Waste liquid collecting device and in-vitro biological reaction system comprising same

Abstract

The utility model provides a waste liquid collecting device and an in vitro biological reaction system comprising the same, which are used for collecting waste liquid in a reaction container and each pipeline, and N is a positive integer; the waste liquid collecting device comprises a collecting box for collecting waste liquid in a centralized manner, a first liquid discharging channel for enabling the waste liquid in the reaction container to enter the collecting box, a second liquid discharging channel which is correspondingly communicated with each pipeline and is used for enabling the waste liquid in the pipeline to enter the collecting box, and a waste liquid discharging pipe for discharging the waste liquid in the collecting box; n is at least 2, one is a feeding pipe, and one is a discharging pipe. Through cooperation of the first liquid discharge channel, the second liquid discharge channel and the collection box, waste liquid in a reaction container and waste liquid in a pipeline can be collected in a centralized mode at the same time, the waste liquid collection efficiency is improved, pollution to the reaction can be avoided by collecting the waste liquid in the pipeline, the quality of produced products is guaranteed, and the production cost is reduced. Classified discharge of waste liquid and subsequent cleaning and sterilization of an in-vitro biological reaction system are facilitated.

Description

TECHNICAL FIELD

[0001] The utility model relates to the field of biological reaction technology especially, a kind of waste liquid collecting device and including its in-vitro biological reaction system. BACKGROUND

[0002] In-vitro biological reaction, such as cell-free in-vitro biosynthesis, obtains the basic components required for transcription and translation in cells, adds DNA templates in vitro to maintain gene transcription, protein translation or metabolic process running, so as to synthesize target products. Cell-free synthetic biology (CFSE) removes cell membranes, can directly regulate internal life activities of cells; remove natural genomes, eliminate unnecessary gene regulation, decouple cell growth and core metabolism regulation; system is open, there is no material transport barrier, easy to add substrate, remove product and monitor and analyze process, has the maximum freedom of engineering, plays an important role in basic disciplines and engineering applications: reveals protein translation mechanism and other life systems; has wide application potential in structural biology, high-throughput screening, biological catalysis, biological medicine and other fields.

[0003] The reaction vessel of the in-vitro biological reaction system in the related art usually includes a reaction vessel and a plurality of pipelines (such as a feed pipe and a discharge pipe) connected with the inside of the reaction vessel, which has a complex structure, and the conventional waste liquid collecting device usually only collects the waste liquid discharged from a total container, and does not collect the waste liquid discharged from the related pipelines. In addition, the existing collection cannot meet the requirements of centralized detection, control, cleaning quality, and classified discharge.

[0004] Therefore, there is still a lack of a waste liquid collecting device suitable for an in-vitro biological reaction system and an in-vitro biological reaction system including the same in the art. UTILITY MODEL CONTENT

[0005] The utility model aims at providing a waste liquid collecting device and an in-vitro biological reaction system including the same, which can meet the requirements of centralized collection and centralized detection of waste liquid of the in-vitro biological reaction system, and can be miniaturized, facilitating complete assembly and use.

[0006] In the first aspect, the utility model provides a waste liquid collecting device applied to an in-vitro biological reaction system, wherein the in-vitro biological reaction system includes a reaction vessel and N pipelines connected with the reaction vessel, and the waste liquid collecting device is used for collecting waste liquid in the reaction vessel and each pipeline, wherein N is a positive integer.

[0007] The waste liquid collecting device comprises a collecting box for collecting waste liquid, a first waste liquid discharge channel for allowing the waste liquid in the reaction container to enter the collecting box, a second waste liquid discharge channel corresponding to each pipeline for allowing the waste liquid in the pipeline to enter the collecting box, and a waste liquid discharge pipe for discharging the waste liquid in the collecting box.

[0008] The N is at least 2, one feeding pipe and one discharging pipe.

[0009] The waste liquid collecting device comprises a collecting box for collecting waste liquid, a first waste liquid discharge channel for allowing the waste liquid in the reaction container to enter the collecting box, a second waste liquid discharge channel corresponding to each pipeline for allowing the waste liquid in the pipeline to enter the collecting box, and a waste liquid discharge pipe for discharging the waste liquid in the collecting box.

[0010] Optionally, in the vertical direction, the height of the waste liquid collecting device is lower than the lowest point of the extracorporeal biological reaction system, the height of the waste liquid discharge pipe is lower than the height of the collecting box, the height of the collecting box is lower than the height of the first waste liquid discharge channel and the height of the second waste liquid discharge channel, preferably, the first waste liquid discharge channel is installed at the lowest point of the reaction container, and / or the second waste liquid discharge channel is installed at the lowest point of the corresponding pipeline.

[0011] Optionally, the first waste liquid discharge channel is not in contact with the waste liquid discharge port of the reaction container; preferably, the first waste liquid discharge channel comprises a waste liquid collector and a first waste liquid discharge pipe.

[0012] The top opening of the waste liquid collector is directly opposite to the liquid outlet of the lowest point of the reaction vessel for receiving the waste liquid discharged from the liquid outlet;

[0013] The bottom opening of the waste liquid collector is connected with the internal space of the collection box through the first liquid outlet pipe;

[0014] And / or a first valve is arranged at the connection between the waste liquid collector and the first liquid outlet pipe; and / or a first valve is arranged at the liquid outlet of the reaction vessel; and / or a first valve is arranged at the connection between each of the N pipes and other equipment outside the reaction vessel, and a first valve is arranged at the connection between each of the N pipes and the second liquid outlet passage corresponding thereto. The beneficial effect is that the first liquid outlet passage is not in contact with the liquid outlet of the reaction vessel for discharging waste liquid, which does not affect the rotation of the reaction vessel, is easy to assemble and combine, and can improve the versatility of the waste liquid collection device.

[0015] Optionally, the waste liquid collector comprises a splash-proof collection opening and a waste liquid buffer zone connected thereto, preferably, the top section of the splash-proof collection opening is larger than the bottom opening of the splash-proof collection opening, and the section of the waste liquid buffer zone is larger than the section of the first liquid outlet pipe. The beneficial effect is that the top section of the splash-proof collection opening is larger than the bottom opening of the splash-proof collection opening, which can prevent the splash of a large amount of waste liquid discharged from the liquid outlet of the reaction vessel from polluting the surrounding environment, and the section of the waste liquid buffer zone is larger than the section of the first liquid outlet pipe, which can buffer the waste liquid when a large amount of waste liquid is discharged from the reaction vessel, thereby avoiding the overflow of the waste liquid directly into the first liquid outlet pipe and improving the stability of the waste liquid collection.

[0016] Optionally, the collection box is provided with a detection module for waste liquid detection, and the detection module is any one or a combination of more than two of a temperature sensor, a flow meter, a pH meter, a turbidity sensor and a conductivity meter. The beneficial effect is that the detection module is any one or a combination of more than two of a temperature sensor, a flow meter, a pH meter, a turbidity sensor and a conductivity meter, which meets different actual needs.

[0017] Optionally, the collection box comprises a cover and a box body;

[0018] The cover and the box body are detachably connected; and / or a sealing ring is arranged at the connection between the cover and the box body. The beneficial effect is that the collection box comprises a cover and a box body; the cover and the box body are detachably connected, which facilitates the installation and maintenance of the collection box, and the sealing ring arranged at the connection between the cover and the box body can improve the sealing performance of the collection box.

[0019] Optionally, the waste liquid discharge pipe comprises a common main pipe and M branch pipes in communication with the common main pipe, wherein M is a positive integer;

[0020] Each branch pipe is provided with a corresponding second valve. Its beneficial effect lies in that, by setting the waste liquid discharge pipe comprising a common main pipe and M branch pipes in communication with the common main pipe, wherein M is a positive integer, and each branch pipe is provided with a corresponding second valve, different waste liquids can be classified and discharged according to actual needs.

[0021] Optionally, it further comprises a cleaning pipe in communication with the reaction container, the feed pipe and the discharge pipe for CIP cleaning, preferably, the communication or closing of the cleaning pipe with the reaction container, the feed pipe and the discharge pipe is controlled by setting the first valve;

[0022] The waste liquid collecting device further comprises a third liquid discharge channel in communication with the cleaning pipe for allowing the waste liquid in the cleaning pipe to enter the collecting box, preferably, the third liquid discharge channel is installed at the lowest point of the cleaning pipe, and / or the communication of the cleaning pipe with the third liquid discharge channel is controlled by setting the first valve. Its beneficial effect lies in that, by setting the cleaning pipe in communication with the reaction container, the feed pipe and the discharge pipe for CIP cleaning, the reaction container, the feed pipe and the discharge pipe can be cleaned to ensure the cleanliness of the reaction container and the pipes after each biological reaction, facilitating the production and use of subsequent products. By setting the third liquid discharge channel and installing it at the lowest point of the cleaning pipe, the waste liquid remaining on the wall of the cleaning pipe during the CIP cleaning process can be collected, avoiding the diffusion of the waste liquid in the cleaning pipe to the inside of the reaction container through the N pipes to affect the product quality.

[0023] Optionally, it further comprises a gas inlet pipe in communication with the reaction container for SIP high-temperature steam sterilization, preferably, the gas inlet pipe is the feed pipe, the discharge pipe or the cleaning pipe, and / or the waste liquid collecting device further comprises a fourth liquid discharge channel in communication with the gas inlet pipe for allowing the waste liquid in the pipe to enter the collecting box. Its beneficial effect lies in that, by separately setting the gas inlet pipe in communication with the reaction container for SIP high-temperature steam sterilization, and configuring the fourth liquid discharge channel in communication with the gas inlet pipe for allowing the waste liquid in the gas inlet pipe to enter the collecting box, the gas inlet pipe can be collected while the reaction container and the N pipes are SIP high-temperature steam sterilized to ensure a sterile environment, or the feed pipe, the discharge pipe or the cleaning pipe can be directly used as the gas inlet pipe, and the waste liquid can be collected by using the corresponding second liquid discharge channel, thereby reducing the complexity of the waste liquid collecting device, improving the utilization rate of the pipes and reducing the cost.

[0024] In the second aspect, the utility model provides a kind of in-vitro biological reaction system, including reaction container and with the reaction container N pipeline of intercommunication, and the waste liquid collecting device of any one possible combination of above-mentioned first aspect.

[0025] The beneficial effects of the second aspect described above can be referred to the description of the first aspect. BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1 The overall structure schematic diagram of a waste liquid collecting device provided by the utility model embodiment is shown in the figure;

[0027] Figure 2 The schematic diagram of explosion structure of a waste liquid collecting device provided by the utility model embodiment is shown in the figure;

[0028] Figure 3 The schematic diagram of principle structure of a waste liquid collecting device provided by the utility model embodiment is shown in the figure;

[0029] Figure 4 The overall structure schematic diagram of in-vitro biological reaction system in an example is shown in the figure;

[0030] Figure 5 The schematic diagram of waste liquid collecting process provided by the utility model embodiment is shown in the figure.

[0031] BRIEF DESCRIPTION OF DRAWINGS

[0032] 1, collection box;2, first drainage channel;3, second drainage channel;4, third drainage channel;5, waste liquid discharge pipe;6, reserved interface;7, detection module;8, in-vitro biological reaction system;

[0033] 11, upper cover;12, box body;13, sealing ring;

[0034] 21, waste liquid collector;22, first drainage pipe;

[0035] 31, feed pipe drainage channel;32, discharge pipe drainage channel;

[0036] 51, common main pipe;52, first branch pipe;53, second branch pipe;54, first branch pipe valve;55, second branch pipe valve;

[0037] 71, temperature sensor;72, flow meter;73, PH meter;74, turbidity sensor;75, conductivity meter;76, controller;

[0038] 81, reaction container;82, slip ring;83, feed pipe;84, discharge pipe. DETAILED DESCRIPTION

[0039] In order to make the purpose, technical scheme and advantages of the utility model clearer, the technical scheme in the utility model embodiment will be clearly and completely described below in combination with the drawings of the utility model. Obviously, the described embodiments are part of the embodiments of the utility model, rather than all the embodiments. Based on the embodiments in the utility model, all other embodiments obtained by those skilled in the art without creative labor belong to the protection scope of the utility model. Unless otherwise defined, the technical terms or scientific terms used herein should be understood as the usual meaning understood by those skilled in the art to which the utility model belongs. The "including" and similar words used in this paper mean that the elements or objects before the word cover the elements or objects listed after the word and their equivalents, without excluding other elements or objects.

[0040] In view of the inconvenience of the current waste liquid collection of the in-vitro biological reaction system, the waste liquid collecting device can meet the centralized collection requirement of the waste liquid of the in-vitro biological reaction system, and can also collect the waste liquid in the pipeline, and can also simultaneously perform cleaning and sterilization treatment, so that pollution to the reaction can be avoided, the quality of the produced product can be ensured, and in addition, the centralized collection facilitates centralized detection and classified discharge of the waste liquid. The technical scheme in the utility model embodiment will be described below in combination with the drawings of the utility model embodiment. In the description of the utility model embodiment, the terms used in the following embodiments are only for the purpose of describing the specific embodiments, and are not intended to be a limitation on the utility model. The singular expression "a", "the", "the", "the" and "this" are intended to also include, for example, the expression "one or more", unless there is clear indication to the contrary in the context. It should also be understood that in the following embodiments of the utility model, "at least one", "one or more" means one or more (including two). The term "and / or" is used to describe the association relationship of the associated objects, which means that there can be three kinds of relationships; for example, A and / or B can represent the following cases: A exists alone, A and B exist simultaneously, and B exists alone, wherein A and B can be singular or plural. The character " / " generally represents that the associated objects before and after are in an "or" relationship.

[0041] Reference to "one embodiment" or "some embodiments" in the present description means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment of the application. The appearances of the phrase "in one embodiment" or "in some embodiments" in various places in the present description are not necessarily all referring to the same embodiment, although it can. The terms "including," "comprising," "having" and variations thereof are meant to encompass the items listed thereafter and equivalents thereof as well as additional items. The terms "connected" and "coupled" are not restricted to direct connections or couplings but include indirect connections or couplings through another component or intervening components. The terms "first," "second," and "third" are used to describe various elements, but can not be understood as indicating or implying relative importance or a number of indicated elements. The term "a number of" means one or more.

[0042] In the present application, "exemplary" or "for example" is used to indicate that the item being described is an example, instance, or illustration. Any embodiment or design solution described as "exemplary" or "for example" in the present application should not be construed as being more preferred or advantageous than other embodiments or design solutions. Rather, "exemplary" or "for example" is simply used to present concepts in a concrete manner.

[0043] As Figure 1As shown, this utility model provides a waste liquid collection device for use in an in vitro bioreactor system. The in vitro bioreactor system includes a reaction vessel (not shown) and N pipes (not shown) connected to the reaction vessel. The waste liquid collection device is used to collect waste liquid from the reaction vessel and each of the pipes. The waste liquid collection device includes a collection box 1 for centralized collection of waste liquid, a first drainage channel 2 for allowing waste liquid from the reaction vessel to enter the collection box 1, a second drainage channel 3 connected to each of the pipes for allowing waste liquid from the pipes to enter the collection box 1, and a waste liquid discharge pipe 5 for discharging waste liquid from the collection box 1. The two pipes are a feed pipe for inputting raw materials required for the bioreactor into the reaction vessel and a discharge pipe for outputting the product after the bioreactor in the reaction vessel. The second drainage channel 3 includes a feed pipe drainage channel 31 (unmarked) and a discharge pipe drainage channel 32 (unmarked). Compared to traditional waste liquid collection devices that can only collect waste liquid inside the reaction vessel and cannot collect waste liquid in the pipelines, and require manual operation to discharge waste liquid into a storage tank, this invention uses a combination of a first drainage channel 2, a second drainage channel 3, and a collection box 1. The first drainage channel 2 collects waste liquid from the reaction vessel, and the second drainage channel 3 collects waste liquid from both pipelines, discharging the waste liquid centrally into the collection box 1. This achieves simultaneous centralized collection of waste liquid from both the reaction vessel and the pipelines, improving waste liquid collection efficiency. Furthermore, collecting waste liquid from the pipelines prevents contamination of the reaction, ensuring the quality of the produced products. It also facilitates the classified discharge of waste liquid and the cleaning and sterilization of the in vitro bioreactor system. It is worth noting that the waste liquid can be generated from different processes, such as waste liquid after a bioreactor (residue or residual product after an in vitro bioreactor), waste liquid generated from CIP cleaning (waste liquid or part of the cleaning solution after cleaning), and waste liquid generated during SIP high-temperature steam sterilization. In this invention, the pipes connected to the reaction vessel refer to pipes and components that come into contact with the products produced in the reaction vessel or that may affect the product quality. The specific number can be adjusted according to actual needs. In one example, there are two pipes connected to the reaction vessel: one for feeding the raw materials used in the reaction and the other for discharging the products after the reaction.

[0044] However, the traditional waste liquid collection usually only sets a liquid outlet at the bottom of the reaction container to discharge the waste liquid in the reaction container and the external pipeline (feeding pipe, discharging pipe), which will cause some problems: on the one hand, due to the actual pipeline layout and product design, the lowest point of the pipeline connected with the reaction container cannot be directly connected with the reaction container, which is easy to cause the waste liquid to remain in the pipeline, on the other hand, although the feeding, discharging, cleaning liquid or pure water can be passed in by using external power (such as pump), but part of the pipeline of the feeding pipe, discharging pipe and cleaning pipe will still have part of the remaining liquid, in addition, due to the liquid surface tension and the attraction between solid-liquid molecules, there is also remaining liquid on the side wall of the pipeline, such as raw material remaining, product remaining after reaction, cleaning liquid remaining, which will affect the cleanliness of the whole extracorporeal biological reaction system. However, the waste liquid collection device of the present application has a collecting channel in the feeding pipe and the discharging pipe, respectively, which can be connected with the lowest point to maximize the discharge of the remaining waste liquid in the pipeline, so as to minimize the influence of the remaining liquid on the reaction.

[0045] In some embodiments, as shown in Figure 1 In order to facilitate the use of gravity to collect the waste liquid in the extracorporeal biological reaction system to the maximum extent and ensure the cleanliness of the extracorporeal biological reaction system, the height of the waste liquid collection device is lower than the lowest point of the extracorporeal biological reaction system in the vertical direction, wherein the height of the waste liquid discharge pipe 5 is lower than the overall height of the collecting box 1, the height of the collecting box 1 is lower than the overall height of the first liquid discharge channel 2 and the overall height of the second liquid discharge channel 3, so that the whole waste liquid collection process is based on gravity, which can discharge the waste liquid in the extracorporeal biological reaction system as much as possible to ensure the cleanliness of the biological reaction system, and the discharge of the waste liquid does not need to use additional power equipment, which will not cause additional energy consumption, energy saving and environmental protection. In some specific embodiments, the first liquid discharge channel 2 receives the waste liquid from the reaction container from the lowest point of the reaction container, that is, the liquid outlet for discharging the waste liquid of the reaction container is located at the lowest point of the reaction container, which can collect the waste liquid in the reaction container to the maximum extent. In another specific embodiment, the second liquid discharge channel 3 is installed at the lowest point of the corresponding pipeline, which can collect the waste liquid in the corresponding pipeline to the maximum extent.

[0046] In some embodiments, as shown in Figure 2 The first liquid discharge channel 2 is not in contact with the liquid outlet of the reaction container for discharging the waste liquid, that is, there is a distance between the waste liquid collector 21 and the liquid outlet, which does not constitute a closed space, the first liquid discharge channel 2 will not affect the rotation of the reaction container, and the closed space is not formed, so that there is a certain buffer space between the waste liquid and the waste liquid collection device, which avoids the overload of the waste liquid collection device caused by too large flow; in addition, due to the non-contact, it is easy to assemble and combine, which improves the versatility of the waste liquid collection device 。In some specific embodiments, the first liquid discharge channel 2 comprises a waste liquid collector 21 and a first liquid discharge pipe 22; the top opening of the waste liquid collector 21 is directly opposite to the liquid discharge port of the lowest point of the reaction container for receiving the waste liquid discharged from the liquid discharge port; the bottom opening of the waste liquid collector 21 is connected to the internal space of the collection box 1 through the first liquid discharge pipe 22. In some specific embodiments, the waste liquid collector 21 comprises a splash-proof collection port and a waste liquid buffer zone connected thereto, preferably, in order to prevent the splash of a large amount of waste liquid discharged from the liquid discharge port of the reaction container, causing pollution to the surrounding environment, in order to be able to buffer the waste liquid when a large amount of waste liquid is discharged from the reaction container, avoiding the waste liquid overflow directly into the first liquid discharge pipe 22, improving the stability of waste liquid collection, the top section size of the splash-proof collection port is larger than the bottom opening of the splash-proof collection port, and the section size of the waste liquid buffer zone is larger than the section size of the first liquid discharge pipe 22. For example, as shown in Figure 2 , the splash-proof collection port is a tapered port with a large top and a small bottom, having good splash-proof effect; and the waste liquid buffer zone is a columnar shape, capable of buffering a large amount of waste liquid.

[0047] In some embodiments, as shown in Figure 3 , in order to meet different actual needs, the collection box 1 is provided with a detection module 7 for waste liquid detection, the detection module 7 being any one or a combination of two or more of a temperature sensor 71, a flow meter 72, a PH meter 73, a turbidity sensor 74 and a conductivity meter 75. For example, as shown in Figure 2 and Figure 3 , the box body 12 of the collection box 1 is provided with a plurality of reserved interfaces 6 for mounting and connecting the detection module 7, the detection module 7 comprising a built-in controller 76, which is electrically connected to the temperature sensor 71, the flow meter 72, the PH meter 73, the turbidity sensor 74 and the conductivity meter 75, respectively, for data analysis. It should be noted that the specific sensors included in the detection module 7 can be selected to be arranged inside or outside the collection box 1 according to actual needs, and the connection mode can be fixed connection (such as welding) or detachable connection (using thread, clamping and other detachable connection modes).

[0048] In other embodiments, as shown in Figure 2 , in order to facilitate the installation and maintenance of the collection box 1, the collection box 1 comprises an upper cover 11 and a box body 12; the upper cover 11 and the box body 12 are detachably connected (using thread, clamping and other detachable connection modes). In some specific embodiments, as shown in Figure 2 , in order to improve the sealing performance of the collection box 1, a sealing ring 13 is installed at the connection between the upper cover 11 and the box body 12.

[0049] In some embodiments, in order to be able to classify and discharge different waste liquid according to actual needs, the waste liquid discharge pipe 5 comprises a common main pipe and M branch pipes in communication with the common main pipe, wherein M is a positive integer; a corresponding second valve is arranged on each branch pipe: for example, as shown in Figure 2 , M is 2, that is, the waste liquid discharge pipe 5 comprises a common main pipe 51, two branch pipes (a first branch pipe 52 and a second branch pipe 53), a first branch pipe valve 54 (that is, a second valve corresponding to the first branch pipe 52) installed on the first branch pipe 52, and a second branch pipe valve 55 (that is, a second valve corresponding to the second branch pipe 53) installed on the second branch pipe 53.

[0050] In some embodiments, as shown in Figure 1 , in order to ensure the cleanliness of the reaction vessel and the pipes after each biological reaction and facilitate the production and use of subsequent products, the waste liquid collecting device further comprises a cleaning pipe in communication with the reaction vessel, the feed pipe and the discharge pipe respectively for CIP cleaning; in order to collect the waste liquid remaining on the wall of the cleaning pipe during the CIP cleaning process and avoid the waste liquid in the cleaning pipe from diffusing into the reaction vessel through the N pipes to affect the product quality, the waste liquid collecting device further comprises a third liquid discharge channel 4 in communication with the cleaning pipe for allowing the waste liquid in the cleaning pipe to enter the collecting box 1.

[0051] In some specific embodiments, by means of different first valve settings and control of the related first valves, the needs of any one process or combination of CIP and SIP after reaction discharge can be met:

[0052] A first valve is arranged at the connection between the waste liquid collector 21 and the first liquid discharge pipe 22;

[0053] A first valve is arranged at the liquid discharge port of the reaction vessel, and by closing or opening the first valve, the reaction vessel can be cut off or connected with the atmospheric environment;

[0054] A first valve is arranged at the end of each of the N pipes in communication with other equipment outside the reaction vessel, and a first valve is arranged at the connection between each of the N pipes and the corresponding second liquid discharge channel 3, and by closing or opening these first valves, the pipes in communication with the reaction vessel can be cut off or connected with the above-mentioned other equipment and the corresponding second liquid discharge channel 3: for example, when the pipes in communication with the reaction vessel are the feed pipe and the discharge pipe, a first valve is arranged at the end of the feed pipe in communication with the raw material supply device, and a first valve is arranged at the end of the discharge pipe in communication with the discharge collection device;

[0055] A first valve is further arranged at the end of each of the reaction vessel, the feed pipe and the discharge pipe in communication with the cleaning pipe;

[0056] The end of the cleaning pipe connected with the third liquid discharge channel 4 is provided with a first valve.

[0057] The cleaning pipe is further provided with a first valve for communicating with the cleaning liquid.

[0058] In some specific embodiments, the third liquid discharge channel 4 is installed at the lowest point of the cleaning pipe.

[0059] In some specific embodiments, as shown in Figure 1 In order to collect the waste liquid by the second liquid discharge channel 3, the complexity of the waste liquid collecting device is reduced, the utilization rate of the pipeline is improved, and the cost is reduced. The gas inlet pipe is designed as a feeding pipe, a discharging pipe or a cleaning pipe. In another specific embodiment, in order to facilitate the waste liquid collection of the gas inlet pipe while ensuring the sterile environment of the SIP high-temperature steam sterilization of the reaction container and the N pipelines, the waste liquid collecting device further comprises a gas inlet pipe connected with the reaction container for the SIP high-temperature steam sterilization and the inlet of steam. The waste liquid collecting device further comprises a fourth liquid discharge channel corresponding to the gas inlet pipe for allowing the waste liquid in the gas inlet pipe to enter the collecting box 1. When the gas inlet pipe is provided, the end of the gas inlet pipe connected with the fourth liquid discharge channel is further provided with a first valve, and the gas inlet pipe is further provided with a first valve for communicating with the steam. The CIP cleaning and waste liquid discharge process of the gas inlet pipe is the same as that of the feeding pipe, the discharging pipe or the cleaning pipe.

[0060] In addition, in some examples, the reaction container of the in-vitro biological reaction system needs to rotate during the reaction. Therefore, as shown in Figure 4 In a specific example, the in-vitro biological reaction system 8 comprises a slip ring 82 arranged on a sealing end cover of a reaction container 81, a feeding pipe 83 and a discharging pipe 84 connected with the slip ring 82 and located outside the reaction container 81. The slip ring 82 has at least one passage for transmitting liquid medium, i.e. one corresponding interface on the rotor and the stator to communicate with the rotating reaction container 81 and the pipeline (feeding pipe 83, discharging pipe 84) located outside the reaction container 81 and static, thereby realizing the communication between the rotating reaction container 81 and the external pipeline. In an example, the reaction container 81 can further be provided with a pipeline connected with the feeding pipe and the discharging pipe, respectively, to feed or discharge through the connected pipeline.

[0061] In addition, in order to prevent the raw material in the reaction container from entering the feeding pipe or the discharging pipe during the reaction, a third valve is arranged at the end of the feeding pipe and the discharging pipe connected with the reaction container.

[0062] An exemplary overall working process and principle of the present application are as follows:

[0063] 1. Waste liquid collection after in-vitro biological reaction

[0064] Firstly, the raw materials required for the reaction are introduced into the reaction vessel through the feed pipe, and then the first valve is closed (if there is a third valve, the third valve is also closed). After the reaction is completed, the first valve on the discharge pipe is opened, and the product after the reaction is discharged from the reaction vessel through the discharge pipe. After the discharge is completed, the first valve on the liquid outlet, the first valve at the connection between the waste liquid collector 21 and the first discharge pipe 22, and the first valve of the N pipelines each connected to the second discharge passage 3 are opened. The waste liquid in the reaction vessel sequentially passes through the waste liquid collector 21 and the first discharge pipe 22 into the collection box 1 under the action of gravity. The waste liquid in each pipeline enters the collection box 1 through the second discharge passage 3 connected thereto. At this time, the detection module 7 detects the waste liquid, and the controller 76 generates a detection result and controls the corresponding branch pipe valve (the first branch pipe valve 54 and the second branch pipe valve 55) to open the corresponding branch pipe (the first branch pipe 52 and the second branch pipe 53) for discharge based on the detection result.

[0065] 2. Collection of waste liquid generated by CIP cleaning

[0066] After the waste liquid remaining after the current reaction is collected, the valves of the feed pipe and the discharge pipe connected to the raw material supply and the discharge collection are closed (if there is an air inlet pipe, the valve of the air inlet pipe connected to the steam is also closed). All the remaining first valves are kept open. The pump is used to introduce cleaning liquid / pure water into the reaction vessel and each pipeline through the cleaning pipe, so as to perform CIP cleaning on the reaction vessel and the pipelines. The waste liquid generated by the cleaning is concentrated into the collection box 1 through the first discharge passage 2 and the second discharge passage 3, and the waste liquid in the cleaning pipe (such as the cleaning liquid / pure water remaining on the side wall) is introduced into the collection box 1 through the third discharge passage 4 (for the same reason, the waste liquid in the air inlet pipe is introduced into the collection box through the fourth discharge passage) to achieve maximum cleaning and ensure the quality of the subsequent production products. At this time, the detection module 7 detects the waste liquid, and the controller 76 generates a detection result and controls the corresponding branch pipe valve (the first branch pipe valve 54 and the second branch pipe valve 55) to open the corresponding branch pipe (the first branch pipe 52 and the second branch pipe 53) for discharge based on the detection result. It is worth noting that the introduction of cleaning liquid / pure water during CIP cleaning requires external power (such as a pump), but the discharge of waste liquid generated by cleaning can be based on gravity alone. In addition, a pipeline is also arranged in the reaction vessel 81 to be connected to the feed pipe and the discharge pipe, respectively. For example, the cleaning liquid is introduced into the feed pipe or the discharge pipe, and part of the cleaning liquid is diverted into the connecting pipeline, so that the connecting pipeline can also be cleaned.

[0067] 3. Collection of waste liquid generated by SIP high-temperature steam sterilization

[0068] After CIP cleaning, SIP high-temperature steam sterilization can be performed according to actual needs to ensure the cleanliness of the extracorporeal biological reaction system. As described above, the SIP inlet pipe can be separately provided or directly use one or more of the feed pipe, the discharge pipe or the cleaning pipe as the steam inlet pipe. The process is as follows:

[0069] Before the steam is introduced, all the second valves, the first valves on the liquid discharge ports, the first valves on the cleaning pipes connected to the cleaning liquid, and the first valves on all the pipes (feed pipes, discharge pipes) connected to the reaction vessels and the above-mentioned other equipment are closed. The first valves on all the pipes connected to the reaction vessels and connected to the second liquid discharge channel 3 are opened, the first valves on the cleaning pipes and the third liquid discharge channel 4 are opened, and the first valves on the reaction vessels, the feed pipes and the discharge pipes and the cleaning pipes are opened. Thus, the reaction vessels, all the pipes connected to the reaction vessels, the cleaning pipes, the first liquid discharge channel 2, the second liquid discharge channel 3, the third liquid discharge channel 4, the collection box 1 and the common main pipe 51 form a closed space. Steam is introduced into the closed space through the feed pipe, the discharge pipe or the cleaning pipe to increase the pressure and sterilize the closed space. After sterilization and pressure relief, the first valves on the liquid discharge ports are opened, and the other valves remain unchanged. The waste liquid generated by SIP is collected into the collection box 1 through the first liquid discharge channel 2, the second liquid discharge channel 3 and the third liquid discharge channel 4. At this time, the detection module 7 detects the waste liquid, and the controller 76 generates a detection result and controls the corresponding branch pipe valve (the first branch pipe valve 54, the second branch pipe valve 55) to open the corresponding branch pipe (the first branch pipe 52, the second branch pipe 53) for discharge based on the detection result of the detection module 7. The corresponding second valve is opened to discharge the waste liquid based on the detection result of the detection module 7. It should be noted that the pressurization and pressure relief are achieved by the pressure control system of the extracorporeal biological reaction system. The external environment can be the external atmosphere, such as the connection between the feed inlet of the feed pipe, the discharge outlet of the discharge pipe and the liquid discharge port of the reaction vessel. It can also be the connection between itself and the adjacent equipment. It should be understood that all the pipes can include the cleaning pipe or not. However, when the cleaning pipe for CIP cleaning is provided, the sterilization of the closed space needs to include the cleaning pipe during SIP high-temperature steam sterilization, otherwise it does not need to include the cleaning pipe.

[0070] As shown in Figures 1-4 Based on the above-mentioned waste liquid collection device, the utility model also provides an extracorporeal biological reaction system 8, including the slip ring 82 which is arranged on the sealed end cover of the reaction vessel 81, the feed pipe 83 and the discharge pipe 84 which are communicated with the slip ring 82 and located outside the reaction vessel 81, and the waste liquid collection device.

[0071] As shown in Figures 1-4 Based on the above-mentioned waste liquid collection device and extracorporeal biological reaction system, as shown in Figure 5As shown, the waste liquid collection process of the above in-vitro biological reaction system is as follows:

[0072] S101, using the collection box 1 to collect the waste liquid in the reaction vessel and the pipeline internal space connected with the reaction vessel through the first liquid discharge channel 2 and the second liquid discharge channel 3 respectively.

[0073] S102, using the detection module 7 to detect the waste liquid to obtain a detection result.

[0074] S103, based on the detection result, using the waste liquid discharge pipe 5 to discharge the waste liquid in the collection box 1.

[0075] Among them, the waste liquid includes one or more than two of the waste liquid after biological reaction, the waste liquid generated by CIP cleaning and the waste liquid generated in the SIP high-temperature steam sterilization process, which realizes the centralized collection, centralized detection and classified discharge of the waste liquid in the reaction, cleaning and sterilization and other processes. Not only improves the production efficiency, but also can ensure the cleanliness of the entire in-vitro biological reaction system after each reaction, and is convenient to ensure the quality of the subsequent processing products.

[0076] In some embodiments, in order to improve the overall cleanliness, it also includes: after biological reaction or CIP cleaning, opening the first valve arranged at the liquid discharge port of the reaction vessel, the first valve of the first liquid discharge channel 2 (i.e. the first valve at the connection between the waste liquid collector 21 and the first liquid discharge pipe 22) and the first valve of each of the N pipelines connected with the second liquid discharge channel 3 (when CIP cleaning, the first valve of the cleaning pipe connected with the third liquid discharge channel also needs to be opened), the waste liquid in the reaction vessel and the N pipelines after biological reaction or CIP cleaning enters the collection box 1 from the first liquid discharge channel 2 and the second liquid discharge channel 3 (when CIP cleaning, the waste liquid (such as the cleaning liquid / pure water remaining on the side wall) in the cleaning pipe enters the collection box 1 through the third liquid discharge channel 4), using the detection module 7 to detect the waste liquid in the waste liquid collection box 1, and based on the detection result of the detection module 7, opening the corresponding second valve to discharge the waste liquid. It is worth noting that the first valve of the cleaning pipe connected with the third liquid discharge channel can also be opened or closed after biological reaction.

[0077] In some other embodiments, in order to maximize the sterilization effect of the SIP, when the SIP is subjected to high-temperature steam sterilization, all the second valves, the first valve on the liquid outlet, the first valve on the cleaning pipe for connecting the cleaning liquid, and the first valves on all the pipes connected to the reaction vessel (the feeding pipe and the discharging pipe) for connecting the above-mentioned other devices are closed, all the first valves on the pipes connected to the reaction vessel for connecting the second liquid outlet channel 3, the first valve on the cleaning pipe for connecting the third liquid outlet channel 4 are opened, and the first valves respectively arranged on the reaction vessel, the feeding pipe and the discharging pipe for connecting the cleaning pipe are opened, so that the reaction vessel, all the pipes connected to the reaction vessel, the cleaning pipe, the first liquid outlet channel 2, the second liquid outlet channel 3, the third liquid outlet channel 4, the collection box 1 and the common main pipe 5 together form a closed space, steam is introduced into the closed space through the feeding pipe, the discharging pipe or the cleaning pipe, and the pressure is increased to sterilize the closed space by high-temperature steam, and after sterilization, the first valve on the liquid outlet is opened, and the states of the other valves remain unchanged, the waste liquid generated by the SIP is collected into the collection box 1 through the first liquid outlet channel 2, the second liquid outlet channel 3 and the third liquid outlet channel 4, the detection module 7 is used to detect the waste liquid in the collection box 1, and based on the detection result of the detection module 7, the corresponding second valve is opened to discharge the waste liquid. It is worth noting that when the cleaning pipe for CIP cleaning is arranged, the closed space formed by the SIP high-temperature steam sterilization needs to include the internal space of the cleaning pipe, and before sterilization, the first valve on the cleaning pipe for connecting the external environment needs to be closed, and after sterilization, the first valve at the connection between the third liquid outlet channel 4 and the cleaning pipe is opened, so that the waste liquid in the cleaning pipe enters the collection box 1 through the third liquid outlet channel 4.

[0078] In yet some embodiments, to ensure the sterilization effect of the SIP, further comprising: detecting the temperature in the collection box 1 during the SIP high-temperature steam sterilization process by the temperature sensor 71 to monitor the temperature required by the waste liquid collection device SIP, for example, only when the temperature sensor 71 detects that the temperature reaches a set threshold value during the SIP process or reaches the set threshold value and lasts for a certain time, it is preliminarily considered that the SIP process is normal, and it is specifically required to further detect the conductivity parameter to determine the cleanliness; and / or any one or more of the following: due to the difference of actual production environment, the amount of waste liquid generated instantaneously during CIP cleaning is large, and the traditional waste liquid collection device is prone to overflow, which pollutes the production environment, in order to improve the application range of the waste liquid collection device, the flow meter 72 is used to detect the flow of waste liquid flowing into and out of the collection box 1, and the flow of waste liquid flowing into or out of the collection box 1 is adjusted based on the detection result to adapt to the drainage amount requirement of different in-vitro biological reaction systems; in order to facilitate the recycling and treatment of waste liquid, the pH meter 73 is used to detect the pH value of the waste liquid in the collection box 1, and the waste liquid is classified and discharged based on the detection result, for example, the waste liquid with a pH value within a set range is discharged through the first branch pipe 52, and the waste liquid with a pH value not within the range is discharged through the second branch pipe 53; in order to ensure the smoothness of waste liquid discharge, avoid blockage and overflow, and determine the cleanliness of the in-vitro biological reaction system and the waste liquid collection device after CIP cleaning based on the detection result, ensure the cleaning effect of CIP, the turbidity sensor 74 is used to detect the turbidity of the waste liquid in the collection box 1, and the flow of waste liquid flowing into or out of the collection box 1 is adjusted based on the detection result, and the cleanliness of the in-vitro biological reaction system and the waste liquid collection device after CIP cleaning is determined based on the detection result; in order to determine whether the subsequent product production needs can be met after cleaning and sterilization, the conductivity meter 75 is used to detect the conductivity of the waste liquid in the collection box 1, and the cleanliness of the in-vitro biological reaction system and the waste liquid collection device after CIP cleaning and SIP high-temperature steam sterilization is determined based on the detection result.

[0079] The above only describes the embodiments of the present application, and does not limit the patent range of the present application, and any equivalent transformation or direct or indirect application in related technical fields based on the content of the present application is also included in the patent protection range of the present application.

Claims

1. A waste liquid collecting device applied to an in-vitro biological reaction system, the in-vitro biological reaction system comprising a reaction container and N pipelines in communication with the reaction container, characterized in that, The waste liquid collecting device is used for collecting waste liquid in the reaction container and in each of the pipelines, wherein N is a positive integer; The waste liquid collecting device comprises a collecting box for collecting waste liquid, a first waste liquid discharge channel for allowing waste liquid in the reaction container to enter the collecting box, a second waste liquid discharge channel corresponding to each of the pipelines for allowing waste liquid in the pipeline to enter the collecting box, and a waste liquid discharge pipe for discharging waste liquid in the collecting box; N is at least 2, one feeding pipe and one discharging pipe.

2. The apparatus of claim 1, wherein, In the vertical direction, the height of the waste liquid collecting device is lower than the lowest point of the in-vitro biological reaction system, the height of the waste liquid discharge pipe is lower than the height of the collecting box, and the height of the collecting box is lower than the height of the first waste liquid discharge channel and the height of the second waste liquid discharge channel.

3. The apparatus of claim 1 or 2, wherein, The first waste liquid discharge channel is not in contact with the waste liquid discharge port of the reaction container.

4. The apparatus of claim 3, wherein, The first waste liquid discharge channel comprises a waste liquid collector and a first waste liquid discharge pipe; the waste liquid collector comprises a splash-proof collecting port and a waste liquid buffer zone in communication.

5. The apparatus of claim 1, wherein, The collecting box is provided with a detection module for detecting waste liquid, and the detection module is any one or a combination of two or more of a temperature sensor, a flow meter, a pH meter, a turbidity sensor and a conductivity meter.

6. The apparatus of claim 1, wherein, The collecting box comprises a cover and a box body. The cover and the box body are detachably connected.

7. The apparatus of claim 1, wherein, The waste liquid discharge pipe comprises a common main pipe and M branch pipes in communication with the common main pipe, wherein M is a positive integer; Each branch pipe is provided with a corresponding second valve.

8. The apparatus of claim 1, wherein, Further comprising a cleaning pipe in communication with the reaction container, the feeding pipe and the discharging pipe respectively for CIP cleaning.

9. The apparatus of claim 1, wherein, Further comprising a gas inlet pipe in communication with the reaction container for introducing steam for SIP high-temperature steam sterilization.

10. The apparatus of claim 2, wherein, The first waste liquid discharge channel is installed at the lowest point of the reaction container; and / or the second waste liquid discharge channel is installed at the lowest point of the corresponding pipeline.

11. The apparatus of claim 4, wherein, The top opening of the waste liquid collector is directly opposite the waste liquid discharge port of the lowest point of the reaction container for receiving waste liquid discharged from the waste liquid discharge port; The bottom opening of the waste liquid collector is in communication with the internal space of the collecting box through the first waste liquid discharge pipe.

12. The apparatus of claim 11, wherein, The connection between the waste liquid collector and the first waste liquid discharge pipe is provided with a first valve; and / or the waste liquid discharge port of the reaction container is provided with a first valve; and / or the connection between each of the N pipelines and other equipment outside the reaction container is provided with a first valve, and the connection between each of the N pipelines and the corresponding second waste liquid discharge channel is provided with a first valve.

13. The apparatus of claim 4, wherein, The top cross-sectional size of the splash-proof collecting port is greater than the bottom opening of the splash-proof collecting port, and the cross-sectional size of the waste liquid buffer zone is greater than the cross-sectional size of the first waste liquid discharge pipe.

14. The apparatus of claim 8, wherein, The communication or closure of the cleaning pipe with the reaction container, the feeding pipe and the discharging pipe is controlled by setting the first valve. The waste liquid collecting device further comprises a third waste liquid discharge channel in communication with the cleaning pipe for allowing waste liquid in the cleaning pipe to enter the collecting box.

15. The apparatus of claim 14, wherein, The third waste liquid discharge channel is installed at the lowest point of the cleaning pipe, and / or the communication between the cleaning pipe and the third waste liquid discharge channel is controlled by setting the first valve.

16. The apparatus of claim 9, wherein, The gas inlet pipe is a feed pipe, a discharge pipe or a cleaning pipe, and / or the waste liquid collecting device further comprises a fourth liquid discharge channel in communication with the gas inlet pipe for allowing the waste liquid in the gas inlet pipe to enter the collecting box.

17. The apparatus of claim 6, wherein, A sealing ring is arranged at the connection between the upper cover and the box body.

18. An in vitro bioreaction system, comprising: The waste liquid collecting device is arranged in a reaction container and N pipes in communication with the reaction container, and the waste liquid collecting device is as claimed in any one of claims 1-17.

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