JP6672502B1 - Liquid level control device for reaction vessel - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a liquid level control device for a reaction container capable of controlling a liquid level of a cleaning liquid in a reaction container to be appropriate. A liquid level control device for controlling a liquid level of a cleaning liquid when a cleaning liquid is supplied to a reaction container 11 provided in a solid-phase synthesis apparatus to clean the inside of the reaction container, The camera 41 is provided to capture an image of the reaction container from the side of the container 11. Further, it has a liquid surface detection unit 422 that detects the liquid surface level of the cleaning liquid supplied into the reaction container 11 based on the image captured by the camera 41. The supply and discharge of the cleaning liquid are controlled so that the liquid surface level of the cleaning liquid detected by the liquid surface detection unit 422 falls within a preset reference level range. [Selection diagram] Fig. 1

Description

  The present invention relates to a liquid level control device for a reaction vessel that controls a liquid level when a cleaning liquid is sent into a reaction vessel provided in a solid phase synthesis apparatus to wash the inside of the reaction vessel.

  2. Description of the Related Art A solid phase synthesizer (for example, a peptide synthesizer) that causes a synthetic reaction on a resin surface using a resin is known. In such a solid-phase synthesizer, a resin (beads, resin) and various chemicals as substances for performing a synthesis reaction are supplied into a reaction vessel to cause a synthesis reaction.

  In such a solid-phase synthesizer, when performing a synthesis reaction, it is necessary to wash the resin charged in the reaction vessel before supplying the chemical solution. As a conventional example of a method for washing a resin, for example, a method is known in which a washing liquid is supplied from above a reaction vessel and discharged from below the reaction vessel through a filter (for example, see Patent Document 1).

JP 2005-296832 A

  However, it is difficult to properly control the speed at which the cleaning liquid is supplied and the speed at which the cleaning liquid is discharged with the above-described related art. In addition, even when the speed is properly controlled, the resin level swells (increases in volume) in the reaction vessel, and the speed at the time of filtration under reduced pressure varies. Difficult to do. When the level of the cleaning liquid is low, the resin cannot be reliably cleaned. On the other hand, when the liquid level of the cleaning liquid is high, the resin diffuses in the cleaning liquid, the cleaning effect is reduced, and there is a problem that the cleaning liquid is excessively used. Therefore, it has been desired to somehow control the level of the cleaning liquid in the reaction vessel to be appropriate.

  The present invention has been made to solve such a conventional problem, and an object of the present invention is to provide a reaction system capable of controlling a cleaning liquid level in a reaction vessel to be appropriate. An object of the present invention is to provide a liquid level control device for a container.

In order to achieve the above object, the invention according to claim 1 of the present application is to supply a cleaning liquid to a transparent or translucent reaction vessel provided in a solid-phase synthesis apparatus, and to supply the cleaning solution inside the reaction vessel and inside the reaction vessel. A liquid level control device for controlling a liquid level of the cleaning liquid when cleaning a resin having a characteristic of being swelled in the cleaning liquid,
An imaging unit that images the reaction container from a side of the reaction container, and a liquid level detection unit that detects a liquid level of the cleaning liquid supplied into the reaction container based on an image captured by the imaging unit. A lower limit level that is higher by a predetermined lower limit Pmin based on an upper surface level of the resin in the reaction vessel that changes due to swelling of the resin, and an upper limit that is a level higher by a predetermined upper limit Pmax based on the upper surface level set the level, liquid level of the cleaning liquid is detected by the liquid level detection unit is higher than the lower limit level, and said to be lower than the upper level, the supply of the cleaning solution, and controls the discharge And a liquid level control unit.

  ADVANTAGE OF THE INVENTION According to this invention, since the upper surface level of the washing | cleaning liquid supplied at the time of washing a reaction container can be set to an appropriate level, it becomes possible to improve washing efficiency.

FIG. 1 is a flow chart of a solid-phase synthesizer that employs a liquid level controller according to an embodiment of the present invention. FIGS. 2A and 2B are flow charts of a container unit of the solid-phase synthesis apparatus employing the liquid level control device according to the embodiment of the present invention, wherein FIG. 2A is a first container unit, and FIG. Is shown. FIG. 3 is a block diagram illustrating a configuration of a cleaning liquid control unit of the liquid level control device according to the embodiment of the present invention. FIG. 4 is a flowchart illustrating a processing procedure of the liquid level control device according to the first embodiment of the present invention. FIGS. 5A and 5B are explanatory diagrams showing the resin and the cleaning liquid in the reaction vessel. FIG. 5A shows the case where the cleaning liquid is small, FIG. 5B shows the case where the cleaning liquid is large, and FIG. FIG. 6 is a flowchart illustrating a processing procedure of the liquid level control device according to the second embodiment of the present invention. FIGS. 7A and 7B are explanatory diagrams showing the resin and the cleaning liquid in the reaction vessel. FIG. 7A shows a case where the upper surface of the resin is appropriate, FIG. Show the case.

Hereinafter, embodiments of the present invention will be described with reference to the drawings.
[Description of First Embodiment]
FIG. 1 and FIG. 2 are flowcharts of a solid-phase synthesizer employing a liquid level control device according to an embodiment of the present invention. As shown in FIGS. 1 and 2, the solid-phase synthesizer 100 includes a reaction vessel 11 that is a vessel for performing a synthesis reaction, and a chemical solution (a liquid containing a reagent necessary for the reaction) supplied into the reaction vessel 11. It comprises two scales for accumulation, a first scale 12 and a second scale 13. Then, the granular resin is filled up to a certain height in the reaction vessel 11, and a chemical solution is further charged to perform a synthesis reaction by a solid phase synthesis method. In addition, in this embodiment, although the two measuring devices of the first measuring device 12 and the second measuring device 13 are described, the number of measuring devices is not limited to two. Further, the “resin” in the present invention is a concept including a natural resin, a synthetic resin, and a plastic.

  The reaction vessel 11 is made of a transparent or translucent material. Therefore, it is possible to take an image of the resin, the chemical solution, the cleaning liquid, and the like filled in the reaction container 11 with the camera 41 provided outside.

  In addition, as shown in FIGS. 2A and 2B, the solid-phase synthesizer 100 includes a first container 24 having a plurality of containers 24 for supplying a desired chemical solution to each of the measuring devices 12 and 13. A container unit 21 and a second container unit 22 having a plurality of containers 25 are provided.

  Each container 24 provided in the first container unit 21 is filled with various chemicals, and a plurality of pipes h <b> 1 serving as supply lines for supplying the chemicals from these containers 24 to the first measuring device 12 include: It is connected to one of a plurality of check valves u1 independently provided. Note that the “check valve” is a valve having a function of allowing a chemical solution to flow toward one side and blocking the flow on the opposite side. Check valves are sometimes referred to as check valves. Therefore, a desired chemical solution among the chemical solutions filled in each container 24 can be supplied into the first measuring device 12 via the pipe h1 and the check valve u1.

  Each container 25 provided in the second container unit 22 shown in FIG. 2 is filled with various kinds of chemicals, similarly to the container 24 of the first container unit 21 described above. A plurality of pipes h2 serving as supply lines for supplying a chemical solution from each container 25 to the second measuring device 13 are independently connected to one of a plurality of check valves u2. Therefore, the chemical liquid filled in each container 25 can be supplied to the second measuring device 13 via the independent pipe h2 and the check valve u2. The containers 24 and 25 have almost the same function, but may have different capacities. For example, the capacity of the container 24 is 50 liters, and the capacity of the container 25 is 15 liters.

  Further, as shown in FIG. 1, a stirrer 31 for stirring the chemical solution supplied into the reaction container 11 is provided inside the reaction container 11. The output shaft of the stirrer 31 is connected to a motor M3, and its rotation is controlled by a drive device (not shown). Specifically, the chemical liquid filled in the reaction vessel 11 is agitated by rotating the motor M3 so that the stirrer 31 reciprocates, for example, by repeating the normal rotation and the reverse rotation at every angle of 90 °.

A filter 34 for filtering impurities is provided on the lower surface of the reaction vessel 11. Further, a discharge pipe h3 is connected via a filter 34. The pipe h3 is connected to the pump P1 via a check valve u5 and an on-off valve v2. The pump P1 is, for example, a diaphragm-type pump, and the pump P1 is operated to reduce the pressure in the bottom of the reaction vessel 11 so that the chemical solution filled in the reaction vessel 11 or the liquid filled in the reaction vessel 11 for cleaning is used. The washing liquid is discharged to the outside as a waste liquid.
The above-described on-off valve v2 is of a normally closed type, and is opened so as to flow in the direction indicated by black when opened. The same applies to the on-off valves v1, v3, v4, v7 to v12, and v21 described below.

  A pipe h4 for supplying a compressed gas (for example, an inert gas such as nitrogen) for making the inside of the reaction vessel 11 a positive pressure (positive pressure) is connected to the upper surface of the reaction vessel 11. The pipe h4 is provided with an on-off valve v11, and a compressed gas supplied from the direction indicated by reference sign x3 is supplied into the reaction vessel 11 via the on-off valve v11. Then, the pressure inside the reaction vessel 11 can be made positive.

  Further, a pipe h5 for exhausting gas present in the reaction vessel 11 to the outside is provided on the upper surface of the reaction vessel 11, and the pipe h5 communicates with the outside via an on-off valve v12. . Further, a safety valve s3 is provided in parallel with the on-off valve v12. After the chemical solution is supplied into the reaction vessel 11, before the synthesis reaction is performed, or while the synthesis reaction is being performed, the on-off valve v12 is opened so that the space above the liquid level in the reaction vessel 11 Exhaust the filled gas. When the pressure in the reaction vessel 11 becomes excessive, the safety valve s3 is opened to avoid an abnormal pressure rise.

  A pipe h10 provided with an on-off valve v1 is connected to the upper surface of the reaction vessel 11. The end of the pipe h10 is connected to a cleaning liquid container (not shown), and the cleaning liquid is supplied into the reaction container 11 via the pipe h10. That is, by controlling the opening and closing of the on-off valve v1, the supply and stop of the cleaning liquid into the reaction vessel 11 can be controlled.

  In addition, the first measuring device 12 is provided with a stirrer 32 that stirs the chemical supplied to the first measuring device 12. The stirrer 32 is rotatable by a motor M2 connected to the output shaft. The stirrer 32 may be rotated in a fixed direction, or may be repeatedly rotated in the forward and reverse directions at an angle of 90 °, similarly to the stirrer 31 described above.

  An opening / closing valve v3 for discharging the chemical introduced into the first measuring device 12 is provided at the bottom of the first measuring device 12. Further, a three-way valve v5 for branching the output side into two systems is provided on the output side of the on-off valve v3, one of which is connected to the reaction vessel 11 and the other is connected to the reaction vessel 11. , Through a check valve u6. That is, by controlling the opening and closing of the three-way valve v5, the chemical solution released via the on-off valve v3 can be supplied to the reaction vessel 11 or discharged as a waste liquid.

  Further, a pipe h6 for supplying a compressed gas (for example, nitrogen gas) for making the inside of the first measuring device 12 a positive pressure is connected to the upper surface of the first measuring device 12. An open / close valve v9 is provided in the pipe h6, and compressed gas is supplied from the direction indicated by reference numeral x4 and supplied into the first measuring device 12 via the open / close valve v9. By supplying the compressed gas, the inside of the first meter 12 can be maintained at a positive pressure.

  Further, a pipe h7 for exhausting gas generated in the first measuring instrument 12 to the outside is provided on the upper surface of the first measuring instrument 12, and the pipe h7 is connected to the outside via an on-off valve v7. Communicating. Further, a safety valve s1 is provided in parallel with the on-off valve v7. Therefore, by controlling the opening and closing of the on-off valve v7, the gas filled in the first measuring device 12 can be discharged to the outside. When the pressure in the first measuring device 12 becomes excessive, the safety valve s1 is opened to avoid an abnormal pressure rise in the first measuring device 12.

  A check valve u3 is provided on the inlet side of the check valve u1 connected to the pipe h1. The outlet side of the check valve u3 is connected to the inlet side of the check valve u1. Then, a compressed gas is supplied to the inlet side of the check valve u3 from the direction indicated by the symbol x5. Accordingly, by supplying the compressed gas from the direction indicated by the symbol x5, the chemical liquid filled in the container (the container 24 provided in the first container unit 21 shown in FIG. 2A) connected to the pipe h1 is removed. It can be sucked and supplied into the first measuring device 12.

  Similarly to the first measuring device 12 described above, the second measuring device 13 is provided with a stirrer 33 for stirring the chemical supplied to the second measuring device 13, and is connected to the output shaft of the stirrer 33. The motor M1 can be driven to rotate.

  An opening / closing valve v4 for discharging the chemical introduced into the second measuring device 13 is provided at the bottom of the second measuring device 13. Further, a three-way valve v6 is provided on the output side of the on-off valve v4 to branch the output side into two systems. One of the branches is connected to the reaction vessel 11, and the other is connected to a waste liquid pipe via a check valve u7. That is, by controlling the opening and closing of the three-way valve v6, the chemical solution released via the on-off valve v4 can be supplied to the reaction vessel 11 or discharged as a waste liquid.

  Further, a pipe h8 for supplying a compressed gas (for example, nitrogen gas) for making the inside of the second measuring device 13 a positive pressure is connected to the upper surface of the second measuring device 13. An open / close valve v10 is provided in the pipe h8, and compressed gas is supplied from the direction indicated by the reference sign x2 and supplied into the second measuring device 13 via the open / close valve v10. By supplying the compressed gas, the inside of the second measuring device 13 can be maintained at a positive pressure.

  Further, on the upper surface of the second measuring device 13, there is provided a pipe h9 for exhausting gas generated in the measuring device 13 to the outside, and this pipe h9 communicates with the outside via an on-off valve v8. ing. Further, a safety valve s2 is provided in parallel with the on-off valve v8. Therefore, by controlling the opening and closing of the on-off valve v8, the gas filled in the second measuring device 13 can be discharged to the outside. When the pressure in the second measuring device 13 becomes excessive, the safety valve s2 is opened to avoid an abnormal increase in the pressure in the second measuring device 13.

  A check valve u4 is provided on the inlet side of the check valve u2 connected to the pipe h2. The outlet side of the check valve u4 is connected to the inlet side of the check valve u2. Then, the compressed gas is supplied to the inlet side of the check valve u4 from the direction indicated by the symbol x1. Therefore, by supplying the compressed gas from the direction indicated by the symbol x1, the chemical liquid filled in the container (the container 25 provided in the second container unit 22 shown in FIG. 2B) connected to the pipe h2 is removed. It can be sucked and supplied into the second measuring device 13.

  On the other hand, the plurality of containers 24 provided in the first container unit 21 shown in FIG. 2A are formed in a completely sealed shape, and various chemicals ( (A chemical solution for performing a synthesis reaction) is accumulated.

  At the bottom of the container 24, the tip of a pipe h1 serving as a supply line for the chemical solution is introduced. A pipe h22 provided with an on-off valve v21 is connected to the upper surface of the container 24. By opening the on-off valve v21, the gas filled in the container 24 can be discharged to the outside.

  Further, a pipe h21 is connected to the upper surface of the container 24, and one end of the pipe h21 is connected to the output side of the three-way valve v22. Compressed gas is supplied to one input side of the three-way valve v22 from the direction of the symbol x11, and compressed gas is supplied to the other input side from the direction of the symbol x12. The output side of the three-way valve v22 is connected to the container 24 via a check valve u21. The compressed gas supplied from the direction of the symbol x12 is a gas for maintaining the inside of the container 24 at a positive pressure, and the compressed gas supplied from the direction of the symbol x11 is obtained by adding the chemical liquid filled in the container 24. This is a gas to be pressurized and sent out from the pipe h1. That is, by controlling the opening and closing of the three-way valve v22, it is possible to switch between sending and stopping the liquid medicine filled in the container 24.

  The plurality of containers 25 provided in the second container unit 22 shown in FIG. 2B have the same configuration as the container 24 shown in FIG. 2A. Detailed description is omitted. However, the container 24 provided in the first container unit 21 and the container 25 provided in the second container unit 22 may have different capacities. For example, container 24 is 50 liters and container 25 is 15 liters.

  Returning to FIG. 1, a camera 41 (imaging unit) that captures an image of the inside of the reaction vessel 11 is provided beside the reaction vessel 11. Further, at the time of cleaning the inside of the reaction container 11, a cleaning liquid control unit 42 is provided which analyzes an image captured by the camera 41 and controls at least one of a supply amount of the cleaning liquid and a discharge amount of the cleaning liquid. . Further, a main controller 51 for controlling the entire solid phase synthesizer according to the present embodiment based on a control signal output from the cleaning liquid controller 42 and other control signals is provided.

  FIG. 3 is a block diagram showing a detailed configuration of the camera 41 and the cleaning liquid control unit 42. As illustrated in FIG. 3, the cleaning liquid control unit 42 includes an image analysis unit 421, a liquid level detection unit 422, a supply amount control unit 423, and a discharge amount control unit 424.

  The image analysis unit 421 analyzes the image captured by the camera 41 and detects the upper surface level of the resin filled in the reaction container 11 and the liquid level of the cleaning liquid.

  The liquid level detection unit 422 calculates the upper surface level of the resin and the liquid level of the cleaning liquid detected by the image analysis unit 421, and further determines whether the liquid level of the cleaning liquid is within a predetermined reference level range. I do. The liquid level detection unit 422 calculates a difference between the upper surface level of the resin and the liquid level of the cleaning liquid, and determines whether or not the difference is within a predetermined threshold range.

  In the first embodiment, the liquid level detection unit 422 sets the reference level range based on the upper surface level of the resin filled in the reaction container 11 when the cleaning liquid is supplied into the reaction container 11. Therefore, during the cleaning of the reaction vessel 11, the reference level range is a fixed range. For example, a range indicated by levels q1 to q2 shown in FIGS. 5A to 5C described later is set as a reference level range (constant range).

  In a second embodiment to be described later, the liquid level detection unit 422 sets a reference level range based on the upper surface level of the resin being cleaned with the cleaning liquid supplied into the reaction vessel 11. Therefore, when the upper surface level of the resin changes during the cleaning of the reaction vessel 11, the reference level range changes in accordance with the change. For example, as shown in FIG. 7 described later, when the upper surface level p2 of the resin 61 changes, the reference level range changes accordingly. In the example shown in FIG. 7A, the range of q11 to q12, in the example of FIG. 7B, the range of q13 to q14, and in the example of FIG. 7C, the range of q15 to q16 is the reference level range. Is set.

  The supply amount control unit 423 controls the amount of the cleaning liquid supplied into the reaction vessel 11 so that the liquid level of the cleaning liquid falls within the reference level range. Specifically, the supply amount of the cleaning liquid is adjusted by controlling the opening and closing of the on-off valve v1 shown in FIG. In a second embodiment described later, the amount of the cleaning liquid supplied into the reaction vessel 11 is controlled such that the difference between the upper surface level of the resin and the liquid level of the cleaning liquid is within a threshold range.

  The discharge amount control unit 424 controls the amount of the cleaning liquid discharged from the reaction vessel 11 so that the liquid level of the cleaning liquid falls within the reference level range. Specifically, the driving of the pump P1 shown in FIG. 1 is controlled to control the discharge amount of the cleaning liquid. In a second embodiment described later, the amount of the cleaning liquid discharged from the reaction vessel 11 is controlled so that the difference between the upper surface level of the resin and the liquid level of the cleaning liquid is within a threshold range. Specifically, the driving of the pump P1 is controlled, and the discharge amount of the cleaning liquid is controlled so that the difference falls within the threshold range.

  That is, the supply amount control unit 423 and the discharge amount control unit 424 supply the cleaning liquid so that the liquid level of the cleaning liquid detected by the liquid level detection unit 422 falls within a preset reference level range. It has a function as a liquid level control unit that controls discharge.

  The cleaning liquid control unit 42 can be configured as an integrated computer including a central processing unit (CPU) and storage means such as a RAM, a ROM, and a hard disk, for example.

  Next, a processing procedure of the liquid level control device according to the present embodiment will be described with reference to a flowchart shown in FIG. 4 and an explanatory diagram shown in FIG. Each process shown in FIG. 4 is executed by the cleaning liquid control unit 42 or the main controller 51 shown in FIG.

  In step S11, the cleaning liquid controller 42 operates the camera 41 to capture an image (monochrome or color image) in the reaction container 11. As described above, since the reaction vessel 11 is formed of a transparent or translucent material, an image inside the reaction vessel 11 can be captured by the camera 41 installed on the side of the reaction vessel 11. .

  In step S12, the cleaning liquid is supplied into the reaction vessel 11 until a desired liquid level is reached. That is, by controlling the opening and closing of the on-off valve v1 under the control of the main controller 51, the cleaning liquid is supplied to a desired liquid level in the reaction vessel 11. By supplying the cleaning liquid into the reaction vessel 11, for example, as shown in FIG. 5C, a reference level range set to a height exceeding the upper surface level p2 of the resin 61 filled in the reaction vessel 11 The cleaning liquid 62 is supplied so as to be in the range (q1 to q2).

  Further, the opening / closing valve v2 is opened and the pump P1 is operated to discharge the cleaning liquid in the reaction vessel 11. That is, the amount of the cleaning liquid discharged from the reaction container 11 and the amount of the cleaning liquid supplied into the reaction container 11 are appropriately controlled so that the level of the cleaning liquid in the reaction container 11 falls within the reference level range. Control.

  In step S13, the image analysis unit 421 detects the level of the cleaning liquid in the reaction container 11 based on the image captured by the camera 41.

  In step S14, the liquid level detection unit 422 determines whether the liquid level p1 of the cleaning liquid is lower than a lower limit level (q1 shown in FIG. 5C) which is the lower limit of the reference level range. If the liquid level p1 is lower than the lower limit level q1 (YES in step S14), the cleaning liquid is supplied into the reaction vessel 11 and the discharge of the cleaning liquid from the reaction vessel 11 is stopped in step S15.

  For example, as shown in FIG. 5A, when the liquid level p1 of the cleaning liquid 62 is lower than the lower limit level q1, the cleaning liquid 62 may not be immersed in the entire resin 61, so that effective cleaning is performed. May not be possible. Accordingly, the pump P1 is stopped to stop the discharge of the cleaning liquid, and the on-off valve v1 is opened to supply the cleaning liquid, thereby raising the liquid level p1.

  On the other hand, when the liquid level p1 of the cleaning liquid 62 is higher than the lower limit level q1 (NO in step S14), in step S16, the liquid level detection unit 422 sets the liquid level of the cleaning liquid to the upper limit level (see FIG. ) Is determined to be higher than q2). If the liquid level is higher than the upper limit level q2 (YES in step S16), in step S17, main controller 51 closes on-off valve v1 to stop supplying the cleaning liquid, and opens on-off valve v2. Then, the pump P1 is operated to discharge the cleaning liquid in the reaction vessel 11.

  For example, as shown in FIG. 5B, when the liquid level p1 of the cleaning liquid 62 is higher than the upper limit level q2, the resin 61 flies and diffuses, and the cleaning effect is reduced. Therefore, the cleaning liquid 62 is discharged to lower the liquid level p1.

  When the liquid level p1 of the cleaning liquid 62 is lower than the upper limit level q2 (NO in step S16), in step S18, the main controller 51 opens the on-off valve v1 to supply the cleaning liquid, and supplies the on-off valve v2 Is opened, and the pump P1 is operated to supply the cleaning liquid into the reaction vessel 11 and discharge the cleaning liquid from the reaction vessel 11, so that the amount of the cleaning liquid in the reaction vessel 11 becomes appropriate. maintain.

  In step S19, main controller 51 determines whether a predetermined time has elapsed since the start of cleaning. If the predetermined time has not elapsed (NO in step S19), the process returns to step S14.

  If the predetermined time has elapsed (YES in step S19), the supply of the cleaning liquid into the reaction vessel 11 is stopped in step S20.

  In step S21, the main controller 51 opens the on-off valve v2 and operates the pump P1 to discharge the cleaning liquid in the reaction vessel 11 to the outside. Then, the present process ends.

  As described above, the liquid level control device for the reaction vessel according to the first embodiment captures an image in the reaction vessel 11 using the camera 41, analyzes the captured image, and analyzes the liquid level, which is the upper surface of the cleaning liquid. Is controlled to be within the reference level range.

  Therefore, control can be performed so that the liquid level of the cleaning liquid in the reaction vessel 11 becomes appropriate, and the cleaning efficiency can be improved. Further, since it is not necessary to supply a large amount of cleaning liquid, the amount of cleaning liquid to be used can be reduced.

  Further, the camera 41 has a function of capturing a color or monochrome image, and based on the color difference in the image, the upper surface level p2 of the resin 61 and the liquid of the cleaning liquid 62 shown in FIGS. Since the surface level p1 is detected, the detection accuracy of the liquid level can be improved, and the liquid level of the cleaning liquid 62 can be maintained at an appropriate liquid level with high accuracy.

  Further, since the liquid level of the cleaning liquid is detected using a real-time image picked up by the camera 41, even when the resin swells in the reaction vessel 11 or the filtration speed by the pump P1 fluctuates, these conditions are maintained. , It is possible to control the liquid level to be surely within a desired reference level range.

[Description of Second Embodiment]
Next, a second embodiment of the present invention will be described. In the first embodiment described above, the supply amount of the cleaning liquid and the supply amount of the cleaning liquid are analyzed so that the level of the cleaning liquid is within a predetermined range (within an initially set range) by analyzing an image captured by the camera 41. Controlling emissions has been described.

  On the other hand, in the second embodiment, the difference between the upper surface level of the resin and the liquid surface level of the cleaning liquid is controlled to be constant. The configuration of the apparatus is the same as that of the above-described first embodiment, and a description of the configuration will be omitted. Hereinafter, a processing procedure of the liquid level control device according to the second embodiment will be described with reference to a flowchart shown in FIG. 6 and an explanatory diagram shown in FIG.

  In the processing procedure shown in the flowchart of FIG. 6, the processing of steps S31 and S32 is the same as the processing of steps S11 and S12, and the processing of steps S39 to S41 is the processing of steps S19 to S21 in comparison with FIG. Is the same as Therefore, the processing of steps S33 to S38 will be described below.

  When the cleaning liquid is supplied to a predetermined level in the reaction container 11 (step S32), in step S33, the liquid level detection unit 422 determines the difference between the height of the resin upper surface in the reaction container 11 and the liquid level of the cleaning liquid. To detect.

  In step S34, the liquid level detection unit 422 determines whether the difference between the upper surface level of the resin and the liquid level of the cleaning liquid is smaller than a lower limit of a preset threshold range. For example, when the lower limit of the threshold range of the difference is Pmin and the upper limit is Pmax, it is determined whether the difference is smaller than the lower limit Pmin.

  More specifically, as shown in FIG. 7A, a level q11 higher than the upper surface level p2 of the resin 61 by the lower limit Pmin and a level q12 higher than the upper surface level p2 of the resin 61 by the upper limit Pmax are set. It is determined whether or not the plane level p1 is within the range of levels q11 to q12. When the difference between the upper surface level p2 of the resin 61 and the liquid level p1 of the cleaning liquid 62 is equal to or greater than the lower limit Pmin and equal to or less than the upper limit Pmax, the liquid level of the cleaning liquid 62 falls within the range of q11 to q12. become. In this case, the supply amount and the discharge amount of the cleaning liquid are maintained without changing the supply amount of the cleaning liquid into the reaction vessel and the discharge amount of the cleaning liquid.

  As shown in FIG. 7B, when the upper surface level p2 of the resin 61 is higher than that in FIG. 7A, the levels q13 and q14 are set, and the liquid level of the cleaning liquid 62 is set. It is determined whether or not p1 is within the range of levels q13 to q14.

  Further, as shown in FIG. 7C, when the upper surface level p2 of the resin 61 is lower than that in FIG. 7A, the levels q15 and q16 are set, and the liquid level of the cleaning liquid 62 is set. It is determined whether or not p1 is within the range of levels q15 to q16. That is, when the upper surface level p2 of the resin 61 changes, the range in which the liquid surface level p1 of the cleaning liquid 62 is determined to be normal is changed accordingly.

  Then, when the difference is smaller than the lower limit Pmin (that is, when p1 is lower than q11 in FIG. 7A, when p1 is lower than q13 in FIG. 7B, p1 is q15 in FIG. 7C). If it is lower than (YES in step S34), in step S35, main controller 51 stops pump P1 to stop the discharge of the cleaning liquid, and opens and closes on-off valve v1 to supply the cleaning liquid. , The liquid level p1 is increased.

  On the other hand, if the difference is larger than the lower limit Pmin (NO in step S34), in step S36, the liquid level detection unit 422 determines that the difference between the resin upper surface level and the cleaning liquid level is larger than the upper limit Pmax of the threshold range. Is also determined.

  When the difference is larger than the upper limit Pmax (that is, when p1 is higher than q12 in FIG. 7A, when p1 is higher than q14 in FIG. 7B, p1 is higher than q16 in FIG. 7C). If it is high (YES in step S36), in step S37, main controller 51 closes on-off valve v1 to stop supplying the cleaning liquid, opens on-off valve v2, and operates pump P1. Then, the cleaning liquid in the reaction vessel 11 is discharged. After that, the processing shifts to the processing of step S39.

  When the difference is smaller than the upper limit Pmax (NO in step S36), in step S38, the main controller 51 opens the on-off valve v1 to supply the cleaning liquid, and opens the on-off valve v2 to open the pump. By activating P1, the supply of the cleaning liquid into the reaction container 11 and the discharge of the cleaning liquid from the reaction container 11 are performed, and the amount of the cleaning liquid in the reaction container 11 is maintained to be appropriate. After that, the processing shifts to the step S39.

  In this manner, the liquid level control device according to the second embodiment calculates the difference between the upper surface level p2 of the resin and the liquid level p1 of the cleaning liquid based on the image captured by the camera 41, and calculates the difference. It is determined whether or not it is within a preset threshold range. If it is equal to or less than the lower limit Pmin of the threshold range, the cleaning liquid is supplied into the reaction vessel 11, and control is performed so that the difference between the upper limit level of the resin and the liquid level of the cleaning liquid falls within the threshold range. On the other hand, when it is equal to or more than the upper limit Pmax of the threshold range, the cleaning liquid in the reaction vessel 11 is discharged, and the difference between the upper limit level of the resin and the liquid level of the cleaning liquid is controlled to be within the threshold range.

  When the above difference is within the threshold range (when it is within the range of the lower limit Pmin to the upper limit Pmax), the supply amount and the discharge amount of the cleaning liquid are maintained, and the amount of the cleaning liquid in the reaction vessel 11 is adjusted to an appropriate value. To maintain.

  Therefore, control can be performed so that the liquid level of the cleaning liquid in the reaction vessel 11 becomes appropriate, and the cleaning efficiency can be improved. Further, since it is not necessary to supply a large amount of cleaning liquid, the amount of cleaning liquid to be used can be reduced.

  Further, since the camera 41 detects the boundary between the resin and the cleaning liquid and the liquid level of the cleaning liquid based on the image, it is possible to improve the detection accuracy of the upper surface level of the resin and the liquid level of the cleaning liquid. Can be maintained as appropriate.

  In addition, since the upper surface level of the resin and the liquid level of the cleaning liquid are detected using a real-time image captured by the camera 41, the resin swells in the reaction vessel 11 or the filtration speed by the pump P1 varies. Even in such a case, it is possible to control such that the difference falls within the threshold range without fail following the change.

Furthermore, according to the first and second embodiments, since the camera 41 is arranged outside the reaction vessel 11, retrofitting, replacement, and calibration can be easily performed. Further, since the chemical liquid does not adhere to the camera 41, there is no need to consider the resistance to the chemical. Furthermore, even if some waves are generated in the reaction vessel 11, the liquid level of the cleaning liquid can be detected without being greatly affected by the waves. Further, it is possible to detect the liquid level of the cleaning solution without being influenced by lighting and intensity of the ambient. Further, if the reaction vessel 11 is transparent, a double structure or a triple structure can be used.

  Although the embodiments of the present invention have been described above, it should not be understood that the description and drawings constituting a part of the present disclosure limit the present invention. From this disclosure, various alternative embodiments, examples, and operation techniques will be apparent to those skilled in the art.

11 reaction vessel 12 first measuring device 13 second measuring device
21 first container unit 22 second container unit 24, 25 container 31, 32, 33 stirrer 34 filter 41 camera (imaging unit)
42 Cleaning liquid control unit 51 Main control device 61 Resin 62 Cleaning liquid 100 Solid phase synthesis device 421 Image analysis unit 422 Liquid level detection unit 423 Supply amount control unit (liquid level control unit)
424 Emission control unit (liquid level control unit)
M1 to M3 Motor P1 Pump h1 to h10, h21, h22 Piping p1 Liquid level of washing liquid p2 Upper surface level of resin s1 to s3 Safety valve u1 to u7, u21 Check valve v1 to v4, v7 to v12, v21 Open / close valve v5, v6 , V22 three-way valve

Claims (1)

A cleaning liquid is supplied to a transparent or translucent reaction vessel provided in a solid-phase synthesizer to wash the inside of the reaction vessel, and a resin that is charged into the reaction vessel and has a property of swelling in the cleaning liquid. A liquid level control device for controlling a liquid level of the cleaning liquid,
An imaging unit that images the reaction container from a side of the reaction container,
A liquid level detection unit that detects a liquid level of the cleaning liquid supplied into the reaction container based on the image captured by the imaging unit,
A lower limit level that is higher by a predetermined lower limit Pmin based on the upper surface level of the resin in the reaction vessel that changes due to swelling of the resin, and an upper limit level that is higher by a predetermined upper limit Pmax based on the upper surface level. And set
A liquid level control unit that controls the supply and discharge of the cleaning liquid so that the liquid level of the cleaning liquid detected by the liquid level detection unit is higher than the lower limit level and lower than the upper limit level. When,
A liquid level control device for a reaction vessel, comprising:

Images