WO2023025274A1 - 微流控芯片 - Google Patents

微流控芯片 Download PDF

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Publication number
WO2023025274A1
WO2023025274A1 PCT/CN2022/115034 CN2022115034W WO2023025274A1 WO 2023025274 A1 WO2023025274 A1 WO 2023025274A1 CN 2022115034 W CN2022115034 W CN 2022115034W WO 2023025274 A1 WO2023025274 A1 WO 2023025274A1
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WO
WIPO (PCT)
Prior art keywords
liquid
chip
microfluidic chip
liquid bag
main body
Prior art date
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PCT/CN2022/115034
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English (en)
French (fr)
Inventor
魏道舜
程晓宇
刘笔锋
钱纯亘
肖育劲
陈鹏
Original Assignee
深圳市亚辉龙生物科技股份有限公司
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Application filed by 深圳市亚辉龙生物科技股份有限公司 filed Critical 深圳市亚辉龙生物科技股份有限公司
Priority to EP22860620.8A priority Critical patent/EP4364850A1/en
Publication of WO2023025274A1 publication Critical patent/WO2023025274A1/zh

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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
    • B01L3/502738—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 characterised by integrated valves
    • 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
    • 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
    • B01L3/50273—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 characterised by the means or forces applied to move the fluids
    • 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
    • B01L3/52—Containers specially adapted for storing or dispensing a reagent
    • B01L3/523—Containers specially adapted for storing or dispensing a reagent with means for closing or opening
    • 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
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/06—Auxiliary integrated devices, integrated components
    • B01L2300/0672—Integrated piercing tool
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0803—Disc shape
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00—Additional constructional details
    • B01L2300/08—Geometry, shape and general structure
    • B01L2300/0809—Geometry, shape and general structure rectangular shaped
    • B01L2300/0816—Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/04—Moving fluids with specific forces or mechanical means
    • B01L2400/0475—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0481—Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure squeezing of channels or chambers
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01L—CHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00—Moving or stopping fluids
    • B01L2400/06—Valves, specific forms thereof
    • B01L2400/0677—Valves, specific forms thereof phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
    • B01L2400/0683—Valves, specific forms thereof phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers mechanically breaking a wall or membrane within a channel or chamber
    • 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
    • B01L3/502715—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 characterised by interfacing components, e.g. fluidic, electrical, optical or mechanical interfaces
    • 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
    • B01L3/52—Containers specially adapted for storing or dispensing a reagent
    • B01L3/527—Containers specially adapted for storing or dispensing a reagent for a plurality of reagents

Definitions

  • the invention relates to the field of microfluidic technology, in particular to a microfluidic chip.
  • POCT point-of-care testing
  • POCT is a detection method that is carried out at the sampling site and uses portable analytical instruments and supporting reagents to quickly obtain test results.
  • POCT can be analyzed immediately at the sampling site, eliminating the need for complex processing procedures during laboratory testing, and has the advantages of quick results and easy use.
  • POCT products mainly include microfluidic chips and reagents applied to microfluidic chips for detection.
  • the reagent storage methods of POCT products are divided into chip internal storage and chip external storage.
  • Internal storage of the chip refers to the introduction of reagent perfusion steps in the process of chip processing and assembly, directly injecting liquid reagents into the storage cavity or storage tank in the chip and then completing the overall packaging of the chip.
  • the chip is stored inside, there is no need to use additional packaging to store reagents, and the reagents are directly built into the chip, but blocking or valve control is required between the chip storage tank and the fluid channel in the chip, otherwise the reagents will flow in advance during storage and transportation.
  • Scrapping is caused in the channel; and reagent packaging and chip processing are placed together, which will increase the difficulty of processing and process control, and the process flow is lengthy and complicated.
  • setting valve control or blocking will increase the complexity of chip design, and it is necessary to consider reagent storage
  • the stability of the test process and the stability of the transportation process must also ensure the introduction of reagents during the test process, which also increases the complexity of the test system control; in addition, generally speaking, when the internal storage of the chip is used, the types of storage reagents are limited, and it is not compatible with the built-in multi-component reagents.
  • the external storage of the chip means that the chip assembly is independent of the reagent filling and packaging process. After the liquid reagent is sealed into the liquid capsule, the liquid capsule and the corresponding position of the chip are then pasted together for assembly and use.
  • the process control is more reliable, and the storage of multiple types of reagents can be easily realized, and the combination with the chip has a high degree of flexibility and freedom.
  • the liquid capsule containing the liquid reagent is attached to the outside of the chip, which is prone to being crushed and scrapped during transportation and storage, and the test repeatability and stability are poor during use.
  • a microfluidic chip comprising:
  • the chip body is provided with a liquid inlet
  • the fluid capsule storage part is located on the main body of the chip, and the fluid capsule storage part is provided with a fluid capsule cavity for placing the fluid capsule, and the fluid capsule cavity has a liquid outlet, and the liquid outlet communicates with the liquid inlet , the sharp piece is arranged in the liquid bag cavity; when the liquid bag is placed in the liquid bag cavity, there is an interval between the liquid bag and the sharp piece; when the liquid bag is subjected to When the extrusion force exceeds a preset value, the sharp part can pierce the liquid bag.
  • the above-mentioned microfluidic chip has a space between the liquid bag and the sharp part when the liquid bag is placed in the liquid bag cavity, so that the liquid bag is not subject to extrusion force (such as the extrusion force received during transportation and storage) It does not puncture when the preset value is exceeded, but can be punctured when an extrusion force exceeding the preset value is applied during use, thereby reducing the scrap rate of the above-mentioned microfluidic chip.
  • the flow rate and flow resistance of the reagent flowing out of the liquid bag can be basically the same, thereby improving the detection repeatability and stability of the above-mentioned microfluidic chip.
  • a drainage groove is provided on the sharp piece, and the drainage groove communicates with the liquid outlet.
  • the spikes are cone-shaped or needle-shaped.
  • the microfluidic chip includes a protection member, the protection member is connected to the chip main body and covers the liquid sac storage member, and the protection member is provided with holes corresponding to the liquid sac cavity. The sac avoidance hole.
  • the microfluidic chip further includes an indicator, the indicator is located between the liquid bag storage member and the protection member, and the material of the indicator is a material that is easily deformed under force.
  • the protection part is a transparent protection part, and/or, the material of the liquid bag storage part and the material of the chip main body are both transparent materials.
  • the material of the indicator is plastic film, aluminum foil, tin foil or paper.
  • the microfluidic chip further includes a first fixing part, and the first fixing part is used for fixedly connecting the liquid bag storage part and the chip main body.
  • the microfluidic chip further includes a second fixing part, and the second fixing part is used for fixedly connecting the protection part and the liquid bag storage part.
  • the microfluidic chip further includes a sealing member, the sealing member is located between the liquid sac storage part and the chip main body, and the sealing member is used to seal the liquid sac storage part
  • the gap between the chip body and the sealing member has a liquid channel, and the liquid outlet communicates with the liquid inlet through the liquid channel.
  • the bottom of the liquid sac cavity is funnel-shaped, the spikes are located on the bottom, and the liquid outlet is located at a distance from the chip main body of the bottom. the nearest distance.
  • FIG. 1 is a perspective view of a microfluidic chip according to an embodiment
  • Figure 2 is an exploded view of the microfluidic chip shown in Figure 1;
  • Fig. 3 is a perspective view of the liquid capsule storage part of the microfluidic chip shown in Fig. 1;
  • FIG. 4 is a cross-sectional view of the microfluidic chip shown in FIG. 1;
  • Fig. 5 is an enlarged view of part B of the fluid bag storage part shown in Fig. 4;
  • Fig. 6 is an enlarged view of part A of the liquid bladder storage part shown in Fig. 3;
  • FIG. 7 is an exploded view of the microfluidic chip shown in FIG. 1 before assembly.
  • Microfluidic chip 110. Chip main body; 120. Liquid sac storage part; 111. Liquid inlet; 121. Liquid sac cavity; 122. Liquid outlet; 123. Spikes; 124. Drainage groove; 125. Sealing element; 126, liquid channel; 130, liquid bag; 140, protective element; 141, avoidance hole; 150, indicator element; 160, first fixing element; 170, second fixing element; 180, positioning hole; 161, The first fixed column; 171, the second fixed column.
  • the microfluidic chip 10 includes a chip body 110 and a liquid bag storage part 120, the chip body 110 is provided with a liquid inlet 111 , the liquid capsule storage part 120 is located on the chip main body 110, the liquid capsule storage part 120 is provided with a liquid capsule chamber 121 for placing the liquid capsule 130, the liquid capsule chamber 121 has a liquid outlet 122, and the liquid outlet 122 and the liquid inlet 111
  • the sharp part 123 is arranged in the liquid bag cavity 121; when the liquid bag 130 is placed in the liquid bag cavity 121, there is an interval between the liquid bag 130 and the sharp part 123; At a preset value, the sharp part 123 can pierce the liquid bag 130 .
  • the liquid bag 130 When the liquid bag 130 is placed in the liquid bag cavity 121, there is a space between the liquid bag 130 and the sharp part 123, so that the liquid bag 130 is subjected to a pressing force (such as the pressing force received during transportation and storage) When it does not exceed the preset value, it will not be punctured by the sharp piece 123 , but when the extrusion force exceeding the preset value is applied during use, it will be punctured by the sharp piece 123 , thereby reducing the scrap rate of the above-mentioned microfluidic chip 10 .
  • the rupture of the liquid sac in the traditional microfluidic chip is to directly squeeze the liquid sac so that the aluminum foil on the side close to the liquid outlet is broken and the liquid flows out.
  • this method will make the liquid sac The rupture is highly random, which easily leads to large differences in the flow rate and flow resistance when the liquid reagent enters the main body of the chip, thus affecting the test repeatability and stability. Therefore, the present application uses the setting of the sharp piece 123 so that the liquid bag 130 is subjected to the same extrusion force (or a different extrusion force greater than the limit value of the liquid bag 130, because after exceeding the limit value, the squeezed The magnitude of the force will not change the opening size of the liquid capsule 130, and thus will not affect the flow rate and flow resistance), after that, the opening sizes of the plurality of liquid capsules 130 are basically the same, so that the flow velocity of the reagent flowing out of each liquid capsule 130 is consistent with the flow rate. The resistances are basically the same, thereby improving the detection repeatability and stability of the above-mentioned microfluidic chip 10.
  • the preset value of the extrusion force received by the liquid bag 130 is related to the material of the liquid bag 130, the liquid bag 130 and the sharp point when the liquid bag 130 is placed in the liquid bag cavity 121.
  • the distance between the stabbing pieces 123 and the extrusion force of the liquid bag 130 during transportation and storage are related.
  • the specific preset value can be based on the material of the liquid bag 130, the distance between the liquid bag 130 and the sharp part 123 when the liquid bag 130 is placed in the liquid bag cavity 121, and the impact of the liquid bag 130 during transportation and storage. Extrusion force is set.
  • the preset value of the extrusion force is designed based on the force actually received by the liquid bag 130 in the direction from the liquid bag 130 to the piercing member 123 .
  • the preset value of the extrusion force is designed based on the size of the liquid bladder 130 that can bear the vertical downward force. For example, if the liquid bladder 130 is subjected to an oblique downward force, the force in the vertical direction is only the component force of this oblique downward force. As long as the magnitude of this component force does not exceed a preset value, the liquid bladder will 130 is not punctured.
  • the material of the side of the liquid bag 130 close to the sharp part 123 is aluminum foil, PET film, PP film or LDPE film. In some other embodiments, the material of the side of the liquid bag 130 close to the sharp part 123 is a composite film of plastic film and aluminum foil. In some embodiments, the thickness of the side of the liquid capsule 130 close to the spike 123 is 50 ⁇ m-200 ⁇ m; the material of the side of the fluid capsule 130 away from the spike 123 is at least one of PP, HDPE, PVC and PET.
  • the liquid bladder 130 is made of the above materials (at least one of PP, HDPE, PVC and PET) through blow molding or injection molding to obtain a dome shell structure. In some embodiments, the thickness of the side of the liquid capsule 130 away from the spike 123 is 75 ⁇ m ⁇ 200 ⁇ m.
  • the distance between the liquid bag 130 and the sharp part 123 is 1 mm ⁇ 10 mm. For example, 2mm, 5mm or 8mm.
  • the distance between the liquid bag 130 and the sharp piece 123 refers to the distance from the nearest point of the sharp piece 123 close to the liquid bag 130 to the side of the liquid bag 130 close to the sharp piece 123 . It can be understood that, when the liquid bag 130 is placed in the liquid bag cavity 121 , the distance between the liquid bag 130 and the spike 123 can be adjusted according to the material of the liquid bag 130 .
  • the distance between the liquid bag 130 and the sharp part 123 can be set farther; if the material of the liquid bag 130 If it is a material that is not easily deformed by extrusion and is not easy to approach the sharp piece 123, then the distance between the liquid bag 130 and the sharp piece 123 can be set shorter.
  • Such arrangement can make the above-mentioned microfluidic chip 10 not easy to be scrapped during transportation and storage, and relatively easy to be punctured during use.
  • the chip body 110 is an important part of a POCT product, and the chip body 110 includes a reaction chamber and a fluid channel communicating with the reaction chamber.
  • the chip body 110 is provided with a liquid inlet 111 .
  • the liquid inlet 111 communicates with the reaction chamber on the chip body 110 .
  • the reagent used for detection enters the chip main body 110 from the liquid inlet 111 .
  • the chip body 110 is provided with a plurality of reaction chambers, and the plurality of reaction chambers are connected through fluid channels. At least some of the reaction chambers have their own liquid inlets 111 , and at this time, the liquid capsule storage element 120 also has liquid capsule chambers 121 and liquid outlets 122 corresponding to these reaction chambers.
  • the chip body 110 has six spaced liquid inlets 111
  • the fluid capsule storage member 120 also has six fluid capsule cavities 121 and six fluid outlets 122 .
  • one liquid capsule cavity 121 corresponds to one liquid outlet 122
  • one liquid outlet 122 corresponds to one liquid inlet 111 .
  • one liquid capsule chamber 121 may also correspond to multiple liquid outlets 122 .
  • Multiple or one liquid outlets 122 correspond to one or more liquid inlets 111 .
  • the number of liquid inlets 111 and liquid outlets 122 can be adjusted according to actual conditions.
  • the sizes of the liquid inlet 111 and the liquid outlet 122 are not particularly limited, and can be adjusted according to actual conditions (such as the flow rate/flow rate of the liquid reagent).
  • the chip body 110 is disc-shaped. It can be understood that, in other embodiments, the shape of the chip body 110 is not limited to a disk shape, but can also be any other shape. For example, square shape or oval shape etc.
  • the material of the chip body 110 is selected from polydimethylsiloxane (PDMS), polyurethane, epoxy resin, polymethyl methacrylate (PMMA), polycarbonate (PC), cycloolefin copolymer At least one of polystyrene (COC/COP), polystyrene (PS), polyethylene (PE), polypropylene (PP) and fluoroplastics. It can be understood that the material of the chip body 110 is not limited to the above, and can also be other materials.
  • the liquid capsule storage part 120 is used to store the liquid capsule 130 filled with liquid reagents.
  • the fluid capsule cavity 121 is provided on the fluid capsule storage part 120 , and the fluid capsule cavity 121 is used for placing the fluid capsule 130 .
  • the liquid bladder storage member 120 is disc-shaped. It can be understood that, in other embodiments, the shape of the liquid bladder storage member 120 is not limited to the above, and can also be adjusted according to actual needs.
  • the number of fluid capsule cavities 121 is six. It can be understood that, in other embodiments, the number of liquid sac cavities 121 is not limited to the above, and can also be adjusted according to actual conditions.
  • the shape of the fluid capsule cavity 121 is not limited, but it needs to match the fluid capsule 130 .
  • the liquid capsule 130 is approximately hemispherical, and the liquid capsule cavity 121 is approximately columnar with a bottom recessed toward the chip main body 110 .
  • the material of the bladder storage member 120 is a rigid material.
  • the bladder 130 in the protective bladder cavity 121 is utilized.
  • the bottom of the liquid sac cavity 121 is funnel-shaped, the sharp part 123 is located on the bottom, and the liquid outlet 122 is located at the bottom closest to the chip main body 110 .
  • the bottom of the liquid bag 130 By setting the bottom of the liquid bag 130 into a funnel shape, there is a certain interval between the sharp piece 123 and the liquid bag 130, and the liquid bag 130 needs to be subjected to a certain extrusion force to be pierced by the sharp piece 123, Instead of being punctured by slight extrusion, the scrap rate of the above-mentioned chips is reduced.
  • the funnel shape of the bottom of the liquid bag 130 also facilitates the flow of the liquid reagent in the liquid bag 130 to the chip main body 110, so that the liquid reagent is not easily wasted.
  • the bottom of the liquid sac chamber 121 is not limited to a funnel shape, and may also be other curved surfaces that are concave toward the chip main body 110 .
  • the spikes 123 are cone-shaped or needle-shaped.
  • the sharp piece 123 is in the shape of a cone or a triangular pyramid. After the sharp piece 123 punctures the sealing film of the liquid bag 130 , as the penetration depth increases, the punctured opening of the sealing film becomes larger.
  • there are multiple spikes 123 and the multiple spikes 123 are arranged around the liquid outlet 122 at intervals. Further, the distances from the plurality of spikes 123 to the center of the liquid outlet 122 are equal.
  • the number of spikes 123 is three, and the three spikes 123 are arranged at intervals around the liquid outlet 122, and the distances from the three spikes 123 to the center of the liquid outlet 122 are equal. . It can be understood that, in other embodiments, the number of spikes 123 is not limited to the above three, and may also be other numbers, such as one, two, five or six, and so on.
  • a drainage groove 124 is also provided on the sharp piece 123 .
  • the drainage groove 124 communicates with the liquid outlet 122 .
  • the drainage groove 124 is used to guide the liquid in the liquid bag 130 to the liquid outlet 122 .
  • the drainage groove 124 is located on a side of the spike 123 close to the liquid outlet 122 .
  • the position of the drainage groove 124 is not limited to the above, and can also be located at other positions of the sharp part 123 . For example, it is located on the side of the spike 123 away from the liquid outlet 122 .
  • the microfluidic chip 10 further includes a sealing member 125 .
  • the sealing member 125 is located between the liquid capsule storage member 120 and the chip main body 110 , and the sealing member 125 is used to seal the gap between the liquid capsule storage member 120 and the chip main body 110 .
  • the seal 125 has a liquid channel 126 , and the liquid outlet 122 communicates with the liquid inlet 111 through the liquid channel 126 .
  • the liquid bag storage part 120 has a liquid outlet channel, one end of the liquid outlet channel communicates with the liquid outlet 122 , and the other end communicates with the liquid inlet 111 .
  • the sealing member 125 is located in the liquid outlet channel, the outer wall of the sealing member 125 is in sealing connection with the side wall of the liquid outlet channel, and the outer wall of the sealing member 125 close to the chip main body 110 is in sealing connection with the chip main body 110 .
  • the seal 125 is an elastic seal 125 .
  • the material of the sealing member 125 is TPU, silicone rubber, rubber or resin. It can be understood that the material of the sealing member 125 is not limited to the above, and can also be other materials that can be used for sealing.
  • the seal 125 may be omitted.
  • the gap between the liquid capsule storage member 120 and the chip body 110 that is not for the liquid reagent to flow into the chip body 110 may be sealed in other ways.
  • a sealant is used to seal the gap between the liquid capsule storage member 120 and the chip body 110 that is not for the liquid reagent to flow into the chip body 110 .
  • the above-mentioned microfluidic chip 10 further includes a liquid capsule 130 .
  • the liquid bag 130 is used for containing liquid reagents.
  • Types of liquid reagents include but are not limited to buffers (ionic solutions, surfactant mixtures), reaction solutions (antigen/antibody dilutions,) protein dilutions, magnetic particle dilutions, luminescence/fluorescence reagent dilutions, nucleic acid dilutions , molecular/protein biological probe diluent, etc.) and at least one of cleaning solution (surfactant mixture, detergent, etc.).
  • the number of liquid capsules 130 is six. It can be understood that, in other embodiments, the number of liquid capsules 130 is not limited to the above, and can also be adjusted according to actual conditions.
  • the microfluidic chip 10 includes a protection member 140 .
  • the protective member 140 is used to reduce the extrusion of the liquid bag 130 by external force during transportation and/or storage, and avoid the liquid bag 130 being pierced in advance due to the extrusion of the liquid bag 130 by the external force during transportation and/or storage.
  • the scrapping of the microfluidic chip 10 further reduces the scrapping rate of the aforementioned microfluidic chip 10 .
  • the protection part 140 covers the side of the liquid capsule storage part 120 away from the chip main body 110 and is fixedly connected with the chip main body 110 .
  • the protection part 140 is provided with an escape hole 141 corresponding to the liquid capsule cavity 121 .
  • the number of escape holes 141 corresponds to the number of liquid capsules 130 .
  • the number of escape holes 141 is six.
  • pressing the fluid capsule 130 through the avoidance hole 141 can make the fluid capsule 130 contact with the sharp part 123 and be pierced.
  • the way of fixed connection is not particularly limited.
  • it may be a detachable fixed connection such as screw connection or snap connection, or may be a non-detachable fixed connection such as bonding, welding, riveting, interference fit or the like.
  • the protector 140 is disc-shaped. It can be understood that, in other embodiments, the shape of the protective member 140 is not limited to the above, and can also be adjusted according to actual conditions.
  • the escape hole 141 is a through hole opened in the axial direction of the protection member 140 .
  • a force is applied to the axial direction of the protection member 140 through the avoidance hole 141 to squeeze the liquid bag 130 , so that the liquid bag 130 is close to the spike 123 and pierced by the spike 123 .
  • the escape hole 141 can also be opened in the radial direction of the protection member 140 .
  • a force is applied to the axial direction of the protection member 140 through the escape hole 141 in the radial direction, and the liquid bag 130 is squeezed, so that the liquid bag 130 is close to the spike 123 and pierced by the spike 123 .
  • the microfluidic chip 10 further includes an indicator 150 .
  • the indicator 150 is used to indicate whether the liquid bag 130 is damaged or whether it is squeezed by external force.
  • the indicating member 150 is located between the liquid bladder storage member 120 and the protective member 140, and the material of the indicating member 150 is a material that is easily deformed under force.
  • the protection member 140 is a transparent protection member 140; and/or, the material of the liquid capsule storage member 120 and the material of the chip main body 110 are both transparent materials.
  • the parts on the indicator 150 (protector 140) and the parts under the indicator 150 (liquid bag storage part 120 and chip main body 110) are set as transparent materials, so that the indication can be observed from above or below the indicator 150.
  • the member 150 is broken or deformed, so as to determine whether the liquid bag 130 is squeezed by external force and whether it is damaged. On the other hand, the completion of the test can also be confirmed through the indicator 150 . For example, during assembly, the indicator 150 is placed on the reagents that have been tested, and there is no indicator 150 on the reagents that have not been tested.
  • the material of the indicator 150 is plastic film, aluminum foil, tin foil or paper.
  • the material of the indicator 150 is at least one of polyester film (PET), polypropylene film (PP) and polyethylene film (PE).
  • the material of the indicator 150 is one of soft/hard label paper with dotted line indentations, printing paper and composite paper. It can be understood that the material of the indicating member 150 is not limited to the above, and may also be other materials that are easily deformed by force.
  • the above-mentioned microfluidic chip 10 further includes a first fixing member 160, and the liquid capsule storage member 120 and the chip main body 110 are fixedly connected through the first fixing member 160.
  • the first fixing part 160 runs through the protection part 140, the indicator part 150 and the liquid bag storage part 120, and is used for fixedly connecting the protection part 140, the indicator part 150 and the liquid bag storage part 120 with the chip main body 110 .
  • the fixed connection of the protective part 140 and the indicating part 150 with the liquid bladder storage part 120 can be fixed by the first fixing part 160 or by other methods.
  • the material of the first fixing member 160 is thermoplastic material.
  • the microfluidic chip 10 further includes a second fixing part 170 , and the protection part 140 and the indicator part 150 are fixedly connected to the liquid bag storage part 120 through the second fixing part 170 .
  • the second fixing part 170 passes through the protection part 140 and the indicator part 150 and is fixedly connected with the liquid bag storage part 120 .
  • the above-mentioned microfluidic chip 10 also has a positioning hole 180 .
  • the positioning hole 180 is used for positioning, which is convenient for assembly and use.
  • the above-mentioned microfluidic chip 10 includes a chip body 110 and a liquid sac storage member 120 located on the chip body 110 . That is to say, the microfluidic chip 10 at this time is a microfluidic chip 10 capable of loading the liquid capsule 130 formed by assembling the chip main body 110 and the liquid capsule storage part 120 .
  • the liquid capsule 130 is freely selected according to specific requirements and then assembled with the microfluidic chip 10 that can be loaded with the liquid capsule 130 , thereby forming the microfluidic chip 10 that can be used directly.
  • the above-mentioned microfluidic chip 10 includes a chip body 110, a liquid sac storage part 120 located on the chip main body 110, a liquid sac 130 located in the liquid sac storage part 120, and a liquid sac storage part 120 located away from the chip main body.
  • the protective part 140 on the 110 side, the chip main body 110 is fixedly connected with the fluid bag storage part 120 and the protective part 140 .
  • the microfluidic chip 10 is a microfluidic chip 10 that can be used directly.
  • the above-mentioned microfluidic chip 10 includes a chip body 110, a liquid sac storage part 120 located on the chip main body 110, a liquid sac 130 located in the liquid sac storage part 120, and a liquid sac storage part 120 located away from the liquid sac storage part 120.
  • the protective part 140 on the side of the chip main body 110 and the indicator 150 located between the protective part 140 and the liquid bag storage part 120, the chip main body 110, the liquid bag storage part 120, the protective part 140 and the indicator 150 pass through the first fixing part 160
  • the liquid bladder storage part 120 , the protection part 140 and the indicator part 150 are also fixedly connected through the second fixing part 170 .
  • the microfluidic chip 10 has a thickness of 10mm-20mm.
  • the thickness of the microfluidic chip 10 refers to the axial length of the microfluidic chip 10, that is, the side of the chip body 110 away from the liquid bag storage part 120 to the side of the protective part 140 away from the indicator 150 distance.
  • the thickness of the microfluidic chip 10 is not limited to the above, and can also be adjusted according to actual conditions.
  • microfluidic chip 10 has at least the following advantages:
  • the opening sizes of the plurality of liquid bags 130 are basically the same, so that the flow rate of the reagent flowing out of each liquid bag 130 is consistent with the flow rate.
  • the resistance is basically the same, which can improve the detection repeatability, stability and consistency of the above-mentioned microfluidic chip 10, and reduce the variance of the POCT test process.
  • the reagent drainage drive can be completed manually or by an external device mechanism, and the operation is simple; the design of the drainage groove 124 and the seal 125 greatly improves the end-use efficiency of the liquid, and reduces the loss and dead volume of the liquid during the flow transfer process.
  • an embodiment of the present application also provides an assembly method of the above-mentioned microfluidic chip 10 , the assembly method makes the chip main body 110 , the liquid bag storage part 120 with the liquid bag 130 placed thereon, and the indicator part 150 through riveting. and the protective member 140 to prepare the above-mentioned microfluidic chip 10 .
  • the assembling method includes step S100 and step S200. specifically:
  • Step S100 Put the liquid capsule storage part 120 on the first fixing post 161 on the chip main body 110, and seal the gap between the liquid outlet 122 and the liquid inlet 111 with the sealing member 125, wherein the first fixing post 161 It is fixed on the side of the chip main body 110 provided with the liquid inlet 111 .
  • Step S200 Place the liquid capsule 130 in the liquid capsule cavity 121 of the liquid capsule storage part 120, and then sequentially set the indicator part 150 and the protection part 140 on the second fixing column 171 on the indicator part 150 and on the chip main body 110.
  • the chip main body 110 , the liquid capsule storage part 120 , the indicator part 150 and the protection part 140 are fixed by riveting.
  • the riveting is a combination of hot air and cold riveting.
  • both the first fixing column 161 and the second fixing column 171 are thermoplastic materials. Hot air from the first fixing post 161 and the second fixing post 171 close to one end of the protector 140 and/or heat, when it melts or softens, after a preset heating time, use a cold jig to depress the first fixing post 161 and the second fixing post 171 form a rivet, so that the chip main body 110 , the liquid capsule storage part 120 , the indicator part 150 and the protection part 140 are fixed.
  • the riveting is ultrasonic riveting.
  • both the first fixing column 161 and the second fixing column 171 are thermoplastic materials.
  • the first fixing column and the second fixing column 171 are heated by ultrasonic high-frequency vibration, and the ultrasonic indenter melts them to form a rivet.
  • ultrasonic heating is very rapid and the cycle is short.
  • Proper riveting design is required to provide a small initial contact between the sonotrode and the fixing post to produce a rapid heating effect.
  • the high-amplitude vibration and the deceleration of the ultrasonic indenter are used to melt and flow the stud, and the ultrasonic indenter is filled to form a rivet cap, so that the chip main body 110 is connected with the liquid bladder storage part 120, the indicator part 150 and the protective part 140. fixed.
  • the riveting is infrared or laser riveting. Specifically, it is similar to ultrasonic riveting, except that the way to melt the first fixing post 161 and the second fixing post 171 is infrared heating or laser heating.
  • the fixing method of the chip main body 110 and the fluid bag storage part 120 , the indicator part 150 and the protection part 140 is riveting. It can be understood that, in other embodiments, the fixing method of the chip main body 110 and the liquid bag storage part 120, the indicator part 150 and the protective part 140 is not limited to riveting, and other fixing methods are also possible, such as glue, ultrasonic welding, laser welding, etc. welding etc.
  • the specific assembly process can be determined according to the actual requirements of the microfluidic chip 10 . For example, if the thickness of the microfluidic chip 10 itself is low or structural design factors lead to limited pressure bearing capacity, riveting is not suitable, and glue or ultrasonic welding is more suitable.
  • the storage reagent itself is not resistant to high temperature, the riveting, ultrasonic and laser welding processes are not suitable (the thermal effect is uncontrollable, affecting the stability and performance of the reagent, and even making the reagent invalid).
  • the normal temperature operation process of the gluing process is more suitable.
  • the method for assembling the above-mentioned microfluidic chip 10 is simple and easy, which is beneficial to industrial production.

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Abstract

本发明涉及一种微流控芯片。该微流控芯片包括芯片主体和液囊储存件，芯片主体上设置有进液口，液囊储存件位于芯片主体上，液囊储存件上设置有用于放置液囊的液囊腔，液囊腔具有出液口，出液口与进液口连通，液囊腔中设置有尖刺件；在液囊放置于液囊腔中时，液囊与尖刺件之间有间隔；在液囊受到的挤压力超过预设值时，尖刺件能刺破所述液囊。上述微流控芯片能降低芯片的报废率，提高芯片的测试重复性和稳定性。

Description

微流控芯片 技术领域
本发明涉及微流控技术领域，特别是涉及微流控芯片。
背景技术
POCT，即时检验(point-of-care testing)，是在采样现场进行的、利用便携式分析仪器及配套试剂快速得到检测结果的一种检测方式。POCT在采样现场即刻进行分析，省去标本在实验室检验时的复杂处理程序，具有快速出结果、使用简单的优势。
目前，POCT产品主要包括微流控芯片和应用于微流控芯片上用于检测的试剂。POCT产品的试剂存储方式分为芯片内部储存和芯片外部储存。芯片内部储存是指在芯片加工和组装过程中引入试剂灌注步骤，直接在芯片内的存储腔或存储槽内注入液体试剂后再完成芯片整体封装。芯片内部储存时，无需额外单独使用包装方式存储试剂，直接将试剂内置于芯片内，但芯片存储槽与芯片内流体通道之间需要做阻挡或阀控，否则试剂在存储和运输过程会提前流入通道内造成报废；并且试剂封装与芯片加工放在一起，会增大加工难度和过程控制难度，工艺流程冗长且复杂，例如设置阀控或阻挡就增加芯片设计复杂度，且既要兼顾试剂存储和运输过程的稳定性还要保证测试过程试剂的引入问题，也增加测试系统控制的复杂度；另外，一般而言，采用芯片内部储存时存储试剂种类有限，无法兼容多组分试剂的内置。
芯片外部储存是指芯片组装与试剂灌装和封装流程独立，液体试剂封入液囊后，再将液囊与芯片对应位置贴合后组装使用。芯片外部储存时，试剂灌装 及封装与芯片加工组装步骤分离，工艺控制更加可靠，并且可轻松实现多类型试剂的存储，与芯片组合灵活度和自由度高。但是，装有液体试剂的液囊贴合于芯片外，在运输和存储过程很容易出现受挤压破损而报废，并且在使用时测试重复性和稳定性较差。
发明内容
基于此，有必要提供一种能降低报废率、提高测试重复性和稳定性的微流控芯片。
一种微流控芯片，包括：
芯片主体，芯片主体上设置有进液口；及
液囊储存件，位于所述芯片主体上，所述液囊储存件上设置有用于放置液囊的液囊腔，液囊腔具有出液口，所述出液口与所述进液口连通，所述液囊腔中设置有尖刺件；在所述液囊放置于所述液囊腔中时，所述液囊与所述尖刺件之间有间隔；在所述液囊受到的挤压力超过预设值时，所述尖刺件能刺破所述液囊。
上述微流控芯片通过在液囊放置于液囊腔中时液囊与尖刺件之间有间隔，使得液囊在受到挤压力(例如在运输和存储过程中受到的挤压力)不超过预设值时不刺破，而在使用时施加超过预设值的挤压力则可以刺破，从而降低了上述微流控芯片的报废率。并且，通过尖刺件的设置，使得液囊中流出的试剂的流速与流阻能够基本相同，从而提高了上述微流控芯片的检测重复性和稳定性。
在其中一个实施例中，所述尖刺件上设置有引流槽，所述引流槽与所述出液口连通。
在其中一个实施例中，所述尖刺件呈锥状或针状。
在其中一个实施例中，所述微流控芯片包括保护件，所述保护件连接于所述芯片主体并覆盖所述液囊储存件，所述保护件上设置有与所述液囊腔对应的液囊避位孔。
在其中一个实施例中，所述微流控芯片还包括指示件，所述指示件位于所述液囊储存件与所述保护件之间，所述指示件的材料为受力易变形的材料；所述保护件为透明保护件，及/或，所述液囊储存件的材料和所述芯片主体的材料均为透明材料。
在其中一个实施例中，所述指示件的材料为塑料薄膜、铝箔、锡箔或纸张。
在其中一个实施例中，所述微流控芯片还包括第一固定件，所述第一固定件用于固定连接所述液囊储存件和所述芯片主体。
在其中一个实施例中，所述微流控芯片还包括第二固定件，所述第二固定件用于固定连接所述保护件和所述液囊储存件。
在其中一个实施例中，所述微流控芯片还包括密封件，所述密封件位于所述液囊储存件与所述芯片主体之间，所述密封件用于密封所述液囊储存件与所述芯片主体之间的间隙，所述密封件具有液体通道，所述出液口与所述进液口经所述液体通道连通。
在其中一个实施例中，微流控芯片，所述液囊腔的底部为呈漏斗状，所述尖刺件位于所述底部上，所述出液口位于所述底部的距所述芯片主体的距离最近处。
附图说明
图1为一实施例的微流控芯片的立体图；
图2为图1所示的微流控芯片的爆炸图；
图3为图1所示的微流控芯片的液囊储存件的立体图；
图4为图1所示的微流控芯片的剖面图；
图5为图4所示的液囊储存件的B部放大图；
图6为图3所示的液囊储存件的A部的放大图；
图7为图1所示的微流控芯片未组装之前的爆炸图。
附图标记：
10、微流控芯片；110、芯片主体；120、液囊储存件；111、进液口；121、液囊腔；122、出液口；123、尖刺件；124、引流槽；125、密封件；126、液体通道；130、液囊；140、保护件；141、避位孔；150、指示件；160、第一固定件；170、第二固定件；180、定位孔；161、第一固定柱；171、第二固定柱。
具体实施方式
为了便于理解本发明，下面将对本发明进行更全面的描述，本发明可以以许多不同的形式来实现，并不限于本文所描述的实施例。相反地，提供这些实施例的目的是使本发明公开内容更加透彻全面。
需要说明的是，当元件被表述“固定于”另一个元件，它可以直接在另一个元件上、或者其间可以存在一个或多个居中的元件。当一个元件被表述“连接”另一个元件，它可以是直接连接到另一个元件、或者其间可以存在一个或多个居中的元件。当使用术语“垂直的”、“水平的”、“左”、“右”、“上”、“下”、“内”、“外”、“底部”等指示方位或位置关系时，是为基于附图所示的方位或位置关系，仅为了便于描述，而不是指示或暗示所指的装置或元件必须具有特定的方位、以特定的方位构造和操作，因此不能理解为对本申请的限制。此外，术语“第一”、“第二”等仅用于描述目的，而不能理解为指示或暗示相对重要 性。
除非另有定义，本文所使用的所有的技术和科学术语与属于本发明的技术领域的技术人员通常理解的含义相同。本文中在本发明的说明书中所使用的术语只是为了描述具体的实施例的目的，不是旨在于限制本发明。
请参阅图1和图2，本申请一实施方式提供了一种微流控芯片10，该微流控芯片10包括芯片主体110和液囊储存件120，芯片主体110上设置有进液口111，液囊储存件120位于芯片主体110上，液囊储存件120上设置有用于放置液囊130的液囊腔121，液囊腔121具有出液口122，出液口122与进液口111连通，液囊腔121中设置有尖刺件123；在液囊130放置于液囊腔121中时，液囊130与尖刺件123之间有间隔；在液囊130受到的挤压力超过预设值时，尖刺件123能刺破液囊130。通过在液囊130放置于液囊腔121中时液囊130与尖刺件123之间有间隔，使得液囊130在受到的挤压力(例如在运输和存储过程中受到的挤压力)不超过预设值时不被尖刺件123刺破，而在使用时施加超过预设值的挤压力则被尖刺件123刺破，从而降低了上述微流控芯片10的报废率。另外，传统的微流控芯片中的液囊的破裂是通过直接挤压液囊使得其靠近出液口一侧的铝箔破裂而液体流出，经本申请的研究发现，这种方式会使得液囊破裂情况随机性大，容易导致液体试剂进入芯片主体时的流速和流阻差异大，从而影响测试重复性和稳定性。因此，本申请通过尖刺件123的设置，使得液囊130在受到相同大小的挤压力(或者大于刺破液囊130的极限值的不同挤压力，因为在超过极限值后，挤压力的大小不会改变液囊130的开口大小，因而也不会影响流速及流阻)之后，多个液囊130的开口大小基本一致，从而使得各液囊130中流出的试剂的流速与流阻基本相同，从而提高上述微流控芯片10的检测重复性和稳定性。
具体地，尖刺件123刺破液囊130时，液囊130受到的挤压力的预设值，与液囊130的材料、液囊130放置于液囊腔121中时液囊130与尖刺件123之间的间隔距离、以及液囊130在运输和存储过程中受到的挤压力相关。具体的预设值可以根据液囊130的材料、液囊130放置于液囊腔121中时液囊130与尖刺件123之间的间隔距离、以及液囊130在运输和存储过程中受到的挤压力进行设定。可以理解的是，挤压力的预设值是基于液囊130实际受到的自液囊130向刺破件123靠近方向上的力设计。例如，在图示的实施例中，挤压力的预设值是基于液囊130能够承受竖直向下的力的大小设计。例如，若液囊130受到的是斜向下的力，则在竖直方向下的力则只是这个斜向下的力的分力，只要这个分力的大小没有超过预设值，则液囊130不被刺破。
在一些实施例中，液囊130的靠近尖刺件123侧的材料为铝箔、PET薄膜、PP薄膜或LDPE薄膜。在另一些实施例中，液囊130的靠近尖刺件123侧的材料为塑料薄膜与铝箔的复合膜。在一些实施例中，液囊130的靠近尖刺件123侧的厚度为50μm～200μm；液囊130的远离尖刺件123侧的材料为PP、HDPE、PVC和PET中的至少一种。液囊130是由上述材料(PP、HDPE、PVC和PET中的至少一种)通过吹塑或注塑工艺制备得到穹顶外壳结构。在一些实施例中，液囊130的远离尖刺件123侧的厚度为75μm～200μm。
在液囊130放置于液囊腔121中时，液囊130与尖刺件123之间的间隔距离为1mm～10mm。例如，2mm、5mm或8mm。液囊130与尖刺件123之间的间隔距离是指尖刺件123的靠近液囊130的最近处到液囊130的靠近尖刺件123的一侧的距离。可以理解的是，在液囊130放置于液囊腔121中时液囊130与尖刺件123之间的间隔距离，可以根据液囊130的材料进行调整。如果液囊130的材料是受到挤压容易发生形变而容易向尖刺件123靠近的材料，则液囊130 与尖刺件123之间的间隔距离可以设置较远一些；如果液囊130的材料是受到挤压不容易发生形变而不容易向尖刺件123靠近的材料，则液囊130与尖刺件123之间的间隔距离可以设置较短一些。如此设置，可以使得上述微流控芯片10在运输和存储过程中不容易报废，使用时比较容易刺破。
具体地，芯片主体110是作为POCT产品的重要部件，芯片主体110包括有反应腔室及与反应腔室连通的流体通道。芯片主体110上设置有进液口111。进液口111与芯片主体110上的反应腔室连通。在检测时，用于检测的试剂从进液口111进入芯片主体110。
在一些实施例中，芯片主体110上设置有多个反应腔室，多个反应腔室通过流体流道连通。至少部分反应腔室具有各自的进液口111，此时，液囊储存件120也具有与这些反应腔室对应的液囊腔121及出液口122。在图示的实施例中，芯片主体110上具有六个间隔的进液口111，液囊储存件120也具有六个液囊腔121及六个出液口122。在图示的实施例中，为一个液囊腔121对应一个出液口122，一个出液口122对应一个进液口111。可以理解的是，在其他实施例中，还可以是一个液囊腔121对应多个出液口122。多个或一个出液口122对应一个或多个进液口111。进液口111和出液口122的数量可以根据实际情况进行调整。当然，在一些实施例中，芯片上的反应腔室也可以只有一个。此时，液囊储存件120上的液囊腔121也对应为一个。可以理解的是，进液口111与出液口122的大小没有特别限制，可以根据实际情况(例如液体试剂的流速/流量)进行调整。
在图示的实施例中，芯片主体110呈圆盘状。可以理解的是，在其他实施例中，芯片主体110的形状不限于圆盘片状，还可以是其他任意形状。例如，方块状或椭圆状等。在一些实施例中，芯片主体110的材料选自聚二甲基硅氧 烷(PDMS)、聚氨酯、环氧树脂、聚甲基丙烯酸甲酯(PMMA)、聚碳酸酯(PC)、环烯烃共聚物(COC/COP)、聚苯乙烯(PS)、聚乙烯(PE)、聚丙烯(PP)和氟塑料中的至少一种。可以理解的是，芯片主体110的材料不限于上述，还可以是其他材料。
请参阅图3～图5，液囊储存件120用于储存装有液体试剂的液囊130。具体地，液囊储存件120上设置液囊腔121，液囊腔121用于放置液囊130。在图示的实施例中，液囊储存件120呈圆盘状。可以理解的是，在其他实施例中，液囊储存件120的形状不限于上述，还可以根据实际需求进行调整。在图示的实施例中，液囊腔121的数量为六个。可以理解的是，在其他实施例中，液囊腔121的数量不限于上述，还可以根据实际情况进行调整。当然，液囊腔121的形状不限，但需与液囊130相匹配。例如，在图示的实施例中，液囊130大致呈半球形，液囊腔121的大致为底部向芯片主体110凹陷的柱状。
在一些实施例中，液囊储存件120的材料为刚性材料。通过采用刚性液囊储存件120，利用保护液囊腔121中的液囊130。
在一些实施例中，液囊腔121的底部为呈漏斗状，尖刺件123位于底部上，出液口122位于底部的距芯片主体110的距离最近处。通过将液囊130的底部设置为漏斗状，使得尖刺件123与液囊130之间有一定的间隔，而液囊130需要在受到的一定的挤压力才能被尖刺件123刺破，而非受到轻微挤压就能刺破，降低了上述芯片的报废率。另外，液囊130的底部呈漏斗状也便于液囊130中的液体试剂向芯片主体110流动，不容易浪费液体试剂。可以理解的是，在其他实施例中，液囊腔121的底部不限于漏斗状，还可以是其他向芯片主体110方向凹陷的曲面。
在一些实施例中，尖刺件123呈锥状或针状。在一个可选地具体示例中， 尖刺件123呈圆锥状或三棱锥状。尖刺件123将液囊130的封膜刺穿后，随着刺入深度的增加，封膜被刺破的开口越大。在一些实施例中，尖刺件123的数量为多个，多个尖刺件123间隔地围绕出液口122排布。进一步地，多个尖刺件123到出液口122的中心的距离相等。在图示的实施例中，尖刺件123的数量为三个，三个尖刺件123间隔地围绕出液口122排布，三个尖刺件123到出液口122的中心的距离相等。可以理解的是，在其他实施例中，尖刺件123的数量不限于上述三个，还可以是其他数量，例如一个、两个、五个或六个等。
请参阅图6，在一些实施例中，尖刺件123上还设置有引流槽124。引流槽124与出液口122连通。引流槽124用于将液囊130中的液体引向出液口122。在图示的实施例中，引流槽124位于尖刺件123的靠近出液口122的一侧。可以理解的是，在其他实施例中，引流槽124的位置不限于上述，还可以位于尖刺件123的其他位置上。例如位于尖刺件123的远离出液口122的一侧。
请参阅图5，在一些实施例中，上述微流控芯片10还包括密封件125。密封件125位于液囊储存件120与芯片主体110之间，密封件125用于密封液囊储存件120与所芯片主体110之间的间隙。密封件125具有液体通道126，出液口122与进液口111经液体通道126连通。具体地，液囊储存件120具有出液通道，出液通道的一端与出液口122连通，另一端与进液口111连通。密封件125位于出液通道内，密封件125的外侧壁与出液通道的侧壁密封连接，密封件125靠近芯片主体110的外壁与芯片主体110密封连接。此时，从出液口122流出的液体试剂经液体通道126进入进液口111。可选地，密封件125为弹性密封件125。在一个可选地具体示例中，密封件125的材料为TPU、硅橡胶、橡胶或树脂。可以理解的是，密封件125的材料不限于上述，还可以是其他可以用于密封的材料。
可以理解的是，在一些实施例中，密封件125可以省略。此时，可以通过其他方式将液囊储存件120与芯片主体110之间并非供液体试剂流入芯片主体110的缝隙密封。例如，采用密封胶密封液囊储存件120与芯片主体110之间并非供液体试剂流入芯片主体110的缝隙。
在一些实施例中，上述微流控芯片10还包括液囊130。液囊130用于承装液体试剂。液体试剂的类型包括但不限于缓冲液(离子溶液、表面活性剂混合液)、反应液(抗原/抗体稀释液、)蛋白稀释液、磁性微粒稀释液、发光/荧光试剂稀释液、核酸稀释液、分子/蛋白生物探针稀释液等)和清洗液(表面活性剂混合液、去污剂等)中的至少一种。在图示的实施例中，液囊130的个数为六个。可以理解的是，在其他实施例中，液囊130的个数不限于上述，还可以根据实际情况进行调整。
在一些实施例中，微流控芯片10包括保护件140。保护件140用于减少运输和/或存储过程中外力对液囊130的挤压，避免在运输和/或存储过程中由于外力对液囊130的挤压使得液囊130提前刺破而使得上述微流控芯片10报废，进一步降低上述微流控芯片10的报废率。保护件140盖于液囊储存件120远离芯片主体110的一侧并与芯片主体110固定连接，保护件140上设置有与液囊腔121对应的避位孔141。避位孔141的数量为液囊130的数量对应。在图示的实施例中，避位孔141的数量为六个。在使用上述微流控芯片10时，通过避位孔141挤压液囊130，可使得液囊130与尖刺件123接触而被刺破。在本文中，在未特别指明的情况下，固定连接的方式没有特别限定。例如，可以是螺接或卡接等可拆卸地固定连接，也可以是粘结、焊接、铆接、过盈配合等的不可拆卸的固定连接。
在图示的实施例中，保护件140呈圆盘状。可以理解的是，在其他实施例 中，保护件140的形状不限于上述，还可以根据实际情况进行调整。
在图示的实施例中，避位孔141是开设在保护件140的轴向上的通孔。通过避位孔141向保护件140的轴向上施加力，挤压液囊130，使得液囊130靠近尖刺件123并被尖刺件123刺破。可以理解的是，在其他一些实施例中，避位孔141还可以开设在保护件140的径向上。此时通过径向上的避位孔141向保护件140的轴向上施加力，挤压液囊130，使得液囊130靠近尖刺件123并被尖刺件123刺破。
在一些实施例中，微流控芯片10还包括指示件150。指示件150用于指示液囊130是否破损或是否有受到外力挤压。具体地，指示件150位于液囊储存件120与保护件140之间，指示件150的材料为受力易变形的材料。此时，保护件140为透明保护件140；及/或，液囊储存件120的材料和芯片主体110的材料均为透明材料。将位于指示件150上的部件(保护件140)和位于指示件150下的部件(液囊储存件120和芯片主体110)设置为透明材料，这样便于从指示件150的上方或下方观察到指示件150是否有破裂或形变，从而判断液囊130是否有受到外力挤压，是否有破损。另一方面，通过指示件150也可以确认测试完成与否。例如，在组装时，在测试完成的试剂上方放置指示件150，未参加测试的试剂上无指示件150。
可选地，指示件150的材料为塑料薄膜、铝箔、锡箔或纸张。在一个可选地具体示例中，指示件150的材料为聚酯薄膜(PET)、聚丙烯薄膜(PP)及聚乙烯薄膜(PE)中的至少一种。在另一个可选地具体示例中，指示件150的材料为带虚线压痕的软/硬标签纸、打印纸和复合纸中的一种。可以理解的是，指示件150的材料不限于上述，还可以是其他容易受力变形的材料。
在一些实施例中，上述微流控芯片10还包括第一固定件160，液囊储存件 120和芯片主体110通过第一固定件160固定连接。在图示的实施例中，第一固定件160贯穿保护件140、指示件150和液囊储存件120，用于将保护件140、指示件150和液囊储存件120与芯片主体110固定连接。可以理解的是，保护件140和指示件150与液囊储存件120的固定连接可以通过第一固定件160，也可以通过其他方式固定。可选地，第一固定件160的材料为热塑性材料。采用热塑性材料可以使得组织上述微流控芯片10时较为便捷。在图示的实施例中，微流控芯片10还包括第二固定件170，保护件140和指示件150通过第二固定件170与液囊储存件120的固定连接。具体地，第二固定件170贯穿保护件140和指示件150并与液囊储存件120固定连接。
在一些实施例中，上述微流控芯片10还具有定位孔180。在组装上述微流控芯片10或使用上述微流控芯片10时，定位孔180用于定位，便于组装和使用。
在一些实施例中，上述微流控芯片10包括芯片主体110和位于芯片主体110上的液囊储存件120。也即是，此时的微流控芯片10是将芯片主体110和液囊储存件120组装而形成的可装载液囊130的微流控芯片10。液囊130根据具体需求自由选择后再与可装载液囊130的微流控芯片10组装，从而形成可以直接使用的微流控芯片10。
在一些实施例中，上述微流控芯片10包括芯片主体110、位于芯片主体110上的液囊储存件120、位于液囊储存件120中的液囊130和位于液囊储存件120远离芯片主体110侧的保护件140，芯片主体110与液囊储存件120和保护件140固定连接。此时的微流控芯片10为可直接使用的微流控芯片10。在图示的实施例中，上述微流控芯片10包括芯片主体110、位于芯片主体110上的液囊储存件120、位于液囊储存件120中的液囊130、位于液囊储存件120远离芯片 主体110侧的保护件140、和位于保护件140和液囊储存件120之间的指示件150，芯片主体110、液囊储存件120、保护件140和指示件150通过第一固定件160固定连接，并且液囊储存件120、保护件140和指示件150还通过第二固定件170固定连接。
在一些实施例中，上述微流控芯片10的厚度为10mm～20mm。本文中，微流控芯片10的厚度是指微流控芯片10的轴向长度，也即是芯片主体110的远离液囊储存件120的一侧到保护件140的远离指示件150的一侧的距离。当然，若无保护件140和指示件150，则指的是芯片主体110的远离液囊储存件120的一侧到液囊储存件120的远离芯片主体110的一侧的距离。可以理解的是，上述微流控芯片10的厚度不限于上述，还可以根据实际情况进行调整。
上述微流控芯片10至少具有如下优点：
(1)在液囊130放置于液囊腔121中且未被使用时，通过液囊130与尖刺件123之间的间隔，使得液囊130在受到不超过预设值的挤压力时(一般的运输或存储过程中受到的挤压力)不刺破，而超过预设值的挤压力可以刺破，降低上述微流控芯片10的报废率。
(2)通过尖刺件123的设置，使得液囊130在受到相同大小的挤压力之后，多个液囊130的开口大小基本一致，从而使得各液囊130中流出的试剂的流速与流阻基本相同，可以提高上述微流控芯片10的检测重复性、稳定性和一致性，降低POCT测试过程的差异性。并且，试剂引流驱动可依靠手动或外部设备机构的方式完成，操作简单；引流槽124及密封件125的设计极大的提高液体终末利用效率，减少液体在流动转移过程的损失和死体积。
(3)多种与芯片的键合装配工艺适用，装配位置在芯片功能反应区以外，不影响芯片内的流体设计与反应流程设计，仅仅需要芯片上表面有接口可与装 置底部液体进样口对应即可实现试剂引入，此模块化设计能够匹配不同检测需求、不同结构设计的芯片。
(4)多个液囊130的设计及采用不同颜色的液囊130可区分不同试剂，使得上述微流控芯片10的检测用途广泛，可作为模块化的芯片；并且，多种试剂可以自由搭配，试剂兼容性腔，且试剂种类较多时不易混淆。
请参阅图7，本申请一实施方式还提供了一种上述微流控芯片10的组装方法，该组装方法通过铆接使得芯片主体110、放置有液囊130的液囊储存件120、指示件150和保护件140固定，制备上述微流控芯片10。具体地，该组装方法包括步骤S100和步骤S200。具体地：
步骤S100：将液囊储存件120穿设于芯片主体110上的第一固定柱161上，并用密封件125密封出液口122与进液口111之间的间隙，其中，第一固定柱161固定在芯片主体110上设有进液口111的一面上。
步骤S200：将液囊130置于液囊储存件120的液囊腔121中，然后依次将指示件150和保护件140套设于指示件150上的第二固定柱171和芯片主体110上的第一固定柱161上，并使用铆接方式使得芯片主体110、液囊储存件120、指示件150和保护件140固定。
在其中一个实施例中，铆接为热风与冷铆相结合。具体地，第一固定柱161和第二固定柱171均为热塑性材料。热空气从第一固定柱161和第二固定柱171靠近保护件140的一端和/或加热，当其熔化或软化时，在预设的加热时间后，使用冷治具下压第一固定柱161和第二固定柱171形成铆钉，从而使得芯片主体110、液囊储存件120、指示件150和保护件140固定。
在其中一个实施例中，铆接为超声铆接。具体地，第一固定柱161和第二固定柱171均为热塑性材料。利用超声高频振动对一固定柱和第二固定柱171 进行加热，超声压头将其融化后形成铆钉。与其他铆接方法相比，超声波加热非常迅速，周期短。适当的铆接设计需要在超声压头和固定柱之间提供较小的初始接触，以产生快速加热效果。在超声铆接过程中，采用高振幅振动和超声压头减速下降，使螺柱融化流动，填充超声压头形成铆钉帽，从而使得芯片主体110与液囊储存件120、指示件150和保护件140固定。
在其中一个实施例中，铆接为红外或激光铆接。具体地，与超声铆接类似，只是促使第一固定柱161和第二固定柱171融化的方式是通过红外加热或激光加热。
在上述实施方式的组装方法中，芯片主体110与液囊储存件120、指示件150和保护件140的固定方式为铆接。可以理解的是，在其他实施方式中，芯片主体110与液囊储存件120、指示件150和保护件140的固定方式不限于铆接，还可以是其他固定方式，例如胶黏、超声焊接、激光焊接等方式进行。具体组装工艺可根据实际微流控芯片10需求确定。例如，若微流控芯片10本身厚度较低或结构设计因素，导致承压能力有限，则采用铆接方式不适宜，而胶黏或超声焊接工艺更合适。又例如，若存储试剂本身不耐高温，则铆接、超声和激光焊接工艺不适宜(热效应不可控，影响试剂稳定性和性能，甚至使得试剂失效)，此时胶黏工艺这种常温操作工艺更加合适。
上述微流控芯片10的组装方法简捷易行，利于工业化生产。
以上所述实施例的各技术特征可以进行任意的组合，为使描述简洁，未对上述实施例中的各个技术特征所有可能的组合都进行描述，然而，只要这些技术特征的组合不存在矛盾，都应当认为是本说明书记载的范围。
以上所述实施例仅表达了本发明的几种实施方式，便于具体和详细地理解本发明的技术方案，但并不能因此而理解为对发明专利保护范围的限制。应当 指出的是，对于本领域的普通技术人员来说，在不脱离本发明构思的前提下，还可以做出若干变形和改进，这些都属于本发明的保护范围。应当理解的是，在本领域技术人员在本发明提供的技术方案的基础上，通过合乎逻辑的分析、推理或有限的试验得到的技术方案，均在本发明所附权利要求的保护范围内。因此，本发明专利的保护范围应以所附权利要求的内容为准，说明书及附图可以用于解释权利要求的内容。

Claims (10)

  1. 一种微流控芯片，其特征在于，包括：
    芯片主体，芯片主体上设置有进液口；及
    液囊储存件，位于所述芯片主体上，所述液囊储存件上设置有用于放置液囊的液囊腔，液囊腔具有出液口，所述出液口与所述进液口连通，所述液囊腔中设置有尖刺件；在所述液囊放置于所述液囊腔中时，所述液囊与所述尖刺件之间有间隔；在所述液囊受到的挤压力超过预设值时，所述尖刺件能刺破所述液囊。
  2. 根据权利要求1所述的微流控芯片，其特征在于，所述尖刺件上设置有引流槽，所述引流槽与所述出液口连通。
  3. 根据权利要求1所述的微流控芯片，其特征在于，所述尖刺件呈锥状或针状。
  4. 根据权利要求1～3中任一项所述的微流控芯片，其特征在于，所述微流控芯片包括保护件，所述保护件连接于所述芯片主体并覆盖所述液囊储存件，所述保护件上设置有与所述液囊腔对应的液囊避位孔。
  5. 根据权利要求4所述的微流控芯片，其特征在于，所述微流控芯片还包括指示件，所述指示件位于所述液囊储存件与所述保护件之间，所述指示件的材料为受力易变形的材料；所述保护件为透明保护件，及/或，所述液囊储存件的材料和所述芯片主体的材料均为透明材料。
  6. 根据权利要求5所述的微流控芯片，其特征在于，所述指示件的材料为塑料薄膜、铝箔、锡箔或纸张。
  7. 根据权利要求1所述的微流控芯片，其特征在于，所述微流控芯片还包括第一固定件，所述第一固定件用于固定连接所述液囊储存件和所述芯片主体。
  8. 根据权利要求5～7任一项所述的微流控芯片，其特征在于，所述微流控芯 片还包括第二固定件，所述第二固定件用于固定连接所述保护件和所述液囊储存件。
  9. 根据权利要求4所述的微流控芯片，其特征在于，所述微流控芯片还包括密封件，所述密封件位于所述液囊储存件与所述芯片主体之间，所述密封件用于密封所述液囊储存件与所述芯片主体之间的间隙，所述密封件具有液体通道，所述出液口与所述进液口经所述液体通道连通。
  10. 根据权利要求1～3、5～7及9中任一项所述的微流控芯片，其特征在于，所述液囊腔的底部为呈漏斗状，所述尖刺件位于所述底部上，所述出液口位于所述底部的距所述芯片主体的距离最近处。
PCT/CN2022/115034 2021-08-27 2022-08-26 微流控芯片 WO2023025274A1 (zh)

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CN114100711B (zh) * 2021-11-17 2022-11-29 江苏液滴逻辑生物技术有限公司 一种芯片试剂的包装、预埋与注样装置及方法与用途
CN114100710B (zh) * 2021-11-17 2022-12-13 江苏液滴逻辑生物技术有限公司 一种芯片检测样本定量注样的系统装置、方法与用途
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CN114308166A (zh) * 2022-02-24 2022-04-12 含光微纳科技(太仓)有限公司 一种液体试剂预埋及释放结构

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