Control method and device for automatic dispensing and exhausting of soft bag preparation

Abstract

The application discloses a kind of soft bag preparation automatic subpackaging exhaust control method and device, the exhaust control method includes the exhaust method based on liquid level detection, the exhaust method based on pressure detection and exhaust method controlled according to priority strategy.The device uses the control method of overall exhaust to bag preparation, under the comprehensive judgment of controller to device component signal, in combination with high-precision liquid level sensor and pressure sensor, intelligent selection of exhaust strategy is realized, so that exhaust process is more flexible, can adapt to different production needs and conditions, while ensuring that air in all subpackaging bags is effectively exhausted, further improve production efficiency and reduce production cost.

Description

Technical Field

[0001] This invention relates to the field of biopharmaceutical technology, and in particular to a method and apparatus for controlling the degassing of soft bag formulations during automatic dispensing. Background Technology

[0002] Formulation repackaging technology is a crucial component of the biopharmaceutical field, particularly essential for formulations used in cell therapy and gene therapy. Bioactive formulations typically require storage at extremely low temperatures to maintain their biological activity. Cellular formulations, in particular, need to be frozen to below -90°C via programmed or gradient cooling before being stored or transported in a cryogenic environment of -150°C. Limiting the amount of residual gas within the bag during this storage or transportation process is a critical step in ensuring the effectiveness of the freezing and cooling process.

[0003] Currently, automated dispensing and degassing primarily relies on pressure or liquid level detection to determine whether degassing is complete for each bag. However, degassing based solely on pressure is ineffective, exhibiting problems such as inconsistent liquid levels between bags, large deviations from expected values, and poor repeatability. While liquid level detection utilizes non-contact sensors like ultrasonic sensors, its accuracy is difficult to achieve 100% due to the interaction between the sensor and the cryopreservation bag material (e.g., EVA or PVC), sometimes falling below 80%. For example, in a degassing operation involving 10 bags, the probability of successful degassing is only 10.7% (P = 0.8^10). Pressure-based degassing schemes may have a failure rate as high as 10%, with a success rate of only 34.9% under the same conditions (P = 0.9^10). For large-scale dispensing and degassing systems, such as dispensing hundreds or even thousands of bags per batch, this inefficiency and reliability severely impact dispensing efficiency and may damage the activity of the formulation. Summary of the Invention

[0004] The purpose of this invention is to provide a method and apparatus for controlling the automatic dispensing and venting of soft bag formulations, thereby improving the success rate of automatic dispensing and venting and minimizing the fluctuation in liquid height between the dispensing bags after venting.

[0005] To address the aforementioned technical problems, this invention provides a method and apparatus for controlling exhaust gas in automatic dispensing of soft bag formulations. The exhaust gas control method includes:

[0006] The venting method based on liquid level detection includes using a peristaltic pump to draw in N dispensing bags and connected pipelines as a whole, so that the liquid in the dispensing bags is squeezed by atmospheric pressure, forcing the air in the dispensing bags to enter the pipeline. When the liquid in the dispensing bags is squeezed into the liquid level sensor installed on its corresponding pipeline, the liquid level sensor triggers a liquid detection success signal. The controller obtains the signal and uses it as the basis for judging that the venting of the dispensing bags is successful.

[0007] The pressure detection-based venting method includes using the peristaltic pump to draw in N dispensing bags and connected pipelines as a whole, so that the liquid in the dispensing bags is squeezed by atmospheric pressure, forcing the air in the dispensing bags to enter the pipeline. If the air pressure in the pipeline is lower than the preset judgment pressure of the controller, it is considered that the liquid in the dispensing bags has been squeezed to the target position of its corresponding pipeline, and the controller judges that the venting is successful.

[0008] The venting method controlled by a priority strategy includes the following steps: During the filling process of N dispensing bags, the controller reads the number N1 of liquid level sensors that detect liquid signals during the filling process; during the venting process, the controller compares N1 with g(N); when N1 < g(N), the controller uses the pressure-based venting control method for venting; when N1 ≥ g(N), the controller uses the liquid level-based venting control method for venting; where g(N) = floor(4.15739 × N) 0.174579 -2.58425).

[0009] Optionally, the pressure-based exhaust control method includes the following steps for exhaust:

[0010] The peristaltic pump continuously reverses, and when the pressure value detected by the pressure sensor is less than or equal to the preset judgment pressure p of the controller, N dispensing clamp valves are closed.

[0011] Where p = a + b × V + c × L, V is the dispensing amount set for each of the dispensing bags, L is the liquid column height preset in the dispensing process, a is a constant term, and b and c are coefficients respectively.

[0012] Optionally, the venting control method based on liquid level includes venting the liquid level by:

[0013] The peristaltic pump continuously reverses, and the number N2 of liquid level sensors that detect liquid signals during the exhaust process is recorded.

[0014] When N2≥g(N), the controller determines that the exhaust is successful and closes N dispensing clamp valves;

[0015] When N2 < g(N), the controller reads the pressure data from the pressure sensor. If the pressure value of the pressure sensor is ≤ p - Δp, it indicates that the liquid level sensor has a high error rate in detecting the liquid level, causing the liquid to rise in the dispensing branch pipe beyond the limit. At this time, the controller determines that the venting is complete and closes N dispensing clamp valves. If the pressure value of the pressure sensor is > p - Δp, the peristaltic pump continues to reverse, and the controller continues to record the number of liquid level sensors N2, and performs a judgment on the magnitude of the number of liquid level sensors N2 and g(N), repeating the judgment process. Here, Δp is the difference between the pressure value of the pressure sensor and the preset judgment pressure p of the controller.

[0016] Optionally, an automatic dispensing and venting method includes:

[0017] To prepare for dispensing, turn on the peristaltic pump to fill the dispensing main pipeline with liquid;

[0018] Dispensing liquid: dispensing the liquid in the mother liquor bag into the dispensing bags of each dispensing component;

[0019] The controller controls the relevant components to simultaneously vent the sub-bags in multiple sub-packaging components based on the venting control method;

[0020] After the venting is complete, the peristaltic pump stops.

[0021] Optionally, the venting of the dispensing bag includes:

[0022] The controller reads the number N1 of liquid level sensors detected during the dispensing process, reads the number N of bags to be dispensed, opens the dispensing clamp valves corresponding to N dispensing bags, and vents air according to the venting method controlled by the priority strategy.

[0023] Optionally, the dispensing preparation includes:

[0024] Open the drain clamp valve and the peristaltic pump;

[0025] The peristaltic pump rotates in the forward direction, causing the liquid to flow from the mother liquor bag to the main dispensing pipeline;

[0026] The main dispensing pipeline is filled with liquid for a fixed time t, or the main dispensing pipeline is filled with liquid to a specific position on the main dispensing pipeline, and the drain clamp valve is closed.

[0027] Optionally, the liquid dispensing process includes:

[0028] The controller gradually opens the dispensing clamp valve in each of the dispensing components;

[0029] Each of the dispensing bags is continuously dispensed for a fixed time t2, wherein the fixed dispensing time t2 = dispensing volume V / average flow rate of the peristaltic pump Q;

[0030] After the dispensing is completed, close the dispensing clamp valve of the corresponding branch, and then sequentially dispense the other dispensing bags.

[0031] The controller determines whether the N dispensing bags have been dispensed. After all the N dispensing bags have been dispensed, the controller determines whether all the dispensing clamp valves are in the closed state and reverses the peristaltic pump.

[0032] And liquid recovery, recovering the liquid in the main dispensing pipeline to the mother liquor bag.

[0033] Optionally, the liquid recovery process includes:

[0034] Open the drain clamp valve, and the peristaltic pump reverses to allow the liquid in the main dispensing pipeline to flow back into the mother liquor bag;

[0035] After a duration of t3, the peristaltic pump stops.

[0036] Open the dispensing clamp valves corresponding to N dispensing bags to allow the liquid in the dispensing branch pipes to flow into the dispensing bags;

[0037] After a duration of t4, the drain clamp valve and the dispensing clamp valves corresponding to the N dispensing bags are closed.

[0038] An automatic dispensing and venting device for soft bag formulations includes a liquid transfer component, a control component, and multiple dispensing components;

[0039] The liquid transfer assembly is used for liquid transport;

[0040] The control components are used to monitor and regulate the dispensing and venting processes;

[0041] Multiple dispensing components are connected to the liquid transfer component and the control component. The control component accurately distributes liquid into the dispensing bags of each dispensing component through the liquid transfer component, and adjusts the venting control mode of the dispensing bags according to liquid level detection data and pressure detection data.

[0042] Optionally, the liquid transfer assembly includes a mother liquor bag, a dispensing main pipeline, a peristaltic pump, and an emptying pipeline; one end of the dispensing main pipeline is connected to the mother liquor bag, the peristaltic pump is installed on the dispensing main pipeline and is close to the mother liquor bag; the emptying pipeline is located at the other end of the dispensing main pipeline and is connected to the dispensing main pipeline.

[0043] Optionally, each of the dispensing components includes a dispensing bag, a dispensing branch line, a dispensing clamp valve, and a liquid level sensor; one end of the dispensing branch line is connected to the dispensing main line after the peristaltic pump is installed, and the other end of the dispensing branch line is connected to the dispensing bag; the dispensing clamp valve and the liquid level sensor are sequentially installed on the dispensing branch line, with the dispensing clamp valve located above the liquid level sensor, and the liquid level sensor set at a predetermined position on the dispensing branch line; the length of the pipeline between the dispensing clamp valve and the dispensing bag is greater than a preset liquid column height L.

[0044] Optionally, the control components include a first sterile air filter, a pressure detection line, a pressure sensor, a venting clamp valve, a second sterile air filter, and a controller;

[0045] One end of the first sterile air filter is connected to the other end of the main dispensing pipeline, and the other end of the first sterile air filter is connected to the pressure sensor through the pressure detection pipeline; the venting pinch valve and the second sterile air filter are installed sequentially on the venting pipeline;

[0046] The controller is connected to the pressure sensor and is used to read the data from the pressure sensor, control the exhaust control logic, and provide control signals to the clamp valves on each branch pipe.

[0047] Compared with the prior art, the present invention has at least the following beneficial effects:

[0048] This invention employs an overall venting control method for bagged formulations. Based on the controller's comprehensive judgment of component signals, combined with high-precision liquid level and pressure sensors, it enables intelligent selection of venting strategies, making the venting process more flexible and adaptable to different production needs and conditions. At the same time, it ensures that air in all packaging bags is effectively vented, further improving production efficiency and reducing production costs. Attached Figure Description

[0049] Figure 1 This is a schematic diagram of the structure of an automatic dispensing and venting device for soft bag formulations in one embodiment of the present invention;

[0050] Figure 2 This is a flowchart of the pre-exhaust liquid level sensor signal recording process in one embodiment of the present invention;

[0051] Figure 3 This is a schematic flowchart of an exhaust control method according to an embodiment of the present invention;

[0052] Figure 4 This is an example graph of the control function curve in one embodiment of the present invention;

[0053] Figure 5This is a preferred diagram showing the number of effective signals from a liquid level sensor in one embodiment of the present invention.

[0054] Reference numerals: 1. Mother liquor bag; 2. Main dispensing line; 3. Peristaltic pump; 4. First sterile air filter; 5. Pressure detection line; 6. Pressure sensor; 7. Drain clamp valve; 8. Drain line; 9. Second sterile air filter; 10. Dispensing branch line; 11. Dispensing clamp valve; 12. Liquid level sensor; 13. Dispensing bag; 14. Liquid column height; 15. Controller; 100. Dispensing assembly. Detailed Implementation

[0055] The following is a more detailed description of a method and apparatus for controlling the degassing of soft-bag formulations during automatic dispensing, with reference to schematic diagrams. Preferred embodiments of the invention are shown. It should be understood that those skilled in the art can modify the invention described herein while still achieving its advantageous effects. Therefore, the following description should be understood as being of general knowledge to those skilled in the art and is not intended to limit the invention.

[0056] The invention is described more specifically by way of example in the following paragraphs with reference to the accompanying drawings. The advantages and features of the invention will become clearer from the following description. It should be noted that the drawings are in a very simplified form and use non-precise proportions, and are only used to facilitate and clarify the illustration of the embodiments of the invention.

[0057] like Figures 1 to 5 As shown in the figure, this embodiment of the invention proposes a method and device for controlling the automatic dispensing and venting of bagged preparations. The device vents air from the dispensing bags 13 in all dispensing components 100 under the control of the method.

[0058] Specifically, such as Figure 1 As shown, the device includes a liquid transfer component, a control component, and multiple dispensing components 100.

[0059] The liquid transfer assembly is used for liquid transport;

[0060] The control components are used to monitor and regulate the dispensing and venting processes;

[0061] Multiple dispensing components are connected to the liquid transfer component and the control component. The control component accurately distributes liquid into the dispensing bag 13 of each dispensing component through the liquid transfer component, and adjusts the venting control mode of the dispensing bag 13 according to the liquid level detection data and pressure detection data.

[0062] In this embodiment, the liquid transfer assembly includes a mother liquor bag 1, a dispensing main pipeline 2, a peristaltic pump 3, and an emptying pipeline 8; one end of the dispensing main pipeline 2 is connected to the mother liquor bag 1, the peristaltic pump 3 is installed on the dispensing main pipeline 2 and close to the mother liquor bag 1; the emptying pipeline 8 is located at the other end of the dispensing main pipeline 2 and is connected to the dispensing main pipeline 2.

[0063] Each of the dispensing components 100 includes a dispensing bag 13, a dispensing branch pipe 10, a dispensing clamp valve 11, and a liquid level sensor 12. One end of the dispensing branch pipe 10 is connected to the dispensing main pipe 2 after the peristaltic pump 3 is installed, and the other end of the dispensing branch pipe 10 is connected to the dispensing bag 13. The dispensing clamp valve 11 and the liquid level sensor 12 are sequentially installed on the dispensing branch pipe 10, with the dispensing clamp valve 11 located above the liquid level sensor 12. The liquid level sensor 12 is set at a predetermined position on the dispensing branch pipe 10 to monitor and determine in real time whether there is liquid at that position, thereby providing necessary feedback signals to the controller 15. The dispensing clamp valve 11 is used to control the opening and closing of the dispensing branch pipe 10, and the pipe length between the dispensing clamp valve 11 and the dispensing bag 13 should be greater than a preset liquid column height 14. All the dispensing branch pipes 10 in the dispensing assembly 100 have the same length and inner diameter to ensure that the liquid volume contained in the dispensing branch pipes 10 is consistent, so that the liquid level rises at a relatively consistent rate when the air is vented from the dispensing bag 13.

[0064] The control components include a first sterile air filter 4, a pressure detection line 5, a pressure sensor 6, a venting clamp valve 7, a second sterile air filter 9, and a controller 15.

[0065] One end of the first sterile air filter 4 is connected to the other end of the main dispensing pipeline 2, and the other end of the first sterile air filter 4 is connected to the pressure sensor 6 through the pressure detection pipeline 5. To ensure the sterile and airtight nature of the pipeline, the first sterile air filter 4 typically needs to have a filtration accuracy of 0.2 μm and be hydrophobic. There should be sufficient distance between the first sterile air filter 4 and the dispensing branch pipeline 10 in the adjacent dispensing assembly 100, or the pipeline between the two should have sufficient space volume. This is because during the filling and venting process before dispensing, the liquid in the main dispensing pipeline 2 should be controlled to maintain a sufficient distance from the first sterile air filter 4 and the second sterile air filter 9 to avoid the filter membrane from contacting the liquid and affecting the accuracy of the pressure sensor 6 reading and preventing sterile sealing. The specific setting principle will not be described in detail in this example.

[0066] In addition, multiple dispensing components 100 can be installed on the dispensing main pipeline 2 located between the first sterile air filter 4 and the mother liquor bag 1. The number of dispensing components 100 installed ranges from 1 to 30. The number of dispensing components 100 installed can be changed according to the dispensing needs of the device, thereby improving the efficiency of single-batch exhaust.

[0067] The venting pinch valve 7 and the second sterile air filter 9 are sequentially installed on the venting pipeline 8. The controller 15 is connected to the pressure sensor 6 and the liquid level sensor 12, and is used to read the data from the pressure sensor 6 and the liquid level sensor 12, and to provide control signals to the pinch valves on each branch pipeline to realize the venting control of the dispensing bag 13. The pressure sensor 6 has positive and negative pressure measurement functions, and the measurement range includes -100kPa to 100kPa.

[0068] In this embodiment, the exhaust control method includes:

[0069] The venting method based on liquid level detection includes using a peristaltic pump 3 to draw in N dispensing bags 13 and their connected pipes as a whole, so that the liquid in the dispensing bags 13 is squeezed by atmospheric pressure, forcing the air in the dispensing bags 13 to enter the pipes. When the liquid in the dispensing bags 13 is squeezed into the liquid level sensor 12 installed on its corresponding pipe, the liquid level sensor 12 triggers a liquid detection success signal. The controller 15 obtains this signal and uses it as the basis for judging that the venting of the dispensing bags 13 is successful.

[0070] The pressure detection-based venting method includes using the peristaltic pump 3 to draw air from the N dispensing bags 13 and the connected pipelines as a whole, so that the liquid in the dispensing bags 13 is squeezed by atmospheric pressure, forcing the air in the dispensing bags 13 to enter the pipeline. If the air pressure in the pipeline is lower than the preset judgment pressure of the controller 15, it is considered that the liquid in the dispensing bags 13 has been squeezed to the vicinity of the target position of its corresponding pipeline, and the controller 15 judges that the venting is successful.

[0071] The venting method controlled by a priority strategy includes the following steps: during the filling process of N dispensing bags 13, the controller 15 reads the number of liquid level sensors 12 that detect liquid signals during the filling process (i.e., the number of valid signals during the filling process) N1; during the venting process, the controller 15 compares N1 with g(N); when N1 < g(N), the controller 15 uses the pressure-based venting control method to vent; when N1 ≥ g(N), the controller 15 uses the liquid level-based venting control method to vent.

[0072] Where, g(N) = floor(4.15739·N) 0.174579 -2.58425).

[0073] Specifically, the pressure-based exhaust control method for exhaust includes:

[0074] The peristaltic pump 3 continuously reverses. When the pressure value detected by the pressure sensor 6 is less than or equal to the preset judgment pressure p of the controller, N dispensing clamp valves 11 are closed. Here, p = a + b × V + c × L, where V is the dispensing amount set for each dispensing bag 13, L is the preset liquid column height 14 of the dispensing process, a is a constant, and b and c are coefficients. When p is in kPa, V is in mL, and L is in mm, a ∈ (-5, 5), b ∈ (0, 1), and c ∈ (-0.1, 0).

[0075] The venting control method based on liquid level includes the following steps:

[0076] The peristaltic pump 3 continuously reverses, and the number of liquid level sensors 12 that detect liquid signals during the exhaust process (i.e., the number of valid signals during the exhaust process) N2 is recorded.

[0077] When N2≥g(N), the controller 15 determines that the exhaust is successful and closes the above N dispensing clamp valves 11;

[0078] When N2 < g(N), the controller 15 reads the pressure data of the pressure sensor 6. If the pressure value of the pressure sensor 6 is ≤ p - Δp, it indicates that the liquid level sensor 12 has a high error rate in liquid level detection, causing the liquid to rise in the dispensing branch pipe 10 to exceed the limit. At this time, the controller 15 determines that the venting is complete and closes N dispensing clamp valves 11. If the pressure value of the pressure sensor 6 is > p - Δp, the peristaltic pump 3 continues to reverse, and the controller 15 continues to record the number of liquid level sensors 12 N2, and performs a judgment on the size of the number of liquid level sensors 12 N2 and g(N) and repeats the judgment process. Wherein, Δp is the difference between the pressure value of the pressure sensor 6 and the judgment pressure p preset by the controller.

[0079] In a preferred embodiment, when N1≥g(N) and the pressure value detected by the pressure sensor 6 is ≤p-Δp, the controller 15 still does not detect g(N) signals and ends the venting, thereby eliminating the impact of this event and ending the venting with a relatively safe pressure signal, avoiding excessive liquid level in the dispensing branch pipe 10 or excessive liquid being drawn.

[0080] In this embodiment, since the liquid being pumped up during the venting process may be intermittent, and the intermittent liquid column will rise faster, in order to avoid venting failure caused by such signal misjudgment, the liquid level-based venting control method is adopted to vent N of the dispensing bags 13 simultaneously. The N dispensing bags 13 correspond to N of the sensors, and venting is judged to be successful only when at least m of the N sensors detect it successfully, thereby reducing the probability of misjudgment.

[0081] If the probability of the liquid level sensor 12 failing to detect is PA, and the probability of successful detection is 1-PA; the probability of intermittent liquid column interference during the venting process in the liquid level-based venting control method is PC, and the probability of no interference is 1-PC; when using the pressure detection-based venting method, the probability of venting failure is PD; the probability that at least m of the N sensors will successfully detect the venting is:

[0082]

[0083] Only when m sensors are successfully detected simultaneously, and there is no discontinuous liquid column in more than one of the pipelines corresponding to these m sensors, can the N dispensing bags 13 be successfully vented. The success probability is: P1 = P(m, N, 1-PA) × P(1, m, 1-PC).

[0084] When the condition that at least m of the sensors simultaneously detect success is not met, the pressure detection-based venting method will be used to address the issue and further improve the venting success rate. This situation is more likely to occur when the number of the dispensing bags 13 is small, and the probability of this occurrence is: P2 = [1 - P(m, N, 1 - PA)] × (1 - PD) × N.

[0085] Clearly, a criterion is needed to determine the impact of differences in the values ​​of the quantities N and m of the various packaging bags 13 on the probability of successful sensor detection and the probability of successful exhaust. Here, the function Po is used to determine the optimal value of m by taking its maximum value.

[0086] Po(m,N)=P1+P2=P(m,N,1-PA)×P(1,m,1-PC)+[1-P(m,N,1-PA)]×(1-PD)×N.

[0087] For example, for the number of the dispensing bags 13 N∈[1,30], the number of the dispensing bags 13 that are vented at the same time and the number of the liquid level sensors 12 that participate in the detection are equal. Under the requirement of maximizing the reliability of venting (i.e. all dispensing bags are vented successfully), there is an optimal value for the minimum number of liquid level sensors 12 that can correctly detect the liquid signal.

[0088] like Figure 5 As shown, the optimal value is set based on the maximum probability that all dispensing bags successfully release air (see the red curve in the figure). Figure 5 In the graph, the horizontal axis represents the number of the dispensing bags 13, and the vertical axis represents the probability that all dispensing bags 13 successfully release air. The squares, circles, diamonds, and crosses in the graph represent the optimal values ​​g(N) for the number of valid signals from the level sensor 12, respectively, being 1, 2, 3, and 4. The red curve represents the maximum probability of all dispensing bags 13 successfully releasing air. Specifically, when the number of dispensing bags 13 is 1, according to the red curve, the optimal value g(N) = 1; when the number of dispensing bags 13 is 2-6, the optimal value g(N) = 2; and when the number of dispensing bags 13 is 7-15, the optimal value g(N) = 3. Therefore, according to... Figure 5 Can obtain such as Figure 4 The curve showing the optimal value g(N) is shown.

[0089] In the formula for calculating g(N), floor(X) is a function that rounds X down; such functions exist in existing software. It should be noted that the expression for g(N) is not unique and can be expressed in other forms, as long as the integer value of N satisfies the following... Figure 4 The g(N) curve is shown. In particular, when N≥16, g(N) can take the value 3 or 4. Although theoretically, a value of 4 for g(N) would be better than a value of 3, considering that the reliability of the final exhaust success is very close, in this case, if g(N) is expressed in other forms, the value of g(N) should not be less than 3.

[0090] During the use of the exhaust control method, valve control, sensor data reading, control flow logic, and pressure value p are all performed by the controller 15.

[0091] In this embodiment, an automatic dispensing and venting method includes:

[0092] To prepare for dispensing, turn on the peristaltic pump to fill the dispensing main pipeline 2 with liquid;

[0093] Dispensing liquid: dispensing the liquid in the mother liquor bag 1 into the dispensing bags 13 of each dispensing component;

[0094] The dispensing bag 13 is vented, and the controller 15 controls the relevant components to vent the mother liquor bag 1 in multiple dispensing components 100 simultaneously based on the venting control method.

[0095] After the venting is completed, peristaltic pump 3 stops.

[0096] Specifically, such as Figures 2-3 As shown, the dispensing preparation includes:

[0097] Open the drain clamp valve 7 and the peristaltic pump 3;

[0098] The peristaltic pump 3 rotates in the forward direction, causing the liquid to flow from the mother liquor bag 1 to the dispensing main pipeline 2;

[0099] The main dispensing pipeline 2 is filled with liquid for a fixed time t or the main dispensing pipeline 2 is filled with liquid to a specific position of the main dispensing pipeline 2, and the drain clamp valve 7 is closed.

[0100] The liquid dispensing process includes:

[0101] The controller 15 gradually opens the dispensing clamp valve 11 in each of the multiple dispensing components 100 according to the information of N dispensing bags 13 in the multiple dispensing components 100;

[0102] Each of the dispensing bags 13 is continuously dispensed for a fixed time t2, wherein the fixed dispensing time t2 = dispensing volume V / average flow rate Q of peristaltic pump 3;

[0103] After the dispensing is completed, close the dispensing clamp valve 11 of the corresponding branch, and then sequentially dispense the other dispensing bags 13.

[0104] The controller 15 determines whether the N dispensing bags 13 have been dispensed. After all the N dispensing bags 13 have been dispensed, the controller 15 determines whether all the dispensing clamp valves 11 are in the closed state and reverses the peristaltic pump 3.

[0105] And liquid recovery, recovering the liquid in the main dispensing pipeline 2 to the mother liquor bag 1.

[0106] In one specific embodiment, the liquid recovery process includes:

[0107] Open the drain clamp valve 7, and the peristaltic pump 3 reverses to allow the liquid in the main dispensing pipeline 2 to flow back to the mother liquor bag 1;

[0108] After a duration of t3, the peristaltic pump 3 stops.

[0109] Open the dispensing clamp valves 11 corresponding to N dispensing bags 13 to allow the liquid in the dispensing branch pipe 10 to flow into the dispensing bags 13;

[0110] After a duration of t4, the drain clamp valve 7 and the dispensing clamp valves 11 corresponding to the N dispensing bags 13 are closed.

[0111] In one specific embodiment, such as Figure 3 As shown, the venting of the dispensing bag 13 includes:

[0112] The controller 15 reads the number N1 of liquid level sensors 12 detected during the dispensing process, reads the number N of bags to be dispensed, opens the dispensing clamp valves 11 corresponding to N dispensing bags 13, and vents air according to the venting method controlled by the priority strategy. Specific operation steps are as follows:

[0113] When the peristaltic pump 3 reverses, the controller 15 reads the number N1 of liquid level sensors 12 that detect liquid level information during the dispensing process, reads the number of dispensing bags 13 that need to be dispensed, and opens the dispensing clamp valves 11 corresponding to N dispensing bags 13.

[0114] The controller 15 compares the magnitudes of N1 and g(N). When N1 < g(N), the controller 15 employs the pressure-based exhaust control method. The peristaltic pump 3 continuously reverses direction. When the pressure value detected by the pressure sensor 6 is ≤ p, N of the dispensing clamp valves 11 are closed, and the peristaltic pump 3 stops rotating.

[0115] When N1≥g(N), the controller 15 adopts the level-based exhaust control method, the peristaltic pump 3 continuously reverses, and the controller 15 records the number N2 of the level sensors 12 that can detect liquid signals during this process.

[0116] When N2≥g(N), the controller 15 determines that the exhaust is successful, closes N of the dispensing clamp valves 11, and stops the peristaltic pump 3.

[0117] When N2 < g(N), the controller 15 reads the pressure data from the pressure sensor 6. If the read pressure value is ≤ p - Δp, the liquid level sensor 12 may have a high error rate, causing the liquid level in the dispensing branch pipe 10 to rise beyond the limit. In this case, the controller 15 determines that venting is complete, then closes N clamp valves 11 and stops the peristaltic pump 3. If the read pressure value is > p - Δp, the peristaltic pump 3 continues to reverse, and the controller 15 continues to record the N2 value, and makes judgments and corresponding decisions regarding the magnitudes of N2 and g(N).

[0118] Obviously, those skilled in the art can make various modifications and variations to this invention without departing from its spirit and scope. Therefore, if these modifications and variations fall within the scope of the claims of this invention and their equivalents, this invention also intends to include these modifications and variations.

Claims

1. A method for controlling the venting of gas during automatic dispensing of bagged preparations, characterized in that, The exhaust control method includes: The venting method based on liquid level detection includes using a peristaltic pump to draw in N dispensing bags and connected pipelines as a whole, so that the liquid in the dispensing bags is squeezed by atmospheric pressure, forcing the air in the dispensing bags to enter the pipeline. When the liquid in the dispensing bags is squeezed into the liquid level sensor installed on its corresponding pipeline, the liquid level sensor triggers a liquid detection success signal. The controller obtains the signal and uses it as the basis for judging that the venting of the dispensing bags is successful. The pressure detection-based venting method includes using the peristaltic pump to draw in N dispensing bags and connected pipelines as a whole, so that the liquid in the dispensing bags is squeezed by atmospheric pressure, forcing the air in the dispensing bags to enter the pipeline. If the gas pressure in the pipeline is lower than the preset judgment pressure of the controller, it is considered that the liquid in the dispensing bags has been squeezed to the target position of its corresponding pipeline, and the controller judges that the venting is successful. The venting method controlled by a priority strategy includes the following steps: During the filling process of N dispensing bags, the controller reads the number N1 of liquid level sensors that detect liquid signals during the filling process; during the venting process, the controller compares N1 with g(N); when N1 < g(N), the controller uses the pressure-based venting control method for venting; when N1 ≥ g(N), the controller uses the liquid level-based venting control method for venting; where g(N) = floor(4.15739 × N) 0.174579 -2.58425).

2. The control method as described in claim 1, characterized in that, The pressure-based exhaust control method includes the following steps for exhaust: The peristaltic pump continuously reverses, and when the pressure value detected by the pressure sensor is less than or equal to the preset judgment pressure p of the controller, N dispensing clamp valves are closed. Where p = a + b × V + c × L, V is the dispensing amount set for each of the dispensing bags, L is the liquid column height preset in the dispensing process, a is a constant term, and b and c are coefficients respectively.

3. The control method as described in claim 1, characterized in that, The venting control method based on liquid level includes the following steps: The peristaltic pump continuously reverses, and the number N2 of liquid level sensors that detect liquid signals during the exhaust process is recorded. When N2≥g(N), the controller determines that the exhaust is successful and closes N dispensing clamp valves; When N2 < g(N), the controller reads the pressure data from the pressure sensor. If the pressure value of the pressure sensor is ≤ p - Δp, it indicates that the liquid level sensor has a high error rate in detecting the liquid level, causing the liquid to rise in the dispensing branch pipe beyond the limit. At this time, the controller determines that the venting is complete and closes N dispensing clamp valves. If the pressure value of the pressure sensor is > p - Δp, the peristaltic pump continues to reverse, and the controller continues to record the number of liquid level sensors N2, and performs a judgment on the magnitude of the number of liquid level sensors N2 and g(N), repeating the judgment process. Here, Δp is the difference between the pressure value of the pressure sensor and the preset judgment pressure p of the controller.

4. An automatic dispensing and venting method, characterized in that, include: To prepare for dispensing, turn on the peristaltic pump to fill the dispensing main pipeline with liquid; Dispensing liquid: dispensing the liquid in the mother liquor bag into the dispensing bags of each dispensing component; The controller controls the relevant components to simultaneously vent the sub-bags in a plurality of the sub-packaging components based on the venting control method as described in any one of claims 1-3. After the venting is complete, the peristaltic pump stops.

5. The exhaust method as described in claim 4, characterized in that, The venting of the packaging bag includes: The controller reads the number N1 of liquid level sensors detected during the dispensing process, reads the number N of bags to be dispensed, opens the dispensing clamp valves corresponding to N dispensing bags, and vents air according to the venting method controlled by the priority strategy.

6. The exhaust method as described in claim 5, characterized in that, The dispensing preparation includes: Open the drain clamp valve and the peristaltic pump; The peristaltic pump rotates in the forward direction, causing the liquid to flow from the mother liquor bag to the main dispensing pipeline; The main dispensing pipeline is filled with liquid for a fixed time t, or the main dispensing pipeline is filled with liquid to a specific position on the main dispensing pipeline, and the drain clamp valve is closed.

7. The exhaust method as described in claim 6, characterized in that, The liquid dispensing process includes: The controller gradually opens the dispensing clamp valve in each of the dispensing components; Each of the dispensing bags is continuously dispensed for a fixed time t2, wherein the fixed dispensing time t2 = dispensing volume V / average flow rate of the peristaltic pump Q; After the dispensing is completed, close the dispensing clamp valve of the corresponding branch, and then sequentially dispense the other dispensing bags. The controller determines whether the N dispensing bags have been dispensed. After all the N dispensing bags have been dispensed, the controller determines whether all the dispensing clamp valves are in the closed state and reverses the peristaltic pump. And liquid recovery, recovering the liquid in the main dispensing pipeline to the mother liquor bag.

8. The exhaust method as described in claim 7, characterized in that, The liquid recovery process includes: Open the drain clamp valve, and the peristaltic pump reverses to allow the liquid in the main dispensing pipeline to flow back into the mother liquor bag; After a duration of t3, the peristaltic pump stops. Open the dispensing clamp valves corresponding to N dispensing bags to allow the liquid in the dispensing branch pipes to flow into the dispensing bags; After a duration of t4, the drain clamp valve and the dispensing clamp valves corresponding to the N dispensing bags are closed.

9. A device for automatic dispensing and venting of soft-bag formulations, characterized in that, Includes liquid transfer components, control components, and multiple dispensing components; The liquid transfer assembly is used for liquid delivery; The control components are used to monitor and regulate the dispensing and venting processes; Multiple dispensing components are connected to the liquid transfer component and the control component. The control component accurately distributes liquid into the dispensing bags of each dispensing component through the liquid transfer component, and adjusts the venting control mode of the dispensing bags according to liquid level detection data and pressure detection data.

10. The apparatus as claimed in claim 9, characterized in that, The liquid transfer assembly includes a mother liquor bag, a dispensing main pipeline, a peristaltic pump, and an emptying pipeline; One end of the main dispensing pipeline is connected to the mother liquor bag, the peristaltic pump is installed on the main dispensing pipeline and close to the mother liquor bag; the venting pipeline is located at the other end of the main dispensing pipeline and is connected to the main dispensing pipeline.

11. The apparatus as claimed in claim 10, characterized in that, Each of the aforementioned dispensing components includes a dispensing bag, a dispensing branch line, a dispensing clamp valve, and a liquid level sensor; One end of the dispensing branch pipeline is connected to the main dispensing pipeline after the peristaltic pump is installed, and the other end of the dispensing branch pipeline is connected to the dispensing bag; the dispensing clamp valve and the liquid level sensor are installed sequentially on the dispensing branch pipeline, with the dispensing clamp valve located above the liquid level sensor, and the liquid level sensor set at a predetermined position on the dispensing branch pipeline; the pipeline length between the dispensing clamp valve and the dispensing bag is greater than a preset liquid column height.

12. The apparatus as claimed in claim 11, characterized in that, The control components include a first sterile air filter, a pressure detection line, a pressure sensor, a drain clamp valve, a second sterile air filter, and a controller. One end of the first sterile air filter is connected to the other end of the main dispensing pipeline, and the other end of the first sterile air filter is connected to the pressure sensor through the pressure detection pipeline; the venting pinch valve and the second sterile air filter are installed sequentially on the venting pipeline; The controller is connected to the pressure sensor and the liquid level sensor, and is used to read the data from the pressure sensor and the liquid level sensor, and to provide control signals to the clamp valves on each branch pipe to realize the venting control of the dispensing bag.

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