JP7175740B2 - Chemical synthesis apparatus and chemical synthesis method - Google Patents

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a chemical synthesizing apparatus and a chemical synthesizing method that involve stirring when synthesizing a chemical.

2. Description of the Related Art In chemical synthesizers for chemically synthesizing proteins, peptides, polymers, nucleic acids, etc., chemical synthesis is performed by supplying a plurality of chemical solutions (reagents) to reaction vessels. For example, when synthesizing nucleic acids, a large number of carriers (porous beads, hereinafter referred to as beads) are provided in a reaction vessel, and chemical solutions are sequentially supplied to the reaction vessel while detritylation, coupling, oxidation, Treatments such as capping are repeated to bind successive bases to the beads.

As a general chemical synthesis apparatus, for example, as shown in FIG. The chemical liquid tank 101 and the reaction vessel 100 are respectively connected by a first pipe 103, and the waste liquid tank 102 and the reaction vessel 100 are connected by a second pipe 105. It is Then, chemical synthesis with the chemical solution is performed in the reaction container 100 by supplying the chemical solution from the chemical solution tank 101 through the first pipe 103 to the reaction container 100 , and the synthesized chemical solution is finally discharged through the second pipe 105 . It is discharged to the liquid tank 102 .

In such a chemical synthesizing apparatus, the supply of the chemical to the reaction vessel 100 and the discharge of the chemical from the reaction vessel 100 are performed by the liquid sending means 104 for pressurizing the chemical tank 101 . That is, the liquid feeding means 104 has a gas tank 104a filled with gas. The chemical liquid supplied to the reaction vessel 100 undergoes chemical synthesis with the beads in the reaction vessel 100, and the chemical liquid after the reaction and the surplus chemical liquid are pressurized in the chemical liquid tank 101 by the liquid feeding means 104. As a result, the liquid is discharged to the drainage tank 102 .

In addition, the reaction vessel 100 is provided with a circulation circuit. In other words, there are cases where the chemical solution and all the beads in the reaction vessel cannot fully react with a single supply of the chemical solution, and some chemical solutions take a long time to react with the beads. Therefore, the chemical liquid may be drained to the drain tank 102 without sufficient chemical synthesis. In order to avoid this problem, the same chemical solution is again supplied to the reaction vessel 100 through the circulation circuit to produce an agitation effect between the chemical solution and the beads. In the example of FIG. 8, the circulation circuit is provided with a circulation pipe 106 that communicates from the second pipe 105 to the first pipe 103, and the valve 107 of the second pipe 105 and the valve 108 of the first pipe 103 are closed. By driving the pump 109 of the circulation pipe in this state, the chemical liquid discharged from the reaction container 100 can be supplied again to the reaction container 100 through the circulation pipe 106 .
Thus, by supplying the chemical solution to the entire beads and securing the reaction time of the chemical solution, the beads and the chemical solution can be sufficiently reacted.

WO2010/038613

However, in the above-described chemical synthesizing apparatus, since agitation is performed using a circulation circuit within the reaction vessel, there is a problem that the overall size of the apparatus increases and the cost increases. That is, since the circulation pipe 106 for returning the chemical once discharged to the second pipe 105 to the reaction vessel 100 is required, the circulation pipe 106 and the pump 109 dedicated to the circulation circuit are separately required. In addition to the circulation circuit, it is conceivable to vibrate the reaction vessel 100 for stirring or to provide a stirrer in the reaction vessel 100. There is a problem of complicating the device configuration and increasing the cost of the entire device.

In addition, in the above circulation circuit, the inside of the circulation pipe must be filled with the chemical solution in order to circulate the chemical solution. Therefore, it is necessary to supply the chemical solution in an amount larger than that required for the reaction with the beads, and the chemical solution is wasted. There was a problem of becoming

SUMMARY OF THE INVENTION The present invention has been made in view of the above problems, and provides a chemical synthesizing apparatus and a chemical synthesizing method that can increase the reaction efficiency of chemical solutions while avoiding complication of the device configuration and increase in cost. It is intended to

In order to solve the above problems, the chemical synthesizing apparatus of the present invention comprises: a reaction vessel for reacting the filled carrier and the supplied chemical; A first pipe that is connected to the reaction vessel, a second pipe that is arranged downstream in the liquid feeding direction when viewed from the first pipe, and a chemical liquid sent to the reaction vessel through the first pipe. liquid supply means; gas supply means for returning the chemical solution contained in the reaction container to the first pipe side by supplying gas to the reaction container through the second pipe; and stirring the supplied chemical solution. agitation control means, wherein the agitation control means is formed by the first pipe, the reaction vessel, and the second pipe by controlling the progressive liquid feeding means and the gas supply means; The liquid chemical in the reaction vessel is stirred by displacing the liquid surface position of the chemical liquid a plurality of times in the liquid feeding path, and the stirring control means moves the liquid surface position of the chemical liquid to a predetermined position in the reaction vessel. This local stirring function finely displaces the liquid surface position of the chemical solution in the reaction vessel, and locally concentrates at a selected position in the reaction vessel. It is characterized by stirring .

According to the chemical synthesizing apparatus, the agitation control means displaces the surface position of the chemical supplied to the reaction container within the liquid supply path formed by the first pipe, the reaction container, and the second pipe. As a result, the chemical solution in the reaction vessel can exhibit a stirring effect, and the reaction efficiency between the chemical solution and the carriers (beads) in the reaction vessel can be improved. In addition, since the liquid surface of the chemical solution is displaced in the first pipe and the second pipe connected to the reaction vessel and within the reaction vessel, there is no need to provide a separate device or instrument such as a conventional circulation circuit, Since the chemical solution can be stirred using the original chemical solution path of the chemical solution synthesizing device, it is possible to avoid the problems of complication of the device configuration and high cost of the entire device. In addition, it is possible to avoid the problem of wasteful consumption of chemicals because it is only necessary to supply only the chemicals necessary for the chemical synthesis reaction and displace the liquid surface without using chemicals more than necessary for stirring. can. The local stirring function allows the chemical solution and the beads in the reaction container to be locally and intensively collided with each other and stirred, so that the stirring efficiency can be improved.

In addition, the stirring control means has a local stirring function that displaces the liquid surface position of the chemical solution a plurality of times at a predetermined position in the reaction vessel. It may be configured to be executed multiple times.

According to this configuration, the local stirring function allows the chemical solution and the beads in the reaction container to collide intensively and stir, so that the stirring efficiency can be improved. In addition, by performing this process multiple times at different positions in the reaction vessel, the chemical solution can be distributed and stirred even in areas where the stirring efficiency is low in the reaction vessel, and the entire beads in the reaction vessel can be uniformly reacted. can be made

Further, the agitation control means is configured to perform control including positioning the liquid surface position of the chemical liquid at the first pipe or the second pipe when displacing the liquid level position of the chemical liquid a plurality of times. good too.

According to this configuration, since the liquid surface of the chemical liquid is largely displaced, the entire chemical liquid supplied and the beads can be agitated, and the entire chemical liquid can be reacted.

Further, the agitation control means has a supply-side valve provided on the first pipe and a drain-side valve provided on the second pipe. A configuration may be adopted in which control is performed to simultaneously close the supply side valve and the drainage side valve.

According to this configuration, since the liquid surface of the chemical liquid can be stopped instantly, the change in the liquid surface position from the liquid supply to the stop and from the liquid supply to the liquid supply becomes rapid, and the liquid surface of the chemical liquid collides with the beads. The stirring effect can be improved.

Further, in order to solve the above problems, the method for synthesizing a chemical solution according to the present invention provides a chemical solution through a first pipe to a reaction vessel in which the carrier is accommodated, thereby causing the chemical solution and the carrier to react in the reaction vessel. a chemical synthesis method in which the chemical solution after the reaction is discharged through the second pipe, the forward flow step of supplying the chemical solution through the first pipe to send the chemical solution to the second pipe side through the reaction vessel; a forward flow stop step of stopping the liquid transfer, a reverse flow step of causing the chemical solution to flow backward in the direction opposite to the forward flow step by supplying gas through the second pipe, and a backflow stop step of stopping the liquid transfer in the reverse flow step and further comprising a stirring step of repeating the forward flow step, the forward flow stop step, the backflow step, and the backflow stop step , wherein the stirring step is performed so that the liquid surface of the chemical is in the reaction vessel This local stirring step finely displaces the liquid surface position of the chemical solution in the reaction vessel, and localized at a selected position in the reaction vessel It is characterized by intensively stirring .

According to the chemical synthesis method, the forward flow step, the forward flow stopping step, the backflow step, and the backflow stopping step are repeated, thereby displacing the liquid surface of the chemical solution in the liquid feeding path and increasing the reaction vessel. A chemical liquid can be made to exhibit a stirring effect. Therefore, it is possible to improve the reaction efficiency between the chemical solution and the carriers (beads) in the reaction vessel. Since it is only necessary to stop the feeding of the supplied chemical solution and reverse the liquid feeding direction, there is no need to provide a separate device or equipment such as a conventional circulation circuit, and the chemical solution path of the original chemical synthesis device is eliminated. can be used to agitate the chemical solution, it is possible to avoid the problems of complication of the device configuration and high cost of the entire device. In addition, it is possible to avoid the problem of wasteful consumption of chemicals because it is only necessary to supply only the chemicals necessary for the chemical synthesis reaction and displace the liquid surface without using chemicals more than necessary for stirring. can. In addition, the local stirring step allows the chemical liquid and the beads in the reaction vessel to locally and intensively collide and stir, thereby improving the stirring efficiency.

Further, the stirring step includes a local stirring step performed in a state where the liquid surface of the chemical solution is positioned at a predetermined position in the reaction vessel, and the local stirring step is performed multiple times at different positions in the reaction vessel. It may be configured to be

According to this configuration, the chemical liquid and the beads in the reaction container can be agitated by intensively colliding with each other in the local agitation step, so that the agitation efficiency can be improved. In addition, by performing this process multiple times at different positions in the reactor, even in areas where the stirring efficiency is low in the reaction vessel, the chemical solution can be distributed and stirred, and the entire bead in the reaction vessel can be uniformly reacted. be able to.

Further, the stirring step may be configured such that the liquid surface of the chemical liquid is positioned at the first pipe or the second pipe.

According to this configuration, since the liquid surface of the chemical liquid is largely displaced, the entire chemical liquid supplied and the beads can be agitated, and the entire chemical liquid can be reacted.

Further, the first pipe is provided with a supply-side valve, and the second pipe is provided with a drain-side valve. and the drain side valve may be closed at the same time to stop the feeding of the chemical solution.

According to this configuration, since the liquid surface of the chemical liquid can be stopped instantly, the change in the liquid surface position from the liquid supply to the stop and from the liquid supply to the liquid supply can be sharply controlled, and the collision between the liquid surface of the chemical liquid and the beads The stirring effect can be improved.

ADVANTAGE OF THE INVENTION According to the chemical|medical-solution synthesizing apparatus and chemical|medical-solution synthesizing method of this invention, the reaction efficiency of a chemical-solution can be improved, avoiding the complication of an apparatus structure and an increase in cost.

1 is a schematic piping route diagram of a chemical synthesis apparatus of the present invention; FIG. It is an enlarged view near the reaction container of the said chemical-solution synthesizing apparatus. It is a figure which shows the liquid level position of a chemical|medical solution, and the opening-and-closing state of a valve, (a) is a figure which shows a forward flow process, (b) is a figure which shows a forward flow stop process. It is a figure which shows the liquid level position of a chemical|medical solution, and the opening-and-closing state of a valve, (a) is a figure which shows a backflow process, (b) is a figure which shows a backflow stop process. It is a figure which shows the liquid level position of a chemical|medical solution in a local stirring process, and the opening-and-closing state of a valve, (a) is a figure which shows a forward flow process, (b) is a figure which shows a forward flow stop process. FIG. 4 is a diagram showing the liquid surface position of the chemical solution and the opening/closing state of the valve in the local stirring process, (a) showing the backflow process, and (b) showing the backflow stopping process. FIG. 10 is a diagram showing changes in the liquid surface position of the reaction vessel in the local stirring process; It is a figure which shows the conventional chemical|medical-solution synthesizing apparatus.

DESCRIPTION OF THE PREFERRED EMBODIMENTS An embodiment of a chemical synthesizing apparatus and a chemical synthesizing method of the present invention will be described with reference to the drawings.

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

As shown in FIG. 1, the chemical synthesizing apparatus includes a chemical liquid tank 1 in which chemical liquid is stored, a reaction vessel 2 containing carriers (porous beads, hereinafter also referred to as beads), and discharge from the reaction vessel 2. and a waste liquid tank 11 for storing the discharged waste liquid. When the chemical solution is supplied from the chemical solution tank 1 to the reaction container 2 , the chemical solution is chemically synthesized by contacting the beads and the chemical solution in the reaction container 2 , and the chemical solution after chemical synthesis is discharged to the drainage tank 11 . For example, when synthesizing nucleic acids, the reaction vessel 2 contains a large number of porous beads. The process is repeated to bind successive bases to the beads.

The chemical liquid tank 1 is for storing reagents used in chemical synthesis. Although three chemical tanks 1 are shown in the example of FIG. there is In the example of FIG. 1, each chemical liquid tank 1 is connected to a first pipe 44 mainly for supplying the chemical liquid to the reaction vessel 2, and these pipes are gathered in the middle to form one first pipe 44. It is connected to the reaction vessel 2 .

A pressure adjusting means 6 is connected to the chemical tank 1 , and the chemical in the chemical tank 1 is fed by the pressure adjusting means 6 . The pressure adjusting means 6 has a gas tank 61 filled with gas and a gas pipe 41 connecting the gas tank 61 and the chemical tank 1 . can be supplied to That is, by supplying gas from the gas tank 61 , the pressure of the chemical tank 1 is adjusted to the pressure of the gas tank 61 , and the chemical in the chemical tank 1 is sent to the reaction vessel 2 . By adjusting the pressure of the gas tank 61, the flow rate of the chemical solution sent from the chemical solution tank 1 can be adjusted. That is, when the differential pressure between the pressure of the chemical tank 1 and the reaction vessel 2 is increased, the liquid supply speed of the chemical liquid from the chemical tank 1 is increased, and the amount of the chemical liquid can be increased. When the differential pressure between the tank 1 and the reaction container 2 is reduced, the speed of the chemical solution sent from the chemical solution tank 1 is reduced, and the amount of the chemical solution can be suppressed.

A valve 51 is provided in the first pipe 44 and the gas pipe 41 . That is, the first pipe 44 connected to each chemical tank 1 and the gas pipe 41 are each provided with a valve 51, and the unified first pipe 44 has a supply side valve 52 near the reaction vessel 2 and a gas pipe 41. , and an upstream supply side valve 53 near the chemical liquid tank 1 are provided. That is, with the valve 51 of the chemical liquid tank 1 selected as a supply target, the supply side valve 52, and the upstream supply side valve 53 in the open state, the gas is supplied from the gas tank 61 of the pressure adjustment means 6 to the chemical liquid tank. 1 is pressurized to control the pressure in the chemical tank 1 to be higher than the pressure in the reaction vessel 2, and the chemical in the selected chemical tank 1 is sent to the reaction vessel 2 through the first pipe 44. In addition, as will be described later, when the chemical solution tank 1 side is caused to flow back from the reaction container 2, the pressure of the reaction container 2 is controlled to be higher than that of the chemical solution tank 1, and the chemical solution supplied to the reaction container 2 is returned. be able to. In this way, the pressure adjusting means 6 can adjust the differential pressure between the chemical liquid tank 1 and the reaction vessel 2, and can control the liquid feeding direction of the chemical liquid.

In this embodiment, the pressure adjusting means 6 adjusts the differential pressure by adjusting the pressure of the gas tank 61. Regulators and valves are provided in the pipes connected to the gas tank 61, the reaction vessel 2, and the chemical solution tank 1, respectively. Thus, the pressures of the chemical liquid tank 1 and the reaction vessel 2 may be controlled to adjust the differential pressure between the chemical liquid tank 1 and the reaction vessel 2 . The gas in the gas tank 61 is a gas (for example, argon gas) that does not react with the chemical solution in the chemical solution tank 1 .

Further, the reaction vessel 2 provides a reaction field for chemically synthesizing the beads contained in the reaction vessel 2 and the supplied chemical liquid or the like by bringing them into contact with each other. The reaction vessel 2 uses a glass cylindrical tube extending in one direction, and beads are accommodated in the reaction vessel 2 . Ports 21 to which the pipes 4 can be connected are provided at both ends of the reaction vessel 2 , and the first pipes 44 and the second pipes 45 are connected to the respective ports 21 . In this embodiment, the first pipe 44 is connected to the lower side of the reaction vessel 2, and the second pipe 45 is connected to the upper side. That is, the first pipe 44, the reaction vessel 2, and the second pipe 45 form a liquid feeding path, and when the chemical liquid tank 1 selected by the pressure adjusting means 6 is pressurized, the chemical liquid is fed from the chemical liquid tank 1. The chemical solution is introduced into the reaction vessel 2 through the first pipe 44 and the port 21 . The chemical solution and the beads are chemically synthesized in the reaction vessel 2, and the chemical solution after the reaction is drained to the drain tank 11 through the second pipe 45 arranged downstream in the liquid feeding direction. In the present embodiment, the direction in which the liquid is fed from the chemical solution tank 1 to the reaction vessel 2 and eventually to the drain tank 11 is called the forward liquid feeding direction, and the pressure adjusting means 6 functions as the progressive liquid feeding means of the present invention.

By adopting a system in which the chemical solution is introduced from the lower side of the reaction container 2 as in the present embodiment, the chemical solution can be spread throughout the reaction container 2, and the chemical solution can be mixed with the beads in the reaction container 2. It can be chemically synthesized without waste. That is, since the chemical liquid introduced into the reaction vessel 2 from the lower first pipe 44 is affected by gravity, it is stored in the reaction vessel 2 while spreading in the radial direction, and the entire bead contained in the reaction vessel 2 and the chemical Synthesis is started. If the drug solution were introduced from above, the drug solution immediately after the port 21 would flow directly into the port 21 below due to the effect of gravity, and would be less likely to spread in the radial direction. Therefore, the chemical solution introduced from above undergoes chemical synthesis with the beads existing in the axial direction directly below the port 21, but does not easily react with the beads located at a distance in the radial direction, and locally unreacted beads may remain. Therefore, the method of introducing the chemical solution from below as in the present embodiment can cause the beads in the reaction vessel 2 to react with the chemical solution without waste.

Further, on the downstream side (outflow side) of the reaction vessel 2, a drainage tank 11 is provided for storing the chemical liquid or the like that has been discharged from the reaction vessel 2 after the reaction is completed. The drain tank 11 is formed to have a capacity larger than that of the reaction vessel 2, and is formed to have a capacity capable of storing even when the liquid is discharged from the reaction vessel 2 a plurality of times.

In addition, the waste liquid tank 11 is connected to the reaction vessel 2 by a second pipe 45, and the waste liquid discharged from the reaction vessel 2 is sent to the waste liquid tank 11 through the second pipe 45 connected from above. It has become so. Specifically, the second pipe 45 is provided with a drainage-side valve 55 and a downstream drainage-side valve 56. When these drainage-side valves 55 and downstream drainage-side valves 56 are opened, By supplying gas from the gas tank 61 of the pressure regulating means 6 and pressurizing it, the chemical liquid can be drained to the drain tank 11 through the second pipe 45 . That is, the chemical solution in the reaction container 2 is sent in the forward direction by the pressure adjusting means 6 and then discharged.

Further, the second pipe 45 is mainly used as a pipe for draining the chemical solution from the reaction container 2 as described above, but it is also used as a pipe for supplying gas to the reaction container 2 . That is, the second pipe 45 is connected to the gas tank 61 of the pressure adjusting means 6 and the gas supply pipe 47 , and the gas supply pipe 47 is provided with the gas valve 57 . On the other hand, the first pipe 44 is connected to the second pipe 45 by a bypass line 48 near the drain tank 11 , and the bypass line 48 is provided with a bypass valve 58 . As a result, the chemical in the reaction vessel 2 can be quickly drained to the drain tank 11 through the bypass line 48 .

That is, the gas valve 57 and the drain-side valve 55 are open, the downstream drain-side valve 56 is closed, the supply-side valve 52 and bypass valve 58 are open, and the upstream supply-side valve 53 is closed. By supplying the gas from the gas tank 61 of the means 6 , the gas is introduced into the reaction vessel 2 through the gas supply pipe 47 and the second pipe 45 . Then, when the gas is introduced into the reaction vessel 2, the chemical liquid in the reaction vessel 2 is pressurized by the gas, and the chemical liquid is pushed back to the first pipe 44 side. 11 is discharged. In this way, by introducing the gas from the upper side of the reaction container 2 in the direction of gravity, the chemical solution is efficiently pushed out of the reaction container 2 by its own weight and the applied pressure. As a result, the chemical solution in the reaction container 2 can be drained quickly. In this embodiment, the pressure adjusting means 6 also functions as a gas supplying means for returning the chemical solution from the reaction vessel 2 to the first pipe 44 side.

The reaction container 2 and the first pipe 44 and the second pipe 45 in the vicinity thereof are provided with a sensor P for detecting passage of the chemical solution. As shown in FIG. 2, the first pipe 44, the reaction vessel 2, and the second pipe 45 are provided with sensors P1, P2, and P3, respectively. In this embodiment, a gas-liquid sensor is used, and reacts when the state of the sensor region changes, such as from gas to liquid or from liquid to gas. Therefore, the sensor P1 provided in the first pipe 44 on the upstream side of the reaction vessel 2 detects that when the chemical solution is sent from the chemical solution tank 1, the chemical solution passes through the sensor area of the first pipe 44 and the first pipe 44 It reacts by changing from an empty state (gas) to a liquid. Further, when the chemical in the reaction container 2 is drained through the bypass line 48, the gas changes to liquid when the chemical is passed through, and the sensor area changes from the liquid to the air after the chemical is completely drained. , and can detect the start and completion of drainage. Similarly, the sensor P3 provided in the second pipe 45 on the downstream side of the reaction container 2 can detect when the chemical liquid discharged from the reaction container 2 passes and when the liquid discharge is completed. there is The sensors P1 to P3 are simply referred to as sensors P when there is no particular need to distinguish between them.

In the example of FIG. 2, the sensors P2 in the reaction container 2 are provided at six locations, and the two sensors having a small interval are located upstream (sensor P21, sensor P22) and near the center (sensor P23, sensor P24). ) and downstream (sensor P25, sensor P26). These sensors P2 are also designed to react when the inside of the reaction container 2 changes from gas to liquid, or from liquid to gas, in the same manner as described above. It can detect whether it is located or not.

In addition, the chemical synthesizing apparatus is provided with a control device (not shown), which drives the pressure adjusting means 6, the valves 51 to 58, etc. in order to execute a series of chemical synthesizing operations according to a pre-stored program. Drive control is possible.

This control device functions as an agitation control means by controlling the pressure adjustment means 6 and the valves 51-58. The agitation control means is formed by the pressure adjustment means 6, the valves 51 to 58, and the sensor P in this embodiment. This agitation control means has a function of agitating the chemical solution in the liquid feeding path, and stirs the chemical solution in the reaction vessel 2 by displacing the liquid surface of the chemical liquid supplied to the reaction vessel 2 in the liquid feeding path. It is.

For example, after the liquid level of the chemical liquid supplied to the reaction vessel 2 is positioned in the second pipe 45, the liquid chemical is pushed back in the reverse flow direction opposite to the forward liquid feeding direction, and the liquid level of the chemical liquid reaches the first pipe 44. position. By repeating this, the chemical solution can be stirred. Here, FIGS. 3 and 4 are diagrams showing the liquid surface position of the chemical solution and the open/closed states of the valves. Of the circled valves, black indicates the closed state and white indicates the open state.

Specifically, as shown in FIG. 3( a ), the controller opens the drain side valve 55 and the downstream drain side valve 56 while the chemical liquid is supplied to the reaction vessel 2 , and the pressure adjusting means 6 (forward feeding means) is operated to feed the chemical liquid to the second pipe 45 (forward feeding direction) (forward flow step). When the chemical liquid is sent to the second pipe 45, the sensor area of the sensor P3 changes from gas to liquid, and it is detected that the liquid surface of the chemical liquid has reached the position of the sensor P3. Upon receiving the signal from the sensor P3, the control device closes the drain side valve 55 and the supply side valve 52 as shown in FIG. .

Next, as shown in FIG. 4A, the control device closes the downstream drainage side valve 56 and opens the drainage side valve 55, the gas valve 57, the supply side valve 52, and the upstream supply side valve. Thus, the liquid medicine is caused to flow back in the direction opposite to the forward feeding direction (backflow step). Specifically, the pressure adjusting means 6 is operated to supply air from the gas supply pipe, and the liquid surface pushes back the chemical liquid that has reached the sensor P3 in the reverse flow direction. Then, the chemical liquid is pushed back from the second pipe 45 to the reaction vessel 2 and further to the first pipe, and the sensor area of the sensor P1 changes from liquid to gas. detected. Upon receiving the signal from the sensor P1, the control device closes the supply-side valve 52 and the drain-side valve 55 as shown in FIG. ). By performing the forward flow step, the forward flow stopping step, the backflow step, and the backflow stopping step, the chemical reciprocates in the reaction vessel 2, so that the beads and the chemical in the reaction vessel 2 are agitated to promote the chemosynthetic reaction. can be made By repeating these forward flow process, forward flow stop process, backflow process, and backflow stop process, the chemical solution in the reaction vessel 2 is further stirred and the chemical solution is spread throughout the reaction vessel 2. Agitation can be carried out, and all the beads in the reaction container 2 can be uniformly reacted.

Further, the stirring control means has a local stirring function. This local agitation function displaces the surface position of the chemical liquid at a predetermined position in the reaction vessel 2 a plurality of times, so that the chemical liquid and the beads in the reaction vessel 2 can be agitated by intensively colliding with each other. Therefore, the stirring efficiency is improved.

For example, FIGS. 5 and 6 are diagrams showing the case where the local stirring process is performed at the positions of the sensors P21 and P22. First, as shown in FIG. 5(a), the forward liquid feeding step is performed in the same manner as described above, the liquid discharge side valve 55 and the downstream liquid discharge side valve 56 are opened, and the pressure adjusting means 6 is operated to feed the chemical liquid. do. When the level of the chemical solution reaches the position of the sensor P22, as shown in FIG. to stop Next, as shown in FIG. 6(a), the downstream drainage side valve 56 is closed and the drainage side valve 55, the gas valve 57, and the supply side valve 52 are opened by the reverse flow process to sequentially feed the chemical solution. Backflow in the direction opposite to the liquid direction. Then, when the liquid level reaches the sensor P21, as shown in FIG. 6B, the supply side valve 52 and the drainage side valve 55 are closed by the backflow stop step to stop backflow of the chemical liquid. In this way, by repeating the forward flow process, the forward flow stop process, the reverse flow process, and the back flow stop process at the positions of the sensors P21 and P22, the position of the liquid surface of the chemical solution is finely displaced, and the chemical solution and the beads are mixed in the reaction vessel 2. can be locally and intensively collided and stirred.

The control device can also perform this local stirring process multiple times at different positions, and as shown in FIG. It can be done at three locations at P26. This allows intensive stirring at each selected position. In the example of FIG. 7, the local agitation process is performed by the sensors at positions adjacent to each other. You may set so that a local stirring process may be performed. By performing the local stirring step a plurality of times at different positions in the reaction vessel 2 in this way, it is possible to locally and intensively stir the reaction vessel 2, so that unreacted beads in the reaction vessel 2 can be minimized. Then, by setting the target position of the local stirring step to the part where the unreacted beads remain in the reaction vessel 2, the problem of the unreacted beads remaining can be efficiently solved.

Here, in the forward flow stop step and the back flow stop step, both the supply side valve 52 and the drain side valve 55 are closed at the same time to stop liquid feeding or back flow. By closing both valves at the same time in this way, it is possible to instantaneously stop the flow of the chemical solution in the form of feeding or backflow. That is, by instantaneously stopping, when switching from the forward flow stop process to the reverse flow process, or from the reverse flow stop process to the forward flow process, the liquid supply direction of the chemical solution is rapidly reversed, thereby gently stopping and reversing. In comparison, the stirring effect can be improved. In the forward flow stopping step and the backflow stopping step, liquid transfer can be stopped by closing only the drain side valve 55 (the supply side valve 52 in the case of the backflow stopping step). However, for example, in the forward liquid feeding process, the chemical liquid is pressurized and fed by the pressure adjusting means 6, but in the forward flow stopping process, if only the drain side valve 55 is closed, the pressurized chemical liquid The air confined in the section from the surface to the drain side valve 55 is pressurized, and the liquid surface position does not stop until the pressure of the air and the pressure of the chemical liquid are balanced, and the liquid surface position of the chemical liquid is in the forward liquid feeding direction. Moving. In this way, it is difficult to stop the liquid level instantaneously, so it is preferable to close both valves at the same time in order to obtain a better stirring effect.

As described above, according to the chemical synthesizing apparatus of the above-described embodiment, the liquid surface position of the chemical supplied to the reaction vessel 2 is formed by the first pipe 44, the reaction vessel 2, and the second pipe 45 by the agitation control means. By displacing it in the liquid feeding path, the chemical solution in the reaction container 2 can exhibit a stirring effect, and the reaction efficiency between the chemical solution and the carriers (beads) in the reaction container 2 can be improved. In addition, in order to displace the liquid surface of the chemical solution in the first pipe 44 and the second pipe 45 connected to the reaction container 2, and in the reaction container 2, a separate device or equipment such as a conventional circulation circuit is provided. Since the chemical solution can be agitated using the original chemical solution path of the chemical solution synthesizing device, it is possible to avoid the problems of complication of the device configuration and high cost of the entire device. In addition, it is possible to avoid the problem of wasteful consumption of chemicals because it is only necessary to supply only the chemicals necessary for the chemical synthesis reaction and displace the liquid surface without using chemicals more than necessary for stirring. can.

Further, in the above-described embodiment, an example in which the stop position of the liquid surface in the stirring step is set to the first pipe 44 and the second pipe 45 has been described, but the stop position may be set inside the reaction vessel 2. . That is, after stopping the liquid level in the first pipe 44 in the forward flow stopping step, it stops in the reaction vessel 2 in the backflow stopping step, stops in the reaction vessel 2 in the next forward flow stopping step, and then stops the backflow stopping step. may be stopped at the second pipe. That is, the stop position of the liquid surface is not particularly limited, and the sensor P may be installed at an arbitrary position to switch between the forward liquid feeding direction and the reverse liquid flow direction.

In the above-described embodiment, both the supply-side valve 52 and the drain-side valve 55 are closed at the same time in the forward flow stopping step and the backflow stopping step to stop the liquid supply or the backflow. If stop is not required, only the drain side valve 55 may be closed in the forward flow stopping step, and only the supply side valve 52 may be closed in the backflow stopping step to stop liquid feeding or backflow. Only the supply-side valve 52 may be closed in the stopping step, and only the drain-side valve 55 may be closed in the backflow stopping step to stop liquid feeding or backflow.

In the above embodiment, the sensors P1 to P3 are used to detect the liquid surface position of the stirring control means, but the number of sensors P may be increased. In the above embodiment, the stirring control means is formed by the pressure adjusting means 6, valves 51 to 58, and sensor P. It may be one that performs detection. That is, after the forward flow process is started, the forward flow stop process is performed after a predetermined time has passed, the reverse flow process is started, and the reverse flow stop process is performed after the predetermined time has passed. It may be managed by time.

Further, in the above-described embodiment, an example in which the pressure adjusting means 6 is shared as the sequential liquid feeding means and the gas supplying means has been described, but they may be provided independently of each other.

2 reaction vessel 4 pipe 6 pressurizing means 44 first pipe 45 second pipe 47 gas supply pipe 48 bypass line 52 supply side valve 53 upstream supply side valve 55 drain side valve 56 downstream supply side valve 57 gas valve 58 bypass valve

Claims (8)

a reaction vessel for reacting the filled carrier and the delivered chemical solution;
a first pipe connected to the reaction vessel and mainly for supplying a chemical solution to the reaction vessel;
a second pipe connected to the reaction vessel and arranged downstream in the liquid feeding direction when viewed from the first pipe;
a forward liquid feeding means for feeding the chemical liquid to the reaction vessel through the first pipe;
gas supply means for returning the chemical liquid contained in the reaction vessel to the first piping side by supplying gas to the reaction vessel through the second piping;
an agitation control means for agitating the supplied chemical solution;
with
The agitation control means controls the sequential liquid feeding means and the gas supply means so that in a liquid feeding path formed by the first pipe, the reaction vessel, and the second pipe,
stirring the chemical solution in the reaction vessel by displacing the liquid surface position of the chemical solution a plurality of times ;
The agitation control means has a local agitation function that displaces the liquid surface position of the chemical liquid at a predetermined position in the reaction vessel a plurality of times. is finely displaced to locally and intensively stir at a selected position in the reaction vessel . The agitation control means has a local agitation function that displaces the liquid surface position of the chemical liquid at a predetermined position in the reaction vessel a plurality of times. 2. The chemical synthesizer according to claim 1, wherein: The agitation control means is characterized in that when the liquid level position of the chemical liquid is displaced a plurality of times, the liquid level position of the chemical liquid is controlled to be positioned in the first pipe or the second pipe. 3. The chemical synthesis device according to claim 1 or 2 . The agitation control means has a supply-side valve provided on the first pipe and a drain-side valve provided on the second pipe. 3. The chemical synthesizing apparatus according to claim 1, wherein control is performed to simultaneously close the valve and the drain side valve. A method for synthesizing a chemical solution by supplying a chemical solution through a first pipe to a reaction container containing a filled carrier, causing the chemical solution and the carrier to react in the reaction container, and discharging the chemical solution after the reaction through a second pipe. hand,
A forward flow step of supplying a chemical solution through the first pipe to send the liquid to the second pipe side through the reaction vessel;
a forward flow stop step of stopping liquid transfer in the forward flow step;
A reverse flow step of supplying gas through the second pipe to flow the chemical solution backward in a direction opposite to the forward flow step;
a backflow stop step of stopping liquid transfer in the backflow step;
and
It further has a stirring step that repeats the forward flow step, the forward flow stop step, the backflow step, and the backflow stop step ,
The stirring step includes a local stirring step performed in a state where the liquid surface of the chemical is positioned at a predetermined position in the reaction vessel. and locally and intensively stirred at a selected position within the reaction vessel . The stirring step includes a local stirring step performed in a state where the liquid surface of the chemical solution is positioned at a predetermined position in the reaction vessel, and the local stirring step is performed multiple times at different positions in the reaction vessel. The chemical synthesis method according to claim 5, characterized by: 7. The chemical synthesis method according to claim 5 , wherein the stirring step is performed with the liquid surface of the chemical liquid positioned at the first pipe or the second pipe. The first pipe is provided with a supply-side valve, and the second pipe is provided with a drain-side valve. 7. The method of synthesizing a chemical solution according to claim 5 , wherein the liquid-side valve is closed at the same time to stop the supply of the chemical solution.

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