CN214032537U - Alternate tangential flow filtration perfusion culture system - Google Patents
Alternate tangential flow filtration perfusion culture system Download PDFInfo
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- CN214032537U CN214032537U CN202021842811.3U CN202021842811U CN214032537U CN 214032537 U CN214032537 U CN 214032537U CN 202021842811 U CN202021842811 U CN 202021842811U CN 214032537 U CN214032537 U CN 214032537U
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Abstract
The utility model discloses an alternate tangential flow filtered perfusion culture system, which comprises a bioreactor, a TCU system, a feeding system, a gas supply system, an exhaust system, a stirring system, a harvesting pipeline, a sampling system, a CIP system, an SIP system and an automatic control system, wherein the bioreactor is provided with a functional accessory, the outside of the bioreactor is provided with a jacket which is connected with the TCU system, the feeding system, the gas supply system, the exhaust system and the sampling system are all connected to the bioreactor through pipelines, and the stirring system and the harvesting pipeline are arranged at the bottom of the bioreactor; the side wall of the bioreactor is connected with a metabolite discharge system. The utility model discloses a cell sap flows in turn in filter equipment as power realization cell sap in atmospheric pressure and vacuum, has avoided the injury to the cell with the shearing force that the pump produced as power, and the fine protection cell of this kind of power process prevents that the cell from breaking the inside impurity of release cell to increase the pressure of low reaches purification.
Description
Technical Field
The utility model relates to a cell culture system especially relates to a filterable perfusion culture system of tangential flow in turn.
Background
At present, batch culture and fed-batch culture are most widely applied, and perfusion culture can produce products with higher quality and accumulate higher cell concentration than batch fed-batch culture. Perfusion culture techniques are still in the laboratory or pilot plant stage and have not been applied to production on a large scale. The perfusion culture technique is a method of increasing the discharge of harmful metabolites or products on the basis of fed-batch culture. The cell culture mode of supplementing substrates required by cell growth, discharging products produced after cell metabolism or substances harmful to cell growth, and trapping cells in a reactor realizes high-density cell culture and high product yield. Commonly used perfusion culture techniques are: inclined sedimentation, sonic sedimentation, centrifugation, vortex separation, rotary filtration, wave filtration, Tangential Flow Filtration (TFF).
The perfusion culture method firstly pays attention to sterility guarantee and rejection rate, the cell culture process is a sterile culture process, and long-time cell culture can be realized only by guaranteeing sterility. The retention rate is not high and the aim of accumulating high cell density is not achieved. The sterility of the inclined sedimentation is difficult to guarantee, the retention rate of the acoustic sedimentation, the rotary filtration and the vortex separation is not high, and the large-scale application of the inclined sedimentation in perfusion culture is limited. Secondly, shear force, too much shear force can damage cells and affect the activity of the cells. The excessive shearing force of centrifugation also limits the application of the centrifugal force in perfusion culture. There is also concern over long term operation, with wave filtration being less capable. The most promising perfusion culture techniques are Tangential Flow Filtration (TFF) and alternating tangential flow filtration (ATF). In comparison, TFF is more limited in application than ATF. Because TFF has higher shear than ATF, and accumulates lower cell concentration and cell viability, TFF is much poorer in sterility and long-term operation capability than ATF.
TFF requires a pump to provide the motive force for the self-circulation of cellular fluids and therefore also generates relatively large shear forces, which can damage cells or affect their activity, and TFF technology can cause filter membrane clogging during long-term operation. Therefore, the development of a perfusion culture system with alternating tangential flow filtration is a problem to be solved by those skilled in the art.
SUMMERY OF THE UTILITY MODEL
The utility model provides a perfusion culture system with alternative tangential flow filtration, which aims to solve the defects.
The above object of the present invention is achieved by the following technical solutions: a perfusion culture system with alternate tangential flow filtration comprises a bioreactor, a TCU (thermal communication unit) system, a feeding system, an air supply system, an exhaust system, a stirring system, a harvesting pipeline, a sampling system, a CIP (cleaning in place) system, an SIP (session initiation protocol) system and a self-control system, wherein the bioreactor is provided with functional accessories, a jacket is arranged outside the bioreactor and connected with the TCU system, the feeding system, the air supply system, the exhaust system and the sampling system are all connected to the bioreactor through pipelines, and the stirring system and the harvesting pipeline are arranged at the bottom of the bioreactor; the CIP system is connected with a CIP station, and the CIP system, the SIP system and the automatic control system are all connected with the bioreactor, the TCU system, the feeding system, the gas supply system, the exhaust system, the stirring system, the harvesting pipeline and the sampling system; the side wall of the bioreactor is connected with a metabolite discharge system.
Furthermore, the metabolite discharge system comprises a filtering device, a collecting tank, a buffer tank and a control system, the side wall of the bioreactor is connected with the filtering device through a pipeline, the filtering device is divided into two paths to be respectively connected with the collecting tank and the buffer tank, both the collecting tank and the buffer tank are connected with a gas filter, the gas filter is connected with an exhaust port, and a CIP system and an SIP system are connected between the filtering device and the bioreactor; cleaning solution/condensed water outlets are connected between the filtering device and the collecting tank, between the bottom of the buffer solution and between the gas filter and the exhaust port; the control system is connected to and controls valves in the metabolite removal system.
Furthermore, the bioreactor is provided with functional accessories, wherein the accessories comprise one or more of a temperature instrument, a pressure instrument, a pH instrument, a DO instrument, a weighing and metering instrument, a liquid level metering instrument, a defoaming electrode, a liquid level switch, a sight glass, a sight lamp, a mounting device and a spraying ball. These meters or devices are connected to the tank. The instrument accessories directly monitor the relevant data in the tank body and transmit the data to the automatic control system in real time.
Furthermore, the bioreactor is provided with a safety device which is a safety valve or a rupture disk and is used for protecting the tank body and preventing the pressure in the tank from being overhigh. The spraying ball is used for cleaning the inner wall of the tank body.
Furthermore, the TCU system is a temperature control unit, the medium is continuously circulated in the tank jacket and the TCU system through a circulating pump in the TCU system, and the circulating direction is the downward inlet and the upward outlet of the tank jacket. The TCU is typically provided with heating and cooling means for heating/cooling the circulating medium, thus effecting both temperature rise and temperature fall of the bioreactor. The temperature in the bioreactor can be controlled in real time through the automatic control system. Further, the heating and cooling means of the TCU system may be two plate heat exchangers, one for heating the circulating medium and the other for cooling the circulating medium. The other side of the heated plate heat exchanger is heated by industrial steam, and the other side of the cooled plate heat exchanger is cooled by cooling water or chilled water.
Further, the feeding system is filled with a basal medium, inoculation, acid/alkali, defoaming, culture medium, etc., which are all added to the bioreactor through the feeding system at one time or intermittently or continuously. The feeding control generally has a plurality of modes, the feeding with smaller capacity is added to the bioreactor in a mode of a platform scale, a peristaltic pump and four valve banks, and the feeding control is controlled by an automatic control system according to the data feedback of related instruments of the bioreactor. The feed supplement with larger capacity is generally connected to the bioreactor through a feed supplement tank (or a feed supplement bag) by a pipeline, the addition amount of the feed supplement liquid is controlled by a flowmeter and an adjusting valve before entering the bioreactor, and the feed supplement amount is controlled by an automatic control system to control the opening of the adjusting valve through real-time feedback of instrument data of the bioreactor so as to adjust the feed supplement flow.
Further, the gas supply system is a system for introducing gas into the bioreactor, and generally comprises bottom layer aeration and surface layer aeration, wherein the bottom layer aeration comprises a gas distributor (a large bubble distributor and a micro bubble distributor which are connected with an air system outside the bioreactor through pipelines) arranged inside the bioreactor, and mainly comprises introducing gas into the bioreactor and distributing bubbles into the culture solution through the gas distributor. The surface layer is ventilated for maintaining the pressure in the tank body and can be used for pressure conveying of discharging at the end of production. Generally, each ventilation pipeline is provided with an independent gas filter, and the front end of the filter is connected with a gas flow and a regulating valve for controlling the flow of the introduced gas. These gases may be compressed air, oxygen, carbon dioxide, etc. The automatic control system feeds back data of the bioreactor instrument to the air inlet regulating valve and the flowmeter in real time to regulate the flow of the inlet air in real time.
Furthermore, the exhaust system exhausts waste gas generated by cell metabolism in the bioreactor, controls the pressure in the bioreactor through the tail-period regulating valve, and the automatic control system controls the opening of the tail-gas regulating valve through real-time feedback of instrument data of the bioreactor to maintain a constant pressure value in the bioreactor.
Furthermore, the stirring system is used for uniformly mixing various media in the bioreactor, and the uniformity of the temperature in the bioreactor can be maintained through the heat exchange of the jacket, so that the required mass transfer and heat transfer effects are achieved. The automatic control system adjusts the stirring speed in real time according to the data of the bioreactor instrument so as to ensure that the required mass transfer and heat transfer effects are achieved inside the bioreactor, and the data of the instrument is recorded in real time.
Further, the sampling system is used for taking out a small amount of culture solution in the reactor through a sampling device connected to the bioreactor. The method is used for analyzing some indexes off line and indirectly judging the culture state in the reactor.
Further, the CIP system is a pipe and valve integrated into the bioreactor system for cleaning the bioreactor. The CIP system is connected with a CIP station, cleaning liquid is provided to the bioreactor through the CIP station, the inner wall of the tank body of the bioreactor and tank body accessories, stirring, an air supply system, a feeding system, a sampling system, a tail gas system and a harvesting pipeline in the bioreactor all need to be cleaned through the cleaning liquid of the CIP station. This function is achieved by the autonomous system controlling the valve switches of the CIP pipes and the cleaning medium of the CIP system.
Further, the SIP system is related pipes, valves and meters sterilized by pure steam in order to ensure the sterility of the bioreactor, the feeding system, the gas supply system, the exhaust system, the tail gas system and the sampling system. Each cold spot is provided with low spot hydrophobic and temperature probe detection. The SIP process is performed by the autonomous system controlling the associated valve instrumentation.
Furthermore, the automatic control system comprises a software part and a hardware part, wherein the software part comprises a server, an operation station, a PLC, a touch screen, a frequency converter, a valve island and the like, and the electric hardware connects the automatic control upper-layer part with the on-site valve instrument or the stirring part and the like.
Further, the filter device: such as hollow ultrafiltration membrane filtration, the liquid at the upstream end of the membrane flows up and down and the permeate end can flow to a permeate collection tank.
Further, the surge tank and accessories: the liquid in the bioreactor can flow to the buffer tank through the filtering device and also can flow to the bioreactor from the buffer tank. The buffer tank is equipped with high-low liquid Level Switch (LS) and level gauge (LT), and control system passes through the change of LT real-time supervision buffer tank internal liquid level under normal condition, and control system passes through the switching of liquid level data control admission and evacuation. The high liquid level switch is used for interlocking with a valve between the air filter and the buffer tank and is used as double protection to prevent liquid from entering the gas filter due to overhigh liquid level. The low liquid switch interlocks with the buffer tank outlet valve as a double protection preventing gas from entering the filter unit and further into the bioreactor interior.
Further, the air supply system and the air exhaust system: the gas enters the buffer tank through the gas inlet filter, so that the liquid in the buffer tank can be discharged, the gas can be discharged through the gas outlet filter, and meanwhile, the liquid can enter the buffer tank. Realize pressurizeing and exhaust in the buffer tank through the gas filter on the buffer tank, liquid in buffer tank and the filter equipment can flow to bioreactor inside when the pressurization in the buffer tank, can realize liquid in the bioreactor flows to the buffer tank direction when the exhaust in the buffer tank. Thus, the alternating flow of liquid in the filter device can be well controlled by controlling the frequency of pressurizing and exhausting the buffer tank.
Further, the permeate collection device is: when the filter device is filled with liquid, the liquid at the permeation end is collected to a collection tank, and the collection tank can be kept in a negative pressure state in a vacuum pumping mode or the permeation liquid is conveyed from the permeation end of the filter device to the collection tank through a pump. Thus, the discharge of cell metabolites or metabolic wastes inside the bioreactor during perfusion culture is realized.
Compared with the prior art, the utility model the advantage be:
1. the cell sap flows alternately in the filtering device by taking air pressure and vacuum as power, so that the damage of shearing force generated by taking a pump as power to cells is avoided, the cells are well protected by the power process, the cells are prevented from being broken and releasing impurities in the cells, and the pressure of downstream purification is increased.
2. The cell culture fluid flows alternately in the filtering device, so that the problem that the filtering membrane is easy to stack is solved, the cell culture fluid flows continuously and alternately, alternate and reciprocating scouring is formed on the surface of the filtering membrane, and the filtering membrane can be in a good filtering state for a long time.
3. Can be repeatedly used: filter equipment, jar body pipeline all can use stainless steel, through washing liquid washing and pure steam sterilization, realize the used repeatedly of this system.
4. Guarantee of sterile interface: the long-term sterility in the system can be effectively maintained through the gas filter. The gas filter is sterilized with the system prior to use.
Drawings
Fig. 1 is a schematic structural diagram of the present invention.
Detailed Description
The present invention will be described in detail with reference to the accompanying drawings.
As shown in fig. 1, an alternate tangential flow filtration perfusion culture system comprises a bioreactor 1, a TCU system 2, a feeding system 3, a gas supply system 4, an exhaust system 5, a stirring system 6, a harvesting pipeline 18, a sampling system 7, a CIP system 8, an SIP system 9 and an automatic control system 10, wherein the bioreactor 1 is provided with functional accessories, a jacket is arranged outside the bioreactor 1 and connected with the TCU system 2, the feeding system 3, the gas supply system 4, the exhaust system 5 and the sampling system 7 are all connected to the bioreactor 1 through pipelines, and the stirring system 6 and the harvesting pipeline are arranged at the bottom of the bioreactor 1; the CIP system 8 is connected with a CIP station, and the CIP system 8, the SIP system 9 and the automatic control system 10 are all connected with the bioreactor 1, the TCU system 2, the feeding system 3, the gas supply system 4, the exhaust system 5, the stirring system 6, the harvesting pipeline and the sampling system 7; the side wall of the bioreactor 1 is connected with a metabolite discharging system.
Further, the metabolite discharging system comprises a filtering device 11, a collecting tank 14, a buffer tank 12 and a control system 15, the side wall of the bioreactor 1 is connected with the filtering device 11 through a pipeline, the filtering device 11 is divided into two paths to be respectively connected with the collecting tank 14 and the buffer tank 12, the collecting tank 14 and the buffer tank 12 are both connected with a gas filter 13, the gas filter 13 is connected with an exhaust port 16, and a CIP system 8 and an SIP system 9 are connected between the filtering device 11 and the bioreactor 1; a cleaning liquid/condensed water outlet 17 is connected between the filtering device 11 and the collecting tank 14, between the bottom of the buffer solution and between the gas filter 13 and the exhaust port; the control system 15 is connected to and controls valves in the metabolite removal system.
Furthermore, bioreactor 1 is equipped with functional accessories, the accessories include one or more of temperature instrument, pressure instrument, pH instrument, DO instrument, weighing and metering instrument, liquid level metering instrument, defoaming electrode, liquid level switch, sight glass, sight lamp, installation device, spray ball. These meters or devices are connected to the tank. The instrument accessories directly monitor the relevant data in the tank body and transmit the data to the automatic control system 10 in real time.
Further, the bioreactor 1 is provided with a safety device, and the safety device is a safety valve or a rupture disk and is used for protecting the tank body and preventing the pressure in the tank from being too high. The spraying ball is used for cleaning the inner wall of the tank body.
Further, the TCU system 2 is a temperature control unit, and the medium is continuously circulated in the tank jacket and the TCU system 2 through a circulation pump in the TCU system 2, and the circulation direction is downward and upward of the tank jacket. The TCU is typically provided with heating and cooling means for heating/cooling the circulating medium, thus achieving a temperature rise and a temperature drop of the bioreactor 1. The temperature in the bioreactor 1 can be controlled in real time by the automatic control system 10. Further, the heating and cooling means of the TCU system 2 may be two plate heat exchangers, one for heating the circulating medium and the other for cooling the circulating medium. The other side of the heated plate heat exchanger is heated by industrial steam, and the other side of the cooled plate heat exchanger is cooled by cooling water or chilled water.
Further, the feeding system 3 is filled with a basal medium, inoculation, acid/alkali, defoaming, culture medium, etc., which are all added to the bioreactor 1 through the feeding system 3 at one time or intermittently or continuously. The feeding control generally has a plurality of modes, feeding with smaller capacity is added to the bioreactor 1 in a mode of a platform scale, a peristaltic pump and four valve banks, and the feeding control is controlled by an automatic control system 10 according to data feedback of related instruments of the bioreactor 1. The material supplement with large volume ratio is generally connected to the bioreactor 1 through a material supplement tank (or a material supplement bag) by a pipeline, the addition amount of the material supplement is controlled by a flow meter and an adjusting valve before entering the bioreactor 1, and the control of the material supplement amount is realized by an automatic control system 10 through the real-time feedback control of instrument data of the reactor to control the opening of the adjusting valve so as to adjust the material supplement flow.
Further, the gas supply system 4 is a system for introducing gas into the bioreactor 1, and generally includes bottom layer aeration and surface layer aeration, wherein the bottom layer aeration includes a gas distributor (a large bubble distributor and a micro bubble distributor, which are connected with an air system outside the bioreactor 1 through a pipeline) installed inside the bioreactor 1, and mainly introduces gas into the bioreactor 1 and distributes bubbles into the culture solution through the gas distributor. The surface layer is ventilated for maintaining the pressure in the tank body and can be used for pressure conveying of discharging at the end of production. Typically, each vent line is equipped with a separate gas filter 13, the front end of which is connected to a gas flow and regulating valve for controlling the flow of gas introduced. These gases may be compressed air, oxygen, carbon dioxide, etc. The automatic control system 10 feeds back data of the instrument of the bioreactor 1 to the air inlet regulating valve and the flowmeter in real time to regulate the flow of the inlet air in real time.
Further, the exhaust system 5 exhausts the waste gas generated by cell metabolism in the bioreactor 1, controls the pressure inside the bioreactor 1 through a tail gas regulating valve, and the automatic control system 10 controls the opening of the tail gas regulating valve through the instrument data of the bioreactor 1 in real time and maintains a constant pressure value inside the bioreactor 1.
Furthermore, the stirring system 6 is used for uniformly mixing various media in the bioreactor 1, and the uniformity of the temperature in the bioreactor 1 can be maintained through the heat exchange of the jacket, so that the required mass transfer and heat transfer effects are achieved. The automatic control system 10 adjusts the stirring speed in real time according to the data of the instrument of the bioreactor 1, so that the required mass transfer and heat transfer effects inside the bioreactor 1 are achieved, and the data of the instrument is recorded in real time.
Further, the sampling system 7 is used for taking out a small amount of culture solution in the reactor through a sampling device connected to the bioreactor 1. The method is used for analyzing some indexes off line and simply judging the culture state in the reactor.
Further, CIP system 8 is the entire piping and valves within the perfusion culture system for cleaning bioreactor 1. The CIP system 8 is connected with a CIP station, and provides cleaning liquid to the bioreactor 1 through the CIP station, the inner wall of the tank body of the bioreactor 1 and tank body accessories and stirring inside the bioreactor, the gas supply system 4, the feeding system 3, the sampling system 7, the tail gas system and the harvesting pipeline are cleaned through the cleaning liquid of the CIP station. This is accomplished by autonomous system 10 controlling the opening and closing of the valves of the CIP lines and the cleaning medium of CIP system 8.
Further, the SIP system 9 is related pipes, valves and meters sterilized by pure steam in order to ensure the sterility of the bioreactor 1, the feeding system 3, the gas supply system 4, the gas exhaust system 5, the tail gas system and the sampling system 7. Each cold spot is provided with low spot hydrophobic and temperature probe detection. The SIP process is performed by the autonomous system 10 controlling the associated valve meters.
Further, the automatic control system 10 includes a software part and a hardware part, including a server, an operation station, a PLC, a touch screen, a frequency converter, a valve island, etc., wherein the electrical hardware connects the upper part of the automatic control with the on-site valve instrument or stirring, etc., and the subsystems of the bioreactor 1 system are controlled by the automatic control system 10 to operate in order.
Further, the filtering device 11: such as hollow ultrafiltration membrane filtration, the upstream end of the membrane flows up and down and the permeate end can flow to the permeate collection tank 14.
Further, the buffer tank 12 and accessories: the liquid in the bioreactor 1 can flow to the buffer tank 12 through the filtering device 11, and can also flow to the bioreactor 1 from the buffer tank 12. The buffer tank 12 is provided with a high-low liquid Level Switch (LS) and a liquid level meter (LT), the control system 15 monitors the change of the liquid level in the buffer tank 12 in real time through the LT under the normal condition, and the control system 15 controls the switching of air inlet and vacuum pumping through liquid level data. The high level switch is used to interlock with the valve between the air filtration and buffer tank 12 as a double protection against liquid levels entering the gas filter 13 too high. The bottom liquid switch interlocks with the buffer tank 12 outlet valve as a double protection against gas entering the filter unit 11 and the filter further into the interior of the bioreactor 1.
Further, the air supply system 4 and the air discharge system 5: the gas enters the buffer tank 12 through the gas inlet filter, so that the liquid in the buffer tank 12 can be discharged, the gas can be discharged through the gas outlet filter, and meanwhile, the liquid can enter the buffer tank 12. The pressurization and the air discharge in the buffer tank 12 are realized by the gas filter 13 on the buffer tank 12, the liquid in the buffer tank 12 and the filter device 11 flows into the bioreactor 1 when the buffer tank 12 is pressurized, and the liquid in the bioreactor 1 flows towards the buffer tank 12 when the buffer tank 12 is exhausted. This allows for good control of the alternating flow of liquid within the filter unit 11 by controlling the frequency of pressurization and venting of the buffer tank 12.
Further, the permeate collection device is: the permeate side is collected into a collection tank 14 when the filter unit 11 is filled with liquid, and the collection tank 14 may be maintained at a negative pressure by pumping the permeate from the permeate side of the filter unit 11 to the collection tank 14 by vacuum. Thus, the discharge of the cell metabolites or metabolic wastes inside the bioreactor 1 during perfusion culture is realized.
The dashed line in fig. 1 shows the device for discharging the products or harmful metabolites metabolized by the cells in the bioreactor 1 in the perfusion culture technique, and the function is described as follows:
pressurization and vacuum pumping (one or two gas filters 13 may be used herein) in the buffer tank 12 are realized by the gas filter 13 on the buffer tank 12, liquid in the buffer tank 12 and the filtering device 11 flows into the bioreactor 1 when the buffer tank 12 is pressurized, and liquid in the bioreactor 1 flows into the buffer tank 12 when the buffer tank 12 is vacuum pumped. Thus, by controlling the frequency of pressurization and evacuation of the buffer tank 12, the alternating flow of liquid within the filter device 11 can be well controlled. The permeate is collected in the permeate side of the filter device 11 to the collection tank 14 when the filter device is filled with liquid, and the collection tank 14 may be evacuated to maintain a negative pressure state and may be suction filtered to collect permeate (or a pump may be used to pump permeate from the permeate side of the filter device 11 to the collection tank 14). Thus, the discharge of the cell metabolites or metabolic wastes inside the bioreactor 1 during perfusion culture is realized.
The buffer tank 12 is provided with a high-low liquid Level Switch (LS) and a liquid level meter (LT), the control system 15 monitors the change of the liquid level in the buffer tank 12 in real time through the LT under the normal condition, and the control system 15 controls the switching of air inlet and vacuum pumping through liquid level data. The high level switch is used to interlock with the valve between the air filtration and buffer tank 12 as a double protection against liquid levels entering the gas filter 13 too high. The bottom liquid switch interlocks with the outlet valve of the buffer tank 12 as a double protection against gas entering the filter device 11 further into the interior of the bioreactor 1.
The above only is the embodiment of the present invention, not limiting the patent scope of the present invention, all the equivalent structures or equivalent processes that are used in the specification and the attached drawings or directly or indirectly applied to other related technical fields are included in the patent protection scope of the present invention.
Claims (8)
1. An alternate tangential flow filtration perfusion culture system, characterized in that: the system comprises a bioreactor, a TCU system, a feeding system, an air supply system, an exhaust system, a stirring system, a harvesting pipeline, a sampling system, a CIP system, an SIP system and an automatic control system, wherein the bioreactor is provided with functional accessories, a jacket is arranged outside the bioreactor and connected with the TCU system, the feeding system, the air supply system, the exhaust system and the sampling system are all connected to the bioreactor through pipelines, and the stirring system and the harvesting pipeline are arranged at the bottom of the bioreactor; the CIP system is connected with a CIP station, and the CIP system, the SIP system and the automatic control system are all connected with the bioreactor, the TCU system, the feeding system, the gas supply system, the exhaust system, the stirring system, the harvesting pipeline and the sampling system; the side wall of the bioreactor is connected with a metabolite discharge system.
2. An alternate tangential flow filtration perfusion culture system according to claim 1, wherein: the metabolite discharge system comprises a filtering device, a collecting tank, a buffer tank and a control system, wherein the side wall of the bioreactor is connected with the filtering device through a pipeline, the filtering device is divided into two paths and is respectively connected with the collecting tank and the buffer tank, the collecting tank and the buffer tank are both connected with a gas filter, the gas filter is connected with an exhaust port, and a CIP system and an SIP system are connected between the filtering device and the bioreactor; cleaning solution/condensed water outlets are connected between the filtering device and the collecting tank, between the bottom of the buffer solution and between the gas filter and the exhaust port; the control system is connected to and controls valves in the metabolite removal system.
3. An alternate tangential flow filtration perfusion culture system according to claim 1, wherein: the bioreactor is provided with functional accessories, and the accessories comprise one or more of a temperature instrument, a pressure instrument, a pH instrument, a DO instrument, a weighing and metering instrument, a liquid level metering instrument, a defoaming electrode, a liquid level switch, a sight glass, a sight lamp, a mounting device and a spraying ball.
4. An alternate tangential flow filtration perfusion culture system according to claim 1, wherein: the bioreactor is provided with a safety device which is a safety valve or a rupture disk.
5. An alternate tangential flow filtration perfusion culture system according to claim 1, wherein: the TCU system is a temperature control unit, the medium is continuously circulated in the tank jacket and the TCU system through a circulating pump in the TCU system, and the circulating direction is the downward inlet and the upward outlet of the tank jacket.
6. An alternate tangential flow filtration perfusion culture system according to claim 1, wherein: the heating and cooling device of the TCU system is two plate heat exchangers, wherein one plate heat exchanger is used for heating the circulating medium, and the other plate heat exchanger is used for cooling the circulating medium; the other side of the heated plate heat exchanger is heated by industrial steam, and the other side of the cooled plate heat exchanger is cooled by cooling water or chilled water.
7. An alternate tangential flow filtration perfusion culture system according to claim 2, wherein: the filtering device is a hollow ultrafiltration membrane.
8. An alternate tangential flow filtration perfusion culture system according to claim 2, wherein: the buffer tank is equipped with a high-low Level Switch (LS) and a liquid level meter (LT).
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Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113952786A (en) * | 2021-10-21 | 2022-01-21 | 上海艾众生物科技有限公司 | Biological filtration system and control method thereof |
| CN113999767A (en) * | 2021-11-02 | 2022-02-01 | 安及义实业（上海）有限公司 | Stainless steel bioreactor for mammalian cell culture and use method thereof |
| CN116987586A (en) * | 2023-07-28 | 2023-11-03 | 安及义实业（上海）有限公司 | Bioreactor and continuous flow reaction system |
-
2020
- 2020-08-28 CN CN202021842811.3U patent/CN214032537U/en active Active
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113952786A (en) * | 2021-10-21 | 2022-01-21 | 上海艾众生物科技有限公司 | Biological filtration system and control method thereof |
| CN113999767A (en) * | 2021-11-02 | 2022-02-01 | 安及义实业（上海）有限公司 | Stainless steel bioreactor for mammalian cell culture and use method thereof |
| CN116987586A (en) * | 2023-07-28 | 2023-11-03 | 安及义实业（上海）有限公司 | Bioreactor and continuous flow reaction system |
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