chamber is arranged in communication with the outlet and is used for communicating with the outside through the outlet; the reagent box can be produced separately during production, for example, the reagent box main body and the reagent box bottom plate are integrally formed, and then the outlet is formed by slotting. The sealing plug is usually matched with the sealing plug for use. In one embodiment, the liquid reagent storage cartridge further comprises a closure disposed at the outlet to close the storage chamber; namely a liquid reagent storage box, which comprises a reagent box main body, a reagent box bottom plate and a sealing plug; the reagent box bottom plate is matched with the reagent box main body and forms a storage cavity together; the liquid reagent storage box is provided with an outlet far away from the rotation center of the liquid reagent storage box, and the outlet is positioned at the adjacent position of the kit bottom plate and the kit main body; the storage cavity is communicated with the outlet and is communicated with the outside through the outlet, and the sealing plug is arranged at the outlet to seal the storage cavity; the reagent box bottom plate is also provided with an outflow structure at the outlet, and the outflow structure and other structures of the reagent box bottom plate adjacent to the outflow structure form a height difference. The rest of the examples are analogized. On one hand, the liquid reagent storage box is beneficial to conveniently and effectively storing the liquid reagent required by centrifugal microfluidics through the design of the storage cavity; on the other hand, the design of the height difference of the outflow structure at the outlet is beneficial to ensuring that liquid can completely flow out in the centrifugal process, avoiding reagent waste or shortage, saving cost and ensuring the reaction effect of centrifugal microfluidics; on the other hand, the design of the sealing plug is beneficial to controlling the release of the liquid reagent, and particularly, the control of the release condition of the liquid reagent can be accurately realized by controlling the strength of the storage cavity closed by the sealing plug. In one embodiment, the shape of the sealing plug is matched with the shape of the outermost side of the outlet, in one embodiment, the shape of the sealing plug is matched with the outlet and/or the outflow structure, and in one embodiment, the sealing plug has a T-shaped cross section; in one embodiment, the closure plug is removably disposed in the outlet to centrifugally open the storage chamber. Further, in one embodiment, the sealing plug is movably disposed at the outlet to close the storage chamber, and the sealing plug automatically leaves the outlet to open the storage chamber when the force exceeds a design limit value, so that the liquid reagent in the storage chamber can flow out. In one embodiment, the sealing plug is made of an elastic material and closes the storage chamber in an elastically deformable manner, or the sealing plug has a rigid structure and an adhesive layer and closes the storage chamber in an adhesive manner. In one embodiment, the sealing plug is fixedly arranged on the outlet to close the storage cavity, and the sealing plug is melted when being heated to exceed a design limit value to open the storage cavity so that the liquid reagent in the storage cavity can flow out. In one embodiment, the closure plug has a hot melt structure to open the storage chamber by hot melt. The design is favorable for controlling the release of the liquid reagent, and particularly, the control of the release condition of the liquid reagent can be accurately realized by controlling the strength of the sealing plug for closing the storage cavity.
In one embodiment, the reagent box bottom plate is further provided with an outflow structure at the outlet, and the outflow structure forms a height difference with other structures of the reagent box bottom plate adjacent to the outflow structure, that is, the outflow structure has a height difference with other structures of the reagent box bottom plate adjacent to the outflow structure. In one embodiment, the end of the cassette base plate at the position away from the center of rotation of the liquid reagent storage cassette is provided with the outflow structure in an extending manner; in one embodiment, the outflow structure forms a stair-step shape with the rest of the structure of the reagent cartridge bottom plate adjacent to it, and in one embodiment, the outflow structure forms a ramp shape with the rest of the structure of the reagent cartridge bottom plate adjacent to it; further, in one embodiment, the slope of the ramp shape is less than 65 degrees; further, in one embodiment, the slope of the ramp shape is less than 55 degrees; if the gradient is too large, an air gap is easily generated when the liquid reagent flows out, and a certain blocking effect may be generated on a fine output channel. Further, in one embodiment, the height difference is less than 60% of the thickness of the cassette base plate. Such design is favorable to guaranteeing that liquid can flow out completely in the centrifugation process, avoids reagent extravagant or not enough, has practiced thrift the expense and has ensured centrifugal micro-fluidic reaction effect. Further, in one embodiment, the reagent cassette base plate has a flat end at the outflow structure, and further, in one embodiment, the flat end is provided with an elastic layer or the liquid reagent storage cassette is sleeved with an elastic sleeve at the flat end. Such design is favorable to promoting the safety in utilization of liquid reagent storage box avoids having the potential safety hazard so that the staff receives the injury.
In order to facilitate production and installation of the sealing plug, in one embodiment, the kit body is provided with a matching structure at the end part close to the outflow structure, the matching structure forms a height difference with other adjacent structures of the kit body, and the matching structure is used for matching with the outflow structure to install the sealing plug together; further, in one embodiment, the height difference formed by the outflow structure and the rest of the reagent box bottom plate adjacent to the outflow structure is equal to the height difference formed by the matching structure and the rest of the reagent box main body adjacent to the matching structure; further, in one embodiment, the height difference formed by the outflow structure and the rest of the reagent box bottom plate adjacent to the outflow structure is symmetrically arranged with the height difference formed by the matching structure and the rest of the reagent box main body adjacent to the matching structure. In one embodiment, the height difference formed by the outflow structure and the rest of the reagent box bottom plate adjacent to the outflow structure is symmetrically arranged with the height difference formed by the matching structure and the rest of the reagent box main body adjacent to the matching structure, and the sealing plug forms a cylinder shape at the symmetrically arranged position. Such design is favorable to the installation on the one hand seal the stopper and realize better sealed effect, and on the other hand is favorable to the cooperation design seal the stopper, reduce its production technology, make seal the stopper easily production.
In order to facilitate the fixation of the liquid reagent storage cartridge in or on the microfluidic chip structure to which it is applied, in one embodiment the cartridge body is further extended with a protruding structure and/or the cartridge base plate is further extended with a protruding structure. Further, in one embodiment, the number of the protruding structures is one, two or more. In one embodiment, the protruding structure is provided with a through hole; in one embodiment, the through holes may be round holes, square holes, or the like. In one embodiment, the cross-section of the perforations includes, but is not limited to, circular; the projection structure and the outlet are respectively positioned at two opposite sides of the kit body, and the projection structure is closer to the rotation center of the liquid reagent storage box than the outlet. In one embodiment, the protruding structure is provided with a through hole; and the protruding structures and the outlet are respectively positioned at two opposite sides of the kit body, and the protruding structures are closer to the rotation center of the liquid reagent storage box than the outlet. By adopting the design, the liquid reagent storage box can be fixed in the corresponding designed position in the microfluidic chip structure by the protruding structure in a matching way, and the liquid reagent storage box can also be fixed in the microfluidic chip structure by a through-hole matching plug connector, such as a plug rod and the like.
In one embodiment, the end of the cassette base plate at the position away from the center of rotation of the liquid reagent storage cassette is provided with the outflow structure in an extending manner; the outflow structure and the rest of the adjacent reagent box bottom plate form a step shape, or the outflow structure and the rest of the adjacent reagent box bottom plate form a slope shape; the kit main body is provided with a matching structure at the end part close to the outflow structure, the matching structure and other adjacent structures of the kit main body form a height difference, and the matching structure is used for matching with the outflow structure to jointly install a sealing plug; the kit main body and the kit bottom plate are integrally arranged; the kit main body and the kit bottom plate are made of hard aluminum foil, metal plates or low-permeability thermoplastic plastics. In one embodiment, the end of the cassette base plate at the position away from the center of rotation of the liquid reagent storage cassette is provided with the outflow structure in an extending manner; the outflow structure and the rest of the adjacent reagent box bottom plate form a step shape, or the outflow structure and the rest of the adjacent reagent box bottom plate form a slope shape; the kit main body is provided with a matching structure at the end part close to the outflow structure, the matching structure and other adjacent structures of the kit main body form a height difference, and the matching structure is used for matching with the outflow structure to jointly install the sealing plug; the shape of the sealing plug is matched with the shape of the outermost side of the outlet, or the shape of the sealing plug is matched with the outlet and/or the outflow structure, and/or the sealing plug has a T-shaped section; the kit main body and the kit bottom plate are integrally arranged; the kit main body and the kit bottom plate are made of hard aluminum foil, metal plates or low-permeability thermoplastic plastics. The design is beneficial to realizing the production and manufacturing of the liquid reagent storage box on the one hand, and ensuring the sealing effect of the outlet on the other hand, so that the liquid reagent in the storage cavity can accurately and completely flow out in a controlled manner, the release condition of the liquid reagent is accurately controlled, the waste or deficiency of the reagent is avoided on the other hand, the cost is saved, and the reaction effect of centrifugal microfluidics is guaranteed.
In one embodiment, a liquid reagent storage box is shown in fig. 1, the liquid reagent storage box comprises a reagent box, the reagent box comprises a reagent box main body 2 and a reagent box bottom plate 1; referring to fig. 2c, the reagent box bottom plate 1 and the reagent box main body 2 are matched and form a storage chamber 6 together, and the outlet 3 is located at a position adjacent to the reagent box bottom plate 1 and the reagent box main body 2, wherein the reagent box bottom plate and the reagent box main body are made of low-permeability thermoplastic plastics or hard aluminum foil or metal plate.
As shown in fig. 2a, 2b and 2c, the main body of the reagent kit is extended with a protruding structure 4, and the protruding structure 4 is provided with a through hole 5; i.e. a kit using a protruding structure 4 with perforations 5, it is of course also possible to use a protruding structure without perforations 4, wherein the perforations are not limited to circles; the projection arrangement 4 may be provided in a plurality, distributed at the top end of the cartridge body, i.e. near or closest to the centre of rotation. In practical applications, the reagent cartridge shown in fig. 2c is rotated 90 degrees to the right and used, and the reagent cartridge bottom plate is located at the lower part of the liquid reagent storage box, i.e. the reagent cartridge bottom plate is closer to the ground.
Wherein the liquid reagent is stored in advance in the cavity of the cartridge body 2 through the outlet 3, and in one embodiment, the liquid reagent storage cartridge further comprises a closure; referring to fig. 3a, the outlet 3 is sealed by a sealing plug 23. In one embodiment, the opening of the outlet 3 is close to the bottom plate 1 of the reagent box and is positioned at the outer side of the centrifugal structure, the opening is in a step shape, the inner part of the opening is flush with the bottom of the cavity for storing the reagent, and the outer part of the opening is lower than the top end of the protruding part of the bottom plate 1 of the reagent box, so that the liquid can completely flow out in the centrifugal process. Referring to fig. 3b and 3c, after the reagent kit is loaded with liquid reagent upside down, the reagent kit is sealed by using a sealing plug 23, and the shape of the sealing plug 23 is matched with the outermost structure of the outlet 3 to ensure that the liquid does not seep out after sealing. In the specific implementation, the examples of the sealing plug are classified into the following 3 types.
In one embodiment, the sealing plug 23 is made of an elastic material, the liquid is prevented from seeping out by the expansion stress of the elastic structure, and the liquid in the chamber reaches the set pressure by high-speed centrifugation, and the sealing plug 23 is extruded to achieve the liquid release effect. In this embodiment, the centrifugal speed of the centrifugal flow control can be designed by the expansion stress of the elastic structure, and the expansion stress of the elastic structure can also be designed by the centrifugal speed of the centrifugal flow control in the reverse direction, so as to achieve the technical effect of controlling the accurate output of the liquid reagent.
In another embodiment, a rigid closure 23 is used, and on the outside of the closure base 23b, a layer of sealing material 23a is attached, previously fixed to the surface of the closure base 23b, optionally with adhesive double-sided tape, or with an aluminum foil seal for ultrasonic welding, which requires a layer of aluminum foil to be previously attached on the outside of the outlet 3, and which also extrudes the closure 23 by centrifugation. In this embodiment, the centrifugal speed of the centrifugal flow control can be designed by the viscous force, and the viscous force can also be designed by the centrifugal speed of the centrifugal flow control in the reverse direction, so as to achieve the technical effect of controlling the accurate output of the liquid reagent.
In another embodiment, a thermal phase-change material may be used as the sealing material 23a, and the key points are to control the heating time to melt the outer sealing material 23a, and after sealing, the sealing material 23a is rapidly solidified to fix the sealing plug 23, thereby preventing liquid from leaking out. The phase change material for sealing includes, but is not limited to, paraffin such as solid wax, microcrystalline wax, synthetic wax, organic or inorganic gel material such as various kinds of resins — PAM, COC, EVA, PMMA, PET, PS, PVDF, PA, PP, and the like. In this embodiment, the liquid reagent can be heated to a certain temperature/time to achieve the technical effect of controlling the accurate output of the liquid reagent.
In one embodiment, as shown in fig. 6a, the outlet 3 is located adjacent to the reagent cartridge bottom plate 1 and the reagent cartridge main body 2, the outflow structure 110 and the remaining structure 120 of the reagent cartridge bottom plate adjacent thereto form a slope shape with a height difference, and the liquid reagent a flows out from the outlet 3, and referring to fig. 6b, the shape of the sealing plug 23 matches with the outlet 3 to close the storage chamber.
In one embodiment, as shown in fig. 7a, the outlet 3 is located adjacent to the reagent cartridge base plate 1 and the reagent cartridge main body 2, and the outflow structure 110 and the remaining structure 120 of the reagent cartridge base plate adjacent thereto are formed in a stepped shape having a height difference, so that the outlet 3 also forms an inner port 310 and an outer port 320 adjacent to the storage chamber, and the passage area of the outer port 320 is larger than that of the inner port 310; liquid reagent a flows out of outlet 3. referring also to fig. 7b, closure 23 is shaped to fit outlet 3 to close the storage chamber, and closure 23 is shaped to fit inner opening 310 and outer opening 320, forming a shape similar to an L.
In one embodiment, as shown in fig. 8a, the outlet 3 is located adjacent to the reagent cartridge base plate 1 and the reagent cartridge main body 2, the outflow structure 110 and the rest of the structure 120 of the reagent cartridge base plate adjacent to the outflow structure 110 form a step shape with a height difference, the reagent cartridge main body 2 is provided with a fitting structure 210 at the end thereof close to the outflow structure 110, the fitting structure 210 and the rest of the structure 220 of the reagent cartridge main body adjacent to the fitting structure 210 form a height difference, so that the outlet 3 also forms an inner opening 310 and an outer opening 320 close to the storage cavity, and the passing area of the outer opening 320 is larger than that of the inner opening 310; liquid reagent a flows out of outlet 3. referring also to fig. 8b, the shape of closure 23 matches that of outlet 3 to close the storage chamber, and the shape of closure 23 matches that of inner and outer ports 310 and 320, forming a T-like shape.
In one embodiment, as shown in fig. 9a, the outlet 3 is located adjacent to the cartridge base plate 1 and the cartridge main body 2, the end of the cartridge base plate at the position far away from the rotation center of the liquid reagent storage cartridge is provided with the outflow structure 110 in an extending manner, i.e. the outflow structure 110 protrudes out of the cartridge main body 2, the outflow structure 110 and the rest structure 120 of the cartridge base plate adjacent to the outflow structure 110 form a step shape with a height difference, the cartridge main body 2 is provided with the matching structure 210 at the end close to the outflow structure 110, the matching structure 210 and the rest structure 220 of the cartridge main body adjacent to the matching structure 210 form a height difference, so that the outlet 3 also forms an inner opening 310 and an outer opening 320 close to the storage cavity, and the passing area of the outer opening 320 is larger than the passing area of; liquid reagent a flows out of outlet 3. referring also to fig. 9b, closure 23 is shaped to fit with outlet 3 to close the storage chamber, and closure 23 is shaped to fit with inner and outer ports 310 and 320, forming a T-like shape.
In one embodiment, a microfluidic chip structure comprises the liquid reagent storage cartridge of any of the embodiments. In one embodiment, the number of the liquid reagent storage cartridges in the microfluidic chip structure is one, two or more. In one embodiment, the microfluidic chip structure is further provided with a holding groove for holding the liquid reagent storage box and a positioning member for fixing the liquid reagent storage box. In one embodiment, the number of the holding grooves is the same as the number of the liquid reagent storage cartridges or the number of the holding grooves is larger than the number of the liquid reagent storage cartridges. In one embodiment, the protruding structure is provided with a through hole, and the positioning element is a plug connector matched with the through hole, and the like. By adopting the design, the liquid reagent storage box introduces the liquid reagent through the outlet and is sealed by the special sealing plug, so that the sealing plug is withdrawn at a specific centrifugal rotating speed or temperature to release the liquid reagent. The liquid reagent storage box is fixed in a specific groove chamber of the microfluidic chip structure in a clamping groove and insertion rod mode, and the reagent storage device is prevented from falling off in the transportation and use processes of the microfluidic chip structure.
In one embodiment, as shown in fig. 4, the microfluidic chip structure is provided with a holding groove 8 or 9 for holding the liquid reagent storage cartridge, that is, there may be one holding groove 8 or 9, or two holding grooves, including the holding groove 8 and the holding groove 9. The top of the holding tank is connected with a tank chamber 18 capable of holding the protruding structure 4 of the reagent kit, and the perforation 3 in the protruding structure 4 of the reagent kit corresponds to the bottom structure 17b of the slot 17 of the microfluidic chip structure. The bottom of the accommodating cavity 8 or 9 is provided with a groove 22 capable of accommodating the protruding structure of the reagent box bottom plate 1, so as to ensure that the reagent box is prevented from shaking during chip transportation and use. In order to allow the reagent vessel base plate 1 and the top projection 4 of the reagent vessel to be inserted into the recess 22 and the well 18, a space is reserved in the receiving space 8 or 9 to ensure that the reagent vessel can be slid into the well from the right to the left. To further secure the reagent cartridge, the plunger 24 is inserted into the slot 17, the bottom of the plunger 24 enters the bottom structure 17b of the slot 17, and the protruding structure of the plunger 24 is secured by screwing or gluing completely into the top structure 17a of the slot 17. In the process of packaging the reagent box of the liquid reagent storage box, firstly, liquid reagent is injected from the reagent box outlet 3, after the reagent box is sealed by the sealing plug 23, the reagent box is inserted into the rightmost side of the accommodating groove 8 or 9, the reagent box slides leftwards to enable the protruding structure 4 and the reagent box bottom plate 1 of the reagent box to enter the groove chamber 18 and the groove 22, the reagent box is inverted, the inserting rod 24 is inserted into the inserting groove 17 to fix the reagent box, and finally, the accommodating groove 8 or 9 is sealed by the sealing film or the plate body 19. By the design, the liquid reagent of the centrifugal microfluidic control is pre-stored, so that the in-vitro diagnosis and analysis process of the centrifugal microfluidic control is simpler and more convenient; the controlled release process of the pre-stored reagent is realized by controlling a centrifugation or heating mode, and the sequential release process of various reagents is realized; compared with the prior art, the clamping groove design of the microfluidic chip structure enables reagent pre-storage to be more stable, and the transportation requirement is lower; and the structure of the kit and the microfluidic chip structure is easy to process and assemble in batches, and the cost is lower.
In one embodiment, the liquid reagent storage box for centrifugal flow control is used for loading in a microfluidic chip structure singly or in multiple ways to achieve the preset and controlled release effect of a specific liquid reagent. The kit of the liquid reagent storage box comprises a kit bottom plate 1, a kit main body 2, an opening 3, a protruding structure 4 and a perforation 5, and two different embodiments of the microfluidic chip structure of the sequential release scheme of the pre-stored reagents are continuously provided below based on a centrifugal microfluidic platform.
In one embodiment, the 2 kits are packaged in the same scheme, and can be made of phase-change materials, viscous double-sided adhesive tapes, elastic materials or aluminum foils welded and sealed as sealing plugs, and only the heating or centrifugation mode is needed to be adopted, so that the two liquids are released simultaneously and are sequentially mixed with the sample through the microfluidic chip structure. As shown in fig. 4a and 4b, the base body 7 of the microfluidic chip structure comprises 2 accommodating grooves capable of accommodating a reagent kit, namely, an accommodating groove 8 and an accommodating groove 9 (wherein the groove 22 is not shown), a reagent buffer chamber 11, pipelines 10 and 13, a siphon valve 12, a sample chamber 14, a gas conducting pipeline 15, and an air hole 16, and a fixing slot 17 communicating with a chamber 18 (not shown) in the accommodating grooves 8 and 9 is formed in the back. In application, the microfluidic chip structure is left standing, and a sample is added from a sample introduction hole (not shown in the figure) of the sample cavity 14; simultaneously breaking through the sealing plug the reagent kit liquid reagents in the holding tanks 8 and 9 by a heating or centrifugation method, wherein the liquid b is released into the holding tank 8, and the liquid a is released into the holding tank 9; in the process of high-speed rotation of the microfluidic chip structure, the liquid b in the holding tank 8 enters the buffer cavity 11 (the volume of the buffer cavity 11 needs to be ensured to be larger than the total volume of the liquid reagent b) through the pipeline 10 under the action of centrifugal force, the liquid a in the holding tank 9 enters the sample cavity 14 through the pipeline 13 to be mixed with a sample, and a first-step reaction (such as a cracking reaction) occurs; the centrifugal rotation speed is reduced so that the liquid b in the buffer chamber 11 passes through the siphon valve 12, and the rotation speed is increased again so that the liquid b completely enters the sample chamber 14 to be mixed with the sample. It should be noted that the above-mentioned microfluidic chip structure is only one of the microfluidic chip structures described in the present application, and should not be considered as a strict limitation on the microfluidic chip structure described in the present application.
In another embodiment, reagent boxes sealed by double-sided adhesive with different adhesive strengths, sealing plugs with different elasticity or aluminum foils with different welding strengths are adopted to ensure that the sealing plugs of specific reagent boxes can be extruded by high-speed and low-speed centrifugation to achieve the purpose of sequential release of reagents. As shown in fig. 5a and 5b, the base body 7 of the microfluidic chip structure comprises 2 accommodating grooves 8 and 9 (including a groove 22) capable of accommodating a reagent cartridge, communicating channels 20 and 21, a sample chamber 14, a gas conducting channel 15, and a gas hole 16, and a fixing slot 17 on the back for communicating a chamber 18 (not shown) in the accommodating grooves 8 and 9. In application, the microfluidic chip structure is left standing, and a sample is added from a sample introduction hole (not shown in the figure) of the sample cavity 14; through a low-speed centrifugation mode, a liquid reagent a pre-stored in a reagent box in the accommodating groove 9 breaks through the sealing plug, enters the accommodating groove 9, enters the sample cavity 14 through the communicating pipeline 21, is mixed with a sample, and performs a first-step reaction (such as a cell lysis reaction); the centrifugal speed is raised so that the liquid reagent b of the reagent kit in the holding tank 8 breaks through the sealing plug and enters the holding tank 8, and then enters the sample chamber 14 through the communication pipeline 20 to further react with the sample.
Further, in one embodiment, the microfluidic chip structure further comprises a reagent sequential loading structure, and the reagent sequential loading structure comprises at least two of the accommodating grooves which are sequentially arranged. In one embodiment, the reagent sequential loading structure includes a loading communicating port, a target communicating port, at least one target chamber, and at least two sequentially arranged accommodating grooves, each accommodating groove corresponding to a target chamber; the microfluidic chip structure or the reagent sequential loading structure is provided with a target rotation center; in each accommodating groove, the first accommodating groove is communicated with the loading communicating port and is communicated with a corresponding target chamber through a first loading pipeline, the position, close to the target rotation center, of the next accommodating groove is communicated with the previous loading pipeline at the target position of the previous loading pipeline through a communicating pipeline of the next accommodating groove, and the position, far away from the target rotation center, of the next accommodating groove is communicated with the corresponding target chamber through a loading pipeline of the next accommodating groove; each target chamber is communicated with a target communicating port. By the design, the sequential loading of the reagent can be realized only by the structure of the microfluidic chip at a constant centrifugal rotating speed, and the sequential loading is simple without an additional valve device. The sequential loading mode of the kit mainly simplifies the design of the chip and reduces the complexity of controlling release by various reagent valves; the centrifugal rotating speed can be controlled, so that the time interval for loading different reagents is controlled, the time is reserved for the reaction of the reagents, and the device is particularly suitable for the situation that a plurality of reagents are loaded respectively in sequence; and the processing technology and the processing quality control cost of the micro-fluidic chip are facilitated to be simplified. In one embodiment, the target rotation center may be a solid or an imaginary bit; the target rotation center may be inside or outside the reagent sequential loading structure, but is usually assumed to be outside the reagent sequential loading structure, i.e. the target rotation center is an external relative reference. In one embodiment, the reagent sequential loading structure is configured to be disposed in a microfluidic chip structure, and the target rotation center is a centrifugal center of the microfluidic chip structure. Further, in one embodiment, the reagent sequential loading structure is provided with a loading pipeline at a position of each accommodating groove away from the target rotation center, and the accommodating grooves are communicated with a target chamber corresponding to the accommodating groove through the loading pipeline; besides the first holding tank, the reagent sequential loading structure is provided with communicating pipelines at the positions of the other holding tanks close to the target rotation center, and the holding tanks are communicated with the loading pipeline of the previous holding tank through the communicating pipelines. In one embodiment, the loading communication port may serve as a liquid injection port for injecting the reagent into the first holding tank, and in one embodiment, each holding tank is provided with a liquid injection port, and after the reagent is injected, the liquid injection ports other than the liquid injection port of the first holding tank are sealed so that the outside environment can be communicated only through the loading communication port, i.e., the liquid injection port of the first holding tank, except for the target communication port. Alternatively, in one embodiment, each holding tank is provided with a loading opening and a loading cover thereof, and when the reagent is required to be added, the loading cover is opened to expose the loading opening, the reagent is added into the holding tank, and then the loading cover is covered to seal the loading opening. Further, in one embodiment, the second receiving groove is communicated with the first loading channel at a first target position close to the target rotation center through a second communication channel, and the second receiving groove is communicated with a corresponding target chamber at a position far away from the target rotation center through a second loading channel, the first target position is located in the first loading channel, the minimum distance between the second receiving groove and the target rotation center is smaller than the distance between the first target position and the target rotation center, and the maximum distance between the first receiving groove and the target rotation center is smaller than the distance between the first target position and the target rotation center; the other accommodating grooves are communicated with the previous accommodating groove and a corresponding target chamber in the sequence. Each holding tank that the cooperation order set up has realized the effect of order loading control like this for other holding tanks except first holding tank, reagent wherein all load to a certain extent and even enter into corresponding target cavity after the loading is accomplished at the reagent of preceding holding tank. Each target chamber is communicated with a target communicating port. That is, the other accommodating tanks except the first accommodating tank communicate with the loading communicating port not only through the communicating pipe and the first accommodating tank, but also communicate with the target communicating port through the loading pipe and the corresponding target chamber. Further, in one embodiment, each target chamber is in communication with a respective target communication port. In one embodiment, each target chamber communicates with a target communication port through the same target communication channel. In one embodiment, the number of the target communication ports is multiple, and each target chamber is communicated with one target communication port. By adopting the design, a reagent sequential loading system from far to near relative to the target rotation center is formed, and the reagent enters the target chamber from each accommodating groove under the action of centrifugal force. In one embodiment, the loading communication port is arranged at a position where the first accommodating tank is closest to the target rotation center, or the first accommodating tank is communicated with the loading communication port through the first air duct, and the maximum distance between the loading communication port and the target rotation center is greater than or equal to the distance between the position where the first accommodating tank is communicated with the first air duct and the target rotation center; that is, the loading communicating opening may be disposed in the first accommodating groove or disposed outside the first accommodating groove. In one embodiment, the reagent sequential loading structure is provided with a target communicating port in each target chamber, or each target chamber is communicated with the target communicating port through a target communicating channel, and the maximum distance between the target communicating port and the target rotation center is greater than or equal to the distance between the position where each target chamber is communicated with the target communicating channel and the target rotation center. That is, the target communication port may be disposed in the target chamber or may be disposed outside the target chamber. In one embodiment, the loading communication port is arranged at a position where the first accommodating tank is closest to the target rotation center, or the first accommodating tank is communicated with the loading communication port through the first air duct, and the maximum distance between the loading communication port and the target rotation center is greater than or equal to the distance between the position where the first accommodating tank is communicated with the first air duct and the target rotation center; the reagent sequential loading structure is characterized in that a target communicating port is respectively arranged in each target chamber, or each target chamber is respectively communicated with the target communicating ports through a target communicating pipeline, and the maximum distance between each target communicating port and the target rotation center is larger than or equal to the distance between the position where each target chamber is communicated with the target communicating pipeline and the target rotation center.
In one embodiment, each accommodating groove is communicated with a corresponding target chamber at a position, close to a target rotation center, of the corresponding target chamber through a loading pipeline of the accommodating groove; that is, the accommodating groove communicates with the target chamber at a position closer to the target rotation center, which is beneficial for outputting the reagent to the target chamber at a position with relatively small centrifugal force and collecting the reagent at a position away from the target rotation center of the target chamber under the action of the centrifugal force. In one embodiment, each accommodating groove has a contracted shape at a position away from the target rotation center; in one embodiment, each receiving groove is in an inverted triangle shape, a circle shape, a shuttle shape, an oval shape, or the like. Such a design is advantageous in that the reagent is transported out of the contracted shape to allow full loading. In one embodiment, each target chamber has a contracted shape at a location away from the target center of rotation; in one embodiment, each target chamber is in the shape of an inverted triangle, circle, shuttle, or oval, among others. Such a design is advantageous for cleaning or delivering the reagent in the target chamber on the one hand, and for achieving the reagent delivery function in cooperation with the embodiment having the collection chamber and the waste liquid chamber on the other hand. In one embodiment, the center position of each accommodating groove is the same or close to the target rotation center, or the position of each accommodating groove closest to the target rotation center is the same or close to the target rotation center; wherein, the similarity is that the maximum value is not more than 111% of the average value and the minimum value is not less than 90% of the average value; in one embodiment, the closeness is such that the maximum is no greater than 108% of the average and the minimum is no less than 91% of the average. Such a design is advantageous for controlling the centrifugal force conditions experienced by the reagents in the holding tank, thereby assisting in controlling the loading of the reagents in coordination with the centrifugal speed. In one embodiment, the communication pipeline comprises an ascending pipeline, a transition pipeline, a descending pipeline and a connecting pipeline which are sequentially arranged, and the connecting pipeline is communicated with the previous loading pipeline at the target position of the previous loading pipeline; the maximum distance between the transition pipeline and the target rotation center is smaller than the maximum distance between the ascending pipeline and the target rotation center, the maximum distance between the descending pipeline and the target rotation center and the minimum distance between the connecting pipeline and the target rotation center. Such design is favorable to coordinating the target position and forms the control effect of atmospheric valve for reagent in the holding tank can enter into its corresponding target cavity only after reagent in the preceding holding tank enters into corresponding target cavity. Further, the target location is formed with a bending zone. The design is beneficial to increasing the length and resistance of the corresponding loading pipeline, and the effect of increasing the flow resistance of the liquid is achieved. In one embodiment, each accommodating groove is communicated with a corresponding target chamber at a position, close to a target rotation center, of the corresponding target chamber through a loading pipeline of the accommodating groove; and/or each accommodating groove has a contracted shape at a position far away from the target rotation center; and/or each target chamber has a contracted shape at a position away from the target rotation center; and/or the distance between the center position of each accommodating groove and the target rotation center is the same or similar, or the distance between the position of each accommodating groove closest to the target rotation center and the target rotation center is the same or similar; wherein, the similarity is that the maximum value is not more than 111% of the average value and the minimum value is not less than 90% of the average value; and/or the communication pipeline comprises an ascending pipeline, a transition pipeline, a descending pipeline and a connecting pipeline which are sequentially arranged, and the connecting pipeline is communicated with the previous loading pipeline at the target position of the previous loading pipeline; the maximum distance between the transition pipeline and the target rotation center is smaller than the maximum distance between the ascending pipeline and the target rotation center, the maximum distance between the descending pipeline and the target rotation center and the minimum distance between the connecting pipeline and the target rotation center. In one embodiment, the microfluidic chip structure further comprises a collection chamber and a waste liquid chamber, wherein the minimum distance between the collection chamber and the target rotation center is greater than the maximum distance between the target chamber and the target rotation center, and the minimum distance between the waste liquid chamber and the target rotation center is greater than the maximum distance between the target chamber and the target rotation center; the bottom of the target chamber is provided with a filtering area, namely the bottom is far away from the target rotation center; the collecting chamber is communicated with the filtering area through a collecting pipeline, and the waste liquid chamber is communicated with the filtering area through a waste liquid pipeline; the target communicating port comprises a collecting communicating port and a waste liquid communicating port; relative to a connecting line of the center of the filtering area and the target rotation center, the collecting chamber and the waste liquid chamber are respectively positioned at two sides of the connecting line, and the collecting communicating port and the waste liquid communicating port are also respectively positioned at two sides of the connecting line; the collecting communicating port is arranged at the position, closest to the target rotation center, of the collecting chamber, or the collecting communicating port is communicated with the collecting chamber through the collecting vent pipe, and the maximum distance between the collecting communicating port and the target rotation center is larger than or equal to the distance between the position, communicated with the collecting vent pipe, of the collecting chamber and the target rotation center; the waste liquid communicating port is arranged at the position, closest to the target rotation center, of the waste liquid chamber, or the waste liquid communicating port is communicated with the waste liquid chamber through a waste liquid ventilating pipeline, and the maximum distance between the waste liquid communicating port and the target rotation center is larger than or equal to the distance between the position, communicated with the waste liquid ventilating pipeline, of the waste liquid chamber and the target rotation center; the target chamber is communicated with the collecting communicating port through the collecting pipeline and the collecting chamber in sequence, and is communicated with the waste liquid communicating port through the waste liquid pipeline and the waste liquid chamber in sequence. Further, in one embodiment, a filter membrane such as a silica gel membrane is disposed inside the filtering region.
In one embodiment, the reagent sequential loading structure comprises only one target chamber, and the reagent sequential loading structure comprises four accommodating grooves; in each accommodating groove, the first accommodating groove is communicated with the loading communicating port and is communicated with the target cavity through a first loading pipeline; the second accommodating groove is communicated with the first loading pipeline at a first target position close to the target rotation center through a second communication pipeline, and the second accommodating groove is communicated with the target chamber at a position far away from the target rotation center through a second loading pipeline, wherein the first target position is positioned in the first loading pipeline, the minimum distance between the second accommodating groove and the target rotation center is smaller than the distance between the first target position and the target rotation center, and the maximum distance between the first accommodating groove and the target rotation center is smaller than the distance between the first target position and the target rotation center; the third accommodating groove is communicated with the second loading pipeline at a second target position close to the target rotation center through a third communicating pipeline, and the third accommodating groove is communicated with the target chamber at a position far away from the target rotation center through a third loading pipeline, wherein the second target position is positioned in the second loading pipeline, the minimum distance between the third accommodating groove and the target rotation center is smaller than the distance between the second target position and the target rotation center, and the maximum distance between the second accommodating groove and the target rotation center is smaller than the distance between the second target position and the target rotation center; the fourth accommodating groove is communicated with the third loading pipeline at a third target position close to the target rotation center through a fourth communication pipeline, the fourth accommodating groove is communicated with the target chamber at a position far away from the target rotation center through a fourth loading pipeline, the third target position is located in the third loading pipeline, the minimum distance between the fourth accommodating groove and the target rotation center is smaller than the distance between the third target position and the target rotation center, and the maximum distance between the third accommodating groove and the target rotation center is smaller than the distance between the third target position and the target rotation center. This design is exemplified by four holding tanks and one target chamber, but is equally applicable to other numbers of holding tanks and/or a reagent sequential loading configuration of multiple target chambers.
It should be noted that other embodiments of the present application further include a liquid reagent storage box and a microfluidic chip structure, which are formed by combining technical features of the above embodiments with each other and can be implemented. The embodiments described above provide a novel liquid reagent storage device of a centrifugal microfluidic platform, namely a liquid reagent storage cartridge and a storage method thereof, a sequential release method that can be used for the liquid reagent storage device, a corresponding centrifugal microfluidic platform, namely a microfluidic chip structure, and a method for fixing the reagent storage device on the microfluidic chip structure; on one hand, the design of the storage cavity is beneficial to conveniently and effectively storing and storing the liquid reagent required by centrifugal microfluidics; on the other hand, the design of the height difference of the outflow structure at the outlet is beneficial to ensuring that liquid can completely flow out in the centrifugal process, avoiding reagent waste or shortage, saving cost and ensuring the reaction effect of centrifugal microfluidics; on the other hand, the design of the sealing plug is beneficial to controlling the release of the liquid reagent, and particularly, the control of the release condition of the liquid reagent can be accurately realized by controlling the strength of the storage cavity closed by the sealing plug.
The technical features of the above embodiments can be arbitrarily combined, and for the sake of brevity, all possible combinations of the technical features in the above embodiments are not described, but should be considered as the scope of the present specification as long as there is no contradiction between the combinations of the technical features. The above examples only express several embodiments of the present application, and the description thereof is more specific and detailed, but not construed as limiting the claims. It should be noted that, for a person skilled in the art, several variations and modifications can be made without departing from the concept of the present application, which falls within the scope of protection of the present application. Therefore, the protection scope of the present application shall be subject to the appended claims.
Claims (10)
1. A liquid reagent storage cassette for centrifugal fluidic, comprising a reagent cartridge body and a reagent cartridge floor;
the reagent box bottom plate is matched with the reagent box main body and forms a storage cavity together;
the liquid reagent storage box is provided with an outlet far away from the rotation center of the liquid reagent storage box, and the outlet is positioned at the adjacent position of the kit bottom plate and the kit main body;
the storage cavity is communicated with the outlet and is used for being communicated with the outside through the outlet;
the reagent box bottom plate is also provided with an outflow structure at the outlet, and the outflow structure and other structures of the reagent box bottom plate adjacent to the outflow structure form a height difference.
2. A liquid reagent storage cassette as claimed in claim 1, wherein a side of the cassette body remote from the rotation center has an arcuate surface, and the outlet is provided at a position where the arcuate surface is at a maximum distance from the rotation center.
3. The liquid reagent storage cassette of claim 1, wherein the cassette body or the cassette base plate is further extended with a protruding structure.
4. The liquid reagent storage cartridge of claim 3, wherein the protruding structure is perforated; and/or the projection structure and the outlet are respectively positioned at two opposite sides of the kit body, and the projection structure is closer to the rotation center of the liquid reagent storage box than the outlet.
5. A liquid reagent storage cartridge as claimed in claim 1, further comprising a closure plug disposed at the outlet to close the storage chamber.
6. A liquid reagent storage cassette as claimed in claim 5, wherein the closure has a hot melt structure to open the storage chamber by hot melt.
7. The liquid reagent storage cartridge of claim 5, wherein the bung is removably positioned at the outlet to centrifugally open the storage chamber; further, the sealing plug is made of elastic materials and seals the storage cavity in an elastic deformation mode, or the sealing plug is provided with a rigid structure and an adhesive layer and seals the storage cavity in an adhesive mode.
8. The liquid reagent storage cassette of any of claims 5 to 7, wherein the cassette base plate is provided with the outflow structure extending at its end away from the centre of rotation of the liquid reagent storage cassette;
the outflow structure and the rest of the adjacent reagent box bottom plate form a step shape, or the outflow structure and the rest of the adjacent reagent box bottom plate form a slope shape;
the kit main body is provided with a matching structure at the end part close to the outflow structure, the matching structure and other adjacent structures of the kit main body form a height difference, and the matching structure is used for matching with the outflow structure to jointly install a sealing plug;
the shape of the sealing plug is matched with the shape of the outermost side of the outlet, or the shape of the sealing plug is matched with the outlet and/or the outflow structure, and/or the sealing plug has a T-shaped section;
the kit main body and the kit bottom plate are integrally arranged;
the kit main body and the kit bottom plate are made of hard aluminum foil, metal plates or low-permeability thermoplastic plastics.
9. A microfluidic chip structure comprising a liquid reagent storage cassette as claimed in any one of claims 1 to 8.
10. The microfluidic chip structure according to claim 9, wherein a receiving groove for receiving the liquid reagent storage cartridge and a positioning member for fixing the liquid reagent storage cartridge are further provided.
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| CN115283027A (en) * | 2022-07-22 | 2022-11-04 | 武汉新烽光电股份有限公司 | Liquid bag storage and release device of water quality detection micro-fluidic chip |
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| CN104155463A (en) * | 2014-08-27 | 2014-11-19 | 南京大学 | Device and method for producing and measuring droplet on micro-fluidic chip |
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| KR102176587B1 (en) * | 2013-10-15 | 2020-11-10 | 삼성전자주식회사 | Sample analysis method, and dynamic valve operating method |
| DE102016121764A1 (en) * | 2016-11-14 | 2018-05-17 | Testo SE & Co. KGaA | Microfluidic processing chamber and associated method |
| CN207521025U (en) * | 2017-11-01 | 2018-06-22 | 清华大学 | Micro-fluidic chip and micro fluidic device |
| CN108479867B (en) * | 2018-03-01 | 2021-02-12 | 北京世纪沃德生物科技有限公司 | Centrifugal micro-fluidic chip reagent packaging structure and centrifugal micro-fluidic chip assembly |
| CN108899980B (en) * | 2018-08-01 | 2024-03-08 | 深圳市呈晖医疗科技有限公司 | Power supply system of centrifugal microfluidic device |
| CN208878612U (en) * | 2018-08-06 | 2019-05-21 | 东莞东阳光科研发有限公司 | A kind of control valve and centrifugal microfluidic control chip |
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Effective date of registration: 20240102 Address after: 518000 room 504, Block E, building 3, Yunzhi Science Park, south of Shuangming Avenue, Dongzhou community, Guangming Street, Guangming District, Shenzhen City, Guangdong Province Patentee after: Shenzhen Chenghui Medical Technology Co.,Ltd. Address before: 511-1, Shenzhen integrated circuit design and application Industrial Park, 1089 chaguang Road, Xili street, Nanshan District, Shenzhen, Guangdong 518051 Patentee before: SHENZHEN GANGZHU MEDICAL TECHNOLOGY Co.,Ltd. |