An automated sterile sampling docking biochemical analyzer device and method

Abstract

The application relates to the technical field of biopharmaceutical equipment, and provides an automatic sterile sampling docking biochemical analyzer device and method, which comprises a controller, a sampling pipeline, a CIP pipeline and a SIP pipeline. The sampling pipeline comprises a sample temporary storage tube and a sampling hose. One end of the sampling hose is in communication with the sample temporary storage tube, and the other end is in communication with an external biochemical analyzer. The CIP pipeline comprises a CIP liquid inlet pipe and a CIP liquid return pipe. One end of the CIP liquid inlet pipe is in communication with an external cleaning liquid output device, and the other end is in communication with the output end of a first valve. One end of the CIP liquid return pipe is in communication with the top end of the sample temporary storage tube, and the other end is in communication with an external CIP liquid return collection device. The SIP pipeline comprises a SIP gas inlet pipe and a SIP gas return pipe. The automatic sterile sampling docking biochemical analyzer device can improve sampling efficiency and reduce the risk of sample contamination.

Description

Technical Field

[0001] This application relates to the technical field of biopharmaceutical equipment, and in particular to an automated aseptic sampling and docking device and method for biochemical analyzers. Background Technology

[0002] Bioreactors are widely used in the biopharmaceutical industry. They can be used to produce antibiotics, enzymes, proteins, and other biological products, as well as to treat wastewater and solid waste. During the biopharmaceutical process, it is necessary to sample the feed liquid (mainly reactants and organisms) in the bioreactor.

[0003] To prevent microbial contamination of the bioreactor and sampling environment, aseptic sampling is generally employed during the sampling process. The typical procedure involves first sterilizing the sampling bottle in an autoclave, connecting it to the sampling tubing, then sterilizing the tubing with steam before sampling. After sampling, the bottle is then connected to the biochemical analyzer for final analysis. However, this method is cumbersome, time-consuming, and carries the risk of sample contamination. Therefore, a device is needed that can automatically sample and deliver samples to the biochemical analyzer, and automatically perform CIP / SIP before and after sampling to ensure the samples are not contaminated. Summary of the Invention

[0004] To improve sampling efficiency and reduce the risk of sample contamination, this application provides an automated aseptic sampling device and method for docking with a biochemical analyzer.

[0005] Firstly, the automated aseptic sampling and docking biochemical analyzer device provided in this application adopts the following technical solution:

[0006] An automated aseptic sampling and biochemical analyzer docking device includes a controller, sampling tubing, CIP tubing, and SIP tubing. The sampling tubing includes a sample storage tube and a sampling hose connected sequentially. The sample storage tube is connected to a bioreactor and a first valve is installed between them. One end of the sampling hose is connected to the bottom of the sample storage tube via a second valve, and the other end is connected to an external biochemical analyzer. The CIP tubing includes a CIP inlet tube and a CIP return tube. One end of the CIP inlet tube is connected to an external cleaning solution output device, and the other end... One end of the CIP return pipe is connected to the output end of the first valve via the third valve. One end of the CIP return pipe is connected to the top of the sample storage tube, and the other end is connected to the external CIP return collection device via the fourth valve. The SIP pipeline includes a SIP inlet pipe and a SIP return pipe. One end of the SIP inlet pipe is connected to the external steam generator, and the other end is connected to the CIP inlet pipe. One end of the SIP return pipe is connected to the top of the sample storage tube, and the other end is connected to the external condensate recovery device via the fifth valve. All valves are connected to the controller.

[0007] By adopting the above technical solution, through the setting of sampling pipelines, CIP pipelines, and SIP pipelines, the third and fourth valves are opened while the first, second, and fifth valves are closed, and cleaning solution is introduced through the cleaning solution output device to clean the pipelines. After cleaning, the third and fifth valves are opened while the first, second, and fourth valves are closed, and steam is introduced through the steam generator to sterilize the pipelines. After sterilization, the first and fifth valves are opened while the third and fourth valves are closed, allowing the feed liquid in the bioreactor to enter the sample storage tube through the first valve. When it reaches the set height, the first valve is closed and the second valve is opened, and the biochemical analyzer can obtain the sample to be analyzed from the bioreactor output from the sample storage tube. The CIP pipeline and SIP pipeline work together to clean and sterilize the sample storage tube, ensuring that the sample is not contaminated during subsequent sampling. The entire process can be completed by the controller controlling the coordinated action of each valve, without manual intervention, resulting in high sampling efficiency.

[0008] Optionally, the sample storage tube is vertically arranged, and an injection tube is connected to the bottom end of the sample storage tube. The end of the injection tube away from the sample storage tube is connected to the bioreactor. The injection tube is inclined, and the first valve is located on the injection tube. The connection point between the injection tube and the bioreactor is not higher than the lowest liquid level of the feed liquid in the bioreactor. A flow regulating valve is connected to the bottom end of the sample storage tube.

[0009] By adopting the above technical solution, the vertically arranged sample storage tube is more conducive to sample storage. Simultaneously, by controlling the opening time of the first valve, the amount of liquid entering the sample storage tube can be controlled, preventing waste due to excessive sampling. Furthermore, the placement of the injection tube ensures a positive pressure between the input and output ends of the first valve, facilitating the entry of liquid into the sample storage tube and improving sampling efficiency.

[0010] Optionally, the SIP return pipe is sequentially equipped with a temperature sensor for detecting the temperature inside the pipe and a steam trap to prevent steam from escaping. The temperature sensor and the steam trap are both located between the fifth valve and the external condensate recovery device. The controller is signal-connected to the temperature sensor.

[0011] By employing the above technical solution, the steam trap is used to drain condensate and prevent steam from escaping, maintaining the sterilization pressure within the pipeline. The temperature sensor controls the sterilization temperature; it can be linked to the SIP steam inlet valve to control the steam flow and ensure thorough sterilization.

[0012] Optionally, the first valve, the second valve, the third valve, the fourth valve, and the fifth valve are all pneumatic diaphragm valves, and the flow regulating valve is a manual diaphragm valve.

[0013] Optionally, the bottom periphery of the sample storage tube is connected to an installation branch tube, and the end of the sampling tube away from the biochemical analyzer is connected to the installation branch tube. The sampling tube is connected to the sample storage tube through the installation branch tube. A connecting component is provided between the installation branch tube and the sampling tube, and the sampling tube is detachably installed to the installation branch tube through the connecting component.

[0014] By adopting the above technical solution and setting the connecting components, the sampling tube can be detachably installed on the sample storage tube. After the sampling tube has been used multiple times, it can be disassembled through the connecting components for offline sterilization.

[0015] Optionally, the connecting assembly includes a connecting joint, a mating ring, and a mating sleeve. The connecting joint includes an integrally formed first connecting portion and a second connecting portion. One end of the sampling hose is sleeved on the outer peripheral wall of the first connecting portion, and the outer diameter of the sampling hose is smaller than the outer diameter of the second connecting portion. One end of the mounting branch pipe is inserted into the second connecting portion. The mating ring is disposed on the outer peripheral wall of the mounting branch pipe, and the outer diameter of the mating ring is adapted to the outer diameter of the second connecting portion. The mating sleeve includes an integrally formed first mating portion and a second mating portion. The first mating portion is sleeved on the outer peripheral wall of the sampling hose, and the second mating portion is sleeved on both the outer peripheral wall of the second connecting portion and the outer peripheral wall of the mating ring and is threadedly connected to the mating ring.

[0016] By adopting the above technical solution, and through the setting of the connecting joint, the docking ring, and the docking sleeve, when installing the sampling hose, the sampling hose is sleeved on the outer peripheral wall of the first connecting part, and then the second connecting part is aligned with one end of the installation branch pipe and pushed, so that one end of the installation branch pipe is inserted into the second connecting part. Then, the docking sleeve is slid to align the second connecting part with the docking ring and the docking sleeve is rotated. After the second connecting part is tightened, the sampling hose, the connecting joint, and the installation branch pipe are connected as one unit, improving the ease of disassembly and assembly of the overall structure.

[0017] Optionally, the outer peripheral wall of the first connecting part is provided with a first sealing ring groove, and a first sealing ring is provided in the first sealing ring groove; the first sealing ring groove has a guide surface, and the outer diameter of the guide surface gradually increases from the side near the second connecting part to the side away from the second connecting part; a pushing ring is slidably installed in the first sealing ring groove, and the pushing ring is located on the side of the first sealing ring near the second connecting part; the second connecting part is provided with a driving assembly, and when the second mating part tightens the mating ring, the driving assembly drives the pushing ring to move away from the second connecting part, so that the first sealing ring abuts against the inner peripheral wall of the sampling tube.

[0018] By adopting the above technical solution, through the setting of the first sealing ring, guide surface, and push ring, during the installation of the first sealing ring, the first sealing ring is fitted into the first sealing ring groove and displaced to the side of the first sealing ring groove closer to the second connecting part, so that the first sealing ring is completely embedded in the first sealing ring groove. The first sealing ring being completely embedded in the first sealing ring groove in its normal state facilitates the placement of the sampling hose on the outer peripheral wall of the first connecting part, avoiding any obstruction to the placement of the sampling hose due to the exposure of the first sealing ring, thereby improving the ease of assembly and disassembly between the sampling hose and the first connecting part. After the sampling hose is placed on the first connecting part and the installation branch is inserted into the second connecting part, the second mating part is forced to tighten the mating ring. At this time, the drive component can drive the push ring to move away from the second connecting part to squeeze the first sealing ring, causing the first sealing ring to expand under the action of the guide surface and partially expose itself in the first sealing ring groove to press against the inner peripheral wall of the sampling hose, improving the sealing effect between the sampling hose and the first connecting part. After the first sealing ring is pressed against the inner circumferential wall of the sampling tube, the first sealing ring and the first mating part form a clamping and fixing of the sampling tube, improving the ease of disassembly and assembly of the sampling tube.

[0019] Optionally, a rotating arc groove is provided in the first connecting part. One end of the rotating arc groove passes through the guide surface, and the other end passes through the outer peripheral wall of the first connecting part. A pushing arc strip is slidably arranged in the rotating arc groove. When the pushing ring moves away from the second connecting part, the pushing ring pushes the pushing arc strip, so as to force the end of the pushing arc strip away from the pushing ring to abut against the inner peripheral wall of the sampling tube, and exert a pushing force on the sampling tube to move closer to the second connecting part.

[0020] By adopting the above technical solution, when the second mating part tightens the mating ring by setting the pushing arc strip, the pushing ring pushes the first sealing ring to move along the guide surface away from the second connecting part, and makes the first sealing ring press against the inner circumferential wall of the sampling tube, causing the sampling tube to be squeezed by the first sealing ring and have a retraction squeezing force; while the pushing ring pushes the first sealing ring, the pushing ring can also push the pushing arc strip, forcing the pushing arc strip to rotate around its own central axis, so that one end of the pushing arc strip can abut against the sampling tube and form a pushing force that drives the sampling tube to move closer to the second connecting part. This pushing force cancels out the squeezing force on the sampling tube, thereby reducing the possibility of the sampling tube retraction when the first sealing ring presses against the sampling tube, and thus improving the connection stability between the sampling tube and the first connecting part.

[0021] Optionally, a diversion ring is provided at the end of the first connecting part away from the second connecting part, and the inner diameter of the diversion ring is smaller than the inner diameter of the first connecting part; a diversion channel is formed between the diversion ring and the first connecting part, and the diversion channel is arranged in a ring shape around the central axis of the diversion ring, and the diameter of the diversion channel gradually increases from the side closer to the second connecting part to the side farther away from the second connecting part.

[0022] By adopting the above technical solution, and by setting up a diversion ring and a diversion channel, a diversion ring is added to the end of the first connection part away from the second connection part to form a diversion channel through which the feed liquid flows. After the feed liquid enters the diversion channel, it is discharged outward from the outlet end of the diversion channel, thereby pushing the feed liquid located at the end face of the first connection part away from the second connection part, making it difficult for the feed liquid in the sampling hose to enter the gap between the outer peripheral wall of the first connection part and the inner peripheral wall of the sampling hose, thereby improving the sealing performance of the overall structure.

[0023] Secondly, the automated aseptic sampling method provided in this application adopts the following technical solution:

[0024] An automated aseptic sampling method specifically includes: maintaining a flow regulating valve in a normally open state; an automatic CIP step, controlling the opening of the third and fourth valves, closing the first, second, and fifth valves, introducing cleaning fluid from an external cleaning fluid output device to clean the pipeline, and controlling the closing of the third and fourth valves after a set duration; an automatic SIP step, controlling the opening of the third and fifth valves, closing the first, second, and fourth valves, introducing steam from an external steam generator to sterilize the pipeline, acquiring data from a temperature sensor, and controlling the closing of the third and fifth valves after the temperature reaches a set value and continues for a set duration; and an automatic sampling step, controlling the opening of the first and fifth valves, closing the third and fourth valves, allowing the liquid to enter the sample storage tube through the first valve and the flow regulating valve, closing the first valve after it rises to a set height, then controlling the opening of the second valve, and automatically extracting the liquid sample from the sample storage tube using a peristaltic pump in an external biochemical analyzer to complete the sampling.

[0025] In summary, this application includes at least one of the following beneficial technical effects:

[0026] 1. By setting up sampling pipelines, CIP pipelines, and SIP pipelines, the third and fourth valves are opened while the first, second, and fifth valves are closed. Cleaning solution is introduced through the cleaning solution output device to clean the pipelines. After cleaning, the third and fifth valves are opened while the first, second, and fourth valves are closed. Steam is introduced through the steam generator to sterilize the pipelines. After sterilization, the first and fifth valves are opened while the third and fourth valves are closed, allowing the feed liquid in the bioreactor to enter the sample storage tube through the first valve. When the sample reaches the set height, the first valve is closed and the second valve is opened. The biochemical analyzer can then obtain the sample to be analyzed from the bioreactor output from the sample storage tube. The CIP and SIP pipelines work together to clean and sterilize the sample storage tube, ensuring that the sample is not contaminated during subsequent sampling. The entire process can be completed by the controller controlling the coordinated action of each valve, requiring no manual intervention and resulting in high sampling efficiency.

[0027] 2. Through the arrangement of the first sealing ring, guide surface, and push ring, during installation of the first sealing ring, the first sealing ring is fitted into the first sealing ring groove and displaced to the side of the first sealing ring groove closer to the second connecting part, so that the first sealing ring is completely embedded in the first sealing ring groove. The complete embedding of the first sealing ring in the first sealing ring groove under normal conditions facilitates the placement of the sampling hose on the outer peripheral wall of the first connecting part, preventing the exposed first sealing ring from obstructing the placement of the sampling hose, thereby improving the ease of assembly and disassembly between the sampling hose and the first connecting part. After the sampling hose is placed on the first connecting part and the installation branch is inserted into the second connecting part, the second mating part is forced to tighten the mating ring. At this time, the drive assembly can drive the push ring to move away from the second connecting part to compress the first sealing ring, causing the first sealing ring to expand under the action of the guide surface and partially expose itself in the first sealing ring groove to press against the inner peripheral wall of the sampling hose, improving the sealing effect between the sampling hose and the first connecting part. After the first sealing ring is pressed against the inner circumferential wall of the sampling tube, the first sealing ring and the first mating part form a clamping and fixing of the sampling tube, improving the ease of disassembly and assembly of the sampling tube.

[0028] 3. By setting the pusher ring, when the second mating part tightens the mating ring, the pusher ring pushes the first sealing ring to move along the guide surface away from the second connecting part, and makes the first sealing ring press against the inner circumferential wall of the sampling tube, causing the sampling tube to be squeezed by the first sealing ring and have a retraction squeezing force; while the pusher ring pushes the first sealing ring, the pusher ring can also push the pusher ring, forcing the pusher ring to rotate around its own central axis, so that one end of the pusher ring can abut against the sampling tube and form a pushing force that drives the sampling tube to move closer to the second connecting part. This pushing force cancels out the squeezing force on the sampling tube, thereby reducing the possibility of the sampling tube retraction when the first sealing ring presses against the sampling tube, and thus improving the connection stability between the sampling tube and the first connecting part. Attached Figure Description

[0029] Figure 1 This is a schematic diagram of the overall structure of Example 1;

[0030] Figure 2 This is a schematic diagram illustrating the structure of the sampling pipeline, CIP pipeline, and SIP pipeline in Example 1;

[0031] Figure 3 This is a partial cross-sectional view of the connecting components in Embodiment 1;

[0032] Figure 4 This is a partial cross-sectional view of the connecting components in Embodiment 2;

[0033] Figure 5 yes Figure 4 Enlarged view of point A in the middle;

[0034] Figure 6 This is a partial cross-sectional view of Embodiment 3 illustrating the pushing arc strip;

[0035] Figure 7 This is a partial cross-sectional view of the diversion channel in Example 4.

[0036] Explanation of reference numerals in the attached drawings: 1. Sampling pipeline; 11. Sample storage tube; 111. First valve; 112. Second valve; 113. Inlet tube; 114. Flow regulating valve; 12. Sampling hose; 13. Installation branch pipe; 131. Third sealing ring groove; 2. CIP pipeline; 21. CIP inlet pipe; 211. Third valve; 22. CIP return pipe; 221. Fourth valve; 3. SIP pipeline; 31. SIP air inlet pipe; 32. SIP return pipe; 321. Fifth valve; 322. Temperature sensor; 323. Steam trap; 4. Bioreactor; 5. Biochemical analyzer; 6. Cleaning solution output device; 61. CIP return liquid collection device; 7. Steam generator; 71. Condensate recovery device; 8. Connecting assembly; 81. Connecting joint; 8111. First connecting part; 8111 8112. First sealing ring groove; 8113. Guide surface; 8114. Rotating arc groove; 812. Second connecting part; 8121. Second sealing ring groove; 8122. Mounting ring groove; 813. First sealing ring; 814. Pushing ring; 815. Pushing arc strip; 816. Diverting ring; 8161. Diverting channel; 8162. Countersunk bolt; 8163. Isolating ball; 817. Pushing piece; 82. Butt ring; 83. Butt sleeve; 831. First butt part; 832. Second butt part; 84. Pagoda connector; 841. Insertion part; 842. Rotating part; 843. Sleeving part; 844. Third sealing ring; 85. Locking fastener; 9. Drive assembly; 91. First drive ring; 911. Second sealing ring; 92. First drive rod; 93. Second drive ring; 94. Second drive rod; 95. Return spring. Detailed Implementation

[0037] The following is in conjunction with the appendix Figure 1 - Appendix Figure 7 This application will be described in further detail.

[0038] Example 1:

[0039] This application discloses an automated aseptic sampling and biochemical analysis device, which is mainly used in the pharmaceutical industry to efficiently and aseptically sample the liquid in the bioreactor 4, especially the fermenter.

[0040] Reference Figure 1 , Figure 2An automated aseptic sampling and biochemical analyzer docking device includes a controller, a sampling pipeline 1, a CIP pipeline 2, and a SIP pipeline 3. The sampling pipeline 1 includes a sample storage tube 11 and a sampling hose 12, which are sequentially connected. The sample storage tube 11 is connected to the wall of a bioreactor 4, and a first valve 111 is installed between them. The sample storage tube 11 is vertically arranged. One end of the sampling hose 12 is connected to the bottom end of the sample storage tube 11 via a second valve 112, and the other end is connected to an external biochemical analyzer 5.

[0041] Reference Figure 1 , Figure 2 The bottom end of the sample storage tube 11 is connected to the sample inlet tube 113. One end of the sample inlet tube 113 is connected to the sample storage tube 11, and the other end is connected to the wall of the bioreactor 4 and connected to the inside of the bioreactor 4. The sample inlet tube 113 is inclined and its height gradually decreases from the end close to the sample storage tube 11 to the end far away from the sample storage tube 11. The first valve 111 is installed on the sample inlet tube 113. The connection point between the sample inlet tube 113 and the bioreactor 4 is not higher than the lowest liquid level of the feed liquid in the bioreactor 4.

[0042] During the sampling process, the internal pressure of the bioreactor 4 can be set to positive. When the first valve 111 is opened, the liquid will automatically enter the sample storage tube 11. By controlling the opening time of the first valve 111, the amount of liquid entering the sample storage tube 11 can be controlled to prevent excessive sampling and waste of liquid. Then, the peristaltic pump in the external biochemical analyzer 5 is used to draw the liquid in the sample storage tube 11 for analysis, thus achieving sampling.

[0043] Reference Figure 1 , Figure 2 The bottom end of the sample storage tube 11 is connected to a flow regulating valve 114. When the docking device is idle, the sampling line 1 can be shut off, and the flow rate can be controlled during device use. The amount of liquid entering the sample storage tube 11 can be controlled by the opening time of the first valve 111. During the first sampling, the flow regulating valve 114 is used to ensure the amount of liquid entering the sample storage tube 11 to prevent over-sampling. In practical applications, adjustment is required during the first sampling, while subsequent sampling can maintain the initial state of the flow regulating valve 114. Preferably, the first valve 111 and the flow regulating valve 114 adopt a combined valve structure to avoid dead zones in cleaning and sterilization.

[0044] Reference Figure 1 , Figure 2The CIP pipeline 2 includes a CIP inlet pipe 21 and a CIP return pipe 22. One end of the CIP inlet pipe 21 is connected to the external cleaning fluid output device 6, and the other end is connected to the output end of the first valve 111 via the third valve 211. A CIP inlet valve (not shown in the figure) is configured between the external cleaning fluid output device 6 and the CIP inlet pipe 21. One end of the CIP return pipe 22 is connected to the top of the sample storage tube 11, and the other end is connected to the external CIP return collection device 61 via the fourth valve 221.

[0045] In this embodiment, the connections between the above-mentioned pipelines are all made in a smooth, integrated manner to avoid dead zones in the flow of liquid. With the above solution, when it is necessary to clean the pipelines, it is only necessary to close the first valve 111 and the second valve 112, and open the third valve 211 and the fourth valve 221 to flush and clean the pipelines with cleaning fluid.

[0046] Reference Figure 1 , Figure 2 The SIP pipeline 3 includes a SIP inlet pipe 31 and a SIP return pipe 32. In this embodiment, high-temperature steam is mainly used to sterilize the cleaned pipeline. Therefore, one end of the SIP inlet pipe 31 is connected to an external steam generator 7, and the other end is connected to a CIP liquid inlet pipe 21. A SIP steam inlet valve (not shown in the figure) is configured between the external steam generator 7 and the SIP inlet pipe 31. One end of the SIP return pipe 32 is connected to the top of the sample storage tube 11, and the other end is connected to an external condensate recovery device 71 via a fifth valve 321.

[0047] In this embodiment, when sterilization of the pipeline is required, it is only necessary to close the first valve 111, the second valve 112, and the fourth valve 221, and open the third valve 211 and the fifth valve 321. This allows external high-temperature steam to be introduced into the sample storage tube 11 via the SIP inlet pipe 31, and then discharged via the SIP return pipe 32, thus achieving pipeline sterilization. To simplify the pipeline structure, the aforementioned SIP inlet pipe 31 and CIP liquid inlet pipe 21 are reused in a time-sharing manner.

[0048] Reference Figure 1 , Figure 2 In this embodiment, the controller (not shown in the figure) adopts a PLC or microcontroller control module. The first valve 111, the second valve 112, the third valve 211, the fourth valve 221 and the fifth valve 321 are all pneumatic diaphragm valves. Each pneumatic diaphragm valve is connected to the controller. The flow regulating valve 114 is a manual diaphragm valve.

[0049] Reference Figure 1 , Figure 2To ensure the sterilization effect of the pipeline, a temperature sensor 322 and a steam trap 323 are installed sequentially along the exhaust direction of the SIP return pipe 32. The temperature sensor 322 is used to detect the temperature inside the pipeline, and the steam trap 323 is used to prevent steam from being discharged. Both the temperature sensor 322 and the steam trap 323 are located between the fifth valve 321 and the external condensate recovery device 71.

[0050] The controller is connected to temperature sensor 322, which collects the steam temperature in the SIP return pipe 32. The controller receives and responds to the temperature data to control the steam intake. Preferably, the temperature in the pipe is maintained at 121°C. Steam trap 323 blocks steam and discharges condensate, maintaining the pressure in the pipe within a set range, preferably greater than 0.1 MPa. By detecting the temperature in the SIP pipe 3, the sterilization status of the sample storage tube 11 and related valves is determined. After sterilization is complete, the controller controls the fifth valve 321 and the third valve 211 to close.

[0051] Reference Figure 1 , Figure 2 The bottom periphery of the sample storage tube 11 is connected to an installation branch tube 13. The installation branch tube 13 is located on the side of the flow regulating valve 114 away from the first valve 111. The end of the installation branch tube 13 away from the sample storage tube 11 is used to connect to the sampling tube 12. The end of the sampling tube 12 away from the biochemical analyzer 5 is connected to the sample storage tube 11 through the installation branch tube 13. A connecting component 8 is provided between the installation branch tube 13 and the sampling tube 12, and the sampling tube 12 can be detachably installed and installed on the installation branch tube 13 through the connecting component 8. In practical applications, the sampling tube 12 needs to be sterilized offline after multiple uses (i.e., the sampling tube 12 needs to be detached) to reduce the bioburden.

[0052] Reference Figure 2 , Figure 3 In this embodiment, the connecting component 8 includes a pagoda connector 84 and a locking fastener 85. The pagoda connector 84 includes an integrally formed insertion part 841, a rotating part 842, and a fitting part 843. The rotating part 842 is disposed between the insertion part 841 and the fitting part 843. The rotating part 842 has a polygonal shape for connecting tools such as wrenches. The insertion part 841 is inserted into the sampling hose 12, and the outer diameter of the insertion part 841 is adapted to the inner diameter of the sampling hose 12. The fitting part 843 is fitted onto the outer peripheral wall of the mounting branch pipe 13, and the inner peripheral wall of the fitting part 843 is threadedly connected to the outer peripheral wall of the mounting branch pipe 13 (the thread is not shown in the figure). In this embodiment, the locking fastener 85 is a hose clamp, which is tightened onto the outer peripheral wall of the sampling hose 12 to fix the connection between the sampling hose 12 and the insertion part 841.

[0053] Reference Figure 3The outer peripheral wall of the insertion part 841 is provided with multiple embedding annular grooves. The multiple embedding annular grooves are arranged at intervals along the central axis of the insertion part 841. Each embedding annular groove is opened in a ring around the central axis of the insertion part. Each embedding annular groove is provided with a third sealing ring 844. The third sealing ring 844 is partially exposed outside the embedding annular groove to press against the inner peripheral wall of the sampling tube 12.

[0054] The implementation principle of Embodiment 1 of this application is as follows: The third valve 211 and the fourth valve 221 are opened while the first valve 111, the second valve 112, and the fifth valve 321 are closed. Cleaning fluid is introduced through the cleaning fluid output device 6 to clean the pipeline. After cleaning, the third valve 211 and the fifth valve 321 are opened while the first valve 111, the second valve 112, and the fourth valve 221 are closed. Steam is introduced through the steam generator 7 to sterilize the pipeline. After sterilization, the first valve 111 and the fifth valve 321 are opened while the third valve 211 is closed. The fourth valve 221 allows the feed liquid in the bioreactor 4 to enter the sample storage tube 11 through the first valve 111. When it reaches the set height, the first valve 111 is closed and the second valve 112 is opened. The biochemical analyzer 5 can obtain the sample to be analyzed from the bioreactor 4 from the sample storage tube 11. The CIP pipeline 2 and SIP pipeline 3 work together to clean and sterilize the sample storage tube 11, ensuring that the sample is not contaminated during subsequent sampling. The whole process can be completed by the controller controlling the coordinated action of each valve, without manual intervention, and the sampling efficiency is high.

[0055] Example 2:

[0056] This application discloses an automated aseptic sampling and docking device for biochemical analysis.

[0057] Reference Figure 4 , Figure 5 The difference between the automated aseptic sampling and biochemical analyzer device disclosed in this application and Embodiment 1 is that:

[0058] In this embodiment, the connecting component 8 includes a connecting joint 81, a docking ring 82, and a docking sleeve 83. The connecting joint 81 includes a first connecting part 811 and a second connecting part 812 integrally formed. The first connecting part 811 and the second connecting part 812 are coaxially arranged. The end of the sampling tube 12 away from the biochemical analyzer 5 is sleeved on the outer peripheral wall of the first connecting part 811. The inner diameter of the sampling tube 12 is adapted to the outer diameter of the first connecting part 811, and the outer diameter of the sampling tube 12 is smaller than the outer diameter of the second connecting part 812. The end of the mounting branch tube 13 away from the sample storage tube 11 is inserted into the second connecting part 812. The outer diameter of the mounting branch tube 13 is adapted to the inner diameter of the second connecting part 812.

[0059] Reference Figure 4 , Figure 5The docking ring 82 is fixedly installed on the outer peripheral wall of the mounting branch pipe 13. The docking ring 82 and the mounting branch pipe 13 are integrally formed. The outer diameter of the docking ring 82 is adapted to the outer diameter of the second connecting part 812. The docking sleeve 83 includes an integrally formed first docking part 831 and a second docking part 832. The first docking part 831 is sleeved on the outer peripheral wall of the sampling hose 12. The inner diameter of the first docking part 831 is adapted to the outer diameter of the sampling hose 12. The second docking part 832 is sleeved on both the outer peripheral wall of the second connecting part 812 and the outer peripheral wall of the docking ring 82. The inner diameter of the second docking part 832 is adapted to the outer diameter of the docking ring 82. The second docking part 832 and the docking ring 82 are threadedly connected.

[0060] Reference Figure 4 , Figure 5 The outer peripheral wall of the first connecting part 811 is provided with a first sealing ring groove 8111. The first sealing ring groove 8111 is opened in a ring around the central axis of the first connecting part 811. A first sealing ring 813 is embedded in the first sealing ring groove 8111. The inner wall of the first sealing ring groove 8111 has a guide surface 8112. The outer diameter of the guide surface 8112 gradually increases from the side closer to the second connecting part 812 to the side farther away from the second connecting part 812.

[0061] Reference Figure 4 , Figure 5 A push ring 814 is slidably installed in the first sealing ring groove 8111. The push ring 814 is slidably installed in the first sealing ring groove 8111 and can be displaced along the central axis of the first connecting part 811. The outer diameter of the push ring 814 is not greater than the outer diameter of the first connecting part 811. The push ring 814 is located on the side of the first sealing ring 813 close to the second connecting part 812. The second connecting part 812 is provided with a drive assembly 9. When the second docking part 832 tightens the docking ring 82, the drive assembly 9 drives the push ring 814 to move away from the second connecting part 812 so that the first sealing ring 813 abuts against the inner peripheral wall of the sampling tube 12.

[0062] Reference Figure 4 , Figure 5 The inner wall of the second connecting part 812 is provided with a second sealing ring groove 8121, which is arranged in a ring around the central axis of the second connecting part 812. The driving assembly 9 includes a first driving ring 91, a first driving rod 92 and a driving member. The first driving ring 91 is slidably installed in the second sealing ring groove 8121 and can be displaced along the central axis of the second connecting part 812. Multiple first driving rods 92 are provided, and the multiple first driving rods 92 are arranged at intervals around the central axis of the second connecting part 812. One end of each first driving rod 92 is fixedly installed on the side wall of the first driving ring 91, and the other end passes through the first sealing ring groove 8111 and is fixedly connected to the pushing ring 814. The pushing ring 814 and the first driving ring 91 are connected by multiple first driving rods 92.

[0063] Reference Figure 4 , Figure 5 A second sealing ring 911 is fixedly installed on the side wall of the first driving ring 91 away from the pushing ring 814. The second sealing ring 911 is partially exposed in the second sealing ring groove 8121. The inner peripheral wall of the second connecting part 812 is provided with a mounting ring groove 8122, which is arranged in a ring around the central axis of the second connecting part 812. The driving component includes a second driving ring 93, a second driving rod 94, and a return spring 95. The second driving ring 93 is slidably installed in the mounting ring groove 8122 and can be displaced along the central axis of the second connecting part 812. The inner diameter of the second driving ring 93 is smaller than the inner diameter of the second connecting part 812. The end face of the mounting branch pipe 13 is provided with a third sealing ring groove 131 for the second sealing ring 911 to be embedded. When the mounting branch pipe 13 is inserted into the second connecting part 812, the second driving ring 93 is embedded in the third sealing ring groove 131 to compress the second sealing ring 911.

[0064] Reference Figure 4 , Figure 5 Multiple second drive rods 94 are provided, and the multiple second drive rods 94 are arranged at intervals around the central axis of the second connecting part 812. One end of each second drive rod 94 is fixedly connected to the side wall of the second drive ring 93, and the other end extends to the side of the second connecting part 812 away from the first connecting part 811 for the docking ring 82 to abut. When the second docking part 832 tightens the docking ring 82, the docking ring 82 pushes the second drive rod 94, so that the first drive ring 91 and the second drive ring 93 are simultaneously clamped in the second sealing ring 911, and the pushing ring 814 pushes the first sealing ring 813 to move along the guide surface 8112 toward the side away from the second connecting part 812, so as to abut against the inner peripheral wall of the sampling tube 12.

[0065] The reset spring 95 is installed in the mounting ring groove 8122. One end of the reset spring 95 is fixedly connected to the inner wall of the mounting ring groove 8122, and the other end is fixedly connected to the side wall of the second drive ring 93. Normally, the reset spring 95 causes one end of the second drive rod 94 to extend out of the second connecting part 812 so that the docking ring 82 can abut against it.

[0066] The implementation principle of Embodiment 2 of this application is as follows: When installing the first sealing ring 813, the first sealing ring 813 is fitted into the first sealing ring groove 8111 and the first sealing ring 813 is moved to the side of the first sealing ring groove 8111 close to the second connecting part 812, so that the first sealing ring 813 is completely embedded in the first sealing ring groove 8111. The fact that the first sealing ring 813 is completely embedded in the first sealing ring groove 8111 under normal conditions makes it easy for the sampling hose 12 to be fitted on the outer peripheral wall of the first connecting part 811, avoiding the exposure of the first sealing ring 813 from hindering the fitting of the sampling hose 12, thereby improving the ease of disassembly and assembly between the sampling hose 12 and the first connecting part 811.

[0067] After the sampling hose 12 is fitted onto the first connecting part 811 and the mounting branch pipe 13 is inserted into the second connecting part 812, the second docking part 832 is forced to tighten the docking ring 82. At this time, the docking ring 82 can push the second drive rod 94, so that the first drive ring 91 and the second drive ring 93 are simultaneously clamped on the second sealing ring 911, and the push ring 814 pushes the first sealing ring 813 to move along the guide surface 8112 toward the side away from the second connecting part 812, so as to press against the inner peripheral wall of the sampling hose 12, which greatly improves the sealing effect of the overall structure and the ease of disassembly and assembly of the overall structure.

[0068] Example 3:

[0069] This application discloses an automated aseptic sampling and docking device for biochemical analysis.

[0070] Reference Figure 6 The difference between the automated aseptic sampling and biochemical analyzer device disclosed in this application and Embodiment 2 is that:

[0071] In this embodiment, a rotating arc groove 8113 is provided in the first connecting part 811. The number of rotating arc grooves 8113 is set to multiple. The multiple rotating arc grooves 8113 are arranged at intervals around the central axis of the first connecting part 811. One end of the rotating arc groove 8113 penetrates the guide surface 8112, and the other end penetrates the outer peripheral wall of the first connecting part 811. A pushing arc strip 815 is slidably installed in each rotating arc groove 8113. The end of the pushing arc strip 815 near the second connecting part 812 extends out of the rotating arc groove 8113 and is connected to a pushing piece 817 located in the first sealing ring groove 8111. When the push ring 814 moves away from the second connecting part 812, the push ring 814 pushes the push plate 817, causing the push arc strip 815 to slide along the arc of the rotating arc groove 8113, and forcing the end of the push arc strip 815 away from the push ring 814 to abut against the inner peripheral wall of the sampling tube 12, and the push arc strip 815 has a pushing force on the sampling tube 12 to move closer to the second connecting part 812.

[0072] The implementation principle of Embodiment 3 of this application is as follows: When the second docking part 832 tightens the docking ring 82, the pushing ring 814 pushes the first sealing ring 813 to move along the guide surface 8112 away from the second connecting part 812, and makes the first sealing ring 813 press against the inner peripheral wall of the sampling hose 12, causing the sampling hose 12 to be squeezed by the first sealing ring 813 and have a retraction squeezing force; while the pushing ring 814 pushes the first sealing ring 813, the pushing ring 814 can also push the pushing arc strip 815. The pusher is forced to rotate the pusher arc 815 around its own central axis, so that one end of the pusher arc 815 can come into contact with the sampling hose 12 and generate a pushing force that drives the sampling hose 12 toward the second connection part 812. This pushing force cancels out the squeezing force on the sampling hose 12, thereby reducing the possibility of the sampling hose 12 retracting when the first sealing ring 813 is pressed against the sampling hose 12, and thus improving the connection stability between the sampling hose 12 and the first connection part 811.

[0073] Example 4:

[0074] This application discloses an automated aseptic sampling and docking device for biochemical analysis.

[0075] Reference Figure 7 The difference between the automated aseptic sampling and biochemical analyzer device disclosed in this application and Embodiment 2 is that:

[0076] In this embodiment, a diverter ring 816 is detachably installed at the end of the first connecting part 811 away from the second connecting part 812. The diverter ring 816 is coaxially arranged with the first connecting part 811, and the inner diameter of the diverter ring 816 is smaller than the inner diameter of the first connecting part 811. The diverter ring 816 is equipped with a plurality of countersunk bolts 8162, which are arranged at intervals around the central axis of the diverter ring 816. The countersunk bolts 8162 are sequentially inserted into the diverter ring 816 and the first connecting part 811 and are threadedly connected to the first connecting part 811.

[0077] The end face of the first connecting part 811 away from the second connecting part 812 has a first diversion surface, and the side wall of the diversion ring 816 near the first connecting part 811 has a second diversion surface. The outer wall of the countersunk bolt 8162 is fitted with an isolation ball 8163. The surface of the isolation ball 8163 abuts against the first diversion surface and the second diversion surface respectively. The isolation ball 8163 makes the first diversion surface of the first connecting part 811 and the second diversion surface of the diversion ring 816 spaced apart to form a diversion channel 8161 for the flow of the feed liquid. The diversion channel 8161 is arranged in a ring around the central axis of the diversion ring 816, and the diameter of the diversion channel 8161 gradually increases from the side near the second connecting part 812 to the side away from the second connecting part 812.

[0078] The implementation principle of Embodiment 4 of this application is as follows: A diversion ring 816 is added to the end of the first connecting part 811 away from the second connecting part 812 to form a diversion channel 8161 through which the feed liquid flows. After the feed liquid enters the diversion channel 8161, it is discharged outward from the outlet end of the diversion channel 8161, thereby pushing the feed liquid located at the end face of the first connecting part 811 away from the second connecting part 812, so that the feed liquid in the sampling hose 12 is less likely to enter the gap between the outer peripheral wall of the first connecting part 811 and the inner peripheral wall of the sampling hose 12, thereby improving the sealing performance of the overall structure.

[0079] Example 5:

[0080] This application also discloses an automated aseptic sampling method.

[0081] An automated aseptic sampling method, which keeps the flow regulating valve 114 in a normally open state, mainly includes:

[0082] Automatic CIP procedure: Control the opening of the third valve 211 and the fourth valve 221, and close the first valve 111, the second valve 112 and the fifth valve 321. Cleaning fluid is introduced from the external cleaning fluid output device 6 to clean the pipeline. After a set duration, control the closing of the third valve 211 and the fourth valve 221.

[0083] Automatic SIP steps: control the opening of the third valve 211 and the fifth valve 321, and close the first valve 111, the second valve 112 and the fourth valve 221. Steam is introduced from the external steam generator 7 to sterilize the pipeline. Data from the temperature sensor 322 is acquired. When the temperature reaches the set value and continues for the set time, the third valve 211 and the fifth valve 321 are controlled to close.

[0084] Automatic sampling steps: Control the opening of the first valve 111 and the fifth valve 321, and close the third valve 211 and the fourth valve 221. The liquid enters the sample storage tube 11 through the first valve 111 and the flow regulating valve 114. When it rises to the set height, the first valve 111 is closed. Then, control the opening of the second valve 112. The peristaltic pump in the external biochemical analyzer 5 automatically extracts the liquid sample from the sample storage tube 11, completing the sampling.

[0085] In detail, in the embodiments of this application, the sample storage tube 11 has a vertical pipe space of 300mm above the flow regulating valve 114. By adjusting the flow of the flow regulating valve 114 and setting the opening time of the first valve 111, the liquid is allowed to rise to a height of 200~300mm. A pipe sight glass is installed at the top to prevent excessive sampling and waste.

[0086] It should be noted that the method disclosed in this application includes detailed descriptions of each implementation step. The order of the descriptions of each step should not be construed as a limitation on the specific implementation order. In practical applications, the above steps can be performed individually or in combination according to a selected order, as needed.

[0087] The above are preferred embodiments of this application, and are not intended to limit the scope of protection of this application. Therefore, all equivalent changes made to the structure, shape and principle of this application should be covered within the scope of protection of this application.

Claims

1. An automated aseptic sampling and docking device for biochemical analyzers, characterized in that: The system includes a controller, a sampling pipeline (1), a CIP pipeline (2), and a SIP pipeline (3). The sampling pipeline (1) includes a sample storage tube (11) and a sampling hose (12) connected in sequence. The sample storage tube (11) is connected to the bioreactor (4) and a first valve (111) is provided between them. One end of the sampling hose (12) is connected to the bottom end of the sample storage tube (11) via a second valve (112), and the other end is connected to an external biochemical analyzer (5). The CIP pipeline (2) includes a CIP inlet pipe (21) and a CIP return pipe (22). One end of the CIP inlet pipe (21) is connected to an external cleaning fluid output device (6), and the other end is connected to the output end of the first valve (111) via a third valve (211). One end of the CIP return pipe (22) is connected to the top of the sample storage tube (11), and the other end is connected to an external CIP return fluid collection device (61) via a fourth valve (221). The SIP pipeline (3) It includes a SIP inlet pipe (31) and a SIP return pipe (32). One end of the SIP inlet pipe (31) is connected to an external steam generator (7), and the other end is connected to a CIP liquid inlet pipe (21). One end of the SIP return pipe (32) is connected to the top of the sample storage tube (11), and the other end is connected to an external condensate recovery device (71) via a fifth valve (321). Each valve is connected to the controller. The sample storage tube (11) is vertically arranged. The bottom end of the storage tube (11) is connected to the injection tube (113). The end of the injection tube (113) away from the sample storage tube (11) is connected to the bioreactor (4). The injection tube (113) is inclined. The first valve (111) is located on the injection tube (113). The connection point between the injection tube (113) and the bioreactor (4) is not higher than the lowest liquid level of the feed liquid in the bioreactor (4). The bottom end of the sample storage tube (11) is connected to the flow regulating valve (114).

2. The automated aseptic sampling and biochemical analyzer device according to claim 1, characterized in that: The SIP return pipe (32) is sequentially equipped with a temperature sensor (322) for detecting the temperature inside the pipe and a steam trap (323) to prevent steam from escaping. The temperature sensor (322) and the steam trap (323) are both located between the fifth valve (321) and the external condensate recovery device (71). The controller is signal-connected to the temperature sensor (322).

3. The automated aseptic sampling and biochemical analysis device according to claim 1, characterized in that: The first valve (111), the second valve (112), the third valve (211), the fourth valve (221) and the fifth valve (321) are all pneumatic diaphragm valves, and the flow regulating valve (114) is a manual diaphragm valve.

4. The automated aseptic sampling and biochemical analyzer device according to claim 1, characterized in that: The bottom periphery of the sample storage tube (11) is connected to an installation branch tube (13). The end of the sampling tube (12) away from the biochemical analyzer (5) is connected to the installation branch tube (13). The sampling tube (12) is connected to the sample storage tube (11) through the installation branch tube (13). A connecting component (8) is provided between the installation branch tube (13) and the sampling tube (12). The sampling tube (12) is detachably installed on the installation branch tube (13) through the connecting component (8).

5. The automated aseptic sampling and biochemical analyzer device according to claim 4, characterized in that: The connecting assembly (8) includes a connecting joint (81), a docking ring (82), and a docking sleeve (83). The connecting joint (81) includes an integrally formed first connecting part (811) and a second connecting part (812). One end of the sampling hose (12) is sleeved on the outer peripheral wall of the first connecting part (811). The outer diameter of the sampling hose (12) is smaller than the outer diameter of the second connecting part (812). One end of the mounting branch pipe (13) is inserted into the second connecting part (812). The docking ring (811) 82) The outer diameter of the docking ring (82) is adapted to the outer diameter of the second connecting part (812) and is disposed on the outer peripheral wall of the mounting branch pipe (13); the docking sleeve (83) includes an integrally formed first docking part (831) and a second docking part (832). The first docking part (831) is sleeved on the outer peripheral wall of the sampling hose (12), and the second docking part (832) is sleeved on both the outer peripheral wall of the second connecting part (812) and the outer peripheral wall of the docking ring (82) and is threadedly connected to the docking ring (82).

6. The automated aseptic sampling and biochemical analyzer device according to claim 5, characterized in that: The outer peripheral wall of the first connecting part (811) is provided with a first sealing ring groove (8111), and a first sealing ring (813) is provided in the first sealing ring groove (8111); the first sealing ring groove (8111) has a guide surface (8112), and the outer diameter of the guide surface (8112) gradually increases from the side near the second connecting part (812) to the side away from the second connecting part (812); a push ring (814) is slidably installed in the first sealing ring groove (8111), and the push ring (814) is located on the side of the first sealing ring (813) near the second connecting part (812); the second connecting part (812) is provided with a drive assembly (9), and when the second docking part (832) tightens the docking ring (82), the drive assembly (9) drives the push ring (814) to move away from the second connecting part (812), so that the first sealing ring (813) abuts against the inner peripheral wall of the sampling tube (12).

7. The automated aseptic sampling and biochemical analyzer device according to claim 6, characterized in that: A rotating arc groove (8113) is provided in the first connecting part (811). One end of the rotating arc groove (8113) passes through the guide surface (8112), and the other end passes through the outer peripheral wall of the first connecting part (811). A pushing arc strip (815) is slidably arranged in the rotating arc groove (8113). When the pushing ring (814) moves away from the second connecting part (812), the pushing ring (814) pushes the pushing arc strip (815) to force the end of the pushing arc strip (815) away from the pushing ring (814) to abut against the inner peripheral wall of the sampling hose (12) and exert a pushing force on the sampling hose (12) to move closer to the second connecting part (812).

8. The automated aseptic sampling and biochemical analyzer device according to claim 5, characterized in that: The first connecting part (811) is provided with a diversion ring (816) at the end away from the second connecting part (812). The inner diameter of the diversion ring (816) is smaller than the inner diameter of the first connecting part (811). A diversion channel (8161) is formed between the diversion ring (816) and the first connecting part (811). The diversion channel (8161) is arranged in a ring shape around the central axis of the diversion ring (816). The diameter of the diversion channel (8161) gradually increases from the side closer to the second connecting part (812) to the side away from the second connecting part (812).

9. An automated aseptic sampling method, based on the automated aseptic sampling and biochemical analyzer device according to any one of claims 1-8, comprising: Keep the flow regulating valve (114) in the normally open position; Automatic CIP steps: control the opening of the third valve (211) and the fourth valve (221), and close the first valve (111), the second valve (112) and the fifth valve (321). Cleaning fluid is introduced from the external cleaning fluid output device (6) to clean the pipeline. After a set duration, control the closing of the third valve (211) and the fourth valve (221). In the automatic SIP step, the third valve (211) and the fifth valve (321) are opened, and the first valve (111), the second valve (112) and the fourth valve (221) are closed. Steam is introduced from the external steam generator (7) to sterilize the pipeline. Data from the temperature sensor (322) is obtained. When the temperature reaches the set value and continues for the set time, the third valve (211) and the fifth valve (321) are closed. In the automatic sampling step, the first valve (111) and the fifth valve (321) are opened, and the third valve (211) and the fourth valve (221) are closed. The liquid enters the sample storage tube (11) through the first valve (111) and the flow regulating valve (114). When the liquid rises to the set height, the first valve (111) is closed. Then the second valve (112) is opened. The peristaltic pump in the external biochemical analyzer (5) automatically extracts the liquid sample from the sample storage tube (11) to complete the sampling.

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