Chemical solution synthesis device

Abstract

To provide a medical liquid synthesis device capable of easily feeding medical liquid to a reaction vessel part for enhancing reaction efficiency of the medical liquid without bringing the medical liquid into contact with the ambient air.SOLUTION: A medical liquid synthesis device comprises: a medical liquid storage part for storing medical liquid; and a reaction vessel part for reacting the medical liquid and a carrier, in which the medical liquid is fed from the medical liquid storage part to the reaction vessel part without bringing the medical liquid into contact with the ambient air. The medical liquid synthesis device further comprises: a first medical liquid feeding part which is coupled to the reaction vessel part and feeds the medical liquid; and a second medical liquid feeding part, and further comprises: a discharge part for discharging fluid in the reaction vessel part.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to a chemical solution synthesizing apparatus for synthesizing a chemical solution that is fed without being exposed to the atmosphere, and more particularly to a chemical solution synthesizing apparatus capable of suppressing a decrease in synthesis efficiency.

Background Art

[0002] In a chemical solution synthesizing apparatus for chemically synthesizing proteins, peptides, polymers, nucleic acids, etc., a plurality of chemical solutions (reagents) are supplied to a reaction vessel section and chemical synthesis is performed. For example, when synthesizing nucleic acids, a carrier (porous beads) is provided in the reaction vessel section, and while sequentially supplying chemical solutions to this reaction vessel section, treatments such as detritylation, coupling, oxidation, capping, etc. are repeatedly performed to sequentially bind bases to the beads.

[0003] As a general chemical solution synthesizing apparatus, for example, as shown in FIG. 7, a reaction vessel section 100 that houses a carrier 110 (see FIG. 8) and to which a chemical solution is supplied, a chemical solution storage section 101 such as a chemical solution tank 101 that stores the chemical solution to be supplied to the reaction vessel section 100, and a drain tank 102 that stores the drained liquid discharged from the reaction vessel section 100 are provided, and each is connected by a pipe 103. Specifically, the reaction vessel section 100 has a first port 105 through which the chemical solution passes at the upper end in the vertical direction and a second port 106 through which the chemical solution passes at the lower end in the vertical direction, and the supply and discharge of the chemical solution are performed through the first port 105 and the second port 106 according to the situation. And when storing and reacting the chemical solution in the reaction vessel section 100, usually the chemical solution is supplied through the second port 106 at the lower end and discharged from the first port 105 at the upper end (see FIG. 8(a)). Also, when supplied from the first port 105 at the upper end, the chemical solution is supplied so as to pass through the reaction vessel with the second port 106 in an open state. Thereafter, the chemical solution after the reaction is discharged to the drain tank 102 through the first port 105 or the second port 106. That is, in such a chemical solution synthesizing apparatus, the chemical solution and the carrier 110 can be subjected to a synthesis reaction without the chemical solution being exposed to the atmosphere (for example, see Patent Document 1 below).

Prior Art Documents

Patent Document

[0004]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0005] However, in the above chemical solution synthesizing apparatus, there was a risk that the synthesis efficiency in the reaction vessel section 100 would decrease. That is, in the above chemical solution synthesizing apparatus, when it is desired to store the chemical solution in the reaction vessel section 100, the chemical solution is supplied through the second port 106 at the lower end in order to increase the synthesis efficiency with the carrier 110. However, after storing the chemical solution in the reaction vessel section 100 and causing a synthesis reaction, when the chemical solution is discharged from the first port 105 at the upper end (see Fig. 8(a)), as shown in Fig. 8(b), a phenomenon occurs where the carrier 110 remains attached to the upper part of the reaction vessel section 100. When it is desired to store a small amount of the chemical solution in the reaction vessel section 100 in this state and cause a reaction, when the chemical solution is supplied from the second port 106, the chemical solution does not reach the attached carrier 110, and there is a problem that the reaction cannot be sufficiently carried out.

[0006] To solve this problem, the chemical solution may be supplied and stored through the first port 105. However, when trying to supply the chemical solution from the first port 105 and store it in the reaction vessel section 100, there is no escape path for the air in the reaction vessel section 100, and it is very difficult to fill the entire reaction vessel section 100 with the chemical solution. Therefore, there is a problem that a predetermined amount of the chemical solution cannot be reacted with the carrier 110, and the synthesis efficiency deteriorates.

[0007] The present invention has been made in view of the above problems, and an object thereof is to provide a chemical solution synthesizing apparatus capable of easily supplying a chemical solution to a reaction vessel section without exposing the chemical solution to the atmosphere and increasing the reaction efficiency of the chemical solution.

Means for Solving the Problems

[0008] To solve the above problems, the chemical solution synthesizing apparatus of the present invention includes a chemical solution storage unit for storing a chemical solution, and a reaction vessel unit for reacting the chemical solution with a carrier, and is a chemical solution synthesizing apparatus in which the chemical solution is fed from the chemical solution storage unit to the reaction vessel unit without contacting the atmosphere, and has a first chemical solution feeding unit connected to the reaction vessel unit for feeding the chemical solution, and a second chemical solution feeding unit, and further includes a discharging unit for discharging the fluid in the reaction vessel unit. The second chemical solution delivery unit is disposed vertically below the first chemical solution delivery unit, and the discharge unit is disposed at a height position equal to or higher than the height position of the first chemical solution delivery unit. It is characterized by the following.

[0009] According to the above chemical solution synthesizing apparatus, since the reaction vessel unit is provided with a discharging unit, the air and the fluid containing the chemical solution in the reaction vessel unit can be discharged through the discharging unit. That is, when supplying the chemical solution from the first chemical solution feeding unit to store the chemical solution in the reaction vessel unit, even if the first chemical solution feeding unit is arranged at the upper part, by opening the discharging unit, the fluid in the reaction vessel unit can be discharged through the discharging unit. Thereby, even if the first chemical solution feeding unit is arranged at the upper part, the chemical solution can be smoothly supplied, and the chemical solution can be stored in the reaction vessel unit. Further, since the chemical solution can be smoothly supplied from the first chemical solution feeding unit at the upper part, the carrier attached in the reaction vessel unit can be dropped by the flow of the chemical solution, and the chemical solution and the carrier can be sufficiently reacted. Therefore, by providing a discharging unit separately from the first chemical solution feeding unit, the chemical solution can be easily supplied to the reaction vessel unit without contacting the atmosphere, and the reaction efficiency of the chemical solution can be improved. Since the discharge unit is disposed at the highest position, the chemical solution delivered from the first chemical solution delivery unit cannot be directly discharged from the discharge unit, and the fluid in the reaction vessel unit can be discharged from the discharge unit.

[0012] Also, a forward supply state in which the chemical solution is supplied from the second chemical solution feeding unit to the reaction vessel and a reverse supply state in which the chemical solution is supplied from the first chemical solution feeding unit to the reaction vessel unit are formed to be switchable, and in the reverse supply state, the configuration may include an open state of the discharging unit for discharging the fluid in the reaction vessel unit.

[0013] According to this configuration, both the first chemical solution feeding unit and the second chemical solution feeding unit can supply a chemical solution to the reaction vessel unit and discharge the chemical solution from the reaction vessel unit. Furthermore, in the reverse supply state, since the discharge part is in an open state, the chemical solution supplied from the first chemical solution feeding unit can be stored in the reaction vessel unit.

[0014] In addition, the first chemical solution feeding unit and the second chemical solution feeding unit are configured to be able to switch between a liquid feeding state in which the chemical solution is fed and a liquid feeding stop state in which the feeding of the chemical solution is stopped. In the reverse supply state, the discharge part is in a closed state, and a chemical solution supply state in which the chemical solution is supplied with the first chemical solution feeding unit in an open state, and a container discharge state in which the fluid in the reaction vessel unit is discharged with the discharge part in an open state and the first chemical solution feeding unit in a closed state are alternately switched, so that the chemical solution may be configured to be supplied to the reaction vessel unit.

[0015] According to this configuration, in the chemical solution supply state, since the discharge part is in a closed state, it is possible to suppress the chemical solution fed through the first chemical solution feeding unit from being directly discharged from the discharge part before being accommodated in the reaction vessel unit. And in this chemical solution supply state, since the pressure in the reaction vessel unit gradually increases, when a certain pressure is reached, the fluid (air) is discharged from the discharge part by the container discharge state to return the pressure. By repeating this, it is possible to reliably supply the chemical solution from the first chemical solution feeding unit to the reaction vessel unit without discharging the chemical solution from the discharge part.

[0016] In addition, it may have a sensor for detecting whether or not the feeding from the first chemical solution feeding unit is completed, and after the sensor detects, Residual in the pipe from the mounting position of the sensor a residual feeding operation for feeding the residual chemical solution may be performed.

[0017] According to this configuration, since a residual feeding operation for feeding the residual chemical solution is performed after the sensor reacts, the degree of freedom in the mounting position of the sensor is improved, and the measured chemical solution can be reliably fed to the reaction vessel unit.

[0018] Further, the specific mode of the residual liquid feeding operation may be configured to be performed by alternately repeating the chemical liquid supply state and the container discharge state.

[0019] Further, a storage container portion capable of storing a fluid is provided on the downstream side of the reaction vessel portion, the discharge portion is connected to the storage container portion, and the fluid discharged from the discharge portion may be configured to be discharged into the storage container portion without contacting the atmosphere.

[0020] According to this configuration, since a storage container is provided on the downstream side of the discharge portion, compared with the case where the discharge portion is an atmosphere release valve, it is possible to suppress the gas in the reaction vessel portion from leaking to the outside and prevent the atmosphere from flowing into the reaction vessel from the atmosphere release valve. Further, by controlling the pressure of the storage container to be lower than that of the reaction vessel portion, the discharge amount from the discharge portion can be controlled by the differential pressure. That is, compared with the case where the discharge portion is an atmosphere release valve, the discharge state from the discharge portion can be controlled.

[0021] Further, the reaction vessel portion may be configured to include a filter that suppresses the discharge of the carrier.

[0022] According to this configuration, the carrier can be retained in the reaction vessel even if the chemical liquid is discharged from any of the first chemical liquid feeding portion, the second chemical liquid feeding portion, and the discharge portion.

[0023] Further, a guiding member for guiding the chemical liquid fed from the first chemical liquid feeding portion to the side wall of the reaction vessel portion may be provided in the reaction vessel portion.

[0024] According to this configuration, the chemical liquid fed from the first chemical liquid feeding portion is guided to the side wall of the reaction vessel portion by the guiding member, and the guided chemical liquid flows along the side wall. Thereby, the carrier attached to the side wall can be washed off.

[0025] As a specific mode of the guiding member, the configuration can be simplified by sharing it with the filter.

[0026] Further, the first chemical solution feeding section may be configured to be in contact with the filter.

[0027] According to this configuration, since the pressure of the chemical solution fed from the first chemical solution feeding section acts on the filter, the chemical solution can be pressure-fed to the reaction vessel section without being discharged from the discharge section.

[0028] Further, the discharge section may be configured to be provided with a filter that suppresses the discharge of the carrier.

[0029] According to this configuration, it is possible to suppress the carrier in the reaction vessel section from being discharged through the discharge section. That is, even when the reaction vessel section is filled with the chemical solution and the fluid (air) is discharged from the discharge section, the problem of the carrier being discharged from the discharge section can be avoided.

Effect of the Invention

[0030] According to the chemical solution synthesizing apparatus of the present invention, the chemical solution can be easily supplied to the reaction vessel section without exposing the chemical solution to the atmosphere, and the reaction efficiency of the chemical solution can be increased.

Brief Description of the Drawings

[0031]

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Figure 7

Figure 8

Embodiments for Carrying Out the Invention

[0032] Embodiments of the chemical solution synthesizing apparatus according to the present invention will be described with reference to the drawings.

[0033] FIG. 1 is a piping route diagram showing a chemical solution synthesizing apparatus according to an embodiment of the present invention. In this embodiment, an example in which a chemical solution (reagent) is used as a fluid will be described. However, the present invention is not limited to chemical solutions and can also be applied when performing chemical synthesis, mixing, etc. on liquids other than chemical solutions.

[0034] As shown in FIG. 1, the chemical solution synthesizing apparatus includes a chemical solution tank 1 which is a chemical solution storage section for storing a chemical solution, a measuring section 3 for measuring the chemical solution, a reaction vessel section 2 for accommodating a carrier S (porous beads. Hereinafter also referred to as beads. See FIG. 2), and a drainage tank 11 which is a storage container section for storing the drained liquid discharged from the reaction vessel section 2, and they are connected by piping 4 respectively. Then, after the chemical solution supplied from the chemical solution tank 1 is measured by the measuring section 3, when the chemical solution is supplied to the reaction vessel section 2, the chemical solution and the carrier S come into contact in the reaction vessel section 2 and are chemically synthesized. Then, the chemically synthesized chemical solution is discharged by being sent to the drainage tank 11. For example, when synthesizing nucleic acids, a large number of porous carriers S are contained in the reaction vessel section 2, and while sequentially supplying the measured chemical solution to the reaction vessel section 2, processes such as detritylation, coupling, oxidation, and capping are repeatedly performed to sequentially bind bases to the beads.

[0035] The chemical liquid tank 1 is for storing reagents used in chemical synthesis. In the example of Fig. 1, three chemical liquid tanks 1 are illustrated, but actually a number of chemical liquid tanks 1 are provided, and each chemical liquid tank 1 is connected to the metering unit 3 by a pipe 42. That is, the chemical liquid contained in each chemical liquid tank 1 is fed to the metering unit 3 without being mixed with other chemical liquids.

[0036] A pressure adjusting means 6 is connected to the chemical liquid tank 1, and the chemical liquid in the chemical liquid tank 1 is configured to be fed by pressure by this pressure adjusting means 6. 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 can be supplied to the chemical liquid tank 1 through this pipe 41. That is, when the gas in the gas tank 61 is supplied, the pressure of the chemical liquid tank 1 is adjusted to the pressure of the gas tank 61, and the chemical liquid in the chemical liquid tank 1 is fed to the metering unit 3 by forming a differential pressure with the pressure in the metering unit 3. And by adjusting the pressure of the gas tank 61, the flow rate of the chemical liquid fed from the chemical liquid tank 1 can be adjusted. That is, when the differential pressure between the pressure of the chemical liquid tank 1 and the metering unit 3 is increased, the feeding speed of the chemical liquid fed from the chemical liquid tank 1 is increased and the amount of chemical liquid can be increased, and when the differential pressure between the pressure of the chemical liquid tank 1 and the metering unit 3 is decreased, the feeding speed of the chemical liquid fed from the chemical liquid tank 1 is decreased and the amount of chemical liquid can be suppressed.

[0037] Also, valves 51 are provided in the pipes 42 and 41. These valves 51 selectively connect the target chemical liquid tank 1 and the metering unit 3. That is, with the valve 51 of the chemical liquid tank 1 selected as the supply target in the open state (open state), by supplying gas from the gas tank 61 to pressurize the chemical liquid tank 1, the pressure of the chemical liquid tank 1 is controlled to be greater than the pressure of the metering unit 3, and the chemical liquid in the selected chemical liquid tank 1 is fed to the metering unit 3 through the pipe 42. Note that when there is no need to particularly distinguish the pipes 41, 42, ···, they are simply referred to as pipe 4.

[0038] In addition, in this embodiment, the pressure regulating means 6 will be described by taking the example of using a gas tank 61. However, instead of the gas tank 61, a gas supply source provided in the building where the chemical solution synthesizing apparatus is installed may be used. Further, the gas in this gas tank 61 is a gas that does not react with the chemical solution in the chemical solution tank 1 (for example, argon gas or the like).

[0039] In addition, the metering unit 3 accurately measures the supplied chemical solution. In this embodiment, the mass of the supplied chemical solution is measured so that the amount of the chemical solution to be reacted with the carrier S in the reaction vessel unit 2 can be accurately measured. That is, the metering unit 3 has a metering container 31 and a load cell (not shown) connected to the metering container 31, and the chemical solution stored in the metering container 31 is measured by the load cell.

[0040] A pipe 42 is connected to the upper end of the metering container 31, and a pipe 43 is connected to the lower end. The chemical solution sent from the chemical solution tank 1 is supplied through the pipe 42, and the chemical solution after metering is discharged through the pipe 43. Specifically, with the valve 51 of the pipe 4 connecting the selected chemical solution tank 1 and the metering container 31 in the open state, and the selected chemical solution tank 1 being pressurized by the gas tank 61, the chemical solution is supplied to the metering container 31 through the pipe 42. Then, in the reaction vessel unit 2, when the amount of the chemical solution required for one synthesis reaction is measured and at the same time the liquid feeding is stopped, the chemical solution required for the synthesis reaction is stored in the metering container 31. Then, the chemical solution after metering is fed from the metering container 31 to the reaction vessel unit 2 through the pipe 43.

[0041] The liquid feeding from this metering unit 3 is performed by the gas tank 62 (pressure regulating means 6). That is, a gas tank 62 is connected to the metering container 31 separately from the gas tank 61 so that gas can be supplied from the gas tank 62 to the metering container 31. Then, when gas is supplied from the gas tank 62 to the metering container 31, the pressure of the metering container 31 is regulated, and the differential pressure between the metering unit 3 and the reaction vessel unit 2 is regulated, so that the chemical liquid in the metering container 31 is fed to the reaction vessel unit 2. In the example of FIG. 1, the chemical liquid after metering is supplied to the reaction vessel unit 2 through the pipes 43 and 44 (or the pipe 45 via the pipe 46). Note that for this gas tank 62, a gas supply source installed in the building may be used.

[0042] Further, the reaction vessel unit 2 provides a reaction field for chemically synthesizing by bringing the carrier S contained in the reaction vessel unit 2 into contact with the supplied chemical liquid and the like. In the present embodiment, a glass cylindrical tube extending in one direction is used for the reaction vessel unit 2, and the carrier S is accommodated in the reaction vessel unit 2 (see FIG. 2). In addition, a first chemical liquid feeding portion 71 for feeding the chemical liquid and a second chemical liquid feeding portion 72 are connected to both vertical ends of the reaction vessel unit 2. That is, the chemical liquid is supplied and discharged to and from the reaction vessel unit 2 through the first chemical liquid feeding portion 71 and the second chemical liquid feeding portion 72. In the present embodiment, the first chemical liquid feeding portion 71 is provided on the upper side in the vertical direction, and the second chemical liquid feeding portion 72 is provided on the lower side in the vertical direction, and the chemical liquid can be supplied and discharged from either of them, and can be switched according to the situation.

[0043] The first chemical solution delivery unit 71 supplies or discharges the chemical solution above the reaction vessel unit 2 in the vertical direction. In this embodiment, it is formed by the first port 21a and the pipe 45. That is, as shown in FIG. 2, the reaction vessel unit 2 has the first port 21a above it in the vertical direction, and the pipe 45 is connected to this first port 21a. This pipe 45 is connected to the pipe 46 by a three-way valve 55, and the pipe 46 is connected to the pipe 43 by a three-way valve 53. Therefore, the chemical solution sent from the metering unit 3 through the pipe 43 is supplied to the reaction vessel unit 2 through the three-way valve 53, the pipe 46, the three-way valve 55, and the pipe 45.

[0044] Also, the second chemical solution delivery unit 72 supplies or discharges the chemical solution below the reaction vessel unit 2 in the vertical direction. In this embodiment, it is formed by the second port 21b and the pipe 44. That is, as shown in FIG. 2, the reaction vessel unit 2 has the second port 21b below it in the vertical direction, and the pipe 44 is connected to this second port 21b. Therefore, the chemical solution sent from the metering unit 3 through the pipe 43 is supplied to the reaction vessel unit 2 through the three-way valve 53 and the pipe 44.

[0045] In this way, the chemical solution can be supplied to the reaction vessel unit 2 from either the first chemical solution delivery unit 71 or the second chemical solution delivery unit 72. In particular, when the chemical solution is supplied from the second chemical solution delivery unit 72, the supplied chemical solution is stored while spreading in the radial direction of the reaction vessel unit 2 under the influence of gravity. Therefore, the chemical solution can reach all parts of the reaction vessel unit 2, and the chemical solution can be chemically synthesized with the carrier S in the reaction vessel unit 2 without waste. The form in which the chemical solution is supplied from the second chemical solution delivery unit 72 to the reaction vessel unit 2 is called the forward supply state, and usually, the chemical solution is supplied to the reaction vessel unit 2 in the forward supply state. On the other hand, the form in which the chemical solution is supplied from the first chemical solution delivery unit 71 to the reaction vessel unit 2 with respect to this forward supply state is called the reverse supply state. The forward supply state and the reverse supply state can be set by switching the opening and closing states of the valves, and the supply state can be selected according to the appropriate reaction form for each chemical solution.

[0046] Further, a drainage tank 11, which will be described later, is provided on the downstream side of the reaction vessel section 2, and the reaction vessel section 2 and the drainage tank 11 are connected by a pipe 45. That is, the chemical solution in the reaction vessel section 2 can be discharged through the pipe 45. That is, the chemical solution in the reaction vessel section 2 can be discharged through the first chemical solution feeding section 71. Further, the pipe 44 is connected to the pipe 45 through the pipe 48 by a valve 58, and the reaction vessel section 2 is connected to the drainage tank 11 through the pipe 44, the pipe 48, and the pipe 45. That is, the chemical solution in the reaction vessel section 2 can also be discharged through the second chemical solution feeding section 72.

[0047] Also, on the downstream side of the reaction vessel section 2, a drainage tank 11 is provided as a storage container section for storing the chemical solution and the like drained after the reaction is completed in the reaction vessel section 2. The drainage tank 11 is formed to have a larger capacity than the reaction vessel section 2, and is formed to have a capacity that can store the chemical solution even when it is discharged from the reaction vessel section 2 multiple times. In the present embodiment, the chemical solution after the reaction is discharged into the drainage tank 11 through the first chemical solution feeding section 71 and the second chemical solution feeding section 72. That is, the chemical solution after the reaction is discharged into the drainage tank 11 through the first chemical solution feeding section 71 or the second chemical solution feeding section 72 when the reaction vessel section 2 is pressurized by supplying gas from the gas tank 62. In this way, the chemical solution synthesizing apparatus of the present invention is configured such that the chemical solution is fed without coming into contact with the atmosphere from the chemical solution tank 1 to the drainage tank 11.

[0048] Further, as shown in FIG. 2, the reaction vessel section 2 includes a reaction vessel main body 22 that houses a carrier S (beads), and lid portions 23 provided at both axial ends of the reaction vessel main body 22. The lid portions 23 are provided with a first port 21a and a second port 21b, and a chemical solution can be supplied to or discharged from the reaction vessel main body 22 through the first port 21a or the second port 21b. A filter 24 is provided at the inlet and outlet of the reaction vessel main body 22 so as to block the flow path leading from the reaction vessel main body 22 to the first port 21a and the second port 21b. Thus, if impurities are contained in the chemical solution supplied through the first port 21a or the second port 21b, these impurities can be removed. When the chemical solution after the reaction is discharged from the reaction vessel section 2, it is discharged from the first port 21a and the second port 21b, but the filter 24 prevents the carrier S from being discharged, and it is possible to prevent the carrier S in the reaction vessel section 2 from leaking to the outside.

[0049] Further, the filter 24 is formed in a circular flat plate shape, and its outer edge portion is provided so as to contact a wall surface continuous with the side wall 22a of the reaction vessel main body 22. That is, the reaction vessel main body 22 is formed with a protruding portion connected to the lid portion 23, and the filter 24 is disposed so as to contact the wall surface of the protruding portion. Thereby, the chemical solution supplied from the first port 21a is supplied into the reaction vessel main body 22 along the side wall 22a of the reaction vessel main body 22. That is, when the chemical solution is supplied from the first port 21a, as shown by the arrow in FIG. 2, the chemical solution penetrates into the filter 24 and moves over the entire surface of the filter 24. Then, as more chemical solution is supplied, the chemical solution cannot be retained in the filter 24, and since the outer edge portion of the filter 24 is continuous with the side wall 22a of the main body of the reaction vessel section 2, the chemical solution 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. That is, this filter 24 functions as a guiding member 8 that guides the chemical solution to the side wall 22a of the reaction vessel section 2.

[0050] In addition to the first port 21a, the reaction vessel section 2 is provided with a discharge port 91 as a discharge section 9. This discharge section 9 is for discharging the fluid, i.e., gas and chemical solution, inside the reaction vessel section 2. This discharge port 91 is connected to a pipe 49 that is connected to the drain tank 11, and the fluid discharged from the discharge port 91 is discharged into the drain tank 11 through this pipe 49. A valve 59 is provided in this pipe 49 so that the flow of the fluid discharged from the discharge port 91 can be controlled. That is, when the valve 59 is in the open state and the reaction vessel main body 22 is pressurized, the fluid inside the reaction vessel main body 22 is discharged through the pipe 49, and when in the closed state, the flow of the fluid discharged from the discharge port 91 can be stopped.

[0051] The discharge port 91 is provided on the lid portion 23, like the first port 21a, and is arranged at a height position above the height position of the first chemical solution feeding section 71. In the present embodiment, the first chemical solution feeding section 71 is formed by the first port 21a and the pipe 45 and extends until the pipe 45 abuts against the filter 24. Therefore, the discharge port 91 is arranged at a position higher than the lower end portion of the first chemical solution feeding section 71, i.e., the position P where the pipe 45 abuts against the filter 24. Thereby, the chemical solution can be smoothly supplied from the first port 21a. That is, when the chemical solution is supplied from the first port 21a, the pressure inside the reaction vessel main body 22 increases. However, by keeping the discharge port 91 in the open state, since the discharge port 91 is at a position higher than the first port 21a, it is possible to avoid the chemical solution supplied from the first port 21a being directly discharged from the discharge port 91. Therefore, the gas inside the reaction vessel main body 22 can be efficiently discharged from the discharge port 91, and the chemical solution can be smoothly supplied from the first port 21a.

[0052] Furthermore, since the pipe 45 of the first chemical solution delivery unit 71 is in contact with the filter 24, the chemical solution pumped from the pipe 45 passes through the filter 24 and is directly introduced into the reaction vessel main body 22. That is, when the pipe 45 is separated from the filter 24, the chemical solution pumped from the pipe 45 may flow over the surface of the filter 24 and directly flow to the discharge port 91. However, since the pipe 45 is in contact with the filter 24 and the chemical solution flows through the filter 24 and enters the reaction vessel main body 22, it is possible to avoid the chemical solution being directly discharged from the discharge port 91 before entering the reaction vessel main body 22.

[0053] In addition, the nucleic acid synthesizer has a control device (not shown), and the control device controls each valve and the pressure regulating means 6 so that the flow of the chemical solution is controlled. That is, the control device also controls the supply and discharge modes of the chemical solution to the reaction vessel unit 2, and controls the above-mentioned forward supply state and reverse supply state.

[0054] The forward supply state is a form in which the chemical solution is supplied from the second chemical solution delivery unit 72. Specifically, as shown in FIG. 3, when the three-way valve 53 is set to the open state in the direction of flowing from the pipe 43 to the pipe 44, the valve 52 is set to the open state, and the three-way valve 55 is set to the open state in the direction of flowing into the pipe 45, the chemical solution measured by the metering unit 3 is supplied to the reaction vessel unit 2 through the second chemical solution delivery unit 72. Here, the open / closed states of the valves are indicated by white for the open state and black for the closed state. Then, when the metering container 31 is pressurized by the gas tank 62, a differential pressure is generated with respect to the reaction vessel unit 2, and the chemical solution is fed from the metering container 31. The chemical solution supplied to the reaction vessel unit 2 undergoes a synthesis reaction by contacting the carrier S in the reaction vessel unit 2.

[0055] This forward supply state is the normal chemical solution supply state, and the synthesis reaction can be carried out efficiently. That is, by being fed from the second chemical solution feeding section 72, the chemical solution is introduced from the lower side of the reaction vessel section 2, and the chemical solution can be spread throughout the reaction vessel section 2. That is, since the chemical solution introduced into the reaction vessel section 2 from the lower pipe 44 is affected by gravity, it is stored in the reaction vessel section 2 while spreading radially, and chemical synthesis is carried out with the entire carrier S accommodated in the reaction vessel section 2. If it is introduced from above, due to the influence of gravity, the chemical solution supplied from the first port 21a will directly proceed to the second port 21b, so it is difficult to spread radially. Therefore, although the chemical solution introduced from above undergoes chemical synthesis with the carrier S existing in the axial direction directly below the first port 21a, it is difficult to react with the carrier S located radially away, and there may be a case where unreacted carrier S remains locally. Therefore, in the forward supply state, the carrier S and the chemical solution in the reaction vessel section 2 can react without waste, and it is used as the normal chemical solution supply path.

[0056] And when the reaction between the chemical solution supplied to the reaction vessel section 2 and the carrier S is completed, the chemical solution is discharged. That is, by pressurizing with the gas tank 62, the chemical solution is discharged from the first port 21a and discharged to the drainage tank 11 through the pipe 45 (see Fig. 4(a)).

[0057] The reverse supply state is a chemical solution supply state in the opposite direction to the forward supply state. When the chemical solution is sent from the first chemical solution liquid feeding unit 71, the chemical solution is introduced from above the reaction vessel unit 2 and supplied to the reaction vessel unit 2. Usually, in a chemical solution synthesis apparatus of a type in which each processing unit is connected by piping and a synthesis reaction is carried out without allowing the chemical solution to come into contact with the atmosphere, since the carrier S can be efficiently subjected to a synthesis reaction only in the above-described forward supply state, there is no need to separately provide a path for supplying the chemical solution from above the reaction vessel unit 2. However, when the carrier S is accommodated in the reaction vessel unit 2, if the chemical solution is discharged from the upper first port 21a as in the forward supply state, it may remain attached to the side wall 22a (especially the upper part) of the reaction vessel main body 22 and the upper filter 24 (see Fig. 4(b)). Thus, when the amount of the next chemical solution for the synthesis reaction is small with the carrier S attached, it becomes difficult for the chemical solution to come into contact with the carrier S to which the chemical solution is attached even if the chemical solution is supplied to the reaction vessel unit 2, and there is a problem that it is difficult to efficiently carry out the synthesis reaction. To solve this problem, by setting the reverse supply state, the chemical solution introduced from above can wash away the attached carrier S, thereby enhancing the synthesis efficiency between the chemical solution and the carrier S.

[0058] The reverse supply state is a form in which the chemical solution is supplied from the first chemical solution liquid feeding unit 71. Specifically, as shown in Fig. 5, by setting the three-way valve 53 to the open state in the direction of flow from the piping 43 to the piping 46 and the three-way valve 55 to the open state in the direction of flow from the piping 46 to the reaction vessel unit 2 side, the chemical solution measured by the measuring unit 3 is supplied to the reaction vessel unit 2 through the first chemical solution liquid feeding unit 71. That is, similarly to the forward supply state, the pressure vessel 31 is pressurized by the gas tank 62, thereby generating a differential pressure with respect to the reaction vessel unit 2, and the chemical solution is sent from the measuring vessel 31.

[0059] Here, in order to store the chemical solution in the reaction vessel section 2 in the reverse supply state, the valve 52 is set to the closed state. Therefore, when the chemical solution is supplied and pressurized in the reaction vessel section 2, it will eventually reach a state where liquid feeding is impossible. Thus, in the reverse supply state, by setting the discharge section 9 to the open state, the fluid (mainly gas) in the reaction vessel section 2 can be released into the drain tank 11, enabling the storage of the chemical solution.

[0060] However, if the discharge section 9 is always set to the open state, the fluid (mainly gas) in the reaction vessel section 2 will be discharged. Depending on the type of the filter 24 (fluid resistance by the filter 24), there is a risk that the chemical solution will be discharged from the discharge section 9 without passing through the filter 24. Therefore, in the reverse supply state, 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 where the discharge section 9 is in the closed state and the first chemical solution liquid feeding section 71 is in the liquid feeding state to supply the chemical solution. Also, the container discharge state is a state where the first chemical solution liquid feeding section 71 is in the liquid feeding stop state and the discharge section 9 is in the open state.

[0061] That is, when the valve 59 is closed due to the chemical solution supply state and the chemical solution is supplied from the first port 21a with the discharge part 9 in the closed state, the pressure in the reaction vessel part 2 increases. However, since the discharge part 9 is in the closed state, the chemical solution is introduced into the reaction vessel part 2 against the fluid resistance of the filter 24. That is, the chemical solution is supplied to the reaction vessel part 2 without accumulating between the discharge part 9 and the filter 24. If this state is continued, the pressure in the reaction vessel part 2 increases, and the chemical solution supplied from the first chemical solution liquid feeding part 71 cannot enter. When the pressure in the reaction vessel part 2 becomes higher than a certain level, the valve 59 is opened, and further, the three-way valve 55 is closed to stop the supply of the chemical solution and switch to the container discharge state, so that the fluid in the reaction vessel part 2 can be discharged and the increased pressure can be restored. Then, the chemical solution supply state is set again to supply the chemical solution. In this way, by switching between the chemical solution supply state and the container discharge state, the problem that the supplied chemical solution is discharged from the discharge part 9 without passing through the filter 24 can be avoided, and the chemical solution can be supplied. The timing for 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 in the reaction vessel part 2 or by time control or the like.

[0062] Further, the control device is set to perform a residual liquid feeding operation so that the chemical solution after metering is supplied to the reaction vessel unit 2 without any remaining. In the present embodiment, the residual liquid feeding operation can be performed by the gas-liquid sensor 32a. After the gas-liquid sensor 32a is turned off, the residual liquid is fed by performing an extra feeding operation. Specifically, the gas-liquid sensor 32a is provided in the pipe 45 and can detect whether or not the chemical solution exists in the pipe 45. This gas-liquid sensor 32a can detect that the passage of the chemical solution is completed when it turns off after turning on by the passage of the chemical solution. And, by grasping in advance how much the feeding operation should be performed from the mounting position of the gas-liquid sensor 32a so that the residual liquid in the pipe 45 is fed to the reaction vessel unit 2, the residual liquid in the pipe 45 can be fed. For example, when the chemical solution remaining in the first port 21a from the mounting position of the gas-liquid sensor 32a flows into the reaction vessel unit 2 by alternately performing the above-described chemical solution supply state and the container discharge state three times, from the time when the gas-liquid sensor 32a changes from ON to OFF, as the residual liquid feeding operation, the chemical solution supply state and the container discharge state are alternately performed three times each, so that the residual liquid in the pipe 45 can be reliably fed. That is, by repeating the above-described chemical solution supply state and the container discharge state, the residual liquid in the pipe 45 is supplied to the reaction vessel unit 2 without the chemical solution accumulating between the discharge unit 9 and the filter 24. Further, by this residual liquid feeding operation, the sensor mounting position can be freely set. That is, usually, in order to detect the completion of feeding, it is preferable to mount the sensor near the reaction vessel to minimize the residual liquid in the pipe 4. However, since the above-described residual liquid feeding operation is performed, the chemical solution remaining in the pipe 4 after the sensor reaction can be fed without leaving it in the pipe 4 without affecting the sensor mounting position, so the sensor can be mounted at a desired position.

[0063] Also, the residual liquid feeding operation is similarly performed in the forward supply state. That is, in the forward supply state, a gas-liquid sensor 32b is provided in the pipe 44. After this gas-liquid sensor 32b changes from ON to OFF, the metering container 31 is pressurized by the gas tank 62 for a predetermined time, so that the chemical liquid remaining in the second port 21b from the gas-liquid sensor 32b is fed into the reaction vessel section 2 without leaving any residue. In the above embodiment, an example in which the residual liquid feeding operation in the reverse supply state is controlled by the number of repetitions of the chemical liquid supply state and the container discharge state has been described, but it may be controlled by the time of the chemical liquid supply state.

[0064] Thus, according to the chemical liquid synthesizing apparatus in the above embodiment, since the discharge section 9 is provided in the reaction vessel section 2, the fluid containing air and chemical liquid in the reaction vessel section 2 can be discharged through the discharge section 9. That is, when supplying the chemical liquid from the first chemical liquid feeding section 71 to store the chemical liquid in the reaction vessel section 2, even if the first chemical liquid feeding section 71 is arranged at the upper part, by opening the discharge section 9, the fluid in the reaction vessel section 2 can be discharged through the discharge section 9. Thereby, even if the first chemical liquid feeding section 71 is arranged at the upper part, the chemical liquid can be supplied smoothly, and the chemical liquid can be stored in the reaction vessel section 2. Further, since the chemical liquid can be supplied smoothly from the first chemical liquid feeding section 71 at the upper part, the carrier S attached to the inside of the reaction vessel section 2 can be dropped by the flow of the chemical liquid, and the chemical liquid and the carrier S can react sufficiently. Therefore, by providing the discharge section 9 separately from the first chemical liquid feeding section 71, the chemical liquid can be easily supplied to the reaction vessel section 2 without exposing the chemical liquid to the atmosphere, and the reaction efficiency of the chemical liquid can be increased.

[0065] Also, in the above embodiment, an example in which the chemical liquid is supplied to the reaction vessel section 2 by alternately switching between the chemical liquid supply state and the container discharge state in the reverse supply state has been described, but the chemical liquid may be supplied only in the chemical liquid supply state. That is, when the carrier S attached to the reaction vessel main body 22 can be completely dropped in one chemical liquid supply state, the chemical liquid may be supplied only in one chemical liquid supply state to perform the synthesis reaction.

[0066] In the above embodiment, the case where the sensors for detecting whether the liquid feeding is completed are the gas-liquid sensors 32a and 32b has been described. However, as long as it is a sensor that can detect the chemical solution in the pipe 4, other sensors may be used. For example, a capacitance type proximity sensor, a transmissive photomicrosensor, etc. can be used.

[0067] In the above embodiment, the example where the guiding member 8 is shared with the filter 24 has been described. However, any member can be used as long as it is a member that guides the fed chemical solution to the side wall 22a of the reaction vessel portion 2. For example, as shown in FIG. 6, a conical member may be provided near the inlet and outlet of the reaction vessel portion 2, and its outer edge portion may be provided so as to lead to a wall surface continuous with the side wall 22a of the reaction vessel main body 22. Even with such a member, since the chemical solution supplied from the first port 21a is supplied into the reaction vessel main body 22 along the side wall 22a of the reaction vessel main body 22, the carrier S attached to the side wall 22a can be washed away.

[0068] In the above embodiment, the example where the filter 24 is provided in the reaction vessel portion 2 has been described. However, it may be provided in the first chemical solution feeding portion 71. For example, as shown in FIG. 6, it may be provided in the pipe 4 connected to the first port portion 21a and the discharge port portion 91.

Explanation of Signs

[0069] 1 Chemical solution storage portion 2 Reaction vessel portion 3 Measuring portion 4 Pipe 8 Guiding member 9 Discharge portion 11 Drain tank (accommodating container portion) 21a First port 21b Second port 24 Filter 31 Measuring container 32 Gas-liquid sensor 71 First chemical solution feeding portion 72 Second chemical solution feeding portion 91 Discharge port S support (beads)

Claims

1. A chemical solution storage unit that stores a chemical solution, A reaction vessel unit that reacts the chemical solution with a carrier, A chemical solution synthesizing apparatus comprising: a chemical solution being sent from the chemical solution storage unit to the reaction vessel unit without contacting the atmosphere, having a first chemical solution sending unit and a second chemical solution sending unit that are connected to the reaction vessel unit and to which the chemical solution is sent, further comprising a discharge unit that discharges the fluid in the reaction vessel unit, wherein the second chemical solution sending unit is disposed vertically below the first chemical solution sending unit, and the discharge unit is disposed at a height position equal to or higher than the height position of the first chemical solution sending unit A chemical solution synthesizing apparatus characterized by the above.

2. A forward supply state in which a chemical solution is supplied from the second chemical solution sending unit to the reaction vessel unit and a reverse supply state in which a chemical solution is supplied from the first chemical solution sending unit to the reaction vessel unit are formed to be switchable, and in the reverse supply state, an open state of the discharge unit that discharges the fluid in the reaction vessel unit is included. The chemical solution synthesizing apparatus according to claim 1, characterized by the above.

3. The first chemical solution sending unit and the second chemical solution sending unit are formed to be switchable between a sending state in which a chemical solution is sent and a sending stop state in which the sending of the chemical solution is stopped. In the reverse supply state, the discharge unit is in a closed state, and a chemical solution supply state in which the first chemical solution sending unit is in a sending state and a chemical solution is supplied, and an open state of the discharge unit and a container discharge state in which the first chemical solution sending unit is in a sending stop state and the fluid in the reaction vessel unit is discharged are alternately switched, whereby the chemical solution is supplied to the reaction vessel unit. The chemical solution synthesizing apparatus according to claim 2, characterized by the above.

4. having a sensor that detects whether or not the sending from the first chemical solution sending unit has been completed, and after the sensor detects, a residual sending operation of sending the residual chemical solution remaining in the pipe from the mounting position of the sensor is performed. The chemical solution synthesizing apparatus according to claim 3, characterized by the above.

5. The chemical solution synthesizing apparatus according to claim 4, wherein the residual liquid feeding operation is performed by alternately repeating the chemical solution supply state and the container discharge state.

6. Downstream of the reaction vessel section, there is a storage vessel section capable of storing a fluid. The discharge section is connected to the storage vessel section, and the fluid discharged from the discharge section is discharged into the storage vessel section without coming into contact with the atmosphere. The chemical solution synthesizing apparatus according to claims 1 to 5, characterized in that.

7. The reaction vessel section is provided with a filter for suppressing the discharge of the carrier. The chemical solution synthesizing apparatus according to claims 1 to 6, characterized in that.

8. The reaction vessel section is provided with a guiding member for guiding the chemical solution fed from the first chemical solution feeding section to the side wall of the reaction vessel section. The chemical solution synthesizing apparatus according to claim 7, characterized in that.

9. The guiding member is shared with the filter. The chemical solution synthesizing apparatus according to claim 8, characterized in that.

10. The first chemical solution feeding section is formed in contact with the filter. The chemical solution synthesizing apparatus according to claims 7 to 9, characterized in that.

11. The discharge section is provided with a filter for suppressing the discharge of the carrier. The chemical solution synthesizing apparatus according to claims 1 to 10, characterized in that.

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