阅读说明：本技术 合成装置和计量机构 (Synthesizer and metering mechanism ) 是由 井中千草 丹羽主 岩出卓 中北和德 于 2018-03-16 设计创作，主要内容包括：本发明涉及用于选择性地输送多种溶液而进行化学合成的合成装置,提供改善溶液的利用效率、装置结构简化、可靠性高的合成装置。另外,提供准确地进行溶液的计量以改善溶液的利用效率的计量机构。具体地,合成装置(3)具有：多个导出管(6),它们分别从收纳有溶液的多个收纳容器(2)设置；送液单元(24),其通过导出管(6)进行输送；反应容器(9),所输送的溶液进入该反应容器而生成合成物；以及计量机构(15),其在收纳容器(2)与反应容器(9)之间设置于整体流路(25)的中途,对向反应容器(9)输送的溶液进行计量。并且,计量机构(15)选择性地获取多种溶液而进行计量。计量机构(15)具有：保持部(27),其对导出管(6)的下游侧端部(6a)侧进行保持；计量容器(7),其接受从下游侧端部(6a)流出的溶液；以及重量传感器(26),其对计量容器(7)中的重量进行测量。(The invention relates to a synthesis device for selectively delivering a plurality of solutions to perform chemical synthesis, and provides a synthesis device with improved solution utilization efficiency, simplified device structure and high reliability. Further, a metering mechanism is provided which accurately measures the solution to improve the utilization efficiency of the solution. Specifically, the synthesizing device (3) comprises: a plurality of delivery pipes (6) provided from a plurality of containers (2) that contain solutions; a liquid feeding unit (24) which feeds the liquid through the delivery pipe (6); a reaction vessel (9) into which the solution is fed to produce a composition; and a metering mechanism (15) which is provided in the middle of the entire flow path (25) between the storage container (2) and the reaction container (9) and meters the solution to be transferred to the reaction container (9). The metering mechanism (15) selectively takes in and meters a plurality of solutions. The metering mechanism (15) comprises: a holding section (27) that holds the downstream end (6a) side of the delivery pipe (6); a metering container (7) that receives the solution flowing out from the downstream end (6 a); and a weight sensor (26) that measures the weight in the measuring container (7).)

1. A synthesis apparatus for selectively transporting a plurality of solutions to perform chemical synthesis, wherein,

the synthesizing device comprises:

a plurality of pipes extending from a plurality of containers containing a plurality of solutions;

a liquid feeding unit that feeds the solution in the storage container through the pipe;

a reaction container into which a solution selectively transferred from the storage container enters to produce a composition; and

and a metering mechanism provided in the middle of the entire flow path including the plurality of pipes between the storage container and the reaction container, for metering the solution to be transferred to the reaction container.

2. The synthesis apparatus according to claim 1,

the metering mechanism includes a metering container, and a plurality of pipes are collectively provided in the metering container, and a solution is introduced into each of the metering containers through the pipes, and the solution is metered into the metering container.

3. The synthesis apparatus according to claim 1 or 2,

the metering mechanism has:

a measuring container provided in the middle of the entire flow path; and

a sensor that measures a weight in the metering container or detects a level of a solution stored in the metering container.

4. The synthesis apparatus according to any one of claims 1 to 3,

the synthesizing apparatus includes an adjusting means for adjusting a liquid feeding speed of the solution to be measured.

5. The synthesis apparatus according to any one of claims 1 to 4,

the synthesizing device includes an adjusting means for decreasing the liquid feeding speed at an end time period for the measured liquid feeding as compared with a time period before the end time period.

6. The synthesis apparatus according to any one of claims 1 to 5,

the synthesizing apparatus further has:

a valve that stops the liquid feeding for the metering; and

and a control device that constantly acquires a signal from a sensor for measuring the amount of the fluid, and outputs a signal for starting a closing operation to the valve based on the signal.

7. The synthesis apparatus according to any one of claims 1 to 6,

the synthesizing apparatus further has a valve for stopping the liquid feeding for the metering,

the valve begins to close before the solution reaches a specified amount.

8. A synthesis apparatus for selectively transporting a plurality of solutions to perform chemical synthesis, wherein,

the synthesizing device comprises:

a plurality of pipes extending from a plurality of containers containing a plurality of solutions;

a liquid feeding unit that feeds the solution in the storage container through the pipe;

an intermediate container in which a plurality of the pipes are collected and into which a solution is introduced from each of the pipes; and

a reaction vessel into which the solution delivered from the intermediate vessel enters to produce a composition.

9. The synthesis apparatus of claim 8,

the synthesis apparatus has a closed container which accommodates the intermediate container and is filled with a gas.

10. The synthesis apparatus of claim 8,

the intermediate container is a closed container filled with gas.

11. The synthesis apparatus according to any one of claims 8 to 10,

the synthesis apparatus has a metering mechanism including the intermediate container and a sensor for metering the solution introduced into the intermediate container.

12. The synthesis apparatus of claim 11,

the sensor is a weight sensor that measures the weight in the intermediate container,

the metering mechanism further includes a holding portion that holds the plurality of pipes together and is provided so as not to contact the intermediate container.

13. The synthesis apparatus according to claim 11 or 12,

downstream end portions of the plurality of pipes open into the intermediate container at positions lower than an upper end of the intermediate container,

the plurality of pipes include a pipe for introducing a cleaning liquid into the intermediate container,

the sensor is configured to be able to detect the following states:

a state in which the solution is introduced with a first position lower than the opening of the downstream-side end portion as an upper limit; and

the cleaning liquid is introduced to a second position higher than the opening of the downstream end.

14. The synthesis apparatus according to any one of claims 8 to 12,

downstream end portions of the plurality of pipes open into the intermediate container at positions lower than an upper end of the intermediate container,

the plurality of pipes include a pipe for introducing a cleaning liquid into the intermediate container,

the liquid feeding unit feeds the solution to any one of the following states:

a state in which the solution is introduced at a first position lower than the opening of the downstream end portion as an upper limit; and

the cleaning liquid is introduced to a second position higher than the opening of the downstream end.

15. The synthesis apparatus according to any one of claims 8 to 14,

the synthesizing device has a holding part for collecting and holding a plurality of pipes,

introducing a solution into the intermediate container from each of the plurality of pipes collected and held by the holding portion,

the holding portion holds a plurality of pipes in a state where a downstream end portion of one of the plurality of pipes is not in contact with a downstream end portion of another pipe.

16. A metering mechanism selectively takes in a plurality of solutions for metering, wherein,

the metering mechanism has:

a holding section that holds a downstream end side of a pipe through which the solution passes;

a measuring container for receiving the solution flowing out from the downstream end of the pipe; and

a weight sensor that measures a weight in the metering container,

the holding portion is provided so as not to contact the measuring container.

17. The metering mechanism of claim 16,

the holding unit holds a plurality of pipes through which the plurality of types of solutions respectively pass, and the measuring container receives the solutions flowing out from the plurality of pipes.

18. The metering mechanism of claim 16 or 17,

the metering mechanism includes a closed container that accommodates the metering container and is filled with a gas.

19. The metering mechanism of any one of claims 16 to 18,

the metering mechanism has an outlet-side pipe connected to the metering container for sending the metered solution to another region, the outlet-side pipe being composed of the following extra length parts: the excess length portion has one end connected to the measuring container and the other end supported by another member, and is formed to be longer than a distance between the one end and the other end and to be deformable as a whole.

20. The metering mechanism of claim 18,

the metering mechanism has an adjusting means for adjusting the pressure of the gas in the closed container,

the solution in the measuring container is pumped to the outside by the pressure of the gas acting on the solution in the measuring container through the opening of the measuring container formed by the holding portion not being in contact with the measuring container.

Technical Field

The present invention relates to a device for chemical synthesis of proteins, peptides, nucleic acids, etc. The present invention also relates to a metering mechanism used in a synthesis apparatus or the like for chemically synthesizing proteins, peptides, nucleic acids, and the like.

Background

As a method for chemically synthesizing proteins, peptides, nucleic acids, and the like, there is a method in which a plurality of solutions (reagents) are sequentially supplied to a reaction vessel and a reaction is carried out in the reaction vessel. For example, in the case of synthesizing nucleic acids, a large number of beads (beads) are placed in a reaction vessel, and the treatment of detritylation, coupling, acidification, and coating is repeated while sequentially supplying solutions to the reaction vessel, thereby binding bases one by one from the beads.

In some cases, tens of solutions (for example, 20 solutions) are used, and these solutions are selectively transferred to a reaction vessel to generate a composition (nucleic acid) from a molecular material contained in the solution. As an apparatus for performing such chemical synthesis, for example, a synthesis apparatus described in patent document 1 is known.

Disclosure of Invention

Problems to be solved by the invention

Fig. 8 is an explanatory diagram showing a conventional synthesis apparatus in a simplified manner. The synthesizing device comprises: storage containers 90a, 90b, and 90c that respectively store a plurality of solutions 99a, 99b, and 99 c; a reaction vessel 94 for mixing the solutions 99a, 99b, 99 c; and a chamber 95 for accommodating the reaction container 94, wherein the respective accommodating containers 90a, 90b, and 90c are connected to the chamber 95 via pipes 91a, 91b, and 91 c. In the example of fig. 8, the pipes 91a, 91b, and 91c are provided corresponding to the first position P1, the second position P2, and the third position P3, respectively. On the other hand, the reaction container 94 is configured to be movable within the chamber 95 by an actuator not shown, and movable and stopped at the first position P1, the second position P2, and the third position P3. Therefore, the reaction container 94 is configured to be selectively moved to positions (the first position P1, the second position P2, and the third position P3) of the solutions 99a, 99b, and 99c to be mixed, which are necessary for the production of the compound (nucleic acid), and to receive the solutions 99a, 99b, and 99c supplied from the downstream end portions of the pipes 91a, 91b, and 91c in order at the respective positions.

The solutions 99a, 99b, and 99c in the containers 90a, 90b, and 90c are pressurized to supply the solutions 99a, 99b, and 99c to the reaction container 94, and the containers 90a, 90b, and 90c are supplied with an inert gas or the like to deliver the solution. However, when the solutions 99a, 99b, and 99c are supplied under pressure, the liquid is fed only by setting the pressure and the time, and therefore, the amount of the fed liquid is likely to vary due to the influence of pressure fluctuation or the like. Therefore, the supply amount to the reaction container 94 may be excessive or insufficient, and the synthesis of a predetermined reagent may not be performed. Therefore, for safety, the plurality of solutions 99a, 99b, 99c are respectively supplied to the reaction vessel 94 in an amount several times more than the amount theoretically required. As described above, the cost is increased when an excessive amount of the solution is used in the past, particularly when the composition is mass-produced.

Therefore, the object of the invention 1 is to improve the utilization efficiency of the solution.

Further, in the conventional synthesis apparatus, a mechanism for moving the reaction container 94 is required, and the reaction container 94 needs to be moved every time the solution is transferred, and particularly, when the kind of the solution is increased, there is a problem that the apparatus configuration and the processing operation become complicated. Therefore, a failure is likely to occur during operation, and if a failure occurs, the treatment of chemical synthesis is stopped. Further, since the reaction vessel 94 receives the supply of the solution after moving to each position corresponding to the downstream end of the pipes 91a, 91b, and 91c, there is a problem that the operation time required for the synthesis becomes long.

Therefore, the object of the invention 2 is to provide a highly reliable synthesizer with a simplified device configuration.

Therefore, the object of the invention 3 is to provide a metering mechanism that accurately measures a solution to improve the utilization efficiency of the solution.

Means for solving the problems

The synthesis apparatus of the present invention is an apparatus for selectively feeding a plurality of solutions to perform chemical synthesis, wherein the synthesis apparatus comprises: a plurality of pipes extending from the plurality of containers containing the plurality of solutions; a liquid feeding unit that feeds the solution in the storage container through the pipe; a reaction container into which a solution selectively transferred from the storage container enters to produce a composition; and a metering mechanism provided in the middle of the entire flow path including the plurality of pipes between the storage container and the reaction container, for metering the solution to be transferred to the reaction container.

According to this synthesis apparatus, a required amount of the solution can be measured and transferred to the reaction vessel, and the solution utilization efficiency can be improved as compared with the conventional apparatus.

Preferably, the metering mechanism includes a metering container, and a plurality of pipes are collectively provided in the metering container, and the metering container is introduced with the solution from each of the pipes, and the solution is metered into the metering container. According to the metering mechanism, the plurality of solutions are selectively introduced into the metering container, and the solution introduced into the metering container is metered. Since the metering container is shared by a plurality of pipes, it is not necessary to provide a metering mechanism for each pipe (solution), and the synthesis apparatus can be simplified. Further, it is also possible to mix and measure a plurality of solutions in a measuring vessel, and if the solutions are mixed at a stage earlier than the stage of introducing each solution into the reaction vessel, it is possible to shorten the mixing time.

Further, it is preferable that the metering mechanism includes: a measuring container provided in the middle of the entire flow path; and a sensor that measures the weight in the metering container or detects the level of the solution stored in the metering container. According to this configuration, the solution can be temporarily stored in the measuring container and measured, and the measured solution can be transferred to the reaction container.

Further, it is preferable that the synthesizing apparatus includes an adjusting means for adjusting a liquid feeding speed of the solution to be measured. When the liquid feeding speed is high (particularly, when the target amount is small), an error is likely to occur in the measurement, but the liquid feeding speed is reduced by the adjusting means, so that the measurement error can be suppressed.

Further, when the liquid feeding speed is always decreased for the purpose of measurement, it takes time and the work efficiency is sometimes decreased, and when the liquid feeding speed is always increased for the purpose of measurement, a measurement error is likely to occur. Therefore, it is preferable to have an adjusting means for decreasing the liquid feeding speed in the end time period for the measured liquid feeding as compared with the time period before the end time period. According to this configuration, in the liquid feeding for metering, the operation efficiency can be improved by increasing the start liquid feeding speed, and the metering error can be suppressed by decreasing the liquid feeding speed at the end of metering.

Further, it is preferable that the synthesizing apparatus further includes: a valve that stops the liquid feeding for the metering; and a control device that constantly acquires a signal from a sensor for measuring the amount of the fluid, and outputs a signal for starting a closing operation to the valve based on the signal. According to this configuration, the solution can be measured in real time, and a predetermined amount of solution can be obtained with high accuracy.

Preferably, the synthesis apparatus further includes a valve for stopping the liquid feeding for the measurement, and the valve starts a closing operation before the solution reaches a predetermined amount. According to this configuration, the solution flowing during the valve closing operation is estimated, and the valve closing operation is started at an early timing in advance, whereby the metering can be performed with high accuracy.

The present invention also provides an apparatus for selectively transporting a plurality of solutions to perform chemical synthesis, wherein the synthesis apparatus comprises: a plurality of pipes which are respectively extended from a plurality of containers for storing a plurality of solutions; a liquid feeding unit that feeds the solution in the storage container through the pipe; an intermediate container which is provided by collecting a plurality of the pipes and into which the solution is introduced from each of the pipes; and a reaction vessel into which the solution delivered from the intermediate vessel enters to produce a composition.

According to this synthesis apparatus, the solutions transferred from the respective storage containers are once introduced into the intermediate container, and then the solution transferred from the intermediate container to the reaction container is used to generate a synthesis product. Therefore, a mechanism for moving the reaction container is not required, and the reaction container does not need to be moved every time the solution is transferred as in the conventional case, and therefore, the processing operation is simplified. This simplifies the configuration of the device, reduces the number of portions where defects may occur, and provides a highly reliable synthesis device. In addition, the operation time required for synthesis can be shortened.

In addition, when it is necessary to mix a plurality of solutions, the solutions can be mixed in an intermediate container and then transferred to a reaction container, thereby improving the reaction efficiency.

The synthesis apparatus may further include a closed container that accommodates the intermediate container and is filled with a gas. In this case, even if the plurality of solutions used include a solution that changes or deteriorates when brought into contact with the atmosphere (outside air), the composition can be produced without deteriorating the quality.

Alternatively, the intermediate container may be a closed container filled with a gas. In this case, even if the plurality of solutions used include a solution that changes or deteriorates when brought into contact with the atmosphere (outside air), the composition can be produced without deteriorating the quality.

Further, it is preferable that the synthesis apparatus has a metering mechanism including the intermediate container and a sensor for metering the solution introduced into the intermediate container. In this case, an intermediate container is used as the metering container. Further, a required amount of the solution can be measured and transferred to the reaction container, and the utilization efficiency of the solution can be improved. In addition, although there are a plurality of solutions required, since a plurality of pipes are collected and each solution is received in an intermediate container, a single set of metering means (intermediate container and sensor) for metering may be provided.

Preferably, the sensor is a weight sensor for measuring a weight in the intermediate container, and the metering mechanism further includes a holding unit for holding the plurality of pipes in a state of being collected and not contacting the intermediate container. When the pipe extending from the storage container is in contact with the intermediate container, for example, when tension acts on the pipe, the pipe adversely affects the measurement result of the weight sensor.

Further, since a plurality of pipes are provided in a collective manner in the intermediate container, the intermediate container is brought into contact with a plurality of solutions, and therefore, it is sometimes necessary to clean the intermediate container. Therefore, it is preferable that downstream end portions of the plurality of pipes open into the intermediate container at positions lower than an upper end of the intermediate container, and the plurality of pipes include a pipe for introducing a cleaning liquid into the intermediate container, and the sensor is configured to be able to detect a state of: a state in which the fluid is easily introduced with a first position lower than the opening of the downstream end portion as an upper limit; and a state in which the cleaning liquid is introduced to a second position higher than the opening of the downstream-side end portion.

Alternatively, as another means, a plurality of pipes may be configured such that downstream end portions of the pipes open into the intermediate container at positions lower than an upper end of the intermediate container, a pipe for introducing a cleaning liquid into the intermediate container is included in the plurality of pipes, and the liquid feeding unit may feed the solution in any one of the following states: a state in which the solution is introduced at a first position lower than the opening of the downstream end portion as an upper limit; and a state in which the cleaning liquid is introduced to a second position higher than the opening of the downstream-side end portion.

According to these respective configurations, the intermediate container and the downstream end portion of the pipe in the intermediate container can be cleaned by the cleaning liquid introduced to the second position. Further, when the solution is measured, the introduced solution is introduced into the first position, so that the introduced solution can be prevented from contacting other piping, and the purity of the solution can be prevented from being lowered.

Further, it is preferable that the cleaning solution is a main solvent used for a plurality of solutions, and thus, even if the cleaning solution remains in the intermediate container, the purity of the solution can be prevented from being lowered.

Preferably, the synthesis apparatus further includes a holding unit configured to collect and hold the plurality of pipes, and the solution is introduced into the intermediate tank from each of the plurality of pipes collected and held by the holding unit, and the holding unit holds the plurality of pipes in a state where a downstream end of one of the plurality of pipes is not in contact with a downstream end of another pipe. According to this configuration, the solution flowing out from the downstream end of one pipe can be prevented from contacting the downstream end of the other pipe, and it is preferable for the solution temporarily stored in the intermediate tank to be kept pure when necessary.

The present invention also provides a metering mechanism for selectively taking and metering a plurality of solutions, the metering mechanism comprising: a holding section that holds a downstream end side of a pipe through which the solution passes; a measuring container for receiving the solution flowing out from the downstream end of the pipe; and a weight sensor for measuring the weight in the measuring container, wherein the holding part is provided in a state of not contacting with the measuring container.

According to the present invention, the amount of the solution can be managed. Further, when the pipe through which the solution passes is in contact with the measuring container, for example, when tension is applied to the pipe, the measurement result of the weight sensor is adversely affected, but according to the above configuration, the influence of the pipe does not affect the weight sensor, and high-precision measurement can be performed.

Preferably, the holding unit holds a plurality of pipes through which the plurality of types of solutions pass, respectively, in a collected manner, and the measuring container receives the solutions flowing out from the plurality of pipes. In this case, although there are a plurality of solutions required, a measuring container and a sensor for measuring can be used in common.

Preferably, the measuring mechanism further includes a closed container which accommodates the measuring container and is filled with a gas. According to this configuration, even if the plurality of solutions to be used include a solution that is deteriorated or deteriorated when brought into contact with the atmosphere (outside air), the quality is not degraded.

The metering mechanism further includes an outlet-side pipe connected to the metering container for sending the metered solution to another region, and the outlet-side pipe includes the extra length portion: the excess length portion has one end connected to the measuring container and the other end supported by another member, and is formed to be longer than a distance between the one end and the other end and to be deformable as a whole. In the case where, for example, tension is applied to the outlet-side pipe as an external force, the external force can be released by elastically deforming the entire extra-length portion, and the influence of the outlet-side pipe does not easily affect the weight sensor, thereby enabling highly accurate measurement.

Preferably, the metering mechanism having the closed container further includes an adjusting means for adjusting a pressure of a gas in the closed container, and the solution in the metering container is pressure-fed to the outside by the pressure of the gas acting on the solution in the metering container through an opening of the metering container formed by the holding portion not being in contact with the metering container. According to this configuration, the solution in the measuring container can be fed under pressure by the gas in the closed container. Therefore, a pump for feeding liquid is not required.

Effects of the invention

According to the invention of claim 1, a required amount of the solution can be measured and transferred to the reaction vessel, and the solution utilization efficiency can be improved as compared with the conventional one.

Further, according to the invention of claim 2, a mechanism for moving the reaction container is not required, and the reaction container does not need to be moved every time the solution is transferred, and the processing operation is simplified. This simplifies the configuration of the device, reduces the number of portions where defects may occur, and provides a highly reliable synthesis device.

Further, according to the invention of claim 3, the amount of the solution can be managed and the solution can be measured with high accuracy to improve the utilization efficiency of the solution.

Drawings

Fig. 1 is a configuration diagram showing an example of a synthesizing apparatus of the present invention.

Fig. 2 is a view showing a schematic configuration of the metering mechanism.

Fig. 3 is a schematic configuration diagram showing a second example of the metering mechanism.

Fig. 4 is a schematic configuration diagram showing a third example of the metering mechanism.

Fig. 5 is an explanatory view of the holding portion as viewed from below.

Fig. 6 is a block diagram showing another example of the synthesizing apparatus.

Fig. 7 is a configuration diagram showing another example of the synthesizing apparatus.

Fig. 8 is an explanatory diagram showing a conventional synthesis apparatus in a simplified manner.

Fig. 9 is a reference diagram of a synthesizing apparatus using a pump.

Detailed Description

[ Overall Structure of Synthesis apparatus ]

Fig. 1 is a configuration diagram showing an example of a metering mechanism of the present invention and a synthesizing apparatus of the present invention having the metering mechanism. The synthesis apparatus of the present invention is an apparatus for chemically synthesizing proteins, peptides, nucleic acids, etc., and a plurality of solutions (reagents) are sequentially supplied into a reaction vessel 9, and chemical synthesis is performed in the reaction vessel 9. In the case of synthesizing a nucleic acid, a large number of beads are placed in the reaction vessel 9, and the detritylation, coupling, acidification, and coating processes are repeated while sequentially supplying the solution to the reaction vessel 9, whereby a molecular material such as a base is bound from the bead one by one, for example. The number of solutions used is several tens (for example, 20 kinds), and these solutions are selectively transferred to the reaction vessel 9, and a composition (nucleic acid) is generated from the molecular material contained in the solution.

In the present embodiment, 19 kinds of solutions (reagents) are used. The amount varies depending on the product to be chemically synthesized. The synthesizer 3 has a region in which the same number (19) of containers (reagent bottles) 2-1, 2-2, and … as the number of types of solutions are installed, and the solutions are stored in the containers 2-1 and 2-2 …, respectively. In FIG. 1, only two storage containers (2-1 and 2-2) are shown, and the other storage containers (2-3 to 2-19) are not shown. The synthesizing apparatus 3 further includes storage containers 2 to 20 for storing the cleaning liquid. The storage containers 2-1 to 2-20 have the same structure (although the sizes may be different). Hereinafter, the reference numeral attached to the storage container will be abbreviated as "2". Each storage container 2 is a closed container, and an introduction pipe 5 and a discharge pipe 6 are connected thereto.

The synthesizing apparatus 3 has: a tank 4 for storing a pressurized gas, the introduction pipe 5, the delivery pipe 6, an intermediate container 7, an intermediate pipe 8, a reaction container 9, a metering mechanism 15, and a control device 16. The tank 4 is filled with a gas having a pressure higher than that of the atmosphere, and in the present embodiment, argon gas is filled as an inert gas. Instead of the inert gas, a sterilized gas (air) may be used. The same number of inlet pipes 5 (20 pipes in the present embodiment) as the plurality of storage containers 2 are branched from a common upstream pipe 10, and a regulator (electropneumatic regulator) 11 and an opening/closing valve 12 are provided in the upstream pipe 10. The upstream pipe 10 is connected to the tank 4, supplies pressurized gas to each storage container 2, and adjusts the internal pressure of each storage container 2 by a pressurizer 11. The solution in each storage container 2 is pumped from the delivery pipe 6 by increasing the internal pressure of the storage container 2 by the pressurized gas. That is, the solution in each storage container 2 is pressure-fed to the intermediate container 7 through the delivery pipe 6 by the pressure difference between each storage container 2 and the intermediate container 7. As described above, in the present embodiment, the liquid feeding unit 24 for feeding the solution in the storage container 2 is of a pressure-feed type, and the liquid feeding unit 24 includes: a tank 4, an upstream pipe 10, a pressurizer 11, an opening/closing valve 12, and an introduction pipe 5.

Valves 14 are provided in the delivery pipes 6 connected to the container 2 for storing the solution. The valve 14 of the present embodiment is a pinch valve. The delivery pipe 6 is formed of a pipe (tube) at least a part of which is elastically deformable, and the pinch valve 14 has a function of stopping the flow of the solution from the storage container 2 in the delivery pipe 6 by pressing the delivery pipe 6 (the part) and a function of adjusting the flow rate of the solution flowing therethrough. By selecting the pinch valve 14 placed in the open state, a specific solution among the solutions in the plurality of containers 2 can be selectively transferred (pumped) to the intermediate container 7 through the delivery pipe 6. The selection of the pinch valve 14 placed in the open state is performed by the control device 16. That is, the control device 16 sends a signal for placing in the open state to a specific pinch valve 14 and maintains the other pinch valves 14 in the closed state according to a program stored in its internal memory. The valve provided in the delivery pipe 6 may be a valve other than the pinch valve 14.

The intermediate container 7 is a container for measuring each solution, and will be described later. The intermediate container 7 is a bottomed cylindrical container (see fig. 2) capable of storing each solution, and in the present embodiment, a plurality of delivery pipes 6 are provided so as to be collected in an inlet region (opening 7a) of the intermediate container 7. Therefore, the solution selectively delivered through the delivery pipe 6 is introduced into the intermediate container 7 and stored in the intermediate container 7. The number of intermediate containers 7 is smaller than that of the storage containers 2, and only one intermediate container 7 is provided in the present embodiment. That is, the intermediate container 7 is used for a plurality of solutions in common.

The metering mechanism 15 meters the solution stored in the intermediate container 7. In the metering mechanism 15, the intermediate container 7 functions as a metering container. The measurement result of the measurement mechanism 15 is sent to the control device 16 (see fig. 1), and the control device 16 controls the opening and closing operation of the pinch valve 14 based on the measurement result to take a predetermined amount of solution into the intermediate container 7. Then, the predetermined amount of the solution is transferred to the reaction vessel 9 through the intermediate pipe 8. An on-off valve 21 is provided in the intermediate pipe 8, and the on-off valve 21 is closed during metering.

The solution is supplied from the intermediate container 7 to the reaction container 9 under pressure, and pressurized gas from the tank 4 is used. At this pressure feeding, the on-off valve 21 is opened. In order to perform this pressure feeding, the metering mechanism 15 has a closed container 29 that houses the intermediate container 7. A pipe 17 for pressurized gas is provided between the closed casing 29 and the tank 4. A second regulator (electropneumatic regulator) 18 is provided in the pipe 17. As will be described later, the intermediate container 7 is opened (opening 7a) in the closed container 29, the pressure (internal pressure) of the pressurized gas in the closed container 29 acts on the solution stored in the intermediate container 7, and the solution in the intermediate container 7 is pressure-fed to the reaction container 9 through the intermediate pipe 8 by the pressure difference between the closed container 29 (intermediate container 7) and the reaction container 9.

As described above, when the solution is selectively transferred from at least one of the plurality of storage containers 2 to the intermediate container 7 and is metered by the intermediate container 7, the solution is transferred to the reaction container 9. Such supply of the solution to the reaction vessel 9 is repeated while changing the kind of the solution, and a plurality of kinds of solutions are sequentially supplied to the reaction vessel 9, and chemical synthesis is performed in the reaction vessel 9. In this embodiment, a large number of beads are provided in the reaction vessel 9, and nucleic acids are synthesized by binding bases one by one from the beads.

In the reaction vessel 9, when a solution is supplied from the intermediate pipe (primary side passage) 8, the solution is passed through the discharge side pipe 19 (secondary side passage) and discharged.

The operation of the various valves (pinch valve 14, opening/closing valves 12, 21) is controlled by the control device 16. The operation of the regulators 11 and 18 is also controlled by the control device 16.

As described above, the synthesis apparatus 3 selectively feeds a plurality of solutions to the reaction vessel 9, and chemically synthesizes the solutions in the reaction vessel 9 using the materials contained in the solutions. In the present embodiment, the configuration is such that: a plurality of delivery pipes 6 as a plurality of pipes extend from the plurality of containers 2 containing the plurality of solutions, and the solution in each container 2 is delivered to the intermediate container 7 through the delivery pipe 6 and further to the reaction container 9 by a liquid delivery unit 24 including the tank 4, the upstream pipe 10, the inlet pipe 5, and the like. A metering mechanism 15 is provided in the middle of the overall flow path 25 including the plurality of pipes (delivery pipes 6) between the storage containers 2 and the reaction container 9, and the solution to be fed to the reaction container 9 is metered in the intermediate container 7 by the metering mechanism 15. In the reaction container 9, a predetermined amount of solution selectively transferred from the plurality of containers 2 is input, and a composition is generated from the materials contained in each solution. The overall flow path 25 includes a flow path on the downstream side (the reaction vessel 9 side) of the storage vessel 2, and includes an intermediate pipe 8 in addition to the delivery pipe 6. The piping or the devices included in the entire flow path 25 have properties (solvent resistance) to withstand the solvent (solvent) of the solution.

[ concerning the measuring mechanism 15]

The measuring mechanism 15 includes the intermediate container 7 functioning as a measuring container and a sensor 26. As described above, the intermediate container (measuring container) 7 is provided in the middle of the entire flow path 25, and receives the solution selectively flowed out from the plurality of delivery pipes 6. The weighing mechanism 15 shown in fig. 2 has a sensor 26 for measuring the weight in the intermediate container 7. A specific configuration will be described, in which the sensor 26 is a weight sensor, and in the present embodiment, is constituted by a strain gauge load cell. By measuring the weight of the solution stored in the intermediate container 7 by the measuring mechanism 15, the solution can be measured in the intermediate container 7 with high accuracy. In the present embodiment, an example in which a strain-type load cell is used has been described, but any load cell such as an electromagnetic type, a piezoelectric type, a capacitance type, a magnetic bias type, or a gyro type may be used, and the load cell may be used to configure the weight sensor of the present invention.

Instead of the weight sensor 26, a sensor 26-2 (see fig. 3) that detects the liquid level of the solution stored in the intermediate container 7 may be used. A specific structure in this case will be described later.

The metering mechanism 15 shown in fig. 2 includes a holding portion 27 in addition to the intermediate container 7 that receives the solution flowing out of the delivery pipe 6 and the weight sensor 26 that measures the weight in the intermediate container 7. The holding portion 27 is provided in the vicinity of the opening 7a of the intermediate container 7, and holds the plurality of delivery tubes 6 in a single position. In the present embodiment, 20 delivery tubes 6, the number of which is the same as that of the storage container 2, are collected and held by the holding portion 27. As shown in fig. 2, the plurality of delivery pipes 6 penetrate through a flange portion 36 provided on the upper wall 29a of the closed casing 29, and the holding portion 27 holds the delivery pipes 6 so as to be aligned with the downstream end portion 6a side thereof. The delivery pipe 6 penetrates the flange portion 36, but airtightness (i.e., sealing) is ensured therebetween. In the present embodiment, although the same number of delivery pipes 6 as the number of storage containers 2 are described, in the case where there are storage containers 2 in which a solution is not required to be metered, the delivery pipes 6 extending from the storage containers 2 may be connected to the intermediate pipe 8 located on the downstream side of the intermediate container 7 without being held by the holding portion 27.

The intermediate container 7 is suspended in the closed container 29. Therefore, the support member 28 is provided in the closed casing 29, the intermediate casing 7 is supported by the first arm portion 28a of the support member 28, and the first arm portion 28a receives the weight of the intermediate casing 7 and the solution stored in the intermediate casing 7. A weight sensor (e.g., a load cell) 26 is attached to the base portion side of the first arm portion 28a, and the weight sensor 26 measures the weight of the intermediate container 7 (containing the solution) via the arm portion 28 a. The signal of the weight sensor 26 is input to the control device 16 (see fig. 1). The holding portion 27 (first member 27a) is supported by the second arm portion 28b of the support member 28. The first arm portion 28a and the second arm portion 28b are provided independently, and do not transmit force therebetween.

The holding portion 27 has: a first member 27a holding a plurality of delivery pipes 6 by collecting portions 6b on the upstream side of the downstream end 6 a; and a second member 27b that holds the downstream end portion 6a together and is connected by a connection portion not shown. The first member 27a is a plate-like member, and the delivery pipe 6 penetrates the first member 27 a. The second member 27b is a plate-like member, and the downstream end portion 6a of the delivery pipe 6 penetrates the second member 27 b. Fig. 5 is an explanatory view of the holding portion 27 (second member 27b) as viewed from below. In the second member 27b, all the downstream-side end portions 6a are arranged at intervals narrower than the intervals held by the first members 27 a. That is, the second member 27b functions as a spacer, and brings the one downstream side end portion 6a into a state of not contacting the other downstream side end portion 6a, and the solution flowing out from the downstream side end portion 6a of the one delivery pipe 6 does not contact the downstream side end portion 6a of the other delivery pipe 6 (that is, it is ensured that the solution flowing out from the downstream side end portion 6a of the one delivery pipe 6 to be supplied and the solution adhering to the downstream side end portion 6a of the other delivery pipe 6 are not mixed).

In fig. 2, the first member 27a is positioned above (outside) the intermediate container 7, and the second member 27b is positioned inside the intermediate container 7, but the holding portion 27 including these first member 27a and second member 27b and the plurality of delivery tubes 6 (downstream-side end portions 6a) held by the holding portion 27 are not in contact with the intermediate container 7. Therefore, the intermediate container 7 is opened at the upper portion, that is, the intermediate container 7 is not covered by the holding portion 27 and is opened in the closed container 29. As a result, as described above, the pressure (internal pressure) of the pressurized gas in the closed vessel 29 can act on the solution stored in the intermediate vessel 7, and after the solution is measured, the solution in the intermediate vessel 7 is pressure-fed to the reaction vessel 9 by the pressure difference between the closed vessel 29 and the reaction vessel 9.

In this way, in the metering mechanism 15 of the present embodiment, since the plurality of delivery pipes 6 are collected in the intermediate container 7 and the solution is selectively supplied from the plurality of delivery pipes 6, it is possible to selectively take in and meter a plurality of solutions. Therefore, the amount of the solution can be controlled, and a predetermined amount of the solution can be accurately transferred to the reaction container 9. As described above, the holding portion 27 and the intermediate container 7 are provided in a non-contact state. Therefore, although tension may act on the delivery tube 6, the load due to the tension does not affect the measurement of the weight sensor 26. If the delivery tube 6 (and the holding portion 27) comes into contact with the intermediate container 7, if tension acts on the delivery tube 6, the measurement result of the weight sensor 26 is adversely affected. However, according to the configuration of the present embodiment, the influence of the lead-out tube 6 does not affect the weight sensor 26, and the measurement can be performed with high accuracy, and a predetermined amount of solution can be more accurately transferred to the reaction container 9.

As shown in fig. 2, the metering mechanism 15 includes an outlet-side pipe 30 connected to the intermediate tank 7, and the outlet-side pipe 30 is connected to the intermediate pipe 8. The outlet-side pipe 30 is a flow path for sending the solution measured in the intermediate container 7 to the reaction container 9 (other region) through the intermediate pipe 8. The outlet-side pipe 30 is disposed in the closed casing 29, one end 30a of the outlet-side pipe 30 is connected to the lower end of the intermediate casing 7, and the other end 30b of the outlet-side pipe 30 is supported by the bottom wall 29b (other member) of the closed casing 29. The outlet-side pipe 30 is formed of an elastic pipe having a spiral shape as a whole. When a tension force acting as an external force acts on the outlet-side pipe 30, the measurement result of the weight sensor 26 is adversely affected, but according to the configuration of the present embodiment, the entire spiral pipe is elastically deformed, and the tension force can be released. As a result, the influence of the outlet-side pipe 30 does not easily affect the weight sensor 26, and more accurate measurement is possible. The outlet-side pipe 30 of the present embodiment has been described as having a spiral shape, but may be bent into a U-shape or the like as long as it has an extra length to such an extent that it does not affect the weight sensor 26 holding the measuring container 7. Thus, the outlet-side pipe 30 may be constituted by the following extra length portions: the excess length portion is formed to be longer than the distance (linear distance) between the one end portion 30a and the other end portion 30b and to be deformable as a whole, with one end portion 30a connected to the intermediate container 7 and the other end portion 30b supported by the closed container 29. That is, the extra length portion may be a pipe having a spiral shape or a pipe bent in a U shape.

As described above, the closed casing 29 accommodates the intermediate casing 7, and the upper portion of the intermediate casing 7 opens into the closed casing 29. Therefore, the gas in the closed vessel 29 comes into contact with the solution introduced into the intermediate vessel 7. Therefore, the closed casing 29 is filled with a gas having a small influence on the solution. As the gas, an inert gas or a sterilized gas (air) can be used as described above. In the present embodiment, the closed vessel 29 is filled with argon gas as an inert gas, and the gas is supplied from the tank 4. Therefore, even if the plurality of solutions used in the synthesis apparatus 3 include a solution that is deteriorated or deteriorated when brought into contact with the atmosphere (outside air), the synthesis apparatus can produce a synthesis product without deteriorating the quality.

The gas filled in the closed vessel 29 is also used as a medium for pressure-feeding the (metered) solution stored in the intermediate vessel 7 to the reaction vessel 9. The regulator 18 provided in the pressurized gas pipe 17 (see fig. 1) connecting the closed casing 29 and the tank 4 adjusts the amount of gas to be supplied to the closed casing 29. Accordingly, the pressure of the solution stored in the intermediate container 7 is controlled by adjusting the internal pressure of the closed container 29. Thereby, a pressure difference is generated between the closed vessel 29 (intermediate vessel 7) and the reaction vessel 9, and the solution in the intermediate vessel 7 is pressure-fed to the reaction vessel 9 by the pressure difference.

As described above, the metering mechanism 15 of the present embodiment also has a function of transferring the solution stored in the intermediate container 7 and metered to the reaction container 9. That is, the pressure regulator 18 is provided as an adjusting means for adjusting the pressure of the gas in the closed casing 29. As described above, the holding portion 27 holding the plurality of delivery tubes 6 together does not contact the intermediate container 7, and the opening 7a is formed in the intermediate container 7 in the closed container 29. The solution in the intermediate container 7 can be pumped to the outside by the pressure of the gas acting on the solution in the intermediate container 7 through the opening 7 a.

In the present embodiment, since the solution transfer from the plurality of storage containers 2 to the intermediate container 7 and the solution transfer from the intermediate container 7 to the reaction container 9 are performed by the liquid transfer unit 24 including the tank 4, a pump (electric pump or hydraulic pump) for transferring the solution is not required. Further, the solution transfer from the plurality of containers to the intermediate container 7 and the solution transfer from the intermediate container 7 to the reaction container 9 are performed by the pressurized air of the common tank 4, so that the synthesizer 3 can be simplified.

[ modification of the measuring mechanism 15]

Next, a case where the sensor provided in the metering mechanism 15 detects the liquid level of the solution stored in the intermediate container 7 will be described (hereinafter, referred to as a second example). Fig. 3 is a schematic configuration diagram showing a second example of the measuring mechanism 15. In the second example, the metering mechanism 15 also includes the intermediate container 7 functioning as a metering container. As in the embodiment shown in fig. 2 (first example), the intermediate container 7 is provided in the middle of the entire flow path 25 (see fig. 1) and receives the solution selectively flowed out from the plurality of delivery pipes 6. The plurality of delivery pipes 6 are collected in the holding portion 27, and the downstream end portions 6a of the delivery pipes 6 are introduced into the opening portion 7a of the intermediate container 7.

The sensor 26-2 of the metering mechanism 15 of the second example is different from the first example in that it detects the liquid level 37 of the solution introduced into the intermediate container 7. That is, the sensor 26-2 is provided at a specific height position with respect to the intermediate container 7, the liquid surface 37 is gradually raised by introducing the solution from the delivery pipe 6 into the intermediate container 7, and when the liquid surface 37 of the solution reaches a predetermined height, the sensor 26-2 detects this and sends a signal to the control device 16. As the sensor 26-2, a noncontact type displacement sensor, such as a laser sensor, can be employed.

In the case of the second example, it is preferable to make the intermediate container 7 an elongated container. This is to improve the resolution in the measurement. That is, the reason for this is that by making the intermediate container 7 slim, a minute difference in volume becomes a difference in height and is easily visualized. For example, in the case of the intermediate container 7 having a circular cross section, it is preferably an elongated shape having a height of 10 times or more the cross-sectional diameter.

A predetermined amount of the solution is measured in the intermediate container 7, but the predetermined amount differs depending on the solution. That is, in the second example as well, since one intermediate container 7 is used in common when measuring a plurality of solutions (a plurality of storage containers 2), the height of the liquid surface 37 of the intermediate container 7 is different when a predetermined amount (required amount) differs depending on the type of the solution. Therefore, in the second example, the sensor 26-2 is supported by the support member 31 so as to be able to move up and down, and the height position of the sensor 26-2 can be changed by the up-and-down actuator 38 in accordance with the measured solution. This change is performed in response to a signal from the control device 16.

In the second example, the sensor 26-2 detects the liquid level of the solution in the intermediate container 7, and therefore the influence of the tension of the delivery pipe 6 is not related to the metering result. Therefore, the holding portion 27 for holding the plurality of delivery tubes 6 together and the intermediate container 7 do not need to be in contact with each other as in the first example. The outlet-side pipe 30 connected to the bottom of the intermediate tank 7 may not be a spiral pipe. When the holding portion 27 is in contact with the intermediate container 7, the closed container 29 is not necessary. That is, as shown in the third example of fig. 4, the holding portion 27 functions as a lid of the intermediate container 7, and the holding portion 27 closes the opening of the intermediate container 7 to form a closed space in the intermediate container 7. When the solutions are supplied to the closed intermediate container 7 and the metering is completed, the gas is supplied from the tank 4 through the pipe 17 into the intermediate container 7, and the solution in the intermediate container 7 can be pumped to the reaction container 9. In the first, second, and third embodiments, the same components are denoted by the same reference numerals, and the description of the same components will be omitted.

In the third example, the intermediate container 7 is a closed container filled with gas. In the third example, the first member 27a of the holding portion 27 closes the upper opening of the intermediate container 7. The plurality of lead-out pipes 6 penetrate the first member 27a, but airtightness (i.e., sealing) is ensured between the lead-out pipes 6 and the first member 27 a. The upper opening of the intermediate container 7 is narrow, and the first member 27a uses a diaphragm 39 in order to ensure airtightness between the first member 27a covering such upper opening and each of the plurality of (20 in the present embodiment) delivery tubes 6. The diaphragm 39 is a rubber-made film member, and can block the inside and outside of the intermediate container 7 by sealing the hole due to penetration with an elastic force in a state where the delivery pipe 6 is penetrated. As a result, the intermediate container 7 is filled with the gas, and even if the plurality of solutions to be used include a solution that is deteriorated or deteriorated when it comes into contact with the atmosphere (outside air), a composition can be produced without deteriorating the quality.

[ measuring mechanisms 15 for respective modes ]

As in the case of the first example shown in fig. 2, the second example shown in fig. 3 and the third example shown in fig. 4 are each configured such that: the metering mechanism 15 has a holding portion 27 for holding the plurality of lead-out tubes 6 in a collected state, and introduces the solution into the intermediate container 7 from each of the plurality of lead-out tubes 6 held in the collected state by the holding portion 27. In the second and third examples, as in the first example, the second member 27b of the holding portion 27 holds the plurality of delivery tubes 6 in a state where the downstream end portion 6a of one delivery tube 6 of the plurality of delivery tubes 6 is not in contact with the downstream end portion 6a of the other delivery tube 6, as shown in fig. 3, 4, and 5. Therefore, the solution flowing out of the downstream end portion 6a of one delivery pipe 6 can be prevented from contacting the downstream end portion 6a of the other delivery pipe 6, that is, the solutions can be prevented from being mixed. This ensures purity of the solution temporarily stored in the intermediate container 7.

In the metering mechanism 15 of each embodiment, as described above, the plurality of delivery pipes 6 are collectively provided in the intermediate container 7, and the intermediate container 7 is brought into contact with the plurality of solutions. Therefore, it is sometimes necessary to clean the intermediate container 7. Therefore, the metering mechanism 15 has the following structure. In the following, the description will be made by taking the case of the first example as a representative example, but the same applies to the second example and the third example.

As shown in fig. 1, the synthesizing apparatus 3 has a storage container 2-20 for storing the cleaning liquid, and the delivery pipe 6 extending from the storage container 2-20 is also collected together with other delivery pipes 6 by the holding portion 27, so that the cleaning liquid can be supplied to the intermediate container 7. That is, as shown in fig. 2, the plurality of lead pipes 6 collected in the holding portion 27 include the lead pipe 6 for introducing the cleaning liquid into the intermediate container 7. The supply of the cleaning liquid to the intermediate container 7 is performed by the gas in the tank 4 (i.e., pressure-feeding) as in the case of the solution. The downstream end 6a of each of the delivery pipes 6 is open in the intermediate container 7 at a position below the upper end 40 of the intermediate container 7. That is, the discharge port (downstream end 6a) of the solution in the delivery pipe 6 is located below the upper end 40 of the intermediate container 7.

The sensor 26 can detect the state where the cleaning liquid is introduced to the second position Y2 in addition to the state where the solution is introduced to the first position Y1 as an upper limit. The first position Y1 is located at a position lower than the position of the opening of the downstream side end 6a as indicated by an arrow (Y1) in fig. 2, and the second position Y2 is located at a position higher than the opening of the downstream side end 6a as indicated by an arrow (Y2) in fig. 2. In addition, the second position Y2 is located at a position lower than the upper end 40 of the intermediate container 7.

When the solution is selectively supplied to the intermediate container 7 from the storage containers 2-1 and 2-2 (2-19) storing the solution shown in fig. 1 and measured, the sensor 26 detects the state where the solution is introduced with the first position Y1 as the upper limit. In the present embodiment, the closing operation of the pinch valve 14 is started by this detection, which will be described later. That is, when a specific amount of the solution is introduced with the first position Y1 as an upper limit, the supply of the solution is stopped. In this way, in the case where the metering of the solution for the chemical synthesis in the reaction vessel 9 is performed using the intermediate vessel 7, the sensor 26 detects so that the solution does not exceed the first position Y1. To explain the specific operation, the solution is measured at or below the first position Y1 by the sensor 26, and when the sensor 26 detects that the solution exceeds the first position Y1, the control device 16 receives the detection result of the sensor 26 and outputs an error signal, for example.

On the other hand, when the intermediate container 7 is cleaned without measurement, the sensor 26 detects a state (full state) in which the cleaning liquid is introduced to the second position Y2. By this detection, the pinch valve 14 of the delivery pipe 6 extending from the storage container 2-20 storing the cleaning liquid is closed. That is, when the cleaning liquid is introduced to the second position Y2, the supply of the cleaning liquid is stopped. In this way, when the intermediate container 7 is cleaned, the sensor 26 detects the second position Y2 as a reference.

According to this configuration, when the solution is measured, the solution is measured with the first position Y1 as the upper limit. Since the first position Y1 is located at a position lower than the position of the opening of the downstream-side end portion 6a, the solution supplied to the intermediate container 7 can be prevented from contacting the downstream-side end portion 6a of the delivery pipe 6, and the purity of the solution supplied from each delivery pipe 6 can be prevented from decreasing. On the other hand, when the intermediate container 7 is cleaned, the intermediate container 7 and the downstream end portion 6a of the delivery pipe 6 in the intermediate container 7 can be cleaned by the cleaning liquid introduced to the second position Y2. That is, since the second position Y2 is located higher than the opening of the downstream-side end portion 6a, the cleaning liquid supplied to the intermediate tank 7 contacts all of the downstream-side end portions 6a, and the downstream-side end portions 6a can be cleaned. The cleaning solution is preferably a main solvent (main solvent) used for a plurality of solutions, and thus even if the cleaning solution remains in the intermediate container 7, the purity of the solution can be prevented from being lowered. Similarly, when the liquid level 37 of the solution in the intermediate container 7 is detected by the sensor 26-2, the measurement is performed with the first position Y1 as the upper limit, and when the cleaning is performed, the cleaning liquid is supplied to the second position Y and the cleaning is performed.

As described above, the following case is explained: the solution is introduced into the intermediate container 7 with the sensor 26 at the first position Y1 as an upper limit, and the cleaning solution is introduced into the intermediate container 7 at the second position Y2. Thus, the solution and the cleaning liquid can be accurately measured so as to avoid the contact of the solution with the downstream end 6a of each lead-out tube 6 during the measurement and to prevent the contact of the cleaning liquid with the downstream end 6a of each lead-out tube 6 during the cleaning. As this modification, the following state may be formed without using the sensor 26: a state in which the solution is introduced into the intermediate container 7 with the first position Y1 as an upper limit; and a state where the cleaning liquid is introduced to the second position Y2 of the intermediate container 7. That is, the following state is also possible: the control device 16 manages the liquid feeding time and the like of each solution by the liquid feeding unit 24 including the introduction pipe 5 and the like, the liquid feeding unit 24 feeds each solution for a predetermined liquid feeding time to introduce the solution with the first position Y1 lower than the opening of the downstream end portion 6a as an upper limit, and the liquid feeding unit 24 feeds the cleaning liquid for a predetermined liquid feeding time to introduce the cleaning liquid to the second position Y2 higher than the opening of the downstream end portion 6 a. In this way, the liquid feeding unit 24 including the introduction tube 5 and the like can be configured to feed the respective solutions so as to be in the following states: a state in which the solution is introduced with the first position Y1 as an upper limit; and a state where the cleaning liquid is introduced to the second position Y2. In this case, although the accuracy of the supply amount of the solution or the cleaning liquid is slightly lowered, the same effect as that in the case of using the sensor 26 can be obtained.

[ treatment for measurement ]

The solution metering process performed by the metering mechanism 15 in the synthesis apparatus 3 having the above-described configuration will be described. The difference lies in that: while the sensor 26 measures a predetermined amount of solution by weight in the first example, the sensor 26-2 detects a predetermined amount of solution by liquid level in the second example (and the third example). Therefore, the signal output from the sensor 26(26-2) differs in each example, but the measurement processing is common. Therefore, the description will be made by taking the measurement process performed by the measurement mechanism 15 of the first example as a representative.

In order to improve the accuracy of the measurement, the synthesizer 3 includes an adjusting unit 32 (see fig. 1) for adjusting the liquid feeding speed of the solution. The adjustment means 32 may be provided in each of the delivery pipes 6 to adjust the liquid delivery rate (flow rate per unit time) of the solution flowing through each of the delivery pipes 6, but in the present embodiment, the regulator 11 provided in the upstream pipe 10 functions as the adjustment means 32. With this configuration, it is not necessary to provide the adjusting means 32 on each of the plurality of delivery pipes 6, and the synthesizer 3 can be simplified.

In the present embodiment, as described above, the solution is transferred from each storage container 2 to the intermediate container 7 to be measured by the pressure feed method. When the internal pressure of the storage container 2 is increased, the liquid feeding speed when the solution is supplied to the intermediate container 7 is increased, and when the internal pressure is decreased, the liquid feeding speed when the solution is supplied to the intermediate container 7 is decreased. That is, the liquid feeding speed to the intermediate tank 7 can be increased by adjusting the pressurizer 11 to increase the internal pressure of the storage tank 2. Conversely, the liquid feeding speed to the intermediate tank 7 can be reduced by adjusting the pressurizer 11 to reduce the internal pressure of the storage tank 2.

Therefore, in the present embodiment, the solution is pressure-fed to the intermediate container 7 for the process of metering in the intermediate container 7, but the liquid feeding speed of the solution to be metered is adjusted by the pressurizer 11 (adjusting means 32). This is because, when the liquid feeding speed is high, an error is likely to occur in the measurement particularly when the target amount to be measured is small. For example, the possibility of metering beyond the target amount is increased. Therefore, in the present embodiment, the liquid feeding rate of the solution to the intermediate tank 7 is made lower than a preset threshold value by the pressurizer 11. Thereby, a metering error is suppressed.

However, when the liquid feeding speed is always reduced for metering, it takes time, and the work efficiency may be reduced. In addition, when the liquid feeding speed is always increased for metering, a metering error is liable to occur. Therefore, in the present embodiment, the liquid feeding speed is changed while the solution is supplied to the intermediate tank 7. That is, in the measurement, the liquid feeding speed is made relatively high (higher than the threshold value) in a time period (first half stage) in which the predetermined amount (target amount) is not reached, thereby achieving a reduction in the liquid feeding time. In a time period (latter half) when the predetermined amount (target amount) is reached, the liquid feeding speed is changed to be relatively low (to be lower than the threshold value), thereby suppressing the metering error. In this way, in the end period of the liquid feeding for metering, the regulator 11 decreases the liquid feeding speed as compared with a period before the end period (a period earlier than the end period). The operation of the regulator 11 is controlled based on an operation signal supplied from the control device 16 to the regulator 11. In this way, when the solution is supplied to the intermediate tank 7 for metering, the solution feed rate is set to two stages. As a result, the work efficiency can be improved by increasing the start liquid feeding speed, and the measurement error can be suppressed by decreasing the liquid feeding speed at the end of measurement.

The timing of changing the liquid feeding speed can be managed by the timer function of the control device 16, but in the present embodiment, since the sensor 26 detects the weight at every moment as described above, when a specific amount (for example, 70% of the predetermined amount) of the solution smaller than the predetermined amount is supplied to the intermediate container 7, the control device 16 outputs a signal to the pressurizer 11 to control the liquid feeding speed to be lowered.

In the case of the sensor 26-2 for detecting the liquid level 37 of the solution in the intermediate tank 7 as in the second example (third example), the (first) sensor 26-2 may be provided at a position lower than the liquid level corresponding to a predetermined amount, and when the sensor 26-2 detects the liquid level 37, the control device 16 may output a signal to the regulator 11 to control the liquid feeding speed to be decreased. Further, a (second) sensor 26-2 may be provided at the liquid level corresponding to the predetermined amount, and the sensor 26-2 may check that the predetermined amount is reached.

In addition, the synthesizing apparatus 3 of the present embodiment has the following configuration in order to reduce the measurement error. The valves (pinch valves 14) provided in the respective delivery pipes 6 function as valves for stopping the supply of liquid to the intermediate container 7 for metering. The opening and closing of the pinch valve 14 is based on a command signal from the control device 16. Therefore, the control device 16 outputs a command signal for closing the pinch valve 14 before the solution stored in the intermediate container 7 reaches a predetermined amount (target amount). In order to perform the processing for starting the closing operation as soon as possible, the time required for the closing operation of the pinch valve 14 is measured, and the control device 16 starts the closing operation of the pinch valve 14 before the solution reaches a predetermined amount (target amount) based on the information on the time. Alternatively, as another means, in order to perform processing for starting the closing operation as soon as possible, information on the flow rate of the solution to be fed during the closing operation of the pinch valve 14 is acquired in advance, and based on the information on the flow rate, the control device 16 starts the closing operation of the pinch valve 14 before the solution reaches a predetermined amount (target amount). As another means, the time required for closing the pinch valve 14 may be measured, information on the flow rate of the solution to be fed during the closing operation may be acquired in advance, and the control device 16 may start the closing operation of the pinch valve 14 before the solution reaches a predetermined amount (target amount) based on the information on the time and the information on the flow rate during the closing operation. According to the configurations of the above-described respective aspects, the predetermined amount (target amount) can be obtained with high accuracy by estimating the solution flowing during the closing operation of the pinch valve 14 and starting the closing operation of the pinch valve 14 at an early timing in advance.

While the solution is supplied to the intermediate container 7 for metering, the sensor 26 measures the amount of the solution at every moment, and the control device 16 acquires a signal from the sensor 26 for metering at every moment and outputs a signal for starting the closing operation to the pinch valve 14 based on the signal. Thus, the pinch valve 14 can be started to close as described above before the solution supplied to the intermediate container 7 reaches a predetermined amount (target amount). With this configuration, the solution can be measured in real time. That is, in this configuration, since the target predetermined amount can be measured while monitoring it, a mechanical measurement error or the like can be avoided as compared with the case of measuring by a pressure-feed method or a pump method, and as a result, a predetermined amount of solution can be obtained with high accuracy.

Further, when the pinch valve 14 is closed by the detection of the sensor 26 to stop the supply of the solution to the intermediate tank 7, the control device 16 can determine whether or not the solution stored in the intermediate tank 7 is accurately in a predetermined amount. When it is determined to be accurate (within a predetermined error range), the solution in the intermediate container 7 is transferred to the reaction container 9. And if the judgment result is inaccurate, performing unqualified treatment. The solution in the intermediate container 7 is treated as a waste liquid as a defective treatment.

[ Synthesis apparatus 3]

As described above, the synthesis apparatus 3 of the present embodiment is an apparatus for selectively transferring a plurality of solutions from a plurality of containers 2 to perform chemical synthesis, and the synthesis apparatus 3 includes: a reaction vessel 9 into which the solution is selectively fed, the composition being generated by the material contained in the solution; and a metering mechanism 15 provided between the storage container 2 and the reaction container 9, for metering the solution to be transferred to the reaction container 9. According to the synthesis apparatus 3, a required amount of the solution can be measured by the measuring mechanism 15 and transferred to the reaction container 9, and the solution utilization efficiency can be improved as compared with the conventional apparatus.

As described above, the synthesis apparatus 3 of the present embodiment is an apparatus for selectively transferring a plurality of solutions from a plurality of containers 2 to perform chemical synthesis, and includes an intermediate container 7 provided between the containers 2 and the reaction container 9, a plurality of delivery pipes 6 collectively provided in the intermediate container 7, and the solutions are introduced from the delivery pipes 6, respectively. According to the synthesis apparatus 3, the solution transferred from each of the plurality of containers 2 is once introduced into the intermediate container 7, and then the synthesis product is produced from the solution transferred from the intermediate container 7 to the reaction container 9. Therefore, a mechanism for moving the reaction container 9 is not required, and the reaction container 94 does not need to be moved every time the solution is discharged in the conventional manner (see fig. 8), and the processing operation is simplified. This simplifies the device structure, reduces the number of portions where defects may occur, and provides a highly reliable synthesizer 3. In addition, the operation time required for synthesis can be shortened. In addition, according to the configuration of the present embodiment, when it is necessary to mix a plurality of solutions, the solutions can be mixed in the intermediate container 7 and then transferred to the reaction container 9, thereby improving the reaction efficiency.

The synthesizer 3 of the present embodiment includes a measuring mechanism 15, the measuring mechanism 15 is provided between the storage container 2 and the reaction container 9, and measures the solution to be transferred to the reaction container 9, and the measuring mechanism 15 includes a sensor 26(26-2) that measures the solution introduced into the intermediate container 7. According to the synthesis apparatus 3, a required amount of the solution can be measured by the measuring mechanism 15 and transferred to the reaction container 9, and the solution utilization efficiency can be improved as compared with the conventional apparatus.

Further, since a plurality of lead pipes 6 are collectively provided in the intermediate container 7 and the solutions are introduced from the lead pipes 6, a plurality of metering mechanisms 15 (the intermediate container 7 and the sensors 26(26-2)) for metering may be provided in a single set, although a plurality of solutions are required. That is, by sharing the intermediate container 7, it is not necessary to provide the metering mechanism 15 for each delivery pipe 6 (solution), and the configuration of the synthesizer 3 can be simplified. In addition, by making the solutions supplied to the intermediate container 7 two or more, it is also possible to mix and meter a plurality of solutions in the intermediate container 7. In this case, the solutions are mixed at a stage earlier than the stage of introducing each solution into the reaction vessel 9, and therefore the mixing time can be shortened.

In the first example (see fig. 2), the metering mechanism 15 has a sensor 26 for measuring the weight in the intermediate container 7, and in the second example (fig. 3) and the third example (fig. 4), the metering mechanism 15 has a sensor 26-2 for measuring the liquid level of the solution stored in the intermediate container 7. Here, a device using a pump 93 for transporting a solution is considered (see fig. 9). In the apparatus using the pump 93 shown in fig. 9, the total liquid feed amount is calculated in consideration of the liquid feed amount per unit time (rated liquid feed amount) of the pump 93 and the operation time of the pump 93. However, it is expected that the total liquid-feeding amount obtained by calculation is inaccurate due to loss in the flow path or the like. That is, in the case of using the pump 93, the actual liquid feed amount often deviates from the value obtained by calculation, and therefore, even if a pump is used, an amount larger than the theoretically required amount is provided for each of the plurality of solutions, and an excessive amount of solution is used, and therefore, particularly in the case of mass-producing a composition, the cost is increased. Therefore, in the present embodiment, since the solution can be directly measured as a result of liquid feeding without measuring the target solution under the liquid feeding condition by temporarily storing and measuring the solution in the intermediate container 7, the solution can be measured with high accuracy and the measured solution can be transferred to the reaction container 9, and therefore wasteful use of the solution can be suppressed and the cost can be reduced. As described above, the metering mechanism 15 according to the present embodiment is technically completely different from the flow rate control according to the driving of the pump 93.

In the example of fig. 9, even if the solution is fed by the plunger pump 93 and the solution can be measured with high accuracy by controlling the amount of liquid fed per unit time (rated liquid feed amount) by the plunger pump 93, there is a concern that the solution is crystallized in the plunger pump 93 and a load is applied to the plunger pump 93, which may damage the drive member by tying it with a tape such as a seal breakage, and the durability of the entire device is likely to be lowered. In contrast, in the synthesizing apparatus 3 of the present embodiment, a pump for feeding liquid is not used, and therefore, the durability of the entire apparatus can be improved.

In the present embodiment (the first example, fig. 2), since the metering mechanism 15 can selectively take and meter a plurality of solutions, the metering mechanism 15 includes: a holding unit 27 for holding the plurality of delivery tubes 6 through which the plurality of solutions pass, respectively, in a collected state; an intermediate container (metering container) 7 that receives the solution flowing out of these delivery pipes 6; and a weight sensor 26 that measures the weight in the intermediate container 7. As described above, the holding portion 27 and the intermediate container 7 are provided in a non-contact state. Therefore, the accuracy of the measurement can be improved. This is because, as described above, if the delivery pipe 6 through which the solution passes is in contact with the intermediate container 7, for example, if tension is applied to the delivery pipe 6, the measurement result of the weight sensor 26 is adversely affected, but according to the configuration of the present embodiment, the influence of the delivery pipe 6 does not affect the weight sensor 26.

Further, since the outlet-side pipe 30 connected to the downstream side of the intermediate tank 7 is formed of the spiral elastic tube as described above, even when a tensile force acting as an external force acts on the outlet-side pipe 30, the external force can be released by elastic deformation of the entire tube. As a result, the external force does not easily affect the measurement result of the weight sensor 26, and highly accurate measurement is possible.

In the present embodiment, a plurality of lead pipes 6 are collectively provided in the intermediate container 7, and the solution is introduced from each of the lead pipes 6. Therefore, although there are a plurality of solutions required, the metering mechanism 15 (the intermediate container 7 and the sensor 26) for metering may be provided in one set. That is, by sharing the intermediate container 7, it is not necessary to provide the metering mechanism 15 for each delivery pipe 6 (solution), and the configuration of the synthesizer 3 can be simplified. In addition, by making the solutions supplied to the intermediate container 7 two or more, it is also possible to mix and measure a plurality of solutions in the intermediate container 7. In this case, the solutions are mixed at a stage earlier than the stage of introducing each solution into the reaction vessel 9, and therefore the mixing time can be shortened.

In the synthesis apparatus 3 shown in fig. 1, the means for transporting the solution is a pressure-feed system, and the solution is transported by a pressure difference between the upstream side container and the downstream side container using the gas filled in the tank 4. Therefore, the failure and non-recovery due to clogging of the contaminants and foreign matter in the entire flow path 25 are advantageous compared to a case where a pump (an electric pump or a hydraulic pump) is included in the liquid feeding unit. That is, in the case of using the pump, since the movable portion of the pump is exposed to the flow path, it is disadvantageous in terms of clogging with contaminants and foreign substances due to peeling of sliding members and the like included in the movable portion or generation of abrasion powder. In addition, when the solvent contained in the solution is hardened (crystallized), a failure of the pump may be caused. In the synthesis apparatus 3, it is necessary to replace the liquid-receiving portion such as piping or equipment with which the solution comes into contact, periodically or at a specific timing (at a specific frequency). As described above, in the present embodiment, the start and stop of the supply of the solution from each storage container 2 to the intermediate container 7 are performed by the pinch valve 14, and the drive portion of the pinch valve 14 does not come into contact with the solution, and therefore, the solution is not replaced. That is, only the flexible tube held by the pinch valve 14 may be replaced, and therefore, this is advantageous in terms of non-recyclability.

[ Synthesis device 3 (1) of other embodiment ]

The following is explained above: the metering mechanism 15 of the above-described embodiment (fig. 1) has one intermediate container 7 functioning as a metering container, a plurality of lead pipes 6 are collectively provided in the intermediate container 7, and a solution is introduced into the intermediate container 7 from each of the lead pipes 6 to meter the solution in the intermediate container 7. Hereinafter, a mode in which a plurality of intermediate containers 7 functioning as metering containers are provided will be described. Fig. 6 is a configuration diagram showing another example of the synthesizing apparatus 3. In the synthesizing apparatus 3 shown in fig. 6, the same components as those of the synthesizing apparatus 3 shown in fig. 1 are denoted by the same reference numerals. The synthesizing apparatus 3 shown in fig. 6 is provided with intermediate containers 7-1, 7-2, and 7-3 … for each of the containers 2-1, 2-2, and 2-3 …, and is connected to each other through the delivery pipe 6. That is, the metering mechanism 15 has a plurality of intermediate containers 7-1, 7-2, 7-3 …. The solutions selectively fed from the storage containers 2-1, 2-2, and 2-3 … and measured in the intermediate containers 7-1, 7-2, and 7-3 … were fed to one reaction container 9. Therefore, the synthesizing apparatus 3 has: storage containers 2-1, 2-2, 2-3 … for storing a plurality of solutions, respectively; a reaction vessel 9 for mixing the solutions; the chamber 29 for accommodating the reaction vessel 9 is connected to the chambers 29 by the delivery pipes 6 via the respective accommodating vessels 2-1, 2-2, and 2-3 …. The downstream-side end portions of the delivery pipes 6 are provided corresponding to the first position P1, the second position P2, and the third position P3, respectively. The reaction container 9 is movable in the chamber 29 by an actuator not shown, and is configured to be movable and stopped at a first position P1, a second position P2, and a third position P3. Therefore, the reaction container 9 is configured to be selectively moved to positions (the first position P1, the second position P2, and the third position P3) of the solution to be mixed necessary for producing the composition and to sequentially receive the solution supplied from the downstream-side end portion of the delivery pipe 6 at each position. By moving the reaction vessel 9 in this manner, the solution selectively transferred from the plurality of containers 2-1, 2-2, and 2-3 … to the plurality of intermediate containers 7-1, 7-2, and 7-3 … enters the reaction vessel 9 in a specific order, and a composition is produced in the reaction vessel 9.

As described above, the synthesis apparatus 3 shown in fig. 6 is an apparatus for performing chemical synthesis by metering and selectively delivering a plurality of types of solutions metered by the intermediate vessels 7-1, 7-2, and 7-3 … independently provided for each of the plurality of storage vessels 2-1, 2-2, and 2-3 …, and the synthesis apparatus 3 includes: a plurality of delivery pipes 6 extending from the plurality of containers 2-1, 2-2, 2-3 … for storing the plurality of solutions; and a liquid feeding unit for feeding the solutions in the storage containers 2-1, 2-2, and 2-3 … through the delivery pipe 6. The liquid feeding unit may be a liquid feeding unit based on pressure feeding as in the case of fig. 1. The synthesis apparatus 3 further has a metering mechanism 15 and a reaction vessel 9. The metering mechanism 15 is provided in the middle of the entire flow path 25 including the plurality of delivery pipes 6 between the storage containers 2-1, 2-2, 2-3 … and the reaction container 9, and meters the solution to be fed to the reaction container 9. Then, the solution selectively transferred from the containers 2-1, 2-2, and 2-3 … finally enters the reaction container 9 to produce a composition.

[ Synthesis device 3 (2) of other embodiment ]

Fig. 7 is a configuration diagram showing another example of the synthesizing apparatus 3. In the synthesizing apparatus 3 shown in fig. 7, the same components as those of the synthesizing apparatus 3 shown in fig. 1 are denoted by the same reference numerals. In the synthesizing apparatus 3 shown in FIG. 7, the metering mechanism 15 also has a plurality of intermediate containers 7-1, 7-2, 7-3 …. The synthesizing apparatus 3 shown in fig. 7 is provided with intermediate containers 7-1, 7-2, and 7-3 … for each of the containers 2-1, 2-2, and 2-3 …, and is connected to each other through the delivery pipe 6. The solutions metered by the intermediate containers 7-1, 7-2, 7-3 …, respectively, are delivered to one reaction vessel 9. Therefore, the intermediate pipes 8 extending from the intermediate vessels 7-1, 7-2, and 7-3 merge into a common pipe 8a, and the common pipe 8a is connected to the reaction vessel 9. Thus, the solution selectively transferred from the plurality of containers 2-1, 2-2, and 2-3 … to the plurality of intermediate containers 7-1, 7-2, and 7-3 … enters the reaction container 9 in a specific order, and a composition is produced in the reaction container 9.

As described above, the synthesis apparatus 3 shown in fig. 7 is an apparatus for performing chemical synthesis by metering a plurality of solutions and selectively transporting the metered solutions using the intermediate containers 7-1, 7-2, and 7-3 … that are independent for each of the plurality of containers 2-1, 2-2, and 2-3 …, and the synthesis apparatus 3 includes: a plurality of delivery pipes 6 extending from the plurality of containers 2-1, 2-2, 2-3 … for storing the plurality of solutions; and a liquid feeding unit for feeding the solutions in the storage containers 2-1, 2-2, and 2-3 … through the delivery pipe 6. The liquid feeding unit may be a liquid feeding unit based on pressure feeding as in the case of fig. 1. The synthesis apparatus 3 further has a metering mechanism 15 and a reaction vessel 9. The metering mechanism 15 is provided in the middle of the entire flow path 25 including the plurality of delivery pipes 6 between the storage containers 2-1, 2-2, 2-3 … and the reaction container 9, and meters the solution to be fed to the reaction container 9. Then, the solution selectively transferred from the containers 2-1, 2-2, and 2-3 … finally enters the reaction container 9 to produce a composition.

In fig. 6 and 7, the sensor for measuring is the sensor 26-2 for detecting the liquid level, but may be a weight sensor in the same manner as in fig. 1. The respective configurations described as shown in fig. 1 can be applied to the synthesizing apparatus 3 shown in fig. 6 and 7. In the synthesis apparatus 3 shown in fig. 6 and 7, a required amount of the solution can be measured and transferred to the reaction vessel 9, and the solution utilization efficiency can be improved compared with the conventional apparatus.

The embodiments disclosed above are illustrative in all respects and are not restrictive. That is, the synthesizing apparatus of the present invention is not limited to the illustrated embodiment, and may be other embodiments within the scope of the present invention. For example, although the sensor 26 of the measuring mechanism 15 is described as a weight sensor based on a strain gauge load cell, a weight sensor based on another structure may be used. The structure for mounting the sensor 26 may be designed to be other than the illustrated one. The case where the regulator 11 provided in the upstream pipe 10 constitutes the adjusting means 32 for adjusting the liquid feeding speed of the solution to the intermediate tank 7 has been described, but a configuration other than this is also possible. In the above embodiment, the solution is transported by pressure, but some or all of the solution may be transported by other power. In the above embodiment, the description has been given of the case where the pinch valve 14 is used as a valve for stopping the supply of the solution from each of the storage containers 2 to the intermediate container 7, but another type of valve may be used.

Description of the reference symbols

2: a storage container; 3: a synthesizing device; 6: an outlet pipe (tubing); 6 a: a downstream-side end portion; 7: an intermediate container (metering container); 9: a reaction vessel; 11: a regulator (adjustment unit); 14: pinch valves (valves); 15: a metering mechanism; 16: a control device; 18: a regulator (adjustment unit); 24: a liquid feeding unit; 25: an integrated flow path; 26: a sensor; 26-2: a sensor; 27: a holding section; 29: a closed container; 30 a: an end portion; 30 b: the other end; 40: an upper end; y1: a first position; y2: a second position.