Metrology

Abstract

To expand a cleaning possible range in a measuring container compared with a conventional one.SOLUTION: A measuring mechanism 15 is used for a device for replacing and reacting a plurality kinds of liquids. The measuring mechanism 15 comprises: a measuring container 7 having a bottom wall 31 and a side wall 32, and an opened upper part to store liquid; an outer container (sealing container 29) for storing the measuring container 7; a cleaning piping 34 for supplying a cleaning solution to the measuring container 7; and a drainage mechanism 50 having a drain flow channel 51 for sending a cleaning solution supplied from the cleaning piping 34 to the measuring container 7 and filling the entire inner wall of the measuring container 7 to the outside of the outer container.SELECTED DRAWING: Figure 2

Description

[Technical Field]

[0001] The present disclosure relates to a metering mechanism used in a synthesizer or the like for chemically synthesizing proteins, peptides, nucleic acids, and the like. [Background technology]

[0002] One method for chemically synthesizing proteins, peptides, nucleic acids, etc. involves sequentially supplying multiple types of solutions (reagents) to a reaction vessel and allowing the reaction to proceed in the reaction vessel. For example, when synthesizing nucleic acids, a large number of beads are placed in the reaction vessel, and while solutions are sequentially supplied to the reaction vessel, detritylation, coupling, oxidation, and capping processes are repeatedly carried out, thereby binding bases one after another from the beads.

[0003] Dozens of different solutions may be used, and these solutions are selectively sent to reaction vessels to produce synthetic products (e.g., nucleic acids) from the molecular materials contained in the solutions. Patent Document 1, for example, describes a known device for performing such chemical synthesis. Patent Document 1 discloses a metering mechanism used in such a synthesis device. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Japanese Patent Application Laid-Open No. 2018-167161 Summary of the Invention [Problem to be solved by the invention]

[0005] As described above, each solution must be weighed before being sent to the reaction vessel, and the measuring mechanism disclosed in Patent Document 1 includes a measuring vessel that can store a solution to be selectively sent from among multiple types of solutions. In other words, the measuring vessel is shared by multiple types of solutions. Furthermore, the measuring vessel needs to be cleaned every time the type of solution to be measured is changed.

[0006] A common technique for cleaning containers is to spray a cleaning solution onto the inside of the container using a spray nozzle. However, this method can cause electrostatic discharge, and if the solution is flammable, cleaning using a spray nozzle cannot be used. Therefore, Patent Document 1 discloses that a cleaning liquid is supplied by flowing it out from a pipe into a measuring container, and the cleaning liquid is stored in the container to perform cleaning.

[0007] In this case, the cleaning liquid must be supplied so that the liquid level is lower than the top of the measuring container, which may result in insufficient cleaning at the top of the measuring container. Even if the amount of solution supplied to the measuring container is small and the liquid level is low, when the solution is supplied from the nozzle to the measuring container, the solution may splash from the nozzle and adhere to the top of the measuring container. Also, if the solution is highly volatile, the solution may adhere to the top of the container. Such a solution also needs to be cleaned.

[0008] As described above, with the conventional cleaning method, the area that can be cleaned in the measuring container is narrow, and there is a possibility that the cleaning will be insufficient. Therefore, an object of the present disclosure is to provide a measuring mechanism that enables the cleaning range of a measuring container to be expanded more than ever before. [Means for solving the problem]

[0009] (1) The measuring mechanism of the present disclosure is a measuring mechanism used in an apparatus for exchanging and reacting multiple types of liquids, and includes a measuring container having a bottom wall and side walls, an open top that is not sealed, and capable of storing liquids; an outer container that houses the measuring container; a cleaning pipe for supplying a cleaning solution to the measuring container; and a drainage mechanism that receives the cleaning solution that is supplied to the measuring container from the cleaning pipe and fills the entire inner wall of the measuring container. The drainage mechanism includes a drain pan that is not in contact with the measuring container and receives the cleaning solution that overflows from the measuring container. a drain passage for sending the cleaning solution out of the outer container;and wherein the cleaning solution overflows from the measuring container to clean the inner wall surface of the measuring container. The overflowing cleaning solution is received in the drain pan, and the cleaning solution flows from the drain pan into the drain passage.

[0010] According to the measuring mechanism, the cleaning solution supplied from the cleaning pipe is stored in the measuring container, filling the entire inner wall of the measuring container, making it possible to thoroughly clean the inner surface of the side wall of the measuring container. It is possible to expand the cleanable area of ​​the measuring container more than before. Even if the cleaning solution fills the entire inner wall of the measuring container and overflows from the measuring container, the overflowing cleaning solution can be caught.

[0011] (2) Preferably, the measuring device further comprises a pressurized gas pipe for supplying pressurized gas to the outer container, an outlet pipe connected to the bottom wall of the measuring container for discharging liquid, a support member for supporting the measuring container while keeping the cleaning pipe and the outer container out of contact with the measuring container, and a weight sensor for measuring the weight of the measuring container through the support member.

[0012] According to the above configuration, the pressurized gas supplied to the outer container acts on the liquid stored in the measuring container, causing the liquid to flow out through the outflow pipe, making it possible to pump the measured liquid. The liquid in the measuring container is measured by measuring its weight. The weight of the measuring container acts only on the support member, and the weight sensor measures that weight. Therefore, the measurement of the weight in the measuring container is not affected by other parts such as the outer container, and measurement accuracy is improved.

[0013] (3) In the configuration of (2), it is further preferable that the cleaning solution is supplied to the measuring container while the pressure of the pressurized gas supplied into the outer container is maintained. While the measuring container cannot be cleaned from the outside while the pressure inside the outer container is maintained, this configuration makes cleaning possible.

[0014] (4) Preferably, the drainage mechanism is The drain panThe measuring mechanism has a drain flow path for sending the cleaning solution outside the outer container, and further includes a sensor for detecting the cleaning solution in the drain flow path and a control unit that controls the stopping of the supply of cleaning solution from the cleaning piping to the measuring container based on the detection signal of the sensor. According to the above configuration, it is possible to detect when the cleaning solution has overflowed from the measuring container, which means that it can be determined that the inner surface of the side wall has been thoroughly cleaned, and it is possible to proceed to the next step.

[0015] (5) Preferably, the measuring device further comprises a cover for holding the liquid supply pipe and the cleaning pipe, the cover being provided with a gap around the entire periphery between the cover and the side wall of the measuring container. According to the above configuration, the cover makes it difficult for foreign matter to enter the measuring container. It is possible to prevent the liquid in the measuring container from volatilizing and the volatile components from adhering to the outer container. Furthermore, the cleaning solution can flow through the gap and overflow from the measuring container. In some cases, the cleaning solution overflowing from the measuring container can clean the underside of the cover.

[0016] (6) Preferably, the cover has a lower cover portion provided on the inner periphery of the upper portion of the cylindrical side wall with a first gap between it and the upper portion, and an upper cover portion provided above the upper end of the side wall with a second gap between it and the upper end, and having a larger outer peripheral contour shape than the lower cover portion. According to the above configuration, the gap formed between the side wall of the measuring container and the cover has a bent shape (i.e., a labyrinth shape) due to the first gap and the second gap, which makes it even more difficult for foreign matter to enter the measuring container. The lower surface of the lower cover portion is cleaned with the cleaning solution.

[0017] (7) Preferably, the upper cover is provided at a height position where the cleaning solution that passes through the second gap and overflows the measuring container touches the underside of the upper cover. According to the above configuration, the underside of the upper cover is also cleaned by the cleaning solution overflowing from the measuring container.

[0018] (8) Preferably, the underside of the cover has a slope that increases in height toward the outside of the underside. When the cleaning solution is supplied to the measuring container, the liquid level gradually increases, reaches the underside of the cover, and continues to rise. In this case, with this configuration, air does not accumulate under the cover, preventing the underside from being left unwashed.

[0020] (10) Preferably, the measuring container has an annular portion extending radially outward from the upper end of the cylindrical side wall, along which the overflowing cleaning solution flows, and a cylindrical portion extending downward from the outer periphery of the annular portion, and the drainage mechanism The drain pan The measuring container has an inner peripheral wall provided radially inward from the cylindrical portion, an outer peripheral wall provided radially outward from the cylindrical portion, and an annular bottom wall connecting the inner peripheral wall and the outer peripheral wall, and is not in contact with the measuring container and receives the cleaning solution that has overflowed from the measuring container. R . According to this configuration, the cleaning solution that overflows the measuring container and flows down the upper surface of the annular portion is received by the drain pan, not by the outer container. The cylindrical portion of the measuring container ensures that the overflowing cleaning solution is received by the drain pan. [Effects of the Invention]

[0024] According to the invention of the present disclosure, it is possible to expand the washable area of ​​the measuring container more than ever before. [Brief explanation of the drawings]

[0025] [Figure 1] FIG. 1 is a configuration diagram illustrating an example of a synthesis device equipped with a metering mechanism. [Figure 2] FIG. 2 is an explanatory diagram of the measuring mechanism, showing a cross section of the sealed container and the measuring container. [Figure 3] FIG. 4 is a cross-sectional view showing a part of the measuring mechanism. [Figure 4] FIG. 2 is a perspective view showing a part of the metering mechanism. DETAILED DESCRIPTION OF THE INVENTION

[0026] [Overall configuration of the synthesis apparatus] FIG. 1 is a structural diagram showing an example of a synthesizer equipped with a metering mechanism. The synthesizer is an apparatus that exchanges multiple types of solutions to cause reactions. The synthesizer of this embodiment is an apparatus for chemically synthesizing proteins, peptides, nucleic acids, etc., and sequentially supplies multiple types of solutions (reagents) to a reaction vessel 9, and chemical synthesis proceeds within this reaction vessel 9. When synthesizing nucleic acids, a large number of beads are placed within the reaction vessel 9, and while solutions are sequentially supplied to this reaction vessel 9, detritylation, coupling, oxidation, and capping processes are repeatedly performed, and molecular materials such as bases are sequentially bonded from the beads. Multiple types of solutions are selectively sent to the reaction vessel 9, and a synthetic product (nucleic acid) is produced from the molecular materials contained in the solutions.

[0027] The number of solutions used varies depending on the product to be chemically synthesized. The synthesis apparatus 3 has an area for providing storage containers (reagent bottles) 2-1, 2-2, etc., equal to or greater than the number of types of solutions. Each storage container 2-1, 2-2, etc. stores a solution. Note that FIG. 1 shows only two storage containers (2-1 and 2-2), and the other storage containers are omitted. The synthesis apparatus 3 further includes a storage container 2-20 for storing a cleaning solution. Hereinafter, the reference numeral for the storage container may simply be "2." Each storage container 2 is a sealed container, but is connected to an inlet pipe 5 and an outlet pipe 6. The cleaning solution in this disclosure may be a cleaning solution that does not contain materials for chemical synthesis, or may be the materials themselves for chemical synthesis, or may include a liquid that can replace the previous solution (reagent) without affecting the next step (next solution (reagent)).

[0028] The synthesis apparatus 3 includes a tank 4 for storing pressurized gas, an upstream pipe 10, an inlet pipe 5, an outlet pipe 6, an intermediate pipe 8, an outlet pipe 19, a reaction vessel 9, a metering mechanism 15, and a control device 16 for controlling the opening and closing of each valve.

[0029] The tank 4 is filled with a gas at a higher pressure than the atmosphere, and in the present disclosure, argon gas or nitrogen gas is used as the inert gas. Sterilized gas or air may be used instead of the inert gas. The same number of inlet pipes 5 as the number of storage containers 2 are pipes branching off from a common upstream pipe 10, and this upstream pipe 10 is provided with a regulator (electropneumatic regulator) 11 and a valve 12. The upstream pipe 10 is connected to the tank 4, and pressurized gas is supplied to each storage container 2, and the internal pressure of each storage container 2 is adjusted by the regulator 11. The internal pressure of each storage container 2 is increased by the pressurized gas, and the solution in the storage container 2 is pressure-fed through the outlet pipe 6.

[0030] A pressurized gas pipe 17 is provided between the tank 4 and a sealed container 29 (described later) of the measuring mechanism 15. A second regulator (electropneumatic regulator) 18 is provided on the pressurized gas pipe 17. The gas in the tank 4 is supplied to the sealed container 29.

[0031] Each outlet pipe 6 is provided with a valve 14. The piping portion downstream of each valve 14 (on the measuring container 7 side) serves as an inlet pipe 20 of a measuring mechanism 15. By selecting a valve 14 to be opened, a predetermined solution can be selectively sent (pressurized) from among the solutions in the multiple storage containers 2 to the measuring container 7 through the outlet pipe 6 and inlet pipe 20. The selection of valves 14 to be opened is performed by a control device 16. Furthermore, when the valve 14 of the outlet pipe 6 connected to a storage container 2-20 that stores a cleaning solution is opened, cleaning can be sent (pressurized) from that storage container 2-20 to the measuring container 7 through the inlet pipe 20.

[0032] The metering mechanism 15 selectively acquires and measures multiple types of solutions supplied from the storage container 2. The metering mechanism 15 has a function of measuring the solutions stored in the metering container 7. The measurement results by the metering mechanism 15 are sent to the control device 16, and the control device 16 controls the opening and closing operation of the valve 14 based on the measurement results, and a specified amount of solution is acquired in the metering container 7. The specified amount of solution is sent to the reaction container 9 through the intermediate pipe 8.

[0033] As described above, a solution is selectively sent from at least one of the plurality of storage vessels 2 to the measuring vessel 7, and after being measured in this measuring vessel 7, it is sent to the reaction vessel 9. The supply of the solution to the reaction vessel 9 is repeated while changing the type of solution, and multiple types of solutions are supplied to the reaction vessel 9 in sequence, and chemical synthesis proceeds in the reaction vessel 9. After the solution passes through the reaction vessel 9, the solution is discharged through the discharge pipe 19.

[0034] [Regarding Measuring Mechanism 15] 2 is an explanatory diagram of the weighing mechanism 15, showing a cross section of the sealed container 29 and the weighing container 7. The weighing mechanism 15 includes the sealed container 29 to which the gas (pressurized gas) is supplied, a plurality of inlet pipes 20, the weighing container 7, a weight sensor 26, a cover 35, an outlet pipe 37, a discharge pipe 38, and a drainage mechanism 50.

[0035] The measuring container 7 is a cylindrical container with a bottom, a bottom wall 31, and a cylindrical side wall 32, and is open at an upper portion 7u. A solution and a cleaning solution are stored in the measuring container 7. The sealed container 29 serves as an outer container that houses the measuring container 7. The sealed container 29 is isolated from the outside, and the inside thereof is kept out of contact with the outside air. The solution used for synthesis does not overflow from the measuring container 7 (side wall 32), but the cleaning solution overflows from the measuring container 7 (side wall 32) to clean the inner wall surface 7a of the measuring container 7 and the underside of the cover 35. Cleaning of the measuring container 7 will be described later.

[0036] The multiple inlet pipes 20 include multiple solution pipes 33 and one cleaning pipe 34. The solution pipe 33 is connected to a storage container (e.g., storage container 2-1) that stores the solution, and the solution flows through the solution pipe 33 by pressure feeding as described above. The solution pipe 33 is a pipe for causing the solution to flow out from the upper part 7u side of the measuring container 7 and supply it to the measuring container 7. The cleaning pipe 34 is connected to a storage container 2-20 that stores the cleaning solution, and the cleaning solution flows through the cleaning pipe 34 by pressure feeding as described above. The cleaning pipe 34 is a pipe for causing the cleaning solution to flow out from the upper part 7u side of the measuring container 7 and supply it to the measuring container 7.

[0037] The multiple solution pipes 33 and one cleaning pipe 34 are bundled together and penetrate the wall of the upper part 29u of the sealed container 29. The multiple solution pipes 33 and one cleaning pipe 34 are provided in an inlet region (opening) in the upper part 7u of the measuring container 7, and are gathered together by a cover 35. The multiple solution pipes 33, one cleaning pipe 34, and the cover 35 are provided inside the sealed container 29 in a state where they are not in contact with the measuring container 7 (the edges are cut off).

[0038] An outlet pipe 37 equipped with a valve 36 is connected to the lower portion 7b of the measuring container 7. When the valve 36 is closed, the solution or cleaning solution is introduced into the measuring container 7 and stored in the measuring container 7. When the valve 36 is open, the outlet pipe 37 allows the solution or cleaning solution in the measuring container 7 to flow out. The outlet pipe 37 is connected to a discharge pipe 38. The solution flowing out from the outlet pipe 37 flows to the reaction container 9 through the discharge pipe 38 and the intermediate pipe 8 (see FIG. 1) connected further downstream.

[0039] Weight sensor 26 measures the weight in weighing container 7. Weight sensor 26 of the present disclosure is configured as a strain-type load cell. Weight sensor 26 is installed on a support member (first support member) 27 provided inside sealed container 29. Weighing container 7 is supported on sealed container 29 via support member 27 equipped with weight sensor 26. Weighing container 7 is provided in a state supported from below via support member 27 equipped with weight sensor 26. Therefore, the weight of weighing container 7 and the solution stored in this weighing container 7 is received by weight sensor 26. Weight sensor 26 measures the weight of the solution stored in weighing container 7. Weight sensor 26 may be a sensor of other types, and is configured as, for example, an electromagnetic, piezoelectric, capacitance, magnetostrictive, gyroscopic, or other load cell.

[0040] The measuring mechanism 15 includes a pressurized gas pipe 17 for supplying pressurized gas to the sealed container 29 (outer container), and an outlet pipe 37 connected to the bottom wall 31 of the measuring container 7 for discharging the solution or cleaning solution. Therefore, the pressurized gas supplied to the sealed container 29 acts on the liquid (solution or cleaning solution) stored in the measuring container 7, causing the liquid to flow out from the outlet pipe 37. In other words, it is possible to pressure-feed the liquid even after it has been measured.

[0041] The measuring mechanism 15 includes a support member 27 that supports the measuring container 7, with the solution pipe 33, the cleaning pipe 34, and the sealed container 29 not in contact with the measuring container 7. The measuring mechanism 15 also includes a weight sensor 26 that measures the weight of the measuring container 7 through the support member 27. The liquid (solution or cleaning solution) in the measuring container 7 is measured by measuring its weight. The weight of the measuring container 7 acts only on the support member 27, and is measured by the weight sensor 26. Therefore, a configuration is obtained in which the measurement of the weight of the measuring container 7 is not affected by other parts such as the sealed container 29 and cover 35, improving measurement accuracy.

[0042] [Regarding measuring container 7] The measuring container 7 will now be described in further detail. The measuring container 7 has a bottom wall 31 and a cylindrical side wall 32, as well as an annular portion 22 and a tubular portion 23, as shown in FIGS. 3 and 4. FIG. 3 is a cross-sectional view showing a portion of the measuring mechanism 15. FIG. 4 is a perspective view showing a portion of the measuring mechanism 15. The annular portion 22 is provided so as to extend radially outward from the upper end 32u of the cylindrical side wall 32. Note that the "radial direction" refers to the horizontal direction extending outward from the center of the cylindrical measuring container 7. The cleaning solution spilling over from the container body 21, which is formed by the bottom wall 31 (see FIG. 2) and the cylindrical side wall 32, can flow over the upper surface 22a of the annular portion 22. The tubular portion 23 extends downward from the outer peripheral end of the annular portion 22. The tubular portion 23 prevents the spilled cleaning solution from flowing downward toward the bottom surface of the annular portion 22 and guides it to a drain pan 52, which will be described later.

[0043] The upper surface 22a of the annular portion 22 may be sloped downward toward the outer periphery. This prevents the cleaning solution that has passed over the side wall 32 from flowing back and allows it to flow toward the drain pan 52. To prevent the backflow, the upper end of the measuring container 7 may have a stepped shape in which the upper end 32u of the side wall 32 is higher than the upper surface 22a of the annular portion 22.

[0044] [About Cover 35] The cover 35 is a lid member that covers the opening of the measuring container 7, and is provided with a gap e around the entire periphery between it and the side wall 32 of the measuring container 7. The cover 35 also functions as a member that holds the solution pipe 33 and the cleaning pipe 34. The cover 35 has a lower cover part 42 and an upper cover part 41 that has a larger outer peripheral contour shape than the lower cover part 42. The lower cover part 42 and the upper cover part 41 are integrally constructed.

[0045] Lower cover part 42 is provided on the inner periphery of the upper part of cylindrical side wall 32, with a first gap e1 formed around the entire circumference between lower cover part 42 and the upper part. Upper cover part 41 is provided above upper end 32u of cylindrical side wall 32, with a second gap e2 formed around the entire circumference between upper end 32u and lower cover part 42. This gap e allows the cleaning solution to overflow from measuring container 7, and also allows the pressurized gas in sealed container 29 to act on the solution (cleaning solution) stored in measuring container 7 through this gap e, thereby pressurizing and feeding the solution (cleaning solution).

[0046] The upper cover part 41 is provided close to the upper end 32u of the side wall 32 so that the second gap e2 is narrow. Specifically, the upper cover part 41 is provided at a height position where the cleaning solution that passes through the second gap e2 and overflows the measuring container 7 comes into contact with the lower surface 41L of the upper cover part 41. The second gap e2 is set narrower than the first gap e1. In other words, because the opening area of ​​the second gap e2 is smaller than the opening area of ​​the first gap e1, the cleaning solution that passes through the first gap e1 can come into contact with the lower surface 41L of the upper cover part 41, and the upper surface 22a of the annular part 22 and the lower surface 41L of the upper cover 41 can be thoroughly cleaned over the entire circumference.

[0047] The lower surface of the cover 35, i.e., the lower surface 42L of the lower cover portion 42, gradually becomes higher from the center 42c of the lower surface 42L toward the outside in the radial direction. A plurality of solution pipes 33 and one cleaning pipe 34 are provided to protrude downward from the lower surface 42L of the lower cover portion 42. Therefore, these protruding portions can also be cleaned with the cleaning solution.

[0048] [Regarding the drainage mechanism 50] As described above, in order to clean the inner wall surface 7a of the measuring container 7 and the underside of the cover 35, the cleaning solution overflows from the entire periphery of the side wall 32 of the measuring container 7. Therefore, the measuring mechanism 15 is provided with a drainage mechanism 50. The drainage mechanism 50 is a mechanism for sending the cleaning solution that is supplied to the measuring container 7 from the cleaning piping 34 and overflows from the measuring container 7 to the outside of the sealed container (outer container) 29. The drainage mechanism 50 has a drain passage 51 and a drain pan 52. The drain pan 52 receives the cleaning solution that overflows the measuring container 7. The drain passage 51 is a pipe that penetrates the wall of the sealed container 29. The gap between the drain passage 51 and the wall of the sealed container 29 is sealed. The cleaning solution flows from the drain pan 52 to the drain passage 51.

[0049] The drain pan 52 is annularly shaped and surrounds the upper portion of the measuring container 7. The drain pan 52 is supported on the sealed container 29 by a second support member 56. Specifically, the drain pan 52 has an inner peripheral wall 53, an outer peripheral wall 54, and an annular bottom wall 55 connecting the inner peripheral wall 53 and the outer peripheral wall 54. The inner peripheral wall 53 is located radially inward from the cylindrical portion 23 of the measuring container 7. The outer peripheral wall 54 is located radially outward from the cylindrical portion 23. The inner peripheral wall 53 is not in contact with the cylindrical portion 23, the annular portion 22, or the side wall 32. In other words, the drain pan 52 is not in contact with the measuring container 7. Therefore, the measurement of the solution or cleaning solution in the measuring container 7 is not affected by the drain pan 52.

[0050] The height of the upper surface of bottom wall 55 decreases toward inlet 51a of drain channel 51. The cleaning solution that overflows measuring container 7 and falls onto bottom wall 55 of drain pan 52 is collected at inlet 51a of drain channel 51a and flows through drain channel 51.

[0051] As shown in FIG. 3 , the drainage mechanism 50 has a sensor 57 that detects the cleaning solution in the drain passage 51. The sensor 57 may be of various types, as long as it can detect the cleaning solution flowing through the drain passage 51. In this embodiment, the sensor 57 is provided outside the sealed container 29. However, since the solution contains a flammable solution and the metering mechanism 15 (synthesizer 3) requires high explosion-proofing, an optical sensor without electrical contacts is used. Specifically, the sensor 57 is an optical sensor having a light-emitting element and a light-receiving element. Therefore, the drain passage 51 has a transparent pipe 58, part of the wall of which is transparent, outside the sealed container 29. The sensor 57 detects the cleaning solution flowing through the transparent pipe 58. The detection of the cleaning solution by the sensor 57 means that the cleaning solution has overflowed from the metering container 7.

[0052] A drain valve 59 is provided downstream of the transparent pipe 58. The drain valve 59 is normally closed. Therefore, the cleaning solution that flows into the drain passage 51 is collected in the transparent pipe 58. The cleaning solution collected in the transparent pipe 58 in this way is detected by the sensor 57. When the cleaning of the measuring container 7 is completed, the drain valve 59 is opened and the cleaning solution in the drain passage 51 is discharged. The opening and closing operation of the drain valve 59 is performed by the control device 16.

[0053] Here, the measuring container 7 needs to be cleaned every time the type of solution to be measured is changed. To start cleaning, the storage container 2-20 (see FIG. 1) that stores the cleaning solution is pressurized, and the cleaning solution from the storage container 2-20 is pressure-fed to the measuring container 7 through the cleaning pipe 34. At this time, the valve 14 of the outlet pipe 6 connected to the cleaning pipe 34 changes from a closed state to an open state. The operation of this valve 14 is controlled by the control device 16. Note that the valve 36 of the outflow pipe 37 is closed.

[0054] The control device 16 further controls the stopping of the supply of the cleaning solution from the cleaning pipe 34 to the measuring container 7 based on the detection signal of the sensor 57. In other words, when the sensor 57 detects the cleaning solution, the control device 16 changes the valve 14 (hereinafter also referred to as the "cleaning valve 14") of the outlet pipe 6 connected to the cleaning pipe 34 from the open state to the closed state. In the first cleaning method, when the sensor 57 detects the cleaning solution, the cleaning valve 14 is closed. The measuring container 7 is filled with the cleaning solution and left for a predetermined time (for example, 30 seconds to 1 minute) to perform cleaning. In a second cleaning method, even if sensor 57 detects cleaning solution, cleaning valve 14 remains open for a specified time (for example, 30 seconds to 1 minute) to continue supplying cleaning solution, while drain valve 59 is opened, and after the specified time has elapsed, cleaning valve 14 and drain valve 59 are closed. In this case, cleaning is carried out for a while with the cleaning solution allowed to overflow from measuring container 7 for more than the specified time.

[0055] [Regarding the measuring mechanism 15 of this embodiment] As described above, the metering mechanism 15 of this embodiment is used in a synthesis apparatus 3 in which multiple types of solutions are exchanged and reacted. Therefore, each solution needs to be measured, and changing the type of solution requires cleaning of the metering container 7. Therefore, the metering mechanism 15 includes the metering container 7, a sealed container 29 as an outer container that houses the metering container 7, multiple solution pipes 33 for supplying solutions to the metering container 7, (at least one) cleaning pipe 34 for supplying cleaning solution to the metering container 7, and a drainage mechanism 50. The metering container 7 has a bottom wall 31 and a side wall 32, and is open at the top. The metering container 7 stores solutions and cleaning solution. The drainage mechanism 50 has a drain passage 51.

[0056] The drain flow path 51 is a flow path for sending the cleaning solution that is supplied from the cleaning piping 34 to the measuring container 7 and has filled the entire inner wall surface 7a of the measuring container 7 to the outside of the sealed container 29. In other words, when the cleaning solution fills the entire inner wall surface 7a of the measuring container 7 and the cleaning solution overflows from the measuring container 7, the overflowing cleaning solution is sent to the outside of the outer container through the drain flow path 51 and treated as wastewater. In this embodiment, cleaning is performed by overflowing the cleaning solution from the measuring container 7. For this reason, the drain flow path 51 is a flow path for sending the cleaning solution that has overflowed from the measuring container 7 to the outside of the sealed container 29.

[0057] 3 and 4, the drainage mechanism 50 has a drain pan 52 that receives the cleaning solution that has overflowed the measuring container 7. The cleaning solution flows from the drain pan 52 to a drain passage 51. With this configuration, the cleaning solution that has overflowed the measuring container 7 is received by the drain pan 52, not by the sealed container 29. The measuring container 7 has an annular portion 22 that extends radially outward from the upper end 32u of the side wall 32, and overflowing cleaning solution flows along an upper surface 22a, and a tubular portion 23 that extends downward from the outer periphery of the annular portion 22. With this configuration, cleaning solution that overflows the side wall 32 of the measuring container 7 and flows along the upper surface 22a of the annular portion 22 is received in the drain pan 52, not in the sealed container 29. Furthermore, the tubular portion 23 allows the overflowing cleaning solution to be reliably received in the drain pan 52.

[0058] When the solution is supplied from the solution pipe 33 to the measuring container 7, the solution may splash from the outlet at the lower end of the solution pipe 33, possibly resulting in adhesion of the solution to the upper part of the measuring container 7. Furthermore, if the solution is highly volatile, the solution may adhere to the upper part of the measuring container 7. Even in such a case, according to the measuring mechanism 15 of this embodiment, the cleaning solution supplied from the cleaning pipe 34 is stored in the measuring container 7, filling the entire inner wall surface 7a of the measuring container 7. Furthermore, the cleaning solution overflows the side wall 32 of the measuring container 7, making it possible to thoroughly clean the inner surface of the side wall 32 of the measuring container 7. This makes it possible to expand the cleanable area of ​​the measuring container 7 compared to conventional methods.

[0059] Note that, when cleaning the measuring container 7, care may be taken to prevent the cleaning solution from overflowing from the measuring container 7. For example, cleaning may be performed by supplying the cleaning solution up to the upper end (upper end 32u of the side wall 32) of the measuring container 7 and filling the entire inner wall surface 7a of the measuring container 7 with the cleaning solution. In this case, the drainage mechanism 50 (drain passage 51 and drain pan 52) is used as an auxiliary means to receive any cleaning solution that overflows from the measuring container 7. However, to ensure reliable cleaning, it is preferable for the cleaning solution to overflow from the measuring container 7.

[0060] 3, the drainage mechanism 50 has a sensor 57 that detects the cleaning solution in the drain passage 51. Based on the detection signal from the sensor 57, the control device 16 performs control to stop the supply of the cleaning solution from the cleaning pipe 34 to the measuring container 7. With this configuration, it is possible to detect when the cleaning solution has overflowed from the measuring container 7. In other words, it can be determined that the inner surface of the side wall 32 has been cleaned thoroughly, and it is possible to proceed to the next process.

[0061] The next process is the draining process of the cleaning solution remaining in the measuring container 7. In this draining process, the control device 16 controls the valve 36 of the outlet pipe 37 (see FIG. 2) to change from a closed state to an open state, and the cleaning solution in the measuring container 7 is drained out of the sealed container 29 through the outlet pipe 37 and the drain pipe 38. Although not shown, for example, the drain pipe 38 preferably has a branched flow path that branches off, so that the cleaning solution flows not to the reaction container 9 but to a drain tank. Then, once the draining of the cleaning solution from the measuring container 7 is complete, the next solution is supplied to the measuring container 7 and measured. Furthermore, the cleaning solution remaining in the drain flow path 51 is drained by opening the drain valve 59.

[0062] The weighing mechanism 15 is provided with a cover 35 provided with a gap e around the entire periphery between it and the side wall 32 of the weighing container 7. This cover 35 makes it difficult for foreign matter to enter the weighing container 7. It also prevents the solution in the weighing container 7 from volatilizing and the volatile components from adhering to the inner surface of the sealed container 29. The cleaning solution flows through the gap e and overflows from the weighing container 7. The overflowing cleaning solution can clean the underside of the cover 35, particularly the underside 41L of the upper cover part 41.

[0063] The amount of cleaning solution supplied from the cleaning pipe 34 to the measuring container 7 is greater than the amount of cleaning solution that can flow out to the drain flow path 51 side (drain pan 52 side) through the gap e. As a result, the cleaning solution fills the entire gap e and flows through the gap e. The dimensions of the gap e, particularly the dimensions of the gap e1 on the opening side, are set so that this relationship in liquid volume is obtained.

[0064] The cover 35 has a lower cover portion 42 and an upper cover portion 41 whose outer peripheral contour is larger than that of the lower cover portion 42. The lower cover portion 42 is provided on the inner periphery of the upper portion of the side wall 32, with a first gap e1 between it and the upper portion. The upper cover portion 41 is provided above the upper end 32u of the side wall 32, with a second gap e2 between it and the upper end 32u. With this cover 35, the gap e formed between the cover 35 and the side wall 32 has a bent shape (i.e., a labyrinth shape) due to the first gap e1 and the second gap e2. This makes it even more difficult for foreign matter to enter the weighing container 7.

[0065] The height position of the upper cover part 41, that is, the installation position of the cover 35, is set as follows: That is, the upper cover part 41 is provided at a height position where the cleaning solution overflowing from the measuring container 7 passes through the second gap e2 and touches the underside 41L of the upper cover part 41. By providing the cover 35 at this height position, the cleaning solution overflowing from the measuring container 7 cleans not only the underside 42L of the lower cover part 42, but also the side surface 41R and underside 41L of the upper cover part 41. Furthermore, the portion of the inlet pipe 20 (solution piping 33) that protrudes downward from the underside 42L is also cleaned by the cleaning solution.

[0066] When cleaning solution is supplied to the measuring container 7, the liquid level gradually rises, reaches the underside 42L of the lower cover part 42, and continues to rise. Therefore, as shown in Figure 3, the underside of the cover 35, i.e., the underside 42L of the lower cover part 42, has a slope that rises from the center of the underside 42L toward the outside. With this configuration, air does not accumulate on the underside 42L of the lower cover part 42, and the underside 42L is prevented from being left unwashed.

[0067] Furthermore, the upper end 32u of the cylindrical side wall 32 is at the same height all around. This configuration allows the cleaning solution to overflow from the entire circumference of the cylindrical side wall 32. In other words, it is possible to prevent the cylindrical side wall 32 from leaving unwashed areas. Note that the upper end 32u may be partially lower along the circumferential direction. In this case, the cleaning solution will preferentially overflow the side wall 32 from that portion.

[0068] In the above embodiment, a case has been described in which the cleaning solution overflows from the measuring container 7 in order to clean the measuring container 7. As explained above, in order to expand the cleanable area of ​​the measuring container 7 more than before, there are cases in which the cleaning solution does not need to overflow. To achieve this, the measuring mechanism 15 has the following configuration. That is, the measuring mechanism 15 includes a measuring container 7 having a bottom wall 31 and a side wall 32, an open top, and in which liquid (solution and cleaning solution) is stored, a cleaning pipe 34 for supplying cleaning solution to the measuring container 7, and a cover 35 that holds the cleaning pipe 34 and covers the top of the measuring container 7. The cover 35 has a lower cover portion 42 that extends into the measuring container 7 as a part facing the inner wall surface of the measuring container 7. A gap e2 is formed around the entire periphery between the lower cover portion 42 and the side wall 32.

[0069] According to this measuring mechanism 15, the cleaning solution supplied from the cleaning pipe 34 is stored in the measuring container 7. If the cleaning solution is supplied from the cleaning pipe 34 to the measuring container 7 so that the liquid level of the cleaning solution is equal to or higher than the lower surface 42L of the cover 35 (lower cover part 42), it becomes possible to clean the side wall 32 of the measuring container 7 and also the lower surface 42L of the cover 35 (lower cover part 42). Therefore, it becomes possible to expand the washable range of the measuring container 7 compared to conventional methods.

[0070] The configurations described in the above embodiments can be applied to this weighing mechanism 15. For example, in addition to the lower cover portion 42, the cover 35 has an upper cover portion 41 whose outer peripheral contour is larger than that of the lower cover portion 42. The lower cover portion 42 is provided on the inner periphery of the upper portion of the side wall 32, with a first gap e1 between it and the upper portion. The upper cover portion 41 is provided above the upper end 32u of the side wall 32, with a second gap e2 between it and the upper end 32u.

[0071] 〔others〕 In the above embodiment, the metering mechanism 15 has been described as being used in a synthesizer 3 for chemically synthesizing nucleic acids, but the present invention is not limited to this and may be used in a synthesizer 3 for chemically synthesizing proteins, peptides, etc. Any metering mechanism 15 may be used in a synthesizer 3 for exchanging and reacting multiple types of solutions.

[0072] The embodiments disclosed herein are illustrative in all respects and are not restrictive. The scope of the present invention is not limited to the above-described embodiments, but includes all modifications within the scope of the claims and equivalents thereof. [Explanation of symbols]

[0073] 3 Synthesizer 7 Measuring container 15 Metering mechanism 16 Control device (control unit) 17 Pressurized gas piping 22 Annular section 22a Top side 23 Cylinder part 26 Weight Sensor 27 Support member 29 Sealed container (outer container) 31 Bottom wall 32 Side wall 33 Solution piping 34 Cleaning piping 35 Cover 37 Outflow pipe 41 Upper cover part 41L bottom surface 42 Lower cover part 42L bottom surface 50 Drainage mechanism 51 Drain passage 52 Drain pan 53 Inner wall 54 Outer wall 55 bottom wall 57 Sensors e Gap e1 First gap e2 Second gap

Claims

1. A measuring mechanism used in an apparatus for exchanging and reacting a plurality of types of liquid, a measuring container having a bottom wall and a side wall, an open top and not sealed, and capable of storing a liquid; an outer container containing the measuring container; a cleaning line for supplying a cleaning solution to the metered vessel; a drainage mechanism for receiving the cleaning solution supplied from the cleaning pipe to the measuring container and filling the entire inner wall of the measuring container; Equipped with the drainage mechanism includes a drain pan that is not in contact with the measuring container and that receives the cleaning solution that overflows from the measuring container, and a drain flow path that sends the cleaning solution to the outside of the outer container; the cleaning solution overflows from the measuring container to clean the inner wall surface of the measuring container, the overflowing cleaning solution is received by the drain pan, and the cleaning solution flows from the drain pan into the drain flow path; Metering mechanism.

2. a pressurized gas pipe for supplying pressurized gas to the outer container; an outlet pipe connected to the bottom wall of the measuring container for discharging liquid; a support member for supporting the measuring container such that the cleaning pipe and the outer container are not in contact with the measuring container; a weight sensor for measuring the weight of the measuring container through the support member; The metering mechanism of claim 1 further comprising:

3. The metering mechanism of claim 2 , wherein cleaning solution is supplied to the metered container while the pressure of the pressurized gas supplied within the outer container is maintained.

4. the drainage mechanism has a drain passage for sending the cleaning solution in the drain pan out of the outer container; a sensor for detecting cleaning solution in the drain passage; The measuring mechanism according to claim 1 , further comprising: a control unit that performs control to stop the supply of the cleaning solution from the cleaning pipe to the measuring container based on the detection signal of the sensor.

5. The measuring mechanism according to claim 1 , further comprising a cover that holds the liquid supply pipe and the cleaning pipe and is provided with a gap around the entire periphery between the cover and the side wall of the measuring container.

6. The cover is a lower cover portion provided on an inner circumferential side of an upper portion of the cylindrical side wall with a first gap between the upper portion and the lower cover portion; an upper cover portion provided above an upper end of the side wall with a second gap between the upper end and the upper cover portion, the upper cover portion having a larger outer peripheral contour than the lower cover portion; 6. The metering mechanism of claim 5, wherein:

7. The measuring container according to claim 6, wherein the upper cover part is provided at a height position where the cleaning solution that passes through the second gap and overflows the measuring container comes into contact with the lower surface of the upper cover part.

8. 8. The weighing mechanism according to claim 6, wherein the lower surface of the cover has a slope that becomes higher toward the outside of the lower surface.

9. The measuring container comprises: an annular portion that is provided so as to extend radially outward from an upper end of the cylindrical side wall and over which the overflowing cleaning solution flows; a cylindrical portion extending downward from an outer circumferential side of the annular portion; and The drain pan of the drainage mechanism has an inner wall located radially inward from the cylindrical portion, an outer wall located radially outward from the cylindrical portion, and an annular bottom wall connecting the inner wall and the outer wall, and is not in contact with the measuring container and receives cleaning solution that overflows from the measuring container.

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