Oligonucleotide synthesizer

By using a pressure sensor and an electrical proportional valve in an oligonucleotide synthesizer to adjust the air pressure to maintain stability, the problems of gas source pressure attenuation and increased gas resistance of the synthetic carrier during oligonucleotide synthesis are solved, and the quality of the synthetic products is improved.

CN119657027APending Publication Date: 2025-03-21SHENZHEN XINSAISI BIOTECHNOLOGY CO LTD
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Patent Information

Application Number
CN202510159769.6
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Priority Date
2024-10-23
Filing Date
2025-02-13
Publication Date
2025-03-21

AI Technical Summary

Technical Problem

During the oligonucleotide synthesis process, the attenuation of the gas source pressure leads to insufficient elimination of the reagents, affecting the quality of the synthetic product. As the polyoligonucleotide chain lengths, the gas resistance of the synthetic carrier increases, further affecting the product quality.

Method used

An oligonucleotide synthesizer is designed, including a casing, a pressure sensor, an electrical proportional valve and a control component. By monitoring the air pressure of the intake chamber and adjusting the opening of the electrical proportional valve, the air pressure is maintained to ensure that the residual reagents at each reaction step can be eliminated cleanly.

Benefits of technology

By maintaining the air pressure stability, ensuring that the residual reagents at each reaction step are completely eliminated, the quality of the synthetic product is improved, and the problems of gas source pressure attenuation and increased gas resistance of the synthetic carrier are solved.

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Abstract

The oligonucleotide synthesizer comprises a machine shell, an air pressure sensor, an electric proportional valve and a control assembly, an air inlet cavity is formed in the machine shell, an air inlet and a communication opening are formed in the air inlet cavity, the electric proportional valve is arranged on the machine shell, the air inlet is used for being communicated with an air source through the electric proportional valve, and the air pressure sensor is used for being communicated with the air source through the communication opening. The machine shell is used for fixing a synthesis container, the communication opening is used for being matched with the synthesis container so that the liquid inlet side of the synthesis container can be communicated with the air inlet cavity and the liquid outlet side of the synthesis container can be communicated with the outside, and the air pressure sensor is arranged on the machine shell and used for detecting the air pressure of the air inlet cavity. The control assembly is electrically connected with the air pressure sensor and the electric proportional valve. The control assembly can control the electric proportional valve so as to adjust the required amount of gas introduced into the gas inlet cavity, so that residual reagents in each reaction step can be completely removed, and the quality of reaction products is ensured.
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Description

Technical Field

[0001] The present invention relates to the technical field of oligonucleotide synthesis, in particular to an oligonucleotide synthesizer. Background Art

[0002] Because each additional base in the oligonucleotide synthesis process requires four reagent exclusion processes, when synthesizing a longer chain of DNA (for example, 90 bases), the entire process requires hundreds of reagent exclusion processes. Generally, positive pressure is provided to the synthesis tube through the gas source to achieve reagent exclusion. Due to the long synthesis process and the large number of exclusions, the gas source pressure will be significantly reduced. After the gas source pressure decays, the reagents in the subsequent reaction steps will not be fully excluded, which will seriously affect the quality of the synthetic product. In addition, as the length of the oligonucleotide chain increases, the micropores on the synthetic carrier will become smaller, resulting in an increase in the gas resistance of the synthetic carrier. Fixed gas source pressure will lead to insufficient reagent exclusion in the subsequent reaction steps, which will also seriously affect the quality of the synthetic product. Summary of the invention

[0003] Based on this, it is necessary to provide an oligonucleotide synthesizer.

[0004] An oligonucleotide synthesizer includes a casing, an air pressure sensor, an electric proportional valve and a control component. An air inlet cavity is provided in the casing, and the air inlet cavity is formed with an air inlet port and a connecting port. The electric proportional valve is arranged in the casing, and the air inlet port is used to connect with an air source through the electric proportional valve. The casing is used to fix a synthesis container, and the connecting port is used to cooperate with the synthesis container so that the liquid inlet side of the synthesis container is connected with the air inlet cavity, and the liquid discharge side of the synthesis container is connected with the outside. The air pressure sensor is arranged in the casing and is used to detect the air pressure of the air inlet cavity. The control component is electrically connected to the air pressure sensor and the electric proportional valve respectively.

[0005] It is worth mentioning that the existing synthesis container is set with openings on both sides, and the openings on both sides are respectively a liquid inlet and a liquid outlet. The side with the liquid inlet is the liquid inlet side of the synthesis container, and the side with the liquid outlet is the liquid discharge side of the synthesis container. The synthesis container can be tubular or dish-shaped. The tubular synthesis container can be called a synthesis tube or a synthesis column, which is hollow inside and tubular. In some embodiments, one end of the synthesis tube is conical, and the internal diameter of the conical position of the synthesis tube gradually decreases to play a guiding role when removing residual reagents and speed up the removal of residual reagents. When the synthesis container is dish-shaped, a liquid outlet is opened at the bottom of the dish of the synthesis container, and the position of the bottom of the dish is the liquid discharge side of the synthesis container.

[0006] The housing of the above-mentioned oligonucleotide synthesizer can fix the synthesis container. After the synthesis container with the synthesis carrier and the reaction reagent is placed in the housing, the liquid inlet side of the synthesis container can be connected with the air inlet chamber through the connecting port, and the liquid discharge side of the synthesis container can be connected with the outside. After the reaction of the reaction reagent on the synthesis carrier is completed, the gas source passes gas into the air inlet chamber through the air inlet, which can form a positive pressure difference between the liquid inlet side and the liquid discharge side of the synthesis container to drive the residual reagent to detach from the synthesis carrier and realize the removal of the residual reagent. In the process of removing the residual reagent, the air pressure sensor can continuously monitor the air pressure in the air inlet chamber, and the control component can obtain the air pressure data of the air pressure sensor, and when it is identified that the air pressure in the air inlet chamber is too high or too low, the opening of the electric proportional valve is adjusted to control the amount of gas input from the air source to the air inlet chamber, thereby maintaining the air pressure in the air inlet chamber stable. In this way, even if the internal pressure of the gas source becomes unstable with use, for example, when the gas source pressure decays, the control component can control the electrical proportional valve to adjust the required amount of gas entering the air inlet chamber, stabilize the air pressure in the air inlet chamber, and thereby ensure that the residual reagents in each reaction step can be completely removed to ensure the quality of the reaction product.

[0007] In addition, the inventors have found that in the reaction steps of oligonucleotides, the viscosity of the various reaction reagents used is different due to their different functions. Conventional synthesis systems can only set a constant air pressure, so that the time required to exhaust each residual reagent is different. With the increase of reaction steps, the length of the product on the synthesis carrier increases, and impurities in the reagents accumulate on the synthesis carrier, which will increase the exhaust resistance. At this time, the use of constant pressure to eliminate the residual reagents for a long time cannot completely eliminate the residual reagents, thereby affecting the quality of the final synthetic product. In the present application, the residual reagents are fully eliminated by adjusting the air pressure, ensuring that the residual reagents in each reaction step can be eliminated cleanly, thereby ensuring the quality of the reaction product.

[0008] In one of the embodiments, the housing is further provided with an exhaust cavity, the exhaust cavity is formed with an exhaust port communicating with the outside, and the air inlet cavity is communicated with the exhaust cavity through the communication port.

[0009] In one embodiment, at least one synthesis container is further included, wherein the synthesis container has a liquid inlet side and a liquid discharge side that are connected, and the liquid inlet side and the liquid discharge side are used to fix the synthesis carrier, and the synthesis container includes at least one of the following configurations: i) the synthesis container is fixed in the air inlet cavity, and the liquid discharge side of the synthesis container abuts against the communication port of the housing; ii) the synthesis container is fixed outside the air inlet cavity, and the liquid inlet side of the synthesis container abuts against the communication port of the housing; iii) The communication port of the casing is used for passing a synthesis container.

[0010] In one embodiment, the number of the communication ports is set to be multiple, and each of the communication ports is used to correspond to the synthesis container.

[0011] In one embodiment, each of the communication ports is disposed corresponding to one of the synthesis containers; or The communication ports are divided into a plurality of groups, and each group of the communication ports is arranged corresponding to one of the synthesis containers.

[0012] In one of the embodiments, it further comprises an air source, and the air source is connected to the air inlet through the electrical proportional valve.

[0013] In one of the embodiments, a reagent delivery mechanism is further included, and the reagent delivery mechanism is disposed in the housing and is disposed toward the air inlet cavity.

[0014] In one embodiment, the control component includes one of a PID controller, a single chip microcomputer, and a PLC controller.

[0015] In one of the embodiments, a display component is further included, the control component includes a PID controller, and the display component is electrically connected to the PID controller.

[0016] In one of the embodiments, a pressure reducing valve is further included, and the electrical proportional valve is used to communicate with the gas source through the pressure reducing valve.

[0017] In one embodiment, the air pressure sensor is used to detect the air pressure data of the air inlet cavity, and the control component is used to control the opening of the electrical proportional valve according to the air pressure data of the air inlet cavity; and / or The air pressure detection component is used to detect the air pressure data of the air intake chamber at preset time intervals, and the control component is used to calculate the air pressure drop rate of the air intake chamber based on the air pressure data at the preset time intervals. When the air pressure drop rate is less than the preset drop rate, the control component increases the opening of the electrical proportional valve. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 Schematic diagram of the principle of oligonucleotide synthesis.

[0019] Figure 2 The figure is a schematic diagram of the structure of an oligonucleotide synthesizer according to an embodiment.

[0020] Figure 3 The figure is a schematic diagram of the structure of a synthesis container of an oligonucleotide synthesizer according to an embodiment.

[0021] In the figure, 10, oligonucleotide synthesizer; 100, housing; 200, air pressure sensor; 300, electric proportional valve; 400, control component; 101, air inlet chamber; 102, air inlet port; 103, connecting port; 500, synthesis container; 104, exhaust chamber; 105, exhaust port; 610, gas cylinder; 620, gas flow meter; 630, reagent storage bottle; 710, display screen; 720, pressure reducing valve; 730, gas tank; 111, split flow injector; 510, liquid inlet side; 520, liquid discharge side; 530, synthesis carrier. DETAILED DESCRIPTION

[0022] For ease of understanding of the application, the application will be described more fully below. The application can be implemented in many different forms and is not limited to the embodiments described herein. On the contrary, the purpose of providing these embodiments is to make the understanding of the disclosure of the application more thorough and comprehensive.

[0023] In addition, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance or implicitly indicating the number of technical features indicated. Therefore, a feature defined as "first" or "second" may explicitly or implicitly include at least one of the features. In the description of the application, the meaning of "multiple" is at least two, such as two, three, etc., unless otherwise clearly and specifically defined. In the description of the present application, the meaning of "several" is at least one, such as one, two, etc., unless otherwise clearly and specifically defined.

[0024] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those generally understood by those skilled in the art to which the present application belongs. The terms used herein in the specification of the present application are only for the purpose of describing specific embodiments and are not intended to limit the present application. The term "and / or" used herein includes any and all combinations of one or more of the related listed items.

[0025] In the present application, the technical features described in an open manner include closed technical solutions composed of the listed features, and also include open technical solutions containing the listed features.

[0026] like Figure 1 As shown, the steps of oligonucleotide synthesis reaction include the following cycles in sequence: deprotection, coupling reaction, capping, oxidation...aminolysis.

[0027] Each step needs to go through three processes: adding reagents, waiting for reaction, and removing reagents. The process of removing reagents mainly removes the residual reagents by adding inert gas in a positive direction, and then prepares for the next reaction. The residual reagents need to be fully removed.

[0028] To ensure that the residual reagents are removed completely, Figure 2 and Figure 3 As shown, in one embodiment, an oligonucleotide synthesizer 10 is provided, including a housing 100, an air pressure sensor 200, an electrical proportional valve 300 and a control component 400. An air inlet cavity 101 is provided in the housing 100, and the air inlet cavity 101 is formed with an air inlet port 102 and a connecting port 103. The electrical proportional valve 300 is arranged in the housing 100, and the air inlet port 102 is used to communicate with an air source through the electrical proportional valve 300. The housing 100 is used to fix a synthesis container 500, and the connecting port 103 is used to cooperate with the synthesis container 500 so that a liquid inlet side 510 of the synthesis container 500 is connected with the air inlet cavity 101, and a liquid discharge side 520 of the synthesis container 500 is connected with the outside. The air pressure sensor 200 is arranged in the housing 100 and is used to detect the air pressure of the air inlet cavity 101. The control component 400 is electrically connected to the air pressure sensor 200 and the electrical proportional valve 300, respectively.

[0029] It is worth mentioning that the existing synthesis container 500 is set with openings on both sides, and the openings on both sides are respectively a liquid inlet and a liquid outlet. The side with the liquid inlet is the liquid inlet side 510 of the synthesis container 500, and the side with the liquid outlet is the liquid discharge side 520 of the synthesis container 500. The synthesis container can be tubular or dish-shaped. The tubular synthesis container can be called a synthesis tube or a synthesis column, which is hollow inside and tubular. In some embodiments, one end of the synthesis tube is conical, and the internal diameter of the conical position of the synthesis tube gradually decreases to play a guiding role when removing residual reagents and accelerate the removal of residual reagents. When the synthesis container is dish-shaped, a liquid outlet is opened at the bottom of the dish of the synthesis container, and the position of the bottom of the dish is the liquid discharge side of the synthesis container.

[0030] The housing 100 of the above-mentioned oligonucleotide synthesizer 10 can fix the synthesis container 500. After the synthesis container 500 with the synthesis carrier 530 and the reaction reagent is placed in the housing 100, the liquid inlet side 510 of the synthesis container 500 can be connected with the air inlet chamber 101 through the connecting port 103, and the liquid discharge side 520 of the synthesis container 500 can be connected with the outside. After the reaction of the reaction reagent on the synthesis carrier 530 is completed, the gas source passes gas into the air inlet chamber 101 through the gas inlet 102, and a positive pressure difference can be formed between the liquid inlet side 510 and the liquid discharge side of the synthesis container 500, so as to drive the residual reagent to separate from the synthesis carrier 530, thereby realizing the removal of the residual reagent. In the process of removing the residual reagent, the air pressure sensor 200 can continuously monitor the air pressure in the air inlet chamber 101, and the control component 400 can obtain the air pressure data of the air pressure sensor 200, and when it is identified that the air pressure in the air inlet chamber 101 is too high or too low, the opening of the electric proportional valve 300 is adjusted to control the amount of air input from the air source to the air inlet chamber 101, thereby maintaining the air pressure in the air inlet chamber 101 stable. In this way, even if the internal pressure of the air source is unstable with use, for example, when the air source pressure decays, the control component 400 can control the electric proportional valve 300 to adjust the required amount of air introduced into the air inlet chamber 101, stabilize the air pressure in the air inlet chamber 101, and ensure that the residual reagents in each reaction step can be completely removed, thereby ensuring the quality of the reaction product.

[0031] In addition, the inventors have found that in the reaction steps of oligonucleotides, the viscosity of the various reaction reagents used is different due to their different functions. Conventional synthesis systems can only set a constant air pressure, so that the time required to exhaust each residual reagent is different. With the increase of reaction steps, the length of the product on the synthesis carrier increases, and impurities in the reagents accumulate on the synthesis carrier, which will increase the exhaust resistance. At this time, the use of constant pressure to eliminate the residual reagents for a long time cannot completely eliminate the residual reagents, thereby affecting the quality of the final synthetic product. In the present application, the residual reagents are fully eliminated by adjusting the air pressure, ensuring that the residual reagents in each reaction step can be eliminated cleanly, thereby ensuring the quality of the reaction product.

[0032] In one embodiment, the housing 100 is further provided with an exhaust cavity 104, and the exhaust cavity 104 is formed with an exhaust port 105 communicating with the outside. In one embodiment, the outside communicated with by the exhaust port 105 is the atmosphere, and the air inlet cavity 101 is communicated with the exhaust cavity 104 through the communication port 103. The exhaust cavity 104 is used to provide a space relatively isolated from the external environment of the housing 100, so as to avoid the product from contacting the external environment as much as possible and to avoid the product from being contaminated by impurities. The exhaust cavity 104 is communicated with the outside through the exhaust port 105, so that it is easy to form an air pressure difference between the air inlet cavity 101 and the exhaust cavity 104.

[0033] In one embodiment, the oligonucleotide synthesizer 10 also includes at least one synthesis container 500, wherein the synthesis container 500 has a through liquid inlet side 510 and a liquid discharge side 520, and the liquid inlet side 510 and the liquid discharge side 520 are used to fix a synthesis carrier 530, and the synthesis container 500 includes at least one of the following settings, i.e., at least one of i, ii and iii. There can be multiple synthesis containers 500, so that the settings of the synthesis containers 500 can be diverse.

[0034] In one embodiment, the synthesis container is fixed in the air inlet cavity, and the drainage side of the synthesis container abuts against the communication port of the housing; in this setting, the drainage side of the synthesis container abuts against the position of the inner surface of the housing near the communication port, so that the liquid inlet of the synthesis container is connected with the communication port, so that the air inlet cavity, the interior of the synthesis container and the communication port are connected in sequence, thereby, a positive pressure difference is easily formed on the liquid inlet side and the drainage side of the synthesis container, so that the residual reagent of the synthesis carrier can be removed. For example, the communication port is set at the inner bottom of the housing, the drainage side of the synthesis container is placed and abutted against the inner bottom of the housing, and the drainage port is connected with the communication port. In one embodiment, a limiting ring is set around the communication port at the inner bottom of the housing, and the synthesis container is placed in the limiting ring to fix the synthesis container. For another example, a fixing mechanism for fixing the synthesis container, such as a clamping assembly, a snap assembly, a magnetic assembly, etc., is provided in the casing, so as to fix the synthesis container in the air inlet cavity of the casing and make the discharge side of the synthesis container abut against the connecting port of the casing.

[0035] like Figure 2 As shown, in one embodiment, the synthesis container 500 is fixed outside the air inlet cavity 101. The synthesis container 500 of this embodiment is arranged in the exhaust cavity 104, and the liquid inlet side 510 of the synthesis container 500 abuts against the communication port 103 of the housing 100. In this arrangement, the synthesis container 500 is fixed on the side of the housing 100 opposite to the air inlet cavity 101. In one embodiment, a limiting ring is arranged around the communication port 103 on the outer surface of the housing 100, and the synthesis container 500 is inserted into the limiting ring to fix the synthesis container 500. For another example, a fixing mechanism for fixing the synthesis container 500 is arranged on the outer side of the housing 100, such as a clamping assembly, a buckle assembly, a magnetic suction assembly, etc., so that the synthesis container 500 is fixed on the side of the housing 100 away from the air inlet cavity 101, and the liquid inlet side 510 of the synthesis container 500 abuts against the communication port 103 of the housing 100.

[0036] In one embodiment, the communication port of the housing is used to pass through the synthesis container. In this arrangement, the synthesis container is directly inserted into the communication port, and the outer surface of the synthesis container abuts against the side wall of the communication port, so as to facilitate the fixing of the synthesis container, and at the same time, the air inlet cavity is connected to the atmosphere through the interior of the synthesis container, forming a positive pressure difference. In one embodiment, the side wall of the synthesis container and the communication port are interference fit, so as to close the gap between the synthesis container and the side wall of the communication port to avoid air leakage, so that the air pressure of the air inlet cavity can better act on the reaction reagent of the synthesis container, which is conducive to removing residual reagents.

[0037] In one embodiment, the number of the communication ports 103 is set to be multiple, and each of the communication ports 103 is used to be set corresponding to the synthesis container 500. In one embodiment, each of the communication ports 103 is set corresponding to one of the synthesis containers 500. In this embodiment, multiple synthesis containers 500 can be set to perform multiple reactions simultaneously. Alternatively, each of the communication ports 103 is divided into multiple groups, and each group of the communication ports 103 is set corresponding to one of the synthesis containers 500. In this embodiment, multiple communication ports 103 are all connected to the interior of the synthesis container 500, so that the gas in the air inlet chamber 101 is diverted and sent to the interior of the synthesis container 500. Some of the communication ports 103 can guide the gas to blow the gas to a specific position, so as to better remove the residual reagents on the synthesis carrier 530.

[0038] In one embodiment, the oligonucleotide synthesizer 10 further includes a gas source, which is connected to the air inlet 102 through the electrical proportional valve 300. For example, the gas source is a gas tank 730, in which non-reactive gas is stored, and the non-reactive gas is a gas that does not participate in the synthesis of oligonucleotides. For example, the non-reactive gas is an inert gas to avoid reaction with the raw materials of the oligonucleotides and will not corrode the equipment. For another example, the gas source is an air pump, which is used to draw air from the environment and pass it into the air inlet cavity 101.

[0039] In one embodiment, the oligonucleotide synthesizer 10 further includes a reagent delivery mechanism, which is disposed in the housing 100 and is disposed toward the air inlet chamber 101. The reagent delivery mechanism is used to deliver the reaction reagents for oligonucleotide synthesis into the synthesis container 500, so as to realize automatic filling of the reaction reagents and improve the reaction efficiency. In this embodiment, the reagent delivery mechanism includes a gas cylinder 610, a gas flow meter 620, and a reagent storage bottle 630 connected in sequence. In this embodiment, the gas delivery pipe led out of the gas flow meter 620 is inserted above the reagent storage bottle 630, and the liquid outlet pipe of the reagent storage bottle 630 is led out from the bottom of the reagent storage bottle 630 to the air inlet chamber 101 and is disposed toward the synthesis container 500. In this way, the gas in the gas cylinder 610 drives the reagent in the reagent storage bottle 630 to the synthesis container 500, so as to realize automatic liquid addition. In this embodiment, there are multiple reagent storage bottles 630, and the oligonucleotide synthesizer 10 also includes a shunt injector 111. The gas flow meter 620 is connected to each reagent storage bottle 630 through the shunt injector 111, wherein each reagent storage bottle can store different reagents, that is, each reagent storage bottle 630 is respectively set to correspond to the synthesis container 500.

[0040] In one embodiment, the control component 400 includes a PID controller. The PID controller is composed of a proportional unit P, an integral unit I and a differential unit D. In this embodiment, the PID controller is used to obtain the air pressure data of the air pressure sensor 200, and when it is identified that the air pressure of the air inlet chamber 101 is too high or too low, the opening of the electric proportional valve 300 is adjusted to control the amount of air input from the air source to the air inlet chamber 101, thereby maintaining the air pressure in the air inlet chamber 101 stable. In this embodiment, the PID controller is combined with the electric proportional valve to be a simple and practical control method with high reliability. Of course, the control component 400 can also be implemented in other ways, such as a computer, etc. In this solution, the PID controller has a smaller volume than the complex control component 400 such as a computer, and can realize the control function. In other embodiments, the control component can also be a single-chip microcomputer or a PLC controller, both of which can realize the control function.

[0041] In one embodiment, the oligonucleotide synthesizer 10 further includes a display component, which is electrically connected to the PID controller, and specifically, the display component includes a display screen 710. The display screen 710 of the display component can display the readings and operation keys of the PID controller, thereby facilitating the adjustment of different modes.

[0042] In one embodiment, the oligonucleotide synthesizer 10 also includes a pressure reducing valve 720, and the electrical proportional valve 300 is used to communicate with the gas source 730 through the pressure reducing valve 720. The gas in the gas source is in a high-pressure state. The pressure reducing valve 720 is used to reduce the output pressure of the gas source to a more appropriate level to avoid excessive pressure release.

[0043] In one embodiment, the air pressure detection component is used to detect the air pressure data of the air inlet chamber at a preset time interval, and the control component is also used to calculate the air pressure drop rate of the air inlet chamber according to the air pressure data at the preset time interval. When the air pressure drop rate is less than the preset drop rate, the control component increases the opening of the electrical proportional valve. This is because when the air pressure drop rate is slow or does not drop, it means that the air pressure of the air inlet chamber is difficult to remove the residual reagent from the synthetic carrier. At this time, the control component will increase the opening of the electrical proportional valve to remove the reagent in a shorter time, thereby improving the efficiency of the entire synthetic reaction.

[0044] 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.

[0045] The above-mentioned embodiments only express several implementation methods of the present invention, and the descriptions thereof are relatively specific and detailed, but they cannot be understood as limiting the scope of the invention patent. It should be pointed out that, for ordinary technicians in this field, several variations and improvements can be made without departing from the concept of the present invention, and these all belong to the protection scope of the present invention. Therefore, the protection scope of the patent of the present invention shall be subject to the attached claims.

Claims

1. An oligonucleotide synthesizer, characterized in that It includes a casing, an air pressure sensor, an electric proportional valve and a control component. An air inlet cavity is opened in the casing, and the air inlet cavity is formed with an air inlet port and a connecting port. The electric proportional valve is arranged in the casing. The air inlet port is used to communicate with an air source through the electric proportional valve. The casing is used to fix a synthesis container. The connecting port is used to cooperate with the synthesis container so that the liquid inlet side of the synthesis container is connected with the air inlet cavity, and the liquid discharge side of the synthesis container is connected with the outside. The air pressure sensor is arranged in the casing and is used to detect the air pressure of the air inlet cavity. The control component is electrically connected to the air pressure sensor and the electric proportional valve respectively.

2. The oligonucleotide synthesizer according to claim 1, characterized in that The housing is further provided with an exhaust cavity, wherein the exhaust cavity is formed with an exhaust port communicating with the outside, and the air inlet cavity is communicated with the exhaust cavity through the communication port.

3. The oligonucleotide synthesizer according to claim 1, characterized in that: It also includes at least one synthesis container, wherein the synthesis container has a liquid inlet side and a liquid discharge side that are connected, and the liquid inlet side and the liquid discharge side are used to fix the synthesis carrier, and the synthesis container includes at least one of the following configurations: i) the synthesis container is fixed in the air inlet cavity, and the liquid discharge side of the synthesis container abuts against the communication port of the housing; ii) the synthesis container is fixed outside the air inlet cavity, and the liquid inlet side of the synthesis container abuts against the communication port of the housing; iii) The communication port of the casing is used for passing a synthesis container.

4. The oligonucleotide synthesizer according to claim 1, characterized in that The number of the communication ports is set to be multiple, and each of the communication ports is used to correspond to the synthesis container.

5. The oligonucleotide synthesizer according to claim 1, characterized in that: Each of the communication ports is provided corresponding to one of the synthesis containers; or The communication ports are divided into a plurality of groups, and each group of the communication ports is arranged corresponding to one of the synthesis containers.

6. The oligonucleotide synthesizer according to claim 1, characterized in that: It also includes an air source, the air source is connected to the air inlet through the electrical proportional valve; and / or A pressure reducing valve is also included, and the electrical proportional valve is used to communicate with the gas source through the pressure reducing valve.

7. The oligonucleotide synthesizer according to claim 1, characterized in that: It also includes a reagent delivery mechanism, which is arranged on the housing and faces the air inlet cavity.

8. The oligonucleotide synthesizer according to claim 1, characterized in that: The control component includes one of a PID controller, a single chip microcomputer and a PLC controller.

9. The oligonucleotide synthesizer according to claim 8, characterized in that: It also includes a display component, the control component includes a PID controller, and the display component is electrically connected to the PID controller.

10. The oligonucleotide synthesizer according to any one of claims 1 to 9, characterized in that: The air pressure sensor is used to detect the air pressure data of the air intake chamber, and the control component is used to control the opening of the electric proportional valve according to the air pressure data of the air intake chamber; and / or The air pressure detection component is used to detect the air pressure data of the air intake chamber at preset time intervals, and the control component is used to calculate the air pressure drop rate of the air intake chamber based on the air pressure data at the preset time intervals. When the air pressure drop rate is less than the preset drop rate, the control component increases the opening of the electrical proportional valve.