Synthesis device

Abstract

The object of the present invention is to provide a synthesis apparatus that can prevent a solution from remaining in a reaction vessel and suppress a decrease in the purity of the solution. [Solution] The system comprises a reaction vessel into which a solution is supplied, a drainage pipe for discharging the solution from the reaction vessel, a pressure reduction section for reducing the pressure inside the reaction vessel, and an exhaust pipe for discharging the volatile components of the solution that have evaporated in the reaction vessel as a result of the pressure reduction in the reaction vessel by the pressure reduction section, and the exhaust pipe is configured to be connected to the upper end of the reaction vessel.

Description

[Technical Field]

[0001] The present invention relates to a synthesis apparatus for chemically synthesizing a solution. [Background technology]

[0002] In synthesizers for chemically synthesizing proteins, peptides, polymers, nucleic acids, etc., chemical synthesis is performed by supplying multiple solutions (reagents) to a reaction vessel. For example, when synthesizing nucleic acids, multiple carriers (porous beads) are placed in the reaction vessel, and while solutions are sequentially supplied to this reaction vessel, processes such as detritylation, coupling, oxidation, and capping are repeatedly performed to successively extend bases onto the carriers.

[0003] 2, such a synthesis apparatus includes storage vessels 911 that store a plurality of types of solutions, a measuring mechanism 921 that measures the solutions, a reaction vessel 931 that stores carriers 932 and to which the solutions are supplied, a waste liquid tank 941 that stores the solutions discharged from the reaction vessels 931, and a pressurizing means 951 that supplies gas to the storage vessels 911, all of which are connected by piping. That is, the solutions pressurized from the selected storage vessels 911 by the pressure from the pressurizing means 951 are measured by the measuring mechanism 921 and sequentially supplied to the reaction vessels 931, thereby enabling chemical synthesis of the solutions and the carriers 932 in the reaction vessels 931.

[0004] Here, in the synthesis apparatus 900, the purity of the solution is important, and in order to prevent the solution previously used in the chemical synthesis in the reaction vessel 931 from mixing with the solution to be used next, a cleaning liquid is sent to the reaction vessel 931 and discharged into a waste liquid tank 941, thereby flushing the previously used solution from the reaction vessel 931 into the waste liquid tank 941 (for example, Patent Document 1). [Prior art documents] [Patent documents]

[0005] [Patent Document 1] Japanese Patent Application Laid-Open No. 2018-167161 Summary of the Invention [Problem to be solved by the invention]

[0006] However, in the synthesis apparatus 900, there have been cases where the purity of the solution in the reaction vessel 931 has decreased. Specifically, in the synthesis apparatus 900, since a large number of carriers 932 are accommodated in the reaction vessel 931, the flow path resistance of the carriers 932 makes it impossible to discharge all of the solution including the cleaning liquid from the reaction vessel 931, and the solution remains in the reaction vessel 931. As a result, there has been a problem in that the solution remaining in the reaction vessel 931 mixes with the solution to be used next, resulting in a decrease in the purity of the solution.

[0007] The present invention has been made in consideration of the above problems, and aims to provide a synthesis apparatus that can prevent solution from remaining in a reaction vessel and suppress a decrease in the purity of the solution. [Means for solving the problem]

[0008] In order to solve the above problems, the synthesis apparatus of the present invention comprises a reaction vessel to which a solution is supplied, a drainage pipe for discharging the solution from the reaction vessel, a pressure reduction section for reducing the pressure in the reaction vessel, and an exhaust pipe for discharging volatile components of the solution that have evaporated in the reaction vessel as a result of the pressure reduction in the reaction vessel by the pressure reduction section, and is characterized in that the exhaust pipe is connected to the upper end of the reaction vessel.

[0009] The synthesis apparatus described above is equipped with a pressure reduction unit, which allows removal of the solution remaining in the reaction vessel. That is, an exhaust pipe is connected to the upper end of the reaction vessel, and the solution remaining in the reaction vessel is volatilized by reducing the pressure of the reaction vessel using the pressure reduction unit. This allows the volatile components of the solution that volatilize in the reaction vessel and rise toward the upper end of the reaction vessel to be discharged into the exhaust pipe. This prevents the solution remaining in the reaction vessel from mixing with the solution to be used next. Therefore, it is possible to prevent the solution from remaining in the reaction vessel and suppress a decrease in the purity of the solution.

[0010] The reaction vessel may further include a liquid receiving tank for receiving the volatile components discharged from the reaction vessel through the exhaust piping, the pressure reducing section being connected to the liquid receiving tank, and the liquid receiving tank may be configured to receive the liquefied volatile components.

[0011] With this configuration, the liquid receiving tank receives the volatile components of the liquefied solution discharged from the reaction vessel through the exhaust pipe, and the liquid receiving tank acts as a buffer to reduce the amount of volatile components of the solution heading toward the pressure reducing section, thereby preventing breakdown of the pressure reducing section that may occur due to the volatile components of the solution flowing into the pressure reducing section.

[0012] Furthermore, a pressure reduction pipe that connects the pressure reduction section and the liquid receiving tank may be provided between the pressure reduction section and the liquid receiving tank, and the pressure reduction pipe may be provided with a collection section that collects the volatile components.

[0013] According to this configuration, the collection unit collects the volatile components of the solution flowing from the liquid receiving tank to the pressure reduction unit through the pressure reduction pipe, preventing the volatile components of the solution from flowing into the pressure reduction unit, thereby preventing breakdown of the pressure reduction unit that may occur due to the volatile components of the solution flowing into the pressure reduction unit.

[0014] Further, a cooling unit for cooling the liquid receiving tank may be provided.

[0015] According to this configuration, by cooling the liquid receiving tank with the cooling unit, the liquefaction of the volatile components of the solution floating in the liquid receiving tank can be promoted, and the amount of volatile components of the solution flowing from the liquid receiving tank to the pressure reduction unit through the pressure reduction pipe can be reduced, which makes it easier to prevent the volatile components of the solution from flowing into the pressure reduction unit.

[0016] The reactor may also be configured to include a heating unit for heating the reactor.

[0017] According to this configuration, the reaction vessel is heated by the heating unit, which can promote the evaporation of the solution remaining in the reaction vessel, thereby making it easier to prevent the solution from remaining in the reaction vessel. [Effects of the Invention]

[0018] According to the synthesis apparatus of the present invention, it is possible to prevent the solution from remaining in the reaction vessel and to suppress a decrease in the purity of the solution. [Brief explanation of the drawings]

[0019] [Figure 1] FIG. 1 is a schematic diagram showing a synthesis apparatus according to one embodiment of the present invention. [Figure 2] FIG. 1 is a diagram showing a conventional synthesis device. DETAILED DESCRIPTION OF THE INVENTION

[0020] An embodiment of a synthesis device according to the present invention will be described with reference to the drawings.

[0021] FIG. 1 is a schematic diagram illustrating a synthesis apparatus 100 according to one embodiment of the present invention.

[0022] As shown in FIG. 1, the synthesis apparatus 100 comprises a storage container 1 containing a solution (reagent), a metering mechanism 2 for metering the solution, a reaction container 3 containing a carrier (porous beads) 31, and a waste tank 4 for storing the solution discharged from the reaction container 3, all of which are connected by piping 5. The metering mechanism 2 measures the predetermined solution required for the reaction delivered from the storage container 1, and the metered solution is sequentially supplied to the reaction container 3, thereby repeatedly carrying out processes such as detritylation, coupling, oxidation, and capping, thereby successively extending the bases attached to the carrier 31. This produces synthetic products such as proteins, peptides, and nucleic acids. After the reaction is complete, the solution is discharged from the reaction container 3 to the waste tank 4.

[0023] The storage vessel 1 is for storing a solution used in chemical synthesis. A plurality of storage vessels 1 are provided to store each of the plurality of types of solutions required for the reaction in the reaction vessel 3, and although only four storage vessels 1 are shown in the example of FIG. 1, many storage vessels 1 are actually provided. Each storage vessel 1 is connected to the metering mechanism 2 by a pipe 51. That is, the solution stored in the storage vessel 1 is sent to the metering mechanism 2 through the pipe 51. Note that the pipes 51, 52, ... will be simply referred to as pipes 5 when there is no particular need to distinguish between them.

[0024] Furthermore, a pressurizing means (gas tank) 6 is connected to the storage container 1 via piping 52. When gas is supplied to the storage container 1 via piping 52 by this pressurizing means 6, the storage container 1 is pressurized and the solution is pressure-fed to the measuring mechanism 2 via piping 51. Each of the pipings 51 and 52 is provided with a valve 71, and by switching the open / close state of the valve 71, only the solution selected from the plurality of storage containers 1 is sent to the measuring mechanism 2. The gas supplied to the storage container 1 by the pressurizing means 6 is a gas that does not react with the solution stored in the storage container 1 (for example, an inert gas such as argon gas).

[0025] Furthermore, a weighing mechanism 2 is provided downstream of the storage container 1. The weighing mechanism 2 is for measuring the solution required for the reaction in the reaction container 3, and has a measuring container 21 that receives the solution sent from the storage container 1, and a load cell 22 that measures the solution in the measuring container 21. In other words, the solution stored in the measuring container 21 is measured by the load cell 22.

[0026] Pipe 51 is connected to the upper end of measuring container 21, and pipe 53 is connected to the lower end thereof, and measuring container 21 and reaction container 3 are connected by pipe 53. That is, the solution sent from storage container 1 is supplied to measuring container 21 through pipe 51, and the solution after being measured by load cell 22 is sent to reaction container 3 through pipe 53. This sending of the solution from measuring container 21 to reaction container 3 is performed by the aforementioned pressurizing means 6. That is, pressurizing means 6 is connected to measuring container 21 through pipe 54, and when gas is supplied from pressurizing means 6 to measuring container 21 through pipe 54, measuring container 21 is pressurized and the solution is pressure-fed to reaction container 3 through pipe 54.

[0027] A reaction vessel 3 is provided downstream of the metering mechanism 2. The reaction vessel 3 serves to provide a reaction field for chemically synthesizing the supplied solution. This reaction vessel 3 is a cylindrical tube extending in one direction, and contains a large number of carriers 31 inside. A pipe 53 is connected to the bottom end of the reaction vessel 3. When a solution is supplied to the reaction vessel 3 through the pipe 53, the solution and the carriers 31 are chemically synthesized inside the reaction vessel 3, and the base attached to the carrier 31 is elongated. As a result, a synthetic product is produced in the reaction vessel 3.

[0028] Pipe 53 is connected to pipe 55, which sends the solution to waste tank 4, via three-way valve 72. That is, the solution after the completion of the reaction is discharged from reaction vessel 3 to pipe 53 and sent to waste tank 4 via pipes 53 and 55. In the following explanation, pipes 53 and 55, which discharge the solution from reaction vessel 3 and send it to waste tank 4, are referred to as drain pipe 83. The solution is sent from reaction vessel 3 to waste tank 4 by the above-mentioned pressurizing means 6. That is, pipe 56, which is connected to pipe 54 by three-way valve 73, is connected to the upper end of reaction vessel 3. When gas is supplied from pressurizing means 6 to reaction vessel 3 via pipes 54 and 56, reaction vessel 3 is pressurized and the solution is pressure-sent to waste tank 4 via drain pipe 83.

[0029] Furthermore, a waste liquid tank 4 is provided downstream of the reaction vessel 3. The waste liquid tank 4 is for storing the solution discharged from the reaction vessel 3. The waste liquid tank 4 is formed to have a larger capacity than the reaction vessel 3, and is formed to have a capacity that can store the solution even if it is discharged from the reaction vessel 3 multiple times.

[0030] Furthermore, one of the storage containers 1 contains a cleaning liquid for cleaning the reaction container 3, and after the solution after the reaction is completed is discharged from the reaction container 3, the cleaning liquid is sent to the reaction container 3 to clean the inside of the reaction container 3. In other words, by sending the cleaning liquid to the reaction container 3 and discharging it into the waste liquid tank 4, the solution remaining in the reaction container 3 is flushed out of the reaction container 3 into the waste liquid tank 4.

[0031] The synthesis apparatus 100 in this embodiment further includes a pressure reduction unit 81 that reduces the pressure in the reaction vessel 3, and an exhaust pipe 82 that discharges the volatile components of the solution that have evaporated in the reaction vessel 3. The pressure reduction unit 81 is configured with a vacuum pump to promote evaporation of the remaining liquid in the reaction vessel 3 after the reaction vessel 3 has been drained, thereby preventing the solution from remaining in the reaction vessel 3. In this embodiment, the pressure reduction unit 81 is configured with a vacuum pump. By reducing the pressure in the reaction vessel 3 using the pressure reduction unit 81, the solution in the reaction vessel 3 is more easily volatilized. An exhaust pipe 82 is also connected to the reaction vessel 3, and the volatile components of the solution that have evaporated in the reaction vessel 3 can be discharged from the reaction vessel 3 through the exhaust pipe 82. The exhaust pipe 82 is connected to the upper end of the reaction vessel 3, and the volatile components of the solution that have evaporated in the reaction vessel 3 rise toward the upper end of the reaction vessel 3 and are discharged through the exhaust pipe 82.

[0032] When the reaction vessel 3 is washed with a washing solution after completion of the reaction, the flow path resistance of the numerous carriers 31 contained in the reaction vessel 3 makes it impossible to discharge all of the solution, including the washing solution, from the reaction vessel 3, and some of the solution remains in the reaction vessel 3. As a result, the solution remaining in the reaction vessel 3 mixes with the next solution, reducing the purity of the solution. In contrast, in the synthesis apparatus 100 of this embodiment, the pressure in the reaction vessel 3 is reduced by the pressure reduction unit 81, which makes it easier to volatilize the solution remaining in the reaction vessel 3 and discharges the volatile components of the volatilized solution into the exhaust pipe 82, thereby preventing the solution remaining in the reaction vessel 3 from mixing with the next solution to be used. Therefore, a decrease in the purity of the solution can be suppressed.

[0033] The synthesis apparatus 100 of this embodiment further includes a liquid receiving tank 84 that receives volatile components discharged through the exhaust pipe 82. The liquid receiving tank 84 is a sealed container formed with a capacity smaller than that of the waste liquid tank 4, and a pipe 57 connected to the three-way valve 73 is connected to its upper end. In the following description, the pipes 56 and 57 connected by the three-way valve 73 are referred to as the exhaust pipe 82. A pressure reducing unit 81 is connected to the liquid receiving tank 84. That is, the pressure reducing unit 81 reduces the pressure of the reaction vessel 3 via the liquid receiving tank 84 and the exhaust pipe 82, and the volatile components of the solution that have evaporated in the reaction vessel 3 are discharged to the liquid receiving tank 84 through the exhaust pipe 82. The liquid receiving tank 84 receives the volatile components of the solution that have liquefied therein. As a result, the liquid receiving tank 84 acts as a buffer to reduce the amount of volatile components of the solution that flow toward the pressure reducing unit 81, thereby preventing malfunction of the pressure reducing unit that may occur due to the volatile components of the solution flowing into the pressure reducing unit 81.

[0034] Here, because the liquid receiving tank 84 is formed to have a smaller capacity than the waste liquid tank 4, the output of the pressure reducing unit 81 required to reduce the pressure in the reaction vessel 3 can be made smaller than when the pressure reducing unit 81 is connected to the waste liquid tank 4 and the pressure in the reaction vessel 3 is reduced via the waste liquid tank 4. This allows the pressure reducing unit 81 to be made smaller, so that the pressure in the reaction vessel 3 can be reduced and the solution can be volatilized without increasing the size of the synthesis apparatus 100 as a whole.

[0035] Furthermore, a pipe 58 is connected to the lower end of the liquid receiving tank 84, and this pipe 58 connects the liquid receiving tank 84 to the waste liquid tank 4; that is, the volatile components of the liquefied solution received in the liquid receiving tank 84 are sent to the waste liquid tank 4 through the pipe 58. This liquid transfer from the liquid receiving tank 84 to the waste liquid tank 4 is performed by the pressurizing means 6 described above. That is, when gas is supplied from the pressurizing means 6 to the liquid receiving tank 84 through the pipes 54 and 57, the liquid receiving tank 84 is pressurized, and the volatile components of the liquefied solution are pressure-transferred to the waste liquid tank 4 through the pipe 58.

[0036] Furthermore, a decompression pipe 85 connecting the decompression unit 81 and the liquid receiving tank 84 is provided between the decompression unit 81 and the liquid receiving tank 84, and the liquid receiving tank 84 is decompressed via this decompression pipe 85, and the reaction vessel 3 is decompressed via the exhaust pipe 82. Here, the decompression pipe 85 is provided with a collector 86 that collects volatile components of the solution. The collector 86 is a cylindrical member filled with an adsorbent (not shown) (e.g., activated carbon or silica gel), and is configured to adsorb and collect the volatile components of the solution flowing from the liquid receiving tank 84 to the decompression unit 81 through the decompression pipe 85. This makes it possible to prevent the volatile components of the solution from flowing into the decompression unit 81, thereby preventing a breakdown of the decompression unit 81 that may occur due to the volatile components of the solution flowing into the decompression unit 81.

[0037] The synthesis apparatus 100 of this embodiment is also provided with a cooling unit 91 that cools the liquid receiving tank 84. The cooling unit 91 is configured, for example, with a Peltier element. By cooling the liquid receiving tank 84 with this cooling unit 91, it is possible to promote the liquefaction of volatile components of the solution floating in the liquid receiving tank 84. This reduces the amount of volatile components of the solution that flow from the liquid receiving tank 84 to the pressure reduction unit 81 through the pressure reduction piping 85, making it easier to prevent the volatile components of the solution from flowing into the pressure reduction unit 81. Furthermore, since the amount of volatile components of the solution that flow toward the collection unit 85 can be reduced, clogging of the collection unit 85 is less likely to occur. This reduces the frequency with which the collection unit 85 needs to be replaced.

[0038] The synthesis apparatus 100 in this embodiment is also provided with a heating unit 92 that heats the reaction vessel 3. The heating unit 92 is configured, for example, with a Peltier element. By heating the reaction vessel 3 with the heating unit 92, it is possible to promote the evaporation of the solution remaining in the reaction vessel 3. This makes it easier to prevent the solution from remaining in the reaction vessel 3.

[0039] As described above, the synthesis apparatus 100 in the above embodiment is equipped with the pressure reducing unit 81, and therefore, it is possible to remove the solution remaining in the reaction vessel 3. That is, the exhaust pipe 82 is connected to the upper end of the reaction vessel 3, and the pressure reducing unit 81 reduces the pressure in the reaction vessel 3 to volatilize the solution remaining in the reaction vessel 3, so that the volatile components of the solution that volatilize in the reaction vessel 3 and rise toward the upper end of the reaction vessel 3 can be discharged to the exhaust pipe 81. This makes it possible to prevent the solution remaining in the reaction vessel 3 from mixing with the solution to be used next. Therefore, it is possible to prevent the solution from remaining in the reaction vessel 3 and suppress a decrease in the purity of the solution.

[0040] The above describes in detail an embodiment of the present invention with reference to the drawings. However, the configurations and combinations thereof in the above embodiment are merely examples, and additions, omissions, substitutions, and other modifications of the configurations are possible within the scope that does not deviate from the spirit of the present invention. [Explanation of symbols]

[0041] 100 Synthesizer 1. Storage container 2 Measuring mechanism 3 Reaction vessel 4 Waste tank 5 Piping 6. Pressurizing means 71 Valve 72 Three-way valve 73 Three-way valve 81 Pressure reducing section 82 Exhaust piping 83 Drainage piping 84 Tank 85 Pressure reducing piping 86 Collection section 91 Cooling section 92 Heating section

Claims

1. a reaction vessel into which a solution is supplied; a drainage pipe for discharging the solution from the reaction vessel; a pressure reducing unit that reduces the pressure in the reaction vessel; an exhaust pipe for discharging volatile components of the solution volatilized in the reaction vessel by decompressing the reaction vessel with the decompression unit, The synthesis apparatus is characterized in that the exhaust pipe is connected to the upper end of the reaction vessel.

2. The apparatus further includes a liquid receiving tank for receiving the volatile components discharged from the reaction vessel through the exhaust pipe, The liquid receiving tank is connected to the pressure reducing unit, 2. The synthesis apparatus according to claim 1, wherein the liquid receiving tank receives the liquefied volatile component.

3. a pressure reducing pipe connecting the pressure reducing unit and the liquid receiving tank is provided between the pressure reducing unit and the liquid receiving tank, 3. The synthesis apparatus according to claim 2, wherein the decompression pipe is provided with a collection section for collecting the volatile components.

4. 4. The synthesis apparatus according to claim 2, further comprising a cooling unit for cooling the liquid receiving tank.

5. 4. The synthesis apparatus according to claim 1, further comprising a heating unit for heating the reaction vessel.

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