Quantitative Dispensing Device and Dispensing Method for Biopharmaceuticals

Abstract

A device and method for quantitatively dispensing a biopharmaceutical. The device for quantitatively dispensing a biopharmaceutical includes a storage container (10), a dispensing container (20), a first non-contact sensor (30), and a second non-contact sensor (40). The biopharmaceutical is stored inside the storage container. The inlet of the dispensing container communicates with the outlet of the storage container through a transfer pipe (60). Both the first non-contact sensor and the second non-contact sensor are installed on the transfer pipe between the inlet of the dispensing container and the outlet of the storage container, and the first non-contact sensor and the second non-contact sensor are separated by a predetermined distance. By installing non-contact sensors on the transfer pipe between the inlet of the dispensing container and the outlet of the storage container, non-contact quantitative dispensing of the biopharmaceutical can be realized, and the dispensing efficiency and dispensing accuracy of the biopharmaceutical can be effectively improved.

Description

Technical Field

[0001] <Cross - reference to Related Applications> This application claims the priority of Chinese Patent Application No. 2022111398036, titled "Quantitative Dispensing Device and Dispensing Method for Biopharmaceuticals", filed on September 19, 2022, and all of its content is incorporated herein by reference. The present invention relates to the technical field of biopharmaceuticals, and particularly to a quantitative dispensing device and a dispensing method for biopharmaceuticals.

Background Art

[0002] The dispensing of biopharmaceuticals is an important component in the field of biotherapy, and is very important for cell therapy and the preparation of pharmaceuticals. When dispensing biopharmaceuticals, in order to prevent the biopharmaceuticals from being contaminated, quantitative dispensing of biopharmaceuticals is carried out without using electronic components such as sensors that directly contact the biopharmaceuticals, but the dispensing operation of biopharmaceuticals has become more difficult.

[0003] In related technologies, the dispensing of biopharmaceuticals is mainly carried out by weighing and manually recording. Although quantitative dispensing of biopharmaceuticals is possible with this method, both the dispensing efficiency and the dispensing accuracy are low.

Summary of the Invention

Problems to be Solved by the Invention

[0004] In order to solve at least one technical drawback in the prior art, the present invention provides a quantitative dispensing device for biopharmaceuticals that can achieve non - contact quantitative dispensing of biopharmaceuticals and can effectively improve the dispensing efficiency and dispensing accuracy of biopharmaceuticals.

[0005] The present invention further provides a quantitative dispensing method for biopharmaceuticals.

Means for Solving the Problems

[0006] To achieve the above object, the present invention provides a quantitative dispensing device for biopharmaceuticals, and the quantitative dispensing device for biopharmaceuticals comprises: a storage container in which a biopharmaceutical is stored therein; a dispensing container having an injection port communicating with an outlet of the storage container via a transfer pipe; a first non-contact sensor and a second non-contact sensor, both of which are installed in the transfer pipe between the injection port of the dispensing container and the outlet of the storage container and are separated by a predetermined distance.

[0007] According to the quantitative dispensing device for biopharmaceuticals according to an embodiment of the present invention, a metering device is installed in the transfer pipe between the first non-contact sensor and the second non-contact sensor.

[0008] According to the quantitative dispensing device for biopharmaceuticals according to an embodiment of the present invention, the metering device includes a main body, a diversion pipe is configured inside the main body, the diversion pipe extends along a predetermined path, and the length of the predetermined path is longer than the distance between the inlet and the outlet of the diversion pipe.

[0009] According to the quantitative dispensing device for biopharmaceuticals according to an embodiment of the present invention, the diversion pipe is installed annularly along the center line of the main body and further communicates with the transfer pipe.

[0010] According to the quantitative dispensing device for biopharmaceuticals according to an embodiment of the present invention, the cross-sectional area of the diversion pipe is equal to the cross-sectional area of the transfer pipe.

[0011] According to the quantitative dispensing device for biopharmaceuticals according to an embodiment of the present invention, the transfer pipe between the first non-contact sensor and the second non-contact sensor is installed in a spiral shape and is suitable for extending the flow path of the transfer pipe.

[0012] According to the quantitative dispensing device for biopharmaceuticals according to an embodiment of the present invention, the transfer pipe further includes a pressure feeding component for supplying a transfer power thereto, and the pressure feeding component is installed in any one of the transfer pipe, the storage container, and the dispensing container.

[0013] According to the bio - preparation metering dispensing device according to an embodiment of the present invention, a plurality of the dispensing containers are installed in parallel, and switching valves are respectively installed in the transfer pipes between the inlets of the respective dispensing containers and the outlet of the storage container.

[0014] In order to achieve the above object, the present invention provides a method for metering and dispensing a bio - preparation, and the method for metering and dispensing the bio - preparation includes: acquiring a first air - bubble detection signal of the transfer pipe detected by a first non - contact sensor; acquiring a second air - bubble detection signal of the transfer pipe detected by a second non - contact sensor; calculating a time difference between the detected first air - bubble detection signal and the second air - bubble detection signal; acquiring an actual volumetric flow rate of the bio - preparation in the transfer pipe according to the relationship between the time difference and the volume or capacity of the transfer pipe between the first non - contact sensor and the second non - contact sensor; realizing metering and dispensing of the bio - preparation by controlling the time for which the bio - preparation flows through the transfer pipe.

[0015] According to the method for metering and dispensing a bio - preparation according to an embodiment of the present invention, realizing metering and dispensing of the bio - preparation by controlling the time for which the bio - preparation flows through the transfer pipe means controlling the switching time of the switching valve at the inlet of each dispensing container at a predetermined flow rate of the peristaltic pump.

Effects of the Invention

[0016] According to the quantitative dispensing device for biopharmaceuticals according to an embodiment of the present invention, by installing a first non-contact sensor and a second non-contact sensor in the transfer pipe between the inlet of the dispensing container and the outlet of the storage container, after grasping the volume or capacity of the transfer pipe between the first non-contact sensor and the second non-contact sensor, by detecting and calculating the time difference passing through the first non-contact sensor and the second non-contact sensor when the biopharmaceutical flows through the transfer pipe, the volume flow rate of the biopharmaceutical in the transfer pipe between the first non-contact sensor and the second non-contact sensor, that is, the actual flow rate in the transfer pipe can be obtained. Thereby, by controlling the time when the biopharmaceutical flows through the transfer pipe, constant-volume dispensing of the biopharmaceutical, that is, quantitative dispensing of the biopharmaceutical is realized.

Brief Description of the Drawings

[0017] To more clearly explain the technical solutions of the present invention or the prior art, the drawings necessary for the description of the embodiments or the prior art will be briefly described below. Obviously, the drawings described below are an example of the embodiments of the present invention, and those skilled in the art can obtain other drawings based on these drawings without creative effort.

Figure 1

Figure 2

Figure 3

Figure 4

Modes for Carrying Out the Invention

[0018] To make the objectives, technical solutions, and advantages of the present invention clearer, the following will clearly and completely describe the technical solutions of the present invention with reference to the drawings of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, not all of them. Based on the embodiments of the present invention, any other embodiments obtained by those skilled in the art without creative efforts shall fall within the protection scope of the present invention.

[0019] In the description of the embodiments of the present invention, it should be noted that unless otherwise clearly defined and limited, the terms "connection" and "coupling" should be understood in a broad sense. For example, it may be a fixed connection, a detachable connection, or an integral connection, may be a mechanical connection or an electrical connection, and may be a direct connection or an indirect connection through an intermediate element. Those skilled in the art can understand the specific meaning of the above terms in the embodiments of the present invention according to the specific situation.

[0020] In the embodiments of the present invention, unless otherwise clearly defined and limited, for a first feature being "above" or "below" a second feature, it may mean that the first and second features are in direct contact, or that the first and second features are in indirect contact through an intermediate medium. Further, for a first feature being "above", "upper", and "upper surface" of a second feature, it may mean that the first feature is directly above or obliquely above the second feature, or simply that the horizontal height of the first feature is higher than that of the second feature. For a first feature being "below", "lower", and "lower surface" of a second feature, it may mean that the first feature is directly below or obliquely below the second feature, or simply that the horizontal height of the first feature is lower than that of the second feature.

[0021] In the description of this specification, the descriptions of reference terms such as "one embodiment", "several embodiments", "example", "specific example", or "several examples" mean that the specific features, structures, materials, or characteristics described with reference to the embodiment or example are included in at least one embodiment or example of the embodiments of the present invention. In this specification, the schematic descriptions of the above terms are not necessarily for the same embodiment or example. Moreover, the described specific features, structures, materials, or characteristics may be combined in a suitable manner in any one or more embodiments or examples. Also, as long as they do not conflict with each other, those skilled in the art can combine or combine different embodiments or examples and the features of different embodiments or examples described in this specification.

[0022] Hereinafter, embodiments of the present invention will be described with reference to FIGS. 1 to 4. It should be understood that the following description is merely a schematic embodiment of the present invention and does not limit the present invention in any way.

[0023] Referring to FIGS. 1 to 3, in a first aspect of the present invention, a quantitative dispensing device for a biopharmaceutical is provided. The biopharmaceutical mainly includes a cell preparation, an effective antigen component of a microorganism and its metabolite, an animal toxin, a bioproduct processed from human or animal blood or tissue, etc., for preventing, treating, or diagnosing a corresponding infectious disease or other related diseases.

[0024] The quantitative dispensing device for the biopharmaceutical includes a storage container 10, a dispensing container 20, a first non-contact sensor 30, and a second non-contact sensor 40. The biopharmaceutical to be dispensed is stored inside the storage container 10. The inlet of the dispensing container 20 communicates with the outlet of the storage container 10 through a transfer pipe 60. Both the first non-contact sensor 30 and the second non-contact sensor 40 are installed on the transfer pipe 60 between the inlet of the dispensing container 20 and the outlet of the storage container 10, and the first non-contact sensor 30 and the second non-contact sensor 40 are separated by a predetermined distance.

[0025] This predetermined distance may be understood as the first non-contact sensor 30 and the second non-contact sensor 40 being installed on the transfer pipe 60 at a certain distance apart. The volume or capacity of the transfer pipe 60 between the first non-contact sensor 30 and the second non-contact sensor 40 can be grasped. Thereby, when the biopharmaceutical flows through the transfer pipe 60, the time difference passing through the first non-contact sensor 30 and the second non-contact sensor 40 is detected and calculated. And based on the volume flow relationship between the volume or capacity of the transfer pipe 60 between the first non-contact sensor 30 and the second non-contact sensor 40 and the time difference, the actual volume flow rate of the biopharmaceutical in the transfer pipe 60 between the first non-contact sensor 30 and the second non-contact sensor 40, that is, the actual flow rate of the biopharmaceutical in the transfer pipe 60 is obtained. Furthermore, by controlling the flow time of the biopharmaceutical in the transfer pipe 60, non-contact quantitative dispensing of the biopharmaceutical can be realized.

[0026] Needless to say, in the present invention, by installing the first non-contact sensor 30 and the second non-contact sensor 40 on the transfer pipe 60 between the injection port of the dispensing container 20 and the discharge port of the storage container 10, after grasping the volume or capacity of the transfer pipe 60 between the first non-contact sensor 30 and the second non-contact sensor 40, when the biopharmaceutical flows through the transfer pipe 60, the time difference passing through the first non-contact sensor 30 and the second non-contact sensor 40 is detected and calculated, so that the actual volume flow rate of the biopharmaceutical in the transfer pipe 60 between the first non-contact sensor 30 and the second non-contact sensor 40 can be obtained. Thereby, by controlling the flow time of the biopharmaceutical in the transfer pipe 60, constant-volume dispensing of the biopharmaceutical, that is, quantitative dispensing of the biopharmaceutical can be realized.

[0027] As shown in FIGS. 1 to 3, in order to further improve the dispensing accuracy of the quantitative dispensing device for biopharmaceuticals, based on the above-mentioned embodiment, the differences from the above-mentioned embodiment can be understood as the following points. A metering device 50 is installed in the transfer pipe 60 between the first non-contact sensor 30 and the second non-contact sensor 40. The metering device 50 has a certain structural strength and stability as an independent component, facilitates the flow of the biopharmaceutical through the inside of the metering device 50, and facilitates detection by the non-contact sensor.

[0028] As shown in FIGS. 2 and 3, the metering device 50 can be made of a resin material, and the structure of the metering device 50 can be set according to actual use needs. For example, the shape of the metering device 50 may be cylindrical, cubic, rectangular parallelepiped, spherical, etc. When the structure of the metering device 50 is cylindrical, a through hole can be opened at the middle position of the cylinder to make the cross section along the radial direction of the cylinder annular, which facilitates the structural design.

[0029] Specifically, the metering device 50 includes a main body 51, and a diversion pipe 52 is constructed inside the main body 51. The diversion pipe 52 extends along a predetermined path to facilitate the connection between the diversion pipe 52 and the conveying pipe 6. An inlet 53 and an outlet 54 are installed on the diversion pipe 52, and the length of the predetermined path is longer than the straight-line distance between the inlet 53 and the outlet 54. Needless to say, the predetermined path is a path through which the pipeline between the inlet 53 and the outlet 54 communicates, and the predetermined path can be determined by needs or the shape of the metering device. The predetermined path is to extend the distance between the inlet 53 and the outlet 54 of the diversion pipe 52 to achieve the effect of accurately measuring the actual volume flow rate.

[0030] As shown in FIG. 3, in order to facilitate the processing of the diversion pipe 52, the diversion pipe 52 can be installed annularly along the center line of the main body 51. That is, inside the main body 51, a diversion pipe 52 installed annularly along the center line or central axis of the main body 51 is configured. The diversion pipe 52 communicates with the conveying pipe 60. Since the diversion pipe 52 is configured inside the main body 51, it can be understood that the diversion pipe 52 is a rigid pipe and does not deform according to the pressure of the fluid medium inside the diversion pipe 52. Thereby, it is possible to avoid the situation that the pressure of the liquid in the conveying pipe 60 is too large and the conveying pipe 60 is deformed, so that the flow rate of the biopharmaceutical in the conveying pipe 60 changes and the metering and dispensing accuracy of the biopharmaceutical decreases.

[0031] As shown in FIG. 3, in order to easily and accurately calculate the volumes of the diversion pipe 52 and the conveying pipe 6, the cross-sectional area of the diversion pipe 52 and the cross-sectional area of the conveying pipe 60 can be set to be equal.

[0032] Of course, it is also possible to set the cross-sectional area of the flow guide pipe 52 to be different from the cross-sectional area of the transfer pipe 60, and the specific setting can be selected according to the actual usage situation.

[0033] As shown in FIG. 3, in order to dispense the biopharmaceutical more accurately, the inlet 53 of the flow guide pipe 52 is installed below the main body 51, and the outlet 54 of the flow guide pipe 52 is installed above the main body 51. Thereby, the biopharmaceutical in the transfer pipe 6 enters from below the metering device 50 and flows out from above the metering device 50, ensuring that the flow guide pipe 52 is filled with the biopharmaceutical, and improving the calculation accuracy of the volume or capacity of the flow guide pipe 52.

[0034] Also, a connection segment can be installed at the end of the transfer pipe 6, the inner diameters of the passages of the inlet 53 and the outlet 54 are set to be the same as the inner diameter of the transfer pipe 60, and the inner diameter of the connection segment can be set to be larger than the inner diameters of the passages of the inlet 53 and the outlet 54. Thereby, the transfer pipe 6 can be interference-fitted outside the inlet 53 and the outlet 54 by the connection segment installed at the end. When calculating the volume or capacity of the transfer pipe 60 between the first non-contact sensor 30 and the second non-contact sensor 40, it can be directly determined from the length and inner diameter of the transfer pipe 60 between the first non-contact sensor 30 and the second non-contact sensor 40.

[0035] Also, in order to improve the sealing performance between the transfer pipe 6 and the inlets 53 and outlets 54 of the flow guide pipe 52, the transfer pipe 6 can be screwed to the inlets 53 and outlets 54 of the flow guide pipe 52.

[0036] After the production of the metering device 50 is completed, the volume or capacity of the flow guide pipe 52 is known and constant. Therefore, when calculating the volume or capacity of the transfer pipe 60 between the first non-contact sensor 30 and the second non-contact sensor 40, it is only necessary to calculate the volume or capacity of the transfer pipe 60 between the inlet 53 of the metering device 50 and the first non-contact sensor 30, and calculate the volume or capacity of the transfer pipe 60 between the outlet 54 of the metering device 50 and the second non-contact sensor 40, which is more convenient to use.

[0037] In this embodiment, in the quantitative dispensing process, the storage container 10 can be installed above the dispensing container 20. That is, the height of the horizontal plane where the discharge port of the storage container 10 is located is higher than the height of the horizontal plane where the injection port of the dispensing container 20 is located, so that the biopharmaceutical stored in the storage container 10 automatically enters the transfer pipe 60 under the action of gravity. When the biopharmaceutical moves along the transfer pipe 60 and passes through the location of the first non-contact sensor 30, the first non-contact sensor 30 detects the biopharmaceutical, and at this time, the time of the first time of the detected first bubble detection signal is recorded. When the cell preparation continues to move along the transfer pipe 60 and passes through the location of the second non-contact sensor 40, when the second non-contact sensor 40 detects the biopharmaceutical, the time of the second time of the detected second bubble detection signal is recorded at this time. The difference obtained by subtracting the first time from the recorded second time is the time difference for the cell preparation to flow through the transfer pipe 60 and pass through the first non-contact sensor 30 and the second non-contact sensor 40.

[0038] Based on the above time difference and the volume or capacity of the transfer pipe 60 located between the first non-contact sensor 30 and the second non-contact sensor 40 (including the volume or capacity of the diversion pipe 52 and including the volume or capacity of a part of the transfer pipe 60), the actual flow rate of the biopharmaceutical in the transfer pipe 60 can be obtained by the volume flow rate calculation formula. Therefore, by calculating the time for the biopharmaceutical to flow through the first non-contact sensor 30 or the second non-contact sensor 40, the actual volume of the biopharmaceutical in the dispensing container 20 can be obtained. That is, the quantitative dispensing of the biopharmaceutical can be realized.

[0039] In some embodiments of the present invention, different from the above embodiments, in order to avoid the flow rate of the biopharmaceutical in the conveying pipe 60 being too fast and the speed of passing through the first non-contact sensor 30 and the second non-contact sensor 40 being too fast to be accurately detected, the conveying pipe 60 between the first non-contact sensor 30 and the second non-contact sensor 40 is installed in a spiral shape, so that the flow path of the conveying pipe 60 between the first non-contact sensor 30 and the second non-contact sensor 40 can be extended. That is, it corresponds to extending the time for the biopharmaceutical to flow through the conveying pipe 60 between the first non-contact sensor 30 and the second non-contact sensor 40. Thereby, the time difference for the biopharmaceutical to pass through the first non-contact sensor 30 and the second non-contact sensor 40 when flowing through the conveying pipe 60 can be detected more accurately.

[0040] As shown in FIG. 1, as an embodiment of the present invention, based on the above embodiments, in order to make the flow rate in the conveying pipe 60 more stable and uniform, different from the above embodiments, the quantitative dispensing device for biopharmaceuticals further includes a pressure-feeding component for supplying conveying power to the conveying pipe 60, and the pressure-feeding component can be installed on any one of the conveying pipe 60, the storage container 10, and the dispensing container 20.

[0041] For example, when the pressure-feeding component is a peristaltic pump 70, as if the finger sandwiches the conveying pipe 60 filled with the biopharmaceutical as a whole, as the finger slides forward, the biopharmaceutical in the conveying pipe 60 also moves forward. The peristaltic pump 70 uses rollers instead of fingers and pumps the biopharmaceutical by alternately extruding and releasing the conveying pipe 60 fixed to the peristaltic pump 70.

[0042] The peristaltic pump 70 can be installed on the conveying pipe 60 between the storage container 10 and the first non-contact sensor 30, and the peristaltic pump 70 can also be installed on the conveying pipe 60 between the dispensing container 20 and the second non-contact sensor 40.

[0043] In order to make the control by the peristaltic pump 70 more accurate, the peristaltic pump 70 is installed in front of the inlet 53 of the metering device 50. That is, the peristaltic pump 70 is installed on the conveying pipe 60 between the storage container 10 and the first non-contact sensor 30.

[0044] For example, when the pumping component is an air pump, the air pump can be attached to the storage container 10, and the air pump increases the pressure inside the storage container 10, so that the biopharmaceutical in the storage container 10 can enter the transfer pipe 60.

[0045] For example, when the pumping component is a vacuum pump, the vacuum pump can be attached to the dispensing container 20. The vacuum pump evacuates the air inside the dispensing container 20 to make the dispensing container 20 in a negative pressure state, so that the biopharmaceutical in the storage container 10 can be adsorbed and put into the transfer pipe 60.

[0046] As shown in FIG. 1, as an embodiment of the present invention, different from the above embodiments, one dispensing container 20 may be installed. After the quantitative dispensing into one dispensing container 20 is completed, the next dispensing container 20 may be replaced to continue the quantitative dispensing.

[0047] A plurality of dispensing containers 20 can also be installed in parallel, and switching valves 80 are respectively installed in the transfer pipes 60 between the inlets of each dispensing container 20 and the outlet of the storage container 10.

[0048] That is, a first dispensing container, a second dispensing container, a third dispensing container... an Nth dispensing container, etc. are sequentially installed in the dispensing container 20, and a switching valve 80 is installed in the transfer pipe 60 at the inlet of each dispensing container 20. That is, a first switching valve corresponds to the first dispensing container, and an Nth switching valve corresponds to the Nth dispensing container.

[0049] This is a transfer pipe with the main trunk between the inlet of the first dispensing container and the outlet of the storage container 10, and another branch transfer pipe passes through the inlets of the second dispensing container, the third dispensing container... the Nth dispensing container, and the switching valve is installed in the branch transfer pipe.

[0050] The switching valve 80 is an electromagnetic pinch valve (abbreviated as pinch valve), which is driven by an electromagnetic solenoid and controls the on / off of the transfer pipe 60 by extruding or releasing the transfer pipe 60. The biopharmaceutical only passes through the transfer pipe 60, and other parts of the pinch valve do not come into contact with the biopharmaceutical. Therefore, non-contact quantitative dispensing of the biopharmaceutical can be easily realized.

[0051] In this embodiment, after the actual flow rate of the biopharmaceutical in the transfer pipe 60 is obtained by the first non-contact sensor 30 and the second non-contact sensor 40, the flow rate of the peristaltic pump 70 is calibrated to stabilize the flow rate of the biopharmaceutical in the transfer pipe 60. Thereby, by controlling the on-time of the corresponding switching valve 80 on the dispensing container 20, the actual volume or capacity of the biopharmaceutical packed in the dispensing container 20 can be indirectly grasped, thereby realizing quantitative dispensing of the biopharmaceutical.

[0052] In the embodiments of the present invention, both the first non-contact sensor 30 and the second non-contact sensor 40 are bubble sensors, and are used to feedback the elapsed time of the bubbles in the transfer pipe 60 by monitoring the bubbles in the transfer pipe 60 in real time.

[0053] The bubble sensor can be attached to the transfer pipe 60 in an engaged manner, without the need to cut the transfer pipe 60, without contaminating the dispensed biopharmaceutical, and meeting the non-contact dispensing requirements of the biopharmaceutical. Also, the bubble sensor does not need to use an external power supply, and can use the 12V power supply inside the peristaltic pump 70, and can be operated more easily by cooperating with the peristaltic pump 70.

[0054] In the embodiments of the present invention, the bubble sensor can be detected by using methods such as infrared detection, capacitance detection, and ultrasonic detection. That is, the first non-contact sensor 30 and the second non-contact sensor 40 may be capacitance-type sensors, ultrasonic sensors, or separated photoelectric sensors.

[0055] In an embodiment of the present invention, both the storage container 10 and the dispensing container 20 may be tubular or bag-shaped containers, such as liquid storage bags, liquid storage tubes, liquid separation bags, and liquid separation tubes. The transfer pipe 60 is an elastic hose, which is easy to hold a peristaltic pump 70 and a non-contact sensor.

[0056] Referring to FIGS. 1 and 4, a second aspect of the present invention provides a method for quantitatively dispensing a biopharmaceutical, and the quantitative dispensing device for the biopharmaceutical used is as follows.

[0057] Two bubble sensors of the same standard (for example, the first bubble sensor and the second bubble sensor), one peristaltic pump 70, one metering device 50 (the volume of the metering device 50 is known), a plurality of transfer pipes 60, and a plurality of liquid separation bags are selected and used, and a plurality of pinch valves installed corresponding to the liquid separation bags. After connecting the plurality of liquid separation bags in parallel, connect them to the discharge port of the liquid storage bag by the transfer pipe 60, connect the metering device 50 to the transfer pipe 60 between the inlet of the liquid separation bag closest to the liquid storage bag and the discharge port of the liquid storage bag, sandwich two bubble sensors of the same standard at both ends of the inlet 53 and the outlet 54 of the metering device 50, install the peristaltic pump 70 on the transfer pipe 60 between the first bubble sensor and the liquid storage bag, and sandwich a pinch valve on each transfer pipe 60 of the liquid separation bag.

[0058] It should be noted that before dispensing the biopharmaceutical in the liquid storage bag, the air in the liquid separation bag and the transfer pipe 60 is extracted into the liquid storage bag by the peristaltic pump 70. This prevents excess gas from occupying the volume of the liquid separation bag or the transfer pipe and further affecting the dispensing accuracy of the liquid separation bag.

[0059] The method for quantitatively dispensing a biopharmaceutical mainly includes the following steps S10 to S50. Step S10: Obtain the first bubble detection signal of the biopharmaceutical flowing through the transfer pipe 60 detected by the first non-contact sensor 30.

[0060] That is, after calibrating the flow rate of the peristaltic pump 70, it is confirmed that the flow rate of the biopharmaceutical in the transfer pipe 60 is stable. The biopharmaceutical in the liquid storage bag flows from the liquid storage bag into the transfer pipe 60 by the pumping action of the peristaltic pump 70, and the biopharmaceutical flows along the transfer pipe 60 until it passes through the location of the first bubble sensor, and the first bubble detection signal detected by the first bubble sensor is transmitted to and stored in the controller.

[0061] Step S20: Obtain the second bubble detection signal of the biopharmaceutical flowing through the transfer pipe 60 detected by the second non-contact sensor 40. That is, the biopharmaceutical passes through the first bubble sensor along the transfer pipe 60 and flows into the metering device 50. After the biopharmaceutical fills the entire diversion pipe 52 of the metering device 50, the biopharmaceutical flows out of the metering device 50 and enters another transfer pipe 60 and passes through the location of the second bubble sensor, and the second bubble detection signal detected by the second bubble sensor is transmitted to and stored in the controller. Step S30: Calculate the time difference t between the detected first bubble detection signal and the second bubble detection signal. That is, the controller stores the time for the biopharmaceutical to pass through the first bubble sensor and the second bubble sensor when flowing through the transfer pipe 60, and calculates the time difference t for the biopharmaceutical to pass through the entire metering device 50 and a part of the transfer pipe 60 when flowing through the transfer pipe 60.

[0062] Step S40: Obtain the actual flow rate of the biopharmaceutical in the transfer pipe 60 according to the relationship between the time difference t and the volume or volume of the transfer pipe 60 (including the diversion pipe 52 and a part of the transfer pipe 60) between the first non-contact sensor 30 and the second non-contact sensor 40. That is, the volume of the metering device 50, the volume of the transfer pipe 60 between the first bubble sensor and the inlet 53 of the metering device 50, and the volume of the transfer pipe 60 between the second bubble sensor and the outlet 54 of the metering device 50 are added to obtain the total volume of the transfer pipe 60 between the first bubble sensor and the second bubble sensor, and the total volume is divided by the time difference t to obtain the actual volume flow rate Q of the biopharmaceutical in the transfer pipe 60 at this time. The volume flow rate of the present invention is expressed by the formula Qv = V / t = u×A (1-1). In the formula, V represents the volume per unit flow rate, t represents time, u represents the average flow velocity in the pipe, A represents the cross-sectional area of the pipe.

[0063] Step S50 realizes the quantitative dispensing of the biopharmaceutical by controlling the time for the biopharmaceutical to flow through the transport pipe 60.

[0064] That is, after calibrating the flow rate of the peristaltic pump 70, that is, after determining the flow velocity of the biopharmaceutical in the transport pipe 60, the switching time of the pinch valve on each liquid separation bag is controlled to control the actual volume of the biopharmaceutical in the corresponding liquid separation bag, thereby realizing the quantitative dispensing of the biopharmaceutical. The dispensing process is performed in order from the first liquid separation bag to the Nth liquid separation bag.

[0065] In some embodiments of the present invention, in the above step S50, in order to realize the quantitative dispensing of the biopharmaceutical at a predetermined flow velocity of the peristaltic pump 70, the flow time of the biopharmaceutical in 60 is controlled. Quantitative dispensing is realized by controlling the switching time of the switching valve 80 at the injection port of each dispensing container 20 at the calibrated and stable flow velocity of the peristaltic pump 70

[0066] For example, assume that the volume of the biopharmaceutical stored in the liquid storage bag is 304 ml and it needs to be dispensed into 6 liquid separation bags. It is known that the volume of the metering device 50 is 5 ml, the flow velocity of the peristaltic pump 70 is 24 ml / min, the volume of the transport pipe 60 from the second bubble sensor to the injection port of the sixth liquid separation bag is 1.5 ml, and the volume of the branch pipe between the injection ports of the remaining liquid separation bags and the main transport pipe is 0.5 ml.

[0067] After starting to dispense the biopharmaceutical, the biopharmaceutical passes through the first bubble sensor along the transfer pipe 60 and flows into the metering device 50. After the biopharmaceutical fills the entire diversion pipe 52 of the metering device 50, the biopharmaceutical flows out of the metering device 50, enters another transfer pipe 60, and passes through the location of the second bubble sensor. The second bubble sensor transmits and stores the detected second bubble detection signal to the controller. The time difference between the second bubble detection signal and the first bubble detection signal is calculated to be 12 s. The actual flow velocity of the biopharmaceutical in the transfer pipe 60 at this time calculated by the volume flow rate calculation formula is 5 ml / 12 s = 25 ml / min.

[0068] If the volume of each liquid separation bag is 50 ml, the time required to dispense into the last liquid separation bag, that is, the sixth liquid separation bag, is (50 + 1.5) / 25 = 123.6 s, but the time required to dispense into the remaining five liquid separation bags is (50 + 0.5) / 25 = 121.2 s.

[0069] The present invention measures the relationship between the time for the biopharmaceutical to flow through one metering device 50 and the volume of the metering device 50 by two bubble sensors of the same specification, calculates the actual liquid supply flow rate of the biopharmaceutical in the transfer pipe 60, calibrates the rotation speed of the peristaltic pump 70 according to the actual liquid supply flow rate of the biopharmaceutical in the transfer pipe 60, and further controls the time for the biopharmaceutical to enter the liquid separation bag at the set flow rate of the peristaltic pump 70, that is, the stable flow velocity of the transfer pipe 60, so as to determine the true volume or capacity of the biopharmaceutical in the liquid separation bag, thereby realizing non-contact dispensing of the biopharmaceutical.

[0070] Note that the flow rate of the peristaltic pump 70 is the volume of the biopharmaceutical flowing through the peristaltic pump 70 per unit time, and the flow rate of the peristaltic pump 70 and the rotation speed are in a directly proportional relationship.

[0071] The present invention combines two bubble sensors of the same specification and the metering device 50 to measure the actual flow rate of the biopharmaceutical in the transfer pipe 60, calibrate the rotation speed of the peristaltic pump 70, and thereby improve the dispensing accuracy and efficiency of the biopharmaceutical.

[0072] The present invention indirectly measures the actual flow rate in the transfer tube 60 based on the relationship between the volume of the biopharmaceutical in the transfer tube 60 and the flow time of the biopharmaceutical in a transfer tube 60 of a predetermined length, thereby calibrating the flow rate of the peristaltic pump 70 and further calibrating the flow rate of the peristaltic pump 70. When the actual flow rate in the transfer tube 60 is determined, quantitative dispensing of the biopharmaceutical is achieved by controlling the flow time of the biopharmaceutical in the transfer tube 60.

[0073] In addition, the method for quantitatively dispensing a biopharmaceutical provided by the present invention can achieve accurate control of the dispensed volume of the biopharmaceutical by avoiding errors caused by vibration or rocking of the quantitative dispensing device for the biopharmaceutical in the dispensing process, without directly contacting the biopharmaceutical throughout the dispensing process and without destroying the integrity and activity of the biopharmaceutical, and has high practicality.

[0074] It should be noted that the technical solutions of the embodiments of the invention can be combined with each other, but the basis of the mutual combination is based on what can be achieved by those skilled in the art. If the combination of technical solutions conflicts with each other or cannot be realized, such a combination of technical solutions does not exist, that is, it should be considered not to belong to the protection scope of the present invention.

[0075] Finally, it should be noted that the above embodiments are for explaining the technical solutions of the present invention and do not limit it. Although the present invention has been described in detail with reference to the above embodiments, those skilled in the art can modify the technical solutions described in the above embodiments or equivalently replace some of the technical features therein. However, it should be understood that these modifications or replacements do not deviate from the gist and scope of the technical solutions of the embodiments of the present invention for the corresponding technical solutions.

Industrial Applicability

[0076] The present invention provides a quantitative dispensing device and a dispensing method for biopharmaceuticals. The quantitative dispensing device for biopharmaceuticals includes a storage container, a dispensing container, a first non-contact sensor, and a second non-contact sensor. The biopharmaceutical is stored inside the storage container. The inlet of the dispensing container communicates with the outlet of the storage container through a transfer pipe. Both the first non-contact sensor and the second non-contact sensor are installed on the transfer pipe between the inlet of the dispensing container and the outlet of the storage container, and the first non-contact sensor and the second non-contact sensor are separated by a predetermined distance. By installing a non-contact sensor on the transfer pipe between the inlet of the dispensing container and the outlet of the storage container, the present invention can achieve non-contact quantitative dispensing of biopharmaceuticals, effectively improve the dispensing efficiency and dispensing accuracy of biopharmaceuticals, and has excellent economic value and application prospects.

Explanation of reference numerals

[0077] 10 Storage container 20 Dispensing container 30 First non-contact sensor 40 Second non-contact sensor 50 Quantitative device 51 Main body 52 Conduit 53 Inlet 54 Outlet 60 Transfer pipe 70 Peristaltic pump 80 Switching valve

Claims

1. A quantitative dispensing device for biopharmaceuticals, comprising: a storage container in which the biopharmaceutical is stored; a dispensing container whose injection port communicates with the discharge port of the storage container via a transfer pipe; A quantitative dispensing device for biopharmaceuticals, characterized in that a first non-contact sensor and a second non-contact sensor, both installed in the transfer pipe between the injection port of the dispensing container and the discharge port of the storage container and separated by a predetermined distance, are provided.

2. The quantitative dispensing device for biopharmaceuticals according to claim 1, wherein a metering device is installed in the transfer pipe between the first non-contact sensor and the second non-contact sensor.

3. The quantitative dispensing device for biopharmaceuticals according to claim 2, wherein the metering device includes a main body, a diversion pipe is formed inside the main body, the diversion pipe extends along a predetermined path, and the length of the predetermined path is longer than the distance between the inlet and the outlet of the diversion pipe.

4. The quantitative dispensing device for biopharmaceuticals according to claim 3, wherein the diversion pipe is installed annularly along the center line of the main body and further communicates with the transfer pipe.

5. The quantitative dispensing device for biopharmaceuticals according to claim 4, wherein the cross-sectional area of the diversion pipe is equal to the cross-sectional area of the transfer pipe.

6. The quantitative dispensing device for biopharmaceuticals according to claim 1, wherein the transfer pipe between the first non-contact sensor and the second non-contact sensor is installed spirally and is suitable for extending the flow path of the transfer pipe.

7. The quantitative dispensing device for biopharmaceuticals according to claim 1, further comprising a pressure-feeding component for supplying transfer power to the transfer pipe, wherein the pressure-feeding component is installed in any one of the transfer pipe, the storage container, and the dispensing container.

8. The quantitative dispensing device for biopharmaceuticals according to claim 1, wherein a plurality of dispensing containers are installed in parallel, and switching valves are respectively installed in the transfer pipes between the injection ports of the respective dispensing containers and the discharge port of the storage container.

9. A method for quantitatively dispensing biopharmaceuticals, comprising: The method for quantitatively dispensing biopharmaceuticals is realized by the quantitative dispensing device for biopharmaceuticals according to any one of claims 1 to 8, and acquiring a first bubble detection signal of the transfer pipe detected by a first non-contact sensor; acquiring a second bubble detection signal of the transfer pipe detected by a second non-contact sensor; calculating a time difference between the detected first bubble detection signal and the second bubble detection signal; obtaining an actual volumetric flow rate of the biopharmaceutical in the transfer pipe based on the relationship between the time difference and the volume or capacity of the transfer pipe between the first non-contact sensor and the second non-contact sensor; realizing metered dispensing of the biopharmaceutical by controlling the time for which the biopharmaceutical flows through the transfer pipe. A method for metered dispensing of a biopharmaceutical, characterized by including these steps. **Claim 10** Realizing metered dispensing of the biopharmaceutical by controlling the time for which the biopharmaceutical flows through the transfer pipe is characterized by controlling the switching time of the switching valve at the inlet of each dispensing container at a predetermined flow rate of the peristaltic pump. The method for metered dispensing of a biopharmaceutical according to claim 9.

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