Whole-surface negative pressure flow control device based on high-flux microwell plate

Abstract

The utility model relates to a whole-surface negative pressure flow control device based on a high-flux microwell plate, which comprises a positioning clamp, a flow control module, a flow control module, a flow control module, a flow control module, a flow control module, a flow control module, a flow control module and a flow control module, wherein the top of the positioning clamp is provided with a positioning cavity for mounting a composite plate; the positioning clamp is internally provided with an action cavity communicated with the positioning cavity; one end of the suction pipeline is communicated with the acting cavity; and the vacuum suction device is communicated with the other end of the suction pipeline. According to the whole-surface negative pressure flow control device, a sealed cavity can be formed below a synthetic plate, and the whole-surface negative pressure acts on the sealed cavity, so that uniform suction and liquid discharge of each micropore of the synthetic plate are realized, and the drying effect on a synthetic carrier is ensured.

Description

Technical Field

[0001] The utility model relates to the technical field of synthetic biology, in particular to a whole-surface negative pressure flow control device based on a high-throughput microporous plate. Background Art

[0002] In the traditional commercial oligonucleotide synthesis process, in-situ chemical solid phase synthesis is often used. This method is generally based on low-throughput synthesis on standard SBS synthesis well plates (such as 96-well plates or 384-well plates) on the market. During the synthesis process, after the chemical reagents react on the low-throughput synthesis plate carrier for a certain period of time, positive pressure nitrogen is usually applied to the synthesis well plate, and the large volume of waste liquid on the synthesis carrier is driven by the inward pressure to flow through the waste liquid tank and finally discharged into the waste liquid collection barrel.

[0003] However, the above-mentioned traditional synthesis methods have some shortcomings. First, the synthesis flux is low and cannot meet the growing demand for gene synthesis. Secondly, a large amount of inert gas is consumed during the synthesis process, which increases costs and resource consumption. In order to increase the synthesis flux, it is necessary to greatly increase the number of microwells while keeping the size of the synthesis plate unchanged, such as upgrading the 96-well plate and 384-well plate to a 1536 array microwell plate on the basis of the same size. After increasing the flux, each microwell will be smaller in size, volume and spacing than before, resulting in the need for the liquid separation nozzle to have higher printing accuracy. If the traditional full-surface positive pressure driving and drainage method from top to bottom is still used, the full-surface positive pressure driving method cannot make the drainage of each synthetic microwell uniform, and a large amount of inert gas is consumed, and the synthetic carrier in each microwell cannot be completely dried. Utility Model Content

[0004] Based on this, it is necessary to provide a full-surface negative pressure fluid control device based on a high-throughput microporous plate that can form a sealed cavity under the synthetic plate and act on the sealed cavity with full-surface negative pressure to achieve uniform suction and drainage of each micropore of the synthetic plate, thereby ensuring the drying effect of the synthetic carrier, in order to address the problem that the positive pressure liquid driving method from top to bottom causes uneven drainage of each micropore and fails to thoroughly dry the synthetic carrier in each micropore.

[0005] A whole-surface negative pressure fluid control device based on a high-throughput microplate, comprising:

[0006] A positioning fixture, with a positioning cavity for installing the synthetic board on the top, and an action cavity communicating with the positioning cavity is provided inside the positioning fixture;

[0007] A suction pipe, one end of which is connected to the action chamber; and

[0008] A vacuum suction device is connected to the other end of the suction pipeline.

[0009] The above-mentioned full-surface negative pressure flow control device based on a high-throughput microporous plate installs the synthetic plate in the positioning cavity of the positioning fixture, and a connected working cavity is provided below the positioning cavity. The suction pipe is respectively connected to the working cavity and the vacuum suction device. After the vacuum suction device starts working, the gas in the working cavity and the positioning cavity is sucked, so that a full-surface negative pressure effect is generated in the working cavity. The waste liquid in each micropore of the synthetic plate can be automatically and evenly discharged to ensure the drying effect of the synthetic carrier.

[0010] In one of the embodiments, the vertical cross-sectional area of ​​the action chamber gradually decreases from the end communicating with the positioning chamber to the end communicating with the suction pipe.

[0011] In one embodiment, the action chamber is funnel-shaped.

[0012] In one embodiment, the positioning fixture includes a first sealing ring and at least two positioning pins, a positioning hole is provided at the bottom of the composite board, a skirt structure is provided at the periphery, a sealing notch is provided at the periphery of the positioning cavity, the first sealing ring is embedded in the sealing notch, the two positioning pins are spaced apart at the outside of the positioning cavity, the skirt of the composite board abuts against the first sealing ring, and the positioning holes of the composite board are correspondingly plugged into the positioning pins. The composite board is precisely positioned on the positioning fixture through the matching of the pin holes.

[0013] In one of the embodiments, it also includes a locking pressure plate and a lock, one end of the locking pressure plate is rotatably connected to the positioning fixture, and the other end is a free end. The lock is arranged on the positioning fixture, and the locking pressure plate can be rotated to press the synthetic board into the positioning cavity, and the lock can lock or release the free end of the locking pressure plate.

[0014] In one embodiment, the positioning fixture further comprises a guide plate, the guide plate is provided with a plurality of guide holes, and the guide plate is arranged in the working chamber; the vacuum suction device generates negative pressure in the working chamber, and the reaction liquid in the micropores of the synthetic plate is sucked out through the working chamber, the guide holes and the suction pipe. During the suction process, the gas can be evenly dispersed through the guide holes of the guide plate, the resistance is even, the gas flow rate is more stable, and the synthetic carrier in each micropore of the synthetic plate can be dried more evenly.

[0015] In one of the embodiments, it also includes a knob driving component, a base and a rotating table. The rotating table is rotatably disposed on the base, and the rotating table is fixedly connected to the positioning fixture. The knob driving component is disposed on the base and can drive the rotating table to drive the positioning fixture to rotate an angle.

[0016] In one of the embodiments, it also includes a second sealing ring, a microfluidic solenoid valve and a filter screen. The end of the suction pipe is clamped with the port of the working chamber, and the second sealing ring is sleeved on the suction pipe; the microfluidic solenoid valve is connected to the suction pipe and is used to adjust the negative pressure flow; the filter screen is arranged in the suction pipe and is located between the working chamber and the microfluidic solenoid valve.

[0017] In one of the embodiments, it also includes a glass slide substrate, an elastic clip and a calibration glass slide, the glass slide substrate is provided with a glass slide mounting cavity on the top, the glass slide substrate is arranged on the positioning fixture, the calibration glass slide is arranged in the glass slide mounting cavity, and the elastic clip is arranged on the glass slide substrate and can clamp the calibration glass slide.

[0018] In one embodiment, the vacuum suction device includes a vacuum pump and at least one air pressure regulating pipeline, and the air pressure regulating pipeline is respectively connected to the vacuum pump and the suction pipeline; the air pressure regulating pipeline includes a vacuum reducing valve, a flow digital display meter, a stop valve, a negative pressure digital display meter, a vacuum filter and a waste liquid collector which are arranged in sequence, and the waste liquid collector is connected to the suction pipeline. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 This is a structural schematic diagram of Embodiment 1 of the whole surface negative pressure flow control device of the utility model;

[0020] Figure 2 This is a structural schematic diagram of Embodiment 2 of the whole surface negative pressure flow control device of the utility model;

[0021] Figure 3 This is a structural schematic diagram of Embodiment 3 of the whole surface negative pressure flow control device of the utility model;

[0022] Figure 4 This is a structural schematic diagram of a fourth embodiment of the whole surface negative pressure flow control device of the utility model;

[0023] Figure 5 The utility model is a schematic diagram of a positioning structure of a calibration glass slide.

[0024] In the accompanying drawings, the components represented by the reference numerals are listed as follows:

[0025] 100. Whole-surface negative pressure fluid control device; 1. Positioning fixture; 11. Positioning cavity; 12. Working cavity; 2. Suction pipe; 3. Vacuum suction device; 31. Vacuum pump; 32. Vacuum pressure reducing valve; 33. Flow digital display instrument; 34. Stop valve; 35. Negative pressure digital display instrument; 36. Vacuum filter; 37. Waste liquid collector; 41. First sealing ring; 42. Positioning pin; 43. Locking plate; 44. Lock buckle; 441. Hook; 442. Wrench buckle; 5. Guide plate; 61. Knob drive; 62. Base; 63. Rotating table; 71. Second sealing ring; 72. Microfluidic solenoid valve; 73. Filter; 81. Glass slide substrate; 82. Elastic clamp; 83. Calibration glass slide; 200. Synthetic plate. DETAILED DESCRIPTION

[0026] In order to make the above-mentioned purposes, features and advantages of the utility model more obvious and easy to understand, the specific implementation methods of the utility model are described clearly and completely below in conjunction with the accompanying drawings. Obviously, the specific details described below are only part of the embodiments of the utility model, and the utility model can also be implemented in many other embodiments different from those described here. Based on the embodiments of the utility model, all other embodiments obtained by ordinary technicians in this field without making creative work belong to the protection scope of the utility model.

[0027] It should be noted that when an element is referred to as being "fixed to" another element, it may be directly on the other element or there may be a central element. When an element is considered to be "connected to" another element, it may be directly connected to the other element or there may be a central element at the same time. The terms "vertical", "horizontal", "left", "right" and similar expressions used herein are for illustrative purposes only and do not represent the only implementation method.

[0028] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art of the present invention. The terms used herein in the specification of the present invention are only for the purpose of describing specific embodiments and are not intended to limit the present invention.

[0029] See also Figure 1 and Figure 2 In one embodiment, a whole-surface negative pressure fluid control device 100 based on a high-throughput microplate includes: a positioning fixture 1, a suction pipe 2, and a vacuum suction device 3. A positioning cavity 11 for installing a synthetic plate 200 is provided on the top of the positioning fixture 1, and an action cavity 12 connected to the positioning cavity 11 from top to bottom is provided inside the positioning fixture 1. One end of the suction pipe 2 is connected to the action cavity 12. The vacuum suction device 3 is connected to the other end of the suction pipe 2.

[0030] The whole-surface negative pressure flow control device 100 based on a high-throughput microplate installs a synthetic plate 200 in a positioning cavity 11 of a positioning fixture 1, and a connected working cavity 12 is provided below the positioning cavity 11, and a suction pipe 2 is respectively connected to the working cavity 12 and a vacuum suction device 3. After the vacuum suction device 3 starts working, the gas in the working cavity 12 and the positioning cavity 11 is sucked, so that a whole-surface negative pressure effect is generated in the working cavity 12, and the waste liquid in each micropore of the synthetic plate 200 can be automatically and evenly discharged to ensure the drying effect of the synthetic carrier.

[0031] See also Figure 2 In one embodiment of the action chamber 12, the vertical cross section of the action chamber 12 is wide at the top and narrow at the bottom, which can facilitate the rapid and smooth downward flow of gas. Further, the action chamber 12 is funnel-shaped.

[0032] See also Figure 3 and Figure 4 In another embodiment, a positioning hole is provided at the bottom of the composite board 200, and a skirt structure is provided at the periphery. The positioning fixture 1 includes a first sealing ring 41 and at least two positioning pins 42. A sealing notch is provided at the periphery of the positioning cavity 11. The first sealing ring 41 is embedded in the sealing notch. Two positioning pins 42 are spaced apart outside the positioning cavity 11. The skirt of the composite board 200 abuts against the first sealing ring 41, and the positioning holes of the composite board 200 are correspondingly plugged into the positioning pins 42. This matching method can ensure that the composite board 200 forms a stable installation structure with two positioning points on one side, and the composite board 200 is precisely positioned on the positioning fixture 1 through the matching of the pin holes.

[0033] It should be noted that a plurality of positioning cavities 11 and action cavities 12 structures can be arranged on the positioning fixture 1 as required, and the synthesis plate 200 can select a 1536-well plate. When four groups of positioning cavities 11 and action cavities 12 are arranged at intervals, 6144 flux synthesis can be supported.

[0034] In order to improve the positioning of the synthetic board 200, the whole surface negative pressure flow control device 100 also includes a locking plate 43 and a lock 44. One end of the locking plate 43 is rotatably connected to the positioning fixture 1 through a hinge, and the other end is a free end. The lock 44 is arranged on the positioning fixture 1, and the locking plate 43 can be rotated to press the synthetic board 200 into the positioning cavity 11, and the lock 44 can lock or release the free end of the locking plate 43. The lock 44 can be a conventional quick buckle, which includes a hook 441 arranged on the outer side of the locking plate 43 and a wrench buckle 442 arranged on the positioning fixture 1. The hook 441 is pulled downward by the wrench buckle 442, so that the locking plate 43 presses the synthetic board 200.

[0035] See also Figure 2In other embodiments, the positioning fixture 1 further includes a guide plate 5, which is provided with a plurality of guide holes, and the guide plate 5 is arranged in the working chamber 12. The vacuum suction device 3 works to generate negative pressure in the working chamber 12, and the reaction liquid in the micropores of the synthetic plate 200 is sucked out through the working chamber 12, the guide holes and the suction pipe 2. During the suction process, the gas can be evenly dispersed through the guide holes of the guide plate 5, the resistance is uniform, the gas flow rate is more stable, and the synthetic carrier in each micropore of the synthetic plate 200 can be dried more evenly.

[0036] See also Figure 3 and Figure 4 Considering that in actual operation, the position of the composite plate 200 needs to be finely adjusted, the whole surface negative pressure flow control device 100 also includes a knob driver 61, a base 62 and a rotating table 63. The rotating table 63 is rotatably arranged on the base 62, and the rotating table 63 is fixedly connected to the positioning fixture 1. The knob driver 61 is arranged on the base 62, and can drive the rotating table 63 to drive the positioning fixture 1 to rotate an angle. The specific rotation drive matching structure can be a conventional worm gear and worm gear matching transmission. A worm gear is arranged in the knob driver 61, and a worm gear is arranged in the rotating table 63. The worm gear is meshed with the worm gear. When the worm gear is driven to rotate, the rotating table 63 can achieve horizontal rotation displacement.

[0037] In another embodiment, the whole surface negative pressure flow control device 100 further includes a second sealing ring 71, a microfluidic solenoid valve 72 and a filter 73. The end of the suction pipe 2 is clamped with the port of the action chamber 12. The second sealing ring 71 is sleeved on the suction pipe 2 so that the suction pipe 2 and the action chamber 12 are tightly fitted without gap. The microfluidic solenoid valve 72 is connected to the suction pipe 2 and is used to adjust the negative pressure flow. The microfluidic solenoid valve 72 can avoid the instantaneous opening or closing of the negative pressure suction and cause a large fluctuation in the air pressure in the suction pipe 2. The filter 73 is arranged in the suction pipe 2 and is located between the action chamber 12 and the microfluidic solenoid valve 72. The filter 73 can prevent particulate matter from clogging or damaging the microfluidic solenoid valve 72.

[0038] See also Figure 5 The whole surface negative pressure fluid control device 100 also includes a glass slide substrate 81, an elastic clamp 82 and a calibration glass slide 83. A glass slide mounting cavity is provided on the top of the glass slide substrate 81. The glass slide substrate 81 is arranged on the positioning fixture 1. The calibration glass slide 83 is arranged in the glass slide mounting cavity. The elastic clamp 82 is arranged on the glass slide substrate 81 and can move close to or away from the glass slide substrate 81. When the elastic clamp 82 moves close to the glass slide substrate 81, it can clamp the calibration glass slide 83. During the synthesis operation, the synthetic liquid dispensing nozzle can print droplets on the calibration glass slide 83 at intervals, and observe the landing point of the droplets on the calibration glass slide 83 through a camera to verify the printing accuracy of the liquid dispensing nozzle.

[0039] See also Figure 1 In one embodiment of the vacuum suction device 3, the vacuum suction device 3 includes a vacuum pump 31 and at least one air pressure regulating pipeline, and the air pressure regulating pipeline is respectively connected to the vacuum pump 31 and the suction pipeline 2. The air pressure regulating pipeline includes a vacuum pressure reducing valve 32, a flow digital display instrument 33, a stop valve 34, a negative pressure digital display instrument 35, a vacuum filter 36 and a waste liquid collector 37, which are arranged in sequence, and the waste liquid collector 37 is connected to the suction pipeline 2. After the vacuum pump 31 generates negative pressure, the gas in the action chamber 12 will be sucked, and the external airflow will generate negative pressure in the action chamber 12, and the waste liquid in the micropores of the synthetic board 200 will be brought out and flow into the suction pipe 2, and then flow into the waste liquid collector 37 after passing through the filter 73 and the microfluidic solenoid valve 72. The negative pressure digital display instrument 35 is arranged on the waste liquid collector 37 to detect the air pressure in the waste liquid collector 37. The gas that is not collected will continue to pass through the vacuum filter 36, the stop valve 34, the flow digital display instrument 33, and the vacuum pressure reducing valve 32, and finally be discharged by the vacuum pump 31.

[0040] It should be noted that two air pressure regulating pipelines can be provided, which are respectively set to high-pressure vacuum suction mode and low-pressure vacuum suction mode, and high and low vacuum are switched by switching valves. For example, Hdrain: high-pressure vacuum suction; Ldrain: low-pressure vacuum suction; Pdrain: under low-pressure vacuum suction, the microfluidic solenoid valve 72 is switched on and off at a certain frequency to achieve pulse suction. Each mode can be freely combined or used alone to achieve the best suction and drainage effect.

[0041] The technical features of the above-described embodiments may be arbitrarily combined. To make the description concise, not all possible combinations of the technical features in the above-described embodiments are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of this specification.

[0042] The above-mentioned embodiments only express several implementation methods of the utility model, and the description is relatively specific and detailed, but it cannot be understood as limiting the scope of the utility model patent. It should be pointed out that for ordinary technicians in this field, several deformations, substitutions and improvements can be made without departing from the concept of the utility model, which should be included in the protection scope of the utility model. Therefore, the protection scope of the utility model patent should be based on the claims.

Claims

1. A whole-surface negative pressure fluid control device based on a high-throughput microplate, characterized in that: include: A positioning fixture, with a positioning cavity for installing the synthetic board on the top, and an action cavity communicating with the positioning cavity is provided inside the positioning fixture; A suction pipe, one end of which is connected to the action chamber; and A vacuum suction device is connected to the other end of the suction pipeline.

2. The whole surface negative pressure fluid control device based on a high-throughput microplate according to claim 1, characterized in that: The vertical cross-sectional area of ​​the action cavity gradually decreases from the end communicating with the positioning cavity to the end communicating with the suction pipe.

3. The whole surface negative pressure fluid control device based on a high-throughput microplate according to claim 2, characterized in that: The action cavity is funnel-shaped.

4. The whole surface negative pressure fluid control device based on a high-throughput microplate according to claim 1, characterized in that: The positioning fixture includes a first sealing ring and at least two positioning pins. A positioning hole is provided at the bottom of the synthetic board and a skirt structure is provided at the outer periphery. A sealing groove is provided at the outer periphery of the positioning cavity. The first sealing ring is embedded in the sealing groove. The two positioning pins are spaced apart on the outside of the positioning cavity. The skirt of the synthetic board abuts against the first sealing ring, and the positioning hole of the synthetic board is correspondingly plugged into the positioning pin.

5. The whole surface negative pressure fluid control device based on a high-throughput microplate according to claim 4, characterized in that: It also includes a locking plate and a lock, one end of the locking plate is rotatably connected to the positioning fixture, and the other end is a free end. The lock is arranged on the positioning fixture. The locking plate can be rotated to press the synthetic board into the positioning cavity, and the lock can lock or release the free end of the locking plate.

6. The whole surface negative pressure fluid control device based on a high-throughput microplate according to claim 1, characterized in that: The positioning fixture also includes a guide plate, which is penetrated by a plurality of guide holes and is arranged in the working cavity; the vacuum suction device generates negative pressure in the working cavity, and the reaction liquid in the micropores of the synthetic plate is sucked out through the working cavity, the guide holes and the suction pipe.

7. The whole surface negative pressure fluid control device based on a high-throughput microplate according to claim 1, characterized in that: It also includes a knob driving component, a base and a rotating table. The rotating table is rotatably arranged on the base, and the rotating table is fixedly connected to the positioning fixture. The knob driving component is arranged on the base and can drive the rotating table to drive the positioning fixture to rotate an angle.

8. The whole surface negative pressure fluid control device based on a high-throughput microplate according to claim 1, characterized in that: It also includes a second sealing ring, a microfluidic solenoid valve and a filter screen. The end of the suction pipe is clamped with the port of the working chamber, and the second sealing ring is sleeved on the suction pipe; the microfluidic solenoid valve is connected to the suction pipe and is used to adjust the negative pressure flow; the filter screen is arranged in the suction pipe and is located between the working chamber and the microfluidic solenoid valve.

9. The whole surface negative pressure fluid control device based on a high-throughput microplate according to claim 1, characterized in that: It also includes a glass slide substrate, an elastic clamp and a calibration glass slide. A glass slide mounting cavity is opened on the top of the glass slide substrate. The glass slide substrate is arranged on the positioning fixture. The calibration glass slide is arranged in the glass slide mounting cavity. The elastic clamp is arranged on the glass slide substrate and can clamp the calibration glass slide.

10. The whole surface negative pressure fluid control device based on a high-throughput microplate according to claim 1, characterized in that: The vacuum suction device includes a vacuum pump and at least one air pressure regulating pipeline, and the air pressure regulating pipeline is respectively connected to the vacuum pump and the suction pipeline; the air pressure regulating pipeline includes a vacuum reducing valve, a flow digital display meter, a stop valve, a negative pressure digital display meter, a vacuum filter and a waste liquid collector arranged in sequence, and the waste liquid collector is connected to the suction pipeline.

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