JP7765893B2 - Measuring mechanism - Google Patents

Description

This disclosure relates to a metering mechanism used in synthesizers and the like for chemically synthesizing proteins, peptides, nucleic acids, and the like.

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 within the 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 repeated, allowing bases to be bonded one after another from the beads.

Dozens of different solutions may be used, and these solutions are selectively sent to reaction vessels, where synthetic products (e.g., nucleic acids) are produced from the molecular materials contained in the solutions. One known example of an apparatus for performing this type of chemical synthesis is the apparatus described in Patent Document 1. Patent Document 1 also discloses a metering mechanism used in such a synthesis apparatus.

JP 2018-167161 A

As mentioned above, each solution must be weighed before being sent to the reaction vessel. The weighing mechanism disclosed in Patent Document 1 is equipped with a weighing vessel that can store a solution to be selectively sent from among multiple types of solutions. In other words, the weighing vessel is shared for multiple types of solutions. Furthermore, the weighing vessel needs to be cleaned each time the type of solution to be measured is changed.

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 a method in which 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.

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.

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.

(1) The measuring mechanism of the present disclosure is a measuring mechanism used in an apparatus for exchanging and reacting multiple types of liquid, and includes a measuring container having a bottom wall and side walls, an open top that is not sealed, and capable of storing liquid; an outer container that houses the measuring container; a cleaning pipe for supplying cleaning solution to the measuring container; and a drainage mechanism that receives the cleaning solution that is supplied from the cleaning pipe to the measuring container 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 , and a drain flow path for sending the cleaning solution outside the outer container. The cleaning solution overflows from the measuring container to clean the inner wall surface of the measuring container , the drain pan receives the overflowing cleaning solution, and the cleaning solution flows from the drain pan to the drain flow path.

With this 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. This makes it possible to expand the cleanable area of the measuring container more than ever 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.

(2) Preferably, the system 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.

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.

(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.

(4) Preferably, the drainage mechanism has a drain flow path for sending the cleaning solution in the drain pan out of the outer container, and the metering mechanism further includes a sensor for detecting the cleaning solution in the drain flow path and a control unit for controlling the stopping of the supply of cleaning solution from the cleaning piping to the metering 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.

(5) Preferably, the measuring device further comprises 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.
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.

(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.

(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 this configuration, the underside of the upper cover is also cleaned by the cleaning solution overflowing from the measuring container.

(8) Preferably, the underside of the cover has a slope that rises toward the outside of the underside. When cleaning solution is supplied to the measuring container, the liquid level gradually rises, reaches the underside of the cover, and continues to rise. In this case, this configuration prevents air from collecting on the underside of the cover, preventing areas from remaining unwashed.

(10) Preferably, the measuring container has an annular portion that extends radially outward from the upper end of the cylindrical side wall, along which overflowing cleaning solution flows, and a cylindrical portion that extends downward from the outer periphery of the annular portion, and the drainage mechanism has a drain pan that has an inner wall that is radially inward from the cylindrical portion, an outer wall that is radially outward from the cylindrical portion, and an annular bottom wall that connects 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.
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.

The disclosed invention makes it possible to expand the washable area of a measuring container more than ever before.

FIG. 1 is a configuration diagram illustrating an example of a synthesis device equipped with a metering mechanism. FIG. 2 is an explanatory diagram of the measuring mechanism, showing a cross section of the sealed container and the measuring container. FIG. 4 is a cross-sectional view showing a part of the measuring mechanism. FIG. 2 is a perspective view showing a part of the metering mechanism.

[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 for exchanging and reacting multiple types of solutions. 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, thereby sequentially binding molecular materials such as bases 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.

The number of solutions used varies depending on the product being chemically synthesized. The synthesis apparatus 3 has an area with storage containers (reagent bottles) 2-1, 2-2, etc., equal to or greater than the number of solution types. Each storage container 2-1, 2-2, etc. stores a solution. Note that Figure 1 shows only two storage containers (2-1 and 2-2); the other storage containers are omitted. The synthesis apparatus 3 also has a storage container 2-20 that stores a cleaning solution. Below, the reference number assigned to 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 it may be the materials themselves for chemical synthesis, and may include a liquid that can replace the previous solution (reagent) without affecting the next process (next solution (reagent)).

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 that controls the opening and closing of each valve.

The tank 4 is filled with a gas at a higher pressure than atmospheric pressure, 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 branch off from a common upstream pipe 10, which is equipped 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, with the internal pressure of each storage container 2 being adjusted by the regulator 11. The pressurized gas increases the internal pressure of each storage container 2, and the solution in the storage container 2 is pressure-fed through the outlet pipe 6.

A pressurized gas pipe 17 is provided between the tank 4 and the sealed container 29 (described below) of the metering mechanism 15. A second regulator (electropneumatic regulator) 18 is provided on the pressurized gas pipe 17. Gas from the tank 4 is supplied to the sealed container 29.

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

The metering mechanism 15 selectively acquires and measures multiple types of solution supplied from the storage container 2. The metering mechanism 15 has the function of measuring the solution stored in the metering container 7. The measurement results by the metering mechanism 15 are sent to the control device 16, which 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.

As described above, a solution is selectively sent from at least one of the multiple storage containers 2 to the measuring container 7, and after being measured in this measuring container 7, it is sent to the reaction container 9. The supply of solution to the reaction container 9 is repeated while changing the type of solution, and multiple types of solution are supplied to the reaction container 9 in sequence, and chemical synthesis proceeds within the reaction container 9. Once the solution has passed through the reaction container 9, it is discharged through the discharge pipe 19.

[Regarding the 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.

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. The measuring container 7 stores a solution and a cleaning solution. 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 its interior is kept out of contact with the outside air.
The solution used in 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.

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 that allows 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 the 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 that allows 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.

The multiple solution pipes 33 and one cleaning pipe 34 are bundled together and pass through the wall of the upper part 29u of the sealed container 29. The multiple solution pipes 33 and one cleaning pipe 34 are arranged in an inlet area (opening) at the upper part 7u of the measuring container 7, and are bundled together by a cover 35. The multiple solution pipes 33, one cleaning pipe 34, and the cover 35 are arranged inside the sealed container 29 in a state where they are not in contact with the measuring container 7 (the edges are cut off).

An outlet pipe 37 with a valve 36 is connected to the lower part 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 there. 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 of the outlet pipe 37 flows to the reaction container 9 through the discharge pipe 38 and the intermediate pipe 8 (see Figure 1) connected downstream of the discharge pipe 38.

The weight sensor 26 measures the weight in the weighing container 7. The weight sensor 26 of the present disclosure is composed of a strain-type load cell. The weight sensor 26 is mounted on a support member (first support member) 27 provided inside the sealed container 29. The weighing container 7 is supported on the sealed container 29 via the support member 27 equipped with the weight sensor 26. The weighing container 7 is supported from below via the support member 27 equipped with the weight sensor 26. Therefore, the weight of the weighing container 7 and the solution stored in the weighing container 7 is received by the weight sensor 26. The weight sensor 26 measures the weight of the solution stored in the weighing container 7. The weight sensor 26 may be a sensor of other types, such as an electromagnetic, piezoelectric, capacitance, magnetostrictive, or gyro load cell.

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 through the outlet pipe 37. In other words, the liquid can also be pressure-fed after being measured.

The measuring mechanism 15 includes a support member 27 that supports the measuring container 7, with the solution pipe 33, cleaning pipe 34, and 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, the measurement of the weight of the measuring container 7 is not affected by other components such as the sealed container 29 and cover 35, improving measurement accuracy.

[Regarding measuring container 7]
The measuring container 7 will now be described in further detail. The measuring container 7 includes 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 of a portion of the measuring mechanism 15. FIG. 4 is a perspective view of a portion of the measuring mechanism 15. The annular portion 22 extends 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 overflowing from the container body 21, which is formed by the bottom wall 31 (see FIG. 2 ) and the cylindrical side wall 32, can flow along 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 overflowing cleaning solution from flowing downward toward the bottom surface of the annular portion 22 and guides it to a drain pan 52, described later.

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 this 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.

[About the 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.

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

The upper cover part 41 is located 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 located 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 underside 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 underside 41L of the upper cover part 41, allowing the upper surface 22a of the annular part 22 and the underside 41L of the upper cover 41 to be thoroughly cleaned along the entire circumference.

The underside of the cover 35, i.e., the underside 42L of the lower cover portion 42, gradually becomes higher from the center 42c of the underside 42L toward the outside in the radial direction. Multiple solution pipes 33 and one cleaning pipe 34 protrude downward from the underside 42L of the lower cover portion 42. Therefore, these protruding portions can also be cleaned with the cleaning solution.

[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.

The drain pan 52 is annular 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.

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

As shown in FIG. 3 , the drainage mechanism 50 has a sensor 57 that detects the cleaning solution in the drain flow path 51. The sensor 57 can be of various types, as long as it can detect the cleaning solution flowing through the drain flow path 51. In this embodiment, the sensor 57 is located outside the sealed container 29. However, because 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. For this reason, the drain flow path 51 has a transparent pipe 58 with a transparent wall portion 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 indicates that the cleaning solution has overflowed from the metering container 7.

A drain valve 59 is provided downstream of the transparent pipe 58. The drain valve 59 is normally closed. As a result, the cleaning solution that flows into the drain flow path 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 cleaning of the measuring container 7 is complete, the drain valve 59 opens, and the cleaning solution in the drain flow path 51 is discharged. The opening and closing operation of the drain valve 59 is performed by the control device 16.

The measuring container 7 requires cleaning each time the type of solution to be measured is changed. To start cleaning, the storage container 2-20 (see Figure 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 on 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. The valve 36 on the outlet pipe 37 is closed.

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 presence of cleaning solution, the cleaning valve 14 is closed. The measuring container 7 is filled with cleaning solution and left for a predetermined time (e.g., 30 seconds to 1 minute) to perform cleaning.
In a second cleaning method, even if the sensor 57 detects the cleaning solution, the cleaning valve 14 is left open for a specified time (for example, 30 seconds to 1 minute) to continue supplying the cleaning solution, and the drain valve 59 is opened, and after the specified time has elapsed, the cleaning valve 14 and the drain valve 59 are closed. In this case, cleaning is carried out for a while with the cleaning solution allowed to overflow from the measuring container 7 for at least the specified time.

[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.

The drain flow path 51 is a flow path for sending the cleaning solution, which 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, out of the sealed container 29. In other words, if the cleaning solution fills the entire inner wall surface 7a of the measuring container 7 and overflows from the measuring container 7, the overflowing cleaning solution is sent out 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 serves as a flow path for sending the cleaning solution that overflows from the measuring container 7 out of the sealed container 29.

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 the 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, along which the overflowing cleaning solution flows, and a tubular portion 23 that extends downward from the outer periphery of the annular portion 22. With this configuration, the 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.

When supplying solution from the solution pipe 33 to the measuring container 7, the solution may splash out from the outlet at the lower end of the solution pipe 33, resulting in adhesion of the solution to the top of the measuring container 7. Furthermore, if the solution is highly volatile, the solution may adhere to the top of the measuring container 7. Even in such a case, with 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 and overflows the side wall 32 of the measuring container 7, allowing the inner surface of the side wall 32 of the measuring container 7 to be thoroughly cleaned. This makes it possible to expand the cleanable area of the measuring container 7 compared to conventional methods.

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 of the measuring container 7 (upper end 32u of the side wall 32) 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 catch any cleaning solution that may overflow from the measuring container 7. However, to ensure reliable cleaning, it is preferable for the cleaning solution to overflow from the measuring container 7.

As shown in FIG. 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 controls the stopping of the supply of cleaning solution from the cleaning pipe 34 to the measuring container 7. This configuration detects 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 thoroughly cleaned, and it is possible to proceed to the next step.

The next process is the draining of the cleaning solution remaining in the measuring container 7. Under the control of the control device 16, the valve 36 of the outlet pipe 37 (see Figure 2) is changed 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 via the outlet pipe 37 and the drain pipe 38. Although not shown, it is preferable that the drain pipe 38 has a branched flow path, for example, so that the cleaning solution flows to a drain tank rather than to the reaction container 9. Once the cleaning solution has been drained from the measuring container 7, the next solution is supplied to the measuring container 7 and measured. The cleaning solution remaining in the drain flow path 51 is drained when the drain valve 59 is opened.

The measuring mechanism 15 is equipped with a cover 35 that is provided with a gap e around the entire periphery between it and the side wall 32 of the measuring container 7. This cover 35 makes it difficult for foreign matter to enter the measuring container 7. It also prevents the solution in the measuring 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 measuring container 7. This overflowing cleaning solution can clean the underside of the cover 35, particularly the underside 41L of the upper cover portion 41.

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 through the gap e to the drain flow path 51 (drain pan 52). As a result, the entire gap e is filled with cleaning solution 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 to achieve this liquid volume relationship.

The cover 35 has a lower cover portion 42 and an upper cover portion 41 with a larger outer peripheral contour than 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 side wall 32 and the cover 35 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.

The height position of the upper cover part 41, i.e., the installation position of the cover 35, is set as follows: 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 with the cleaning solution.

When cleaning solution is supplied to the measuring container 7, the liquid level gradually rises until it 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. This configuration prevents air from collecting on the underside 42L of the lower cover part 42, preventing areas of the underside 42L from being left unwashed.

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 areas of the cylindrical side wall 32 from being left unwashed. 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.

In the above embodiment, the case where the cleaning solution overflows from the measuring container 7 when cleaning the measuring container 7 has been described. As explained above, in order to expand the cleanable area of the measuring container 7 more than before, there are cases where the cleaning solution does not need to overflow. For this purpose, 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.

With 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 is above the lower surface 42L of the cover 35 (lower cover portion 42), it is possible to clean the side wall 32 of the measuring container 7 as well as the lower surface 42L of the cover 35 (lower cover portion 42). This makes it possible to expand the washable area of the measuring container 7 compared to conventional methods.

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 with a larger outer peripheral contour than 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.

〔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 that exchanges and reacts multiple types of solutions.

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 equivalents to the configurations described in the claims.

3 Synthesis device 7 Measuring container 15 Measuring mechanism 16 Control device (control unit)
17 Pressurized gas pipe 22 Annular portion 22a Upper surface 23 Cylindrical portion 26 Weight sensor 27 Support member 29 Sealed container (outer container)
31 Bottom wall 32 Side wall 33 Solution pipe 34 Cleaning pipe 35 Cover 37 Outlet pipe 41 Upper cover part 41L Lower surface 42 Lower cover part 42L Lower surface 50 Drainage mechanism 51 Drain flow path 52 Drain pan 53 Inner peripheral wall 54 Outer peripheral wall 55 Bottom wall 57 Sensor e Gap e1 First gap e2 Second gap

Claims (9)

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. 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: The metering mechanism of claim 2, wherein the cleaning solution is supplied to the metering container while the pressure of the pressurized gas supplied within the outer container is maintained. 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. The measuring mechanism described in any one of claims 1 to 4, 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. 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: The measuring container according to claim 6, wherein the upper cover portion is provided at a height position where the cleaning solution that passes through the second gap and overflows the measuring container contacts the underside of the upper cover portion. A weighing mechanism as described in claim 6 or claim 7, wherein the underside of the cover has a slope that becomes higher toward the outside of the underside. 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.