EP4364850A1 - Puce microfluidique - Google Patents

Puce microfluidique Download PDF

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Publication number
EP4364850A1
EP4364850A1 EP22860620.8A EP22860620A EP4364850A1 EP 4364850 A1 EP4364850 A1 EP 4364850A1 EP 22860620 A EP22860620 A EP 22860620A EP 4364850 A1 EP4364850 A1 EP 4364850A1
Authority
EP
European Patent Office
Prior art keywords
liquid
liquid bladder
bladder
chip
microfluidic chip
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
EP22860620.8A
Other languages
German (de)
English (en)
Inventor
Daoshun WEI
Xiaoyu CHENG
Bifeng LIU
Chungen Qian
Yujin XIAO
Peng Chen
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Shenzhen Yhlo Biotech Co Ltd
Original Assignee
Shenzhen Yhlo Biotech Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Shenzhen Yhlo Biotech Co Ltd filed Critical Shenzhen Yhlo Biotech Co Ltd
Publication of EP4364850A1 publication Critical patent/EP4364850A1/fr
Pending legal-status Critical Current

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    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/502738Containers 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
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/50273Containers 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
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/52Containers specially adapted for storing or dispensing a reagent
    • B01L3/523Containers specially adapted for storing or dispensing a reagent with means for closing or opening
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2200/00Solutions for specific problems relating to chemical or physical laboratory apparatus
    • B01L2200/02Adapting objects or devices to another
    • B01L2200/026Fluid interfacing between devices or objects, e.g. connectors, inlet details
    • B01L2200/027Fluid interfacing between devices or objects, e.g. connectors, inlet details for microfluidic devices
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/06Auxiliary integrated devices, integrated components
    • B01L2300/0672Integrated piercing tool
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0803Disc shape
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2300/00Additional constructional details
    • B01L2300/08Geometry, shape and general structure
    • B01L2300/0809Geometry, shape and general structure rectangular shaped
    • B01L2300/0816Cards, e.g. flat sample carriers usually with flow in two horizontal directions
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/04Moving fluids with specific forces or mechanical means
    • B01L2400/0475Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure
    • B01L2400/0481Moving fluids with specific forces or mechanical means specific mechanical means and fluid pressure squeezing of channels or chambers
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L2400/00Moving or stopping fluids
    • B01L2400/06Valves, specific forms thereof
    • B01L2400/0677Valves, specific forms thereof phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers
    • B01L2400/0683Valves, specific forms thereof phase change valves; Meltable, freezing, dissolvable plugs; Destructible barriers mechanically breaking a wall or membrane within a channel or chamber
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/50Containers for the purpose of retaining a material to be analysed, e.g. test tubes
    • B01L3/502Containers for the purpose of retaining a material to be analysed, e.g. test tubes with fluid transport, e.g. in multi-compartment structures
    • B01L3/5027Containers 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
    • B01L3/502715Containers 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
    • BPERFORMING OPERATIONS; TRANSPORTING
    • B01PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01LCHEMICAL OR PHYSICAL LABORATORY APPARATUS FOR GENERAL USE
    • B01L3/00Containers or dishes for laboratory use, e.g. laboratory glassware; Droppers
    • B01L3/52Containers specially adapted for storing or dispensing a reagent
    • B01L3/527Containers specially adapted for storing or dispensing a reagent for a plurality of reagents

Definitions

  • the present invention relates to the technical field of microfluidics, particularly to a microfluidic chip.
  • POCT i.e., point-of-care testing
  • POCT is a detection mode that is carried out at the sampling site and uses portable analytical instruments and supporting reagents to quickly obtain results.
  • POCT performs immediate analysis at the sampling site, simplifying the complicated processing procedures of specimens in laboratory test, thus has advantages of quickly getting results and simple to use.
  • POCT products mainly include microfluidic chips and reagents for detection applied on microfluidic chips.
  • the reagent storage modes of POCT products are divided into internal chip storage and external chip storage.
  • Internal chip storage means that a reagent perfusion step is introduced in the process of chip processing and assembly, where liquid reagents are injected directly into the storage cavity or storage tank within the chip prior to completing the overall package of the chip.
  • an additional separate packing for reagent storage is not required, and the reagent is directly accommodated inside the chip, which in turn requires blocking or valve control between the chip storage tank and the fluid channel inside the chip, otherwise the reagent may flow into the channel in advance during storage and transportation, resulting in scrap.
  • External chip storage means that the chip assembly is independent from reagent filling and encapsulation processes, after the liquid reagent is sealed into a liquid bladder, the liquid bladder is fitted to corresponding position of the chip and assembled for use.
  • the reagent filling and encapsulation are separated from the chip processing and assembling steps. Therefore, the process control is more reliable, the storage of multiple types of reagents can be easily achieved, and has high flexibility and freedom degree when combining with the chip.
  • the liquid bladder containing liquid reagents is fixed outside the chip, which is prone to be damaged by extrusion and thus scrapped during transportation and storage, and the test repeatability and stability are poor in use.
  • a microfluidic chip includes:
  • the spacing is formed between the liquid bladder and the spike member, such that the liquid bladder will not be pierced when subjected to an extrusion force (for example, an extrusion force subjected during transportation and storage) not exceeding the preset value, and can be pierced when the applied extrusion force exceeds the preset value during use, thereby reducing the scrap rate of the aforementioned microfluidic chip.
  • an extrusion force for example, an extrusion force subjected during transportation and storage
  • the flow rate and the flow resistance of the reagent flowing out of the liquid bladder can be substantially the same, thereby improving the detection repeatability and stability of the aforementioned microfluidic chip.
  • the spike member is provided with a liquid guiding groove in communication with the liquid outlet opening.
  • the spike member is shaped as a cone or a needle.
  • the microfluidic chip further includes a protecting member connected to the chip body and covering the liquid bladder storage member, and the protecting member is provided with a liquid bladder avoidance hole corresponding to the liquid bladder cavity.
  • the microfluidic chip further includes an indicating member located between the liquid bladder storage member and the protecting member.
  • the indicating member is made of a material prone to be deformed by a force.
  • the protecting member is a transparent protecting member, and/or both the liquid bladder storage member and the chip body are made of transparent materials.
  • the indicating member is made of plastic film, aluminum foil, tin foil, or paper.
  • the microfluidic chip further includes a first fixing member configured to fixedly connect the liquid bladder storage member and the chip body.
  • the microfluidic chip further includes a second fixing member configured to fixedly connect the protecting member and the liquid bladder storage member.
  • the microfluidic chip further includes a sealing member located between the liquid bladder storage member and the chip body.
  • the sealing member is configured to seal a gap between the liquid bladder storage member and the chip body.
  • the sealing member has a liquid channel, and the liquid outlet opening is in communication with the liquid inlet opening through the liquid channel.
  • a microfluidic chip is provided.
  • a bottom of the liquid bladder cavity is shaped as a funnel, and the spike member is located on the bottom.
  • the liquid outlet opening is located on the bottom at a position closest to the chip body.
  • microfluidic chip 110, chip body; 120, liquid bladder storage member; 111, liquid inlet opening; 121, liquid bladder cavity; 122, liquid outlet opening; 123, spike member; 124, liquid guiding groove; 125, sealing member; 126, liquid channel; 130, liquid bladder; 140, protecting member; 141, avoidance hole; 150, indicating member; 160, first fixing member; 170, second fixing member; 180, positioning hole; 161, first fixing column; 171, second fixing column.
  • a microfluidic chip 10 is provided according to one embodiment of the present application.
  • the microfluidic chip 10 includes a chip body 110 and a liquid bladder storage member 120.
  • the chip body 110 is provided with a liquid inlet opening 111.
  • the liquid bladder storage member 120 is provided on the chip body 110.
  • the liquid bladder storage member 120 is provided with a liquid bladder cavity 121 configured to accommodate a liquid bladder 130.
  • the liquid bladder cavity 121 is provided with a liquid outlet opening 122 in communication with the liquid inlet opening 111.
  • the liquid bladder cavity 121 is provided with a spike member 123. When the liquid bladder 130 is accommodated in the liquid bladder cavity 121, a spacing is formed between the liquid bladder 130 and the spike member 123.
  • the spike member 123 When the liquid bladder 130 is subjected to an extrusion force exceeding a preset value, the spike member 123 is capable of piercing the liquid bladder 130.
  • the spacing is formed between the liquid bladder 130 and the spike member 123, such that the liquid bladder 130 will not be pierced by the spike member 123 when subjected to an extrusion force (for example, an extrusion force subjected during transportation and storage) not exceeding the preset value, and can be pierced by the spike member 123 when the applied extrusion force exceeds the preset value during use, thereby reducing the scrap rate of the aforementioned microfluidic chip 10.
  • an extrusion force for example, an extrusion force subjected during transportation and storage
  • the rupture of the liquid bladder in conventional microfluidic chips is caused by rupture of aluminum foil on the side of the liquid bladder close to the liquid outlet opening due to directly squeezing the liquid bladder, thus the liquid flows out. It has been found by the research of the present application that such manner makes a large randomness of the rupture of the liquid bladder, and is easy to result in a large difference in the flow rate and the flow resistance of the liquid reagent when entering the chip body, thereby affecting the test reproducibility and stability.
  • openings of the plurality of the liquid bladders 130 are substantially the same, such that the flow rate and the flow resistance of the reagent flowing out of each liquid bladder 130 are substantially the same, thereby improving the detection repeatability and stability of the aforementioned microfluidic chip 10.
  • the preset value of the extrusion force to which the liquid bladder 130 is subjected is related to the material of the liquid bladder 130, the spacing distance between the liquid bladder 130 and the spike member 123 when the liquid bladder 130 is accommodated in the liquid bladder cavity 121, and the extrusion force to which the liquid bladder 130 is subjected during transportation and storage.
  • the specific preset value may be determined according to the material of the liquid bladder 130, the spacing distance between the liquid bladder 130 and the spike member 123 when the liquid bladder 130 is accommodated in the liquid bladder cavity 121, and the extrusion force to which the liquid bladder 130 is subjected during transportation and storage.
  • the preset value of the extrusion force is designed based on the actual force to which the liquid bladder 130 is subjected in a direction from the liquid bladder 130 towards the piercing member 123.
  • the preset value of the extrusion force is designed based on a vertical-downward force that the liquid bladder 130 can withstand. For example, if the liquid bladder 130 is subjected to an obliquely downward force, the force in the vertical direction is just a partial force of the obliquely downward force, and the liquid bladder 130 will not be pierced as long as the partial force does not exceed the preset value.
  • a side of the liquid bladder 130 adjacent to the spike member 123 is made of aluminum foil, PET film, PP film, or LDPE film. In some other embodiments, the side of the liquid bladder 130 adjacent to the spike member 123 is made of a composite film of plastic film and aluminum foil. In some embodiments, the side of the liquid bladder 130 adjacent to the spike member 123 has a thickness ranging from 50 ⁇ m to 200 ⁇ m.
  • a side of the liquid bladder 130 away from the spike member 123 is made of at least one of PP, HDPE, PVC, and PET.
  • the liquid bladder 130 with a dome shell structure is prepared from the aforementioned materials (at least one of PP, HDPE, PVC, and PET) by a blow or injection molding process. In some other embodiments, the side of the liquid bladder 130 away from the spike member 123 has a thickness ranging from 75 ⁇ m to 200 ⁇ m.
  • a distance of the spacing between the liquid bladder 130 and the spike member 123 ranges from 1 mm to 10 mm, e.g., 2 mm, 5 mm, or 8 mm.
  • the distance of the spacing between the liquid bladder 130 and the spike member 123 refers to a distance from a position of the spike member 123 closest to the liquid bladder 130 to the side of the liquid bladder 130 close to the spike member 123. It should be understood that when the liquid bladder 130 is accommodated in the liquid bladder cavity 121, the distance of the spacing between the liquid bladder 130 and the spike member 123 can be adjusted according to the material of the liquid bladder 130.
  • the distance of the spacing between the liquid bladder 130 and the spike member 123 can be greater. If the liquid bladder 130 is made of a material that is not easily deformed by extrusion and thus does not easily approach the spike member 123, then the distance of the spacing between the liquid bladder 130 and the spike member 123 can be less. As such, the aforementioned microfluidic chip 10 is not easy to scrap during transportation and storage, and is easy to be pierced in use.
  • the chip body 110 includes a reaction chamber and a fluid channel in communication with the reaction chamber.
  • the chip body 110 is provided with the liquid inlet opening 111, which is in communication with the reaction chamber on the chip body 110.
  • the reagent for detection enters the chip body 110 from the liquid inlet opening 111.
  • the chip body 110 is provided with a plurality of reaction chambers in communication with each other through the fluid channel. At least some of the reaction chambers have respective liquid inlet openings 111, in which case the liquid bladder storage member 120 is provided with the liquid bladder cavities 121 and the liquid outlet openings 122 corresponding to these reaction chambers.
  • the chip body 110 is provided with six spaced liquid inlet openings 111, and the liquid bladder storage member 120 is provided with six liquid bladder cavities 121 and six liquid outlet openings 122.
  • one liquid bladder cavity 121 corresponds to one liquid outlet opening 122
  • one liquid outlet opening 122 corresponds to one liquid inlet opening 111.
  • one liquid bladder cavity 121 can correspond to multiple liquid outlet openings 122.
  • Multiple or one liquid outlet opening 122 may correspond to one or more liquid inlet openings 111.
  • the number of the liquid inlet opening 111 and the liquid outlet opening 122 can be adjusted according to actual conditions. Of course, in some embodiments, there may be only one reaction chamber on the chip. In this case, the number of the liquid bladder 121 on the liquid bladder storage member 120 is one. It should be understood that the sizes of the liquid inlet opening 111 and the liquid outlet opening 122 are not particularly limited, and can be adjusted according to actual conditions (for example, the flow rate or flow of the liquid reagent).
  • the chip body 110 is shaped as a disc. It should be understood that in other embodiments, the chip body 110 is not limited to be shaped as a disc, but may also as any other shape. For example, it may be shaped as a square or an oval.
  • the material of the chip body 110 is at least one selected from the group consisting of polydimethylsiloxane (PDMS), polyurethane, epoxy resin, polymethyl methacrylate (PMMA), polycarbonate (PC), cycloolefin copolymer (COC/COP), polystyrene (PS), polyethylene (PE), polypropylene (PP), and fluoroplastic. It should be understood that the material of the chip body 110 is not limited to the above, but may also be other materials.
  • PDMS polydimethylsiloxane
  • PMMA polymethyl methacrylate
  • PC polycarbonate
  • COC/COP cycloolefin copolymer
  • PS polystyrene
  • PE polyethylene
  • PP
  • the liquid bladder storage member 120 is configured to store the liquid bladder 130 containing the liquid reagent. Specifically, the liquid bladder storage member 120 is provided with the liquid bladder cavity 121 configured to accommodate the liquid bladder 130. In the illustrated embodiments, the liquid bladder storage member 120 is shaped as a disc. It should be understood that in other embodiments, the liquid bladder storage member 120 is not limited to be shaped as the above, but can also be adjusted according to actual requirements. In the illustrated embodiments, six liquid bladder cavities 121 are provided. It should be understood that in other embodiments, the number of the liquid bladder storage member 121 is not limited to the above, but can also be adjusted according to actual conditions.
  • the shape of the liquid bladder cavity 121 is not limited, but is required to match the liquid bladder 130.
  • the liquid bladder 130 is substantially shaped as a hemisphere, and the liquid bladder cavity 121 is substantially shaped as a column with a bottom recessed towards the chip body 110.
  • the liquid bladder storage member 120 is made of rigid materials. By employing the rigid liquid bladder storage member 120, the liquid bladder 130 in the liquid bladder cavity 121 can be protected.
  • the bottom of the liquid bladder cavity 121 is shaped as a funnel, and the spike member 123 is located on the bottom.
  • the liquid outlet opening 122 is located on the bottom at a position closest to the chip body 110.
  • the funnel-shaped bottom of the liquid bladder 130 further facilitates the flow of the liquid reagent in the liquid bladder 130 towards the chip body 110 without wasting the liquid reagent easily.
  • the bottom of the liquid bladder cavity 121 is not limited to be shaped as a funnel, but may also as other curved surfaces recessed towards the chip body 110.
  • the spike member 123 is shaped as a cone or a needle. In one optional specific example, the spike member 123 is shaped as a circular cone or a triangular pyramid. After a sealing film of the liquid bladder 130 is pierced by the spike member 123, the opening of the sealing film pierced increases with the increasing of the piercing depth. In some embodiments, a plurality of spike members 123 are provided, which are spaced apart surrounding the liquid outlet opening 122. Furthermore, the distances between the plurality of spike members 123 and the center of the liquid outlet opening 122 are equal.
  • the three spike members 123 are provided, the three spike members 123 are spaced apart surrounding the liquid outlet opening 122, and the distances between the three spike members 123 and the center of the liquid outlet opening 122 are equal. It should be understood that in other embodiments, the number of the spike member 123 is not limited to be three as described above, but may also be other, such as one, two, five, or six.
  • the spike member 123 is further provided with a liquid guiding groove 124.
  • the liquid guiding groove 124 is in communication with the liquid outlet opening 122.
  • the liquid guiding groove 124 is configured to guide the liquid in the liquid bladder 130 to the liquid outlet opening 122.
  • the liquid guiding groove 124 is provided on a side of the spike member 123 adjacent to the liquid outlet opening 122. It should be understood that in other embodiments, the liquid guiding groove 124 is not limited to be provided at the above position, but may also at other positions on the spike member 123.
  • the liquid guiding groove 124 is provided on a side of the spike member 123 away from the liquid outlet opening 122.
  • the aforementioned chip 10 further includes a sealing member 125.
  • the sealing member 125 is located between the liquid bladder storage member 120 and the chip body 110, and is configured to seal a gap therebetween.
  • the sealing member 125 has a liquid channel 126, and the liquid outlet opening 122 is in communication with the liquid inlet opening 111 through the liquid channel 126.
  • the liquid bladder storage member 120 has a liquid outlet channel, one end of the liquid outlet channel is in communication with the liquid outlet opening 122, and the other end thereof is in communication with the liquid inlet opening 111.
  • the sealing member 125 is located in the liquid outlet channel.
  • the sealing member 125 is an elastic sealing member 125.
  • the sealing member 125 is made of TPU, silicone rubber, rubber, or resin. It should be understood that the sealing member 125 is not limited to be made of the above, but may also be other materials used for sealing.
  • the sealing member 125 can be omitted.
  • the gap between the liquid bladder storage member 120 and the chip body 110 that is not configured for the liquid reagent to flow into the chip body 110 may be sealed by other means.
  • the gap between the liquid bladder storage member 120 and the chip body 110 that is not configured for the liquid reagent to flow into the chip body 110 may be sealed by a sealant.
  • the aforementioned microfluidic chip 10 further includes the liquid bladder 130.
  • the liquid bladder 130 is configured to carry the liquid reagent.
  • the liquid reagent includes but not limited to at least one of buffer solution (ionic solution, surfactant mixture), reaction solution (antigen/antibody dilution, protein dilution, magnetic particle dilution, luminescent/fluorescent reagent dilution, nucleic acid dilution, molecule/protein bio-probe dilution, etc.), and cleaning solution (surfactant mixture, decontaminant, etc.).
  • buffer solution ionic solution, surfactant mixture
  • reaction solution antigen/antibody dilution, protein dilution, magnetic particle dilution, luminescent/fluorescent reagent dilution, nucleic acid dilution, molecule/protein bio-probe dilution, etc.
  • cleaning solution surfactant mixture, decontaminant, etc.
  • the microfluidic chip 10 includes a protecting member 140.
  • the protecting member 140 is configured to reduce extrusion to the liquid bladder 130 by an external force during transportation and/or storage process, which can avoid the aforementioned microfluidic chip 10 from scrapping caused by the liquid bladder 130 being pierced in advance due to extrusion to the liquid bladder 130 by the external force during transportation and/or storage process, thus further reducing the scrap rate of the aforementioned microfluidic chip 10.
  • the protecting member 140 covers a side of the liquid bladder storage member 120 away from the chip body 110 and is fixedly connected to the chip body 110.
  • the protecting member 140 is provided with an avoidance hole 141 corresponding to the liquid bladder cavity 121.
  • the number of the avoidance hole 141 corresponds to the number of the liquid bladder 130.
  • the liquid bladder 130 is squeezed through the avoidance hole 141, such that the liquid bladder 130 can be contact with the spike member 123 and thus be pierced.
  • the manner of fixed connection used herein is not particularly limited, unless specifically indicated.
  • the fixed connection may be removable fixed connection such as screw connection or snap connection, or non-removable fixed connection such as bonding, welding, riveting, interference fitting, or the like.
  • the protecting member 140 is shaped as a disc. It should be understood that in other embodiments, the protecting member 140 is not limited to be shaped as the above, but can also be adjusted according to actual conditions.
  • the avoidance hole 141 is a through hole provided in an axial direction of the protecting member 140.
  • a force is applied in the axial direction of the protecting member 140 through the avoidance hole 141 and the liquid bladder 130 is squeezed, such that the liquid bladder 130 gets close to the spike member 123 and is then pierced by the spike member 123.
  • the avoidance hole 141 may also be provided in a radial direction of the protecting member 140. In this case, a force is applied in the axial direction of the protecting member 140 through the avoidance hole 141 in the radical direction and the liquid bladder 130 is squeezed, such that the liquid bladder 130 gets close to the spike member 123 and is then pierced by the spike member 123.
  • the microfluidic chip 10 further includes an indicating member 150.
  • the indicating member 150 is configured to indicate whether the liquid bladder 130 is broken or has been subjected to an external force.
  • the indicating member 150 is located between the liquid bladder storage member 120 and the protecting member 140, and is made of a material prone to be deformed by a force.
  • the protecting member 140 is a transparent protecting member 140, and/or both the liquid bladder storage member 120 and the chip body 110 are made of transparent materials.
  • the components located on (the protecting member 140) and under (the liquid bladder storage member 120 and the chip body 110) the indicating member 150 are made of transparent materials, which facilitates observation of whether the indicating member 150 is broken or deformed from above or below the indicating member 150, thereby determining whether the liquid bladder 130 is squeezed by an external force and is broken. On the other hand, whether the test is completed can also be confirmed through the indicating member 150. For example, during assembly, the indicating member 150 is placed above the reagents that have completed the test, and there is no indicating member 150 on the reagents that have not participated in the test.
  • the indicating member 150 is made of plastic film, aluminum foil, tin foil, or paper.
  • the indicating member 150 is made of at least one of polyester film (PET), polypropylene film (PP), and polyethylene film (PE).
  • the indicating member 150 is made of one of soft/rigid label paper with a dashed indentation, printing paper, and laminated paper. It should be understood that the indicating member 150 is not limited to be made of the above materials, and can also be made of other materials prone to be deformed by a force.
  • the aforementioned microfluidic chip 10 further includes a first fixing member 160, and the liquid bladder storage member 120 is fixedly connected to the chip body 110 through the first fixing member 160.
  • the first fixing member 160 extends through the protecting member 140, the indicating member 150, and the liquid bladder storage member 120, and is configured to fixedly connect the protecting member 140, the indicating member 150 and the liquid bladder storage member 120 to the chip body 110.
  • the protecting member 140 and the indicating member 150 may be fixedly connected to the liquid bladder storage member 120 through the first fixing member 160, or may by other means.
  • the first fixing member 160 is made of thermoplastic materials. The employment of thermoplastic materials can make it easier to organize the aforementioned microfluidic chip 10.
  • the microfluidic chip 10 further includes a second fixing member 170, the protecting member 140 and the indicating member 150 are fixedly connected to the liquid bladder storage member 120 through the second fixing member 170.
  • the second fixing member 170 extends through the protecting member 140 and the indicating member 150, and is fixedly connected to the liquid bladder storage member 120.
  • the aforementioned microfluidic chip 10 further includes a positioning hole 180.
  • the positioning hole 180 is configured for positioning, which facilitates the assembly and use.
  • the aforementioned microfluidic chip 10 includes the chip body 110 and the liquid bladder storage member 120 provided on the chip body 110.
  • the microfluidic chip 10 is a microfluidic chip 10 capable of loading the liquid bladder 130 formed by assembling the chip body 110 and the liquid bladder storage member 120.
  • the liquid bladder 130 can be freely selected according to specific requirements and then assembled with the microfluidic chip 10 that can load the liquid bladder 130, thereby forming a microfluidic chip 10 that can be used directly.
  • the aforementioned microfluidic chip 10 includes the chip body 110, the liquid bladder storage member 120 provided on the chip body 110, the liquid bladder 130 provided in the liquid bladder storage member 120, and the protecting member 140 provided on the side of the liquid bladder storage member 120 away from the chip body 110.
  • the chip body 110 is fixedly connected to the liquid bladder storage member 120 and the protecting member 140.
  • the microfluidic chip 10 is the microfluidic chip 10 that can be used directly.
  • the aforementioned microfluidic chip 10 includes the chip body 110, the liquid bladder storage member 120 provided on the chip body 110, the liquid bladder 130 provided in the liquid bladder storage member 120, the protecting member 140 provided on the side of the liquid bladder storage member 120 away from the chip body 110, and the indicating member 150 located between the protecting member 140 and the liquid bladder storage member 120.
  • the chip body 110, the liquid bladder storage member 120, the protecting member 140, and the indicating member 150 are fixedly connected through the first fixing member 160, and the liquid bladder storage member 120, the protecting member 140, and the indicating member 150 are further fixedly connected through the second fixing member 170.
  • a thickness of the aforementioned microfluidic chip 10 ranges from 10 mm to 20 mm.
  • the thickness of the microfluidic chip 10 herein refers to an axial length of the microfluidic chip 10, i.e., a distance from a side of the chip body 110 away from the liquid bladder storage member 120 to a side of the protecting member 140 away from the indicating member 150.
  • a distance from a side of the chip body 110 away from the liquid bladder storage member 120 to the side of the liquid bladder storage member 120 away from the chip body 110 it should be understood that the thickness of the aforementioned microfluidic chip 10 is not limited to the above, but can also be adjusted according to actual conditions.
  • microfluidic chip 10 has at least the following advantages:
  • an assembly method of the aforementioned microfluidic chip 10 is further provided according to one embodiment of the present application.
  • the assembly method fixes the chip body 110, the liquid bladder storage member 120 accommodated with the liquid bladder 130, the indicating member 150, and the protecting member 140 by riveting, and the aforementioned microfluidic chip 10 is prepared.
  • the assembly method includes step S100 and step S200. Specifically:
  • the riveting is a combination of hot air and cold riveting.
  • both the first fixing column 161 and the second fixing column 171 are made of thermoplastic materials. Hot air and/or heats from the first fixing column 161 and one end of the second fixing column 171 close to the protecting member 140, when it is melted or softened, after the preset heating time, the first fixing column 161 and the second fixing column 171 are pressed down to form the rivet using a cold fixture, thus the chip body 110, the liquid bladder storage member 120, the indicating member 150, and the protecting member 140 are fixed.
  • the riveting is ultrasonic riveting.
  • both the first fixing column 161 and the second fixing column 171 are made of thermoplastic materials.
  • the fixing column and the second fixing column 171 are heated using ultrasonic highfrequency vibration, and a rivet is formed after melting by an ultrasonic indenter.
  • ultrasonic heating is very rapid and the period is short.
  • Suitable rivet design is required to provide a relatively small initial contact between the ultrasonic indenter and the fixing column, to produce a rapid heating effect.
  • ultrasonic riveting high amplitude vibration and decelerated descent of the ultrasonic indenter are used to melt and flow the studs, and the ultrasonic indenter is filled to form a rivet cap, such that the chip body 110 is fixed with the liquid bladder storage member 120, the indicating member 150, and the protecting member 140.
  • the riveting is infrared or laser riveting. Specifically, similar to ultrasonic riveting, except that the first fixing column 161 and the second fixing column 171 are melted by infrared heating or laser heating.
  • the chip body 110 is fixed with the liquid bladder storage member 120, the indicating member 150, and the protecting member 140 by riveting.
  • the chip body 110 is not limited to be fixed with the liquid bladder storage member 120, the indicating member 150, and the protecting member 140 by riveting, but may also by other means, such as adhesive, ultrasonic welding, laser welding, etc.
  • the specific assembly process may be determined according to actual requirements of the microfluidic chip 10. For example, if the microfluidic chip 10 has limited pressure-bearing capacity due to its low thickness or structural design factors, then riveting is not appropriate, and adhesive or ultrasonic welding processes are more suitable.
  • the storage reagent itself is not resistant to high temperature, then riveting, ultrasonic, and laser welding processes are not suitable (the thermal effect is not controllable, which affects the stability and performance of the reagent, or even makes the reagent ineffective), in this case ambient temperature operation process such as adhesive process is more suitable.
  • the aforementioned assembly methods of the microfluidic chip 10 is convenient and simple to operate, facilitating industrial production.

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Clinical Laboratory Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Analytical Chemistry (AREA)
  • Hematology (AREA)
  • General Health & Medical Sciences (AREA)
  • Dispersion Chemistry (AREA)
  • Medicinal Chemistry (AREA)
  • Automatic Analysis And Handling Materials Therefor (AREA)
  • Engineering & Computer Science (AREA)
  • General Engineering & Computer Science (AREA)
  • Mechanical Engineering (AREA)
EP22860620.8A 2021-08-27 2022-08-26 Puce microfluidique Pending EP4364850A1 (fr)

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CN202110995895.7A CN113578405A (zh) 2021-08-27 2021-08-27 微流控芯片
PCT/CN2022/115034 WO2023025274A1 (fr) 2021-08-27 2022-08-26 Puce microfluidique

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CN113578405A (zh) * 2021-08-27 2021-11-02 深圳市亚辉龙生物科技股份有限公司 微流控芯片
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
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
CN114054111A (zh) * 2021-11-18 2022-02-18 江苏液滴逻辑生物技术有限公司 一种试剂预埋与注样装置、及其注样方法和用途
CN114100712A (zh) * 2021-11-19 2022-03-01 江苏液滴逻辑生物技术有限公司 一种微流控芯片的孔注液装置、及其注液方法和用途
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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WO2006053588A1 (fr) * 2004-11-17 2006-05-26 Agilent Technologies, Inc. Systeme d'alimentation muni d'un element de reservoir d'alimentation et d'un dispositif fluidique
WO2009105711A1 (fr) * 2008-02-21 2009-08-27 Decision Biomarkers, Inc. Essais ayant pour base un écoulement de liquide sur des réseaux
CN206965753U (zh) * 2017-06-09 2018-02-06 北京百康芯生物科技有限公司 一种具有试剂存储单元的微流控芯片
CN109847820A (zh) * 2019-04-18 2019-06-07 天津诺迈科技有限公司 微流控芯片预封装装置及使用方法
CN110252434B (zh) * 2019-06-27 2022-08-09 深圳华迈兴微医疗科技有限公司 一种用于微流控芯片的液体储存结构及微流控芯片
CN113578405A (zh) * 2021-08-27 2021-11-02 深圳市亚辉龙生物科技股份有限公司 微流控芯片

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