Liquid nitrogen droplet generator for vials

Abstract

The present application relates to the technical field of freeze-drying, in particular to a liquid nitrogen droplet machine for a Westlin bottle, comprising a droplet vibration device, a rotating bearing device and a controller. The droplet vibration device comprises a clamping part for fixing a droplet pipe and a vibration driving module. The rotating bearing device comprises a rotating disc rotatingly arranged on a base, a heat preservation box and a bottle bracket. The bottle bracket is provided with Westlin bottle holding grooves on the outer periphery for placing Westlin bottles. The droplet pipe fixed by the clamping part is located at the upper part of the center of one Westlin bottle holding groove. After the liquid droplets are accumulated at the liquid outlet end of the droplet pipe, the controller controls the vibration driving module to drive the clamping part to instantaneously vibrate upward, and then buffer to reset downward and control the rotating driving module to drive the rotating disc to rotate, so as to rotate the next Westlin bottle to the lower part of the droplet pipe. The present application adopts the mode of accumulating and suspending the droplet head first, then rapidly retracting and vibrating slowly recovering, so that the liquid droplets formed each time have more consistent size.

Description

Technical Field

[0001] This invention relates to the field of freeze-drying technology, specifically to a liquid nitrogen dropper for vials. Background Technology

[0002] Solutions of biological agents and pharmaceutical preparations can be lyophilized into lyophilized pellets, which is beneficial for preserving the activity of the preparations and thus has led to their widespread application. However, due to the stringent requirements for quantitative testing during application, the quantitative requirements for lyophilized pellets are also very high. The consistent size control of microdroplets is crucial in many experiments and processes. Ensuring that each droplet has the same or similar volume can greatly improve the accuracy and reproducibility of experimental results. However, during the preparation of lyophilized pellets, due to environmental instability and equipment differences, some preparation processes result in inconsistent pellet sizes, failing to meet the quantitative requirements of lyophilized reagents. Liquid surface tension is an important influencing factor in controlling droplet size. Liquid surface tension is a result of intermolecular interactions on the liquid surface, tending to maintain a minimum surface area. Therefore, when liquid is extruded from the dropping head, surface tension limits the droplet volume. As the droplet volume increases, the surface tension also increases accordingly, thus inhibiting further droplet growth.

[0003] The process of adding liquid nitrogen is a delicate and meticulous technique. When droplets are added to liquid nitrogen, they float and move due to the vaporization of the nitrogen. If droplets are added continuously, they will stick together, forming a single mass; therefore, they need to be added separately to avoid this sticking. After the droplets have formed in the liquid nitrogen, they need to be transferred to a freeze dryer for further processing. However, the low temperature of liquid nitrogen presents several challenges during this transfer process. First, the low temperature causes condensation, which can affect the freeze-drying process. Second, the large amount of liquid nitrogen vaporization produces a significant amount of gas, making manual handling difficult. Furthermore, prolonged operation can cause the micro-core ice balls to melt, affecting the consistency of the freeze-drying. Finally, uneven distribution of the micro-core ice balls within the freeze-drying container makes controlling the consistency of the freeze-drying process even more difficult.

[0004] Traditional plate freezing methods also have their problems. During subsequent unpacking, the micro-core ice balls are easily contaminated and absorb moisture, posing a threat to product quality. To avoid these problems, the method of directly stoppering vials in the freeze dryer can effectively avoid the risk of contamination. Therefore, designing a vial liquid nitrogen dropper that can maintain the consistency of freeze-dried balls has become an urgent requirement. Summary of the Invention

[0005] The technical problem to be solved by this invention is to provide a liquid nitrogen dropper for vials that can maintain the consistency of freeze-dried beads.

[0006] The technical solution to the technical problem to be solved by the present invention is: a liquid nitrogen dropper for vials, comprising a dropper vibration device, a rotating support device, and a controller; the dropper vibration device comprises a clamping part and a vibration drive module, the clamping part being used to fix the dropper tube connected to the solution supply device; the rotating support device comprises a base, a turntable rotatably mounted on the base, an insulated box containing liquid nitrogen placed on the turntable, a rotation drive module for driving the turntable to rotate, and a bottle holder placed inside the insulated box, with vial slots provided on the outer periphery of the bottle holder for placing vials; the rotation drive module, the vibration drive module, and the controller are electrically connected, and the dropper tube fixed by the clamping part is located at the upper part of the center of one of the vial slots; after droplets accumulate at the outlet end of the dropper tube, the controller controls the vibration drive module to drive the clamping part to vibrate upward instantaneously, then buffers and resets downward, and controls the rotation drive module to drive the turntable to rotate the next vial to the lower part of the dropper tube.

[0007] More preferably, the vibration drive module includes:

[0008] support;

[0009] The stepper motor is located on the upper part of the bracket;

[0010] The vibrator is connected to the shaft of the stepper motor at its upper end and to the bottom of the bracket at its lower end via a bearing. The vibrator has a spiral contact surface along its circumference on its side.

[0011] A sliding shaft is vertically mounted on one side of the bracket, and a vibrating spring is fitted on the upper part.

[0012] The clamping part is slidably mounted on the sliding shaft, and the shaking spring is located at the lower part of the clamping part. The clamping part is provided with a linkage protrusion on the side near the bracket, and the linkage protrusion abuts against the spiral contact surface.

[0013] Even better, a trigger is embedded on the upper side of the shaker, and a detection switch is set on the frame at the height of the trigger, and the detection switch is electrically connected to the controller.

[0014] Even better, the vibration drive module includes a housing, an electromagnet is provided in the upper part of the housing, the electromagnet divides the upper part of the housing into an external connecting cavity and a buffer cavity, the electromagnet is provided with a through hole, a one-way plug is provided in the upper part of the through hole, and a micro hole is provided in the middle of the one-way plug; an armature is provided inside the buffer cavity, the upper part of the armature is attached to the inner wall of the buffer cavity, and the lower part extends to the outside of the housing and connects with the clamping part.

[0015] Even better, a control box is provided on one side of the base, the bracket is provided on the upper part of the control box, the rotation drive module is provided inside the control box, the rotation drive module drives the turntable to rotate by meshing with the turntable through gears, and the controller is provided inside the control box.

[0016] Even better, the clamping part includes a temperature control module, and the drip tube is disposed inside the temperature control chamber of the temperature control module; the temperature control module includes:

[0017] Mounting panel;

[0018] A semiconductor cooling chip is embedded in the center of the mounting panel;

[0019] A temperature control block is installed on the front of the mounting panel and abuts against the thermoelectric cooler. A constant temperature chamber is provided in the middle of the temperature control block. A heat sink is installed on the back of the mounting panel and abuts against the thermoelectric cooler. Ears are provided on both sides of the temperature control block and are fixedly connected to the front of the mounting panel. A top cover is provided on the top of the temperature control block and has a through hole for installing a drip tube. A pressure ear is slidably connected to the ears at one end and fixedly connected to the top cover at the other end.

[0020] Even better, fiber optic probes are installed on both sides of the lower part of the mounting panel, and the two fiber optic probes are on the same plane as the trajectory of the falling droplet.

[0021] The vial liquid nitrogen dropper includes a base, a turntable and a control box set on the base, a controller and a rotation drive module set inside the control box, and an installation panel set on the upper part of the control box near the turntable.

[0022] A thermoelectric cooler is embedded in the center of the mounting panel, and a heat sink is provided behind the mounting panel to abut against the thermoelectric cooler. Ears are provided on both sides of the thermoelectric cooler at the front of the mounting panel, and a temperature control block is provided at the front of the thermoelectric cooler, with both sides of the temperature control block fixedly connected to the ears. A constant temperature chamber is provided in the center of the temperature control block. A pressure block is provided on the upper part of the ears, and an upper cover plate is mounted on the two pressure blocks. A through hole for installing a drip tube is provided on the upper part of the upper cover plate, and the through hole coincides vertically with the constant temperature chamber. A turntable holds an insulated box containing liquid nitrogen, and a bottle holder is placed inside the insulated box. A vial slot is provided on the outer periphery of the bottle holder for holding vials.

[0023] Even better, fiber optic probes are installed on both sides of the lower part of the mounting panel, and the two fiber optic probes are on the same plane as the trajectory of the falling droplet.

[0024] A process for preparing freeze-dried beads, using a vial liquid nitrogen dropper, includes the following steps:

[0025] Step 1: Use a vial freeze-drying tray to load vials and arrange them into a ring shape;

[0026] Step 2: Place the ring-shaped set of vials on the top of the vial holder and then put it into the insulated box;

[0027] Step 3: Pour at least one-third of the liquid nitrogen into the vial and pour liquid nitrogen into the insulated box;

[0028] Step 4: Connect the dropper to the solution supply device and start the preparation process;

[0029] Step 5: After preparation, remove the bottle holder and take out a set of ring-shaped vials for freeze-drying.

[0030] The beneficial effects of this invention are as follows:

[0031] 1. This invention avoids the cumulative errors that may occur during natural dripping. During natural dripping, droplets are affected by gravity and air resistance, which may cause fluctuations in droplet size. However, by using a method where the droplet head first accumulates and suspends, and then quickly retracts, these external interference factors can be eliminated, resulting in droplets of a more consistent size each time they are formed.

[0032] 2. This invention can directly form micro-core ice balls in vials and automatically count them. Operation becomes very simple when the vial holder is removed. Furthermore, the automatic rotation and counting function of the turntable ensures a consistent number of micro-core ice balls in each vial. When it is necessary to remove the vial, the central lever acts as a handle, making the operation even simpler and faster. This machine not only solves the problem of transposition in low-temperature environments but also ensures the consistency of the number and distribution of micro-core ice balls, thereby greatly improving the consistency of the freeze-drying process and product quality.

[0033] 3. By placing the dropper inside the constant temperature chamber, this invention maintains the consistency of the solution during long-term preparation, ensuring the consistency of the freeze-dried pellets during long-term and large-scale preparation, and meeting the quantitative requirements during the experiment. Attached Figure Description

[0034] Figure 1 This is a schematic diagram of one embodiment of the present invention.

[0035] Figure 2 This is a cross-sectional view of one embodiment of the present invention.

[0036] Figure 3 This is a schematic diagram of a shaker, clamping part, and bracket according to an embodiment of the present invention.

[0037] Figure 4 This is a schematic diagram of a jitter according to an embodiment of the present invention.

[0038] Figure 5 This is a schematic diagram of the clamping part according to an embodiment of the present invention.

[0039] Figure 6 This is a schematic diagram of one embodiment of the present invention.

[0040] Figure 7This is a schematic diagram of a bottle holder according to an embodiment of the present invention.

[0041] Figure 8 This is a schematic diagram of a rotation drive module according to an embodiment of the present invention.

[0042] Figure 9 This is a schematic diagram of an embodiment of a clamping part for constant temperature control of a dripping tube according to the present invention.

[0043] Figure 10 This is a cross-sectional view of an embodiment of a clamping part for constant temperature control of a dripping tube according to the present invention.

[0044] Figure 11 This is a schematic diagram of an embodiment of the present invention for removing the front cover plate of the clamping part for constant temperature control of a drip tube.

[0045] Figure 12 This is a schematic diagram of the vibration drive module of a dripping vibration device according to the present invention.

[0046] Figure 13 This is a schematic diagram of a liquid nitrogen dropper with constant temperature control according to the present invention.

[0047] In the diagram: 333, fiber optic probe; 312, front cover; 311, thermostatic chamber; 4011, insertion slide; 125, linkage protrusion; 107, sensor slot; 4032, single-point button; 4031, cycle button; 508, positioning tube; 507, armature; 506, micro-hole; 505, one-way plug; 504, buffer chamber; 503, external connecting chamber; 502, electromagnet; 501, housing; 124, locking screw hole; 123, snap-fit ​​hole; 122, protrusion; 121, straight section; 416, light beam sensor; 41 5. Phase plate; 414. Gear plate; 413. Drive gear; 412. Drive motor; 411. Gear holder; 405. Bottle holder; 404. Insulation box; 403. Control box; 402. Turntable; 401. Base; 307. Pressure ear block; 306. Top cover plate; 305. Ear seat; 303. Radiator; 302. Semiconductor cooling chip; 301. Mounting panel; 310. Temperature control block; 111. Trigger; 104. Jitter spring; 103. Sliding shaft; 110. Jitter; 102. Stepper motor; 101. Bracket; Detailed Implementation

[0048] To make the technical solution and beneficial effects of the present invention clearer, the embodiments of the present invention will be explained in further detail below.

[0049] Example 1

[0050] The liquid nitrogen dropper for vials includes a dripping vibration device, a rotating support device, and a controller. The dripping vibration device is used to mount the dripping tube and achieves dripping through vibration. The dripping vibration device is located on top of the rotating support device, which houses the vial to catch the droplets from the dripping tube. The controller acts as a processor to control the entire system. The rotating drive module, vibration drive module, and controller are electrically connected. The dripping tube, fixed by the clamping part, is located above the center of one of the vial holders. After droplets accumulate at the outlet end of the dripping tube, the controller controls the vibration drive module to drive the clamping part to vibrate upwards momentarily, then buffers and resets downwards, and controls the rotating drive module to drive the turntable to rotate the next vial to the bottom of the dripping tube.

[0051] The rotating support device includes a base 401, on which a turntable 402 and a control box 403 are mounted. The turntable 402 is circular. The turntable 402 is rotatably connected to the base 401, such as through a plane bearing. The control box 403 is used to install electrical components such as controllers, power modules, relays, data interfaces, and electrical connection terminals. The control box is used to protect electronic components and operators, preventing equipment damage and electric shock.

[0052] The upper part of the turntable 402 is used to place the insulated box 404. The insulated box 404 is used to hold liquid nitrogen. The insulated box 404 is a wide-mouthed bowl shape. Better still, in order to reduce the evaporation of liquid nitrogen during the transfer process, the insulated box 404 can be equipped with an insulated box lid. As shown in the figure, in order to facilitate a tight seal with the insulated box lid, an external thread is provided on the upper part of the insulated box 404. The insulated box 404 can be made of stainless steel. After preparation is completed, the insulated box lid is closed for the transfer of vials.

[0053] Because droplets are continuously dripped into liquid nitrogen, they tend to stick together, forming a single unit. Therefore, it is necessary to drip them in stages to avoid this sticking. To facilitate operation and sorting while preventing droplet sticking, a bottle holder 405 is provided inside the insulation box 404. The lower part of the bottle holder 405 has grooves evenly arranged around its circumference to hold a ring of vials. Different vials are dripped in at intervals to prevent droplet sticking. In this embodiment, as shown in the figure, the bottom of the bottle holder 405 is a perforated grid plate composed of several spokes and rings, with a handle in the middle. The handle is a vertical rod, and its upper part is bent for easy handling. A wavy baffle is used to form a ring of grooves for better embedding and securing of the vials. Furthermore, to enhance the strength of the bottle holder 405, reinforcing ribs are provided between the handle and the spokes. Designing the bottle holder 405 as a perforated grid primarily saves material costs while improving the liquid nitrogen's cooling effect. In addition, the lower part of the bottle holder 405 can be set as a circular plate, and slots for placing vials are evenly arranged on the outer periphery of the circular plate.

[0054] The rotation drive device is located inside the control box 403. As shown in the figure, the control box 403 is rectangular in shape, and a recessed portion matching the arc of the turntable 402 is provided on the side near the turntable 402. A notch is provided at the lower part of the recessed portion, through which the rotation drive device achieves transmission with the turntable 402. In this embodiment, transmission is achieved through gears. As shown in the figure, the rotation drive device includes a gear fixing frame 411, a drive motor 412 mounted on the upper part of the gear fixing frame, and a drive gear 413 provided in the middle of the gear fixing frame. The lower end of the drive gear shaft is rotatably connected to the gear fixing frame through a bearing, and the upper end of the drive gear shaft is connected to the shaft of the drive motor. The two can be directly connected or connected through a reducer. Correspondingly, a gear disk 414 is fixedly installed on the outside of the turntable 402, and the gear disk 414 meshes with the drive gear 413.

[0055] Furthermore, to achieve precise control over the rotation angle of the drive gear 413, a phase disk 415 is fitted onto the shaft of the drive gear 413. The phase disk 415 has a plurality of through holes evenly distributed along its circumference. Correspondingly, a light beam sensor 416 is disposed on the upper part of the gear holder 411. The light beam sensor can be an infrared light beam sensor, or it can be composed of a light-emitting diode and a phototransistor, or it can be a grating sensor. The two components of the light beam sensor are respectively disposed on the upper and lower parts of the phase disk 415, and their positions coincide with the circumference of the through holes.

[0056] The vibration drive module includes a bracket 101, a stepper motor 102, a vibrator 110, and a sliding shaft 103. As shown in the figure, the bottom of the bracket 101 is a rectangular plate with supports at its four corners, and the upper part of the supports is fixedly connected by a rectangular frame. The stepper motor 102 is located on the upper part of the bracket 101, and the two can be connected by screws. The vibrator 110 is located inside the bracket 101, and a spiral abutment surface is provided along the circumference of the side of the vibrator 110. As shown in the figure, in this embodiment, the vibrator 110 includes an upper disc portion and a rotating shaft. The lower part of the rotating shaft is rotatably connected to the bottom of the bracket 101 via a bearing, the upper part is integrally formed with the disc portion, and the upper part is connected to the rotating shaft of the stepper motor 102.

[0057] The spiral contact surface can be configured by rolling up the longer right-angled side of the right triangle according to the diameter of the disk and then connecting it to the edge of the disk. In this case, the hypotenuse of the right triangle forms a spiral contact surface.

[0058] Alternatively, the vibrator can be a cylinder with a spiral contact surface consisting of a spiral groove on the side of the cylinder, forming a 360-degree spiral, and a vertical groove between the highest and lowest points of the spiral.

[0059] Alternatively, a single-turn spring can be connected to the lower part of the disc, forming a spiral contact surface with the lower end of the spring coinciding with the upper end of the spring in the vertical direction.

[0060] Under normal conditions, the linkage protrusion 125 abuts against the lower end of the spiral contact surface, keeping the vibrator 110 stationary. This position and state allow the solution to accumulate at the end of the dropper. After accumulation, the vibrator 110 rotates under the drive of the stepper motor 102. Simultaneously, under the action of the vibrating spring 104, the linkage protrusion 125, no longer obstructed by the spiral contact surface, slides upwards to the uppermost point of the spiral contact surface. At the same time, the stepper motor drives the vibrator to rotate one revolution, and under the action of the spiral contact surface, the linkage protrusion 125 returns to its normal position. At the instant the linkage protrusion 125 slides upwards, the droplet detaches from the dropper due to inertia, allowing it to fall.

[0061] Furthermore, to reduce friction, a roller is fixedly connected to the linkage protrusion 125. The roller makes rolling contact with the helical abutment surface, resulting in a smoother motion when the driving clamping part moves downward. In this embodiment, a screw hole is provided at the location of the linkage protrusion 125, allowing the roller to be installed in the screw hole.

[0062] In this embodiment, as shown in the figure, a clamping part is installed at the front end of the bracket 101. The upper and lower parts of the front end of the bracket 101 are respectively provided with outwardly extending platforms. Two sets of overlapping screw holes are provided on the platforms, and a sliding shaft 103 is screwed into each set of screw holes. A vibrating spring 104 is sleeved on the sliding shaft 103.

[0063] The clamping part has an overall U-shaped shape, including a straight section 121 and a protruding section 122. The protruding section of the clamping part faces the front end and has a snap-fit ​​hole 123 for mounting a drip tube. A locking screw hole 124 is provided on the side of the protruding section, and the drip tube inside the through hole is fixed by a bolt installed inside the locking screw hole 124. Sliding holes are provided at both ends of the straight section 121, and a sliding shaft 103 is inserted into the sliding holes. A vibrating spring 104 is provided at the lower part of the straight section 121. A linkage protrusion 125 is fixedly connected to the center of the rear end of the straight section 121. The linkage protrusion 125 abuts against the spiral abutment surface.

[0064] Better still, to achieve counting control and linkage with other devices, a recessed hole is provided on the side of the shaker 110, and a trigger 111 is embedded inside the recessed hole. In this embodiment, the trigger can be a magnet. A detection switch is provided on the bracket 101 at the height corresponding to the trigger 111, and the detection switch is electrically connected to the controller. As shown in the figure, a detection switch is provided at the upper rear end of the bracket 101, where the detection switch can use a Hall sensor or a reed switch to identify the signal from the magnet. When a trigger 111 is set, one rotation indicates that a drop of liquid has been dropped. Multiple detection switches can be set, and the solution supply system can be started and stopped by detecting multiple position signals, thereby realizing joint control with the solution supply device. Figure 3 As shown, a sensor slot 107 is provided at the rear of the upper end of the bracket. The sensor can be inserted into the sensor slot 107.

[0065] Furthermore, to achieve single-dispensing and cyclic control, two buttons are provided on the upper part of the control box 403, and these two buttons are electrically connected to the controller inside the control box. The two buttons are a cyclic button 4031 and a single-dispensing button 4032. When the single-dispensing button is pressed, a single dispensing is achieved. When the cyclic button 4031 is pressed, cyclic dispensing is achieved; that is, after one dispensing, the turntable is rotated to move the next vial to the lower part of the dispensing tube.

[0066] In this embodiment, as Figure 3As shown, in this embodiment, one trigger 111 and two detection switches are provided, namely a stop detection switch and a start detection switch, as shown in the figure. The two switches are arranged adjacent to each other. On the circumference of the trigger's rotation, on the arc trajectory intercepted by the two detection switches, the trigger moves from the stop detection switch to the start detection switch. During cyclic preparation, the stepper motor can be controlled to rotate continuously. The two detection switches can be connected to the control interface of the solution supply device. That is, when the trigger is near the stop detection switch, the solution supply device receives a stop signal and stops supplying solution, while the clamping part approaches the lowest point. After continued rotation, the clamping part loses the obstruction of the jitter 110 and vibrates rapidly upward, at which point the droplet falls. After further rotation, the trigger triggers the start detection switch, and the solution supply device receives a start signal and begins supplying solution, at which point the droplet begins to accumulate at the lower end of the drip tube. At the same time, the stepper motor continues to control the jitter 110 to continue rotating, thereby pressing the clamping part downward. The accumulation of the droplet is completed during the process of pressing the clamping part downward. After reaching the lowest point, the stop detection switch is triggered again, forming a cyclic control. Because the downward descent is slow, droplet accumulation can occur simultaneously without affecting the accumulation of droplets, ensuring quantitative droplet distribution and improving preparation efficiency. This also simplifies the integration of the dropper with the solution supply device.

[0067] The vibration drive module has the function of instantaneous rise vibration buffering and fall recovery. In addition to the above embodiment, it can also be implemented through the following embodiment. As shown in the figure, the vibration drive module in this embodiment includes a housing 501. The housing 501 is cylindrical, which can be a round cylinder or a square cylinder. An electromagnet 502 is provided in the upper part of the housing. The electromagnet contains an electromagnetic coil, which is electrically connected to the controller. When the electromagnetic coil is energized, it generates an attractive force, which attracts the armature from the lower part to the upper part. The outer periphery of the electromagnet is sealed to the housing and divides the upper part of the housing into an external connecting cavity 503 and a buffer cavity 504. A through hole is provided on one side of the housing of the external connecting cavity 503 to realize airflow communication with the outside. The electromagnet is provided with a through hole, and a one-way plug 505 is provided in the upper part of the through hole. The one-way plug has a T-shaped cross section, and the area of ​​the upper panel is larger than the area of ​​the through hole, that is, the upper part of the one-way plug can seal the through hole. A micro hole 506 is provided in the middle of the one-way plug 505. As shown in the figure, the upper part of the armature 507 has the same cross-sectional shape as the panel and the cavity inside the housing 501. The lower part of the armature is inserted into the positioning tube 508 inside the housing 501, which limits the sliding range of the armature and its vertical direction. The lower end of the armature extends to the outside of the housing 501 and connects to the clamping part. At the same time, a through hole with the same shape as the outside is provided in the lower part of the housing, located below the upper panel of the armature. In the drip control chamber, after the droplets accumulate at the end of the drip tube, the electromagnet 502 is activated. The electromagnet instantly attracts the armature, and the armature disengages from the drip tube and the accumulated droplets during its rapid ascent. When the armature rises, the one-way plug opens, allowing the armature to rise rapidly. After the electromagnet is de-energized, the armature 507 slides downward under its own gravity. Since the one-way plug 505 is closed at this time, and air is only vented through the micro-hole 506, the armature falls slowly. This prevents the liquid in the dropper from being thrown out when it falls rapidly and stops momentarily at the bottom, thus ensuring that the amount of droplets supplied is equal.

[0068] In addition to the two embodiments mentioned above, based on the previous embodiment, the electromagnet 502 may not contain an electromagnet. Meanwhile, the external connecting cavity 503 is connected to the negative pressure source through an electronically controlled valve. The through hole at the external connecting cavity 503 is set as a micro-hole so that the armature is attracted when the negative pressure source is turned on and the armature falls slowly when the negative pressure source is stopped.

[0069] The bracket 101 is mounted on the upper part of the control box 403 to accommodate vials of different sizes. A insertion slide is provided on the upper part of the control box, as shown in the figure. In this embodiment, the insertion slide 4011 consists of two long strips with right-angled folded edges. The openings of the two strips are positioned opposite each other, forming a set of insertion slides. Correspondingly, the lower edge of the bracket 101 has an outward folded edge. The folded edge at the lower part of the bracket 101 can be inserted into the insertion slide.

[0070] To better maintain the uniformity of droplet volume and control the consistency of droplet size, the clamping part also includes a constant temperature control module. The droplet tube is placed inside the constant temperature chamber of the constant temperature control module, thereby controlling the droplet tube at a set constant temperature.

[0071] The constant temperature control module includes a mounting panel 301, a semiconductor cooling chip 302, a temperature control block 310, a heat sink 303, an ear mount 305, a top cover plate 306, and a pressure ear block 307. As shown in the figure, the constant temperature control module and the clamping part are both mounted on a mounting panel 301.

[0072] A thermoelectric cooler 302 is embedded in the middle of the mounting panel 301. A temperature control block 310 is mounted on the front of the mounting panel 301 and abuts against the thermoelectric cooler 302. More preferably, to ensure heat conduction, a heat-conducting oil is applied between the thermoelectric cooler 302 and the temperature control block 310. A constant temperature chamber 311 is provided in the middle of the temperature control block 310. The temperature control block 310 can be configured as a through-hole extending vertically. Alternatively, as shown in the figure, the lower part of the constant temperature chamber can also communicate with the front, and a front cover plate 312 is installed at the front, providing a sealed and heat-insulating effect. As shown in the figure, this design allows the larger portion of the solution-containing tube of the dropper to be placed in the upper constant temperature chamber, where the temperature can be completely controlled by the temperature control block 310, while the smaller portion is located in the open front constant temperature chamber. This design saves material in manufacturing the temperature control block 310. Furthermore, the cost of a front cover plate made of materials such as plastic is lower than that of aluminum. In this embodiment, the macro temperature control block 310 is made of aluminum. The heat sink 303 is mounted behind the mounting panel 301 and abuts against the thermoelectric cooler 302. In this embodiment, the heat sink 303 is water-cooled. The heat sink is a container with flow channels and has an inlet port and an outlet port for connecting to a cold source. The heat sink 303 can also use a heat sink fin or air cooling. To fix the clamping part and the temperature control block 310, two lugs 305 are provided on both sides of the temperature control block 310 on the upper part of the mounting panel 301. The lugs are fixedly connected to the mounting panel. As shown in the figure, the main body of the lug 305 is a long rectangular cube with a notch on the outer side of the cube. The notch forms upper and lower panels, as well as a panel close to the mounting panel and a panel close to the temperature control block 310. The notch provides a through hole for connecting the temperature control block 310 and the mounting panel 301, and the notch provides a range of motion for the vibration of the clamping part. The upper cover plate 306 is located on the upper part of the temperature control block 310 and has a through hole for installing a drip tube. A rubber ring can be installed on the inner wall of the through hole to fix the drip tube. The upper cover plate 306 is movably fixed to the ear seat 305 via a pressure lug 307. One end of the pressure lug 307 is slidably connected to the ear seat, and the other end is fixedly connected to the upper cover plate. The overall shape of the pressure lug 307 is U-shaped, with one end longer than the other. The shorter end is fixedly connected to the upper cover plate 306, and the longer end is inserted into the through hole in the panel on the upper part of the ear seat. A spring is fitted onto the longer end, and the spring is limited by limiting components such as screws or retaining rings. The spring presses the upper cover plate 306 downwards. At this time, the clamping part is the upper cover plate, which can be connected to the vibration drive module to achieve vibration.

[0073] The semiconductor cooling chip 302 is electrically connected to the controller. According to the set temperature, the controller activates the cooling chip to keep the solution inside the drip tube at a constant low temperature.

[0074] Even better, for better temperature control, a temperature sensor is installed inside the thermostatic chamber. The temperature sensor and the controller are electrically connected.

[0075] A droplet detection sensor is installed at the lower part of the mounting panel 301. The droplet detection sensor and the controller are electrically connected. In this embodiment, the droplet detection sensor is a fiber optic probe 333, one of which is a light source emitting probe and the other is a light source receiving probe. When a droplet falls, it generates light blocking, realizing the feedback signal of the droplet falling. The controller then issues a command to rotate the bottom turntable based on the feedback signal. At the same time, the controller can determine the size of the droplet by the intensity of the received light signal. The size of the droplet varies with the angle of refraction, resulting in different intensities of the light signal received by the receiving probe. A droplet size that meets the requirements can be set, and droplets within this range will generate a corresponding range of light signals. As shown in the figure, the two fiber optic probes are set at the lower part of the constant temperature chamber and are fixedly connected to the lower end of the ear seat. During the preparation process, the size of each freeze-dried bulb is determined by a counter. Since the rotation of the turntable corresponds to the vial, the size of the freeze-dried bulb inside each vial has a parameter. Finally, the parameters in the vials were tested, and the different vials were grouped according to the number of lyophilized bulbs that differed from the set range. They were divided into different specifications such as high quantitative, medium quantitative, and low quantitative, and the higher the standard was used for experiments with higher requirements.

[0076] Example 2

[0077] The vial liquid nitrogen dropper includes a base 401, a turntable 402 and a control box 403 disposed on the base 401, a controller and a rotation drive module disposed inside the control box 403, and an installation panel 301 disposed on the upper part of the control box near the turntable 402.

[0078] A thermoelectric cooler 302 is embedded in the center of the mounting panel 301, and a heat sink 303 is provided at the rear of the mounting panel 301 to abut against the thermoelectric cooler 302. Ears 305 are respectively provided on both sides of the thermoelectric cooler 302 at the front of the mounting panel 301. A temperature control block 310 is provided at the front of the thermoelectric cooler 302, and the two sides of the temperature control block 310 are fixedly connected to the ears 305. A constant temperature chamber is provided in the center of the temperature control block 310. Pressure blocks 307 are provided on the upper part of the ears 305, and an upper cover plate 306 is mounted on the two pressure blocks 307. A through hole for installing a drip tube is provided on the upper part of the upper cover plate 306, and the through hole coincides vertically with the constant temperature chamber. The components and connection methods on the mounting panel 301 in this embodiment are the same as those in the constant temperature control module of Embodiment 1, and will not be described again here.

[0079] The turntable 402 holds an insulated box 404 containing liquid nitrogen, and a bottle holder 405 is placed inside the insulated box 404. The bottle holder 405 has vial slots on its outer periphery for holding vials. The turntable setup and the rotation drive module that drives the turntable in this embodiment are the same as in Embodiment 1, and will not be described again here.

[0080] In this embodiment, to further monitor the droplet quality, a droplet detection sensor is installed at the lower part of the mounting panel 301. The droplet detection sensor is electrically connected to the controller. In this embodiment, the droplet detection sensor is a fiber optic probe 333, one of which is a light source emitting probe and the other is a light source receiving probe. The light source emitting probe and the light source receiving probe are respectively located at the lower part of the two earpieces 305, and the connecting line of the two probes intersects the trajectory of the droplet. The quantitative control of the droplet is achieved through this fiber optic probe, and the method is the same as that in Embodiment 1, and will not be repeated here.

[0081] Example 3

[0082] This invention also discloses a method for preparing freeze-dried pellets using the dripping machine disclosed in this application:

[0083] Step 1: Use a ring-shaped vial freeze-drying tray to load the vials and assemble them into a ring. This vial freeze-drying tray is the one disclosed in our authorized patent CN 113790593 B. The assembly and usage method will not be described in detail here.

[0084] Step 2: Place the ring-shaped set of vials on the upper part of the vial holder 405. The number of vials held in the vial holder is the same as the number of vials held in the vial freeze-drying tray used in Step 1. Then place the vial holder 405 inside the insulated box 404, which is filled with liquid nitrogen, with at least one-third of the liquid nitrogen added to the vials.

[0085] Step 3: Clamp the dropper and connect it to the solution supply device.

[0086] Step 4: Start the preparation process. Start the process by pressing the button. After the droplets accumulate in the dropper, start the vibration. Droplets will then fall into the vial, and the turntable will rotate to position the next vial below the dropper. During the preparation process, a detection switch or droplet detection sensor will be used to count the number of droplets, and the number of rotations of the turntable will be recorded to ensure that the number of droplets inside each vial is the same.

[0087] Step 6: After preparation is complete, stop the preparation process. Remove the bottle holder. After removing the bottle holder, you can partially stopper the vials and proceed with lyophilization.

[0088] This method enables efficient preparation of freeze-dried pellets. Firstly, the finished product is directly packaged in vials. Secondly, the vials contain liquid nitrogen during preparation, but the amount of liquid nitrogen in the insulated container can be reduced, thus lowering nitrogen consumption. During transport and transposition, the freeze-dried pellets remain in a frozen environment, minimizing changes in their properties. Thirdly, using vials for direct reception not only prevents adhesion but also facilitates subsequent freeze-drying. Semi-stopping before freeze-drying reduces damage to the pellets caused by the traditional freeze-drying process of handling and sorting. Therefore, this method also ensures the consistency of the number and distribution of micro-core ice pellets, significantly improving the consistency of the freeze-drying process and product quality.

[0089] In summary, the above description is merely a preferred embodiment of the present invention and is not intended to limit the scope of the invention. Based on the above description, those skilled in the art can make various changes and modifications without departing from the inventive concept. The technical scope of the present invention is not limited to the contents of the specification; all equivalent variations and modifications of the shape, structure, features, and spirit described within the scope of the claims should be included within the scope of the claims.

Claims

1. A vial liquid nitrogen dropper, characterized in that: It includes a dripping vibration device, a rotating bearing device, and a controller; the dripping vibration device includes a clamping part and a vibration driving module, the clamping part being used to fix the dripping tube connected to the solution supply device; The rotating bearing device includes a base (401), a turntable (402) rotatably mounted on the base, a heat preservation box (404) containing liquid nitrogen placed on the turntable (402), a rotation drive module for driving the turntable (402) to rotate, and a bottle holder (405) placed inside the heat preservation box (404). The bottle holder (405) has a vial slot on its outer periphery for placing vials. The rotation drive module, vibration drive module and controller are electrically connected. The drip tube fixed by the clamping part is located at the upper part of the center of one of the vials. After the drip tube discharge end accumulates droplets, the controller controls the vibration drive module to drive the clamping part to vibrate upward instantaneously, then buffers and resets downward and controls the rotation drive module to drive the turntable (402) to rotate and rotate the next vial to the lower part of the drip tube. The vibration drive module includes a housing (501), an electromagnet (502) is provided in the upper part of the housing (501), the electromagnet (502) divides the upper part of the housing into an external connecting cavity (503) and a buffer cavity (504), the electromagnet (502) is provided with a through hole, a one-way plug (505) is provided in the upper part of the through hole, and a micro hole (506) is provided in the middle of the one-way plug (505); an armature (507) is provided inside the buffer cavity (504), the upper part of the armature (507) is attached to the inner wall of the buffer cavity (504), and the lower part extends to the outside of the housing (501) and connects with the clamping part.

2. The vial liquid nitrogen dropper according to claim 1, characterized in that: The vibration drive module includes: Support (101); A stepper motor (102) is mounted on the upper part of the bracket (101); The vibrator (110) is connected at its upper end to the shaft of the stepper motor (102) and at its lower end to the bottom of the bracket (101) via a bearing. The vibrator (110) has a spiral contact surface along its circumference on its side. A sliding shaft (103) is vertically set on one side of the bracket (101), and a shaking spring (104) is sleeved on the upper part. The clamping part is slidably disposed on the sliding shaft (103), and the shaking spring (104) is located at the lower part of the clamping part. A linkage protrusion (125) is provided on the side of the clamping part near the bracket (101), and the linkage protrusion (125) abuts against the spiral contact surface.

3. The vial liquid nitrogen dropper according to claim 2, characterized in that: A trigger (111) is embedded on the upper side of the shaker (110), and a detection switch is set on the frame at the height of the trigger (111). The detection switch is electrically connected to the controller.

4. The vial liquid nitrogen dropper according to any one of claims 2 or 3, characterized in that: A control box (403) is provided on one side of the base (401), the bracket (101) is provided on the upper part of the control box, the rotation drive module is provided inside the control box (403), the rotation drive module meshes with the turntable (402) through gears to drive the turntable (402) to rotate, and the controller is provided inside the control box.

5. The vial liquid nitrogen dropper according to any one of claims 1, 2, or 3, characterized in that: The clamping part includes a temperature control module, and the drip tube is disposed inside the temperature control chamber of the temperature control module; the temperature control module includes: Mounting panel (301); A semiconductor cooling chip (302) is embedded in the middle of the mounting panel (301); A temperature control block (310) is installed at the front of the mounting panel (301) and abuts against the semiconductor cooling chip (302). A constant temperature cavity is provided in the middle of the temperature control block (310). The heat sink (303) is mounted behind the mounting panel (301) and abuts against the thermoelectric cooler (302); Ear mounts (305) are disposed on both sides of the temperature control block (310) and fixedly connected to the front of the mounting panel (301); The upper cover plate (306) is located on the upper part of the temperature control block (310) and has a through hole on the upper part for installing the drip tube; The ear presser (307) has one end slidably connected to the ear seat and the other end fixedly connected to the upper cover plate.

6. The vial liquid nitrogen dropper according to claim 5, characterized in that: Fiber optic probes are installed on both sides of the lower part of the mounting panel (301), and the two fiber optic probes are on the same plane as the trajectory of the falling droplets.

7. A vial liquid nitrogen dropper, characterized in that: It includes a base (401), a turntable (402) disposed on the base (401) and a control box (403), a controller and a rotation drive module disposed inside the control box (403), and a mounting panel (301) disposed on the upper part of the control box near the turntable (402). A semiconductor cooling chip (302) is embedded in the middle of the mounting panel (301), and a heat sink (303) is provided behind the mounting panel (301) to abut against the semiconductor cooling chip (302); ear seats (305) are respectively provided on both sides of the semiconductor cooling chip (302) at the front of the mounting panel (301), and a temperature control block (310) is provided at the front of the semiconductor cooling chip (302). The two sides of the temperature control block (310) are fixedly connected to the ear seats (305); a constant temperature chamber is provided in the middle of the temperature control block (310); a pressure block (307) is provided on the upper part of the ear seat (305), and an upper cover plate (306) is mounted on the two pressure blocks (307). A through hole for installing a drip tube is provided on the upper part of the upper cover plate (306), and the through hole coincides with the constant temperature chamber. The turntable (402) holds an insulated box (404) containing liquid nitrogen, and a bottle holder (405) is placed inside the insulated box (404). The bottle holder (405) has a vial slot on its outer periphery for holding vials.

8. The vial liquid nitrogen dropper according to claim 7, characterized in that: Fiber optic probes are installed on both sides of the lower part of the mounting panel (301), and the two fiber optic probes are on the same plane as the trajectory of the falling droplets.

9. A process for preparing freeze-dried beads, using the vial liquid nitrogen dropper as described in claim 1, characterized in that: Step 1: Use a vial freeze-drying tray to load vials and arrange them into a ring shape; Step 2: Place the ring-shaped set of vials on the upper part of the vial holder (405) and then put it into the insulated box; Step 3: Pour at least one-third of the liquid nitrogen into the vial and pour liquid nitrogen into the insulated box; Step 4: Connect the dropper to the solution supply device and start the preparation process; Step 5: After preparation, remove the bottle holder and take out a set of ring-shaped vials for freeze-drying.

Images