Full-automatic virus inactivation system for liquid biological products

Abstract

The invention provides a liquid biological product full-automatic virus inactivation system which comprises a horizontal track, a first mechanical arm arranged on the horizontal track in a sliding manner, and a light-transmitting container fixedly connected with the tail end of the first mechanical arm, the filling area is used for filling liquid biological products into the light-transmitting container, the ultraviolet irradiation area is provided with an ultraviolet lamp, the collecting area is used for collecting the liquid biological products in the light-transmitting container, the cleaning area is used for cleaning the light-transmitting container, and the console is provided with a numerical control system and a human-computer interaction interface. The biological activity and the recovery rate of the liquid biological product can be reserved to the maximum extent while the virus inactivation effect is guaranteed, and the device has the advantages of being high in automation degree, easy to clean and maintain and the like, and has the great application range and market prospect.

Description

Technical Field

[0001] The present invention belongs to the technical field of virus inactivation, and particularly relates to a fully automatic virus inactivation system for liquid biological products. Background Art

[0002] In the biotech industry, with the increasing variety of biological products and the expanding population using them, the risks of animal-derived virus infection of humans and potential iatrogenic infections have become increasingly prominent. According to the requirements of the "Regulations on the Administration of Drug Registration", products extracted from human or animal tissues or body fluids, animal-derived monoclonal antibodies, and recombinant products expressed by eukaryotic cells need to add data on the verification of virus inactivation processes. Traditional virus inactivation processes include low pH method, organic solvent / detergent (S / D) method, nanofiltration method, chromatography method, pasteurization method, etc. These methods have problems such as high cost, only being effective against lipid-enveloped viruses, genotoxicity, and the optimal inactivation conditions changing with the composition of biological products. In contrast, ultraviolet inactivation of microorganisms is a pure physical disinfection method, which has the advantages of simplicity, convenience, broad spectrum, high efficiency, no secondary pollution, easy management, and automation. The principle of ultraviolet disinfection and sterilization is that light damage causes the formation of abnormal chemical bonds between adjacent pyrimidine molecules in DNA or RNA of microbial cells such as bacteria and viruses, thereby hindering the replication of DNA or RNA and achieving the inactivation of bacteria and viruses.

[0003] With the continuous development of methods and devices for virus inactivation of biological products using the ultraviolet principle, external forces such as centrifugation are used to thin the liquid layer thickness to ensure sufficient effective ultraviolet irradiation, so as to increase the ultraviolet penetration and effectively inactivate viruses. However, due to the laws of hydrodynamics, during the process of processing a large number of biological samples by the centrifugation method, the liquid layer thickness is uneven, and at the same time, the sample denaturation and adhesion to the drum wall will cause parameter changes and the change of liquid flow rules. These factors will affect the ultraviolet dose received by the sample and the activity retention of the sample in the later stage of long-term use. In addition, for example, a device that uses a fixed quartz tube and flowing samples to receive ultraviolet irradiation, although it can coat a high molecular material with anti-protein adhesion on the inner surface to reduce protein denaturation and adhesion, this method cannot avoid the problem of laminar flow of the sample in a fixed container. Laminar flow will cause the sample flow rate near the container edge to be slow, making it easier to denature and adhere to the tube wall, further blocking the ultraviolet penetration to irradiate the faster-flowing liquid in the center, resulting in uneven inactivation efficiency of the sample. At the same time, since there is always a sample flowing in the fixed quartz container and it cannot be cleaned in time, there are also defects in protein activity retention. Summary of the Invention

[0004] The problem to be solved by the present invention is to provide a fully automatic virus inactivation system for liquid biological products that can simultaneously take into account the virus inactivation effect and the activity of liquid biological products.

[0005] To solve the above technical problems, the present invention adopts the following technical solutions: The present invention provides a fully automatic virus inactivation system for liquid biological products, which includes a horizontal track, a first robotic arm slidably disposed on the horizontal track, a light-transmitting container fixedly connected to the end of the first robotic arm, a filling area for filling the liquid biological products into the light-transmitting container, an ultraviolet irradiation area provided with ultraviolet lamps, a collection area for collecting the liquid biological products in the light-transmitting container, a cleaning area for cleaning the light-transmitting container, and a console provided with a numerical control system and a human-machine interface, which are sequentially arranged along the extension direction of the horizontal track.

[0006] Wherein, the upper end of the light-transmitting container is provided with an opening, and the light-transmitting container and its accommodating cavity are both of a flat plate structure. The first robotic arm can drive the light-transmitting container to turn up and down, and the light-transmitting container has three working states. In the first working state, the light-transmitting container is perpendicular to the horizontal plane and the opening faces upward; in the second working state, the light-transmitting container is parallel to the horizontal plane; in the third working state, the light-transmitting container is perpendicular to the horizontal plane and the opening faces downward.

[0007] The present invention adopts a light-transmitting container of a flat plate structure. The first robotic arm drives the light-transmitting container to sequentially pass through the filling area, the ultraviolet irradiation area, the collection area and the cleaning area along the horizontal track. The liquid biological products are filled into the light-transmitting container in the filling area, the light-transmitting container receives ultraviolet irradiation in the ultraviolet irradiation area to inactivate the virus, the virus-inactivated liquid biological products are transferred out of the light-transmitting container in the collection area, and the used light-transmitting container is cleaned in the cleaning area. The cleaned light-transmitting container can be reused for a new round of virus inactivation.

[0008] In the present invention, the light-transmitting container of a flat plate structure can stably limit the thickness of the liquid layer of the liquid biological products receiving ultraviolet irradiation, improve the virus inactivation effect, and cooperate with the first robotic arm and the horizontal track to effectively control the ultraviolet irradiation time and improve the stability of the virus inactivation effect. Combining the liquid layer thickness and the controllable irradiation time can maximize the retention of the biological activity of the liquid biological products while ensuring the virus inactivation effect. The used light-transmitting container can be cleaned in time to avoid the residual adhesion of the liquid biological products on the container wall, resulting in a decrease in the light transmittance of the container and further affecting the subsequent virus inactivation effect. The present invention effectively improves the effect of fully automatic virus inactivation of liquid biological products.

[0009] In the present invention, when the light-transmitting container is filled with liquid biological products, the thickness of the accommodating cavity of the light-transmitting container is the layer thickness of the liquid biological products receiving ultraviolet irradiation. In an embodiment of the present invention, the thickness of the accommodating cavity of the light-transmitting container is preferably 0.1 - 3 cm.

[0010] Preferably, the distances from the center of the accommodating cavity of the light-transmitting container to the inner surfaces on both sides of the light-transmitting container are equal. In an embodiment of the present invention, the wall thickness of the light-transmitting container is preferably 1-5 mm, more preferably 1-4 mm, still more preferably 1-3 mm, and even more preferably 1-2 mm.

[0011] The material of the light-transmitting container in the present invention is preferably a material with a deep ultraviolet light transmittance ≥ 95%. In an embodiment of the present invention, the material of the light-transmitting container is quartz or a polymer material, and the polymer material includes an amorphous fluoropolymer (Teflon™ AF).

[0012] In the present invention, the light-transmitting container is a customized container with a uniform overall thickness and the thickness of its accommodating cavity. It can be integrally formed or laser-cut formed.

[0013] In an embodiment of the present invention, the first robotic arm includes a base slidably disposed on the horizontal track, a bracket fixedly disposed on the base, a clamp rotatably connected to the bracket, a first driving device for driving the base to slide, and a second driving device for driving the clamp to rotate. The first driving device and the second driving device are respectively electrically connected to the console by electrical signals.

[0014] In a specific embodiment of the present invention, the light-transmitting container is square, and the clamp includes a first clamping strip and a second clamping strip. The middle parts of the first clamping strip and the second clamping strip are respectively pivotally connected to the bracket. The first clamping strip is in contact with one side edge of the light-transmitting container, and the second clamping strip is in contact with the other side edge of the light-transmitting container.

[0015] Furthermore, fixing frames that can match the four corners of the light-transmitting container are respectively provided at the upper and lower ends of the first clamping strip and the second clamping strip to improve the effect of the clamp for fixing the light-transmitting container.

[0016] Furthermore, the bracket includes a first support rod perpendicular to the base and fixedly connected to the base at the lower end, a second support rod parallel to the horizontal plane and fixedly connected to the upper end of the first support rod at the rear end, and a third support rod fixedly connected to the front end of the second support rod. The third support rod includes a first part extending in the left-right direction, a second part extending in the front-rear direction and fixedly connected to the left end of the first part at the rear end, and a third part extending in the front-rear direction and fixedly connected to the right end of the first part at the rear end. The front end of the second part is pivotally connected to the middle part of the first clamping strip, and the front end of the third part is pivotally connected to the middle part of the second clamping strip.

[0017] In an embodiment of the present invention, two rows of ultraviolet lamps are provided in the ultraviolet irradiation area, and there is a spacing between the two rows of ultraviolet lamps for a light-transmitting container in the second working state to pass through.

[0018] In an embodiment of the present invention, the ultraviolet lamp is a strip-shaped ultraviolet lamp extending in the front-rear direction, and the number of ultraviolet lamps in each row is 1 or a plurality of spaced-apart ones. Preferably, the number of ultraviolet lamps is adjusted according to the area of the ultraviolet irradiation area, the surface area of the light-transmitting container, the irradiation energy required for the liquid biological product, etc.

[0019] In an embodiment of the present invention, the wavelength of the ultraviolet lamp is 200 - 280 nm, and more preferably 240 - 280 nm.

[0020] In an embodiment of the present invention, an irradiometer is further provided in the ultraviolet irradiation area to monitor the radiation energy received by the liquid biological product in the ultraviolet irradiation area. Further, when the irradiometer is installed, the plane of the photosensitive film coincides with the horizontal plane where the center point of the light-transmitting container in the ultraviolet irradiation area is located.

[0021] In an embodiment of the present invention, the spacing is 10 - 100 cm. Preferably, the ultraviolet lamp can be adjusted up and down, that is, the spacing can be adjusted, so as to adjust the vertical distance from the ultraviolet lamp to the light-transmitting container.

[0022] In an embodiment of the present invention, a light-shielding plate and a second robotic arm for driving the light-shielding plate to approach or move away from the horizontal track are provided in the ultraviolet irradiation area. The ultraviolet lamp is arranged inside the light-shielding plate. The light-shielding plate is preferably made of a light-impermeable material. More preferably, the ultraviolet lamp is arranged inside the light-shielding plate in a liftable manner.

[0023] Further, when the ultraviolet lamp is working, heat will be generated, and the accumulation of heat will affect the irradiation intensity of the ultraviolet lamp. A heat dissipation device, such as a fan, can be selectively arranged on the light-shielding plate.

[0024] In some embodiments of the present invention, the light-shielding plate is a semi-closed structure open at the front, rear and bottom, and the second robotic arm can drive the light-shielding plate to move in the front-rear direction.

[0025] In some other embodiments of the present invention, the bottom of the light-shielding plate is open, and its front side and / or rear side are set to be electrically controllable to open and close, which can further improve the light-shielding effect.

[0026] In an embodiment of the present invention, the filling area is provided with a first automatic filling device and an automatic sealing device for filling liquid biological products into the transparent containers, the collection area is provided with an automatic opening device, and the cleaning area is provided with a second automatic filling device for filling buffer solution into the transparent containers, a third automatic filling device for filling pure water into the transparent containers, a drying device, a cooling device, and a temperature and humidity sensor.

[0027] In the cleaning area, the buffer solution is used to rinse the transparent containers, and the collected buffer solution waste liquid can be used to recover some biological products subsequently. For example, after the buffer solution waste liquid is concentrated to the same protein concentration as the liquid biological product, it is incorporated into the virus-inactivated liquid biological product collected from the collection area.

[0028] Further, in the cleaning area, the transparent containers can be rinsed with buffer solution multiple times and washed with pure water multiple times. After being dried by the drying device, the transparent containers washed with pure water are cooled to room temperature or the required temperature by the cooling device.

[0029] In a specific embodiment of the present invention, the drying device is a heating blower, and the transparent containers are dried under the action of heated air blowing. Monitored by the temperature and humidity sensor, due to the material limitation of the transparent containers, the temperature of the hot air outlet is not higher than 60 °C, and the time does not exceed 20 minutes.

[0030] In a specific embodiment of the present invention, the cooling device is a water-cooled blower, and the temperature is reduced under the action of water-cooled air blowing. Monitored by the temperature and humidity sensor, due to the material limitation of the transparent containers, the pre-cooling temperature is not lower than 0 °C, and the action time does not exceed 20 minutes. Preferably, after the container temperature reaches or is slightly lower than 15 °C, it enters a new round of virus inactivation operation.

[0031] In a specific embodiment of the present invention, the control console is electrically connected to the first automatic filling device, the automatic sealing device, the automatic opening device, the second automatic filling device, the third automatic filling device, the drying device, the cooling device, and the temperature and humidity sensor respectively.

[0032] In an embodiment of the present invention, the full-automatic virus inactivation system for liquid biological products further includes a liquid pool provided in the collection area and a waste liquid pool provided in the cleaning area. Further preferably, the waste liquid pool includes a first waste liquid pool for collecting the waste liquid after rinsing the transparent containers with buffer solution and a second waste liquid pool for collecting the waste liquid after washing the transparent containers with pure water.

[0033] In an embodiment of the present invention, the horizontal track is a circular track structure, and the cleaned transparent containers can be directly returned to the automatic filling area by the first robotic arm.

[0034] In an embodiment of the present invention, it can be designed as an assembly line. Only by sequentially arranging a plurality of first robotic arms equipped with the light-transmitting containers on the horizontal track, continuous circulation of a plurality of light-transmitting containers can be achieved, and the loading capacity and efficiency are significantly improved.

[0035] In an embodiment of the present invention, the operation of all devices in the full-automatic virus inactivation system for liquid bioproducts is controlled by the console. Before operation, the operation parameters of all devices in the system are input on the console. For example, it includes basic cycle parameters such as the process of the first robotic arm rotating the light-transmitting container in each area, the positioning points where the first robotic arm pauses in each area, the residence time at each positioning point, the running speed between each positioning point, etc., the start-stop and running direction of the second robotic arm, the turning on and off of the ultraviolet lamp, the filling speed and filling volume of the automatic filling device, the start-stop of the automatic sealing device and the automatic opening device, the temperature and humidity settings of the drying device, the temperature and humidity settings of the cooling device, etc.

[0036] The present invention has the following advantages compared with the prior art: The full-automatic virus inactivation system for liquid bioproducts of the present invention can stably maintain an extremely low thickness of the liquid bioproduct during the ultraviolet irradiation process, can reduce the denaturation adhesion and activity loss of the liquid bioproduct while ensuring a stable and effective ultraviolet dose received by the liquid bioproduct, thereby maximizing the retention of the biological activity and recovery rate of the liquid bioproduct while ensuring the virus inactivation effect. It also has advantages such as high automation degree, easy cleaning and maintenance, etc., and has a great application scope and market prospect. BRIEF DESCRIPTION OF THE DRAWINGS

[0037] Figure 1 It is a schematic structural diagram of the assembly line of the full-automatic virus inactivation system for liquid bioproducts in Example 1; Figure 2 It is a three-dimensional structural diagram of the first robotic arm equipped with a light-transmitting container in Example 1 (the first robotic arm is in the first working state); In the above drawings, 1, horizontal track; 2, first robotic arm; 21, base; 221, first support rod; 222, second support rod; 223, third support rod; 231, first clamping strip; 232, second clamping strip; 233, fixing frame; 3, light-transmitting container; 4, filling area; 41, first automatic filling device; 42, automatic sealing device; 5, ultraviolet irradiation area; 51, ultraviolet lamp; 52, light-blocking plate; 6, collection area; 61, automatic opening device; 7, cleaning area; 71, second automatic filling device; 72, third automatic filling device; 73, drying device; 74, cooling device; 8, console. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0038] To improve the efficiency of virus inactivation of liquid biological products, the applicant mainly relied on external forces such as centrifugation to thin the liquid layer thickness in previous studies to ensure sufficient effective ultraviolet irradiation, so as to increase the ultraviolet penetration and effectively inactivate viruses. In previous studies, the liquid biological products adhered to the side wall of the container and rose under the action of centrifugal force, or flowed from bottom to top in a fixed quartz tube. Combined with a fixed ultraviolet lamp tube, the liquid biological products were irradiated during the flow process to inactivate viruses. With the increase in the sample volume, the applicant found that due to the laws of hydrodynamics, during the process of processing a large amount of liquid biological samples, the liquid layer thickness was uneven, resulting in unstable and non-uniform virus inactivation effects. Moreover, due to the laminar flow of the liquid biological products inside the quartz tube, the outer liquid biological products close to the inner wall of the quartz tube were more likely to receive a higher ultraviolet dose because they were closer to the light source and had a slower flow rate, which easily led to protein denaturation and adhesion to the tube wall, thus significantly reducing the light transmittance of the tube wall. These factors would affect the ultraviolet dose received by the liquid biological products and the activity retention degree in the later stage of long-term use.

[0039] To solve the above problems, the applicant developed the above-mentioned fully automatic virus inactivation system for liquid biological products, which includes a horizontal track, a first robotic arm slidably arranged on the horizontal track, a transparent container fixedly connected to the end of the first robotic arm, a filling area for filling the liquid biological products into the transparent container, an ultraviolet irradiation area provided with ultraviolet lamps, a collection area for collecting the liquid biological products in the transparent container, a cleaning area for cleaning the transparent container, and a console provided with a numerical control system and a human-machine interaction interface arranged in sequence along the extension direction of the horizontal track.

[0040] The virus inactivation system of the present invention can keep the liquid biological products stationary relative to the transparent container, making the liquid layer thickness of the liquid biological products receiving ultraviolet irradiation extremely low and uniform, thereby reducing the irradiation time, which is beneficial to better retaining the activity of the liquid biological products while obtaining a higher virus inactivation effect. After each ultraviolet irradiation, the transparent container will be immediately automatically cleaned and then reused to ensure the cleanliness of the inner wall of the transparent container and the virus inactivation effect after long-term cyclic operation. The virus inactivation system of the present invention can be designed as an assembly line to increase the loading capacity. Based on the above advantages, the virus inactivation system of the present invention has a great application scope and market prospect and can be applied to the large-scale production lines of biological products in the pharmaceutical industry.

[0041] The present invention can be used for various virus inactivations, including but not limited to Reoviridae, Rhabdoviridae, Orthomyxoviridae, Filoviridae, Coronaviridae, Bunyaviridae, Bornaviridae, Flaviviridae, Paramyxoviridae, Togaviridae, Arenaviridae, Picornaviridae, Caliciviridae, Retroviridae, Poxviridae, Herpesviridae, Iridoviridae, Papovaviridae, Parvoviridae.

[0042] The present invention is applicable to a variety of liquid biological products, including but not limited to vaccine preparations, toxin preparations, toxoid preparations, immune sera, blood products, immunoglobulin preparations, antigen preparations, allergen products, cytokine preparations, hormone preparations, enzyme products, fermentation broths, monoclonal antibody preparations, or in vitro immunodiagnostic products.

[0043] The present invention will be further described below in conjunction with the embodiments shown in the accompanying drawings.

[0044] In the following text, only some exemplary embodiments are simply described. As those skilled in the art can recognize, the described embodiments can be modified in various different ways without departing from the spirit or scope of the embodiments of the present invention. Therefore, the drawings and the description are considered to be exemplary in nature rather than restrictive.

[0045] Figure 1 Part of the devices on the production line of the fully automatic virus inactivation system for liquid biological products in Embodiment 1 is shown. The non - display of some devices does not mean that the corresponding equipment is not provided in the fully automatic virus inactivation system for liquid biological products in Embodiment 1, such as the second robotic arm, the non - displayed section of the horizontal track, the liquid pool, and the waste liquid pool, etc.

[0046] In the description of the present invention, it should be noted that the directional descriptions such as "upper" and "lower" are all defined according to Figure 1 the state of the first robotic arm and the light - transmissive container located in the filling area in ; "inner" and "outer" are positions defined by the distance relative to the center of the device or component. Among them, "inner" is the position close to the center of the device or component, and "outer" is the position far from the center of the device or component. The above - mentioned directional terms are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or component referred to must have a specific orientation, be constructed and operated in a specific orientation, and thus cannot be understood as a limitation to the present invention.

[0047] In the embodiments of the present invention, unless otherwise clearly specified and limited, the terms "installed", "connected", "connected", "fixed", etc. should be understood in a broad sense. For example, it can be a fixed connection, a detachable connection, or integrated. For those of ordinary skill in the art, the specific meanings of the above - mentioned terms in the embodiments of the present invention can be understood according to specific circumstances. To simplify the disclosure of the embodiments of the present invention, the components and settings of specific examples are described below. Of course, they are only examples and are not intended to limit the embodiments of the present invention. The specifications and models of the components can be adjusted according to actual needs.

[0048] Embodiment 1: This embodiment provides a fully automatic virus inactivation system for liquid biological products, which includes a horizontal track 1, a first robotic arm 2 slidably arranged on the horizontal track 1, a light-transmitting container 3 fixedly connected to the end of the first robotic arm 2, a filling area 4 for filling liquid biological products into the light-transmitting container 3, an ultraviolet irradiation area 5 equipped with an ultraviolet lamp 51, a collection area 6 for collecting the liquid biological products in the light-transmitting container 3, a cleaning area 7 for cleaning the light-transmitting container 3, and a console 8 equipped with a numerical control system and a human-machine interface, arranged in sequence along the extension direction of the horizontal track 1.

[0049] As Figure 1 shown, in this embodiment, it is designed as an assembly line, and there are multiple first robotic arms 2 and light-transmitting containers 3 on the horizontal track 1. In this embodiment, the upper end of the light-transmitting container 3 is provided with an opening, and both the light-transmitting container 3 and its accommodating cavity are of flat plate structure. The first robotic arm 2 can drive the light-transmitting container 3 to turn over up and down, and make the light-transmitting container 3 have three working states. In the first working state, the light-transmitting container 3 is perpendicular to the horizontal plane and the opening faces upward; in the second working state, the light-transmitting container 3 is parallel to the horizontal plane; in the third working state, the light-transmitting container 3 is perpendicular to the horizontal plane and the opening faces downward. In this embodiment, the first robotic arm 2 drives the light-transmitting container 3 to pass through the filling area 4, the ultraviolet irradiation area 5, the collection area 6 and the cleaning area 7 along the horizontal track 1. Liquid biological products are filled into the light-transmitting container 3 in the filling area 4, the light-transmitting container 3 receives ultraviolet irradiation to inactivate viruses in the ultraviolet irradiation area 5, the liquid biological products after virus inactivation are transferred out of the light-transmitting container 3 in the collection area 6, and the used light-transmitting container 3 is cleaned in the cleaning area 7. The cleaned light-transmitting container 3 can be used again for a new round of virus inactivation.

[0050] Specifically, the fully automatic virus inactivation system for liquid biological products in this embodiment is an assembly line, and the horizontal track 1 is a circular track. The cleaned light-transmitting container 3 can directly return to the automatic filling area 4 through the first robotic arm 2. Specifically, multiple first robotic arms 2 equipped with light-transmitting containers 3 are sequentially arranged on the horizontal track 1 to realize uninterrupted circulation of multiple light-transmitting containers 3, and the loading capacity and efficiency are significantly improved.

[0051] When the transparent container 3 is filled with the liquid biological product, the thickness of the accommodating cavity of the transparent container 3 is the layer thickness at which the liquid biological product receives ultraviolet irradiation. To ensure the ultraviolet irradiation effect, the distances from the center of the accommodating cavity of the transparent container 3 to the inner surfaces on both sides of the transparent container 3 are equal. Specifically, in this embodiment, the transparent container 3 is square, the side length of the accommodating cavity of the transparent container 3 is 10 cm, the capacity is 2 L, and the wall thickness of the transparent container 3 is 2 mm. In other embodiments, transparent containers 3 of other specifications can be selected according to actual needs. Under the condition that the wall thickness of the transparent container 3 does not exceed 5 mm, a suitable specification of the transparent container 3 can be selected according to the light transmittance of the liquid biological product at the selected wavelength. In this embodiment, the material of the transparent container 3 is quartz. In other embodiments, other materials with a deep ultraviolet light transmittance ≥ 95% can also be used, such as amorphous fluoropolymer (Teflon™ AF). In this embodiment, the thickness of the accommodating cavity of the transparent container is selected according to the absorbance of the liquid biological product at the ultraviolet wavelength of 254 nm, and specific reference can be made to Table 1.

[0052]

[0053] Specifically, in this embodiment, the first robotic arm 2 includes a base 21 slidably arranged on the horizontal track 1, a bracket fixedly arranged on the base 21, a clamp rotatably connected to the bracket, a first driving device for driving the base 21 to slide, and a second driving device for driving the clamp to rotate. The first driving device and the second driving device are respectively electrically connected to the console 8. As Figure 2As shown in the figure, the bracket includes a first support rod 221 perpendicular to the base 21 and fixedly connected to the base 21 at its lower end, a second support rod 222 parallel to the horizontal plane and directly or indirectly fixedly connected to the upper end of the first support rod 221 through a joint at its rear end, and a third support rod 223 fixedly connected to the front end of the support rod. The third support rod 223 includes a first portion extending in the left-right direction, a second portion extending in the front-rear direction and fixedly connected to the left end of the first portion at its rear end, and a third portion extending in the front-rear direction and fixedly connected to the right end of the first portion at its rear end. The front end of the second portion is pivotally connected to the middle of the first clamping strip 231, and the front end of the third portion is pivotally connected to the middle of the second clamping strip 232. The fixture includes a first clamping strip 231 and a second clamping strip 232. The middle parts of the first clamping strip 231 and the second clamping strip 232 are respectively pivotally connected to the bracket. The first clamping strip 231 abuts against one side of the transparent container 3, and the second clamping strip 232 abuts against the other side of the transparent container 3. Fixing frames 233 capable of matching the four corners of the transparent container 3 are respectively provided at the upper and lower ends of the first clamping strip 231 and the second clamping strip 232 to improve the effect of the fixture in fixing the transparent container 3. In this embodiment, the first driving device is a well-known technology in the art, and a chain driving device or a belt driving device can be used, which will not be elaborated here. In this embodiment, the second driving device is a well-known technology in the art, and a small servo motor driver can be used, which will not be elaborated here.

[0054] Specifically, in this embodiment, in the filling area 4, there is a first automatic filling device 41 and an automatic sealing device 42 for filling liquid biological products into the transparent container 3. The first automatic filling device 41 and the automatic sealing device 42 can be selected from existing conventional automatic filling devices and automatic sealing devices 42, without special requirements, which will not be elaborated here. In this embodiment, in the filling area 4, the first robotic arm 2 first keeps the transparent container 3 in the first working state. After filling and sealing are completed, the first robotic arm 2 converts the transparent container 3 from the first working state to the second working state.

[0055] Specifically, in this embodiment, the ultraviolet irradiation area 5 is provided with two rows of ultraviolet lamps 51 distributed vertically. There is a spacing between the two rows of ultraviolet lamps 51 for the light-transmitting container 3 in the second working state to pass through, preferably 10 - 100 cm, and a suitable spacing can be set according to the irradiation dose requirements. In this embodiment, when the light-transmitting container 3 is in the second working state, it passes through along the horizontal center line of the spacing. In this embodiment, the ultraviolet lamp 51 is a strip-shaped ultraviolet lamp 51 extending in the front-rear direction, and the number of each row of ultraviolet lamps 51 is 5 arranged at intervals. In other embodiments, the number of ultraviolet lamps 51 can be adjusted according to the area of the ultraviolet irradiation area 5, the surface area of the light-transmitting container 3, or the irradiation energy required for liquid biological products, etc. In this embodiment, the wavelength of the ultraviolet lamp 51 is 254 nm. Before the light-transmitting container 3 first enters the ultraviolet irradiation area 5, the ultraviolet lamp 51 has been balanced for at least 30 minutes. In other embodiments, ultraviolet lamps 51 with other wavelengths can be selected according to actual needs, and the preferred wavelength is 200 - 280 nm. The length of the ultraviolet lamp 51 is equal to or slightly greater than the width of the light-transmitting container 3 to ensure uniform irradiation. In this embodiment, the ultraviolet irradiation area 5 is provided with a light-shielding plate 52 and a second robotic arm (not shown in the figure) for driving the light-shielding plate 52 to move back and forth. The light-shielding plate 52 is preferably made of a light-impermeable material, and the second robotic arm refers to the prior art. In this embodiment, the ultraviolet lamp 51 is arranged in the light-shielding plate 52 in a liftable manner. When ultraviolet irradiation is required, the light-shielding plate 52 is moved by the second robotic arm to drive the ultraviolet lamp 51 to the position where the light-transmitting container 3 is located. At this time, the light-transmitting container 3 is located in the middle of the two rows of ultraviolet lamps 51, and the vertical distance between the ultraviolet lamp 51 and the light-transmitting container 3 can be adjusted and controlled according to needs through the liftable setting method. The ultraviolet irradiation area 5 is provided with an irradiator (not shown in the figure) to monitor the radiation energy received by the liquid biological product in the ultraviolet irradiation area 5. Specifically, when installing the irradiator, the plane of the photosensitive film coincides with the horizontal plane where the center point of the light-transmitting container 3 in the ultraviolet irradiation area 5 is located. The measured value of the plane intensity of the irradiator is the average value of the unilateral surface, and the intensity is preferably controlled at 1 - 10 mW / cm 2 , and the irradiation time is preferably controlled at 5 - 60 seconds, so that the average received ultraviolet dose at the mid-plane of the liquid biological product is 50 - 6000 J / m 2(Ultraviolet dose = intensity × time). In actual operation, the specific irradiation time is selected according to the virus inactivation effect and the degree of preservation of the activity of the liquid biological product to obtain the actual required ultraviolet dose. In this embodiment, before entering the ultraviolet irradiation area 5, the transparent container 3 is maintained in the second working state for 1 to 5 minutes to make the liquid biological product in the transparent container 3 stationary and stable relative to the transparent container 3. Then, the first robotic arm drives the transparent container 3 to the ultraviolet irradiation area 5. The second robotic arm moves the light shielding plate 52 forward until the transparent container 3 is located in the middle of two rows of ultraviolet lamps 51. After the ultraviolet irradiation time reaches the requirement, the second robotic arm moves the light shielding plate 52 backward to a position where the light shielding plate 52 does not interfere with the first robotic arm 3 driving the transparent container 3 to slide along the horizontal track 1.

[0056] Specifically, in this embodiment, the collection area 6 is provided with an automatic opening device 61 and a liquid pool (not shown in the figure). The automatic opening device 61 can use existing conventional automatic opening devices 61 without special requirements, which will not be elaborated here. In this embodiment, the first robotic arm 2 coming out of the ultraviolet irradiation area 5 first converts the transparent container 3 from the second working state to the first working state. After opening through the automatic opening device 61, it is then converted from the first working state to the third working state. During this process, the liquid biological product is poured into the liquid pool.

[0057] Specifically, in this embodiment, the cleaning area 7 is provided with a second automatic filling device 71 for filling the light-transmitting container 3 with buffer solution, a third automatic filling device 72 for filling the light-transmitting container 3 with pure water, a drying device 73, a cooling device 74, a temperature and humidity sensor (not shown in the figure), and a waste liquid tank (not shown in the figure). The waste liquid tank includes a first waste liquid tank for collecting the waste liquid after the buffer solution is used to rinse the light-transmitting container 3 and a second waste liquid tank for collecting the waste liquid after the pure water is used to clean the light-transmitting container 3. In this embodiment, the second automatic filling device 71 and the third automatic filling device 72 are the same as the first automatic filling device 41, and can be existing conventional automatic filling devices without special requirements, which will not be elaborated here. In this embodiment, the drying device 73 is a heating blower, and the light-transmitting container 3 is dried under the action of heating and blowing. Monitored by the temperature and humidity sensor, due to the material limitation of the light-transmitting container 3, the temperature of the hot air outlet does not exceed 60 °C, and the time does not exceed 20 minutes. The cooling device 74 is a water-cooled blower, and the temperature is reduced under the action of water-cooled blowing. Monitored by the temperature and humidity sensor, due to the material limitation of the light-transmitting container 3, the pre-cooling temperature is not lower than 0 °C, and the action time does not exceed 20 minutes. Preferably, after the temperature of the container reaches or is slightly lower than 15 °C, it enters a new round of virus inactivation operation. In the cleaning area 7, the light-transmitting container 3 can be rinsed with buffer solution and washed with pure water multiple times. After being dried by the drying device 73, the light-transmitting container 3 washed with pure water is cooled to room temperature or the required temperature by the cooling device 74. The collected buffer waste liquid can be used to recover some biological products subsequently. For example, after the buffer waste liquid is concentrated to the same protein concentration as the liquid biological product, it is incorporated into the virus-inactivated liquid biological product collected from the collection area 6. During the buffer rinsing and pure water washing, the first robotic arm 2 continuously switches between the first working state and the third working state. During drying and cooling, the first robotic arm 2 is in the second working state, and at the same time, the upper and lower surfaces of the light-transmitting container 3 are dried and cooled.

[0058] In this embodiment, the control console 8 is electrically connected to the electric drive device, the first automatic filling device 41, the automatic sealing device 42, the automatic opening device 61, the second automatic filling device 71, the third automatic filling device 72, the drying device 73, the cooling device 74, and the temperature and humidity sensor respectively to achieve full automation.

[0059] In this embodiment, the horizontal track 1 is a circular track structure connected end to end ( Figure 1(The middle part of the horizontal track is not shown). The cleaned transparent container 3 can directly return to the automatic filling area 4 through the first robotic arm. The multiple first robotic arms 2 each mounting a transparent container 3 on the horizontal track are at different positions and selectively in different or the same states. The operation of all devices in the full-automatic virus inactivation system for liquid bioproducts is controlled by the console 8. Before operation, the operation parameters of all devices in the system are input on the console 8. For example, it includes basic cycle parameters such as the process of the first robotic arm 2 rotating the transparent container 3 in each area, the positioning points where the first robotic arm 2 pauses in each area, the residence time at each positioning point, the running speed between each positioning point, etc., the start-stop and running direction of the second robotic arm, the turning on and off of the ultraviolet lamp 51, the filling speed and filling volume of the automatic filling device, the start-stop of the automatic sealing device 42 and the automatic opening device 61, the temperature and humidity grades of the drying device, the temperature and humidity grades of the cooling device 74, etc., to realize the uninterrupted circulation of multiple transparent containers 3, and the loading capacity and efficiency are significantly improved.

[0060] The full-automatic virus inactivation system for liquid bioproducts in this embodiment has complete functions, high automation degree, convenient operation, saves manpower, and solves the problems of single function, low controllability, waste of human resources, etc. existing in the existing virus inactivation devices for liquid bioproducts.

[0061] The full-automatic virus inactivation system for liquid bioproducts in this embodiment can stably maintain an extremely low thickness of the biological liquid during the ultraviolet irradiation process, reduce the denaturation adhesion and activity loss of the bioproduct while ensuring a stable and effective ultraviolet dose, and solves the problems of denaturation adhesion, decreased light transmittance, difficult to clean, low sample activity retention degree, etc. existing in the existing virus inactivation devices for liquid bioproducts due to the laminar flow of the liquid bioproduct in the container.

[0062] The full-automatic virus inactivation system for liquid bioproducts in this embodiment can continuously and stably inactivate viruses for a long time. The loading capacity and efficiency are significantly better than those of the existing virus inactivation devices for liquid bioproducts, and it is more suitable for the industrial large-scale production of liquid bioproducts, such as being used in the large-scale production lines of bioproducts in the pharmaceutical industry.

[0063] The above has made a detailed description of the present invention, aiming to enable those skilled in this field to understand the content of the present invention and implement it. However, it cannot be used to limit the protection scope of the present invention. Any equivalent changes or modifications made according to the spirit and essence of the present invention should be covered within the protection scope of the present invention.

Claims

1. An automatic virus inactivation system for liquid biological products, characterized in that, It includes a horizontal track (1), a first robotic arm (2) slidably arranged on the horizontal track (1), a light-transmitting container (3) fixedly connected to the end of the first robotic arm (2), a filling area (4) arranged in sequence along the extension direction of the horizontal track (1) for filling liquid biological products into the light-transmitting container (3), an ultraviolet irradiation area (5) provided with an ultraviolet lamp (51), a collection area (6) for collecting the liquid biological products in the light-transmitting container (3), a cleaning area (7) for cleaning the light-transmitting container (3), and a console (8) provided with a numerical control system and a human-machine interface. The upper end of the light-transmitting container (3) is provided with an opening, and both the light-transmitting container (3) and its accommodating cavity are of a flat plate structure. The first robotic arm (2) can drive the light-transmitting container (3) to turn over up and down, and make the light-transmitting container (3) have three working states. In the first working state, the light-transmitting container (3) is perpendicular to the horizontal plane and the opening faces upward; in the second working state, the light-transmitting container (3) is parallel to the horizontal plane; in the third working state, the light-transmitting container (3) is perpendicular to the horizontal plane and the opening faces downward.

2. The fully automatic virus inactivation system for liquid biological products according to claim 1, wherein The thickness of the accommodating cavity of the light-transmitting container (3) is 0.1 - 3 cm.

3. The fully automatic virus inactivation system for liquid biological products according to claim 1, characterized in that The wall thickness of the light-transmitting container (3) is 1 - 5 mm.

4. The fully automatic virus inactivation system for liquid biological products according to claim 1, characterized in that, The first robotic arm (2) includes a base (21) slidably arranged on the horizontal track (1), a bracket fixedly arranged on the base (21), a clamp rotatably connected to the bracket, a first driving device for driving the base (21) to slide, and a second driving device for driving the clamp to rotate. The first driving device and the second driving device are respectively electrically connected to the console (8).

5. The fully automatic virus inactivation system for liquid biological products according to claim 4, wherein, The light-transmitting container (3) is square. The clamp includes a first clamping strip (231) and a second clamping strip (232). The middle parts of the first clamping strip (231) and the second clamping strip (232) are respectively pivotally connected to the bracket. The first clamping strip (231) abuts against one side edge of the light-transmitting container (3), and the second clamping strip (232) abuts against the other side edge of the light-transmitting container (3).

6. The fully automatic virus inactivation system for liquid biological products according to claim 5, wherein The bracket includes a first support rod (221) perpendicular to the base (21) and fixedly connected to the lower end of the base (21), a second support rod (222) parallel to the horizontal plane and fixedly connected to the upper end of the first support rod (221) at the rear end, and a third support rod (223) fixedly connected to the front end of the second support rod (222). The third support rod (223) includes a first part extending in the left-right direction, a second part extending in the front-rear direction and fixedly connected to the left end of the first part at the rear end, and a third part extending in the front-rear direction and fixedly connected to the right end of the first part at the rear end. The front end of the second part is pivotally connected to the middle part of the first clamping strip (231), and the front end of the third part is pivotally connected to the middle part of the second clamping strip (232).

7. The fully automatic virus inactivation system for liquid biological products according to claim 4, wherein The ultraviolet irradiation area (5) is provided with two rows of ultraviolet lamps (51) distributed vertically, and there is a spacing between the two rows of ultraviolet lamps (51) for the transparent container (3) in the second working state to pass through.

8. The fully automatic virus inactivation system for liquid biological products according to claim 7, wherein, The ultraviolet lamp (51) is a strip-shaped ultraviolet lamp (51) extending in the front-rear direction, and the number of ultraviolet lamps (51) in each row is 1 or multiple arranged at intervals; and / or, the wavelength of the ultraviolet lamp (51) is 200-280 nm, and / or, the ultraviolet irradiation area (5) is further provided with an irradiator; and / or, the spacing is 10-100 cm.

9. The fully automatic virus inactivation system for liquid biological products according to claim 7, characterized in that, The ultraviolet irradiation area (5) is provided with a movable light shield (52) and a second robotic arm for driving the light shield (52) to approach or move away from the horizontal track (1), and the ultraviolet lamp (51) is arranged inside the light shield (52).

10. The fully automatic virus inactivation system for liquid biological products according to claim 9, wherein The light shield (52) is a semi-enclosed structure open at the front, rear and bottom, and the second robotic arm can drive the light shield (52) to move in the front-rear direction.

11. The fully automatic virus inactivation system for liquid biological products according to claim 1, wherein The filling area (4) is provided with a first automatic filling device (41) and an automatic sealing device (42) for filling liquid biological products into the transparent container (3), the collection area (6) is provided with an automatic opening device (61), and the cleaning area (7) is provided with a second automatic filling device (71) for filling buffer solution into the transparent container (3), a third automatic filling device (72) for filling pure water into the transparent container (3), a drying device (73), a cooling device (74) and a temperature and humidity sensor.

12. The fully automatic virus inactivation system for liquid biological products according to claim 11, wherein, The control console (8) is electrically connected to the first automatic filling device (41), the automatic sealing device (42), the automatic opening device (61), the second automatic filling device (71), the third automatic filling device (72), the drying device (73), the cooling device (74) and the temperature and humidity sensor respectively.

13. The fully automatic virus inactivation system for liquid biological products according to claim 1, characterized in that, The full-automatic virus inactivation system for liquid biological products further includes a liquid pool arranged in the collection area (6) and a waste liquid pool arranged in the cleaning area (7).

14. The fully automatic virus inactivation system for liquid biological products according to claim 1, wherein The horizontal track (1) is a ring track structure connected end to end.

15. The fully automatic virus inactivation system for liquid biological products according to claim 1, wherein, The material of the transparent container is quartz or polymer material.

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