JP2022153223A - Chemical liquid synthesis device - Google Patents

Abstract

To provide a chemical liquid synthesis device for feeding chemical liquid in a non-contact state with atmosphere, capable of enhancing synthesis efficiency between a carrier and chemical liquid in a reaction vessel part.SOLUTION: A chemical liquid synthesis device comprises: a chemical liquid storage part storing chemical liquid; and a reaction vessel part for reacting, the chemical liquid and the carrier, the chemical liquid synthesis device capable of feeding the chemical liquid from the chemical liquid storage part to the reaction vessel part without contacting to the atmosphere. The chemical liquid synthesis device further comprises: a first chemical liquid supply part for supplying the chemical liquid to the reaction vessel part; and a chemical liquid discharge part provided at a vertically upper side relative to the first chemical liquid supply part; and a second chemical liquid supply part for, after discharging the chemical liquid from the chemical liquid discharge part, falling the carrier adhered to an inner wall of the reaction vessel part.SELECTED DRAWING: Figure 1

Description

TECHNICAL FIELD The present invention relates to a chemical synthesizing apparatus for synthesizing a chemical liquid to be sent without being exposed to the air, and more particularly to a chemical synthesizing apparatus capable of suppressing deterioration in synthesis efficiency.

2. Description of the Related Art In chemical synthesizers for chemically synthesizing proteins, peptides, polymers, nucleic acids, etc., chemical synthesis is performed by supplying a plurality of chemical solutions (reagents) to reaction vessels. For example, in the case of synthesizing nucleic acids, a large number of carriers (porous beads) are provided in the reaction vessel, and chemical solutions are sequentially supplied to the reaction vessel to perform detritylation, coupling, oxidation, capping, and the like. The process is repeated to bind successive bases to the beads.

As a general chemical synthesis apparatus, for example, as shown in FIG. 7, a reaction vessel portion 100 containing a carrier 110 (see FIG. 8) and supplied with a chemical solution, and a chemical solution to be supplied to the reaction container portion 100 are stored. and a waste liquid tank 102 for storing the waste liquid discharged from the reaction container section 100 . Each of them is connected by a pipe 103, and the chemical solution is pumped by the pressure from the pressure supply source 107, so that the chemical solution and the carrier 110 can be synthesized and reacted without the chemical solution coming into contact with the atmosphere ( For example, see Patent Document 1 below). Specifically, the reaction vessel section 100 has a chemical liquid supply section 106 to which the chemical liquid is supplied at the lower end in the vertical direction, and a chemical liquid discharge section 105 from which the chemical liquid is discharged to the upper end in the vertical direction. When the chemical solution is supplied from the chemical solution supply part 106 at the lower end from the chemical solution tank through the pipe 103, the chemical solution and the carrier are synthesized and reacted in the reaction container part 100, and then the chemical solution after the reaction is discharged from the chemical solution discharge part 105 at the upper end. is discharged to the drain tank 102 through the pipe 103 (see FIG. 8(a)).

Here, as described above, the supply of the chemical solution to the reaction container part 100 is performed from the chemical solution supply part 106 at the lower end in the vertical direction. That is, the chemical solution from the chemical solution supply portion 106 at the lower end portion is stored while spreading in the radial direction of the reaction vessel portion 2 due to the influence of gravity. Therefore, the chemical solution can be distributed throughout the reaction container part 2, and the efficiency of synthesis with the carrier 110 is improved compared to the case where the chemical solution is supplied from the upper end side, and the carrier 110 in the reaction container part 2 and the chemical solution can be chemically synthesized without waste.

JP 2020-093236 A

However, in the chemical synthesizing apparatus described above, there is a possibility that the synthesizing efficiency in the reaction vessel section 100 is lowered. That is, after the chemical solution is stored in the reaction container part 100 and the synthesis reaction is performed, as shown in FIG. Thus, a phenomenon occurs in which part of the carrier 110 remains attached to the upper portion of the reaction vessel section 100 . In this state, if a small amount of chemical solution is to be stored in the reaction vessel part 100 and reacted, if the chemical solution is supplied from the chemical solution supply part 106, the chemical solution does not reach the adhered carrier 110, and the reaction cannot be sufficiently carried out. I had a problem.

In addition, some of the carriers immediately after the chemical solution is supplied may float on the surface of the chemical solution in the reaction container part 100, and adhere to the wall surface of the reaction container part 100 due to the shaking of the liquid surface during the chemical solution supply. Sometimes. In such a case, the same problem as the problem described above also occurs, and there is a problem that the reaction cannot be sufficiently performed in a state where the chemical liquid after the completion of supply does not reach the height position where the carrier adheres.

The present invention has been made in view of the above problems, and is a chemical synthesis apparatus capable of increasing the efficiency of synthesizing a carrier and a chemical solution in a reaction vessel in a chemical solution synthesizing apparatus that transfers a chemical solution without contact with the atmosphere. The purpose is to provide a device.

In order to solve the above-mentioned problems, the chemical synthesis apparatus of the present invention includes a chemical storage unit containing a chemical solution, and a reaction container unit for reacting the chemical solution with a carrier. A chemical solution synthesizing device in which a chemical solution is sent without being exposed to the atmosphere, comprising: a first chemical solution supply unit connected to the reaction container unit and supplying a chemical solution to the reaction container unit; and a chemical solution discharge part provided on the upper side in the vertical direction, and a second chemical solution supply part for suppressing adhesion of the carrier to the reaction vessel part.

According to the chemical synthesis apparatus, since it includes the second chemical supply section, it is possible to suppress adhesion of the carrier to the inner wall of the reaction vessel section. That is, even if the carrier tries to adhere to the inner wall of the reaction container section due to the shaking of the liquid surface of the chemical liquid, the carrier is not adhered by being supplied from the second chemical liquid supply section provided above the liquid surface of the chemical liquid. is suppressed, and even if it adheres to the inner wall of the reaction vessel, it can be flowed back to the chemical solution side. Therefore, it becomes easier to contact with the chemical solution supplied from the first chemical solution supply part on the lower end side, and the synthesis efficiency of the carrier and the chemical solution can be enhanced.

Further, in order to solve the above-mentioned problems, the chemical synthesis apparatus of the present invention includes a chemical storage part containing a chemical solution, and a reaction container part for reacting the chemical solution with a carrier, and a chemical solution synthesizing device in which a chemical solution is sent to a part without being exposed to the atmosphere, the first chemical solution supply part being connected to the reaction vessel part and supplying the chemical solution to the reaction vessel part; and a second chemical solution supply unit that drops the carrier adhering to the inner wall of the reaction container after discharging from the chemical solution discharge part. It is characterized by having

According to the chemical synthesis apparatus, since the second chemical supply unit is provided, the carrier adhering to the inner wall of the reaction vessel can be dropped after the chemical is discharged from the chemical discharge unit on the upper side in the vertical direction. That is, when the chemical liquid supplied from the second chemical liquid supply section comes into contact with the carrier adhering to the inner wall of the reaction vessel section, the carrier can be dropped together with the chemical liquid to be supplied, and the carrier can be returned to the lower end of the reaction vessel section. . Therefore, it becomes easier to contact with the chemical solution supplied from the first chemical solution supply part on the lower end side, and the synthesis efficiency of the carrier and the chemical solution can be enhanced.

Further, the second chemical supply section may be connected to the chemical discharge section, and the chemical liquid may be supplied by causing the chemical discharge section to flow backward.

According to this configuration, since the chemical liquid can be supplied using the chemical liquid discharge section, it is not necessary to form an independent port dedicated to the second chemical liquid supply section in the reaction container section. Therefore, the second chemical supply section can be provided without complicating the piping more than necessary.

Further, the chemical liquid supplied from the second chemical liquid supply section may be configured to be supplied along the side wall of the reaction container section.

According to this configuration, the carrier that is about to adhere to the side wall of the reaction vessel or the carrier that has adhered can be flowed back, thereby suppressing deterioration in synthesis efficiency caused by the carrier adhering to the side wall of the reaction vessel. be able to.

Further, the chemical liquid in the reaction vessel may be discharged by causing the first chemical liquid supply section to flow backward.

According to this configuration, since the first chemical supply portion is positioned vertically lower than the chemical discharge portion, the carrier is more likely to be removed from the reaction container portion than when the chemical is discharged from the chemical discharge portion. It can prevent it from sticking to the wall.

Further, the reaction vessel section may be configured to be provided with an exhaust section for discharging the gas in the reaction vessel section.

According to this configuration, the gas in the reaction container can be discharged by providing the discharge section, so that the chemical liquid can be easily supplied from the second chemical liquid supply section.

Further, the reaction container section may be provided with a guide member for guiding the chemical liquid supplied through the second chemical liquid supply section to the side wall of the reaction container section.

According to this configuration, the chemical solution sent from the second chemical solution sending part is guided to the side wall of the reaction container part by the guide member, so that the guided chemical solution easily flows along the side wall. As a result, the carrier stuck to the side wall can be efficiently dropped together with the chemical solution.

As a specific aspect of the guide member, the configuration can be simplified by sharing it with the filter.

Further, the above-described chemical solution may be a cleaning solution, and similar effects can be obtained even if a cleaning solution is used in place of the chemical solution.

INDUSTRIAL APPLICABILITY According to the chemical synthesizing apparatus of the present invention, in the chemical synthesizing apparatus that sends the chemical liquid without contacting the atmosphere, it is possible to increase the efficiency of synthesizing the carrier and the chemical liquid in the reaction container section.

1 is a schematic piping route diagram of a chemical synthesis apparatus of the present invention; FIG. It is a figure of the reaction container part of the said chemical-solution synthesizing apparatus. FIG. 4 is a piping route diagram showing a normal mode in which a chemical solution is supplied from the first chemical solution supply unit to the reaction container unit; FIG. 10A is a diagram showing a state in which a chemical solution is discharged from a reaction vessel, FIG. 14A is a diagram showing a state in which a carrier moves upward while a chemical solution is being discharged from a chemical solution discharge unit, and FIG. FIG. 10 is a diagram showing a state in which the carrier is attached to the upper portion after the chemical solution is discharged from the chemical solution discharge part; FIG. 10 is a piping route diagram showing a carrier return mode in which the chemical solution is supplied to the reaction container by causing the chemical solution discharge part to flow back from the second chemical solution supply part. FIG. 10 is a diagram showing a state in which another guide member is provided in the reaction container section; It is a schematic piping route diagram of the conventional chemical-solution synthesizer. It is a diagram showing a state of discharging a chemical solution from a conventional reaction vessel part, (a) is a diagram showing a state in which the carrier moves upward while discharging the chemical solution from the chemical solution discharge part at the upper end, (b) is a diagram showing a state in which the carrier adheres to the upper portion after the chemical solution is discharged from the chemical solution discharge part. FIG. 10 is a diagram showing a state in which a carrier floating in a reaction container sinks in the chemical solution due to the supplied chemical solution. FIG. 4 is a diagram showing a configuration in which the supplied chemical solution is transmitted to the side wall of the reaction vessel part, (a) is a diagram showing a state in which the pipe is accommodated in the wall surface of the lid part, and (b) is a diagram showing a state in which the pipe is connected to the wall surface of the lid part. It is a figure which shows the state projected from.

BEST MODE FOR CARRYING OUT THE INVENTION An embodiment of a chemical synthesizing apparatus of the present invention will be described with reference to the drawings.

FIG. 1 is a piping route diagram showing a chemical synthesizing apparatus according to one embodiment of the present invention. In this embodiment, an example in which a chemical solution (reagent) is used as a fluid will be described, but the present invention is not limited to chemical solutions, and can also be applied to chemical synthesis, mixing, etc. of liquids other than chemical solutions. be able to.

As shown in FIG. 1, the chemical synthesizing apparatus includes a chemical tank 1, which is a chemical storage unit in which the chemical is stored, a weighing unit 3 for measuring the chemical, and a carrier S (porous beads; see FIG. 2). It is provided with a reaction container part 2 containing the reaction container part 2 and a waste liquid tank 11 which is a container part for storing the waste liquid discharged from the reaction container part 2 , which are connected to each other by a pipe 4 . After the chemical solution supplied from the chemical solution tank 1 is weighed by the measuring unit 3, the chemical solution is supplied to the reaction container unit 2, and chemically synthesized by contacting the carrier S and the chemical solution in the reaction container unit 2. Then, the chemical solution after chemical synthesis is discharged by being sent to the drain tank 11 . For example, in the case of synthesizing nucleic acids, a certain amount of porous carrier S is contained in the reaction container part 2, and while sequentially supplying a weighed chemical solution to the reaction container part 2, detritylation, cupping, Repeated treatments such as ringing, oxidation, capping, etc. are used to attach successive bases to the beads.

The chemical liquid tank 1 is for storing reagents used in chemical synthesis. Although three chemical tanks 1 are shown in the example of FIG. That is, the chemical liquid stored in each chemical liquid tank 1 is sent to the weighing unit 3 without being mixed with other chemical liquids.

A pressure adjusting means 6 is connected to the chemical liquid tank 1, and the chemical liquid in the chemical liquid tank 1 is pumped by the pressure adjusting means 6. As shown in FIG. The pressure adjusting means 6 has a gas tank 61 filled with gas and a pipe 41 connecting the gas tank 61 and the chemical liquid tank 1, and the gas in the gas tank 61 is supplied to the chemical liquid tank 1 through the pipe 41. can do. That is, by supplying the gas of the gas tank 61, the pressure of the chemical tank 1 is adjusted to the pressure of the gas tank 61, and by forming a differential pressure with the pressure in the measuring section 3, the chemical liquid in the chemical tank 1 flows into the measuring section. 3 is sent. By adjusting the pressure of the gas tank 61, the flow rate of the chemical solution sent from the chemical solution tank 1 can be adjusted. That is, when the differential pressure between the pressure of the chemical tank 1 and the measuring unit 3 is increased, the liquid supply speed of the chemical liquid supplied from the chemical tank 1 increases, and the amount of the chemical liquid can be increased. When the differential pressure between the tank 1 and the metering unit 3 is reduced, the liquid feeding speed of the liquid chemical fed from the liquid chemical tank 1 is reduced, so that the amount of the liquid chemical can be suppressed.

Further, in this embodiment, one of the chemical liquid tanks 1 contains a cleaning liquid. If a predetermined chemical solution cannot be mixed with the previously sent chemical solution, the cleaning solution is added after the previous chemical solution is sent and before the subsequent chemical solution is sent. It is for feeding the liquid and cleaning the reaction container part 2 and the pipe 4 . This cleaning liquid is also stored in a chemical liquid tank 1 (chemical liquid tank 1a in FIG. 1) having the same configuration as the chemical liquid described above, and the cleaning liquid is also sent with the same configuration as the chemical liquid described above.

A valve 51 is provided in each of the pipes 41 and 42 . This valve 51 selectively connects the target chemical liquid tank 1 and the weighing unit 3 . That is, with the valve 51 of the liquid chemical tank 1 selected as the supply target being opened (open state), gas is supplied from the gas tank 61 to pressurize the liquid chemical tank 1, thereby increasing the pressure of the liquid chemical tank 1 to the measuring unit 3. , and the chemical liquid in the selected chemical liquid tank 1 is sent to the weighing unit 3 through the pipe 42 . The pipes 41, 42, .

Also, in this embodiment, an example in which the gas tank 61 is used as the pressure adjusting means 6 will be described. good too. The gas in the gas tank 61 is a gas (for example, argon gas) that does not react with the chemical solution in the chemical solution tank 1 .

Also, the weighing unit 3 accurately measures the supplied chemical solution. In this embodiment, the mass of the supplied chemical solution is measured, and the amount of the chemical solution to be reacted with the carrier S in the reaction vessel part 2 can be accurately measured. That is, the weighing unit 3 has a weighing container 31 and a load cell (not shown) connected to the weighing container 31, and the chemical liquid stored in the weighing container 31 is weighed by the load cell.

A pipe 42 is connected to the upper end of the weighing container 31, and a pipe 43 is connected to the lower end of the weighing container 31. It is designed to be discharged. Specifically, when the valve 51 of the pipe 4 connecting the selected chemical tank 1 and the weighing container 31 is open, the selected chemical tank 1 is pressurized by the gas tank 61, so that the chemical is discharged into the pipe. 42 into the weighing container 31 . Then, in the reaction container part 2, the amount of the chemical solution required for one synthesis reaction is measured and at the same time, the supply of the solution is stopped. Become. After being weighed, the chemical solution is sent from the weighing container 31 to the reaction container section 2 through the pipe 43 .

The liquid transfer from the measuring section 3 is performed by the gas tank 62 (pressure adjusting means 6). That is, a gas tank 62 is connected to the measuring container 31 separately from the gas tank 61 so that gas can be supplied from the gas tank 62 to the measuring container 31 . By supplying gas from the gas tank 62 to the measuring container 31, the pressure of the measuring container 31 is adjusted, and by adjusting the differential pressure between the measuring unit 3 and the reaction container unit 2, the pressure inside the measuring container 31 is adjusted. A chemical liquid is sent to the reaction container portion 2 . In the example of FIG. 1, the measured chemical liquid is supplied to the reaction container section 2 through the pipes 43 and 44 . The gas tank 62 may also use a gas supply source installed in the building.

In addition, the reaction vessel part 2 provides a reaction field for chemically synthesizing the carrier S contained in the reaction vessel part 2 and the supplied chemical solution or the like by bringing them into contact with each other. In this embodiment, the reaction container part 2 uses a glass cylindrical tube extending in one direction, and the carrier S is accommodated in the reaction container part 2 (see FIG. 2). A first chemical supply portion 71 to which the chemical is supplied and a chemical discharge portion 72 to which the chemical is discharged are connected to both ends of the reaction container portion 2 in the vertical direction. That is, the reaction vessel section 2 is supplied with the chemical through the first chemical supply section 71 and is discharged through the chemical discharge section 72 . In this embodiment, a chemical solution discharge part 72 is provided on the upper side in the vertical direction, and a first chemical solution supply part 71 is provided on the lower side in the vertical direction.

The first chemical liquid supply part 71 supplies the chemical liquid to the vertically lower side of the reaction container part 2, and is formed by the first port 21a and the pipe 44 in this embodiment. That is, as shown in FIG. 2, the reaction container section 2 has a first port 21a on the lower side in the vertical direction, and a pipe 44 is connected to the first port 21a. Therefore, the chemical liquid sent from the measuring section 3 through the pipe 43 is supplied to the reaction container section 2 through the three-way valve 53 and the pipe 44 . When the chemical solution is supplied from the first chemical solution supply part 71, the supplied chemical solution spreads in the radial direction of the reaction container part 2 due to the influence of gravity and is stored. Therefore, the chemical solution can be distributed throughout the reaction container part 2, and the chemical solution can be chemically synthesized with the carrier S accommodated in the reaction container part 2 without waste.

The chemical solution discharge part 72 discharges the chemical solution on the vertically upper side of the reaction container part 2, and is formed by the second port 21b and the pipe 45 in this embodiment. That is, as shown in FIG. 2, the reaction container part 2 has a second port 21b on the upper side in the vertical direction, and a pipe 45 is connected to the second port 21b.

A drain tank 11 , which will be described later, is provided on the downstream side of the reaction container part 2 , and the reaction container part 2 and the drain tank 11 are connected by a pipe 45 . In other words, the chemical liquid in the reaction container section 2 can be discharged from the chemical liquid discharge section 72 through the pipe 45 .

Further, on the downstream side of the reaction vessel section 2, a drainage tank 11 is provided as a storage vessel section for storing the chemical liquid or the like that has been drained in the reaction vessel section 2 after the completion of the reaction. The drain tank 11 is formed to have a capacity larger than that of the reaction container portion 2, and is formed to have a capacity capable of storing even when the reaction container portion 2 is discharged a plurality of times. In this embodiment, the chemical solution after the reaction is discharged to the drainage tank 11 via the chemical solution discharge part 72 . That is, the chemical solution after the reaction is pressurized by the gas supplied from the gas tank 62 , and is discharged to the drainage tank 11 through the chemical solution discharge part 72 . In this way, the chemical synthesizing apparatus of the present invention is configured so that the chemical is sent from the chemical tank 1 to the drain tank 11 without being exposed to the atmosphere.

In addition to the first chemical supply unit 71, the chemical synthesis apparatus is provided with a second chemical supply unit 73 (see FIG. 1). The second chemical liquid supply part 73 is for suppressing the adherence of the carrier S to the reaction container part 2 and for dropping the carrier S adhering to the reaction container part 2 . In the present embodiment, the second chemical supply unit 73 is formed by a pipe 46 connected to the pipe 43 by the three-way valve 53, and is formed by connecting the pipe 46 to the pipe 45 by the three-way valve 55. there is Then, by the second chemical liquid supply unit 73, the measured chemical liquid is sent from the pipe 43 through the three-way valve 53 through the pipe 46, and then through the three-way valve 55 and the pipe 45 to the reaction container unit 2. It has become so. That is, the chemical liquid is supplied to the reaction container section 2 by causing the chemical liquid discharge section 72 to flow backward by the second chemical liquid supply section 73 . Then, by supplying the chemical solution from the second chemical solution supply part 73, the chemical solution flows along the side wall 22a of the reaction container part 2, and the carrier adhering to the reaction container part 2 can be dropped.

In addition, the chemical solution supplied from the second chemical solution supply part 73 flows through the side wall 22a of the reaction container part 2, so that the carriers S that are about to adhere to the side wall 22a of the reaction container part 2 flow back, and the carriers S adhere to the side wall 22a. You can prevent sticking. Furthermore, as shown in FIG. 9, when the chemical solution is supplied from the second chemical solution supply part 73, the flow of the chemical solution directly hits the carrier S floating on the liquid surface, sinking the carrier, thereby reducing the reaction container part 2. Adherence of the carrier S to the side wall 22a can be suppressed. In particular, when the chemical flows through the side wall 22a of the reaction vessel section 2, the flow of the chemical directly hits the carrier S floating on the liquid surface near the side wall 22a, so that the chemical is supplied from the first chemical supply section 71 on the lower side. Compared to the case where the chemical solution is supplied, the chemical solution is more likely to blend with the carrier S, and furthermore, the carrier S that is about to adhere to the side wall 22a can sink due to the shaking of the liquid surface accompanying the supply of the chemical solution. This can prevent the carrier S from adhering to the sidewall 22a.

Further, the pipe 44 is connected to the pipe 45 via the pipe 48 by the valve 58 , and the reaction container section 2 is connected to the waste liquid tank 11 through the pipe 44 , the pipe 48 , and the pipe 45 . In other words, the chemical liquid in the reaction container section 2 supplied from the second chemical liquid supply section 73 can be discharged by causing the first chemical liquid supply section 71 to flow backward.

In the above description, the chemical solution is used as the object, but the cleaning solution can be used instead of the chemical solution. It is designed to be

As shown in FIG. 2, the reaction vessel section 2 has a reaction vessel main body 22 that accommodates the carrier S (beads), and lid sections 23 that are provided at both ends of the reaction vessel main body 22 in the axial direction. . The lid portion 23 is provided with a first port 21a and a second port 21b, and the chemical solution is supplied from the first port 21a and discharged from the second port 21b.

A filter 24 is provided at the inlet/outlet of the reaction container body 22 so as to block the flow path leading from the reaction container body 22 to the first port 21a and the second port 21b. As a result, if impurities are contained in the chemical liquid supplied through the first port 21a or the second port 21b, the impurities can be removed. Further, when the chemical solution after the reaction is discharged from the reaction container part 2, the filter 24 prevents the carrier S from being discharged, thereby preventing the carrier S in the reaction container part 2 from leaking to the outside. there is

Moreover, the filter 24 is formed in a circular flat plate shape, and is provided so that the outer edge portion of the filter 24 abuts on a wall surface continuous with the side wall 22 a of the reaction container main body 22 . That is, the reaction vessel main body 22 is formed so that a portion connected to the lid portion 23 protrudes, and the filter 24 is arranged so as to be in contact with the wall surface of the protruded portion. As a result, the chemical solution supplied from the second port 21b is supplied into the reaction container main body 22 along the side wall 22a of the reaction container main body 22. As shown in FIG. That is, when the chemical liquid is supplied from the second port 21b, that is, when the chemical liquid is supplied from the second chemical liquid supply section 73 and the chemical liquid is supplied by causing the chemical liquid discharge section 72 to flow backward, as indicated by the arrow in FIG. Secondly, the chemical liquid moves to the entire surface of the filter 24 by penetrating into the filter 24 . As the chemical solution continues to be supplied as it is, the chemical solution cannot be retained in the filter 24, and since the outer edge of the filter 24 is continuous with the side wall 22a of the reaction container main body 22, The chemical liquid that cannot be retained is pulled by the surface tension with the side wall 22a and flows along the side wall 22a. In other words, this filter 24 functions as a guide member 8 that guides the chemical liquid to the side wall 22a of the reaction vessel portion 2. As shown in FIG.

In addition, the reaction vessel section 2 is provided with an exhaust port 91 as the exhaust section 9 in addition to the second port 21b. This exhaust part 9 is for exhausting gas (including gas and air bubbles) in the reaction vessel part 2 . The exhaust port 91 is connected to a pipe 49 connected to the drain tank 11 , and the fluid discharged from the exhaust port 91 is discharged to the drain tank 11 through the pipe 49 . The pipe 49 is provided with a valve 59 so that the flow of fluid discharged from the exhaust port 91 can be controlled. That is, when the valve 59 is open, the reaction vessel body 22 is pressurized, whereby the fluid in the reaction vessel body 22 is discharged through the pipe 49, and when the valve 59 is closed, the flow of fluid discharged from the exhaust port 91 is stopped. It is designed to be able to

The exhaust port 91 is provided in the lid portion 23 similarly to the second port 21b, and is arranged at a height position equal to or higher than the height position of the chemical discharge portion 72. As shown in FIG. In this embodiment, the chemical discharge portion 72 is formed by the second port 21 b and the pipe 45 , and the pipe 45 is formed so as to extend until it contacts the filter 24 . That is, the exhaust port 91 is arranged at a position higher than the lower end portion of the chemical discharge portion 72 , that is, the position P where the pipe 45 contacts the filter 24 . Accordingly, the chemical liquid can be smoothly supplied from the second port 21b. That is, when the chemical solution is supplied from the second port 21b, the pressure inside the reaction vessel main body 22 increases, but by opening the exhaust port 91, the exhaust port 91 is positioned higher than the pipe 45. , the chemical solution supplied from the second port 21 b can be prevented from being directly discharged from the exhaust port 91 . Therefore, the gas in the reaction container main body 22 is efficiently discharged from the exhaust port 91, and the chemical liquid can be smoothly supplied from the second port 21b.

Furthermore, since the pipe 45 of the chemical solution discharge unit 72 is in contact with the filter 24, the chemical solution pressure-fed from the second chemical solution supply unit 73 through the pipe 45 passes through the filter 24 and is directly introduced into the reaction vessel main body 22. be. That is, when the pipe 45 is separated from the filter 24 , the chemical solution pumped from the pipe 45 may flow on the surface of the filter 24 and may flow directly into the exhaust port 91 . Due to the abutment, the supplied chemical flows through the filter 24 and enters the reaction container main body 22, so that the chemical is prevented from being discharged directly from the exhaust port 91 before entering the reaction container main body 22. can be avoided.

In addition, the nucleic acid synthesis apparatus has a control device (not shown), which controls each valve and the pressure control means 6 to control the flow of the chemical solution. That is, the control device also controls the supply and discharge modes of the chemical solution to the reaction vessel section 2, and controls a normal supply mode and a carrier return mode, which will be described later.

The normal supply mode is a mode in which the chemical is supplied from the first chemical supply section 71 . Specifically, as shown in FIG. 3, the three-way valve 53 is set to be open in the direction of flow from the pipe 43 to the pipe 44, the valve 52 is open, and the three-way valve 55 is set to be open in the direction of flow to the pipe 45. As a result, the chemical liquid measured by the measuring section 3 is supplied to the reaction container section 2 through the first chemical liquid supply section 71 . Here, regarding the open/closed state of each valve, white indicates the open state and black indicates the closed state. By pressurizing the weighing container 31 with the gas tank 62 , a differential pressure is generated with respect to the reaction container portion 2 , and the chemical liquid is sent from the weighing container 31 . The chemical solution supplied to the reaction container part 2 is brought into contact with the carrier S in the reaction container part 2 to undergo a synthesis reaction.

This normal supply mode is a chemical solution supply state that is mainly used, and can efficiently perform the synthesis reaction. That is, the chemical is introduced from the lower side of the reaction container portion 2 by being fed from the first chemical solution supply portion 71 , and the chemical solution can be distributed throughout the reaction container portion 2 . That is, since the chemical solution introduced into the reaction vessel part 2 from the lower pipe 44 is affected by gravity, it is stored in the reaction vessel part 2 while spreading in the radial direction, and the entire carrier S accommodated in the reaction vessel part 2 and chemical synthesis. If the chemical solution is introduced from above, the chemical solution supplied from the second port 21b will proceed directly to the first port 21a due to the influence of gravity, and therefore, it will be difficult to spread in the radial direction. Therefore, the chemical solution introduced from above progresses in chemical synthesis with the carrier S present in the axial direction immediately below the second port 21b, but does not easily react with the carrier S positioned radially outwardly, resulting in localized In some cases, unreacted carrier S remains in the . Therefore, in the normal supply mode, the carrier S and the chemical solution in the reaction vessel part 2 can be reacted without waste, and used as a normal chemical solution supply path.

Then, when the reaction between the chemical solution supplied to the reaction container part 2 and the carrier S is completed, the chemical solution is discharged. That is, by pressurizing with the gas tank 62, the chemical liquid is discharged from the second port 21b and discharged to the drainage tank 11 through the pipe 45 (see FIG. 4(a)).

The carrier return mode is a mode for dropping the carrier attached to the side wall of the reaction vessel part 2 and returning the carrier to its original position (lower end portion of the reaction vessel part 2). This carrier return mode is a mode of supplying a chemical liquid in the opposite direction to the normal supply mode, and the liquid is sent from the upper end side of the reaction vessel section 2 . In this embodiment, the liquid is sent from the second chemical liquid supply portion 73 through the chemical liquid discharge portion 72 . Usually, in a chemical synthesizing apparatus of a type in which each processing unit is connected by a pipe and the synthetic reaction is performed without exposing the chemical to the atmosphere, the synthetic reaction with the carrier S can be efficiently performed only in the normal supply mode described above. It is not necessary to separately provide a path for supplying the chemical liquid from the upper side of the reaction vessel section 2 . However, when the carrier S is stored in the reaction container part 2, when the chemical solution is discharged from the upper second port 21b as in the normal supply mode, the side wall 22a (especially the upper part) of the reaction container main body 22, the upper side may remain attached to the filter 24 (see FIG. 4(b)). In this way, when the amount of the next chemical solution to be synthesized is small while the carrier S is attached, it is difficult to touch the carrier S with the attached chemical solution, even if the chemical solution is supplied to the reaction vessel part 2 . , there is a problem that it is difficult to efficiently carry out the synthesis reaction. In order to solve this problem, the carrier return mode is executed to wash off the adhered carrier S with the chemical solution introduced from above, thereby increasing the synthesis efficiency of the chemical solution and the carrier S.

In the carrier return mode, the chemical is supplied from the second chemical supply section 73 . Specifically, as shown in FIG. 5, the three-way valve 53 is set to be open in the direction of flow from the pipe 43 to the pipe 46, and the three-way valve 55 is set to be open in the direction of flow from the pipe 46 to the reaction container section 2 side. As a result, the chemical liquid measured by the measuring section 3 is supplied from the second chemical liquid supply section 73 to the reaction container section 2 through the chemical liquid discharge section 72 . That is, as in the normal supply mode, the measuring container 31 is pressurized by the gas tank 62 to generate a differential pressure with respect to the reaction container portion 2 , and the chemical liquid is sent from the measuring container 31 .

When the chemical solution is supplied to the reaction container part 2, the chemical solution supplied through the first port 21a is guided to the side wall 22a of the reaction container part main body 22 by the filter 24 (guiding member 8). That is, the chemical solution that permeates the filter 24 permeates the filter 24 as indicated by the arrows in FIG. Since the outer edge of the filter 24 is continuous with the side wall 22a of the reaction vessel main body 22, the chemical liquid that cannot be retained in the filter 24 is pulled by the surface tension with the side wall 22a and flows along the side wall 22a. . As a result, the chemical flowing along the side wall 22a lifts the carrier S attached to the side wall 22a (see FIG. 4(b)) from the side wall 22a, causing the carrier S to drop toward the lower end of the reaction container portion 2 along with the flow of the chemical. As a result, the carrier S adhering to the side wall 22a of the reaction container portion 2 can be returned to its original position (lower end portion of the reaction container portion), and the synthesis efficiency of the carrier S and the chemical solution can be enhanced. That is, compared to the state where the carrier S remains attached to the side wall 22a, the chemical solution can be brought into contact with all the carriers, and the synthesis reaction can be carried out efficiently.

In addition, as described above, this carrier return mode not only allows the carriers S that have already adhered to the side wall 22a of the reaction container section 2 to flow off, but can also prevent the carriers S floating in the chemical solution from adhering to the side wall 22a. . That is, since the chemical solution supplied from the second chemical solution supply part 73 flows along the side wall 22a of the reaction container part 2, the flow of this chemical solution directly hits the carrier S floating on the liquid surface, and the carrier can be submerged. . That is, it is possible to prevent the carrier S from adhering to the side wall 22a of the reaction container part 2 even before the chemical solution in the reaction container part 2 is discharged. Further, even if the carrier S tries to adhere to the side wall 22a due to the shaking of the liquid surface due to the supply of the chemical solution, the chemical solution flowing along the side wall 22a flows back the carrier S, thereby suppressing the carrier S from adhering to the side wall 22a. can.

In this carrier return mode, the chemical supplied from the second chemical supply unit 73 is supplied to the reaction container 2 by the guide member 8 (in this embodiment, the filter 24) that guides the chemical to the side wall 22a of the reaction container 2. Since it is configured to flow along the side wall 22a, the chemical can be supplied directly from the vertically upper side of the reaction vessel section 2 (in this embodiment, the chemical liquid discharge section 72). As described above, the chemical solution introduced from above is less likely to spread in the radial direction, so it is less likely to react with the carrier S positioned radially outside. Therefore, the chemical solution can also be supplied to the carrier S located radially outward. Therefore, this carrier return mode can also be used as a normal chemical supply means for the reaction vessel section 2 . In this carrier return mode, the chemical solution can be supplied to the reaction container portion 2 while suppressing the adhesion of the carrier S to the side wall 22a of the reaction container portion 2. FIG.

Here, since the valve 52 is set to the closed state in order to store the chemical solution in the reaction container part 2 in the carrier return mode, the inside of the reaction container part 2 is supplied with the chemical solution and is pressurized, thereby maintaining a constant If the chemical solution exceeds the amount, it will be in a state where it cannot be sent. Therefore, in the carrier return mode, the gas (mainly gas, including air bubbles) in the reaction container part 2 is released to the drain tank 11 by setting the exhaust part 9 to the open state, regardless of the chemical solution to be sent. Therefore, it is possible to store the chemical solution.

However, if the exhaust part 9 is always set to the open state, the fluid (mainly gas) in the reaction container part 2 is discharged, and depending on the type of the filter 24 (fluid resistance by the filter 24), the chemical solution may be removed from the filter 24. There is a possibility that the gas may be discharged from the exhaust portion 9 without passing through the . Therefore, in the carrier return mode, the chemical solution is supplied by alternately switching between the chemical solution supply state and the container discharge state. Here, the chemical solution supply state is a state in which the chemical solution is supplied while the exhaust unit 9 is closed and the second chemical solution supply unit 73 and the chemical solution discharge unit 72 are in the liquid feeding state. Further, the container discharge state is a state in which the second chemical liquid supply unit 73 and the chemical liquid discharge unit 72 are in a liquid supply stop state and the exhaust unit 9 is open.

That is, when the chemical solution is supplied from the second port 21b with the valve 59 closed and the chemical solution supplied from the second port 21b by closing the valve 59, the pressure in the reaction vessel portion 2 increases, but the exhaust portion 9 is closed. Therefore, the chemical solution is introduced into the reaction container main body against the fluid resistance of the filter 24 . If this state is continued, the pressure inside the reaction container portion 2 will increase, and the chemical solution supplied from the chemical solution discharge portion 72 will not enter. When the pressure in the reaction container part 2 is higher than a certain level, the valve 59 is opened, and the three-way valve 55 is closed to stop the supply of the chemical solution and switch to the container discharge state. of fluid is discharged and the increased pressure can be returned. Then, the chemical solution is supplied again in the chemical solution supply state. By switching between the chemical supply state and the container discharge state in this manner, the chemical can be supplied while avoiding the problem that the supplied chemical is discharged from the exhaust unit 9 without passing through the filter 24. The timing of switching between the chemical solution supply state and the container discharge state can be set to a predetermined timing at which the chemical solution can be smoothly introduced by controlling the pressure of the reaction container section 2 or time control.

Further, the control device is set to perform the residual liquid feeding operation so that the chemical liquid after weighing is supplied to the reaction container section 2 without remaining. In this embodiment, the residual liquid feeding operation can be performed by the gas-liquid sensor 32a, and after the gas-liquid sensor 32a is turned off, the residual liquid is removed by performing an extra liquid feeding operation. It is designed to deliver liquid. Specifically, the pipe 45 is provided with a gas-liquid sensor 32 a so that it can be detected whether or not there is a chemical solution in the pipe 45 . The gas-liquid sensor 32a is turned on by the passage of the chemical and then turned off to detect the completion of passage of the chemical. By grasping in advance how much liquid feeding operation is performed from the mounting position of the gas-liquid sensor 32a to feed the residual liquid in the pipe 45 to the reaction container part 2, the liquid in the pipe 45 Residual liquid can be sent. For example, when the chemical liquid remaining in the second port 21b from the mounting position of the gas-liquid sensor 32a flows into the reaction container part 2 by alternately performing the chemical liquid supply state and the container discharge state three times, From the time when the gas-liquid sensor 32a turns from ON to OFF, the chemical liquid supply state and the container discharge state are alternately performed three times as the residual liquid feeding operation, thereby reliably feeding the residual liquid in the pipe 45. can do. The sensor mounting position can be freely set by this residual liquid feeding operation. That is, normally, in order to detect the completion of liquid transfer, it is preferable to install a sensor near the reaction vessel in order to minimize the amount of residual liquid in the pipe 4. Since the chemical solution remaining in the pipe 4 after the sensor reaction can be sent without affecting the sensor mounting position, the sensor can be mounted at a desired position.

Also in the normal supply mode, the residual liquid feeding operation is performed in the same manner. That is, in the normal supply mode, the pipe 44 is provided with the gas-liquid sensor 32b. , the chemical liquid remaining in the first port 21a is sent from the gas-liquid sensor 32b to the reaction vessel part 2 without leaving any liquid. In the above embodiment, an example was described in which the residual liquid feeding operation in the carrier return mode was controlled by the number of repetitions of the chemical liquid supply state and the container discharge state. good too.

In the above description, the target is the chemical liquid, but the cleaning liquid can be the target instead of the chemical liquid, and even when the cleaning liquid is the target, the flow of the cleaning liquid is controlled by the control device described above.

As described above, according to the chemical synthesizing apparatus, since the second chemical supply section 73 is provided, it is possible to prevent the carrier S from adhering to the inner wall of the reaction vessel section 2 . That is, even if the carrier S tries to adhere to the inner wall of the reaction vessel part 2 due to the shaking of the liquid surface of the chemical liquid, the carrier S is supplied from the second chemical liquid supply unit 73 provided above the liquid surface of the chemical liquid. is suppressed from adhering to the inner wall of the reaction vessel part 2, it can be flowed back to the chemical solution side. The inner wall of the reaction container part 2 is the inner wall of the reaction container part 2 formed by the reaction container main body 22 and the lid part 23, although the side wall 22a is mainly described in the above embodiment.

Further, according to the chemical synthesis apparatus of the above embodiment, since the second chemical solution supply unit 73 is provided separately from the first chemical solution supply unit 71, after the chemical solution is discharged from the chemical solution discharge unit 72 on the upper side in the vertical direction, , the carrier adhering to the inner wall of the reaction container part 2 can be dropped. That is, by contacting the carrier with the chemical liquid supplied from the second chemical liquid supply unit 73, the carrier is dropped together with the chemical liquid to be supplied, and the carrier can be returned to the lower end of the reaction container section 2. Therefore, it becomes easier to contact with the chemical solution supplied from the first chemical solution supply part 71 on the lower end side, and the reaction efficiency between the carrier and the chemical solution can be enhanced.

In the above embodiment, the second chemical supply unit 73 is connected to the chemical discharge unit 72, and the chemical supplied from the second chemical supply unit 73 is supplied to the reaction container unit 2 through the chemical discharge unit 72. As described above, the chemical may be supplied directly from the second chemical liquid supply section 73 to the reaction vessel section 2 . Specifically, in FIG. 2, in addition to the second port 21b and the discharge port 91, a third port (not shown) is provided in the upper end lid portion of the reaction container portion 2, and the pipe 46 is connected to the third port. It may be configured such that the measured chemical solution and washing solution are supplied to the reaction vessel section 2 through the pipe 46 and the third port.

Further, in the above-described embodiment, in the carrier return mode, the chemical solution is supplied to the reaction container part 2 by alternately switching between the chemical solution supply state and the container discharge state. It may be supplied. That is, when the carrier S adhering to the reaction vessel main body 22 can be removed in one chemical solution supply state, the chemical solution may be supplied only in one chemical solution supply state to perform the synthesis reaction.

Further, in the above embodiment, the gas-liquid sensors 32a and 32b are used as the sensors for detecting whether or not the liquid transfer is completed. may be used. For example, a capacitive proximity sensor, a transmissive photomicrosensor, or the like can be used.

Moreover, in the above-described embodiment, an example in which the guide member 8 is the filter 24 has been described, but any member may be used as long as it guides the chemical solution that has been sent to the side wall 22 a of the reaction container portion 2 . For example, as shown in FIG. 6, a conical member may be provided near the entrance of the reaction vessel part 2, and the outer edge thereof may be provided so as to lead to the wall surface continuous with the side wall 22a of the reaction vessel main body 22. . Even with such a member, the chemical supplied from the second port 21b is supplied into the reaction container main body 22 along the side wall 22a of the reaction container main body 22. can be dropped.

Further, in the above-described embodiment, an example in which the filter 24 is provided in the reaction vessel section 2 has been described, but it may be provided in the chemical solution discharge section 72 . For example, as shown in FIG. 6, it may be provided inside the pipe 4 connected to the first port portion 21 a and the exhaust port 91 .

Further, in the above-described embodiment, the chemical supplied from the second chemical-solution supply portion 73 (in the above-described embodiment, the pipe 45 inserted through the second port 21b) is supplied to the reaction vessel portion 2 by the guide member 8 (filter 24). Although the example of being guided by the side wall 22a has been described, even without the guide member 8, a wall surface continuing to the side wall 22a of the reaction container part 2 is formed in the lid part 23, and the supplied chemical solution is transmitted to the wall surface. can be configured to Specifically, as shown in FIG. 10A, the lid portion 23 is formed with an insertion hole 23b penetrating to the bottom surface portion 23a, and the pipe 45 is inserted through the insertion hole 23b. The tip of the pipe 45 is provided in contact with the inner wall of the insertion hole 23b. As a result, the chemical solution f supplied from the pipe 45 can be transmitted to the side wall 22a of the reaction container portion 2. As shown in FIG. That is, the chemical solution f supplied from the pipe 45 is in contact with the inner wall of the insertion hole 23b at the tip of the pipe 45, so that the chemical solution f flowing out from the opening of the pipe 45 flows along the inner wall of the insertion hole 23b due to surface tension. flow like Since the inner wall of the insertion hole 23b is formed continuously with the side wall 22a of the reaction vessel portion 2 through the bottom surface portion 23a of the lid portion 23, the chemical solution f flowing along the inner wall of the insertion hole 23b It flows from the portion 23a along the side wall 22a. In this way, by connecting the opening of the pipe 45 to the side wall 22a of the reaction container portion 2, the supplied chemical solution f can be made to flow along the side wall 22a of the reaction container portion 2.

In FIG. 10(a), an example in which the opening of the pipe 45 is accommodated in the insertion hole 23b has been described, but as shown in FIG. It may be provided so as to protrude from 23a. Even in this case, the chemical solution f coming out of the opening of the pipe 45 can be transmitted to the side wall 22a of the reaction container part 2 through the bottom part 23a by surface tension. That is, the structure formed continuously on the side wall 22a of the reaction container part 2 includes a structure in which the chemical solution f coming out of the opening of the pipe 45 finally flows along the side wall 22a due to surface tension. This prevents the carrier S from adhering to the inner wall of the reaction vessel part 2 (the inner wall of the reaction vessel part 2 including the side wall 22a of the reaction vessel part main body 22 and the bottom part 23a of the lid part 23). Even if is adhered, the adhering carrier S can be dropped and flowed back to the chemical liquid side.

REFERENCE SIGNS LIST 1 chemical storage unit 2 reaction container unit 3 weighing unit 4 piping 8 guide member 9 discharge unit 11 drainage tank (container unit)
21a first port 21b second port 24 filter 31 measuring container 32 gas-liquid sensor 71 first chemical supply unit 72 chemical discharge unit 73 second chemical supply unit 91 discharge port S carrier (beads)

Claims (9)

a chemical solution containing portion containing a chemical solution;
a reaction vessel part for reacting the chemical solution and the carrier;
, wherein the chemical solution synthesizing device transfers the chemical solution from the chemical solution storage unit to the reaction container unit without contacting the atmosphere,
a first chemical solution supply unit connected to the reaction container unit and supplying a chemical solution to the reaction container unit; and a chemical solution discharge unit provided vertically above the first chemical solution supply unit,
A chemical synthesizing device comprising a second chemical supply unit for suppressing adhesion of the carrier to the reaction vessel. a chemical solution containing portion containing a chemical solution;
a reaction vessel part for reacting the chemical solution and the carrier;
, wherein the chemical solution synthesizing device transfers the chemical solution from the chemical solution storage unit to the reaction container unit without contacting the atmosphere,
a first chemical solution supply unit connected to the reaction container unit and supplying a chemical solution to the reaction container unit; and a chemical solution discharge unit provided vertically above the first chemical solution supply unit,
A chemical synthesizing apparatus, comprising: a second chemical supply unit for dropping a carrier adhering to an inner wall of the reaction container after discharging the chemical from the chemical discharge unit. 3. The chemical synthesizing apparatus according to claim 1, wherein the second chemical supply unit is connected to the chemical discharge unit, and the chemical is supplied by causing the chemical discharge unit to flow backward. 4. The chemical liquid supply device according to claim 1, wherein the chemical liquid supplied from the second chemical liquid supply section is supplied along a side wall of the reaction container section. 5. The chemical synthesizing apparatus according to claim 1, wherein the chemical in the reaction vessel is discharged by causing a reverse flow through the first chemical supply. 6. The chemical synthesizing apparatus according to claim 1, wherein the reaction container section is provided with an exhaust section for discharging gas in the reaction container section. 7. The reaction vessel part according to claim 1, wherein a guide member is provided to guide the chemical supplied through the second chemical supply part to a side wall of the reaction vessel part. Chemical synthesizer. 8. The chemical synthesizing apparatus according to claim 7, wherein the guiding member is shared with a filter. 9. The chemical synthesizing apparatus according to claim 1, wherein a cleaning liquid is used instead of the chemical liquid.

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