WO2024012260A1 - 一种液瓶 - Google Patents

一种液瓶 Download PDF

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Publication number
WO2024012260A1
WO2024012260A1 PCT/CN2023/104614 CN2023104614W WO2024012260A1 WO 2024012260 A1 WO2024012260 A1 WO 2024012260A1 CN 2023104614 W CN2023104614 W CN 2023104614W WO 2024012260 A1 WO2024012260 A1 WO 2024012260A1
Authority
WO
WIPO (PCT)
Prior art keywords
side wall
liquid bottle
channel opening
liquid
inner cavity
Prior art date
Application number
PCT/CN2023/104614
Other languages
English (en)
French (fr)
Inventor
戴晓兵
Original Assignee
苏州壹达生物科技有限公司
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 苏州壹达生物科技有限公司 filed Critical 苏州壹达生物科技有限公司
Publication of WO2024012260A1 publication Critical patent/WO2024012260A1/zh

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Classifications

    • 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
    • B01L3/508—Containers for the purpose of retaining a material to be analysed, e.g. test tubes rigid containers not provided for above
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M1/00—Apparatus for enzymology or microbiology
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M23/00—Constructional details, e.g. recesses, hinges
    • C12M23/02—Form or structure of the vessel
    • C12M23/08—Flask, bottle or test tube
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12M—APPARATUS FOR ENZYMOLOGY OR MICROBIOLOGY; APPARATUS FOR CULTURING MICROORGANISMS FOR PRODUCING BIOMASS, FOR GROWING CELLS OR FOR OBTAINING FERMENTATION OR METABOLIC PRODUCTS, i.e. BIOREACTORS OR FERMENTERS
    • C12M3/00—Tissue, human, animal or plant cell, or virus culture apparatus
    • 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
    • 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
    • B01L2200/06—Fluid handling related problems
    • B01L2200/0684—Venting, avoiding backpressure, avoid gas bubbles
    • 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
    • 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
    • B01L2300/0848—Specific forms of parts of containers
    • B01L2300/0858—Side walls
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B65—CONVEYING; PACKING; STORING; HANDLING THIN OR FILAMENTARY MATERIAL
    • B65D—CONTAINERS FOR STORAGE OR TRANSPORT OF ARTICLES OR MATERIALS, e.g. BAGS, BARRELS, BOTTLES, BOXES, CANS, CARTONS, CRATES, DRUMS, JARS, TANKS, HOPPERS, FORWARDING CONTAINERS; ACCESSORIES, CLOSURES, OR FITTINGS THEREFOR; PACKAGING ELEMENTS; PACKAGES
    • B65D23/00—Details of bottles or jars not otherwise provided for
    • B65D23/003—Suspension means

Definitions

  • the present invention relates to the field of biotechnology, and in particular to a liquid bottle used for transporting or storing cell fluid in a sterile environment.
  • liquid containers such as liquid bags and bottles to store or transport various liquids such as medicinal solutions, cell fluids, and tissue fluids.
  • the container needs to ensure strict sterile filtration to ensure a sterile environment, and is often a disposable consumable.
  • liquid bags are made of flexible materials with thin walls that can be bent freely. Therefore, during the process of using liquid bags to transport liquids, the liquid easily adheres to the inner wall of the liquid bags due to surface tension. It is blocked and cannot be discharged completely and smoothly, resulting in a large amount of liquid residue and waste.
  • the rigid structure of the liquid bottle can effectively improve the above-mentioned adhesion problem and increase the recovery rate of liquid discharge.
  • the cell liquid flowing in from the liquid inlet directly falls on the liquid surface in the container, which easily produces a large amount of foam and damages the cells, and these foams last for a long time. for a long time, seriously destroying the uniformity of the cell solution, thereby affecting the electrotransfection processing effect.
  • the object of the present invention is to provide a liquid bottle that can improve the cell liquid recovery rate in view of the shortcomings of the existing technology.
  • a liquid bottle is used for transporting and/or storing cell fluid in a sterile environment.
  • the liquid bottle includes a bottle body, the bottle body has a hollow inner cavity, and the bottle body has:
  • a first passage opening is connected with the inner cavity, and the first passage opening is located above the inner cavity;
  • the second channel opening is connected with the inner cavity, and the second channel opening is located below the inner cavity;
  • a third channel opening is connected to the inner cavity, the third channel opening is located above the inner cavity, and the third channel opening and the first channel opening are along the The width direction intervals of liquid bottles are set;
  • a first side wall and a second side wall are respectively located on two different sides in the width direction of the liquid bottle.
  • the third side wall One side wall gradually extends inwardly from top to bottom, and the first side wall can be used to receive liquid falling from the first channel opening.
  • the second side wall gradually extends inwardly from top to bottom, and the second side wall can be used to receive liquid falling from the third channel opening.
  • the second channel port is used for liquid outflow
  • one of the first channel port and the third channel port is used for liquid inlet
  • the other is used for ventilation.
  • the first channel opening is used for liquid inlet
  • the third channel opening is used for ventilation.
  • the first side wall has a first projection on the horizontal plane
  • the first passage opening has a second projection on the horizontal plane
  • the second projection is located inside the first projection. Therefore, the liquid falling from the first channel opening can be received by the first side wall and slide down gently along its slope, preventing the liquid droplets from directly impacting the liquid surface to generate foam and damage cells.
  • the second side wall has a third projection on the horizontal plane
  • the third channel opening has a fourth projection on the horizontal plane
  • the fourth projection is located inside the third projection. Therefore, the liquid falling from the third channel opening can be received by the second side wall and slide down gently along its slope, preventing the liquid droplets from directly impacting the liquid surface to generate foam and damage cells.
  • the axis of the first channel opening and the axis of the third channel opening are both equal.
  • the axis line of the second channel opening is located in the virtual plane, or the axis line of the second channel opening is spaced apart from the virtual plane. The symmetrical arrangement of the first channel opening and the third channel opening helps to simplify the processing and production of the liquid bottle.
  • the first channel opening and the third channel opening are respectively provided at the left and right ends of the bottle body. Therefore, the liquid falling from the first channel opening or the third channel opening can be caught by the first side wall or the second side wall when it first enters the inner cavity, minimizing the acceleration of the free fall of the liquid and eliminating foam or liquid. Effect of droplet splash on cell fluid.
  • the first channel opening, the second channel opening, and the third channel opening are all provided at the front end of the bottle body. Therefore, the third side wall of the inner cavity can also play an auxiliary guiding role in the flow of cell fluid and prevent droplets from splashing.
  • the bottom of the inner cavity has a first guide ramp, the first guide ramp is located below the first side wall, and the first guide ramp smoothly connects with the first side wall. .
  • the bottom of the inner cavity has a second guide ramp, the second guide ramp is located below the second side wall, and the second guide ramp smoothly connects with the second side wall.
  • the bottom of the inner cavity has a first guide ramp and a second guide ramp, the first guide ramp is located below the first side wall, and the first guide ramp and the third guide ramp are One side wall is smoothly connected, the second guide ramp is located below the second side wall, and the second guide ramp is smoothly connected with the second side wall; along the width direction of the liquid bottle:
  • the second pass The crossing is located between the first guide slope and the second guide slope, and the first guide slope and the second guide slope respectively extend from the second passage opening to both sides and gradually slope upward. Therefore, when the liquid flows to the bottom of the inner cavity, it can automatically converge into the second channel mouth under its own gravity and the guidance of the first guide and the second guide slope, effectively reducing the residual cell fluid in the bottle. quantity.
  • the bottom of the inner cavity also has a third guide slope
  • the third guide slope is located on one side of the thickness direction of the liquid bottle, and along the thickness direction of the liquid bottle, the third guide slope
  • Three guide slopes extend outwardly and gradually upward from the second passage opening.
  • the guide ramps at the bottom of the inner cavity may not be limited to three sets of first guide ramps, second guide ramps, and third guide ramps. Four, five or more sets of guide ramps may also be provided. Multiple sets of guide ramps jointly form a cone structure around the bottom of the inner cavity to promote smooth discharge of liquid.
  • first guide ramp and the second guide ramp are arranged symmetrically with respect to the axis of the second passage opening.
  • the bottom of the inner cavity is in the form of a cone structure, thereby further eliminating potential problems such as liquid adhesion and residue that may be caused by the edge structure.
  • the acute angle between the tangential surface of the first side wall and the horizontal plane is greater than the acute angle between the tangential surface of the first guide ramp and the horizontal plane.
  • the acute angle between the tangential surface of the second side wall and the horizontal plane is greater than the acute angle between the tangential surface of the second guide slope and the horizontal plane.
  • both the first side wall and the second side wall have a relatively vertical inclination angle, so that the flow rate of the liquid is not instantly reduced and the volume of the inner cavity is not significantly reduced; when the liquid flows to When the bottom of the inner cavity is about to be discharged, the first guide slope and the second guide slope have a relatively horizontal inclination angle, which can guide the liquid to be discharged from the second channel opening without significantly increasing the length of the liquid bottle, ensuring a simple appearance of the liquid bottle. practical.
  • the acute angle between the section of the first side wall and the horizontal plane is 75° to 85°
  • the angle between the section of the second side wall and the horizontal plane is 75° to 85°.
  • the acute angle between them is 75° ⁇ 85°.
  • first side wall and the second side wall are arranged left and right symmetrically with respect to the axis of the second passage opening, and the acute angles between the tangential surfaces of the two and the horizontal plane are both 82°.
  • the bottle body also has a third side wall and a fourth side wall, and the third side wall and the fourth side wall are respectively provided on different sides of the thickness direction of the liquid bottle,
  • the thickness of the liquid bottle is smaller than the width of the liquid bottle, and the extending direction of the third side wall and the extending direction of the fourth side wall are parallel to each other.
  • the liquid bottle is relatively flat as a whole and can be placed on the outer wall of instruments such as electrotransfection machines, reducing the overall volume of the equipment. It can also improve the stability of the liquid bottle when used, and it is not easy to shake when suspended. swing.
  • the liquid bottle further includes a hanging portion provided on the fourth side wall. Therefore, when the liquid bottle is suspended outside an instrument such as an electrotransfection instrument, the fourth side wall can fit against the outer wall of the equipment.
  • the first channel opening, the second channel opening, and the third channel opening are all provided on a side close to the third side wall, and the liquid bottle further includes a hanging portion, so The hanging portion is provided on the fourth side wall. Therefore, when the liquid bottle is hung on the outer wall of the equipment, the first channel port, the second channel port, the third channel port, etc. are all located on the outer side, and the equipment, pipelines, etc. have less interference with the use of the liquid bottle.
  • the transparent third side wall is marked with scale lines.
  • the bottom of the inner cavity also has a third guide slope.
  • the third guide slope is located on one side of the inner cavity in the thickness direction. Along the thickness direction of the liquid bottle, the third guide slope is The guide ramp extends outwardly and gradually upward from the second channel opening, and the third guide ramp smoothly connects with the fourth side wall along the length direction.
  • the bottle body also has a fourth channel opening, the fourth channel opening is connected with the inner cavity, the fourth channel opening is located above the inner cavity, and the fourth channel opening is connected with the inner cavity.
  • the opening, the first channel opening, and the third channel opening are arranged at intervals along the width direction of the liquid bottle.
  • the fourth channel port can be used to pass in buffer solution and further fully discharge the remaining cell fluid out of the liquid bottle by flushing the inner wall.
  • the first side wall is vertically connected to the inner wall of the first channel opening along the length direction of the liquid bottle, and/or the second side wall is connected to the third side wall vertically.
  • the inner side walls of the channel opening are vertically connected along the length direction of the liquid bottle. Therefore, the liquid falling from the first channel opening or the third channel opening can directly slide along the corresponding first side wall or second side wall, further reducing the impact force on the liquid level.
  • the liquid bottle further includes a hanging portion, the hanging portion is connected to the bottle body, and at least part of the hanging portion is located above the bottle body.
  • the hanging part can be used to hang the liquid bottle on an external bracket.
  • the bottle body is made of integral injection molding and welding of hard materials.
  • At least one side wall of the bottle body is made of transparent material.
  • the arrangement of the three sets of channel openings can make the air pressure in the inner cavity consistent with the ambient air pressure during the process of transporting liquid, which helps the liquid to be discharged smoothly; the tilted arrangement
  • the first side wall and the second side wall can receive the cell fluid flowing in from above to prevent the cell fluid from directly impacting the liquid surface to generate foam and damage the cells, thereby effectively improving the uniformity of the cell fluid in the inner cavity and helping Improve the recovery rate of cell fluid.
  • Figure 1 is a schematic three-dimensional view of a liquid bottle in use in a specific embodiment of the present invention
  • Figure 2 is a three-dimensional schematic diagram of the liquid bottle in Example 1;
  • Figure 3 is a schematic three-dimensional view of the liquid bottle from another angle in Embodiment 1;
  • Figure 4 is a schematic side view of the liquid bottle in Example 1;
  • Figure 5 is a schematic bottom view of the liquid bottle in Example 1;
  • Figure 6 is a schematic top view of the liquid bottle in Example 1;
  • Figure 7 is a schematic front view of the liquid bottle in Example 1;
  • Figure 8 is a three-dimensional schematic diagram of the liquid bottle in Example 2.
  • Figure 9 is a schematic top view of the liquid bottle in Embodiment 2, in which the hanging portion is hidden;
  • Figure 10 is a three-dimensional schematic diagram of the liquid bottle in Example 3.
  • Figure 11 is a three-dimensional schematic diagram of the liquid bottle in Example 4.
  • this embodiment provides a liquid bottle, which is mainly used for the transportation or storage of liquids in the fields of biomedicine and medicine, and is especially suitable for flow electrotransfection with poor uniformity, high transfer difficulty and recovery rate requirements. High transport of cellular fluids.
  • the liquid bottle includes a bottle body 10, and the bottle body 10 has a hollow inner cavity.
  • the bottle body 10 is made of integrated injection molding and welding of hard materials, thereby ensuring the relative sealing and sterility of the inner cavity.
  • the rigid structure of the bottle body 10 makes the inner cavity less likely to deform, and the inner walls of the inner cavity will not adhere. Together, the liquid remains on the wall and can be more easily clamped by other mechanisms (such as mixing mechanisms such as swing motors).
  • it is preferable that at least part of one side wall of the bottle body 10 is made of transparent material.
  • the liquid bottle of the present invention when used normally, it generally needs to be placed or hung in the direction shown in Figure 1 or Figure 8.
  • the liquid can flow into the liquid bottle from the first channel opening 11 above, or from the bottom.
  • the liquid bottle flows out of the second channel port 12. Therefore, the length direction Z, width direction X, thickness direction Y, etc. described in this article are all defined based on the orientation shown in Figure 1 or Figure 8, and are only for the convenience of description and understanding. , should not be construed as a limitation of the present invention.
  • the bottle body 10 specifically includes a first side wall 21 , a third side wall 23 , a second side wall 22 and a fourth side wall that are sequentially connected along the circumferential direction of the liquid bottle. wall 24, and a top wall 25 located at the top of the cavity.
  • the first side wall 21 and the second side wall 22 are respectively arranged on different sides of the liquid bottle in the width direction X, and the third side wall 23 and the fourth side wall 24 are respectively arranged on The thickness direction Y of the liquid bottle is on different sides. Viewed from the perspective shown in FIG.
  • the first side wall 21 is located on the right side
  • the second side wall 22 is located on the left side
  • the third side wall 23 is located on the front side
  • the fourth side wall 24 is located on the rear side.
  • the thickness of the liquid bottle is smaller than its width.
  • the first side wall 21 and the second side wall 22 gradually extend inwardly from top to bottom.
  • the extension direction of the third side wall 23 and the extension direction of the fourth side wall 24 are parallel to each other, and both extend along the length direction Z of the liquid bottle respectively.
  • the overall shape of the bottle body 10 is relatively flat, and the fourth side wall 24 can fit on the outer wall of the electrorotator and other equipment, making the placement more stable and saving space.
  • the transparent third side wall 23 is marked with scale lines to facilitate the user to know the approximate volume of the cell fluid in the inner cavity.
  • a hanging portion 5 is fixed on the fourth side wall 24, which can be used to hang the bottle 10 on an external hook or bracket.
  • the liquid bottle can be hung on the outer wall of equipment such as electrotransfection instruments. It is especially suitable for flat side walls. It only needs to be provided with a hook that matches the hanging part 5 on the outer wall of the corresponding equipment. components, the hanging part 5 can be hung up stably.
  • the fourth side wall 24 of the bottle body 10 is stably attached to the above-mentioned outer side wall, and the third side wall 23 is set outward for easy observation.
  • the bottle body 10 has a first channel opening 11 , a second channel opening 12 and a third channel opening 13 that are respectively connected with the inner cavity.
  • the first channel opening 11 and the third channel opening 13 are located above the inner cavity, and the second channel opening 12 is located below the inner cavity, and the third channel opening 13 and the first channel opening 11 are spaced apart along the width direction X of the liquid bottle.
  • the first channel port 11 is specifically used for liquid inlet
  • the second channel port 12 is used for liquid outlet
  • the third channel port 13 is used for ventilation. Since the first channel opening 11 and the third channel opening 13 are arranged completely symmetrically in structure, in other embodiments, the first channel opening 11 can also be used for ventilation and the third channel opening 13 can be used for liquid inlet.
  • the bottom of the inner cavity also has a first guide ramp 31 , a second guide ramp 32 and a third guide ramp 33 .
  • the first guide ramp 31 is located below the first side wall 21 , and the first guide ramp 31 and the first side wall 21 are smoothly connected along the length direction Z of the liquid bottle;
  • the second guide ramp 32 is located at the second side wall 22 below, and the second guide ramp 32 and the second side wall 22 are smoothly connected along the length direction Z of the liquid bottle. It should be noted that in this embodiment, there is no clear dividing line between the first guide ramp 31 and the first side wall 21 and between the second guide ramp 32 and the second side wall 22.
  • the first side of the bottle 10 The wall 21 and the first side wall 22 are both smooth arc surfaces, so that the guiding effect of the two side walls is more natural and gentle, and the problem of cell fluid retention that may be caused by the angular structure can be reduced.
  • the third guide slope 33 is located on one side of the liquid bottle in the thickness direction Y, and the third guide slope 33 and the fourth side wall 24 are smoothly connected along the length direction Z. Along the width direction Gradually extend upwards.
  • the second channel opening 12 is located between the third side wall 23 and the third guide ramp 33 .
  • the third guide ramp 33 extends outwardly and gradually upward from the second channel opening 12 .
  • the cross-sectional area of the inner cavity gradually decreases from top to bottom, and the bottle body 10 as a whole has an inverted cone structure, so that all the cell fluid can be gradually gathered and guided to the second channel port. 12, helps the smooth drainage of cell fluid.
  • the first side wall 21 can be used to receive the liquid falling from the first channel opening 11, and the second side wall 22 can be used to receive the liquid falling from the third channel opening 13 to prevent the liquid from entering the inner cavity. Direct impact on the liquid surface will form foam and damage cells.
  • the first side wall 21 has a first projection 210 on the horizontal plane 1001
  • the first passage opening 11 has a second projection 110 on the horizontal plane 1001
  • the second projection 110 is located inside the first projection 210
  • the second side wall 22 has a third projection 220 on the horizontal plane 1001
  • the third passage opening 13 has a fourth projection 130 on the horizontal plane 1001
  • the fourth projection 130 is located inside the third projection 220 .
  • the first channel opening 11 and the third channel opening 13 are respectively provided at the left and right ends of the top wall 25 of the bottle body 10; see 2 , at this time, the second projection 110 is located at the outer end of the first projection 210 , and the fourth projection 130 is located at the outer end of the third projection 220 .
  • the first side wall 21 and the inner wall of the first channel opening 11 are vertically connected along the length direction Z of the liquid bottle, and the second side wall 22 and the inner wall of the third channel opening 13 are vertically connected along the liquid bottle.
  • the length directions Z of the bottles are vertically connected.
  • the cell fluid flowing in from the first channel port 11 or the third channel port 13 can be directly received by the corresponding side wall without causing the liquid to drip.
  • the impact will be caused by directly hitting the liquid surface, minimizing the generation of foam and damage to cells.
  • the bottle body 10 is arranged symmetrically left and right along the width direction Therefore, while guiding the cell fluid, the inner cavity can also have an appropriate volume and size.
  • a vertical virtual plane 1002 extends along the width direction X of the liquid bottle, and the axis line of the first channel opening 11
  • the axis line of the third channel opening 13 is located in the virtual plane 1002
  • the axis line of the second channel opening 12 is located in the virtual plane 1002 or is spaced apart from the virtual plane 1002 .
  • the axes of the first channel opening 11 , the second channel opening 12 , and the third channel opening 13 are all located in the virtual plane 1002 , and along the thickness direction Y of the liquid bottle, the first channel opening 11
  • the second channel opening 12 and the third channel opening 13 are both provided at the front end of the bottle body 10, that is, on the side close to the third side wall 23. Therefore, the liquid flowing in from the first channel opening 11 or the third channel opening 13 can be introduced into the second channel opening 12 more smoothly, and the third side wall 23 located on the front side and located in the vertical plane will not affect the cells. It can also act as an auxiliary guide to the cellular fluid.
  • the fourth side wall 24 and the third guide ramp 33 are located on the side close to the outer wall of the electrotransfection instrument, and the first channel port 11, the second channel port 12 and The third channel openings 13 are all located on the side away from the outer wall, so that the outer wall of equipment such as electrotransfection instruments is less likely to interfere with structures such as pipelines, and it is also more conducive to smooth drainage and user operation.
  • the axis line of the second channel opening 12 can also be set apart from the virtual plane, which helps to reduce the risk of ultrasound Effect of welding on the second channel opening 12.
  • the liquid bottle is equipped with hoses such as a liquid inlet pipe 111, a liquid outlet pipe 121, a vent pipe 131, and accessories such as a flow stopper 4 and an air filter 6.
  • hoses such as a liquid inlet pipe 111, a liquid outlet pipe 121, a vent pipe 131, and accessories such as a flow stopper 4 and an air filter 6.
  • one end of the liquid inlet pipe 111 is fixed to the first channel opening 11, and the other end is provided with a sealing head 14, which can be used to seal the first channel opening 11; the liquid inlet pipe 111 can also be provided with a Luer.
  • Connectors such as joints (not shown in the figure) are used to connect with external pipelines.
  • liquid outlet pipe 121 is fixed to the second channel opening 12, and the other end can also be provided with a connector such as a sealing head 14 or a Luer connector for sealing the second channel opening 12 or connecting it to an external pipeline.
  • One end of the vent pipe 131 is fixed to the third passage opening 13, and the other end is provided with an air filter 6, thereby maintaining air pressure balance between the inner cavity and the external atmosphere while blocking impurities such as dust and bacteria in the external environment. , to ensure that the inner cavity is sealed and sterile.
  • the above-mentioned liquid inlet pipe 111, liquid outlet pipe 121, and vent pipe 131 are each provided with a set of flow-stop clamps 4 for controlling the on-off flow of the fluid in the corresponding pipelines.
  • the flow-stop clamps 4 are Robert clamps.
  • the liquid bottle in this embodiment can be used to output liquid (hereinafter referred to as the injection liquid bottle), receive liquid (hereinafter referred to as the collection liquid bottle), or store liquid in a sealed manner.
  • the injection liquid bottle receive liquid
  • the collection liquid bottle store liquid in a sealed manner.
  • a set of injection liquid bottles is connected upstream of the electrotransfection device (not shown in the figure) for outputting the cell fluid to be processed to the electrotransfection device.
  • the liquid inlet pipe 111 connected to the first channel port 11 is sealed by the flow stop clamp 4, and its corresponding head 14 is closed; while the liquid outlet pipe 121 and the vent pipe 131 remain unobstructed, and the liquid outlet pipe 121 Directly heat-melt the connection to the external pipeline through a Luer connector or a sterile tube machine and then connect it to the electrotransfection device.
  • the air pressure in the inner cavity is balanced with the external air pressure, and the cell fluid can pass through the second channel port 12 Smoothly and fully discharge the inner cavity, leaving little liquid residue.
  • the liquid outlet pipe 121 connected to the second channel opening 12 is sealed by the flow stopper 4, and its corresponding head 14 is closed; while the liquid inlet pipe 111 and the vent pipe 131 remain unobstructed, and the liquid inlet pipe 111 passes through
  • the Luer connector or sterile tube machine is directly connected to the external pipeline by hot melt and then connected to the electrotransfection device.
  • the cell fluid can flow into the inner cavity smoothly through the first channel port 11 .
  • the liquid inlet pipe 111, the liquid outlet pipe 121, and the vent pipe 131 are all sealed by the corresponding stopper clips 4, forming a completely sealed and sterile storage space in the inner cavity.
  • this embodiment provides another liquid bottle.
  • the usage scenario and usage method of this liquid bottle are basically the same as those in Embodiment 1.
  • the main difference is that the specific shape of the bottle 10 in this embodiment is different. difference.
  • the bottle body 10 includes an upper bottle body 101 and a lower bottle body 102.
  • the upper bottle body 101 is located above the lower bottle body 102 and the two smoothly transition together along the length direction Z of the liquid bottle.
  • the first side wall 21 and the second side wall 22 are respectively arranged on the left and right sides of the upper bottle body 101
  • the first guide ramp 31 and the second guide ramp 32 are respectively arranged on the left and right sides of the lower bottle body 102. It should be noted that in this embodiment, there is no clear gap between the first side wall 21 and the second side wall 22 and between the first guide slope 31 and the second guide slope 32.
  • each of the above-mentioned side walls or guide slopes extends gradually upward and upward along the width direction X of the liquid bottle from the inside to the outside, thereby providing buffering and guidance for the cell fluid entering the inner cavity.
  • all the inner side walls of the lower bottle body 102 are located in the first virtual conical plane, all the inner side walls of the upper bottle body 101 are located in the second virtual conical plane, and the second channel opening 12 is located at the bottom of the lower bottle body 102.
  • the axes of the first virtual cone surface, the second virtual cone surface and the second passage opening 12 extend collinearly.
  • the first guide slope 31 and the second guide slope 32 are both located in the first virtual cone surface
  • the first side wall 21 and the second side wall 22 are both located in the second virtual cone surface
  • the taper of the first virtual cone surface is Greater than the taper of the second virtual conical surface
  • the cell fluid has a relatively greater flow rate in the upper bottle body 101
  • the lower bottle body 102 can introduce the cell fluid into the second channel opening 12 more gently.
  • the first side wall 21 has a first projection 210 on the horizontal plane 1001
  • the first passage opening 11 has a second projection 110 on the horizontal plane 1001
  • the second projection 110 is located on the first projection.
  • the second side wall 22 has a third projection 220 on the horizontal plane 1001
  • the third passage opening 13 has a fourth projection 130 on the horizontal plane 1001
  • the fourth projection 130 is located inside the third projection 220.
  • the liquid can be directly received by the corresponding first side wall 21 or second side wall 22 to reduce the generation of foam and damage to cells.
  • the hanging part 5 is connected to the upper part of the upper bottle body 101, specifically a U-shaped rod located above the top wall 25.
  • the hanging part 5 is located above the bottle body 10 and can be used to hang the liquid bottle. , and is more suitable for brackets or hooks that extend horizontally longer.
  • the liquid bottle in Embodiment 1 can be equipped with the suspension portion 5 given in Embodiment 1 and Embodiment 2 at the same time to adapt to different application scenarios.
  • this embodiment provides another liquid bottle, which is basically the same as Embodiment 1.
  • the main difference is that the bottle body 10 in this embodiment also has a fourth channel opening 15 .
  • the fourth channel opening 15 is connected with the inner cavity, and the fourth channel opening 15 is located above the inner cavity.
  • the first channel opening 11, the fourth channel opening 15, and the third channel are arranged at intervals in sequence, and the fourth passage opening 15 here is relatively close to the first passage opening 11 .
  • the fourth channel port 15 can be used to introduce buffer solution. After the cell fluid in the bottle 10 is basically discharged, some cells may still adhere to the inner wall of the bottle 10 or accumulate at the bottom of the inner cavity. At this time, the buffer solution can be introduced into the fourth channel port 15. The buffer solution It can be flushed downward along the inner wall of the bottle body 10 to flush out the remaining cells, further improving the cell recovery rate.
  • this embodiment provides another liquid bottle, which is basically the same as Embodiment 2.
  • the main difference is that the bottle body 10 in this embodiment also has a fourth channel opening 15 .
  • the fourth channel opening 15 is connected with the inner cavity, and the fourth channel opening 15 is located above the inner cavity.
  • the first channel opening 11, the fourth channel opening 15, and the third channel are arranged at intervals in sequence, and the fourth passage opening 15 here is relatively close to the first passage opening 11 .
  • the use method of the fourth channel opening 15 in this embodiment is basically the same as that of the fourth channel opening 15 in Embodiment 3, and will not be described again here.
  • the liquid bottle provided by the present invention has a rigid cone structure, which is particularly suitable for transporting large-capacity cell liquids, promoting the cell liquids to converge and flow out to the bottom of the inner cavity, improving the recovery rate of the cell liquids; and inflowing into the liquid bottle.
  • the cell fluid in the inner cavity can flow down against the inclined wall surface of the bottle body 10 without generating a large amount of foam and damaging the cells due to impact force, which helps to improve cell processing efficiency such as electrotransfection efficiency.

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Abstract

一种液瓶，用于在无菌环境中细胞液的输送或存储，包括瓶体（10），瓶体（10）具有中空的内腔、分别与内腔相连通的第一通道口（11）、第二通道口（12）及第三通道口（13），以及分设于液瓶的宽度方向的相异两侧的第一侧壁（21）与第二侧壁（22）。其中，第一通道口（11）、第三通道口（13）位于内腔的上方且沿液瓶的宽度方向间隔设置；第二通道口（12）位于内腔的下方。沿液瓶的宽度方向，第一侧壁（21）与第二侧壁（22）分别自上而下逐渐向内倾斜延伸，第一侧壁（21）用于承接从第一通道口（11）落入的液体，第二侧壁（22）用于承接从第三通道口（13）落入的液体。

Description

一种液瓶 技术领域
本发明涉及生物技术领域，尤其涉及一种用于无菌环境中细胞液的输送或存储的液瓶。
背景技术
在生物医疗及制药等领域中，经常需要使用液袋、液瓶等液体容器对药液、细胞液、组织液等各种液体进行存储或输送。为确保液体不受污染，容器需要保证严格的无菌过滤以保障无菌环境，并且往往是一次性消耗品。一般地，液袋由柔性材料制成，其袋壁较薄且可以自由弯折，因此在使用液袋输送液体的过程中，液体由于表面张力的作用，容易粘附在液袋的内壁上而受到阻滞，无法完全顺利排出，造成液体的大量残留和浪费。相较而言，液瓶的硬性结构能够有效改善上述粘附问题，提高液体排出的回收率。
然而，在一些高精度的细胞液处理技术中，现有的液瓶及其他液体容器仍然不能够较好地满足工艺需求。例如，在流式电转染中，需要使用一组进样用容器将待处理的细胞液传输至电转染装置，以及一组收集用容器来接收处理完的细胞液。由于细胞液具有体积小、细胞分布不均匀的特点，且最后一部分富含细胞的液体往往积聚在容器的底部而无法充分排出，导致最终细胞的回收率低，从而整体上降低了细胞处理效率如电转染效率。此外，现有的液体容器一般从其顶部进液、底部出液，从进液口流入的细胞液直接落在容器内的液面上，容易产生大量泡沫并损伤细胞，且这些泡沫持续时间较长，严重破坏了细胞液的均匀性，进而影响了电转染的处理效果。
发明内容
本发明的目的是针对现有技术存在的不足，提供一种能够提高细胞液回收率的液瓶。
为达到上述目的，本发明采用的技术方案是：
一种液瓶，用于无菌环境中细胞液输送和/或存储，所述液瓶包括瓶体，所述瓶体具有中空的内腔，所述瓶体具有：
第一通道口，所述第一通道口与所述内腔相连通，所述第一通道口位于所述内腔的上方；
第二通道口，所述第二通道口与所述内腔相连通，所述第二通道口位于所述内腔的下方；
第三通道口，所述第三通道口与所述内腔相连通，所述第三通道口位于所述内腔的上方，且所述第三通道口与所述第一通道口沿所述液瓶的宽度方向间隔设置；
第一侧壁与第二侧壁，所述第一侧壁与所述第二侧壁分设于所述液瓶的宽度方向的相异两侧，沿所述液瓶的宽度方向，所述第一侧壁自上而下逐渐向内倾斜延伸，所述第一侧壁可用于承接从所述第一通道口落入的液体。
在一些实施方式中，所述第二侧壁自上而下逐渐向内倾斜延伸，所述第二侧壁可用于承接从所述第三通道口落入的液体。
在一些实施方式中，所述第二通道口用于出液，所述第一通道口与所述第三通道口两者中的一者用于进液，另一者用于通气。在一些具体实施方式中，所述第一通道口用于进液，所述第三通道口用于通气。
在一些实施方式中，所述第一侧壁在水平面上具有第一投影，所述第一通道口在所述水平面上具有第二投影，所述第二投影位于所述第一投影的内部。从而从第一通道口落入的液体能够被第一侧壁承接并沿着其斜面平缓下滑，防止液滴直接冲击液面而产生泡沫并损伤细胞。
在一些实施方式中，所述第二侧壁在水平面上具有第三投影，所述第三通道口在所述水平面上具有第四投影，所述第四投影位于所述第三投影的内部。从而从第三通道口落入的液体能够被第二侧壁承接并沿着其斜面平缓下滑，防止液滴直接冲击液面而产生泡沫并损伤细胞。
在一些实施方式中，存在一个竖直的虚拟平面，所述虚拟平面沿所述液瓶的宽度方向延伸，所述第一通道口的轴心线与所述第三通道口的轴心线均位于所述虚拟平面内，所述第二通道口的轴心线位于所述虚拟平面内，或，所述第二通道口的轴心线与所述虚拟平面间隔设置。第一通道口与第三通道口对称设置有助于简化该液瓶的加工生产。
在一些实施方式中，沿所述液瓶的宽度方向，所述第一通道口与所述第三通道口分别设置在所述瓶体的左右两端部。从而从第一通道口或第三通道口落入的液体能够在刚进入内腔时就被第一侧壁或第二侧壁所承接，最大程度减小液体自由下落的加速度，消除泡沫或液滴飞溅对细胞液造成的影响。
在一些实施方式中，沿所述液瓶的厚度方向，所述第一通道口、所述第二通道口、所述第三通道口均设置在所述瓶体的前端部。从而内腔的第三侧壁也能够对细胞液的流动起到辅助导向作用，防止液滴飞溅。
在一些实施方式中，所述内腔的底部具有第一导坡，所述第一导坡位于所述第一侧壁的下方，所述第一导坡与所述第一侧壁平滑相接。
在一些实施方式中，所述内腔的底部具有第二导坡，所述第二导坡位于所述第二侧壁的下方，所述第二导坡与所述第二侧壁平滑相接。
在一些实施方式中，所述内腔的底部具有第一导坡与第二导坡，所述第一导坡位于所述第一侧壁的下方，且所述第一导坡与所述第一侧壁平滑相接，所述第二导坡位于所述第二侧壁的下方，且所述第二导坡与所述第二侧壁平滑相接；沿所述液瓶的宽度方向：所述第二通 道口位于所述第一导坡与所述第二导坡之间，所述第一导坡与所述第二导坡分别自所述第二通道口向两侧且逐渐向上倾斜延伸。从而当液体流动至内腔的底部时，其能够在自身重力及第一导破、第二导坡的导向作用下自动汇聚到第二通道口中，有效减少细胞液在所述瓶体中的残留量。
在一些实施方式中，所述内腔的底部还具有第三导坡，所述第三导坡位于所述液瓶的厚度方向的一侧，且沿所述液瓶的厚度方向，所述第三导坡自所述第二通道口向外侧且逐渐向上倾斜延伸。如此，能够进一步加强内腔的底部对液体的汇聚导向作用，提高液体的回收率。在另一些优选实施方式中，内腔的底部的导坡可以不限于第一导坡、第二导坡、第三导坡三组，还可以设置四组、五组或更多组导坡，多组导坡共同将内腔的底部围设为一锥体结构，促使液体顺畅排出。
在一些实施方式中，所述第一导坡与所述第二导坡相对于所述第二通道口的轴心线对称设置。在一些优选实施方式中，内腔的底部即呈一圆锥体结构，从而进一步消除棱边结构可能带来的液体粘附、残留等问题隐患。
在一些实施方式中，沿所述液瓶的宽度方向：所述第一侧壁的切面与水平面之间的锐角夹角大于所述第一导坡的切面与所述水平面之间的锐角夹角，且所述第二侧壁的切面与所述水平面之间的锐角夹角大于所述第二导坡的切面与所述水平面之间的锐角夹角。当液体刚进入内腔中时，第一侧壁与第二侧壁均具有相对竖直的倾角，从而不至于瞬间降低液体的流速，且不会显著减小内腔的体积；当液体流动至内腔的底部而即将排出时，第一导坡与第二导坡具有相对水平的倾角，能够引导液体从第二通道口排出，且不会显著增加液瓶的长度尺寸，确保液瓶外形简洁实用。
在一些实施方式中，沿所述液瓶的宽度方向，所述第一侧壁的切面与水平面之间的锐角夹角为75°～85°，所述第二侧壁的切面与所述水平面之间的锐角夹角为75°～85°。通过理论计算与实验验证得到，第一侧壁与第二侧壁合适的倾角能够引导液体以适当的流速下落，确保液体回收率的同时不至产生泡沫并损伤细胞，且不会对内腔的容积产生较大影响。
进一步优选地，第一侧壁与第二侧壁相对于所述第二通道口的轴心线左右对称设置，两者的切面与水平面之间的锐角夹角均为82°。
在一些实施方式中，所述瓶体还具有第三侧壁与第四侧壁，所述第三侧壁与所述第四侧壁分设于所述液瓶的厚度方向的相异两侧，所述液瓶的厚度小于所述液瓶的宽度，所述第三侧壁的延伸方向与所述第四侧壁的延伸方向相互平行。此时，液瓶整体较为扁平，能够贴合设置在电转染仪等仪器的外侧壁上，减小设备的整体体积，同时也能够提高液瓶使用时的稳定性，其悬挂时不易晃动、摇摆。
在一些实施方式中，所述液瓶还包括悬挂部，所述悬挂部设置在所述第四侧壁上。从而当该液瓶悬挂于电转染仪等仪器的外部时，第四侧壁能够贴合于设备的外侧壁。
在一些实施方式中，所述第一通道口、所述第二通道口、所述第三通道口均设置在靠近所述第三侧壁的一侧，所述液瓶还包括悬挂部，所述悬挂部设置在所述第四侧壁上。从而当该液瓶悬挂于设备的外侧壁时，第一通道口、第二通道口、第三通道口等均位于靠外的一侧，设备、管路等对液瓶使用的干涉更小。
在一些实施方式中，透明的所述第三侧壁上标注有刻度线。
在一些实施方式中，所述内腔的底部还具有第三导坡，所述第三导坡位于所述内腔的厚度方向的一侧，沿所述液瓶的厚度方向，所述第三导坡自所述第二通道口向外侧且逐渐向上倾斜延伸，所述第三导坡与所述第四侧壁沿长度方向平滑相接。
在一些实施方式中，所述瓶体还具有第四通道口，所述第四通道口与所述内腔相连通，所述第四通道口位于所述内腔的上方，所述第四通道口、所述第一通道口、所述第三通道口三者沿所述液瓶的宽度方向间隔设置。第四通道口可用于通入缓冲液，通过冲洗内壁进一步将残留的细胞液充分排出液瓶。
在一些实施方式中，所述第一侧壁与所述第一通道口的内侧壁沿所述液瓶的长度方向竖直相接，和/或，所述第二侧壁与所述第三通道口的内侧壁沿所述液瓶的长度方向竖直相接。从而从第一通道口或第三通道口落入的液体能够直接沿着对应的第一侧壁或第二侧壁下滑，进一步减小对液面的冲击力。
在一些实施方式中，所述液瓶还包括悬挂部，所述悬挂部与所述瓶体连接，至少部分所述悬挂部位于所述瓶体的上方。悬挂部可用于将液瓶悬挂在外部支架上。
在一些实施方式中，所述瓶体由硬质材料一体化注塑焊接制成。
在一些实施方式中，所述瓶体的至少一侧壁采用透明材料。
由于以上技术方案的运用，本发明提供的液瓶，三组通道口的设置能够使得在输送液体的过程中，内腔中的气压与环境气压保持一致，有助于液体顺畅排出；倾斜设置的第一侧壁与第二侧壁能够承接从上方流入的细胞液，以避免细胞液直接冲击在液面上而产生泡沫并损伤细胞，从而有效提高内腔中细胞液的均匀性，有助于提高细胞液的回收率。
附图说明
为了更清楚地说明本发明的技术方案，下面将对实施例描述中所需要使用的附图作简单的介绍。
附图1为本发明一具体实施例中液瓶使用状态下的立体示意图；
附图2为实施例1中液瓶的立体示意图；
附图3为实施例1中液瓶的另一角度的立体示意图；
附图4为实施例1中液瓶的侧视示意图；
附图5为实施例1中液瓶的仰视示意图；
附图6为实施例1中液瓶的俯视示意图；
附图7为实施例1中液瓶的主视示意图；
附图8为实施例2中液瓶的立体示意图；
附图9为实施例2中液瓶的俯视示意图，其中悬挂部被隐去；
附图10为实施例3中液瓶的立体示意图；
附图11为实施例4中液瓶的立体示意图；
其中：1001、水平面；1002、虚拟平面；10、瓶体；101、上瓶体；102、下瓶体；11、第一通道口；110、第二投影；111、进液管；12、第二通道口；121、出液管；13、第三通道口；130、第四投影；131、通气管；14、封头；15、第四通道口；21、第一侧壁；210、第一投影；22、第二侧壁；220、第三投影；23、第三侧壁；24、第四侧壁；25、顶壁；31、第一导坡；32、第二导坡；33、第三导坡；4、止流夹；5、悬挂部；6、空气过滤器。
具体实施方式
下面结合附图对本发明的较佳实施例进行详细阐述，以使本发明的优点和特征能更易于被本领域的技术人员理解。
实施例1
参见图1所示，本实施例提供一种液瓶，主要用于生物医疗及医药等领域中液体的输送或存储，尤其适用于流式电转染中均匀性差、转移难度高且回收率要求高的细胞液的输送。该液瓶包括瓶体10，瓶体10具有中空的内腔。此处瓶体10由硬质材料一体化注塑焊接制成，从而保证内腔的相对密封与无菌，且瓶体10的硬性结构使得内腔不易变形，内腔的各内侧壁不会粘附在一起而造成液体夹壁残留，并可以更方便地被其他机构(如：摇摆电机等混匀机构)所夹持。为便于使用者观察内腔中的液体，瓶体10优选至少一侧壁的部分采用透明材料。
需要说明的是，本发明的液瓶正常使用时，一般需要以图1或图8所示的方向摆放或悬挂，液体可以从上方的第一通道口11流入液瓶，也可以从下方的第二通道口12流出液瓶，因此本文中所描述的长度方向Z、宽度方向X、厚度方向Y等，均是基于图1或图8所示的方位定义的，仅是为了方便描述和理解，不应理解为对本发明的限定。
参见图2～图7所示，本实施例中，瓶体10具体包括沿液瓶的周向依次相接的第一侧壁21、第三侧壁23、第二侧壁22及第四侧壁24，以及位于内腔顶部的顶壁25。其中第一侧壁21与第二侧壁22分设于液瓶的宽度方向X的相异两侧，第三侧壁23与第四侧壁24分设于 液瓶的厚度方向Y的相异两侧。以图2所示的视角看，具体是第一侧壁21位于右侧，第二侧壁22位于左侧，第三侧壁23位于前侧，第四侧壁24位于后侧。本实施例中，液瓶的厚度小于其宽度，沿液瓶的宽度方向X，第一侧壁21与第二侧壁22分别自上而下逐渐向内倾斜延伸；而沿液瓶的厚度方向Y，第三侧壁23的延伸方向与第四侧壁24的延伸方向相互平行，且两者分别沿液瓶的长度方向Z延伸。如此，瓶体10整体外形较为扁平，第四侧壁24能够贴合在电转仪等设备的外侧壁上，摆放更为稳定，也更节省空间。
本实施例中，如图1～图2所示，透明的第三侧壁23上标注有刻度线，便于使用者知晓内腔中细胞液的大致体积。第四侧壁24上固设有悬挂部5，可用于将瓶体10挂设于外部挂钩或支架上。特别地，该液瓶能够贴合挂设于电转染仪等设备的外侧壁上，尤其适用于平面状的侧壁，只需在对应的设备外侧壁上设置与悬挂部5配合的挂接部件，就能够将悬挂部5稳固地挂设上去，此时瓶体10的第四侧壁24与上述外侧壁稳定贴合，而第三侧壁23朝外设置，便于观察。
本实施例中，该瓶体10具有分别与内腔相连通的第一通道口11、第二通道口12及第三通道口13。其中第一通道口11、第三通道口13位于内腔的上方，第二通道口12位于内腔的下方，且第三通道口13与第一通道口11沿液瓶的宽度方向X间隔设置。本实施例中，第一通道口11具体用于进液，第二通道口12用于出液，第三通道口13用于通气。由于第一通道口11与第三通道口13结构上完全对称设置，因此在其他实施例中，也可以将第一通道口11用于通气，第三通道口13用于进液。
本实施例中，如图1～图5所示，内腔的底部还具有第一导坡31、第二导坡32及第三导坡33。其中，第一导坡31位于第一侧壁21的下方，且第一导坡31与第一侧壁21沿液瓶的长度方向Z平滑相接；第二导坡32位于第二侧壁22的下方，且第二导坡32与第二侧壁22沿液瓶的长度方向Z平滑相接。需要说明的是，本实施例中第一导坡31与第一侧壁21之间、第二导坡32与第二侧壁22之间并没有明确的分界线，瓶体10的第一侧壁21、第一侧壁22均为圆滑的弧面，从而两侧壁的导向作用更为自然平缓，并可减少棱角结构可能导致的细胞液滞留问题。第三导坡33位于液瓶的厚度方向Y的一侧，且第三导坡33与第四侧壁24沿长度方向Z平滑相接。沿液瓶的宽度方向X，第二通道口12位于第一导坡31与第二导坡32之间，第一导坡31与第二导坡32分别自第二通道口12向两侧且逐渐向上倾斜延伸。沿液瓶的厚度方向Y，第二通道口12位于第三侧壁23与第三导坡33之间，第三导坡33自第二通道口12向外侧且逐渐向上倾斜延伸。由上可知，沿液瓶的长度方向Z，内腔的横截面积自上而下逐渐缩小，瓶体10整体呈一倒锥体结构，从而能够将全部细胞液逐渐汇聚引导至第二通道口12中，有助于细胞液的顺畅排出。
参见图2所示，第一侧壁21可用于承接从第一通道口11落入的液体，第二侧壁22可用于承接从第三通道口13落入的液体，防止液体进入内腔后直接冲击在液面上而形成泡沫并损伤细胞。具体地，第一侧壁21在水平面1001上具有第一投影210，第一通道口11在水平面1001上具有第二投影110，第二投影110位于第一投影210的内部。第二侧壁22在水平面1001上具有第三投影220，第三通道口13在水平面1001上具有第四投影130，第四投影130位于第三投影220的内部。进一步地，本实施例中，参见图6所示，沿液瓶的宽度方向X，第一通道口11与第三通道口13分别设置在瓶体10的顶壁25的左右两端部；参见图2，此时第二投影110位于第一投影210的外端部，第四投影130位于第三投影220的外端部。在更优选的实施方式中，第一侧壁21与第一通道口11的内侧壁沿液瓶的长度方向Z竖直相接，第二侧壁22与第三通道口13的内侧壁沿液瓶的长度方向Z竖直相接。如此，即使在液瓶已经存储有较多的细胞液的情况下，从第一通道口11或第三通道口13流入的细胞液也能够直接被对应的侧壁所承接而不至使液滴下落后直接撞击液面而产生冲击，更大限度减少泡沫的产生及对细胞的损伤。
进一步地，参见图7所示，沿液瓶的宽度方向X：第一侧壁21的切面与水平面1001之间的锐角夹角α1大于第一导坡31的切面与水平面1001之间的锐角夹角β1，且第二侧壁22的切面与水平面1001之间的锐角夹角α2大于第二导坡32的切面与水平面1001之间的锐角夹角β2。本实施例中，瓶体10沿液瓶的宽度方向X左右对称设置，α1与α2相等，均约为75°～85°，此处具体采用82°。从而在对细胞液形成导流的同时，内腔也能够具有适当的容积及尺寸。
此外，参见图4～图6所示，为了进一步提高细胞液的回收率，存在一个竖直的虚拟平面1002，虚拟平面1002沿液瓶的宽度方向X延伸，第一通道口11的轴心线与第三通道口13的轴心线均位于虚拟平面1002内，第二通道口12的轴心线位于该虚拟平面1002内或与该虚拟平面1002间隔设置。本实施例中，第一通道口11、第二通道口12、第三通道口13三者的轴心线均位于该虚拟平面1002内，且沿液瓶的厚度方向Y，第一通道口11、第二通道口12、第三通道口13均设置在瓶体10的前端部，即靠近第三侧壁23的一侧。从而从第一通道口11或第三通道口13流入的液体能够更为顺畅地引入第二通道口12中，且位于前侧的、位于竖直平面内的第三侧壁23不会对细胞液产生阻滞，也能够对细胞液起到辅助导向的作用。并且，由前文可知，当该液瓶悬挂使用时，第四侧壁24与第三导坡33位于靠近电转染仪外侧壁的一侧，而第一通道口11、第二通道口12及第三通道口13均位于远离外侧壁的一侧，使得例如电转染仪等设备的外侧壁不易与管路等结构产生干涉，也更有助于排液通畅及使用者操作。在其他实施例中，第二通道口12的轴心线还可与虚拟平面间隔设置，有助于减少超声 焊接对第二通道口12的影响。
参见图1所示，该液瓶在实际使用过程中，配套有进液管111、出液管121、通气管131等软管及止流夹4、空气过滤器6等配件。具体地，进液管111的一端部固设于第一通道口11，另一端部设有封头14，可用于将第一通道口11密封；进液管111的上还可设有鲁尔接头等连接头(图中未示出)，用于与外部管路相连通。出液管121的一端部固设于第二通道口12，另一端部同样可设有封头14或鲁尔接头等连接头，用于将第二通道口12密封或与外部管路连通。通气管131的一端部固设于第三通道口13，另一端部设有空气过滤器6，从而能够在使得内腔与外部大气保持气压平衡的同时，阻隔外部环境中的灰尘和细菌等杂质，保证内腔封闭无菌。上述进液管111、出液管121、通气管131上各夹设有一组止流夹4，用于控制对应管路内流体的通断，本实施例中止流夹4具体采用罗伯特夹。
根据不同场合的实际需求，本实施例中的液瓶可以用于输出液体(下称进样液瓶)、接收液体(下称收集液瓶)或密封存储液体等。以流式电转染为例，沿细胞液的输送方向，电转染装置(图中未示出)的上游连接有一组进样液瓶，用于向电转染装置输出待处理的细胞液；电转染装置的下游连接有一组收集液瓶，用于从电转染装置中接收处理完的细胞液。
在进样液瓶中，与第一通道口11连接的进液管111被止流夹4密封，其对应的封头14封闭；而出液管121与通气管131保持通畅，出液管121通过鲁尔接头或无菌接管机直接热熔的方式与外部管路连接进而连接至电转染装置，排液过程中内腔的气压与外界气压保持平衡，细胞液能够通过第二通道口12顺畅、充分地排出内腔，液体残留量小。
在收集液瓶中，与第二通道口12连接的出液管121被止流夹4密封，其对应的封头14封闭；而进液管111与通气管131保持通畅，进液管111通过鲁尔接头或无菌接管机直接热熔的方式与外部管路连接进而连接至电转染装置，细胞液能够通过第一通道口11顺畅地流入内腔中。
当该液瓶仅用于存储液体时，进液管111、出液管121、通气管131均被相应的止流夹4密封，内腔中形成完全密封无菌的存储空间。
实施例2
参见图8及图9所示，本实施例提供另一种液瓶，该液瓶的使用场景及使用方法与实施例1基本相同，主要区别在于本实施例中瓶体10的具体形状有所差别。
本实施例中，瓶体10包括上瓶体101与下瓶体102，上瓶体101位于下瓶体102的上方且两者沿液瓶的长度方向Z圆滑过渡相接。此时，第一侧壁21与第二侧壁22分设于上瓶体101的左右两侧，而第一导坡31与第二导坡32分设于下瓶体102的左右两侧。需要说明的是，本实施例中第一侧壁21与第二侧壁22之间、第一导坡31与第二导坡32之间并没有明 确的分界线，但与实施例1相同地，上述各侧壁或导坡分别沿液瓶的宽度方向X自内向外逐渐向上倾斜延伸，从而对进入内腔的细胞液提供缓冲与导向。
此处具体地，下瓶体102的全部内侧壁位于第一虚拟圆锥面内，上瓶体101的全部内侧壁位于第二虚拟圆锥面内，第二通道口12位于下瓶体102的底部，且第一虚拟圆锥面、第二虚拟圆锥面及第二通道口12三者的轴心线共线延伸。如此，第一导坡31与第二导坡32均位于第一虚拟圆锥面内，第一侧壁21与第二侧壁22均位于第二虚拟圆锥面内，且第一虚拟圆锥面的锥度大于第二虚拟圆锥面的锥度，从而细胞液在上瓶体101中具有相对更大的流速，而下瓶体102能够将细胞液更为缓和地引入第二通道口12中。
本实施例中，与实施例1相似地，第一侧壁21在水平面1001上具有第一投影210，第一通道口11在水平面1001上具有第二投影110，第二投影110位于第一投影210的内部；第二侧壁22在水平面1001上具有第三投影220，第三通道口13在水平面1001上具有第四投影130，第四投影130位于第三投影220的内部。并且，沿液瓶的宽度方向X，第一通道口11与第三通道口13分别设置在上瓶体101的左右两端部，从而从第一通道口11或第三通道口13流入的细胞液能够直接被对应的第一侧壁21或第二侧壁22承接，以减少泡沫的产生及对细胞的损伤。
本实施例中，同样存在一个竖直的、沿液瓶的宽度方向X延伸的虚拟平面1002，第一通道口11、第二通道口12、第三通道口13三者的轴心线均位于该虚拟平面1002内。
本实施例中，悬挂部5连接于上瓶体101的上部，具体为一根位于顶壁25上方的U形杆，悬挂部5位于所述瓶体10的上方，可用于将液瓶悬挂使用，且更适用于水平延伸较长的支架或挂钩。需要说明的是，实施例一中的液瓶可以同时具备实施例一及实施例二中给定的悬挂部5，以适应不同的应用场景。
实施例3
参见图10所示，本实施例提供另一种液瓶，该液瓶与实施例1基本相同，主要区别在于本实施例中的瓶体10还具有第四通道口15。
本实施例中，第四通道口15与内腔相连通，第四通道口15位于内腔的上方，沿液瓶的宽度方向X，第一通道口11、第四通道口15、第三通道口13三者依次间隔设置，且此处第四通道口15相对靠近第一通道口11。
本实施例中，第四通道口15可用于通入缓冲液。当瓶体10中的细胞液基本排出后，可能仍有部分细胞粘附在瓶体10的内壁上或积聚在内腔的底部，此时可向第四通道口15通入缓冲液，缓冲液能够沿着瓶体10的内壁向下冲刷，将残留的细胞冲出，进一步提高细胞的回收率。
实施例4
参见图11所示，本实施例提供另一种液瓶，该液瓶与实施例2基本相同，主要区别在于本实施例中的瓶体10还具有第四通道口15。
本实施例中，第四通道口15与内腔相连通，第四通道口15位于内腔的上方，沿液瓶的宽度方向X，第一通道口11、第四通道口15、第三通道口13三者依次间隔设置，且此处第四通道口15相对靠近第一通道口11。
本实施例中第四通道口15的使用方法与实施例3中的第四通道口15基本相同，此处不再赘述。
综上所述，本发明提供的液瓶，具有硬性的锥体结构，尤其适配于大容量细胞液的输送，促使细胞液向内腔底部汇聚与流出，提高细胞液的回收率；且流入内腔的细胞液能够贴着瓶体10的斜壁面流下，不会由于冲击力产生大量泡沫并损伤细胞，有助于提高细胞处理效率如电转染效率。
上述实施例只为说明本发明的技术构思及特点，其目的在于让熟悉此项技术的人士能够了解本发明的内容并据以实施，并不能以此限制本发明的保护范围。凡根据本发明精神实质所作的等效变化或修饰，都应涵盖在本发明的保护范围之内。

Claims (27)

  1. 一种液瓶，用于无菌环境中细胞液的输送和/或存储，所述液瓶包括瓶体，所述瓶体具有中空的内腔，其特征在于，所述瓶体具有：
    第一通道口，所述第一通道口与所述内腔相连通，所述第一通道口位于所述内腔的上方；
    第二通道口，所述第二通道口与所述内腔相连通，所述第二通道口位于所述内腔的下方；
    第三通道口，所述第三通道口与所述内腔相连通，所述第三通道口位于所述内腔的上方，所述第三通道口与所述第一通道口沿所述液瓶的宽度方向间隔设置；
    第一侧壁与第二侧壁，所述第一侧壁与所述第二侧壁分设于所述液瓶的宽度方向的相异两侧，沿所述液瓶的宽度方向，所述第一侧壁自上而下逐渐向内倾斜延伸，所述第一侧壁可用于承接从所述第一通道口落入的液体。
  2. 根据权利要求1所述的液瓶，其特征在于：所述第二侧壁自上而下逐渐向内倾斜延伸，所述第二侧壁可用于承接从所述第三通道口落入的液体。
  3. 根据权利要求1或2所述的液瓶，其特征在于：所述第一侧壁在水平面上具有第一投影，所述第一通道口在所述水平面上具有第二投影，所述第二投影位于所述第一投影的内部。
  4. 根据权利要求2或3所述的液瓶，其特征在于：所述第二侧壁在水平面上具有第三投影，所述第三通道口在所述水平面上具有第四投影，所述第四投影位于所述第三投影的内部。
  5. 根据权利要求1-4任一权利要求所述的液瓶，其特征在于：存在一个竖直的虚拟平面，所述虚拟平面沿所述液瓶的宽度方向延伸，所述第一通道口的轴心线与所述第三通道口的轴心线均位于所述虚拟平面内，所述第二通道口的轴心线位于所述虚拟平面内。
  6. 根据权利要求1-4任一权利要求所述的液瓶，其特征在于：存在一个竖直的虚拟平面，所述虚拟平面沿所述液瓶的宽度方向延伸，所述第一通道口的轴心线与所述第三通道口的轴心线均位于所述虚拟平面内，所述第二通道口的轴心线与所述虚拟平面间隔设置。
  7. 根据权利要求1-6任一权利要求所述的液瓶，其特征在于：沿所述液瓶的宽度方向，所述第一通道口与所述第三通道口分别设置在所述瓶体的左右两端部。
  8. 根据权利要求1-7任一权利要求所述的液瓶，其特征在于：沿所述液瓶的厚度方向，所述第一通道口、所述第二通道口、所述第三通道口均设置在所述瓶体的前端部。
  9. 根据权利要求1-8任一权利要求所述的液瓶，其特征在于：所述内腔的底部具有第一导坡，所述第一导坡位于所述第一侧壁的下方，所述第一导坡与所述第一侧壁平滑相接。
  10. 根据权利要求1-9任一权利要求所述的液瓶，其特征在于：所述内腔的底部具有第二导坡，所述第二导坡位于所述第二侧壁的下方，所述第二导坡与所述第二侧壁平滑相接。
  11. 根据权利要求1-8任一权利要求所述的液瓶，其特征在于：所述内腔的底部具有第一导坡与第二导坡，所述第一导坡位于所述第一侧壁的下方，且所述第一导坡与所述第一侧壁 平滑相接，所述第二导坡位于所述第二侧壁的下方，且所述第二导坡与所述第二侧壁平滑相接；沿所述液瓶的宽度方向：所述第二通道口位于所述第一导坡与所述第二导坡之间，所述第一导坡与所述第二导坡分别自所述第二通道口向两侧且逐渐向上倾斜延伸。
  12. 根据权利要求11所述的液瓶，其特征在于：所述内腔的底部还具有第三导坡，所述第三导坡位于所述内腔的厚度方向的一侧，沿所述液瓶的厚度方向，所述第三导坡自所述第二通道口向外侧且逐渐向上倾斜延伸。
  13. 根据权利要求11或12所述的液瓶，其特征在于：所述第一导坡与所述第二导坡相对于所述第二通道口的轴心线对称设置。
  14. 根据权利要求11-13任一权利要求所述的液瓶，其特征在于，沿所述液瓶的宽度方向：所述第一侧壁的切面与水平面之间的锐角夹角大于所述第一导坡的切面与所述水平面之间的锐角夹角，所述第二侧壁的切面与所述水平面之间的锐角夹角大于所述第二导坡的切面与所述水平面之间的锐角夹角。
  15. 根据权利要求1-14任一权利要求所述的液瓶，其特征在于：沿所述液瓶的宽度方向，所述第一侧壁的切面与水平面之间的锐角夹角为75°～85°，所述第二侧壁的切面与所述水平面之间的锐角夹角为75°～85°。
  16. 根据权利要求1-15任一权利要求所述的液瓶，其特征在于：所述第一侧壁与所述第二侧壁相对于所述第二通道口的轴心线对称设置。
  17. 根据权利要求1-16任一权利要求所述的液瓶，其特征在于：所述瓶体还具有第三侧壁与第四侧壁，所述第三侧壁与所述第四侧壁分设于所述液瓶的厚度方向的相异两侧，所述内腔的厚度小于所述内腔的宽度，所述第三侧壁的延伸方向与所述第四侧壁的延伸方向相互平行。
  18. 根据权利要求17所述的液瓶，其特征在于：所述液瓶还包括悬挂部，所述悬挂部设置在所述第四侧壁上。
  19. 根据权利要求17所述的液瓶，其特征在于：所述第一通道口、所述第二通道口、所述第三通道口均设置在靠近所述第三侧壁的一侧，所述液瓶还包括悬挂部，所述悬挂部设置在所述第四侧壁上。
  20. 根据权利要求17-19任一权利要求所述的液瓶，其特征在于：透明的所述第三侧壁上标注有刻度线。
  21. 根据权利要求19或20所述的液瓶，其特征在于：所述内腔的底部还具有第三导坡，所述第三导坡位于所述内腔的厚度方向的一侧，沿所述液瓶的厚度方向，所述第三导坡自所述第二通道口向外侧且逐渐向上倾斜延伸，所述第三导坡与所述第四侧壁沿长度方向平滑相 接。
  22. 根据权利要求1-21任一权利要求所述的液瓶，其特征在于：所述瓶体还具有第四通道口，所述第四通道口与所述内腔相连通，所述第四通道口位于所述内腔的上方，所述第四通道口、所述第一通道口、所述第三通道口三者沿所述液瓶的宽度方向间隔设置。
  23. 根据权利要求1-22任一权利要求所述的液瓶，其特征在于：所述第一侧壁与所述第一通道口的内侧壁沿所述液瓶的长度方向竖直相接。
  24. 根据权利要求1-23任一权利要求所述的液瓶，其特征在于：所述第二侧壁与所述第三通道口的内侧壁沿所述液瓶的长度方向竖直相接。
  25. 根据权利要求1-24任一权利要求所述的液瓶，其特征在于：所述液瓶还包括悬挂部，所述悬挂部与所述瓶体连接，至少部分所述悬挂部位于所述瓶体的上方。
  26. 根据权利要求1-25任一权利要求所述的液瓶，其特征在于：所述瓶体由硬质材料一体化注塑焊接制成。
  27. 根据权利要求1-26任一权利要求所述的液瓶，其特征在于：所述瓶体的至少一侧壁采用透明材料。
PCT/CN2023/104614 2022-07-14 2023-06-30 一种液瓶 WO2024012260A1 (zh)

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