JP6914559B1 - Solid phase synthesizer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a solid-phase synthesizer capable of stirring a chemical solution and a resin charged in a reaction vessel so as not to reduce the reaction efficiency. SOLUTION: A reaction vessel 11 in which a resin R and a chemical solution L are charged to cause a solid-phase synthesis reaction on the surface of the resin to form a synthetic substance on the surface of the resin, and a resin and a chemical solution provided in the reaction vessel 11 are provided. It is provided with a stirring mechanism 31 for stirring the above. The stirring mechanism 31 extends in the vertical direction and is connected to a rotating shaft 60 in which forward rotation and inversion are alternately switched for each set angle, and is connected to the rotating shaft 60 in the direction of a plane orthogonal to the rotating shaft 60. Includes a stirring blade pair 61 consisting of a pair of arranged triangular column rods 61p and columnar rods 61q. The triangular prism rod 61p has an elongated shape having a triangular cross section, and the cylindrical prism rod 61q has an elongated shape formed above the triangular prism rod 61p and having a circular or elliptical cross section. Have. [Selection diagram] Fig. 3

Description

In the present invention, a medium-scale to large-scale chemical solution is put into a reaction vessel, a solid-phase synthesis reaction is caused on the surface of the resin to form a synthetic substance on the surface of the resin, and the chemical solution is drained by filtration. Regarding solid phase synthesizer.

A solid-phase synthesizer (for example, a peptide synthesizer) that uses a resin to cause a synthetic reaction on the surface of the resin is known. In this solid-phase synthesizer, a resin (beads, resin) and various chemicals as substances for a synthetic reaction are put into a reaction vessel to cause a synthetic reaction. After that, after the reaction is completed, the chemical solution is drained leaving the resin by filtration under pressure or reduced pressure.

When carrying out the synthesis reaction, in order to promote the reaction on the resin surface, a stirring mechanism is usually installed in the reaction vessel, and the reaction is appropriately stirred. As a reagent reaction device provided with a stirring mechanism, for example, one disclosed in Patent Document 1 is known. Patent Document 1 discloses that a flat plate-shaped stirrer is rotated in a horizontal direction with the surface of the stirrer upright to stir the liquid in a container. Further, Patent Document 2 discloses that a highly viscous fluid is agitated without generating a large wave or a vortex on the liquid surface by reciprocating a stirring blade having a triangular cross section.

Japanese Unexamined Patent Publication No. 8-196897 JP-A-2007-222711

However, when the chemical solution is administered to the resin compressed by filtration by pressurization or depressurization in the reaction vessel and stirred, the resin expands with air and becomes agglomerates and floats near the liquid surface. Therefore, when the flat plate-shaped stirrer is rotated as in Patent Document 1, the stirrer is well agitated around the stirrer. However, on the other hand, since the stirring force in the vertical direction is low, the resin lumps floating on the liquid surface cannot be broken when the capacity of the container is large. For this reason, the resin may adhere to the vicinity of the liquid surface of the chemical solution and form a lump, which causes a problem that the reaction efficiency is lowered.

On the other hand, if a tilted stirrer is used to increase the stirring force in the vertical direction, or if a stirrer is provided near the surface of the chemical solution to stir the resin and the chemical solution, a large wave is generated or the resin is squeezed. Rise may occur. Therefore, the resin may adhere to the side surface of the reaction vessel or to the ceiling surface. In such a case, the resin adhering to the side surface or the ceiling does not contribute to the reaction, which also causes a problem that the reaction efficiency is lowered.

When using a lab-scale reaction vessel with a production volume of several milliliters, shake or rotate the vessel itself, or administer a full-volume chemical solution to the vessel to cover not only the resin but also the side and ceiling surfaces. The above problem can be solved by applying a chemical solution as well. However, in the case of pre-manufacturing or plant level where the production amount exceeds several liters, it may be dangerous to rotate the container itself, which is not practical.

Further, as disclosed in Patent Document 2, the method of reciprocating and stirring the triangular blade has a high effect of suppressing the fluctuation of the liquid level. Compared with the flat plate-shaped stirring blade, the width and inclination angle of the stirring blade tend to be smaller, and it is necessary to increase the rotation speed in order to have a stirring force sufficient to sink the resin lumps floating on the liquid surface. However, in the field of chemical synthesis dealing with acids that corrode stainless steel, a fluorine-based coating is required for the sealing material of the stirring shaft and the stirring blade itself, so that high-speed rotation is not suitable in consideration of wear of the sealing material.

The present invention has been made to solve such a conventional problem, and an object of the present invention is to use a chemical solution and a resin charged in a medium- to large-scale reaction vessel for reaction efficiency. It is an object of the present invention to provide a solid phase synthesizer capable of stirring so as not to decrease.

In order to achieve the above object, in the present invention, a reaction vessel in which a resin and a chemical solution are charged to cause a solid phase synthesis reaction on the surface of the resin to form a synthetic substance on the surface of the resin, and a reaction vessel in the reaction vessel. The stirring mechanism is provided with a stirring mechanism for stirring the resin and the chemical solution, and the stirring mechanism extends in the vertical direction, and the rotation shaft is provided with a rotation shaft in which forward rotation and inversion are alternately switched for each set angle, and the rotation shaft. The first stirring blade includes a first stirring blade which is connected and arranged in a plane direction orthogonal to the rotation axis, and a stirring blade pair consisting of a pair of second stirring blades. , The second stirring blade has an elongated shape formed in a triangular shape, the second stirring blade is arranged above the first stirring blade, and the cross section is formed in a circular or elliptical shape. It is characterized by having a shape.

According to the present invention, it is possible to stir the chemical solution and the resin charged in the reaction vessel so as not to reduce the reaction efficiency.

FIG. 1 is a flow chart of a solid-phase synthesizer according to an embodiment of the present invention. 2A and 2B are flow charts of a container unit of the solid-phase synthesizer according to the embodiment of the present invention, in which FIG. 2A shows a first container unit and FIG. 2B shows a second container unit. FIG. 3 is a perspective view showing the configuration of the stirring mechanism according to the first embodiment. FIG. 4 is an explanatory view showing how the stirring mechanism according to the first embodiment stirs the material to be agitated in the reaction vessel. FIG. 5 is a perspective view showing the configuration of the stirring mechanism according to the second embodiment. FIG. 6 is an explanatory diagram showing how the stirring mechanism according to the second embodiment stirs the material to be agitated in the reaction vessel. FIG. 7 is a perspective view showing the configuration of the stirring mechanism according to the third embodiment. FIG. 8 is an explanatory view showing how the stirring mechanism according to the third embodiment stirs the material to be agitated in the reaction vessel. FIG. 9 is a perspective view showing the configuration of the stirring mechanism according to the fourth embodiment. FIG. 10 is an explanatory view showing how the stirring mechanism according to the fourth embodiment stirs the material to be agitated in the reaction vessel.

Hereinafter, embodiments of the present invention will be described with reference to the drawings.
[Explanation of the first embodiment]
1 and 2 are flow charts of the solid-phase synthesizer according to the present invention. As shown in FIGS. 1 and 2, the solid-phase synthesizer 100 prepares a reaction vessel 11 which is a container for performing a synthesis reaction and a chemical solution (a liquid containing reagents necessary for the reaction) supplied into the reaction vessel 11. It includes two measuring instruments for accumulating, that is, a first measuring instrument 12 and a second measuring instrument 13. Then, the reaction vessel 11 is filled with the granular resin to a certain height, and further, the chemical solution is added to carry out the synthesis reaction by the solid phase synthesis method. In this embodiment, two measuring instruments, the first measuring instrument 12 and the second measuring instrument 13, are described, but the number of measuring instruments is not limited to two. Further, the "resin" referred to in the present invention is a concept including a natural resin, a synthetic resin, and glass beads. Further, the reaction vessel 11 used in the solid-phase synthesizer 100 according to the present invention is assumed to be a pre-manufactured or plant-level solid-phase synthesizer having a production amount of 1 liter or more. That is, it is assumed that a medium-scale to large-scale reaction vessel 11 is used for the purpose of manufacturing rather than at the experimental level.

Further, as shown in FIGS. 2 (a) and 2 (b), the solid-phase synthesizer 100 is a first unit provided with a plurality of containers 24 for supplying desired chemical solutions to the measuring instruments 12 and 13. A container unit 21 and a second container unit 22 including a plurality of containers 25 are provided.

Each container 24 provided in the first container unit 21 is filled with various chemicals, and a plurality of pipes h1 serving as supply lines for supplying the chemicals from these containers 24 to the first measuring instrument 12 are provided. It is connected to one of a plurality of independently provided check valves u1. The "check valve" is a valve that allows the drug solution to flow toward one side and blocks the flow at the other side. The check valve is sometimes called a check valve. Therefore, the desired chemical solution among the chemical solutions filled in each container 24 can be supplied into the first measuring instrument 12 via the pipe h1 and the check valve u1.

Each container 25 provided in the second container unit 22 shown in FIG. 2 is filled with various chemicals in the same manner as the container 24 of the first container unit 21 described above. A plurality of pipes h2 serving as a supply line for supplying the chemical solution from each container 25 to the second measuring instrument 13 are independently connected to one of a plurality of check valves u2. Therefore, all the chemicals filled in each container 25 can be supplied to the second measuring instrument 13 via the independent pipe h2 and the check valve u2. The container 24 and the container 25 have almost the same functions, but the capacities may differ. For example, the capacity of the container 24 is 50 liters and the capacity of the container 25 is 15 liters.

Further, as shown in FIG. 1, a stirring mechanism 31 for stirring the chemical solution supplied into the reaction vessel 11 is provided inside the reaction vessel 11. The output shaft of the stirring mechanism 31 is connected to the motor M3, and its rotation is controlled by a driving device (not shown). Specifically, by repeating forward rotation and inversion of the motor M3, for example, at intervals of 90 °, the stirring mechanism 31 is rotated so as to reciprocate, and the chemical solution filled in the reaction vessel 11 is stirred. The detailed configuration of the stirring mechanism 31 will be described later.

A filter 34 for filtering impurities by pressurization or depressurization is provided on the lower surface of the reaction vessel 11. Further, the discharge pipe h3 is connected via the filter 34. The pipe h3 is connected to the pump P1 via a check valve u5 and an on-off valve v2. The pump P1 is, for example, a diaphragm type pump, and by operating the pump P1 to depressurize the bottom of the reaction vessel 11, the chemical solution filled in the reaction vessel 11 or the reaction vessel 11 is filled for cleaning. The cleaning liquid is discharged to the outside as waste liquid.

The on-off valve v2 described above is a normally closed type, and when opened, it is opened so as to flow in the direction shown in black. The same applies to the on-off valves v1, v3, v4, v7 to v12, and v21 shown below.

A pipe h4 for supplying a compressed gas (for example, an inert gas such as nitrogen) for creating a positive pressure (positive pressure) in the reaction vessel 11 is connected to the upper surface of the reaction vessel 11. The pipe h4 is provided with an on-off valve v11, and the compressed gas supplied from the direction indicated by reference numeral x3 is supplied into the reaction vessel 11 via the on-off valve v11. Then, the inside of the reaction vessel 11 can be made positive pressure.

Further, on the upper surface of the reaction vessel 11, a pipe h5 for exhausting the gas existing in the reaction vessel 11 to the outside is provided, and the pipe h5 communicates with the outside via an on-off valve v12. .. Further, a safety valve s3 is provided in parallel with the on-off valve v12. After the chemical solution is supplied into the reaction vessel 11, the on-off valve v12 is opened before the synthesis reaction is performed or during the synthesis reaction to enter the space on the liquid surface in the reaction vessel 11. Exhaust the filled gas. Further, when the pressure in the reaction vessel 11 becomes excessive, the safety valve s3 is opened to avoid an abnormal increase in pressure.

Further, a pipe h10 provided with an on-off valve v1 is connected to the upper surface of the reaction vessel 11. The end of the pipe h10 is connected to a cleaning liquid container (not shown), and the cleaning liquid is supplied into the reaction vessel 11 via the pipe h10. That is, by controlling the opening and closing of the on-off valve v1, it is possible to control the supply and stop of the cleaning liquid into the reaction vessel 11.

Further, the first measuring instrument 12 is provided with a stirrer 32 for stirring the chemical solution supplied to the first measuring instrument 12. The stirrer 32 can be rotationally driven by a motor M2 connected to the output shaft. The stirrer 32 may be rotated in a certain direction, or may be repeatedly rotated forward and backward at 90 ° angles.

At the bottom of the first measuring instrument 12, an on-off valve v3 for discharging the chemical solution introduced into the first measuring instrument 12 is provided. Further, on the output side of the on-off valve v3, a three-way valve v5 for branching the output side into two systems is provided, one of which is connected to the reaction vessel 11 and the other branch path is , It is connected to the waste liquid piping via the check valve u6. That is, by controlling the opening and closing of the three-way valve v5, the chemical solution released via the on-off valve v3 can be supplied to the reaction vessel 11 or discharged as a waste liquid.

Further, a pipe h6 for supplying a compressed gas (for example, nitrogen gas) for making the inside of the first measuring instrument 12 a positive pressure is connected to the upper surface of the first measuring instrument 12. An on-off valve v9 is provided in the pipe h6, and compressed gas is supplied from the direction indicated by reference numeral x4 and is supplied into the first measuring instrument 12 via the on-off valve v9. By supplying the compressed gas, the inside of the first measuring instrument 12 can be maintained at a positive pressure.

Further, a pipe h7 for exhausting the gas generated in the first measuring instrument 12 to the outside is provided on the upper surface of the first measuring instrument 12, and the pipe h7 is provided to the outside via an on-off valve v7. Communicating. Further, a safety valve s1 is provided in parallel with the on-off valve v7. Therefore, by controlling the opening and closing of the on-off valve v7, the gas filled in the first measuring instrument 12 can be discharged to the outside. Further, when the pressure in the first measuring instrument 12 becomes excessive, the safety valve s1 is opened to avoid an abnormal increase in pressure in the first measuring instrument 12.

Further, a check valve u3 is provided on the inlet side of the check valve u1 connected to the pipe h1. The outlet side of the check valve u3 is connected to the inlet side of the check valve u1. Then, the compressed gas is supplied to the inlet side of the check valve u3 from the direction indicated by reference numeral x5. Therefore, by supplying the compressed gas from the direction indicated by the reference numeral x5, the chemical solution filled in the container connected to the pipe h1 (the container 24 provided in the first container unit 21 shown in FIG. 2A) is filled. It can be sucked and supplied into the first measuring instrument 12.

Similar to the first measuring instrument 12 described above, the second measuring instrument 13 is also provided with a stirrer 33 for stirring the chemical solution supplied to the second measuring instrument 13, and is connected to the output shaft of the stirrer 33. It can be driven to rotate by the motor M1.

At the bottom of the second measuring instrument 13, an on-off valve v4 for discharging the chemical solution introduced into the second measuring instrument 13 is provided. Further, on the output side of the on-off valve v4, a three-way valve v6 for branching the output side into two systems is provided. One of the branch paths is connected to the reaction vessel 11, and the other branch path is connected to the waste liquid piping via the check valve u7. That is, by controlling the opening and closing of the three-way valve v6, the chemical solution released via the on-off valve v4 can be supplied to the reaction vessel 11 or discharged as a waste liquid.

Further, a pipe h8 for supplying a compressed gas (for example, nitrogen gas) for making the inside of the second measuring instrument 13 a positive pressure is connected to the upper surface of the second measuring instrument 13. An on-off valve v10 is provided in the pipe h8, and compressed gas is supplied from the direction indicated by reference numeral x2 and is supplied into the second measuring instrument 13 via the on-off valve v10. By supplying the compressed gas, the inside of the second measuring instrument 13 can be maintained at a positive pressure.

Further, a pipe h9 for exhausting the gas generated in the measuring instrument 13 to the outside is provided on the upper surface of the second measuring instrument 13, and the pipe h9 communicates with the outside via an on-off valve v8. ing. Further, a safety valve s2 is provided in parallel with the on-off valve v8. Therefore, by controlling the opening and closing of the on-off valve v8, the gas filled in the second measuring instrument 13 can be discharged to the outside. Further, when the pressure in the second measuring instrument 13 becomes excessive, the safety valve s2 is opened to avoid an abnormal increase in pressure in the second measuring instrument 13.

Further, a check valve u4 is provided on the inlet side of the check valve u2 connected to the pipe h2. The outlet side of the check valve u4 is connected to the inlet side of the check valve u2. Then, the compressed gas is supplied to the inlet side of the check valve u4 from the direction indicated by reference numeral x1. Therefore, by supplying the compressed gas from the direction indicated by the reference numeral x1, the chemical solution filled in the container connected to the pipe h2 (the container 25 provided in the second container unit 22 shown in FIG. 2B) is filled. It can be sucked and supplied into the second measuring instrument 13.

On the other hand, the plurality of containers 24 provided in the first container unit 21 shown in FIG. 2A have an overall sealed shape, and various chemical solutions (various chemicals to be supplied to the first measuring instrument 12) are contained therein. A chemical solution for carrying out a synthetic reaction) is accumulated.

At the bottom of the container 24, the tip of the pipe h1 which serves as a supply line for the chemical solution is introduced. Further, a pipe h22 provided with an on-off valve v21 is connected to the upper surface of the container 24, and by opening the on-off valve v21, the gas filled in the container 24 can be discharged to the outside.

Further, a pipe h21 is connected to the upper surface of the container 24, and one end of the pipe h21 is connected to the output side of the three-way valve v22. One input side of the three-way valve v22 is supplied with compressed gas from the direction of reference numeral x11, and the other input side is supplied with compressed gas from the direction of reference numeral x12. The output side of the three-way valve v22 is connected to the container 24 via the check valve u21. The compressed gas supplied from the direction of reference numeral x12 is a gas for maintaining the inside of the container 24 at a positive pressure, and the compressed gas supplied from the direction of reference numeral x11 adds a chemical solution filled in the container 24. It is a gas to be compressed and sent out from the pipe h1. That is, by controlling the opening and closing of the three-way valve v22, it is possible to switch between sending and stopping the chemical solution filled in the container 24.

Further, the plurality of containers 25 provided in the second container unit 22 shown in FIG. 2B also have the same configuration as the container 24 shown in FIG. 2A. Detailed description will be omitted. However, the containers 24 provided in the first container unit 21 and the containers 25 provided in the second container unit 22 may have different capacities. For example, the container 24 is 50 liters and the container 25 is 15 liters.

Returning to FIG. 1, the solid-phase synthesizer 100 according to the present embodiment includes a control device 41. The control device 41 controls the rotation of the motors M1, M2, and M3. It also controls the opening and closing of the above-mentioned on-off valves v1, v2, v3, v4, v7 to v12, and v21. Further, the switching of the three-way valves v5, v6 and v22 is controlled. The control device 41 can be configured as, for example, an integrated computer including a central processing unit (CPU) and storage means such as a RAM, a ROM, and a hard disk.

[Explanation of the stirring mechanism according to the first embodiment]
Next, the detailed configuration of the stirring mechanism 31 will be described. FIG. 3 is a perspective view showing the configuration of the stirring mechanism 31, and FIG. 4 is an explanatory view showing how the stirring mechanism 31 stirs the object to be agitated J in the reaction vessel 11.

As shown in FIG. 3, the stirring mechanism 31 includes a rotating shaft 60 and a stirring blade pair 61. The rotation shaft 60 extends in the vertical direction with respect to the reaction vessel 11 (see FIG. 4), and the upper end thereof is connected to the output shaft of the motor M3 shown in FIG. The rotation shaft 60 forms a columnar body having a circular cross section, and can be rotated by switching between forward rotation and reverse rotation by the motor M3.

The stirring blade pair 61 includes a triangular prism rod 61p (first stirring blade) and a cylindrical rod 61q (second stirring blade). The triangular prism rod 61p and the cylinder rod 61q are formed of a material obtained by coating a metal with a fluororesin or a processed product of a fluororesin. It is desirable to use a processed fluororesin product because there is no concern about coating deterioration and the price is low.

The triangular prism rod 61p has a columnar structure having a regular triangular cross section, and is provided at a position at a predetermined height from the bottom 60s of the rotating shaft 60. Further, a cylindrical rod 61q (second stirring blade) having a circular cross section is provided at a position above the triangular prism rod 61p and at a position slightly separated from the triangular prism rod 61p (for example, 30 mm). ing.

The triangular prism rod 61p and the cylinder rod 61q are installed so as to face in the direction of a plane orthogonal to the rotation axis 60. Further, in the direction of this plane, the triangular prism rod 61p and the cylinder rod 61q are arranged orthogonally to each other. Further, the triangular prism rod 61p is arranged so that the apex of the triangle in the cross section faces upward (convex upward). The present invention shows an example in which the triangular prism rod 61p and the cylinder rod 61q are arranged orthogonally, but the present invention is not limited to this, and the angle may be in the range of 0 ° to 90 °. can.

Further, as shown in FIG. 3, the triangular prism rod 61p has two prisms p1 and p2, and each of the prisms p1 and p2 is provided with flange portions f1 and f2, and the flange portions f1 and p2 are provided with flange portions f1 and f2. Bolt holes are bored in each of f2. The triangular prism rod 61p can be fixed to a desired height of the rotation shaft 60 by inserting and fixing the bolts k1 and k2 into the bolt holes in a state where the flange portions f1 and f2 are butted against each other. .. Further, by making the cross-sectional shape of the rotating shaft 60 a partially cut circular shape (not shown), it is possible to prevent the triangular prism rod 61p from idling with respect to the rotating shaft 60.

The columnar rod 61q also has two columnar bodies q1 and q2 as in the case of the triangular prismatic rod 61p described above, and the columnar bodies q1 and q2 are provided with flange portions f3 and f4, and the flange portions f3, respectively. A bolt hole is bored in f4. The cylindrical rod 61q can be fixed to a desired height of the rotation shaft 60 by inserting and fixing the bolts k3 and k4 into the bolt holes in a state where the flange portions f3 and f4 are butted against each other. .. Further, by making the cross-sectional shape of the rotating shaft 60 a partially cut circular shape (not shown), it is possible to prevent the cylindrical rod 61q from idling with respect to the rotating shaft 60.

FIG. 4 is an explanatory view showing a state in which the stirring blade pair 61 is inserted into the reaction vessel 11 in which the resin R and the chemical solution L are inserted. As shown in FIG. 4, a particulate resin R for causing a synthetic reaction is inserted in the reaction vessel 11. Then, the synthesis reaction is carried out by operating the stirring mechanism 31 with the two types of chemical solutions L inserted in the reaction vessel 11. Hereinafter, the resin R and the chemical solution L will be collectively referred to as the agitated substance J.

As described above, since the triangular prism rod 61p and the cylinder rod 61q can be attached to and detached from the rotating shaft 60, the triangular prism rod 61p and the cylinder rod 61q are based on the height of the liquid level of the object to be agitated J. Set the mounting position. Specifically, the cylindrical rod 61q is fixed to the rotation shaft 60 so that the cylindrical rod 61q is located at a height about 30 mm below the liquid level. Further, the triangular prism rod 61p is fixed at a position below the cylinder rod 61q at an angle of 90 °.

[Explanation of operation and effect of the first embodiment]
Next, the operation and effect of the solid-phase synthesizer 100 according to the first embodiment will be described. When solid-phase synthesis such as peptide synthesis is carried out by the solid-phase synthesizer 100 according to the present embodiment, the resin R is put into the reaction vessel 11 in advance. Further, the chemical solution required for solid-phase synthesis is selected from the first and second container units 21 and 22 shown in FIGS. 2 (a) and 2 (b). The required amount of the chemical solution corresponding to the required amount is supplied from the containers 24 and 25 containing the selected chemical solution to the first measuring instrument 12 and the second measuring instrument 13. Then, the chemical solution measured by the first measuring instrument 12 and the second measuring instrument 13 is introduced into the reaction vessel 11. The chemical solution is not limited to two types, and three or more types of chemical solutions may be introduced. The reaction vessel 11 is filled with two types of chemicals L and resin R.

As described above, the cylindrical rod 61q of the stirring blade pair 61 is located at a height below the upper surface of the object to be agitated J by a slight distance (for example, 30 mm). That is, the cylindrical rod 61q (second stirring blade) is arranged so as to be located near the liquid level in the reaction vessel 11. Further, a triangular prism rod 61p is arranged below the cylinder rod 61q.

In this state, the motor M3 is rotated under the control of the control device 41 to rotationally drive the stirring blade pair 61 to stir the agitated object J. At this time, the stirring blade pair 61 is subjected to reciprocating rotation at a low speed (for example, at a speed of 200 rpm or less) and changing the rotation direction at predetermined set angles (for example, every 90 °). The object J to be agitated is agitated by the reciprocating rotation of the triangular prism rod 61p, a solid-phase synthesis reaction with the chemical solution L occurs, and a synthetic substance is formed on the surface of the resin R.

Further, as described above, the triangles in the cross section of the triangular prism rod 61p are arranged so as to be convex upward. Therefore, when the triangular prism rod 61p reciprocates, the agitated object J is scraped upward by the side surface of the triangular prism rod 61p. Therefore, the agitated material J stagnant below the reaction vessel 11 can be scraped up upward, and the agitated material J in the entire reaction vessel 11 can be agitated.

As a result, the solid-phase synthesis reaction can be promoted. Further, since the rotation speed of the rotation shaft 60 is low (for example, 200 rpm or less) and the rotation shaft 60 reciprocates at each set angle, it is possible to prevent the agitated object J from scattering to the surroundings. Therefore, it is possible to prevent the object to be agitated J from adhering to the wall surface or ceiling of the reaction vessel 11 and suppress a decrease in reaction efficiency. Further, it is possible to prevent the resin R from being damaged.

Further, since the shaft seal for sealing the rotating shaft 60 needs to be made of a material having chemical resistance, a normal metal bearing cannot be used. Therefore, it is difficult to increase the strength. In the present embodiment, since the rotating shaft 60 is reciprocated at a low speed, deterioration of the shaft seal can be suppressed.

On the other hand, when the triangular prism rod 61p rotates at a low speed and reciprocates, the resins R in the reaction vessel 11 may adhere to each other to form a lump. In such a case, the resin R and the chemical solution L do not come into contact with each other efficiently, and the solid-phase synthesis reaction is not promoted. In the present embodiment, the cylindrical rod 61q is arranged at a position slightly lower than the liquid level of the object to be agitated J, and is rotated by the rotation shaft 60 in conjunction with the triangular prism rod 61p. As a result, the lump of resin R is crushed.

The cylindrical rod 61q having a circular or elliptical cross section has a smaller width in the height direction than the above-mentioned triangular prism rod 61p, and the force for scraping the liquid from the cross-sectional shape is low, so that the liquid in the reaction vessel 11 is liquid. It is difficult to generate waves even if it is rotated near the surface. Therefore, the agitated object J can be agitated while preventing the resin R from rising, and the lump of the resin R can be crushed. As a result, it is possible to prevent the formation of lumps of the resin R, and it is possible to promote the solid-phase synthesis reaction.

That is, when only the triangular prism rod 61p is rotated (when the cylindrical prism rod 61q is not provided), it is difficult to increase the rotation speed in order to prevent the sealing material from being worn, as described above. In order to increase the rotation speed, it is necessary to install the triangular prism rod 61p at a position deep to some extent from the liquid surface, but in this case, there arises a problem that the stirring efficiency is lowered. In the present embodiment, by using the stirring blade pair 61 provided with the triangular prism rod 61p and the cylinder rod 61q, it is possible to solve the above problems, improve the stirring efficiency, and promote the synthesis reaction.

Further, in the present embodiment, the triangular prism rod 61p and the cylinder rod 61q are arranged at a predetermined angle on a plane orthogonal to the rotation axis 60. In other words, the triangular prism rod 61p and the cylinder rod 61q do not face in the same direction. Therefore, it is possible to prevent the effect of stirring by the triangular prism rod 61p and the effect of crushing the lump of resin R by the cylindrical rod 61q from interfering with each other, efficiently agitate the object to be agitated J, and form the lump of resin R. It becomes possible to crush efficiently.

Further, in the present embodiment, the triangular prism rod 61p and the cylinder rod 61q are detachably attached to the rotating shaft 60. That is, the triangular prism rod 61p and the cylindrical rod 61q provided on the stirring blade pair 61 can be removed from the rotating shaft 60 by loosening the bolts k1 to k4 shown in FIG. Depending on the situation, the height of the stirring blade pair 61 can be adjusted to an appropriate height. Therefore, even if the height of the liquid level differs due to a difference in the amount of synthetic resin or the like, it is possible to flexibly deal with it.

Further, the rotation shaft 60 is alternately switched between forward rotation and reverse rotation at predetermined set angles set to, for example, 90 ° or less. When the rotating shaft 60 rotates in the normal direction, the surrounding resin R and the chemical solution enter the space formed in the passing portion of the triangular prism rod 61p, so that the torque when reversing the rotating shaft 60 can be reduced. Become. Therefore, the compressive stress acting on the resin R is reduced, and damage to the resin R can be prevented. Further, the motor M3 for rotating the rotation shaft 60 can be miniaturized.

Further, since the vertical width of the cylindrical rod 61q is smaller than the vertical width of the triangular prism rod 61p, the rotation of the cylindrical rod 61q causes a large wave to be generated and the resin to rise. Can be prevented.

Further, since the cylindrical rod 61q and the triangular prism rod 61p are formed of a material coated with a metallic fluororesin or a processed product of a fluororesin, it is possible to improve chemical resistance.

In addition, in the example shown in FIGS. The direction of may be any direction. Further, the cross-sectional shape is not limited to an equilateral triangle, and may be an isosceles triangle or an isosceles triangle.

[Explanation of the second embodiment]
Next, the second embodiment of the present invention will be described. In the second embodiment, only the configuration of the stirring mechanism is different from that of the first embodiment described above, and the other configurations are the same. Therefore, the configuration of the stirring mechanism will be described below.

FIG. 5 is a perspective view showing the configuration of the stirring mechanism 31a according to the second embodiment, and FIG. 6 is an explanatory view showing how the stirring mechanism 31a stirs the agitated object J in the reaction vessel 11.

As shown in FIG. 5, the stirring mechanism 31a according to the second embodiment is provided with a cross-shaped stirring blade 62 below the rotation shaft 60 in addition to the stirring blade pair 61 shown in FIG. It is different.

Specifically, the cross-shaped stirring blade 62 is provided in the vicinity of the bottom 60s of the rotating shaft 60 (for example, at a position 30 mm above the bottom 60s). The cross-shaped stirring blade 62 is composed of two triangular prisms 62a and 62b that intersect each other at right angles on a plane orthogonal to the rotation axis 60. Further, the triangular prisms 62a and 62b are arranged so that the vertices of the triangles in the cross section face downward (convex downward). The cross-shaped stirring blade 62 is also made of a material obtained by coating a metal with a fluororesin or a processed product of a fluororesin, similarly to the triangular prism rod 61p and the cylinder rod 61q described above.

Further, the cross-shaped stirring blade 62 is fixed to the rotating shaft 60 by welding or the like. Since the cross-shaped stirring blade 62 rotates near the bottom in the reaction vessel 11, the compressed resin is stirred. Therefore, a load larger than that of the triangular prism rod 61p and the cylinder rod 61q described above acts on the cross-shaped stirring blade 62. Therefore, by fixing the cross-shaped stirring blade 62 to the rotating shaft 60 by welding or the like, it is possible to prevent the cross-shaped stirring blade 62 from idling with respect to the rotating shaft 60 and to prevent the rotating shaft 60 from swinging. do.

On the other hand, since the above-mentioned triangular prism rod 61p and cylinder rod 61q are in a low-viscosity slurry state in which the resin R and the chemical solution L are mixed to some extent, the load acting on the triangular prism rod 61p and the cylinder rod 61q during rotation is small. Therefore, even if the bolting method is adopted, it does not run idle.

If the problem of idling does not occur, the cross-shaped stirring blade 62 can be attached to and detached from the rotating shaft 60 by using a flange and a bolt, similarly to the triangular prism rod 61p and the cylindrical rod 61q described above. It can also be attached.

The cross-shaped stirring blade 62 reciprocates at a low speed by the rotating shaft 60 and at a predetermined set angle (for example, 90 °).

[Explanation of operation and effect of the second embodiment]
Next, the action and effect of the stirring mechanism 31a according to the second embodiment will be described. The stirring blade pair 61 operates in the same manner as in the first embodiment described above. That is, the triangular prism rod 61p reciprocates at a predetermined set angle to agitate the object to be agitated J in the reaction vessel 11 and promote the synthesis reaction. Further, the cylindrical rod 61q reciprocates to crush the lump of the resin R.

In addition to this, in the second embodiment, the cross-shaped stirring blade 62 reciprocates to agitate the object to be agitated J in the lower part of the reaction vessel 11. As a result, the inside of the reaction vessel 11 can be stirred more efficiently, and the solid-phase synthesis reaction can be further promoted.

That is, in the second embodiment, the rotating shaft 60 is arranged below the stirring blade pair 61 in the direction of the plane orthogonal to the rotating shaft 60, and has a long shape having a triangular cross section. A cross-shaped stirring blade 62 (third stirring blade) having (in this example, a cross shape) is provided. Therefore, it is possible to scrape the agitated material J stagnant below the reaction vessel 11 upward to promote the synthesis reaction.

Further, since the cross-shaped stirring blade 62 has a triangular shape whose cross-sectional shape is convex downward, by rotating the cross-shaped stirring blade 62, the object to be agitated J is sent downward and inside the reaction vessel 11. It becomes possible to uniformly agitate the object to be agitated J staying at the bottom of the agitated object J.

In the example shown in FIG. 5, an example in which the third stirring blade has a cross shape has been described, but the present invention is not limited to this, and a single stirring blade having a long shape is used. It is also possible.

[Explanation of Third Embodiment]
Next, a third embodiment of the present invention will be described. FIG. 7 is a perspective view showing the configuration of the stirring mechanism 31b according to the third embodiment, and FIG. 8 is an explanatory view showing how the stirring mechanism 31b stirs the agitated object J in the reaction vessel 11. In the third embodiment, only the configuration of the stirring mechanism is different from that of the second embodiment described above, and the other configurations are the same.

As shown in FIG. 7, in the stirring mechanism 31b according to the third embodiment, in addition to the stirring blade pair 61 and the cross-shaped stirring blade 62 shown in FIG. 5, a triangular prism rod 63 having a triangular cross section is mounted. It differs in that it is.

The triangular prism rod 63 has a triangular prism shape having a triangular cross section, and is arranged so that the apex of the triangle in the cross section faces downward (convex downward). Further, the triangular prism rod 63 is detachable from the rotating shaft 60 by a flange and a bolt, similarly to the triangular prism rod 61p and the cylindrical rod 61q shown in FIG.

In the stirring mechanism 31b according to the third embodiment, as in the first and second embodiments described above, the rotating shaft 60 is reciprocated at a predetermined set angle to reciprocate the agitated object J in the reaction vessel 11. Can be agitated. Further, a triangular prism rod 63 is arranged between the stirring blade pair 61 and the cross-shaped stirring blade 62. Therefore, since the agitated object J can be agitated at the middle position in the reaction vessel 11, the agitated object J in the reaction vessel 11 can be agitated more efficiently.

In the examples shown in FIGS. 7 and 8, the example in which the apex of the triangle in the cross section of the triangular prism rod 63 faces downward has been described, but it is also possible to have a configuration in which the apex faces upward (convex upward).

[Explanation of Fourth Embodiment]
Next, a fourth embodiment of the present invention will be described. In the fourth embodiment, only the configuration of the stirring mechanism is different from that of the second embodiment (see FIG. 5) described above, and the other configurations are the same. FIG. 9 is a perspective view showing the configuration of the stirring mechanism 31c according to the fourth embodiment, and FIG. 10 is an explanatory view showing how the stirring mechanism 31c stirs the agitated object J in the reaction vessel 11.

As shown in FIG. 9, the stirring mechanism 31c according to the fourth embodiment has a cylindrical rod 64 having a circular or elliptical cross section above the cross-shaped stirring blade 62 with respect to the stirring mechanism 31a shown in FIG. It differs in that it is arranged.

The cylindrical rod 64 is attached to the stirring blade of the cross-shaped stirring blade 62 at a position shifted by 45 °, for example, by welding. With such a configuration, the cylindrical rod 64 reciprocates in the vicinity of the bottom of the reaction vessel 11 even when the resin R stays in a lump due to the pressure when the agitated object J is filtered by the filter 34. This mass can be crushed by rotating. Therefore, it is possible to promote the synthetic reaction.

Similar to the triangular prism rod 61p and the cylinder rod 61q shown in FIG. 3, the columnar rod 64 may be detachably fixed to the rotating shaft 60 by a flange or a bolt. Further, the angle formed by the cross-shaped stirring blade 62 and the cylindrical rod 64 is not limited to 45 °, and may be any angle.

Although embodiments of the present invention have been described above, the statements and drawings that form part of this disclosure should not be understood to limit the invention. Various alternative embodiments, examples and operational techniques will be apparent to those skilled in the art from this disclosure.

11 Reaction vessel 12 1st measuring instrument 13 2nd measuring instrument 21 1st container unit 22 2nd container unit 24, 25 Containers 31, 31a, 31b, 31c Stirring mechanism 34 Filter 41 Control device 60 Rotating shaft 60s Bottom 61 Stirring blade Anti-61p, 63 Triangular prism rod 61q, 64 Cylindrical rod 62 Cross-shaped stirring blade 62a, 62b Triangular prism 100 Solid phase synthesizer f1, f2, f3, f4 Flange part J Stirred material L Chemical solution p1, p2 Pillar P1 Pump q1, q2 Column R resin k1, k2, k3, k4 bolt

Claims (9)

A reaction vessel in which a resin and a chemical solution are charged to cause a solid-phase synthesis reaction on the surface of the resin to form a synthetic substance on the surface of the resin.
It is provided in the reaction vessel and includes a stirring mechanism for stirring the resin and the chemical solution.
The stirring mechanism is
A rotation axis that extends in the vertical direction and alternates between forward and reverse rotation for each set angle,
A stirring blade pair including a first stirring blade connected to the rotation shaft and arranged in a plane direction orthogonal to the rotation shaft, and a pair of second stirring blades.
The first stirring blade has an elongated shape having a triangular cross section.
The solid-phase synthesizer is characterized in that the second stirring blade is arranged above the first stirring blade and has an elongated shape having a circular or elliptical cross section. The solid-phase synthesizer according to claim 1, wherein the second stirring blade is arranged so as to be located near the liquid level in the reaction vessel. The solid-phase synthesizer according to claim 1 or 2, wherein the cross-sectional shape of the first stirring blade is formed in a triangular shape having a convex upper portion. The solid-phase synthesizer according to any one of claims 1 to 3, wherein the set angle is an angle of 90 ° or less. The solid-phase synthesizer according to any one of claims 1 to 4, wherein the vertical width of the second stirring blade is smaller than the vertical width of the first stirring blade. The invention according to any one of claims 1 to 5, wherein the first stirring blade and the second stirring blade are made of a material obtained by coating a metal with a fluororesin or a processed product of a fluororesin. Solid phase synthesizer. Below the pair of stirring blades of the rotating shaft, a third stirring blade is arranged in the direction of a plane orthogonal to the rotating shaft and has a long shape formed in a triangular cross section. The solid-phase synthesizer according to any one of claims 1 to 6, wherein the solid-phase synthesizer is provided. The solid-phase synthesizer according to claim 7, wherein the third stirring blade has a cross shape. The solid-phase synthesizer according to claim 7 or 8, wherein the cross-sectional shape of the third stirring blade is formed in a triangular shape having a convex downward portion.

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