Liquid rationing and dispensing system and dispensing apparatus thereof

Abstract

The application provides a liquid rationing and sub-packaging system and a sub-packaging device, wherein the sub-packaging structure comprises a sample container, a plurality of rationing containers, a sub-packaging container, an on-off valve and a power mechanism for driving the liquid in the sample container to flow into the rationing containers; the bottom of the sample container is connected with a total conveying pipeline which has a plurality of horizontal branch pipelines; the horizontal branch pipelines are connected with the bottoms of the corresponding rationing containers through first vertical pipelines; the top of each rationing container is provided with a second vertical pipeline which is connected with the atmosphere; and the horizontal branch pipelines are also provided with third vertical pipelines which are connected with the sub-packaging containers at positions corresponding to the first vertical pipelines. The sub-packaging device is used in cooperation with the sub-packaging structure and comprises a main body support and a pipe clamp for fixing the corresponding pipelines. The application can greatly improve the sub-packaging precision, control the sub-packaging power and sub-packaging efficiency according to the needs, and has simple sub-packaging operation and high operation efficiency.

Description

Technical Field

[0001] This invention relates to the field of liquid dispensing technology, and in particular to a liquid quantitative dispensing system and dispensing equipment. Background Technology

[0002] Cell therapy, as a novel treatment modality, has experienced rapid development in recent years. It primarily treats diseases by using or modifying the body's own cells (such as stem cells and immune cells). These cells can originate from the patient or others, or be generated through genetic engineering. Currently, the field of cell therapy mainly focuses on autologous cell therapy. However, with increasing treatment demands, the development of universal cell therapy is becoming a trend. Universal cell therapy aims to make cell therapy products widely applicable to different patients through genetic modification and other methods, without considering individual immune rejection. Compared to the preparation of autologous cell products, the production and preparation of universal cell therapy products have higher requirements in terms of efficiency and throughput. Currently, commercially available cell preparation dispensing equipment uses peristaltic pumps to dispense dispensing bags one by one, which is inefficient. Furthermore, due to limitations such as wear and tear on the peristaltic pump tubing, it cannot meet the high-throughput, multi-bag dispensing requirements.

[0003] Patent document CN218198915U discloses a drug dispenser for Western medicine research. Although it utilizes communicating vessels to achieve the drug dispensing function, it still has shortcomings:

[0004] (1) In actual operation, due to factors such as the levelness of the ground and the levelness of the dispensing tank, the liquid level in each dispensing tank cannot reach an absolute level. After the medicine is distributed to each dispensing tank through the communication device, the height difference (Δh) of the liquid in each dispensing tank will cause a dispensing accuracy error ΔV, ΔV=Δh×S, where S is the cross-sectional area of ​​the dispensing tank. Similar to existing dispensing equipment, the dispensing accuracy error of this patented product is above 2%.

[0005] (2) The patent cannot control the power of the dispensing process, nor can it control the dispensing efficiency.

[0006] (3) The connector is equipped with multiple fourth valves. When it is necessary to open or close the fourth valves, they need to be opened and closed one by one, which results in low operating efficiency and greatly reduces the dispensing efficiency.

[0007] In addition, existing quantitative dispensing methods are all inefficient. For example, patent documents with publication numbers CN113022911A, CN118665799A, and CN118665798A disclose a liquid dispensing method and equipment, but in practice, they only imitate manual operation to achieve automated operation, and do not fundamentally solve the problem of rapid and accurate dispensing in a short time, especially the high-efficiency dispensing of large volume cell fluid. Summary of the Invention

[0008] To overcome the shortcomings of the prior art, the present invention provides a liquid quantitative dispensing system and dispensing equipment, which can greatly improve the dispensing accuracy, and can also control the dispensing power and dispensing efficiency as needed. Moreover, the dispensing operation is simple and efficient, solving the problem of rapid and accurate liquid dispensing in a short time.

[0009] To achieve at least one of the above objectives, the technical solution adopted by the present invention is as follows:

[0010] This invention first provides a liquid quantitative dispensing system, including a sample container, several quantitative containers, a dispensing container, a switching valve, and a power mechanism for driving liquid in the sample container into the quantitative container. The bottom of the sample container is connected to a main delivery pipeline, which has several horizontal branch pipelines. Each horizontal branch pipeline is connected to the bottom of a corresponding quantitative container via a first vertical pipeline. The top of the quantitative container is provided with a second vertical pipeline communicating with the atmosphere. A third vertical pipeline connected to the dispensing container is also provided on the horizontal branch pipeline at a position corresponding to the first vertical pipeline. The switching valve includes a first switching valve for opening and closing the horizontal branch pipelines between adjacent first vertical pipelines, a second switching valve for opening and closing the third vertical pipeline, and a main switching valve for opening and closing the main delivery pipeline.

[0011] Preferably, the power mechanism is a gravity-driven mechanism, that is, the sample container is positioned higher than the quantitative container and the height of the sample container is adjustable; or it is a peristaltic pump installed on the main delivery pipeline; or it is an air-blowing mechanism that blows gas into the sample container.

[0012] Preferably, the second vertical pipe is connected to the first dripping bucket via the first connecting pipe, and the top of the first dripping bucket is connected to the first gas filter; the first connecting pipe is also provided with a first pressure sensor, a fourth switching valve, and a second gas filter arranged sequentially thereon.

[0013] Preferably, the sample container is connected to several preparation containers via branch pipes, and each branch pipe is equipped with a third switching valve.

[0014] Preferably, when the power mechanism is a peristaltic pump installed on the main delivery pipeline, the outlet of the peristaltic pump is connected to the horizontal branch pipeline through a second connecting pipeline. A fifth switching valve and a first bubble sensor are sequentially installed on the second connecting pipeline from the direction away from the peristaltic pump. A third gas filter, a second bubble sensor, a metering container, and a sixth switching valve are also sequentially installed on the second connecting pipeline from the farthest to the nearth. An exhaust pipeline is installed on the pipeline between the main switching valve and the peristaltic pump. A seventh switching valve, a second drip chamber, and a fourth gas filter are sequentially installed on the exhaust pipeline.

[0015] The present invention also provides a liquid quantitative dispensing device, which is used in conjunction with the above-mentioned dispensing structure, including: a main support and pipe clamps for fixing corresponding pipelines.

[0016] Preferably, the main support includes a first support portion for fixing the sample container and having an adjustable height, and a second support portion arranged parallel to the first support portion; a plurality of connecting plates are provided between the first support portion and the second support portion, and a plurality of pipe clamps are provided on the connecting plates; the first switching valve includes a first fixing plate disposed on the back of the horizontal branch pipe and a first pressure plate disposed on the front of the horizontal branch pipe, the first pressure plate being provided with a plurality of protrusions for squeezing the horizontal branch pipe; the second switching valve includes a second fixing plate disposed on the back of the third vertical pipe and a second pressure plate disposed on the front of the third vertical pipe; both the first pressure plate and the second pressure plate are provided with a clamping mechanism for pressing the corresponding pressure plate and the fixing plate together; both the first fixing plate and the second fixing plate are disposed on the main support.

[0017] Preferably, the first fixing plate and the second fixing plate are integrally formed or separately arranged; the clamping mechanism is a linkage clamping mechanism; the first pressure plate and the second pressure plate are both detachably connected to the clamping mechanism; the end of the protrusion is provided with a gasket; the main support is also provided with a fixing part for fixing the dripping bucket; the first support part and the second support part are both fixedly arranged on a base; the base is provided with adjustable leveling support feet.

[0018] Preferably, the main support includes a support table, a shell frame, and a fixing bracket for fixing quantitative tubes and dispensing containers. The shell frame is internally divided into a first cavity and a second cavity. The first cavity is an insulated box, and the sample container is installed in the insulated box in a liftable manner. The first cavity is also provided with a squeezing plate that can squeeze the sample container. The front side wall of the second cavity is provided with a display screen and a switch valve control button.

[0019] Preferably, the fixed bracket is a beam type, including a horizontally arranged upper beam bracket and a lower beam bracket, one end of which is hinged to the shell frame and the other end is a movable end; or it is a rotary type, including a circular upper rotating frame, a middle rotating frame, a lower rotating frame and a base arranged sequentially from top to bottom, the upper rotating frame and the middle rotating frame are connected by several support rods, and the lower rotating frame and the base are connected by a rotary bearing.

[0020] The positive effects of this invention:

[0021] (1) The present invention has a vertical pipe connected to the atmosphere at the top of the quantitative container. When the liquid in the sample container is distributed to each quantitative container using the principle of communicating vessels, the vertical pipe allows a small amount of liquid in the quantitative container to overflow, so that the liquid column stops at the vertical pipe. Since the inner cross-sectional area of ​​the vertical pipe is much smaller than the inner cross-sectional area of ​​the quantitative container, the dispensing accuracy error ΔV is greatly reduced. Experimental verification shows that the dispensing error can be controlled within 0.2%, which is much better than the 2% accuracy error of the existing dispensing equipment.

[0022] (2) The height of the sample container of the present invention is adjustable, thereby allowing the height difference ΔH between the sample container and the quantitative container to be adjusted as needed. The larger ΔH is, the greater the hydraulic difference, the greater the power provided for dispensing, the faster the liquid flow during dispensing, and the higher the dispensing efficiency. In other words, this patent allows for on-demand control of the dispensing power and dispensing efficiency. In addition, this patent also supports adding a peristaltic pump or other power device to the lower part of the sample container to provide dispensing power using the peristaltic pump or other device.

[0023] (3) The switch valve structure provided by the present invention can open and close multiple pipelines at one time. When there are many quantitative containers and dispensing containers during dispensing, the switch valve structure can greatly simplify the opening and closing operation of multiple pipelines, effectively improve dispensing efficiency, and reduce the risk of misoperation.

[0024] (4) The present invention uses fully enclosed pipeline consumables, which can realize fully enclosed dispensing to better avoid external contamination of the dispensed liquid.

[0025] (5) While ensuring dispensing accuracy, this invention can achieve simultaneous and rapid dispensing of multiple bags at a controllable speed. Tests have shown that for 10ml / bag dispensing, 100 bags can be dispensed in 10 minutes (total operation time). In contrast, existing patented technologies such as those with publication numbers CN113022911A, CN118665799A, and CN118665798A require at least one bag per minute on average for dispensing 10ml / bag, and approximately 100 minutes for 100 bags. Compared to existing technologies, this invention significantly improves dispensing efficiency (tenfold increase) while maintaining dispensing accuracy.

[0026] (6) The present invention can exhaust the air from the dispensing container after dispensing to avoid residual air in the dispensing container (residual air is not conducive to the subsequent cryopreservation of cells).

[0027] In summary, compared with existing dispensing equipment, the present invention can greatly improve the dispensing accuracy, while also controlling the dispensing power and efficiency as needed. Furthermore, the dispensing operation is simple, efficient, and fully enclosed, making it particularly suitable for the dispensing of biological agents such as cells. Attached Figure Description

[0028] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings described below are only embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on the provided drawings without creative effort.

[0029] Figure 1 This is a schematic diagram of the liquid quantitative dispensing system provided in the first specific embodiment of the present invention;

[0030] Figure 2 This is a schematic diagram of the liquid quantitative dispensing system provided in the second specific embodiment of the present invention;

[0031] Figure 3 This is a schematic diagram of the liquid quantitative dispensing system provided in the third specific embodiment of the present invention;

[0032] Figure 4 This is a schematic diagram of the liquid quantitative dispensing system provided in the fourth specific embodiment of the present invention;

[0033] Figure 5 This is a schematic diagram of the hybrid packaging structure provided in the fifth specific embodiment of the present invention;

[0034] Figure 6 This is a schematic diagram of the liquid quantitative dispensing system provided in the sixth specific embodiment of the present invention;

[0035] Figure 7 This is a schematic diagram showing the stopping position of the liquid column when the metering container is not full;

[0036] Figure 8 This is a schematic diagram showing the stopping position of the liquid column when the liquid overflows from the metering container;

[0037] Figure 9 This is a schematic diagram of the liquid quantitative dispensing device in the compressed state according to the seventh specific embodiment of the present invention;

[0038] Figure 10 yes Figure 9 A magnified schematic diagram of a portion of region A in the middle;

[0039] Figure 11 yes Figure 9 A magnified schematic diagram of a portion of region B in the middle;

[0040] Figure 12 yes Figure 9 A magnified schematic diagram of a portion of region C in the middle;

[0041] Figure 13 This is a schematic diagram of the liquid quantitative dispensing device in the non-compression state provided in the seventh specific embodiment of the present invention;

[0042] Figure 14 This is a schematic diagram of the liquid quantitative dispensing system provided in the eighth specific embodiment of the present invention (before liquid dispensing);

[0043] Figure 15 This is a schematic diagram of the liquid dispensing system provided in the eighth specific embodiment of the present invention (during the process of dispensing liquid into the dispensing tube);

[0044] Figure 16 This is a schematic diagram of the liquid dispensing system provided in the eighth specific embodiment of the present invention (after the liquid is completely dispensed into the dispensing tube);

[0045] Figure 17 This is a schematic diagram of the liquid quantitative dispensing system provided in the eighth specific embodiment of the present invention (during the process of dispensing liquid from the quantitative tube to the dispensing bag);

[0046] Figure 18 This is a schematic diagram of the liquid quantitative dispensing system provided in the ninth specific embodiment of the present invention;

[0047] Figure 19 This is a schematic diagram of the liquid quantitative dispensing system provided in the tenth specific embodiment of the present invention;

[0048] Figure 20 This is a schematic diagram of the liquid quantitative dispensing device provided in the eleventh specific embodiment of the present invention;

[0049] Figure 21 This is a schematic diagram of the rotating fixed bracket provided in the twelfth specific embodiment of the present invention;

[0050] Figure 22 This is a schematic diagram of the liquid quantitative dispensing device provided in the thirteenth specific embodiment of the present invention.

[0051] The attached figures are labeled as follows:

[0052] Sample container 1, quantitative container 2, dispensing container 3, first dropper 4, first gas filter 5, liquid column stop position 6, main delivery pipeline 7, horizontal branch pipeline 8, first vertical pipeline 9, second vertical pipeline 10, third vertical pipeline 11, first connecting pipeline 12, first switch valve 13, second switch valve 14, multi-channel connector 16, third switch valve 17, preparation container 18, peristaltic pump 19; eighth switch valve 20, first pressure sensor 21, fourth switch valve 22, second gas filter 23, first bubble sensor 24, fifth switch valve 25, sixth switch valve 26, quantitative tube 27, second bubble sensor 28, third gas filter 29, seventh switch valve 30, second dropper 31, fourth gas filter 32, fourth gas filter 33, ninth switch valve 34, air pump 35;

[0053] First support part 201, second support part 202, fixing plate 203, first pressure plate 204, second pressure plate 205, pressing mechanism 206, base 207, support foot 208, connecting plate 209, hanging rod 210, hook 211, height adjuster 212, fixing part 213, pipe clamp 214, base 215, first connecting rod 216, second connecting rod 217, drive rod 218, handle 219, protrusion 220;

[0054] Support table 301, shell frame 302, extrusion plate 303, insulation box 304, crossbar 305, hook 306, first bubble sensor fixing position 307, display screen 308, first air pressure sensor fixing position 309, fourth switch valve control key 310, sixth switch valve control key 311, second bubble sensor fixing position 312, fifth switch valve control key 313, second dripping bucket fixing frame 314, peristaltic pump mounting position 315, quantitative tube fixing frame 316, main switch valve control key 317, seventh switch valve control key 318, upper crossbeam support 319, lower crossbeam support 320, first dripping bucket fixing frame 321, upper rotating frame 322, middle rotating frame 323, lower rotating frame 324, base 325, rotary bearing 326, support leg 327, dripping bucket fixing frame 328, third cavity 329, support rod 330. Detailed Implementation

[0055] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.

[0056] Reference Figure 1 This invention provides a liquid quantitative dispensing system, including a sample container 1, several quantitative containers 2, a dispensing container 3, a switching valve, and a power mechanism for driving liquid in the sample container into the quantitative container. The bottom of the sample container 1 is connected to a main delivery pipeline 7, which has several horizontal branch pipelines 8. Each horizontal branch pipeline 8 is connected to the bottom of a corresponding quantitative container 2 via a first vertical pipeline 9. The top of the quantitative container 2 is provided with a second vertical pipeline 10 communicating with the atmosphere. A third vertical pipeline 11 connected to the dispensing container 3 is also provided on the horizontal branch pipeline 8 at a position corresponding to the first vertical pipeline 9. The switching valve includes a first switching valve 13 for opening and closing the horizontal branch pipelines between adjacent first vertical pipelines 9, a second switching valve 14 for opening and closing the third vertical pipeline 11, and a main switching valve 15 for opening and closing the main delivery pipeline 7. In this embodiment, the power mechanism is a gravity-driven mechanism, and the sample container 1 is positioned higher than the quantitative container 2.

[0057] The sample container 1 is used to hold the liquid to be dispensed. It can be any container capable of holding liquid, such as a sample bag or sample box. The present invention preferably uses a sample bag. Similarly, the quantitative container 2 can be any form, such as a quantitative tube, with the bottom of all quantitative tubes at the same level. Since the sample container (sample bag) is higher than the quantitative container (quantitative tube), when the main switch is turned on, the hydraulic pressure formed by the height difference will cause the sample liquid to flow towards each quantitative tube, and simultaneously feed liquid into the quantitative tube. When the liquid in the sample bag has finished flowing down, according to the principle of communicating vessels, the liquid column of each quantitative tube branch stops at the same level, thereby achieving the simultaneous and equal distribution of the sample solution into several quantitative containers, thus realizing rapid dispensing.

[0058] In actual operation, due to factors such as the levelness of the surrounding ground and the levelness of the dispensing equipment, each quantitative container cannot achieve absolute levelness. The height difference (Δh) of the liquid in each quantitative tube after dispensing will cause a dispensing accuracy error ΔV, where ΔV = Δh * S, and S is the cross-sectional area of ​​the liquid column. Figure 7As shown, when the metering tube is not full, the cross-sectional area of ​​the liquid column is equal to the internal cross-sectional area S1 of the metering tube, i.e., S = S1. To reduce the error in dispensing accuracy, when making the dispensing plan, a metering container with a volume slightly smaller than the volume of liquid to be dispensed is selected. Since the present invention has a vertical pipe connected to the atmosphere at the top of the metering container, after the liquid in the sample container is distributed to each metering container using the principle of communicating vessels, a small amount of liquid in the metering container overflows, thus causing the liquid column to stop at position 6 at the vertical pipe (e.g., ...). Figure 8 As shown in the figure, since the inner cross-sectional area of ​​the vertical pipe is much smaller than that of the quantitative container, the dispensing accuracy error ΔV is greatly reduced. Experimental verification shows that the dispensing error can be controlled within 0.2%, which is a significant improvement in dispensing accuracy compared to the 2% accuracy error of existing dispensing equipment.

[0059] Preferably, such as Figure 1 As shown, the second vertical pipe is connected to a first dripping bucket 4 via a first connecting pipe 12, and the top of the first dripping bucket 4 is connected to a first gas filter 5. The first dripping bucket 4 serves as a buffer (if the liquid flows too quickly from the metering tube to the first gas filter 5, it may clog the first gas filter 5 and contaminate the cell preparation; therefore, a dripping bucket is placed between the metering pipe and the first gas filter 5 to prevent the liquid level from rising too quickly and reaching the filter). The first gas filter 5 prevents contamination of the dispensed liquid during the dispensing process.

[0060] Furthermore, the volume specifications of each quantitative container 2 can be the same or different (e.g., Figure 2 As shown in the diagram, the specifications of the quantitative container 2 can be adapted to meet specific needs, such as 5-100ml sizes. During the dispensing process within the same batch, if quantitative containers 2 of the same specifications are selected, even dispensing can be achieved using communicating vessels. If quantitative containers 2 of different specifications are selected, dispensing is performed according to the volume of the quantitative tube, such as... Figure 2 For example, 60ml of sample solution is dispensed into 5 liquid bags. If bag #2 contains 20ml, then the 2nd quantitative tube should be a 20ml volumetric size. If the other 4 liquid bags contain 10ml each, then the corresponding quantitative tubes should be a 10ml volumetric size.

[0061] Preferably, such as Figure 1 As shown, several cross-shaped four-way connectors can be set up so that the horizontal branch pipes are connected to the first vertical pipe 9 above and the third vertical pipe 11 below, respectively.

[0062] Furthermore, the horizontal branch pipeline 8 can be a single line or multiple lines, meaning the present invention can adapt to the packaging requirements of dispensing any number of bags at a time. For example, as... Figure 1The single-path horizontal branch pipeline shown can connect 1 to n sets of metering tubes (n is an integer greater than 1); for example Figure 3 Furthermore, a multi-channel connector 16 can be installed on the delivery pipeline below the sample bag to obtain multiple horizontal branch pipelines that expand in a star shape in multiple horizontal directions. For example, if expanded in m directions (m is an integer greater than 1), the dispensing of liquid into m*n bags can be achieved simultaneously. In addition, star-plus-star expansion is also possible, such as... Figure 4 As shown.

[0063] like Figure 5 As shown, the sample container 2 can also be connected to several preparation containers 18 through branch pipelines. Each preparation container 18 can contain different liquid preparations. At the same time, each branch pipeline is equipped with a third switch valve 17 to realize the mixing and dispensing of various different liquid reagents.

[0064] Preferably, the position of the sample container 1 relative to the position of the quantitative container 2 is adjustable. For example... Figure 1 As shown, since the sample bag is suspended higher than the quantitative tube, the liquid height difference ΔH can be used to provide power for dispensing. The larger ΔH is, the greater the hydraulic pressure difference, the faster the liquid flows during dispensing, and the higher the dispensing efficiency. That is, this invention can control the dispensing speed by adjusting the position and height of the sample container 1, thereby achieving control over the dispensing power and efficiency. Furthermore, since the dispensing speed can be controlled by adjusting the suspension height of the sample bag, a correlation table between the sample bag height and the dispensing flow rate can be established through calculation and combined with a large number of experimental records. In specific dispensing operations, an appropriate dispensing speed can be selected according to the actual situation.

[0065] In addition, a peristaltic pump or other device can be added below the sample container 2, such as a peristaltic pump 19 installed on the main delivery pipeline (e.g., Figure 6 As shown in the figure, the present invention can also utilize a peristaltic pump or other devices to provide dispensing power.

[0066] Reference Figure 9 One embodiment of the present invention provides a liquid quantitative dispensing device, which is used in conjunction with the above-mentioned dispensing structure, including: a main support and tube clamps 214 for fixing corresponding pipelines. The main support can be used to fix components such as sample container 1, quantitative container 2, dispensing container 3, and first dropper 4; the tube clamps 214 can be used to fix each pipeline to ensure that the pipelines remain vertical or horizontal during the dispensing process.

[0067] Specifically, such as Figure 9 and Figure 10As shown, the main support includes a first support 201 with adjustable height for fixing the sample container, and a second support 202 arranged parallel to the first support; a plurality of connecting plates 209 are provided between the first support and the second support, and a plurality of tube clamps 214 are provided on the connecting plates 209. Figure 10 As shown, preferably, the first support part 201 can be in the form of a support rod, and of course, the support rod can also be in the form of a telescopic type; a hanging rod 210 can be provided at the top of the support rod, and the hanging rod 210 is connected to the support rod through a height adjuster 212. Several hooks 211 can be provided on the hanging rod 210 for hanging sample containers such as sample bags; the height adjuster 212 can be a slider provided on the support rod and can slide up and down along the support rod, and the slider is provided with a locking mechanism such as a locking bolt for restricting the movement of the slider.

[0068] Preferred, such as Figure 9 and Figure 13 As shown, the first switching valve 13 includes a first fixing plate 203 disposed on the back of the horizontal branch pipeline and a first pressure plate 204 disposed in front of the horizontal branch pipeline. The first pressure plate 204 is provided with a plurality of protrusions 220 for squeezing the horizontal branch pipeline. The second switching valve 14 includes a second fixing plate disposed on the back of the third vertical pipeline and a second pressure plate 205 disposed in front of the third vertical pipeline. Both the first pressure plate 204 and the second pressure plate 205 are provided with a clamping mechanism 206 for pressing the corresponding pressure plate and the fixing plate together. Both the first fixing plate and the second fixing plate are disposed on the main support.

[0069] Furthermore, the first fixing plate and the second fixing plate are integrally formed (i.e., they are a single plate, such as...). Figure 9 (As shown) or separately (i.e., two separate plates). With the fixed plate as the boundary, the area above the first fixed plate is the quantitative distribution area, used to install each quantitative tube; the area below the second fixed plate is the liquid bag area, used to install and suspend each dispensing liquid bag.

[0070] Preferably, the clamping mechanism 206 is a linkage clamping mechanism, but it can also be any other existing clamping mechanism capable of moving the pressure plate towards and away from the fixed plate. Specifically, the structure of the linkage clamping mechanism can be exemplified by... Figure 12As shown, the system includes a base 215, a drive rod 218, a first connecting rod 216, and a second connecting rod 217. The base 215 is mounted on a fixed plate and has an L-shaped top surface. One end of the first connecting rod 216 is hinged to one end of the L-shaped top surface, and the other end is hinged to the drive rod 218. The second connecting rod 217 is L-shaped, with one end hinged to one end of the L-shaped top surface, a corner end hinged to the end of the drive rod 218, and the other end hinged to a corresponding pressure plate. The drive rod 218 has a handle 219 for easy operation. When the first pressure plate 204 is not pressed against the first fixed plate (i.e., when the horizontal branch pipeline is in the open state), as... Figure 13 As shown, at this time, the first pressure plate 204 and the first fixed plate are parallel to each other. When the handle 219 is pressed down towards the first fixed plate, under the interconnected state of the linkage, the first pressure plate 204 gradually moves towards the direction perpendicular to the fixed plate. When the first pressure plate 204 and the fixed plate are perpendicular to each other (e.g. Figure 9 As shown), several protrusions 220 on the first pressure plate 204 press and close the corresponding horizontal branch pipe. Preferably, a gasket can be provided at the end of the protrusion 220 to assist the pressure plate in pressing the corresponding pipe. Similarly, when the second pressure plate 205 is not pressed against the second fixed plate (i.e., when the corresponding pipe is in the open state), such as Figure 13 As shown, at this time, the second pressure plate 205 and the second fixed plate are parallel to each other. When the handle 219 is pressed down towards the fixed plate, under the interconnected state of the linkage, the second pressure plate 205 gradually moves towards the direction perpendicular to the fixed plate. When the second pressure plate 205 is perpendicular to the fixed plate (as shown), Figure 9 As shown), the side of the second pressure plate 205 near the fixed plate presses and closes each of the third vertical pipes 11.

[0071] Preferably, both the first pressure plate 204 and the second pressure plate 205 are detachably connected to the pressing mechanism 206, for example... Figure 12 As shown, the pressure plate is detachably connected to the second connecting rod, and the detachable method can be a bolt connection or the like.

[0072] like Figure 9 and Figure 11 As shown, the main support is also provided with a fixing part 213 for fixing the dripping bucket; the first support part 201 and the second support part 202 are both fixedly mounted on a base 207; the base 207 is provided with adjustable level support feet 208.

[0073] Figures 14 to 17This invention provides a liquid quantitative dispensing system and corresponding dispensing method. Assuming there is 1000ml of sample solution that needs to be evenly dispensed into 50 cryopreservation bags, with each bag containing 20ml, the specific dispensing steps are as follows:

[0074] (1) Installation of the sub-piping structure

[0075] Take a set of closed tubing consumables containing 50 20ml dosing tubes, connect 50 100ml cryopreservation bags (dispensing containers) to the tubing below each dosing tube (i.e., the third vertical tubing) through sterile connectors, install each tubing consumable (the dispensing system) onto the dispensing equipment, and ensure that all dosing tubes are in the same horizontal position.

[0076] (2) Prepare the liquid to be dispensed

[0077] Prepare a 1L sample bag, and add 100ml of cell culture, 300ml of human albumin solution, and 600ml of cryopreservation solution to the sample bag in a ratio of 1:3:6.

[0078] (3) Mix the cell sap well

[0079] Place the sample bag containing cell solution on a shaker and mix thoroughly for 5 minutes. Then, use a sterile connector to connect the sample bag to the main delivery line and adjust it to the set height.

[0080] (4) Communicating vessels are divided equally

[0081] Close the second valve to shut off all third vertical pipelines, open the first valve to open all horizontal branch pipelines between adjacent first vertical pipelines, and open the main valve for the sample bag. Due to the height difference, the cell solution in the sample container flows rapidly into the 50 quantitative tubes (e.g., Figure 15 As shown), each metering tube achieves equal distribution based on the principle of communicating vessels. When the equal distribution is complete and the stopping positions of each liquid column are consistent (as shown), Figure 16 (As shown), close the main switch valve.

[0082] (5) Transfer into bag

[0083] The first switch valve is closed so that the horizontal branch pipes between adjacent first vertical pipes are all closed. The second switch valve is opened so that each third vertical pipe is opened. The cell fluid in the quantitative tube flows downward into the corresponding cryopreservation bag under the action of gravity.

[0084] (6) Heat-sealed bag

[0085] Manually squeeze to expel the air from each individual packaging bag, then heat seal and remove.

[0086] Reference Figure 18This specific embodiment provides a liquid quantitative dispensing system, including a sample container 1 and several quantitative containers ( Figure 18 The middle section contains a quantitative tube, a dispensing container, a switching valve, and a power mechanism for driving the liquid in the sample container into the quantitative container. Figure 1 The difference between the embodiments shown is that, Figure 18 The power mechanism in the illustrated embodiment is a peristaltic pump 19 on the main delivery pipeline 7. Simultaneously, the first connecting pipeline 12 is also equipped with a first pressure sensor 21, a fourth switching valve 22, and a second gas filter 23, which are sequentially connected to it. The outlet of the peristaltic pump 19 is connected to the horizontal branch pipeline via a second connecting pipeline. On the second connecting pipeline, starting from the direction away from the peristaltic pump 19, a fifth switching valve 25 and a first bubble sensor 24 are sequentially arranged. The second connecting pipeline is also equipped with a third gas filter 29, a second bubble sensor 28, a metering tube 27, and a sixth switching valve 26, which are sequentially arranged from far to near. An exhaust pipeline is also provided between the main switching valve 15 and the peristaltic pump 19, and this exhaust pipeline is sequentially equipped with a seventh switching valve 30, a second drip chamber 31, and a fourth gas filter 32.

[0087] The specific usage process is as follows: First, open the main switch valve 15 and the sixth switch valve 26. The peristaltic pump 19 pumps the liquid in the cell bag (sample container 1) into the quantitative tube 27. The peristaltic pump stops immediately after the second bubble sensor 28 detects the liquid. Calculate the liquid volume L = V / n per rotation of the peristaltic pump using the volume V of the quantitative tube 27 and the number of rotations n of the peristaltic pump. This completes the peristaltic pump calibration step and is used to achieve precise liquid volume control of the peristaltic pump (the peristaltic pump, in conjunction with the bubble sensor, achieves high-precision quantitative transmission). Then, open the fourth switch valve 22, the fifth switch valve 25, the main switch valve 15, the first bubble sensor 24, and all first switch valves 13 to control the peristaltic pump to pump the cell fluid in the cell bag into the quantitative tubes 1-30 (if the liquid in the cell bag is not completely pumped in, it can be pumped through the peristaltic pump). The pump precisely controls the total volume of the dispensed cell solution. Complete dispensing requires the second bubble sensor 24 to detect the presence of bubbles. Once sufficient liquid has been dispensed, the peristaltic pump stops and the corresponding valves are closed, completing the peristaltic pump transport of the cell solution. Waiting for the liquid levels in the metering tubes 1-30 to reach the same height (and stop at the same liquid column position), all first valves 13 are closed, and all second valves 14 are opened. After all the cell solution in the metering tubes 1-30 has flowed into the bag 1-30, all second valves 14 are closed, completing the quantitative dispensing of the cell solution. If there is still a large amount of cell solution in the cell bag that needs to be dispensed, the tubing on the right side of the second bubble sensor 24 can be replaced with a set of tubing consumables on the right side using a sterile connector, allowing for continued quantitative dispensing.

[0088] After each dispensing of the filling bag is completed, air may remain in the liquid bag. The seventh switch valve 30, the fifth switch valve 25, all the first switch valves 13 and the second switch valve 14, and the first pressure sensor 21 can be opened. The eighth switch valve 20 below the first dripping bucket 4, the main switch valve 15, the sixth switch valve 26, and the fourth switch valve 22 can be closed. The peristaltic pump is controlled to rotate to expel the gas in the liquid bag 1-30 and the metering tube 1-30. The first pressure sensor 21 is used to determine whether the gas has been completely expelled (when the air is completely expelled, a negative pressure will be formed in the pipeline, such as -0.1 kPa, which indicates that the air in the liquid bag has been completely expelled).

[0089] Reference Figure 19 This specific embodiment provides a liquid quantitative dispensing system, including a sample container 1 and several quantitative containers ( Figure 18 The middle section contains a quantitative tube, a dispensing container, a switching valve, and a power mechanism for driving the liquid in the sample container into the quantitative container. Figure 1 The difference between the embodiments shown is that, Figure 19 The power mechanism in the illustrated embodiment is an air pumping mechanism for blowing gas into the sample container 1. As an example, the air pumping mechanism is an air pump 35 (which can be a peristaltic pump) connected to the sample container. A ninth switching valve 34 and a fourth gas filter 33 are also connected to this air pump 35. When using this type of power mechanism, the ninth switching valve 34, the main switching valve 15, and the air pump 35 are opened. Gas is blown into the sample container by the air pump. When the pressure inside the sample container reaches a certain level, the cell fluid is pushed into the quantitative tubes 1-30. Subsequent steps are the same as described above.

[0090] Reference Figure 20This embodiment provides another liquid quantitative dispensing device, which is used in conjunction with the dispensing structure and includes: a main support frame and tube clamps for fixing corresponding pipelines. The main support frame includes a support table 301, a shell frame 302, and a fixing bracket for fixing the quantitative tubes and sample containers. The internal cavity of the shell frame 302 is divided into a first cavity and a second cavity. The first cavity is an insulated box 304, and the sample container is mounted in a liftable manner within the insulated box. A squeezing plate 303 for squeezing the sample container is also provided in the first cavity. Specifically, the insulated box 304 is an automatically temperature-controlled type. A hook 306 for suspending the sample container 1 is provided inside the insulated box 304. The hook 306 is mounted on a horizontal bar 305, and both ends of the horizontal bar 305 are connected to a vertical frame in a liftable manner. Simultaneously, the squeezing plate 303 is also located inside the insulated box 304. The squeezing plate can reciprocate in a direction perpendicular to the sample container (for example, an electric sliding mechanism can be used to achieve the reciprocating motion of the squeezing plate). When using this device, first hang the cell bag on the hook, and adjust the lifting height of the crossbar 305 so that the cell bag is in the squeezing plate position (the lifting type of the crossbar can be adapted to different sizes of cell bags); set the temperature control module (e.g., temperature 4℃, accuracy ±0.5℃) to achieve constant temperature storage of the cell bag; by starting the reciprocating motion of the squeezing plate, the sample container is continuously squeezed so that the cells in the sample container 1 are mixed evenly.

[0091] Furthermore, the front side wall of the second cavity is equipped with a display screen 308, a valve control button, a sensor fixing clip, etc., for example, corresponding to... Figure 18 The following can be installed on the front side wall of the second cavity: a first pressure sensor fixing position 309, a fourth switch valve control key 310, a first bubble sensor fixing position 307, a second bubble sensor fixing position 312, a metering tube 27 fixing bracket 316, a sixth switch valve control key 311, a fifth switch valve control key 313, a main switch valve control key 317, a seventh switch valve control key 318, a second dripping bucket fixing bracket 314, and a peristaltic pump mounting position 315.

[0092] like Figure 20As shown, in a preferred embodiment, the fixing bracket is a beam type, including a horizontally arranged upper beam bracket 319 and a lower beam bracket 320. One end of the upper beam bracket 319 and the lower beam bracket 320 is hinged to the side wall of the shell frame, and the other end is a movable end. Several tube clamps can be installed on both the upper beam bracket 319 and the lower beam bracket 320. The upper beam bracket 319 is equipped with a fixing frame 321 for fixing the first dripping bucket. The upper beam bracket 319 is used to fix the position above the metering tube, and the lower beam bracket 320 is used to fix the position below the metering tube. When not in use, the upper beam bracket 319 and the lower beam bracket 320 can be folded down to fit tightly against the side wall of the shell frame, thereby reducing the space occupied by the device.

[0093] like Figure 21 As shown, in another preferred embodiment, the fixed support is rotatable, comprising, from top to bottom, an upper circular rotating frame 322 (which can be configured as an annular ring), a middle rotating frame 323, a lower rotating frame 324, and a base 325. The upper rotating frame 322 and the middle rotating frame 323, and the middle rotating frame 323 and the lower rotating frame 324, are connected by several support rods 330, respectively. The lower rotating frame 324 and the base 325 are connected by a rotary bearing 326. Preferably, a drip-feeder fixing frame 328 is also provided above the upper rotating frame 322, and several feet 327 are provided at the bottom of the base 325.

[0094] This rotating mounting bracket has a rotating bearing at its bottom, allowing the entire bracket to rotate 360 ​​degrees. Multiple mounting and positioning holes (the number can be set as needed) are evenly distributed circumferentially along the upper and lower rotating brackets. During the overall assembly of the modular structure, the piping consumables can be installed by rotating the rotating brackets. The upper rotating bracket secures the upper part of the metering tube, and the lower rotating bracket secures the lower part. Compared to other rotating structures... Figure 20 The beam-type structure shown can make more efficient use of space, and more liquid bags can be hung in the same space. For example, the diameter of the rotating fixing bracket for 30 liquid bags is about 0.5 meters, while the length of the beam-type bracket when unfolded is about 1.2 meters (the beam-type fixing bracket can rotate and fit tightly against the equipment, and is suitable for dispensing a smaller number of liquid bags, such as 20 bags or less).

[0095] The rotating fixing bracket can be placed separately next to the dispensing equipment or placed inside the dispensing equipment, for example... Figure 22 The dispensing equipment shown is used for Figure 20 The difference in the illustrated embodiment is that the internal cavity of the housing frame 302 also includes a third cavity 329, in which the rotating fixing bracket can be placed for use.

[0096] In the description of this invention, it should be understood that the terms "bottom," "longitudinal," "lateral," "upper," "lower," "front," "rear," "left," "right," "inner," and "outer," etc., indicate the orientation or positional relationship based on the orientation or positional relationship shown in the accompanying drawings. They are used only for the convenience of describing the invention and for simplifying the description, and do not indicate or imply that the device or element referred to must have a specific orientation, or be constructed and operated in a specific orientation. Therefore, they should not be construed as limitations on the invention. Furthermore, the terms "first," "second," etc., are used for descriptive purposes only and should not be construed as indicating or implying relative importance or implicitly specifying the number of indicated technical features. Thus, a feature defined with "first," "second," etc., may explicitly or implicitly include one or more of that feature. In the description of this invention, unless otherwise stated, "a plurality of" means two or more.

[0097] The liquid quantitative dispensing system and dispensing equipment provided by the present invention have been described in detail above. Specific examples have been used to illustrate the principle and implementation of the present invention. The description of the above embodiments is only for the purpose of helping to understand the method and core idea of ​​the present invention. At the same time, for those skilled in the art, there will be changes in the specific implementation and application scope based on the idea of ​​the present invention. Therefore, the content of this specification should not be construed as a limitation of the present invention.

Claims

1. A liquid quantitative dispensing system, comprising a sample container, a plurality of quantitative containers, a dispensing container, a switching valve, and a power mechanism for driving liquid in the sample container into the quantitative container, wherein the bottom of the sample container is connected to a main delivery pipeline, characterized in that: The main delivery pipeline has several horizontal branch pipelines, which are connected to the bottom of the corresponding metering container via a first vertical pipeline. The top of the metering container is provided with a second vertical pipeline that communicates with the atmosphere. A third vertical pipeline connected to the dispensing container is also provided on the horizontal branch pipeline at a position corresponding to the first vertical pipeline. The switching valve includes a first switching valve for opening and closing the horizontal branch pipelines between adjacent first vertical pipelines, a second switching valve for opening and closing the third vertical pipeline, and a main switching valve for opening and closing the main delivery pipeline.

2. The liquid quantitative dispensing system according to claim 1, characterized in that: The power mechanism is a gravity-driven mechanism, meaning the sample container is positioned higher than the quantitative container and its height is adjustable; or it is a peristaltic pump installed on the main delivery pipeline; or it is an air-blowing mechanism that injects gas into the sample container.

3. A liquid quantitative dispensing system according to claim 1 or 2, characterized in that: The second vertical pipe is connected to the first drip chamber through the first connecting pipe, and the top of the first drip chamber is connected to the first gas filter; the first connecting pipe is also equipped with a first pressure sensor, a fourth switching valve, and a second gas filter arranged sequentially thereto.

4. A liquid quantitative dispensing system according to claim 1 or 2, characterized in that: The sample container is connected to several formulation containers via branch pipes, and each branch pipe is equipped with a third switch valve.

5. A liquid quantitative dispensing system according to claim 2, characterized in that: When the power mechanism is a peristaltic pump installed on the main delivery pipeline, the outlet of the peristaltic pump is connected to the horizontal branch pipeline through a second connecting pipeline. The second connecting pipeline is provided with a fifth switch valve and a first bubble sensor in sequence from the direction away from the peristaltic pump. The second connecting pipeline is also provided with a third gas filter, a second bubble sensor, a metering container, and a sixth switch valve in sequence from far to near. An exhaust pipeline is provided on the pipeline between the main switch valve and the peristaltic pump. The exhaust pipeline is provided with a seventh switch valve, a second drip chamber, and a fourth gas filter in sequence.

6. A liquid quantitative dispensing device, characterized in that, The device is used in conjunction with the packaging structure described in any one of claims 1-5, and includes: a main support frame and pipe clamps for fixing the corresponding pipelines.

7. A liquid quantitative dispensing device according to claim 6, characterized in that: The main support includes a first support portion for fixing the sample container and having an adjustable height, and a second support portion arranged parallel to the first support portion; a plurality of connecting plates are provided between the first support portion and the second support portion, and a plurality of pipe clamps are provided on the connecting plates; the first switching valve includes a first fixing plate disposed on the back of the horizontal branch pipe and a first pressure plate disposed on the front of the horizontal branch pipe, the first pressure plate being provided with a plurality of protrusions for squeezing the horizontal branch pipe; the second switching valve includes a second fixing plate disposed on the back of the third vertical pipe and a second pressure plate disposed on the front of the third vertical pipe; both the first pressure plate and the second pressure plate are provided with a clamping mechanism for pressing the corresponding pressure plate and the fixing plate together; both the first fixing plate and the second fixing plate are disposed on the main support.

8. A liquid quantitative dispensing device according to claim 7, characterized in that: The first fixing plate and the second fixing plate are integrally formed or separately set; the clamping mechanism is a linkage clamping mechanism; the first pressure plate and the second pressure plate are detachably connected to the clamping mechanism; the end of the protrusion is provided with a gasket; the main support is also provided with a fixing part for fixing the dripping bucket; the first support part and the second support part are both fixedly set on a base; the base is provided with adjustable level support feet.

9. A liquid quantitative dispensing device according to claim 6, characterized in that: The main support includes a support table, a shell frame, and a fixing bracket for fixing quantitative tubes and dispensing containers. The shell frame is internally divided into a first cavity and a second cavity. The first cavity is an insulated box, and the sample container is set in the insulated box in a liftable manner. The first cavity is also provided with a squeezing plate that can squeeze the sample container. The front side wall of the second cavity is provided with a display screen and a switch valve control button.

10. A liquid quantitative dispensing device according to claim 9, characterized in that: The fixed support is a beam type, including a horizontally arranged upper beam support and a lower beam support. One end of the upper beam support and the lower beam support is hinged to the shell frame, and the other end is a movable end; or it is a rotary type, including a circular upper rotating frame, a middle rotating frame, a lower rotating frame and a base arranged from top to bottom. The upper rotating frame and the middle rotating frame are connected by several support rods, and the middle rotating frame and the lower rotating frame are connected by a rotary bearing.

Images