Synthesizer with controllable reaction time, use method and oligonucleotide synthesis method

Abstract

The invention relates to a synthesizer with controllable reaction time, a use method thereof and an oligonucleotide synthesis method, a first cavity and a second cavity which are separated from each other are arranged in a machine body of the synthesizer with controllable reaction time, the machine body is also provided with a channel, a first air hole and a second air hole, the first cavity is communicated with the second cavity through the channel, and the second cavity is communicated with the second air hole through the channel. The channel is used for inserting a synthetic column, the first cavity is communicated with the outside through a first gas hole, the first gas hole is used for introducing non-reaction gas into the first cavity, the second cavity is communicated with the outside through a second gas hole, and the second gas hole is used for introducing the non-reaction gas into the second cavity or discharging the non-reaction gas out of the second cavity. According to the invention, the reaction between the reaction reagent and the synthesis carrier is more sufficient, and the reaction time is controllable, so that the yield and correctness of products obtained in each synthesis column are more uniform.

Description

Technical Field

[0001] The present invention relates to the technical field of oligonucleotides, and in particular to a synthesizer with controllable reaction time and a use method thereof, and a method for synthesizing oligonucleotides. Background Art

[0002] An oligonucleotide synthesizer is a device used to synthesize oligonucleotides. The synthetic products synthesized by the synthesizer have wide applications in gene therapy, gene sequencing, biorecognition and other fields.

[0003] At present, synthesis column is arranged in synthesizer and is used as the container of synthetic oligonucleotide, when synthesizing oligonucleotide, synthetic carrier can be arranged in synthesis column, then synthetic column is placed in synthesizer, and reaction reagent is added to the surface of synthetic carrier in synthesis column. After a period of time, reaction reagent easily flows out from below synthetic carrier under the joint action of gravity and surface tension, causes the contact area of ​​reaction reagent and synthetic carrier to reduce, thereby causes reaction reagent and synthetic carrier reaction insufficient. At present, only add excess reaction reagent, makes synthetic carrier be fully immersed in reaction reagent, and then can ensure that building-up reaction fully proceeds, but, this one side can waste a large amount of reaction reagent, on the other hand, the retention time of reaction reagent in synthesis column and the uniformity of reaction still depend on the property of synthetic carrier, and the time of building-up reaction is uncontrollable. Summary of the invention

[0004] Based on this, it is necessary to provide a synthesizer with controllable reaction time and a method for using the same, as well as a method for synthesizing oligonucleotides.

[0005] A synthesizer with controllable reaction time comprises a body, wherein a first cavity and a second cavity separated from each other are provided inside the body, and the body is further provided with a channel, a first air hole and a second air hole, wherein the first cavity is connected with the second cavity through the channel, and the channel is used for inserting a synthesis column, the first cavity is connected with the outside through the first air hole, and the first air hole is used for introducing or discharging non-reactive gas into the first cavity, and the second cavity is connected with the outside through the second air hole, and the second air hole is used for introducing or discharging non-reactive gas into the second cavity.

[0006] The above-mentioned synthesizer with controllable reaction time can achieve the following effects: 1) It can allow the reaction reagents and the synthetic carrier to fully react, thereby increasing the accuracy of the reaction product. 2) Excessive reaction reagents are no longer required to ensure the full progress of the reaction, thereby reducing the amount of reaction reagents used. 3) The requirements for the characteristics of the synthetic carrier retention reagents can be reduced, which is conducive to reducing the production difficulty of consumables for the upstream production of synthetic carriers. 4) Since the retention time of the reaction reagents in the synthetic column can be controlled to be consistent, it is relatively easy to obtain a final synthetic product with a uniform yield, avoiding problems such as a low final synthetic product yield or a high fragment error rate due to excessive differences in the flow rates of the reaction reagents, thereby improving the efficiency of oligonucleotide synthesis.

[0007] In one of the embodiments, it further includes a first valve body, which is disposed on the body near the first air hole, and the first valve body is used to flexibly open and close the first air hole.

[0008] In one of the embodiments, a second valve body is further included. The second valve body is disposed at a position of the body close to the second air hole, and the second valve body is used to flexibly open and close the second air hole.

[0009] In one embodiment, the second valve body includes a three-way valve, which has an air inlet, an exhaust port and a connecting port. The connecting port is connected to the second air hole, and the connecting port can be selectively connected to the air inlet or the exhaust port. The air inlet is also used to introduce non-reactive gas into the second cavity, and the exhaust port is also used to communicate with the outside to exhaust the non-reactive gas.

[0010] In one embodiment, the body includes a cover and a base, the second cavity is arranged inside the base, and the passage and the second air hole are opened in the base, the cover is detachably fastened to the base, and the first cavity is formed between the cover and the base, and the first air hole is opened in the cover.

[0011] In one embodiment, the first cavity is disposed above the second cavity.

[0012] In one of the embodiments, a synthetic column is further included, and the synthetic column is penetrated in the channel.

[0013] In one of the embodiments, the outer surface of the synthetic column is interference fit with the wall of the channel.

[0014] A method for using a synthesizer with controllable reaction time, comprising the synthesizer with controllable reaction time as in any of the above embodiments, comprising the following steps:

[0015] A synthesis column is inserted in the channel of the fuselage, wherein the synthesis column contains a synthesis carrier and a reaction reagent;

[0016] Closing the first air hole, and introducing a non-reactive gas into the second cavity through the second air hole, so that the gas pressure of the second cavity is greater than the gas pressure of the first cavity, thereby driving the reaction reagent to overcome the gravity and move toward the synthetic carrier;

[0017] Stop introducing non-reactive gas into the second air hole and introduce non-reactive gas into the first air hole, so that the gas pressure of the first cavity is greater than the gas pressure of the second cavity, thereby allowing the reaction reagent to be separated from the synthetic carrier.

[0018] A method for synthesizing an oligonucleotide comprises the following steps:

[0019] A synthesizer is provided, wherein a first cavity and a second cavity separated from each other are provided in a body of the synthesizer, and a channel is also provided in the body, and the first cavity is connected with the second cavity through the channel;

[0020] A synthesis column is inserted in the channel of the fuselage, wherein the synthesis column contains a synthesis carrier and a reaction reagent;

[0021] Extracting the gas from the first cavity or introducing a non-reactive gas into the second cavity, so that the gas pressure in the second cavity is greater than the gas pressure in the first cavity, thereby driving the reaction reagent to overcome gravity and move toward the synthetic carrier;

[0022] The gas in the second cavity is extracted or a non-reactive gas is introduced into the first cavity, so that the gas pressure in the first cavity is greater than the gas pressure in the second cavity, thereby allowing the reaction reagent to be separated from the synthetic carrier. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 A schematic diagram of the structure of a synthesizer with controllable reaction time in one embodiment;

[0024] Figure 2 for Figure 1 A schematic diagram of a synthesizer with controllable reaction time in an embodiment when a reaction reagent leaks out from below a synthesis carrier;

[0025] Figure 3 for Figure 1 A schematic diagram of a synthesizer with controllable reaction time in an embodiment of the present invention when a non-reactive gas is introduced from a second gas hole;

[0026] Figure 4 for Figure 1 A schematic diagram of a synthesizer with controllable reaction time in an embodiment of the present invention when a non-reactive gas is introduced from a first gas hole. DETAILED DESCRIPTION

[0027] In order to facilitate the understanding of the present invention, the present invention will be described more fully below with reference to the relevant drawings. The preferred embodiments of the present invention are given in the drawings. However, the present invention 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 disclosure of the present invention more thoroughly understood.

[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. The term "and / or" used herein includes any and all combinations of one or more related listed items.

[0029] like Figure 1As shown, in one embodiment, a synthesizer is provided, more specifically, a synthesizer 10 with controllable reaction time, including a body 100, wherein the body 100 is provided with a first cavity 101 and a second cavity 102 separated from each other, and the body 100 is further provided with a channel 103, a first air hole 104 and a second air hole 105, wherein the first cavity 101 is connected with the second cavity 102 through the channel 103, the first cavity 101 is connected with the outside through the first air hole 104, the first air hole 104 is used to introduce or discharge non-reactive gas into the first cavity 101, and the second cavity 102 is connected with the outside through the second air hole 105. 105 is connected to the outside, and the second air hole 105 is used to introduce non-reactive gas into the second cavity 102 or discharge non-reactive gas. Specifically, the second air hole 105 is used to introduce non-reactive gas into the second cavity 102 or discharge non-reactive gas from the second cavity 102, wherein, when the reaction reagent 410 needs to overcome the effect of gravity, the non-reactive gas is introduced into the second air hole 105 so that the air pressure of the second cavity 102 is greater than the air pressure of the first cavity 101, so that the gas in the second cavity 102 will squeeze the reaction reagent 410 to drive the reaction reagent 410 to overcome gravity and maintain the reaction reagent 410 in the synthetic carrier 420. When the reaction reagent 410 needs to be separated from the synthesis carrier 420, a non-reactive gas is introduced into the first air hole 104 so that the air pressure of the first cavity 101 is greater than the air pressure of the second cavity 102. In this way, the gas in the first cavity 101 will squeeze the reaction reagent 410, thereby driving the reaction reagent 410 to separate from the synthesis carrier 420. The channel 103 is used to insert the synthesis column 200. In this embodiment, the synthesizer 10 also includes a synthesis column 200, and the synthesis column 200 is penetrated in the channel 103. Among them, the synthesis column 200 is used to set the synthesis carrier 420 and the reaction reagent 410. In this embodiment, a synthetic carrier 420 and a reaction reagent 410 are provided in the synthetic column 200. Specifically, the synthetic column 200 is configured to be tubular. In this embodiment, the inner cross-section of the synthetic column gradually decreases from one end to the other end, so that the synthetic carrier can be stuck on the inner wall of the synthetic column. Specifically, the synthetic carrier 420 is fixed to the inner wall of the synthetic column 200. The reaction reagent 410 is added to the interior of the synthetic column 200 from the upper end of the synthetic column 200 and contacts with the synthetic carrier 420. Specifically, in this embodiment, the end of the synthetic column located in the first cavity is the upper end. In order to better allow the non-reactive gas to pass through the interior of the synthetic column 200, in one embodiment, the outer surface of the synthetic column is interference-fitted with the wall of the channel, so that the synthetic column can be better fixed, and after reducing the gap between the outer surface of the synthetic column and the wall of the channel, the non-reactive gas can better pass through the interior of the synthetic column.

[0030] Specifically, the non-reactive gas does not react with the reaction reagent and the synthetic carrier, so as not to interfere with the reaction, and can achieve the effect of driving the reaction reagent to move. In one embodiment, the non-reactive gas also does not react with the fuselage and the synthetic column, so as not to corrode the fuselage and the synthetic column. In one embodiment, the non-reactive gas includes an inert gas, which does not react with the reaction reagent and the synthetic carrier, can achieve the effect of driving the reaction reagent to move, and does not corrode the fuselage and the synthetic column, avoiding corrosion of the fuselage and the synthetic column.

[0031] Specifically, the synthesizer 10 is used to close the first pore 104 when the non-reactive gas is introduced into the second pore 105, so as to drive the reaction reagent 410 to overcome the gravity and move toward the synthesis carrier 420. In this embodiment, the first cavity 101 is arranged above the second cavity 102, and the channel 103 passes through the partition between the first cavity 101 and the second cavity 102 from the first cavity 101 to the second cavity 102. In one embodiment, after part of the non-reactive gas is introduced into the second pore, the second pore is closed to allow the reaction reagent to infiltrate the synthesis carrier and prevent the reaction reagent from overflowing from the top of the synthesis carrier.

[0032] Please also read Figures 1 to 4 The synthesizer 10 comprises the following steps when in use: Figure 1 and Figure 2 As shown, a synthesis column 200 is inserted into the channel 103 of the fuselage 100, wherein the synthesis column 200 contains a synthesis carrier 420 and a reaction reagent 410. Figure 3 As shown, the first air hole 104 is closed so that the air pressure in the second cavity is greater than the air pressure in the first cavity, thereby driving the reaction reagent 410 to overcome the gravity and move toward the synthetic carrier 420. In this way, the reaction reagent 410 can be prevented from flowing out from the bottom of the synthetic carrier 420 and the reaction reagent 410 can completely infiltrate the synthetic carrier 420 as much as possible, thereby allowing the reaction reagent 410 and the synthetic carrier 420 to react more fully. When there are multiple synthetic columns 200 arranged in the channel 103, it helps to make the contact area between the reaction reagent 410 and the synthetic carrier 420 in each synthetic column 200 close, so that the amount of reaction products in each synthetic column is close. Figure 4As shown, stop introducing non-reactive gas into the second air hole 105, and introduce non-reactive gas into the first air hole 104, so that the air pressure of the first cavity is greater than the air pressure of the second cavity, thereby allowing the reaction reagent 410 to detach from the synthetic carrier 420. In this way, the reaction reagent 410 that has reacted on the synthetic carrier 420 can be blown away, which is conducive to ending the reaction and facilitating the next step of the experiment. By controlling the non-reactive gas to enter the first air hole 104 or the second air hole 105, the relative air pressure of the first cavity 101 or the second cavity 102 can be changed, and the reaction reagent 410 can be maintained inside the synthetic carrier 420 or fall from the synthetic carrier 420, so as to better control the retention time of the reaction reagent 410 in the synthetic column 200. And the following effects are achieved: 1) The reaction reagent 410 and the synthetic carrier 420 can be fully reacted, increasing the accuracy of the reaction product. 2) No more excessive reaction reagent 410 is required to ensure the full progress of the reaction, reducing the amount of reaction reagent 410. 3) The requirements for the characteristics of the retention reagents of the synthetic carrier 420 can be reduced, which is conducive to reducing the difficulty of producing the consumables of the upstream synthetic carrier 420. 4) Since the retention time of the reaction reagent 410 in the synthetic column 200 can be controlled to be consistent, it is relatively easy to obtain a final synthetic product with a uniform yield, avoiding the problem of a low final synthetic product yield or a high fragment error rate caused by a large difference between the actual flow rate and the ideal flow rate of the reaction reagent 410, thereby improving the efficiency of oligonucleotide synthesis.

[0033] It is worth mentioning that the reaction reagent has a relatively ideal flow rate when reacting with the synthetic carrier. Compared with the relatively ideal flow rate, a flow rate of the reaction reagent that is too fast will result in a very low yield of the synthetic product, and a flow rate that is too slow will result in incomplete discharge of a single reagent, resulting in a high error rate of synthetic fragments, and even directly leading to failure of the experiment. Therefore, by controlling the relative air pressure of the first cavity and the second cavity, that is, using a gas-driven method to drive the movement of the reaction reagent to control the residence time of the reaction reagent passing through the synthetic carrier, it is easier to obtain a final synthetic product with uniform yield, avoid the problems of low yield of synthetic products and high error rate of fragments, and improve the efficiency of oligonucleotide synthesis.

[0034] In this embodiment, the body 100 includes a cover 110 and a base 120, the second cavity 102 is arranged inside the base 120, and the channel 103 and the second air hole 105 are opened in the base 120, the cover 110 is detachably buckled on the base 120, and the first cavity 101 is formed between the cover 110 and the base 120, and the first air hole 104 is opened in the cover 110. When the cover 110 is lifted, the synthetic column 200 can be inserted into the channel 103, and when the cover 110 is closed, the first cavity 101 can be formed above the synthetic column 200, and at this time, the first cavity 101 is connected with the second cavity 102 through the inside of the synthetic column 200. In this embodiment, there are multiple channels 103, and each channel 103 is used to set a corresponding synthetic column 200, so as to realize the processing of multiple synthetic columns 200. In this embodiment, the cover 110 is only provided with the first air hole 104, and the base 120 is only provided with the channel 103 and the second air hole 105, so that the airtightness of the first cavity 101 and the second cavity 102 can be increased during use, and the relative air pressure of the first cavity 101 and the second cavity 102 can be changed more easily. In this embodiment, the base includes a detachably connected partition and a base, and a second cavity is formed between the partition and the base, wherein the channel is provided in the partition, and the second air hole is provided in the base. In this embodiment, the partition is configured as a flat plate, and the base is provided with a receiving groove. The partition is buckled in the position of the base close to the receiving groove to close the receiving groove to form a second cavity, and the partition can be removed from the base to facilitate cleaning of the interior of the receiving groove.

[0035] In this embodiment, the synthesizer 10 further includes a first valve body 310, which is disposed at a position of the synthesizer 10 near the first air hole 104, and the first valve body 310 is used to movably open and close the first air hole 104, and the first valve body 310 is used to be connected to the first air intake mechanism, and the first valve is used to allow or prevent the non-reactive gas of the first air intake mechanism from passing through the first air hole 104. In one embodiment, the synthesizer further includes a first air intake mechanism, and the first air intake mechanism is connected to the first valve body to pass the non-reactive gas into the first cavity. In one embodiment, the first air intake mechanism includes a first non-reactive gas high-pressure tank, and the first non-reactive gas high-pressure tank can directly pass the non-reactive gas into the first air hole. In one embodiment, the first air intake mechanism includes a first pump assembly and a first non-reactive gas storage tank connected to each other, wherein the first pump assembly is connected to the first valve, and the first pump assembly can transport the gas of the first non-reactive gas storage tank to the first cavity, thereby enabling the box to supply gas to the first cavity.

[0036] In this embodiment, the synthesizer also includes a second valve body, which is arranged at a position of the synthesizer close to the second air hole, and the second valve body is used to movably open and close the second air hole. The second valve body is used to be connected to the second air intake mechanism, and the second valve is used to allow or prevent the non-reactive gas of the second air intake mechanism from passing through the second air hole to introduce the non-reactive gas into the second cavity.

[0037] In this embodiment, the second valve body includes a three-way valve 320, and the three-way valve 320 has an air inlet 321, an exhaust port 322 and a communication port 323 that are connected to each other. The communication port 323 is connected to the second air hole 105, and the communication port 323 can be selectively connected to the air inlet 321 or the exhaust port 322. The air inlet 321 is also used to introduce non-reactive gas into the second cavity 102, and the exhaust port 322 is also used to communicate with the outside to discharge non-reactive gas. Specifically, the three-way valve 320 has a valve core, and the valve core is used to control the communication port 323 to selectively communicate with the air inlet 321 and the exhaust port 322.

[0038] In one embodiment, the synthesizer further comprises a second air intake mechanism, which is connected to the second valve body. Specifically, the second air intake mechanism is connected to the three-way valve, and the interior of the second air intake mechanism is connected to the air inlet of the three-way valve to introduce non-reactive gas into the second cavity. In one embodiment, the second air intake mechanism comprises a second non-reactive gas high-pressure tank, which can directly introduce non-reactive gas into the second cavity. In one embodiment, the second air intake mechanism comprises a second pump assembly and a second non-reactive gas storage tank connected to each other, wherein the second pump assembly is connected to the three-way valve, and the second pump assembly can transport the gas of the second non-reactive gas storage tank to the second cavity, thereby realizing gas supply to the second cavity of the box.

[0039] In one embodiment, the first valve body and the second valve body are both configured as fluid valves. In one embodiment, the first valve body and the second valve body are both solenoid valves, and the synthesizer further includes a control component, which is used to control the opening and closing of the first valve and the second valve. In one embodiment, the synthesizer further includes an air pressure detection component, which is arranged on the body and is used to detect the air pressure of the first cavity and the second cavity. In one embodiment, the synthesizer further includes a receiving component, which is used to be electrically connected to the control component and the air pressure detection component, and the receiving component is used to receive the signal of the air pressure detection component, and the control component is used to control the opening and closing of the first valve body and the second valve body according to the signal of the air pressure detection component, thereby being able to more automatically complete the control of the air pressure. In one embodiment, the synthesizer further includes an interactive component, which is used to be electrically connected to the control component, so that the user can set the relative air pressure of the first cavity and the second cavity according to the interactive component, and the control component receives the information of the interactive component and controls the opening and closing of the first valve body and the second valve body. In one embodiment, the synthesizer further comprises a timing component, the timing component is electrically connected to the control component, the timing component is used to send time information to the control component, the control component is used to control the valve core of the three-way valve to switch the air inlet to the air outlet and communicate with the communication port according to the time information of the timing component and the time length set by the user, and control the first valve body to open, in this embodiment, the user sets the time length through the interactive component, so that the reaction reagent can be controlled to stay on the surface of the synthetic carrier when synthesizing oligonucleotides. In one embodiment, the control component is also used to control the opening degree of the air inlet of the three-way valve, that is, the control component is used to control the opening area of ​​the air inlet of the three-way valve, that is, the second valve body is used to flexibly open and close the second pore, and is used to control the opening area when opening the second pore to adjust the inlet amount of inert gas, that is, the opening area of ​​the air inlet of the second valve body is controllable, so that the reaction reagent can be controlled to completely stop and infiltrate the synthetic carrier, or the reaction reagent can be controlled to overcome a part of the gravity so that the reaction reagent falls slowly from the synthetic carrier, so that the reaction time of the reaction reagent and the synthetic carrier during the experiment can be more controllable according to the specific experimental conditions required.

[0040] More specifically, a method for using an oligonucleotide synthesizer, or a method for synthesizing an oligonucleotide, is provided, comprising the following steps:

[0041] like Figure 1 As shown, S1: open the cover 110, and set the synthesis column 200 at the channel 103 of the base 120, wherein the synthesis column 200 has a synthesis carrier 420 and a reaction reagent 410. Figure 2 As shown, after a certain period of time, the reaction reagent 410 leaks out from the bottom of the synthesis carrier 420 due to gravity. Figure 3As shown, S2: close the first air hole 104 through the first valve, and open the air inlet 321 of the three-way valve 320 to pass non-reactive gas into the second cavity 102 through the second air hole 105. At this time, the non-reactive gas entering the second air hole 105 will increase the air pressure of the second cavity 102, and maintain the air pressure of the second cavity 102 greater than the air pressure of the first cavity 101 to drive the reaction reagent 410 to overcome the gravity and move toward the synthetic carrier 420. The reaction reagent 410 is maintained inside the synthetic carrier 420, so that the reaction reagent 410 fully infiltrates the synthetic carrier 420. Figure 4 As shown, S3: drive the air inlet 321 of the three-way valve 320 to switch to the exhaust port 322, stop introducing non-reactive gas into the second air hole 105, and open the exhaust port 322, open the first valve and introduce non-reactive gas into the first air hole 104, so that the reaction reagent 410 is separated from the synthetic carrier 420. At this time, the non-reactive gas entering the first air hole 104 will push the waste liquid of the reaction reagent 410 to separate from the bottom of the synthetic carrier 420 to remove the waste liquid of the reaction reagent 410 in the synthetic carrier 420. By setting the first valve and the second valve, the entry or discharge of the non-reactive gas can be flexibly controlled, thereby achieving better infiltration of the reaction reagent 410 into the synthetic carrier 420, so that the condensation reaction between the reaction reagent 410 and the synthetic carrier 420 is more fully reacted, and the reaction time is controllable.

[0042] In one embodiment, a method for synthesizing an oligonucleotide is provided, comprising the following steps:

[0043] S1: A synthesizer is provided, wherein a first cavity and a second cavity separated from each other are provided in a body of the synthesizer, and the body is also provided with a channel, through which the first cavity is connected to the second cavity. The first cavity is located above the second cavity, and the channel is used to insert a synthesis column. In some embodiments, the synthesizer is implemented by using the synthesizer in any of the above embodiments.

[0044] S2: inserting a synthesis column at the channel of the fuselage, wherein the synthesis column contains a synthesis carrier and a reaction reagent. The synthesis column is inserted at the channel, and the reaction reagent is added into the synthesis column from one end of the synthesis column toward the first cavity.

[0045] S3: Extract the gas from the first cavity or introduce non-reactive gas into the second cavity, so that the gas pressure in the second cavity is greater than the gas pressure in the first cavity, thereby driving the reaction reagent to overcome gravity and move toward the direction close to the synthetic carrier. It can be understood that the upper and lower parts of the synthetic column are separated by the reaction reagent, and extracting the gas from the first cavity or introducing non-reactive gas into the second cavity can change the relative gas pressure between the first cavity and the second cavity, thereby changing the relative gas pressure between the upper and lower parts of the synthetic column, so that the gas pressure in the lower part of the synthetic column is greater than the gas pressure in the upper part of the synthetic column. Squeezed by the gas pressure in the lower part of the synthetic column, the reaction reagent overcomes gravity and moves toward the direction close to the synthetic carrier.

[0046] S4: extracting the gas from the second cavity or introducing a non-reactive gas into the first cavity, so that the gas pressure of the first cavity is greater than the gas pressure of the second cavity, thereby causing the reaction reagent to be separated from the synthetic carrier. In this way, the gas pressure of the upper part of the synthetic column can be greater than the gas pressure of the lower part, and the reaction reagent is squeezed by the gas pressure of the upper part of the synthetic column, and leaks out from the bottom of the synthetic carrier, thereby achieving the reaction reagent being separated from the synthetic carrier.

[0047] In one embodiment, a method for synthesizing oligonucleotides is provided. After a synthesis column is set on the body of a synthesizer, the gas in the first cavity is extracted so that the gas pressure in the second cavity is greater than the gas pressure in the first cavity, thereby driving the reaction reagent to overcome gravity and move toward the synthesis carrier. After the reaction between the reaction reagent and the synthesis carrier is completed, the gas in the second cavity is extracted until the gas pressure in the second cavity is lower than the gas pressure in the first cavity, so that the gas pressure in the first cavity is greater than the gas pressure in the second cavity, thereby causing the reaction reagent to be separated from the synthesis carrier. In this embodiment, the relative gas pressures of the first cavity and the second cavity are changed by extracting gas. After the gas is extracted, there is less gas that affects the reaction.

[0048] In one embodiment, a method for synthesizing oligonucleotides is provided. After a synthesis column is set on the body of a synthesizer, the gas in the first cavity is extracted so that the air pressure in the second cavity is greater than the air pressure in the first cavity, thereby driving the reaction reagent to overcome gravity and move toward the direction close to the synthesis carrier. After the reaction between the reaction reagent and the synthesis carrier is completed, a non-reactive gas is introduced into the first cavity so that the air pressure in the first cavity is greater than the air pressure in the second cavity, thereby causing the reaction reagent to be separated from the synthesis carrier. In this embodiment, only the air pressure in the first cavity is changed to change the relative air pressure between the first cavity and the second cavity. This can be achieved by only opening a first air hole in the first cavity of the synthesizer. The structure of the synthesizer is relatively simple. In order to facilitate the extraction and introduction of inert gas, the synthesizer is provided with a first air hole, and a three-way valve is provided at the first air hole. The inlet of the three-way valve is connected to the air intake mechanism, and the outlet is connected to the air pump to achieve the extraction of gas from the first cavity and the introduction of non-reactive gas into the first cavity.

[0049] In one embodiment, a method for synthesizing oligonucleotides is provided. After a synthesis column is set on the body of a synthesizer, a non-reactive gas is introduced into the second cavity so that the air pressure of the second cavity is greater than the air pressure of the first cavity, thereby driving the reaction reagent to overcome gravity and move toward the synthesis carrier. The gas in the second cavity is extracted so that the air pressure of the first cavity is greater than the air pressure of the second cavity, thereby causing the reaction reagent to detach from the synthesis carrier. In this embodiment, the air pressure of the second cavity is changed by introducing a non-reactive gas into the second cavity and the gas in the second cavity is extracted to change the air pressure of the second cavity, thereby changing the relative air pressure of the first cavity and the second cavity. This can be achieved by only opening a second air hole in the second cavity of the synthesizer, and the structure of the synthesizer is relatively simple.

[0050] 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.

[0051] 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. A synthesizer with controllable reaction time, comprising a body, characterized in that: The interior of the fuselage is provided with a first cavity and a second cavity separated from each other, and the fuselage is also provided with a channel, a first air hole and a second air hole. The first cavity is connected with the second cavity through the channel, and the channel is used to insert a synthetic column. The first cavity is connected with the outside through the first air hole, and the first air hole is used to introduce or discharge non-reactive gas into or discharge non-reactive gas into the first cavity. The second cavity is connected with the outside through the second air hole, and the second air hole is used to introduce non-reactive gas into or discharge non-reactive gas into the second cavity.

2. The synthesizer with controllable reaction time according to claim 1, characterized in that: It also includes a first valve body, which is arranged at a position of the body close to the first air hole, and the first valve body is used to flexibly open and close the first air hole.

3. The synthesizer with controllable reaction time according to claim 1, characterized in that: It also includes a second valve body, which is arranged at a position of the body close to the second air hole, and the second valve body is used for movably opening and closing the second air hole.

4. The synthesizer with controllable reaction time according to claim 3, characterized in that: The second valve body includes a three-way valve, which has an air inlet, an exhaust port and a connecting port. The connecting port is connected to the second air hole, and the connecting port can be selectively connected to the air inlet or the exhaust port. The air inlet is also used to introduce non-reactive gas into the second cavity, and the exhaust port is also used to communicate with the outside to exhaust the non-reactive gas.

5. The synthesizer with controllable reaction time according to claim 1, characterized in that: The body includes a cover and a base, the second cavity is arranged inside the base, and the passage and the second air hole are opened in the base, the cover is detachably buckled on the base, and the first cavity is formed between the cover and the base, and the first air hole is opened in the cover.

6. The synthesizer with controllable reaction time according to claim 1, characterized in that: The first cavity is disposed above the second cavity.

7. The synthesizer with controllable reaction time according to claim 1, characterized in that: It also includes a synthetic column, which is arranged in the channel.

8. The synthesizer with controllable reaction time according to claim 7, characterized in that: The outer surface of the synthetic column is interference-fitted with the wall of the channel.

9. A method for using a synthesizer with controllable reaction time, characterized in that: A synthesizer with controllable reaction time as claimed in any one of claims 1 to 8, comprising the following steps: A synthesis column is inserted in the channel of the fuselage, wherein the synthesis column contains a synthesis carrier and a reaction reagent; Closing the first air hole, and introducing a non-reactive gas into the second cavity through the second air hole, so that the gas pressure of the second cavity is greater than the gas pressure of the first cavity, thereby driving the reaction reagent to overcome gravity and move toward the synthetic carrier; Stop introducing non-reactive gas into the second pores and introduce non-reactive gas into the first pores, so that the gas pressure in the first cavity is greater than the gas pressure in the second cavity, thereby allowing the reaction reagent to be separated from the synthetic carrier.

10. A method for synthesizing an oligonucleotide, characterized in that: The steps include: A synthesizer is provided, wherein a first cavity and a second cavity separated from each other are provided in a body of the synthesizer, and a channel is also provided in the body, and the first cavity is connected with the second cavity through the channel; A synthesis column is inserted in the channel of the fuselage, wherein the synthesis column contains a synthesis carrier and a reaction reagent; Extracting the gas from the first cavity or introducing a non-reactive gas into the second cavity, so that the gas pressure in the second cavity is greater than the gas pressure in the first cavity, thereby driving the reaction reagent to overcome gravity and move toward the synthetic carrier; The gas in the second cavity is extracted or a non-reactive gas is introduced into the first cavity, so that the gas pressure in the first cavity is greater than the gas pressure in the second cavity, thereby allowing the reaction reagent to be separated from the synthetic carrier.

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