Aseptic sampling system

Abstract

The utility model relates to aseptic sampling technical field, concretely relates to a kind of aseptic sampling system, comprising: main liquid inlet pipeline is used to connect fermentation tank;At least two sampling containers, all sampling containers are sequentially connected on the main liquid inlet pipeline;Each sampling container is provided with: liquid inlet and gas outlet;The liquid inlet is communicated by sampling bypass and main liquid inlet pipeline;The gas outlet is communicated gas outlet pipeline;The gas outlet pipeline of all sampling containers is connected pipeline switching unit, and the pipeline switching unit is communicated negative pressure source;First switch valve and quantitative pump are set on the main liquid inlet pipeline and close to fermentation tank position position.The utility model can empty the residual liquid in pipeline, avoid affecting the sampling of next time.Moreover, it can also be quantitative sampling as required, to avoid the waste of sampling liquid.In addition, sampling bag is matched with filter membrane, can be freely switched to two modes of liquid filtration and liquid non-filtering, to adapt to a variety of sampling needs.

Description

Technical Field

[0001] This utility model relates to the field of aseptic sampling technology, specifically to an aseptic sampling system, and in particular to an aseptic sampling system with negative pressure driven cleaning function. Background Technology

[0002] Bio-fermentation is a bioengineering technology that utilizes microorganisms to obtain industrial products. The fermentation process using microorganisms is time-varying, nonlinear, and uncertain, involving the growth, reproduction, and metabolism of living organisms, resulting in highly complex mechanisms. Therefore, real-time monitoring of the bioreaction process within the fermenter is crucial for understanding the metabolic state of the organisms and the quality of the expressed proteins, providing a reference for optimizing the bioreaction process, and preventing the adverse effects of sudden changes in biochemical indicators on the fermentation process.

[0003] Currently, there are two main methods for monitoring biological reaction processes: one is to use a bioreactor. A bioreactor can provide controllable environmental conditions for biological reactions in a biological system. Bioreactors can achieve online detection of conditions such as temperature, pH, and dissolved oxygen. However, its monitoring of biological reaction conditions is usually used when online detection of biochemical parameters cannot be obtained in real time.

[0004] Another method is detection and control through sampling. The traditional sampling method uses multiple sampling bags directly connected to the fermenter for sampling. After sampling with one or more sampling bags at a set time, the sampling bags are removed, and other sampling bags are used for the next sampling. This sampling method results in some liquid remaining in the sampling pipeline after each sampling, which affects the next sampling and the accuracy of the test results.

[0005] It has been reported that high-pressure gases such as compressed air are used outside the tank to drive the liquid in the pipeline, blowing it away from the pipeline to reduce its impact on subsequent sampling. However, in some cases, the detection of certain indicators of the sample may be affected by gases such as compressed air. For example, when certain components in fermentation products or fermentation broth are easily oxidized, the risk of oxidation of the analyte by oxygen in compressed air, thus affecting the accuracy of the test results, cannot be ruled out.

[0006] Therefore, it is necessary to provide a sterile sampling system that can remove residual liquid inside the tube while reducing the impact of the high-pressure gas power source outside the tank on the sample liquid to be tested. Utility Model Content

[0007] The purpose of this invention is to provide a sterile sampling system to solve the technical problems of residual liquid in the sampling tube and the influence of the high-pressure gas power source outside the tank on the sampled liquid in the prior art. Simultaneously, this invention installs a filter with a filter membrane on each sampling bag tube, which can be freely switched between two modes: filtered and unfiltered, depending on the properties of the sampled liquid. Samples requiring filtration can be directly purified for product quality testing after sampling, reducing previous steps such as centrifugation and filtration; samples requiring no filtration can be directly tested for cell or microbial growth, metabolism, and other related indicators.

[0008] Terminology Explanation: Unless otherwise defined, all technical terms in this document have the same meanings as commonly understood by one of ordinary skill in the art to which the subject matter of the claims pertains. Unless otherwise stated, all patents, patent inventions, and publications cited in this document are incorporated herein by reference in their entirety. If multiple definitions exist for terms in this document, the definitions in this chapter shall prevail.

[0009] It should be understood that the above brief description and the following detailed description are exemplary and for illustrative purposes only, and do not limit the subject matter of this utility model in any way. In this utility model, the singular is used in conjunction with the plural unless otherwise specified. It should also be noted that, unless otherwise specified, the use of “or” or “or” means “and / or”. Furthermore, the use of the term “comprising” and other forms such as “including,” “containing,” and “contains” are not limiting.

[0010] To achieve the above objectives, the technical solution of this utility model is as follows: A sterile sampling system, comprising: The main inlet pipeline is used to connect to the fermenter, and the end of the main inlet pipeline is closed; a first switch valve and a metering pump are installed on the main inlet pipeline near the fermenter; A waste liquid bag, wherein the waste liquid bag is connected to the main inlet pipe via a waste liquid pipeline, and a third switch valve is installed on the waste liquid pipeline; At least two sampling containers are connected in series on the main inlet pipeline; Each sampling container is equipped with a liquid inlet and a gas outlet; the liquid inlet is connected to the main liquid inlet via a sampling bypass; the gas outlet is connected to the gas outlet. All sampling containers' vent pipes are connected to a pipe switching unit, which is connected to a negative pressure source. The negative pressure source is connected to a suction circuit, which is connected to the main liquid inlet pipe. The connection point between the suction circuit and the main liquid inlet pipe is located between the metering pump and the first sampling container closest to the fermenter. Both the sampling bypass and the gas outlet pipeline are made of thermoplastic tubing; a second switching valve is also installed on the sampling bypass.

[0011] Furthermore, the pipeline switching unit includes at least one multi-way valve.

[0012] Furthermore, a three-way valve is provided on the sampling bypass; a filter inlet is also provided on the sampling container, and the filter inlet is connected to the three-way valve through a filter pipeline; a filter membrane is provided on the filter pipeline.

[0013] Furthermore, the pore size of the filter membrane is 0.2-5 micrometers.

[0014] Furthermore, the sampling container is a sampling bag.

[0015] Furthermore, an air-permeable filter membrane is provided on the air outlet; and the air outlet is connected to the air outlet pipeline via a sterile connector.

[0016] Furthermore, the aseptic connector is a clamp-type quick-connect fitting or a Luer connector.

[0017] Furthermore, the negative pressure source is a vacuum pump.

[0018] Furthermore, the waste liquid bag is positioned between the first sampling container near the fermenter and the metering pump.

[0019] Furthermore, a filter membrane is provided on the suction circuit.

[0020] Compared with the prior art, the present invention has the following beneficial effects: This invention incorporates a pipeline switching unit on the vent pipe of the sampling bag, connected to a negative pressure source. During sampling, a metering pump is used to measure the liquid flow rate. Once the required sampling volume is reached, the first switching valve is closed, and then negative pressure extraction is performed using the negative pressure source. This allows any remaining liquid in the pipe after the first switching valve to flow into the sampling bag under negative pressure. This effectively clears any residual liquid from the pipe, preventing interference with subsequent sampling. Furthermore, it reduces the sample volume and avoids waste of sampling liquid.

[0021] In addition, this utility model is equipped with a three-way valve on the sampling bypass, which can be used to switch between two modes: liquid filtration and liquid non-filtration. After sampling of samples that need to be filtered, the next purification process can be carried out directly for product quality testing, reducing the previous operation steps such as centrifugation and filtration. After sampling of samples that do not need to be filtered, cell or microbial growth, metabolism and other related indicators can be detected directly, thus adapting to a variety of sampling needs.

[0022] The method for removing residual liquid in this invention does not require external gas, thus avoiding the influence of external gas on the sample liquid. At the same time, the entire process is a closed operation with no external substances entering, avoiding the risk of pipeline contamination. Attached Figure Description

[0023] To more clearly illustrate the technical solutions in the embodiments of this utility model or the prior art, the accompanying drawings used in the description of the embodiments or the prior art will be briefly introduced below.

[0024] Figure 1 This is a schematic diagram of the structure of this utility model.

[0025] Explanation of reference numerals in the attached figures: 1. Main inlet pipe, 2. Sampling bag, 3. Inlet, 4. Outlet, 5. Sampling bypass, 6. Outlet pipe, 7. Pipeline switching unit, 8. Three-way valve, 9. Filter inlet, 10. Filter pipe, 11. Filter membrane, 12. First switch valve, 13. Metering pump, 14. Second switch valve, 15. Ventilation filter membrane, 16. Aseptic connector, 17. Waste bag, 18. Suction circuit, 19. Third switch valve, 20. Breathing valve, 21. Fourth switch valve. Detailed Implementation

[0026] The technical solution of this utility model will be clearly described below with reference to the accompanying drawings. Obviously, the described embodiments are not all embodiments of this utility model. All other embodiments obtained by those skilled in the art without creative effort are within the protection scope of this utility model.

[0027] It should be noted that, unless otherwise specifically stated, the relative arrangement and numerical expressions of the components and steps described in these embodiments should not be construed as limiting the scope of this utility model.

[0028] The following description of exemplary embodiments is merely illustrative and is not intended to limit the present invention or its application or use in any way. Techniques, methods, and apparatus known to those skilled in the art may not be discussed in detail herein, but where applicable, such techniques, methods, and apparatus should be considered part of this specification.

[0029] It should be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the exemplary embodiments according to the present invention. As used herein, the singular form is intended to include the plural form as well, unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0030] For ease of description, the words "up," "down," "left," and "right" appearing in this utility model only indicate that they are consistent with the up, down, left, and right directions of the accompanying drawings. They do not limit the structure and are merely for the purpose of facilitating the description of this utility model and simplifying the description. They do not indicate or imply that the device or component referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on this utility model.

[0031] Terminology Explanation: The terms "installation," "connection," "linking," and "fixing" in this utility model should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral part; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; they can refer to the internal connection of two components or the interaction relationship between two components. For those skilled in the art, the specific meaning of the above terms in this utility model can be understood according to the specific circumstances.

[0032] This embodiment provides a sterile sampling system, such as Figure 1 As shown, it includes: Main inlet pipe 1 is used to connect to the fermenter, and the end of the main inlet pipe 1 is closed; A waste liquid bag 17 is connected to the main inlet pipe 1 via a waste liquid pipeline, and a third switch valve 19 is installed on the waste liquid pipeline; At least two sampling containers are connected in series on the main inlet pipeline 1. Each sampling container is equipped with: a liquid inlet 3 and an air outlet 4; the liquid inlet 3 is connected to the main liquid inlet pipeline 1 through a sampling bypass 5; the air outlet 4 is connected to the air outlet pipeline 6; All the vent pipes 6 of the sampling containers are connected to the pipe switching unit 7, which is connected to the negative pressure source; the negative pressure source is connected to the suction circuit 18, which is connected to the main liquid inlet pipe 1, and the connection point between the suction circuit 18 and the main liquid inlet pipe 1 is located between the metering pump 13 and the first sampling container near the fermenter. A first switching valve 12 and a metering pump 13 are installed on the main liquid inlet pipe near the fermenter; the first switching valve 12 can directly use the sampling valve that is built into the fermenter.

[0033] In this embodiment, the sampling container is a disposable sterile sampling bag. The number of sterile sampling bags can be set according to needs. For example, this embodiment shows a connection diagram of six sampling bags 2. The end of the main inlet pipeline 1 is closed, and the connection between the main inlet pipeline 1 and the sampling bypass 5 is achieved through a four-way valve.

[0034] The pipeline switching unit 7 enables independent switching of each outlet pipeline 6, meaning only one outlet pipeline 6 is connected to the negative pressure source at a time. Specifically, the pipeline switching unit 7 includes at least one multi-way valve. The number of multi-way valves depends on the number of outlet pipelines 6; typically, one sampling bag 2 is connected to one outlet pipeline 6. In this embodiment, the multi-way valve can be a seven-way valve, in which case the pipeline switching unit 7 is a seven-way valve. If, in this embodiment, the multi-way valve is a four-way valve, then the pipeline switching unit 7 includes two four-way valves and one three-way valve. The two four-way valves respectively connect three outlet pipelines 6 to the three-way valve, while the three-way valve connects to both the four-way valve and the negative pressure source.

[0035] In this embodiment, the waste liquid bag 17 is preferably positioned between the first sampling container near the fermenter and the metering pump 13, specifically as follows: Figure 1 As shown, it is installed between the connection point of the suction circuit 18 and the main inlet pipe 1 and the first sampling container. Furthermore, a fourth switch valve 21 is installed on the main inlet pipe 1 downstream of the waste liquid pipe. During the process of waste liquid flowing into the waste liquid bag 17, the fourth switch valve 21 is closed. In this way, waste liquid can be prevented from flowing into the rear end of the main inlet pipe 1, thus reducing the amount of waste liquid.

[0036] In addition, a vent pipe is installed on the waste liquid bag 17, and a breather valve 20 is installed on the vent pipe of the waste liquid bag to prevent the gas in the waste liquid from polluting the outside air.

[0037] For all sampling bags 2 in this embodiment, the sampling bypass 5 connected to the main liquid inlet line 1, the settings on the sampling bypass 5, and the settings on the gas outlet line 6 are all the same. The only difference is the position of the sampling bag 2 and the length of the line. The following is a detailed description of only one sampling line.

[0038] To meet the need for sampling liquids where only the liquid components need to be obtained, a three-way valve 8 is installed on the sampling bypass 5; a filter inlet 9 is also provided on the sampling container, which is connected to the three-way valve 8 via a filter pipeline 10; a filter membrane 11 is installed on the filter pipeline 10. The three-way valve 8 can switch the path of the sampling liquid, thereby achieving unfiltered or filtered sampling. The filter membrane 11 installed on the filter pipeline 10 is set according to the type of fermentation broth and sampling requirements.

[0039] The pore size of the filter membrane 11 is 0.2 micrometers to 5 micrometers, and the specific size can be selected according to the requirements.

[0040] In addition, to facilitate the aseptic removal of the sampling bag 2, both the sampling bypass 5 and the air outlet pipe 6 are made of thermoplastic tubing, which can seal the sampling bag through thermoplastic process; in addition, a second switch valve 14 is also provided on the sampling bypass 5.

[0041] To prevent liquid from entering the venting pipe 6 from the sampling bag 2, a venting filter membrane 15 is provided on the venting port 4; the venting filter membrane 15 is a thin film that allows only gas to pass through but not liquid. Additionally, the venting port 4 is connected to the venting pipe 6 via a sterile connector 16. The sterile connector 16 is a clamp-type quick-connect fitting or a Luer connector.

[0042] The negative pressure source is a vacuum pump. Additionally, a filter membrane 11 is installed in the suction circuit 18 to prevent the suctioned material from affecting the main inlet pipeline.

[0043] In this embodiment, the first switching valve 12, the second switching valve 14, the three-way valve 8, and the multi-way valve included in the pipeline switching unit 7 can be either mechanical valves or solenoid valves. If they are solenoid valves, the first switching valve 12, the second switching valve 14, the three-way valve 8 on the sampling bypass 5, the pipeline switching unit 7, and the metering pump 13 are all connected to an external control module. The control module controls the operating status of the first switching valve 12, the second switching valve 14, the three-way valve 8 on the sampling bypass 5, the pipeline switching unit 7, and the metering pump 13.

[0044] In addition, the main inlet line 1 generally has a larger diameter, while the sampling bypass 5, suction circuit 18, and waste liquid line have smaller diameters. The main inlet line 1 can be a flexible tube with a diameter greater than 6 mm, while the sampling bypass 5, suction circuit 18, and waste liquid line can be thermoplastic tubes with a diameter less than 5 mm. Furthermore, the overall pipeline volume of the suction circuit 18 should be set as small as possible, for example, less than 0.25 ml.

[0045] The working principle of the aseptic sampling system provided by this utility model is as follows: When taking the first sample, select the sampling order from the closest to the fermenter to the furthest from the fermenter. For example, you can select the first sampling bag 2 at the bottom left as the container for the sample liquid. Then, open the second switch valve 14 on the sampling bypass 5 corresponding to the first sampling bag 2 at the bottom left and close the second switch valve 14 on the remaining sampling bypass 5.

[0046] Then, depending on whether the liquid needs to be filtered, switch the three-way valve 8 to the required pipeline. For example, if the sampled liquid does not need to be filtered, the three-way valve 8 will close the corresponding interface of the filter pipeline 10 and open the corresponding pipeline of the liquid inlet 3.

[0047] Then open the first switch valve 12 and the fourth switch valve 21, and start the metering pump 13; then use the pipeline switching unit 7 to switch the passage of the gas outlet pipeline 6 so that only the gas outlet pipeline 6 corresponding to the sampling bag 2 in the lower left corner is connected to the negative pressure source, and the other gas outlet pipelines 6 are disconnected from the negative pressure source; and start the negative pressure source.

[0048] The liquid in the fermenter flows into the sampling bag 2 after passing through the metering pump 13. When the volume of liquid flowing through the metering pump 13 reaches the set volume, the first switch valve 12 is closed.

[0049] Then, the air outlet pipe 6 is suctioned using the principle of negative pressure suction. The main liquid inlet pipe 1, the sampling bypass pipe 5, the sampling bag 2, and the air outlet pipe 6 form a connected closed space. Under the action of negative pressure suction, the suctioned air passes through the suction circuit 18 and the filter membrane 11 on the suction circuit 18 before entering the main liquid inlet pipe 1. The liquid remaining in the main liquid inlet pipe 1 and the sampling bypass pipe 5 is pushed into the sampling bag 2.

[0050] Then, thermoplastic seal is applied between the three-way valve 8 on the sampling bypass 5 and the liquid inlet 3 of the sampling bag 2. At the same time, the filter liquid inlet 9 and the air outlet 4 of the sampling bag 2 are also thermoplastic sealed. The sampling bag 2 is then disconnected from the three-way valve 8 and the air outlet pipe 6, and the sampling bag 2 is removed to complete the first sampling.

[0051] During the next sampling, first close all the second and fourth switch valves 21, open the third switch valve 19, and let some of the liquid between the first switch valve 12 and the fermenter flow into the waste liquid bag 17. Then close the third switch valve 19 and start the second sampling. Perform the same sampling operation to achieve multiple sampling.

[0052] The above specific embodiments are only used to illustrate the technical solution of this utility model and are not intended to limit it. Although this utility model has been described in detail with reference to examples, those skilled in the art should understand that modifications or equivalent substitutions can be made to the technical solution of this utility model without departing from the scope of the technical solution of this utility model, and all such modifications or substitutions should be covered within the scope of the claims of this utility model.

Claims

1. A sterile sampling system, characterized in that, include: The main liquid inlet pipeline is used to connect to the fermenter, and the end of the main liquid inlet pipeline is closed. A first switching valve and a metering pump are installed on the main inlet pipeline near the fermenter. A waste liquid bag, wherein the waste liquid bag is connected to the main inlet pipe via a waste liquid pipeline, and a third switch valve is installed on the waste liquid pipeline; At least two sampling containers are connected in series on the main inlet pipeline; Each sampling container is equipped with a liquid inlet and a gas outlet; the liquid inlet is connected to the main liquid inlet via a sampling bypass; the gas outlet is connected to the gas outlet. All sampling containers' vent pipes are connected to a pipe switching unit, which is connected to a negative pressure source. The negative pressure source is connected to a suction circuit, which is connected to the main liquid inlet pipe. The connection point between the suction circuit and the main liquid inlet pipe is located between the metering pump and the first sampling container closest to the fermenter. Both the sampling bypass and the gas outlet pipeline are made of thermoplastic tubing; a second switching valve is also installed on the sampling bypass.

2. The aseptic sampling system according to claim 1, characterized in that, The pipeline switching unit includes at least one multi-way valve.

3. The aseptic sampling system according to claim 1, characterized in that, A three-way valve is provided on the sampling bypass; a filter inlet is also provided on the sampling container, and the filter inlet is connected to the three-way valve through a filter pipeline; a filter membrane is provided on the filter pipeline.

4. The aseptic sampling system according to claim 3, characterized in that, The pore size of the filter membrane ranges from 0.2 micrometers to 5 micrometers.

5. The aseptic sampling system according to claim 1, characterized in that, The sampling container is a sampling bag.

6. The aseptic sampling system according to claim 1, characterized in that, An air-permeable filter membrane is provided on the air outlet; and the air outlet is connected to the air outlet pipeline through a sterile connector.

7. The aseptic sampling system according to claim 6, characterized in that, The sterile connector is a clamp-type quick-connect fitting or a Luer connector.

8. The aseptic sampling system according to claim 1, characterized in that, The negative pressure source is a vacuum pump.

9. The aseptic sampling system according to claim 1, characterized in that, The waste liquid bag is positioned between the first sampling container near the fermenter and the metering pump.

10. The aseptic sampling system according to claim 1, characterized in that, A filter membrane is installed on the suction circuit.

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