CN113769804B - Micro-fluidic device for realizing material mixing and mixing control method - Google Patents
Micro-fluidic device for realizing material mixing and mixing control method Download PDFInfo
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- CN113769804B CN113769804B CN202111167594.1A CN202111167594A CN113769804B CN 113769804 B CN113769804 B CN 113769804B CN 202111167594 A CN202111167594 A CN 202111167594A CN 113769804 B CN113769804 B CN 113769804B
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L3/00—Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
- B01L3/50—Containers for the purpose of retaining a material to be analysed, e.g. test tubes
- B01L3/502—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
- B01L3/5027—Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures by integrated microfluidic structures, i.e. dimensions of channels and chambers are such that surface tension forces are important, e.g. lab-on-a-chip
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/02—Adapting objects or devices to another
- B01L2200/026—Fluid interfacing between devices or objects, e.g. connectors, inlet details
- B01L2200/027—Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
- B01L2200/00—Solutions for specific problems relating to chemical or physical laboratory apparatus
- B01L2200/10—Integrating sample preparation and analysis in single entity, e.g. lab-on-a-chip concept
Abstract
The invention provides a microfluidic device for realizing material mixing and a mixing control method, comprising a microfluidic chip body and at least two containing bottle bodies respectively used for containing different materials, wherein a microfluidic pipeline is constructed in the microfluidic chip body, the at least two containing bottle bodies are respectively positioned in a bottle sleeve arranged on the microfluidic chip body, the two containing bottle bodies are respectively and correspondingly provided with a needle body with a needle opening, the two containing bottle bodies can be communicated with the microfluidic pipeline through the needle bodies respectively, the containing bottle bodies can linearly move along the axial direction of the bottle sleeve under the action of axial force so as to enable the needle bodies to be converted from a first sealing state into a circulating state, and a second sealing component can be close to the first sealing component under the action of the axial force so as to release the materials. According to the invention, the containing bottle bodies and the microfluidic chip are integrated, and materials in the two containing bottle bodies can flow between each other to realize uniform mixing of the materials, so that the accuracy of a detection result is ensured.
Description
Technical Field
The invention belongs to the technical field of consumable materials for biological experiments, and particularly relates to a micro-fluidic device for realizing material mixing and a mixing control method.
Background
Molecular diagnosis is a comprehensive and comprehensive clinical diagnosis technology which detects contents, types and coding information of biomolecules including nucleic acids, proteins, saccharides and other substances in a human body and combines related contents of biomolecular science, and is mainly applied to the fields of diagnosis of genetic diseases, control of infectious diseases and tumor treatment at present. However, the sample collected from the patient is generally complicated and contains many substances that inhibit or interfere with the detection, and thus many pretreatment procedures are required to purify the substance to be detected and perform qualitative or quantitative detection. The conventional molecular diagnostic process generally transfers clinical samples to a testing laboratory with relevant qualifications, depends on relevant equipment of the laboratory and professional operators to perform pretreatment of the samples, and is uniformly operated to perform biochemical testing or analysis. In the process, a long time is delayed, and the detection of some sudden diseases, large-scale infectious diseases and complex diseases is difficult to carry out in real time and in place. In addition, such a testing laboratory requires expensive testing equipment and specialized laboratory staff, and is difficult to be popularized in resource-poor areas.
The advent of microfluidic technology has addressed some of the problems in molecular diagnostics, and microfluidic chips have miniaturized the modules of biochemical assays and integrated them together via microchannels. The chip realizes the operations of accurate distribution of fluid, heating of reactants, uniform mixing of reagents, fluorescence detection and the like under the control of a matched instrument, thereby completing the complex, time-consuming and labor-consuming detection in the traditional laboratory at low cost in a short time and realizing the real 'sample input-result output'. However, to realize high efficiency amplification on a chip, one of the important difficulties is to mix reagents uniformly, generally, the whole chip is totally enclosed, and the channels of the chip are narrow, so that there are few reagents to be mixed uniformly, and it is difficult to ensure the uniformity of the reagents, and thus the accuracy of detection cannot be ensured. Therefore, only by controlling the movement of the fluid, the sufficient and efficient mixing of the materials among the steps can be ensured, and the problems of high cost, poor sensitivity, complex structure, excessively complex operation and related detection equipment and the like in the prior art can be avoided.
Disclosure of Invention
Therefore, the technical problem to be solved by the invention is to provide a microfluidic control device and a mixing control method for realizing material mixing, wherein the accommodating bottle bodies and the microfluidic chip are integrated into a whole, and materials in the two accommodating bottle bodies can flow between each other to realize uniform mixing of the materials, so that the accuracy of a detection result is ensured.
In order to solve the above problems, the present invention provides a microfluidic device for uniformly mixing materials, including a microfluidic chip body and at least two containing bottle bodies for containing different materials, wherein a microfluidic pipeline is configured in the microfluidic chip body, the at least two containing bottle bodies are respectively located in a bottle sleeve disposed on the microfluidic chip body, and a needle body having a needle opening is correspondingly disposed on each of the two containing bottle bodies, the two containing bottle bodies can be communicated with the microfluidic pipeline through the needle body, a first sealing component and a second sealing component are respectively connected to a first end and a second end of each containing bottle body in an axial direction, so as to form an internal sealed containing space of the containing bottle body, the needle body has a first sealed state in which the needle opening is located in the first sealing component, and a flow state in which the needle opening is located in the internal sealed containing space, the containing bottle body can linearly move along an axial direction of the bottle sleeve under an axial force, so that the needle body is converted from the first sealed state to the flow state, and the second sealing component can be close to the first sealing component under the axial force, so as to release the materials.
Preferably, the needle body further has a second sealing state of the needle opening in the second sealing assembly, and the second sealing assembly is further capable of switching the needle body from the flow-through state to the second sealing state under the action of the axial force.
Preferably, the first sealing assembly comprises a first rubber plug and a protective cover, and when the needle body is in the first sealing state, the needle opening is in the first rubber plug; the second sealing component comprises a second rubber plug and a hard gasket positioned on one side of the second rubber plug, which is deviated from the first rubber plug, and the needle body is positioned in the second rubber plug when in the second sealing state.
Preferably, the first end is of a throat structure, the first rubber plug is a first convex rubber plug, and a convex protrusion of the first convex rubber plug is embedded in the throat structure; and/or a sealing convex ring is arranged on the outer circumferential wall of the second rubber plug; and/or a first stop ring which is convex towards the radial inner side of the accommodating bottle body is arranged on the inner circumferential wall of the second end of the accommodating bottle body, and the inner circle diameter of a ring body of the first stop ring is smaller than that of the second rubber plug.
Preferably, the second rubber plug is a second convex-shaped rubber plug, and the shape of the convex-shaped protruding part of the second convex-shaped rubber plug can be matched with the shape of the necking structure, so that the materials in the inner sealed containing space are completely released and discharged through the needle opening.
Preferably, one end of the bottle sleeve, which is far away from the microfluidic chip body, is provided with a second stop ring which is convex inwards along the radial direction of the bottle sleeve; and/or the needle opening is positioned on the circumferential side wall of the needle body.
Preferably, the number of the accommodating bottle bodies is three, the three accommodating bottle bodies are arranged adjacently, and the microfluidic pipeline can communicate the three accommodating bottle bodies.
The invention also provides a blending control method of the microfluidic device, which is used for controlling the microfluidic device for realizing material blending and comprises the following steps:
controlling to apply axial force to the second sealing assemblies respectively arranged on the two accommodating bottle bodies to enable the accommodating bottle bodies to move close to the needle bodies and enable the needle bodies to be respectively converted from the first sealing state to the circulation state;
and controlling to release the axial force applied to the second sealing component of the second accommodating bottle body of the two accommodating bottle bodies, continuously applying the axial force to the second sealing component of the first accommodating bottle body of the two accommodating bottle bodies, releasing the axial force applied to the first accommodating bottle body before the needle body corresponding to the second accommodating bottle body is converted from the flow-through state to the second sealing state, and applying the axial force to the second accommodating bottle body, so that the axial force is alternately applied to the first accommodating bottle body and the second accommodating bottle body for a preset number of times, and then applying the axial force to convert the needle body of one of the first accommodating bottle body and the second accommodating bottle body from the flow-through state to the second sealing state.
The invention also provides a mixing control method of the microfluidic device, which is used for controlling the microfluidic device for realizing the material mixing, and comprises the following steps:
the second sealing components respectively arranged on the first accommodating bottle body and the second accommodating bottle body in the three accommodating bottle bodies are controlled to apply axial force, so that the accommodating bottle bodies can move close to the needle bodies, and the needle bodies are respectively converted into a circulating state from the first sealing state;
controlling to release the axial force applied to the second sealing component of the second accommodating bottle body, continuously applying the axial force to the second sealing component of the first accommodating bottle body, releasing the axial force applied to the first accommodating bottle body before the needle body corresponding to the second accommodating bottle body is converted from the flow state to the second sealing state, and applying the axial force to the second accommodating bottle body, so that the axial force is alternately and respectively applied to the first accommodating bottle body and the second accommodating bottle body for a preset number of times, and the axial force is applied to ensure that the needle body of one of the first accommodating bottle body and the second accommodating bottle body is converted from the flow state to the second sealing state;
and after the needle body of one of the first accommodating bottle body and the second accommodating bottle body is converted from the flowing state to the second sealing state, controlling to release the axial force applied to the second sealing component of the first accommodating bottle body or the second accommodating bottle body, controlling to apply the axial force to the second sealing component of the third accommodating bottle body in order to enable the accommodating bottle body to move close to the needle body, converting the needle body corresponding to the third accommodating bottle body from the first sealing state to the flowing state, and before the needle body of the third accommodating bottle body is converted from the flowing state to the second sealing state, releasing the axial force applied to the third accommodating bottle body, and applying the axial force to the second sealing component of the other one of the first accommodating bottle body and the second accommodating bottle body in the flowing state again, and after the preset times are alternated, applying the axial force to enable the one of the first accommodating bottle body and the second accommodating bottle body in which the materials can flow, and the one of the third needle body to be converted from the flowing state to the second sealing state.
According to the micro-fluidic device for realizing material mixing and the mixing control method, the accommodating bottle body and the second sealing component can move close to the needle body under the action of the axial force, and the needle body is switched from the first sealing state to the circulation state in the moving process, so that the material is released into the micro-fluidic pipeline from the internal sealing accommodating space and enters another accommodating bottle body with different materials through the micro-fluidic pipeline, the integrated design between the micro-fluidic chip and the accommodating bottle body is realized, the automatic mixing of different materials is realized, the uniform mixing can be realized on different accommodating bottle bodies by alternately applying the axial force for multiple times, the accuracy of a detection result is further ensured, and the automation degree of the micro-fluidic device is improved.
Drawings
Fig. 1 is a schematic partial structural view of a microfluidic device for achieving uniform mixing of materials according to an embodiment of the present invention, in which a needle is shown in a first sealing state;
FIG. 2 is an enlarged partial view of FIG. 1;
FIG. 3 is a schematic view of a structure of the needle body of FIG. 1;
FIG. 4 is another schematic view of the needle body of FIG. 1;
FIG. 5 is a schematic view of another embodiment of the needle body of FIG. 1;
fig. 6 shows the state change of the accommodating bottle body in the microfluidic device for achieving material mixing according to the embodiment of the present invention after being subjected to an axial force, wherein (a) the needle body is in a first sealing state, (b) and (c) the needle body is in a flow state, and (d) the needle body is in a second sealing state, which realizes that the material in the accommodating bottle body is released and flows out under the axial force and is finally sealed again;
fig. 7 to 12 are schematic diagrams showing the state of each accommodating bottle body in the process of mixing different materials in two accommodating bottle bodies under the condition that two accommodating bottle bodies are arranged in the microfluidic device for realizing material mixing, wherein the material in the bottle B is soluble solid T, and the material in the bottle a is liquid S;
fig. 13 to 17 show the state of each accommodating bottle body in the process of mixing different materials in the three accommodating bottle bodies in the case that three accommodating bottle bodies are arranged in the microfluidic device for realizing material mixing, wherein the material in the bottle B is soluble solid T, the material in the bottle C is soluble solid T1, and the material in the bottle a is liquid S.
The reference numbers are given as:
1. a microfluidic chip body; 11. a microfluidic conduit; 2. receiving a bottle body; 21. a first stop ring; 3. a bottle cover; 31. a second stop ring; 4. a needle body; 41. a needle opening; 51. a first rubber plug; 52. a protective cover; 61. a second rubber plug; 611. a sealing convex ring; 62. a hard gasket.
Detailed Description
Referring to fig. 1 to 17 in combination, according to an embodiment of the present invention, a microfluidic device for achieving material mixing is provided, which includes a microfluidic chip body 1 and at least two accommodating bottle bodies 2 respectively configured to accommodate different materials (one of the materials needs to be in a liquid state), a microfluidic pipeline 11 is configured in the microfluidic chip body 1, the at least two accommodating bottle bodies 2 are respectively disposed in a bottle sleeve 3 disposed on the microfluidic chip body 1, and the two accommodating bottle bodies 2 are respectively and correspondingly provided with a needle 4 having a needle opening 41, the two accommodating bottle bodies 2 can be communicated with the microfluidic pipeline 11 through the needle 4, an axial first end and an axial second end of the accommodating bottle body 2 are respectively connected to a first sealing component and a second sealing component to form an inner sealed accommodating space of the accommodating bottle body 2, the needle opening 41 is in a first sealing state in the first sealing component, the needle opening 41 is in a flow state in the inner sealed accommodating space, the accommodating bottle body 2 can release a linear movement along an axial direction of the bottle sleeve 3 under an axial force to convert the needle 4 from the first sealing state to the second sealing component, and release the material from the first sealing state to the second sealing component under the axial force, so that the two accommodating bottle bodies 2 can release the material in the first sealing component. In the technical scheme, the containing bottle body and the second sealing component can be close to the needle body under the action of the axial force to move, and in the moving process, the needle body is switched to a circulation state from a first sealing state, so that the materials are released into the micro-fluidic pipeline from the internal sealing containing space and enter into another containing bottle body 2 with different materials through the micro-fluidic pipeline, the automatic mixing of different materials is realized while the integrated design between the micro-fluidic chip and the containing bottle body is realized, the uniform mixing can be realized on different containing bottle bodies 2 by alternately applying the axial force for many times, the accuracy of a detection result is further ensured, and the automation degree of the micro-fluidic device is improved.
It should be noted that the bottle sleeve 3 can restrain the radial displacement of the accommodating bottle body 2 without limiting the axial displacement of the accommodating bottle body 2.
In some embodiments, the needle body 4 further has a second sealing state in which the needle port 41 is located in the second sealing assembly, and the second sealing assembly is further capable of finally switching the needle body 4 from the flow-through state to the second sealing state under the action of the axial force, and in particular, after the material in the accommodating bottle body 2 is completely released, the needle body 4 can be located in the second sealing state, that is, the needle port 41 is sealed again, which is capable of adapting to a situation that the microfluidic device has a plurality of accommodating bottle bodies 2, and the release of the internal material has a certain sequence, so as to prevent the material in other accommodating bottle bodies from being released into the released accommodating bottle body without entering or only partially entering the accommodating bottle body 2 that needs to enter.
The specific structural forms of the first sealing component and the second sealing component are various, but it should be noted that the first sealing component may be specifically implemented in a fixed sealing manner due to the absence of the requirement for displacement, specifically, for example, the first sealing component includes a first rubber plug 51 and a protective cover 52, the protective cover 52 may be an aluminum cover (the specific material is selected based on the principle that the needle 4 can be smoothly punctured), and at this time, when the needle 4 is in the first sealing state, the needle opening 41 is located in the first rubber plug 51. The second sealing component comprises a second rubber plug 61 and a hard gasket 62 which is arranged on one side of the second rubber plug 61, wherein the second rubber plug 61 deviates from the first rubber plug 51, the needle body 4 is arranged in the second sealing state, the needle opening 41 is arranged in the second rubber plug 61, the hard gasket 62 has certain rigidity, and the deformation of the hard gasket is small so as to ensure the effective transmission of the axial force.
In some embodiments, the first end is a throat structure, the first rubber plug 51 is a first rubber plug with a convex shape, and the convex protrusion of the first rubber plug is embedded in the throat structure, so that the first rubber plug with a convex shape is axially positioned in the accommodating bottle body 2 through the structure of the first rubber plug, and the second rubber plug 61 is a second rubber plug with a convex shape, and the shape of the convex protrusion of the second rubber plug can be matched with the shape of the throat structure, so that the material in the inner sealed accommodating space is completely released and discharged through the needle opening 41, and the utilization rate of the material is improved.
In order to effectively prevent the leakage of the material, preferably, a sealing convex ring 611 is arranged on the outer circumferential wall of the second rubber plug 61, and a plurality of sealing convex rings 611 can be arranged at intervals along the axial direction of the second rubber plug 61.
In some embodiments, the inner circumferential wall of the second end of the bottle containing body 2 has a first stop ring 21 protruding toward the inner side of the bottle containing body 2, and the inner circular diameter of the ring body of the first stop ring 21 is smaller than the outer circular diameter of the second rubber plug 61, so as to prevent the second rubber plug 61 from falling out of the bottle containing body 2 from the second end, and effectively prevent the material leakage. The end of the bottle sleeve 3 away from the microfluidic chip body 1 is provided with a second stop ring 31 protruding inwards along the radial direction, so that the accommodating bottle body 2 and all parts assembled with the accommodating bottle body can be limited in the bottle sleeve 3 and prevented from falling out.
One end of the bottle sleeve 3 close to the microfluidic chip body 1 is connected with the microfluidic chip body 1 in a buckling or ultrasonic bonding mode after the accommodating bottle body 2 is arranged in the bottle sleeve 3.
The needle port 41 can be opened at the top end of the needle body 4, and preferably, the needle port 41 is located on the circumferential side wall of the needle body 4, as shown in fig. 3 to 5, so when the needle body 4 is in the first sealing state and the second sealing state, if the needle body receives the reverse thrust pressure of the material in the microfluidic pipeline 11, the needle body can extrude the side wall of the rubber plug, an upward force cannot be generated, and then the rubber plug is bounced to cause leakage, that is, the rubber plug can be bounced when the material is reversely pushed, thereby ensuring the sealing effect of the needle port 41 and effectively preventing the leakage of the material.
In some embodiments, the number of the receiving bottle bodies 2 is three or more, three or more receiving bottle bodies 2 are adjacently arranged, and the microfluidic channel 11 can communicate the receiving bottle bodies 2, so that uniform mixing of more different materials can be realized.
According to an embodiment of the present invention, as shown in fig. 7 to 12, there is also provided a mixing control method for a microfluidic device, for controlling the microfluidic device having two holding bottle bodies 2 for mixing materials, the method including:
controlling the second sealing components respectively arranged on the two accommodating bottle bodies 2 to apply axial force to enable the accommodating bottle bodies 2 to move close to the needle body 4 and enable the needle body 4 to be respectively converted from the first sealing state to the circulating state;
and controlling to release the axial force applied to the second sealing component of the second one of the two accommodating bottle bodies 2, and to continue to apply the axial force to the second sealing component of the first one of the two accommodating bottle bodies 2, and to release the axial force applied to the first one of the two accommodating bottle bodies before the needle body 4 corresponding to the second one of the two accommodating bottle bodies is converted from the flow-through state to the second sealing state, and to apply the axial force to the second one of the two accommodating bottle bodies, so that the axial force is applied alternately after the axial force is applied to the first one of the two accommodating bottle bodies and the second one of the two accommodating bottle bodies for a predetermined number of times, so that the needle body 4 of one of the first one accommodating bottle body and the second one of the two accommodating bottle bodies is converted from the flow-through state to the second sealing state.
According to an embodiment of the present invention, referring to fig. 13 to 17, there is provided a blending control method for a microfluidic device, for controlling the microfluidic device for blending materials, including:
controlling the axial force applied to the second sealing components respectively arranged on the first accommodating bottle body and the second accommodating bottle body in the three accommodating bottle bodies 2 to enable the accommodating bottle bodies 2 to move close to the needle body 4 and enable the needle body 4 to be respectively converted from the first sealing state to the circulating state;
controlling to release the axial force applied to the second sealing component of the second containing bottle body, continuously applying the axial force to the second sealing component of the first containing bottle body, releasing the axial force applied to the first containing bottle body before the needle body 4 corresponding to the second containing bottle body is converted from the flow-through state to the second sealing state, and applying the axial force to the second containing bottle body, so that the axial force is alternately and respectively applied to the first containing bottle body and the second containing bottle body for a preset number of times, and then applying the axial force to convert the needle body 4 of one of the first containing bottle body and the second containing bottle body from the flow-through state to the second sealing state;
after the needle 4 of one of the first and second receiving vials is switched from the flow-through state to the second sealing state, controlling to release the axial force applied to the second sealing member of the first or second receiving vial, controlling to apply the axial force to the second sealing member of the third of the three receiving vials 2 to enable the receiving vial 2 to move closer to the needle 4 and to switch the needle 4 corresponding to the third receiving vial from the first sealing state to the flow-through state, and before the needle 4 of the third receiving vial is switched from the flow-through state to the second sealing state, releasing the axial force applied to the third receiving vial and applying the axial force again to the second sealing member of the one of the first and second receiving vials 4 in the flow-through state, and after the preset number of times is alternated, applying the axial force to switch the needle 4 of the one of the first and second receiving vials to the second sealing state.
It will be understood that the first containment body now relieved of the force has sufficient space for the second sealing member to move to rise under the action of the material entering therein, and that theoretically the volume of the first containment body should be greater than the total volume of the material in both containment bodies to achieve mixing of the material in the first containment body.
Example 1:
the process of mixing the contents with the two receiving flask 2 is further described below with reference to fig. 7 to 12:
before the device is not used, when the bottle A and the bottle B are placed in the bottle sleeve (namely, the bottle sleeve 3, the same below), the needle (namely, the needle body 4, the same below) just pierces a part of a rubber plug (namely, the first rubber plug 51, the same below) of a bottle opening, so that the tail end of the needle (namely, the needle opening 41, the same below) is sealed, and meanwhile, a fluid pipeline (namely, the microfluidic pipeline 11, the same below) at the lower part of the bottle sleeve is sealed. But the needle can not puncture the rubber plug and does not damage the sealing performance of the biological materials in the bottle body, namely the needle is positioned in the rubber plug. Meanwhile, in order to make the fluid in the bottles A and B have a flowing space, the rubber plug of the bottle A or the bottle B is pre-assembled at a position close to the bottle mouth, and here, the rubber plug at the bottom of the bottle B is pre-assembled at a position close to the bottom of the bottle B, as shown in figure 7.
When the material blending device is started, the upper parts of the bottle A and the bottle B are sequentially subjected to downward force (namely, the axial force and the downward force are the same), so that the bottle stopper is punctured by the needle, and two outlets for biological materials to be blended (namely, the material S and the material T) are opened, as shown in fig. 8.
Continue to exert pressure to A bottle bottom, because whole bottle is the restriction inside the bottle cover, the export of two bottles that are equipped with different biological material respectively simultaneously also is punctured by the needle and opens, at this moment, the plug at the bottom of A bottle is under the drive of downward pressure, can slow moving, discharge the inside material of A bottle simultaneously, because the plug of B bottle also is punctured this moment, the plug of B bottle is located the nearer position department of bottleneck, the space of activity that makes progress has, consequently the material in the A bottle is under the drive of pressure, get into B bottle and carry out the mixing with its material, the bottom plug of B bottle also can the rebound simultaneously, its process is as shown in figure 9.
The liquid in the bottle A is completely (or partially) injected into the bottle B, the bottom rubber plug of the bottle A is lowered to a position close to the bottle mouth at this time, and the needle is not pricked into the bottom rubber plug at the time, as shown in fig. 10.
The mixed material in the bottle B is driven into the bottle A, and the process is similar to the process of driving the bottle A into the bottle B, as shown in fig. 11 and 12. The above processes can be repeated for a plurality of times according to the requirements, so that the materials of the bottle A and the bottle B can be fully mixed. It is noted that at least one of the materials in the bottles A and B is in a liquid state.
Example 2:
the process of mixing the materials with three containing bodies 2 is further described below with reference to fig. 13 to 17:
before the device is not used, when the bottle A (the material in the bottle A is S), the bottle B (the material in the bottle B is T1) and the bottle C (the material in the bottle C is T) are placed inside the bottle sleeve, the needle just pricks into one part of a rubber plug of a bottle opening, so that the tail end of the needle is sealed, and meanwhile, a fluid pipeline at the lower part of the bottle sleeve is sealed. But the needle can not puncture the rubber plug and does not damage the sealing performance of the biological materials in the bottle body, namely the needle is positioned in the rubber plug. As shown in fig. 13.
When this material mixing device started, at first, A bottle and B bottle upper portion received downward power in proper order for the bottle plug is punctured to the needle, opens the export of waiting to mix biological material, and the material export of C bottle still is in the closed condition this moment. As shown in fig. 14. Continue to exert pressure to A bottle bottom, because whole bottle is the restriction inside the bottle cover, the export of two bottles that are equipped with different biological material respectively simultaneously also is punctured by the needle and opens, at this moment, the plug at the bottom of A bottle is under the drive of downward pressure, can slow moving, discharge the inside material of A bottle simultaneously, because the plug of B bottle also is punctured this moment, the plug of B bottle is located the nearer position department of bottleneck, the space of activity that makes progress has, consequently the material in the A bottle is under the drive of pressure, get into B bottle and carry out the mixing with its material, the bottom plug of B bottle also can the rebound simultaneously, its process is as shown in figure 14.
The blending process is consistent with the blending process of the two materials, after the blending is finished, the bottom rubber plug of one material bottle is pressed to the bottle mouth, and the needle is pricked into the bottom rubber plug, so that the bottom rubber plug is sealed. Here the needle is inserted into the plug at the bottom of the a vial, which achieves the seal, as shown in fig. 15.
And then, applying pressure to the bottom of the bottle C to puncture the rubber plug of the bottle opening by a needle, opening an outlet for the biological material to be uniformly mixed, communicating the bottle B with the bottle C, and closing the bottle A as shown in fig. 16.
The blending process of the bottle B and the bottle C is similar to the previous blending process, after the blending of the bottle B and the bottle C is finished, all blending liquid is injected into the bottle C, and the bottle B is closed at the same time, as shown in fig. 17.
It is readily understood by a person skilled in the art that the advantageous ways described above can be freely combined, superimposed without conflict.
The present invention is not limited to the above preferred embodiments, and any modifications, equivalents and improvements made within the spirit and principle of the present invention should be included in the protection scope of the present invention. The above is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, several improvements and modifications can be made without departing from the technical principle of the present invention, and these improvements and modifications should also be regarded as the protection scope of the present invention.
Claims (8)
1. The microfluidic device for realizing material mixing is characterized by comprising a microfluidic chip body (1) and at least two containing bottle bodies (2) which are used for containing different materials respectively, wherein a microfluidic pipeline (11) is constructed in the microfluidic chip body (1), the at least two containing bottle bodies (2) are respectively arranged in bottle sleeves (3) arranged on the microfluidic chip body (1), the two containing bottle bodies (2) are respectively and correspondingly provided with a needle body (4) with a needle opening (41), the two containing bottle bodies (2) can be communicated with the microfluidic pipeline (11) through the needle body (4) respectively, an axial first end and an axial second end of each containing bottle body (2) are respectively connected with a first sealing component and a second sealing component to form an inner sealing containing space of each containing bottle body (2), the needle body (4) is provided with a first sealing state that the needle opening (41) is arranged in the first sealing component, the needle opening (41) is arranged in the inner sealing containing space in a circulating state, the needle body (4) can be converted into a linear movement along the axial sealing component (3) under the action of the axial sealing component, so that the needle body (2) can be close to the first sealing component and the second sealing component under the action of the axial sealing component to enable the material to be close to the second sealing component;
the first sealing assembly comprises a first rubber plug (51) and a protective cover (52), and when the needle body (4) is in the first sealing state, the needle opening (41) is positioned in the first rubber plug (51); the second sealing component comprises a second rubber plug (61) and a hard gasket (62) which is arranged at one side of the second rubber plug (61) departing from the first rubber plug (51), the needle body (4) is further provided with a second sealing state that the needle opening (41) is arranged in the second sealing component, and when the needle body (4) is arranged at the second sealing state, the needle opening (41) is arranged in the second rubber plug (61).
2. Microfluidic device according to claim 1, characterized in that the second sealing assembly is also capable of switching the needle (4) from the flow-through state to the second sealing state under the action of the axial force.
3. The microfluidic device according to claim 1, wherein the first end is a throat structure, the first rubber plug (51) is a first convex rubber plug, and a convex protrusion of the first convex rubber plug is embedded in the throat structure; and/or a sealing convex ring (611) is arranged on the outer circumferential wall of the second rubber plug (61); and/or a first stop ring (21) which is convex towards the radial inner side of the accommodating bottle body (2) is arranged on the inner circumferential wall of the second end of the accommodating bottle body (2), and the inner circle diameter of the ring body of the first stop ring (21) is smaller than the outer circle diameter of the second rubber plug (61).
4. The microfluidic device according to claim 3, wherein the second rubber plug (61) is a second embossed rubber plug, and the shape of the embossed projection of the second embossed rubber plug can match the shape of the necking structure, so as to completely release and discharge the material in the inner sealed containing space through the needle port (41).
5. The microfluidic device according to claim 1, wherein the end of the vial sleeve (3) remote from the microfluidic chip body (1) has a second stop ring (31) protruding radially inward along it; and/or the needle opening (41) is positioned on the circumferential side wall of the needle body (4).
6. The microfluidic device according to any of claims 1 to 5, wherein there are three receiving vials (2), three receiving vials (2) are arranged adjacently, and the microfluidic channel (11) is capable of communicating the three receiving vials (2).
7. A blending control method of a microfluidic device, which is used for controlling the microfluidic device for realizing material blending of any one of claims 1 to 5, and comprises the following steps:
controlling to apply axial force to the second sealing components respectively arranged on the two accommodating bottle bodies (2) to enable the accommodating bottle bodies (2) to move close to the needle body (4) and enable the needle body (4) to be respectively converted from the first sealing state to the circulating state;
and controlling to release the axial force applied to the second sealing component of the second one of the two containing bottle bodies (2), continuously applying the axial force to the second sealing component of the first one of the two containing bottle bodies (2), releasing the axial force applied to the first one of the two containing bottle bodies before the corresponding needle body (4) is converted from the flow-through state to the second sealing state, applying the axial force to the second one of the two containing bottle bodies, and applying the axial force to the first one of the two containing bottle bodies after the axial force is alternately applied to the first one of the two containing bottle bodies and the second one of the two containing bottle bodies for a preset number of times so as to convert the needle body (4) of the first one of the two containing bottle bodies and the second one of the two containing bottle bodies from the flow-through state to the second sealing state.
8. A blending control method of a microfluidic device, which is used for controlling the microfluidic device for realizing material blending of claim 6, and comprises the following steps:
controlling to apply axial force to second sealing components respectively arranged on a first accommodating bottle body and a second accommodating bottle body in the three accommodating bottle bodies (2) to enable the accommodating bottle bodies (2) to move close to the needle body (4) and enable the needle body (4) to be respectively converted from the first sealing state to the circulating state;
controlling to release the axial force applied to the second sealing component of the second accommodating bottle body, continuously applying the axial force to the second sealing component of the first accommodating bottle body, releasing the axial force applied to the first accommodating bottle body before the needle body (4) corresponding to the second sealing component is converted from the circulation state to the second sealing state, and applying the axial force to the second accommodating bottle body, so that the axial force is alternately and respectively applied to the first accommodating bottle body and the second accommodating bottle body for preset times, and then applying the axial force to convert the needle body (4) of one of the first accommodating bottle body and the second accommodating bottle body from the circulation state to the second sealing state;
after the needle body (4) of one of the first and second accommodating bottle bodies is switched from the flow state to the second sealing state, the axial force applied to the second sealing member of the first or second accommodating bottle body is released, the second sealing member applied to the third of the three accommodating bottle bodies (2) is controlled to move the accommodating bottle body (2) close to the needle body (4), and the needle body (4) corresponding to the third accommodating bottle body is switched from the first sealing state to the flow state, and the axial force applied to the third accommodating bottle body is released and applied again to the second sealing member of one of the first and second accommodating bottle bodies in the flow state before the needle body (4) of the third accommodating bottle body is switched from the flow state to the second sealing state, and the axial force is applied alternately preset times to switch the flow state of the needle body of the one of the first and second accommodating bottle bodies and the flow state of the needle body of the third accommodating bottle body (4) from the second sealing state.
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| CN113769804A (en) | 2021-12-10 |
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