Sterile sampling device and sterile culture equipment

Abstract

The utility model discloses a sterile sampling device and sterile culture equipment. The sterile sampling device comprises a main communicating pipeline provided with a liquid inlet and a liquid outlet, the liquid inlet is used for being communicated with a liquid discharge port of a reactor, and the liquid outlet is used for being communicated with a liquid return port of the reactor; the pump is arranged on the main communicating pipeline; the more than one sampling branch is respectively communicated with the main communicating pipeline in a selectable on-off manner; the first valve is configured to selectively cut off the culture solution in the reactor from flowing to the main communicating pipeline through the liquid inlet; the second valve is configured to selectively cut off the culture solution in the main communicating pipeline from flowing to the reactor through the liquid outlet; one end of the first filter is connected to the main communicating pipeline through the air inlet valve, and the other end of the first filter is used for being connected with an external positive pressure device; the air inlet valve is positioned at the downstream of the first valve and the upstream of the position where the first sampling branch is connected with the main communicating pipeline according to the sequence of the flowing direction of the culture solution in the main communicating pipeline. The device reduces or even eliminates culture solution residues.

Description

Technical Field

[0001] The utility model relates to the technical field of aseptic sampling, in particular to an aseptic sampling device and aseptic culture equipment. Background Art

[0002] A bioreactor is a device system that uses the biological functions of enzymes or organisms to carry out biochemical reactions in vitro. It is a biological function simulator, such as a fermenter, immobilized enzyme or immobilized cell reactor. A bioreactor is a device that enables biological reactions.

[0003] In actual use, it is necessary to sample the material in the bioreactor multiple times. Specifically, during batch culture, a batch will be sampled at least 18 times. Therefore, the most commonly used sterile sampling device is a multi-sampling bag, such as the Saint-Gobain product The sampling manifold system can meet the needs of multiple sampling. This multi-sampling bag usually includes a reactor, a waste liquid collection container, a main connecting pipeline and multiple sampling branches. The two ends of the main connecting pipeline are respectively connected to the reactor and the waste liquid collection container, and the multiple sampling branches are respectively connected to the main connecting pipeline in an optional on-off manner. Each sampling branch includes a sampling bag, a filter and a sampling pipeline. The sampling bag is connected to the main connecting pipeline through the sampling pipeline. Each sampling bag is connected to a filter. A valve is provided on each sampling pipeline for enabling the corresponding sampling branch to be selectively connected to the main connecting pipeline in an on-off manner. After each sampling bag is sampled, the sampling bag can be removed using an existing sealing machine or other sealing device.

[0004] Before the next sampling, in order to reduce the reduction in detection accuracy caused by the residual culture solution in the connecting line, the operator usually needs to use a certain amount of culture solution to flush the residual culture solution in the connecting line into a waste liquid collection container connected to the end of the connecting line, such as a waste liquid bag or waste liquid bottle. This operation results in waste. Utility Model Content

[0005] Purpose of the utility model: The technical problem to be solved by the utility model is to provide a sterile sampling device and a sterile culture equipment to reduce the residual culture fluid in the main connecting pipeline in response to the shortcomings of the existing technology.

[0006] In order to solve the above technical problems, the first aspect of the present invention discloses a sterile sampling device and a sterile culture device, wherein the sterile sampling device comprises:

[0007] A main connecting pipeline is provided with a liquid inlet and a liquid outlet, wherein the liquid inlet is used to communicate with the liquid discharge port of the reactor, and the liquid outlet is used to communicate with the liquid return port of the reactor;

[0008] A pump is provided on the main connecting pipeline;

[0009] One or more sampling branches are respectively connected to the main connecting pipe in a selectable on-off manner;

[0010] a first valve configured to selectively cut off the flow of the culture solution in the reactor to the main communication line through the liquid inlet;

[0011] a second valve configured to selectively cut off the flow of the culture solution in the main communication line to the reactor through the liquid outlet;

[0012] and a first filter, one end of which is connected to the main connecting line through an air intake valve, and the other end of the first filter is used to be connected to an external positive pressure device; based on the flow direction of the culture fluid in the main connecting line, the air intake valve is located downstream of the first filter and upstream of the position where the first sampling branch is connected to the main connecting line.

[0013] In one embodiment, each of the sampling branches includes a sampling bag, a second filter, and a sampling pipeline, wherein the sampling pipeline connects the sampling bag with the main connecting pipeline. One end of the second filter is connected to the sampling bag, and the other end is used to connect to an external negative pressure device.

[0014] In one embodiment, each of the sampling branches includes a third valve, which is arranged on the corresponding sampling pipeline. The third valve is used to enable the corresponding sampling branch to be selectively connected to the main connecting pipeline.

[0015] In one embodiment, the third valve is a pinch valve.

[0016] The second aspect of the present invention discloses an aseptic culture device, which includes a reactor and any of the aseptic sampling devices and aseptic culture devices. The reactor is configured to store culture fluid. The device has an emptying working condition. In the emptying working condition, the air inlet valve is configured to be turned on, the first valve is configured to cut off the flow of the culture fluid in the reactor to the main connecting line, each of the sampling branches is configured to be disconnected from the main connecting line, and the pump is configured to provide power to cause the culture fluid in the main connecting line to flow back into the reactor.

[0017] In one embodiment, the reactor is connected to the main connecting line to form a circulation loop. The device has a sampling mode. In the sampling mode, the air inlet valve is configured to be closed, and the first valve and the second valve are configured to be open, so that the culture fluid in the reactor can flow into the main connecting line through the liquid inlet, and the culture fluid in the main connecting line flows into the reactor through the liquid outlet. The pump is configured to provide power to enable the culture fluid to flow in the circulation loop.

[0018] In one embodiment, the apparatus comprises a negative pressure device, which is configured to create a negative pressure inside the corresponding sampling bag.

[0019] In one embodiment, the negative pressure device is a vacuum pump.

[0020] In one embodiment, the apparatus includes a positive pressure device, which is configured to form a slight positive pressure in the main communicating line. The slight positive pressure means that the gas pressure in the main communicating line is in the range of 0.01 to 0.02 MPa.

[0021] In one embodiment, the positive pressure device is a double ball, compressed air or a vacuum pump.

[0022] Beneficial effects:

[0023] In the sterile sampling device and sterile culture equipment provided by the present invention, when the liquid inlet of the sterile sampling device is connected to the liquid discharge port of the reactor, and the liquid outlet of the sterile sampling device is connected to the liquid return port of the reactor, the reactor and the main connecting line are connected to form a circulation loop. An external positive pressure device introduces filtered sterile air into the main connecting line through a first filter, thereby forming a slight positive pressure in the main connecting line. Driven by a pump, the culture liquid in the main connecting line is completely refluxed into the reactor, thereby reducing or eliminating liquid residue in the main connecting line and reducing waste. BRIEF DESCRIPTION OF THE DRAWINGS

[0024] The present invention will be further described below in conjunction with the accompanying drawings and specific embodiments, and the above and / or other advantages of the present invention will become more apparent.

[0025] Figure 1 A schematic structural diagram of a sterile sampling device according to an embodiment of the present invention is provided;

[0026] Figure 2 A schematic structural diagram of a sterile culture device according to an embodiment of the present invention;

[0027] Figure 3 for Figure 2 Schematic diagram of the sterile culture equipment in use under sampling conditions;

[0028] Figure 4 for Figure 3 The diagram shown is a schematic diagram of the sterile culture equipment in use under emptying conditions.

[0029] The following are the descriptions of the reference numerals:

[0030] Device 100, main connecting pipeline 110, liquid inlet 111, liquid outlet 112, pump 120, sampling branch 130, sampling bag 131, second filter 132, sampling pipeline 133, third valve 134, first valve 140, second valve 150, first filter 160, air inlet valve 170, reactor 200, positive pressure device 300 and negative pressure device 400. DETAILED DESCRIPTION

[0031] Using Saint-Gobain products When developing a sampling manifold system, the applicant discovered that this sampling manifold system suffers from a large dead volume. Before the next sampling, to reduce the risk of reduced detection accuracy due to residual culture fluid in the main connecting line, a certain amount of culture fluid is typically flushed from the connecting line into a waste fluid collection container, such as a waste fluid bag or bottle, connected to the end of the connecting line. This results in waste.

[0032] Figure 1 The present invention is a schematic structural diagram of a sterile sampling device according to an embodiment of the present invention. Figure 2 The present invention is a schematic structural diagram of a sterile culture device according to an embodiment of the present invention. Figure 3 and Figure 4 They are Figure 2 The diagram shows a schematic diagram of a sterile culture device in use under sampling and emptying conditions. Figures 2 to 4 The solid arrows shown in the figure represent the flow direction of the culture medium, the dotted arrows shown in the figure represent the flow direction of the sterile air, and the thick line × shown in the figure indicates that the pipeline is cut off at this location.

[0033] Now see Figures 1 to 4 The aseptic sampling device 100 includes a main connecting pipeline 110 having a liquid inlet 111 and a liquid outlet 112 , a pump 120 , one or more sampling branches 130 , a first valve 140 , a second valve 150 and a first filter 160 .

[0034] The liquid inlet 111 is used to communicate with the liquid discharge port of the reactor 200, and the liquid outlet 112 is used to communicate with the liquid return port of the reactor 200. When the liquid inlet 111 is connected to the liquid discharge port of the reactor 200, and the liquid outlet 112 is connected to the liquid return port of the reactor 200, the reactor 200 is connected to the main connecting pipe 110 to form a circulation loop.

[0035] Among them, the pump 120 is arranged on the main connecting pipe 110. One or more sampling branches 130 are selectively connected to the main connecting pipe 110. The first valve 140 is configured to selectively cut off the flow of the culture solution in the reactor 200 to the main connecting pipe 110 through the liquid inlet 111. The second valve 150 is configured to selectively cut off the flow of the culture solution in the main connecting pipe 110 to the reactor 200 through the liquid outlet 112. The first filter 160, one end of the first filter 160 is connected to the main connecting pipe 110 through the air intake valve 170, and the other end of the first filter 160 is used to connect to the external positive pressure device 300; based on the flow direction of the culture solution in the main connecting pipe 110, the air intake valve 170 is located downstream of the first filter 160 and upstream of the position where the first sampling branch 130 is connected to the main connecting pipe 110. The first filter 160 is used to purify the air driven by the positive pressure device 300 to enter the main communication pipe 110 from the outside.

[0036] In one embodiment, the first valve 140 is installed at the liquid inlet 111, and the second valve 150 is installed at the liquid outlet 112. The first valve 140 and the second valve 150 can be pinch valves.

[0037] In one embodiment, the intake valve 170 is a pipe clamp or a Robert clamp.

[0038] In one embodiment, a sterile pipe connection machine can be used to aseptically connect the liquid inlet 111 and the liquid discharge port of the reactor 200, as well as the liquid outlet 112 and the liquid return port of the reactor 200.

[0039] Now see Figure 1 In one embodiment, each sampling branch 130 includes a sampling bag 131, a second filter 132 and a sampling pipeline 133, and the sampling pipeline 133 connects the sampling bag 131 with the main connecting pipeline 110; one end of the second filter 132 is connected to the sampling bag 131, and the other end is used to connect to the external negative pressure device 400.

[0040] Now see Figure 1 In one embodiment, each sampling branch 130 includes a third valve 134, which is provided on the corresponding sampling pipeline 133. The third valve 134 is used to connect the corresponding sampling branch 130 to the main connecting pipeline 110 in a selective on-off manner.

[0041] Now see Figure 1 In one embodiment, the third valve 134 is a pinch valve.

[0042] Now see Figures 2 to 4In one embodiment, the present invention further discloses a sterile culture apparatus, comprising a reactor 200 and any of a sterile sampling device and a sterile culture apparatus. The reactor 200 is configured to store a culture fluid. The reactor 200 is provided with a liquid discharge port and a liquid return port.

[0043] Now see Figure 3 , the device has a sampling condition; in the sampling condition, before sampling, the air inlet valve 170 is configured to be cut off, and the first valve 140 and the second valve 150 are configured to be connected, so that the culture solution in the reactor 200 can flow to the main connecting pipe 110 through the liquid inlet 111, and the culture solution in the main connecting pipe 110 flows to the reactor 200 through the liquid outlet 112, and the pump 120 is configured to provide power to make the culture solution flow in the circulation loop, so that the culture solution in the circulation loop is in a dynamic state and consistent with that in the reactor. In a specific embodiment, after circulating for 1 minute, the sampling branch 130 to be sampled is connected to the main connecting pipe 110. After the volume to be sampled meets the required volume, the sampling branch 130 is cut off from the main connecting pipe 110. The cut is plastic-sealed.

[0044] Now see Figure 4 , the device has an emptying working condition. In the emptying working condition, the air inlet valve 170 is configured to be cut off, the first valve 140 is configured to cut off the flow of the culture solution in the reactor 200 to the main connecting line 110, and each sampling branch 130 is configured to be cut off from the main connecting line 110. Subsequently, the external positive pressure device 300 introduces filtered air into the main connecting line 110 through the first filter 160, and forms a micro-positive pressure in the main connecting line 110. The pump 120 is configured to provide power to make the culture solution in the main connecting line 110 flow back into the reactor 200, thereby reducing or eliminating the liquid residue in the main connecting line 110.

[0045] Since the main communication line 110 is transparent, when the user observes that there is no liquid remaining in the main communication line 110 , the second valve 150 and the pump 120 are closed.

[0046] Now see Figure 3 In one embodiment, the apparatus includes a negative pressure device 400 , which is configured to form a negative pressure inside the corresponding sampling bag 131 .

[0047] In one embodiment, the negative pressure device 400 is a vacuum pump.

[0048] Now see Figure 4 In one embodiment, the apparatus includes a positive pressure device 300, which is configured to form a slight positive pressure in the main connecting pipe 110. In this application, slight positive pressure refers to a gas pressure in the main connecting pipe 110 ranging from 0.01 to 0.02 MPa.

[0049] In one embodiment, the positive pressure device 300 is a double ball, compressed air, or a vacuum pump.

[0050] The working process of the sterile culture equipment of one embodiment of the utility model is as follows:

[0051] Before sampling, close the air inlet valve 170, open the first valve 140 and the second valve 150, start the pump 120, and allow the culture solution to flow in the circulation loop formed by connecting the reactor 200 and the main connecting pipe 110. After circulating for 1 minute, open the third valve 134 on the sampling branch 130 to be sampled to connect the sampling branch 130 with the main connecting pipe 110. The third valves 134 on the other sampling branches 130 remain closed. A negative pressure device 400, such as a vacuum pump, creates a negative pressure inside the corresponding sampling bag 131, and the culture solution in the main connecting pipe 110 flows into the sampling bag 131 through the sampling pipe 133. After the volume to be sampled meets the required volume, close the third valve 134 and the negative pressure device 400 to cut off the connection between the sampling branch 130 and the main connecting pipe 110. The sampling bag 131 after sampling can then be removed using an existing sealing machine or other sealing device.

[0052] Before draining the culture fluid from main connecting line 110, close first valve 140, thereby cutting off the flow of culture fluid from reactor 200 into main connecting line 110 via liquid inlet 111. Second valve 150 remains open, and third valve 134 on the remaining sampling branch 130 remains closed. Open air inlet valve 170, and external positive pressure device 300 then introduces filtered, sterile air into main connecting line 110 through first filter 160, creating a slight positive pressure within main connecting line 110. Driven by pump 120, the culture fluid in main connecting line 110 flows entirely back into reactor 200, thereby reducing or eliminating any residual liquid in main connecting line 110.

[0053] The second filter 132 mentioned in this application is operated vertically during use to prevent the culture solution from flowing into it.

[0054] The present invention provides a concept and method for a sterile sampling device and sterile culture equipment. There are many methods and approaches to implement this technical solution. The above is only a preferred embodiment of the present invention. It should be noted that those skilled in the art can make various improvements and modifications without departing from the principles of the present invention, and such improvements and modifications should also be considered within the scope of protection of the present invention. Any components not specified in this embodiment may be implemented using existing technologies.

Claims

1. A sterile sampling device, characterized in that: The aseptic sampling device (100) comprises: A main connecting pipeline (110) is provided with a liquid inlet (111) and a liquid outlet (112), wherein the liquid inlet (111) is used to communicate with a liquid discharge port of a reactor (200), and the liquid outlet (112) is used to communicate with a liquid return port of the reactor (200); a pump (120) is provided on the main connecting pipeline (110); More than one sampling branch (130), respectively connected to the main connecting pipeline (110) in an on-off manner; a first valve (140), the first valve (140) being configured to selectively cut off the flow of the culture solution in the reactor (200) to the main communication pipeline (110) through the liquid inlet (111); a second valve (150), the second valve (150) being configured to selectively cut off the flow of the culture solution in the main communication pipeline (110) to the reactor (200) through the liquid outlet (112); and a first filter (160), one end of which is connected to the main connecting pipe (110) via an air intake valve (170), and the other end of which is used to be connected to an external positive pressure device 300; based on the flow direction of the culture fluid in the main connecting pipe (110), the air intake valve (170) is located downstream of the first filter (160) and upstream of the position where the first sampling branch (130) is connected to the main connecting pipe (110).

2. The aseptic sampling device according to claim 1, characterized in that: Each of the sampling branches (130) comprises a sampling bag (131), a second filter (132) and a sampling pipeline (133); the sampling pipeline (133) connects the sampling bag (131) and the main connecting pipeline (110); one end of the second filter (132) is connected to the sampling bag (131), and the other end is used to connect to an external negative pressure device (400).

3. The aseptic sampling device according to claim 2, characterized in that: Each of the sampling branches (130) comprises a third valve (134), which is arranged on the corresponding sampling pipeline (133). The third valve (134) is used to connect the corresponding sampling branch (130) to the main connecting pipeline (110) in a selectable on-off manner.

4. The aseptic sampling device according to claim 3, characterized in that: The third valve (134) is a pinch valve.

5. A sterile culture device, characterized in that: It comprises a reactor (200) and a sterile sampling device according to any one of claims 1 to 4; the reactor (200) is configured to store culture fluid; the device has an emptying condition; in the emptying condition, the air inlet valve (170) is configured to be turned on, the first valve (140) is configured to cut off the flow of the culture fluid in the reactor (200) to the main connecting line (110), each of the sampling branches (130) is configured to be disconnected from the main connecting line (110), and the pump (120) is configured to provide power to allow the culture fluid in the main connecting line (110) to flow back into the reactor (200).

6. The sterile culture equipment according to claim 5, characterized in that: The reactor (200) is connected to the main connecting pipeline (110) to form a circulation loop; the device has a sampling condition; in the sampling condition, the air inlet valve (170) is configured to be cut off, and the first valve (140) and the second valve (150) are configured to be connected, so that the culture solution in the reactor (200) can flow to the main connecting pipeline (110) through the liquid inlet (111), and the culture solution in the main connecting pipeline (110) flows to the reactor (200) through the liquid outlet (112), and the pump (120) is configured to provide power so that the culture solution flows in the circulation loop.

7. The sterile culture equipment according to claim 5, characterized in that: The device comprises a negative pressure device (400), wherein the negative pressure device (400) is configured to form a negative pressure inside the corresponding sampling bag (131).

8. The sterile culture equipment according to claim 7, characterized in that: The negative pressure device (400) is a vacuum pump.

9. The sterile culture equipment according to claim 5, characterized in that: The device comprises a positive pressure device (300), wherein the positive pressure device (300) is configured to form a slight positive pressure in the main connecting pipeline (110), wherein the slight positive pressure refers to a gas pressure in the main connecting pipeline (110) in the range of 0.01 to 0.02 MPa.

10. The sterile culture equipment according to claim 9, characterized in that: The positive pressure device (300) is a double ball, compressed air or a vacuum pump.

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