JP2007222849A - Microchemical reaction system - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a numbering-up type microchemical reaction system enabling a rapid response in case troubles such as a blockage occur in a part of chips or a chip integrated group (module). <P>SOLUTION: The microchemical reaction system has a constitution that a plurality of reaction lines 10 having a raw material feed section 1 feeding two kinds or more of raw materials, and a microchemical chip 12 advancing the reaction by joining together two kinds or more of raw materials are installed in parallel. The reaction line has a stationary line 10a stationarily operating and at least a preliminary line 10b. On the stationary line 10a, condition detecting means 24, 42, 44 detecting that each stationary line is in abnormal condition are provided, and a supply change valve 40 to flow the raw materials to the preliminary line 10b when the stationary line 10a becomes abnormal is provided among the raw material feed section 1 and a plurality of reaction lines 10. <P>COPYRIGHT: (C)2007,JPO&INPIT

Description

  The present invention relates to a microchemical reaction system that executes a chemical reaction process using a plurality of microchemical chips.

  As a system for performing chemical reaction at high speed and high yield, there is a system using a microchemical chip (microreactor) for performing reaction in a micro space. A microreactor has a microchannel formed therein, and a raw material fluid (reagent) passes through the microreactor, and a chemical reaction proceeds in the process. A microreactor is a device that performs chemical reactions in a minute space, so the molecular diffusion distance in mixing can be reduced, and high-speed and efficient mixing that cannot be achieved with conventional mixers or conventional batch methods. Can do. On the other hand, since a large amount of reaction products cannot be obtained at one time, a policy (numbering-up type microchemical reaction system) for mass production by stacking or paralleling a large number of microreactors is adopted.

  In such a microreactor, there is a possibility that the micro flow path is clogged due to precipitation of reaction products or reaction by-products in the course of the reaction. In addition, foreign matter or the like generated in other parts of the reaction system may enter the microchannel and block the channel in the microreactor. When such a blockage occurs in one or a plurality of microreactors, it may not function as a generation system, and may increase the pressure in the reactor due to the blockage, leading to damage to the reactor or system components. This is a problem that can cause serious accidents, especially when using harmful reagents.

  Normally, in a numbering-up type microchemical reaction system, when a blockage occurs in one or a plurality of microreactor channels, a measure is taken to separately remove the blocked microreactor and clean the channel alone. However, when the reactor is taken out and cleaned every time the clogging occurs, the system needs to be stopped during that time, and the production efficiency is lowered, and the cost efficiency is also lowered in consideration of the time required for the washing. .

  The present invention has been made in view of the above circumstances, and is a numbering-up type micro-controller capable of quickly responding to troubles such as blockage in some chips or chip integrated groups (modules). The object is to provide a chemical reaction system.

  In order to achieve the object, the microchemical reaction system according to claim 1 is a microchemical reaction system in which a reaction is advanced by merging two or more raw materials together with a raw material supply unit that supplies two or more raw materials. A microchemical reaction system in which a plurality of reaction lines having chips are installed in parallel, wherein the reaction line has a steady line that operates constantly and at least one spare line, and each of the steady lines has its own A state detecting means for detecting that the steady line is in an abnormal state is provided, and between the raw material supply unit and the plurality of reaction lines, when the steady line is in an abnormal state, the raw material flows to the spare line. The supply switching valve is provided.

  In the first aspect of the present invention, when an abnormality occurs in the steady line, the state detecting means automatically detects this, and the raw material is caused to flow to the spare line via the supply switching valve, so that production is stagnant. In addition, stable operation can be continued by maintaining constant conditions such as pressure.

The microchemical reaction system according to claim 2, further comprising a cleaning liquid supply unit that supplies a cleaning liquid to the reaction line via a cleaning liquid supply switching valve. .
In the second aspect of the present invention, the cleaning liquid is supplied from the cleaning liquid supply unit to the reaction line where the abnormality has occurred via the cleaning liquid supply switching valve. As a result, the blockage of the reaction line in which an abnormality has occurred is resolved and the line is returned to a steady state, so that stable operation is maintained over a long period of time.

According to a third aspect of the present invention, there is provided the microchemical reaction system according to the second aspect of the present invention, wherein the microchemical chip is provided with one or both of a vibration generating element and a temperature adjusting element for improving the cleaning action of the cleaning liquid. It is characterized by being.
According to the third aspect of the invention, due to the effects of temperature and vibration, a high cleaning action is exerted to promote the return of the abnormality occurrence line.

A microchemical reaction system according to a fourth aspect of the invention is the invention according to any one of the first to third aspects, wherein an abnormality is determined in response to a signal from the state detection means, and the switching operation of the supply switching valve is performed. It has the control apparatus which performs.
In the invention according to the fourth aspect, since the abnormality is determined by the control device and the switching operation of the supply switching valve is performed, an appropriate countermeasure can be taken by inputting the conditions in advance.

  According to the microchemical reaction system according to any one of claims 1 to 4, when an abnormality occurs in the stationary line, the state detecting means automatically detects this, and the raw material is allowed to flow to the spare line, thereby causing pressure and the like. It is possible to maintain stable production conditions and continue stable production.

Embodiments of the present invention will be described below with reference to the drawings.
1 to 3 show a microchemical reaction system according to a first embodiment of the present invention. This system is for two-component mixing, but may be three-component or more.

  The microchemical reaction system of this embodiment includes a raw material supply unit 1 and a reaction unit 2. The reaction unit 2 has a plurality of reaction lines 10, and each reaction line 10 has a mixing / reactor (microreactor) 12 for mixing and reacting two raw material liquids. In this example, the mixing / reactor 12 uses the microreactor 12 having the combined flow path 14 composed of Y-shaped fine flow paths, but may be another type of mixing / reactor 12. The microreactor 12 is provided with a temperature adjustment mechanism such as a heater as necessary.

  The reaction line 10 of the reaction unit 2 includes a steady line 10a that operates steadily and a spare line 10b that operates in place of one of the steady lines 10a when an abnormal state occurs. The number of steady lines 10a is determined according to the required processing amount, and the number of spare lines 10b is determined in consideration of the frequency of abnormal conditions occurring in the steady line 10a, the time required for repairing, and the like.

  The steady line 10a and the spare line 10b are connected to the common liquid supply lines 20a and 20b and the common discharge line 22 via a pair of upstream and downstream on-off valves 16a, 16b, and 16c and pipe joints 18a and 18b therebetween. It is connected. Therefore, by closing these on-off valves 16a, 16b, and 16c and then removing the pipe joints 18a and 18b, a specific line can be removed or replaced while other lines are in operation. The common discharge line 22 is switchably connected to the product container 28 and the waste liquid container 30 via a component measuring device 24 and a discharge switching valve 26 that is a three-way switching valve. The common discharge line 22 is connected to each reaction line 10 via a check valve 31.

  The raw material supply unit 1 includes two raw material liquid containers 32 and 34 and a pair of pumps 36 and 38 for pumping the raw material liquid from the raw material liquid containers 32 and 34 to the reaction unit 2, respectively. The discharge ports are connected to common liquid supply lines 20a and 20b. Between the common liquid supply lines 20a and 20b and each reaction line 10, there is provided a raw material supply valve (supply switching valve) 40 which is an electromagnetic on-off valve for on / off control of the supply of the raw material liquid. In this embodiment, the raw material supply valve 40 of the steady line 10a uses a normally open electromagnetic open / close valve, and the raw material supply valve 40 of the standby line 10b uses a normally closed electromagnetic open / close valve. These raw material supply valves 40 are controlled to be opened and closed by a control signal sent from a control device.

  Each reaction line 10 is provided with a state measurement sensor that automatically measures the state of each reaction line 10. That is, in this embodiment, the pressure sensor 42 is provided on the upstream side of the microreactor 12, and the flow sensor 44 and the component measuring device 24 are provided on the downstream side. The measurement results of these state measurement sensors are output to the control device 46. The control device 46 is configured by a computer or a sequencer. As the component measuring device 24, a densitometer or a pH meter, an optical microscope, a thermal lens microscope, a laser microscope, or the like is used.

  The number and type of state measurement sensors can be selected as appropriate assuming an abnormal state to be detected. The purpose of this embodiment is to deal mainly with blockage of a flow path and component abnormality as an abnormal state. In this embodiment, since the pressure sensor 42 and the flow rate sensor 44 are provided, abnormal pressure, abnormal flow, and blockage are individually detected. For example, if the pressure in one reaction line 10 increases from the other and the flow rate decreases, it is considered that the microreactor 12 is clogged, and that line is determined to be abnormal. On the other hand, when the flow rate decreases and the pressure also decreases, it is considered that the raw material supply amount itself in the raw material supply unit 1 is decreasing, and it is not necessarily determined that the line is abnormal.

  In addition to this, an abnormal state to be detected includes a temperature abnormality when the reaction requires strict control of temperature, and a temperature sensor is appropriately installed for this purpose. The installation of the temperature sensor in the microreactor 12 is used not only for controlling the temperature itself but also for detecting an abnormality.

  The control device 46 determines the operating state of each steady line 10a from the measurement results of these state measurement sensors, and when it determines that a certain steady line 10a is abnormal, it closes the raw material supply valve 40 of that steady line 10a. The raw material supply valve 40 of the spare line 10b is opened, and the raw material liquid corresponding to that is directed to the spare line 10b. On the other hand, if it is determined that the problem is not in the individual lines but in the raw material supply unit 1 or the like, countermeasures (replenishment of raw materials, etc.) are carried out, or an alarm is issued.

Hereinafter, the operation of the thus configured microchemical reaction system will be described.
In the steady operation state shown in FIG. 1, the raw material supply valve 40 of the steady line 10a is in an open state, and the reagent a and the reagent b are introduced and mixed into the microreactors 12 from the respective pumps 36 and 38, and the reaction products are common. It is delivered to the product container 28 via the discharge line 22. The raw material supply valve 40 of the spare line 10b is closed, and each reagent is not introduced. The pressure sensor 42, the flow sensor 44, and the component measuring device 24 installed in each reaction line 10 always perform measurement and detection, and the measured values are output to the control device 46.

  The control device 46 determines the operating state of each reaction line 10 in a timely manner based on the measurement result of the state measurement sensor. As a method of determination, for example, a predetermined allowable value is set for each measured value, it is determined whether the measured value is within the range, and if any measured value is out of the allowable range, The operating state is determined to be abnormal. On the other hand, some measurement values may be comprehensively evaluated to determine whether the measurement is normal or abnormal. In that case, the allowable range may be set stepwise, or the measured value may be evaluated numerically and determined. For example, regarding product components, if they are outside the allowable range, they will be defective products. Therefore, the determination of clogging will affect both the flow rate and the pressure sensor 42. Judge the output comprehensively.

  When the controller 46 determines that a certain steady line 10a is in an abnormal operating state, as shown in FIG. 2, the control device 46 closes the raw material supply valve 40 of the reaction line 10 to stop the supply of liquid, The raw material supply valve 40 is opened and the raw material liquid is directed to the spare line 10b. Thereby, without adjusting the discharge flow rate of the pumps 36 and 38, the flow rate and pressure of the other steady line 10a can be maintained as they are, and stable production can be continued.

  When the component measuring device 24 detects an abnormal value, the detection work itself may take time. In addition, depending on the type of measurement value, there are cases where measurement cannot always be performed continuously. That is, the measurement may be intermittent. In these cases, a time delay occurs in the detection of the abnormal component. Therefore, it is preferable to lengthen the distance L (see FIG. 1) between the component measuring device 24 and the detachable joint in consideration of the outflow due to the time delay. . That is, L> vt, where v is the flow velocity in the line, and t is the time required for component abnormality detection and closing of the material supply valve 40. In this way, in the reaction line 10 after the raw material supply valve 40 is shut off, the flow of the fluid is stopped in that state by closing the raw material supply valve 40, and a component abnormal product does not flow into the common discharge line 22. .

  Further, in this embodiment, the component measuring device 24 is provided on the downstream side of the common discharge line 22, and in the unlikely event that an abnormal component liquid flows into the common discharge line 22, the control device 46 measures this component. A component abnormality is detected by the device 24, and a discharge switching valve 26 that is a three-way switching valve downstream thereof is operated to switch the outflow destination from the product container 28 to the waste liquid tank. This prevents the product container 28 from being contaminated by the abnormal component liquid.

  While the spare line 10b is operating and replacing the function of the abnormality occurrence reaction line 10, as shown in FIG. 3, the stationary line 10a where the abnormality has occurred is removed from the pipe joints 18a and 18b for repair or Perform replacement work. After the repair or replacement work is completed, the spare line 10b is closed as a general rule to operate the steady line 10a. In this example, there is one spare line 10b. However, if a plurality of spare lines 10b are provided, the need for repair and replacement work can be reduced, and the plurality of stationary lines 10a become abnormal simultaneously. Is also available.

  FIG. 4 shows a modification of the first embodiment, in which a discharge switching valve 26a, which is a three-way switching valve, is installed in the spare line 10b, and the spare line 10b is either the waste liquid container 30a or the common discharge line 22. Are connected so as to be switchable. In this embodiment, as shown in FIG. 5, the product is allowed to flow into the waste liquid container 30 for a predetermined time after the standby line 10b starts to operate, and the state of the standby line 10b is stabilized after the predetermined time has elapsed. After that, as shown in FIG. This is because the operation state of the backup line 10b is unstable at the beginning of switching, and impurities may remain in the flow path, so that they do not flow through the common discharge line 22 to be contaminated.

  FIG. 7 shows a further modification of the first embodiment, in which the spare line and the steady line have the same structure. Each reaction line 10 is provided with a discharge switching valve 26 that leads to the waste liquid container 30 before joining the common discharge line 22. Then, the raw material supply valve 40 of any one of the lines is closed to be a preliminary line 10b, and another reaction line 10 is a steady line 10a.

  In this microchemical reaction system, when the stationary line 10a is in an abnormal state and the spare line 10b is operated, it is used as it is as the stationary line 10a. When the abnormal stationary line 10a is repaired, it is used as the spare line 10b. . This eliminates the need for an extra switching operation, which saves time and reduces the component defective products that accompany line switching. Further, in this embodiment, since the discharge switching valves 26 are installed in all the reaction lines 10, the common component discharge line 22 can be used to identify the initial component defect portion where the line has been operated and the component defect portion associated with the occurrence of abnormality. Without being sent to the waste liquid container 30.

  FIG. 8 shows a microchemical reaction system according to another embodiment of the present invention, which includes a raw material supply unit 1, a reaction unit 2, and a cleaning liquid supply unit 3. The configuration of the raw material supply unit 1 and the reaction unit 2 is basically the same as that of the previous embodiment, and the description is omitted with the same reference numerals. Each reaction line 10 is provided on the downstream side of the microreactor 12 with a discharge switching valve 54 for switching connection between the waste liquid line 52 leading to the cleaning liquid discharge container 50 and the common discharge line 22 leading to the product container 28.

  The cleaning liquid supply unit 3 includes a cleaning liquid container 48 that stores the cleaning liquid, a cleaning liquid pump 58 that sends the cleaning liquid from the cleaning liquid container 48 to the cleaning liquid supply line 56, and a cleaning liquid supply that opens and closes between the cleaning liquid supply line 56 and each reaction line 10. And a valve 60. In this embodiment, the cleaning liquid supply valve 60 connects the cleaning liquid supply line 56 to each reaction line 10 on the downstream side of the raw material supply valve 40. The opening and closing of the cleaning liquid supply valve 60 is controlled by the control device 46 together with the raw material supply valve 40. In the description of this embodiment, the connection between the control device 46 and each sensor and control valve is not shown.

  In this embodiment, as shown in FIG. 9, a microreactor base 66 in which a vibration generating element 62 using a piezoelectric element or the like and a temperature adjusting element 64 using a Peltier element or the like are attached to each microreactor 12. It has been. The microreactor 12 is provided with a temperature sensor 68 for measuring the temperature. The vibration generating element 62 and the temperature adjusting element 64 are not for advancing the reaction (which may be used for that purpose), but for increasing the cleaning effect by the cleaning liquid. The vibration generating element 62 and the temperature adjusting element 64 are driven by an electrical control signal from the control device 46 or the sequencer. The frequency and amplitude of the vibration generating element 62 and the temperature of the temperature adjusting element 64 can be appropriately set so as to satisfy conditions suitable for cleaning the system.

The operation of the microchemical reaction system configured as described above will be described.
In the steady operation state shown in FIG. 10, the raw material supply valve 40 of the steady line 10a is in an open state, and the reagent a and the reagent b are introduced and mixed into the microreactors 12 from the respective pumps 36 and 38, and the reaction products are common. It is delivered to the product container 28 via the discharge line 22. The raw material supply valve 40 of the spare line 10b is closed, each reagent is not introduced, and the cleaning liquid supply unit 3 and the cleaning liquid supply line 56 are not operating.

  The control device 46 determines the operating state of each reaction line 10 in a timely manner based on the measurement result of the state measurement sensor. When it is determined that a certain reaction line 10 is in an abnormal state, as shown in FIG. 11, the material supply valve 40 of the reaction line 10 is closed, the supply of liquid to the line is stopped, and the material supply of the spare line 10b is stopped. The valve 40 is opened to direct the raw material liquid to the spare line 10b. The discharge switching valve 26 of the spare line 10b is connected to the cleaning liquid discharge container 50 side until a predetermined time has elapsed and the state of this line is stabilized, and then is connected to the common discharge line 22.

  When it is determined that this abnormal state is due to blockage, as shown in FIG. 12, the discharge switching valve 26 of the abnormal reaction line 10 is switched to the waste liquid line 52, and further to this reaction line 10. The cleaning liquid supply valve 60 of the cleaning liquid supply line 56 is opened, and the cleaning liquid is supplied to the microreactor 12 and cleaned. The remaining raw material liquid and cleaning liquid in the middle of the reaction are discharged to the cleaning liquid discharge container 50 through the waste liquid line 52. At this time, the control device 46 oscillates by sending a signal to the vibration generating element 62 installed in the lower part of the microreactor 12. At the same time, a signal is sent to the temperature adjustment element 64 to perform cleaning under temperature conditions that facilitate cleaning of the microreactor 12.

  The cleaning operation is performed while monitoring the measured value of the blocked line by the pressure sensor 42 with the control device 46. When the line is plugged, the pressure measured when supplying the cleaning liquid at a predetermined flow rate should be higher than when it is not plugged. Accordingly, the cleaning operation is continued until the detection value from the pressure sensor 42 returns to the normal value. When the detected value of the pressure sensor 42 returns to the normal value, as shown in FIG. 13, the cleaning liquid supply valve 60 is closed, the raw material supply valve 40 is opened, and the cleaning liquid in the reaction line 10 and the microreactor 12 is used as the raw material. Replace with liquid.

  The discharge switching valve 26 is kept on the cleaning liquid discharge container 50 side until the remaining cleaning liquid is discharged. After switching the supply side, after confirming that a predetermined time has passed and the measurement result of the component measuring device has detected a normal reaction product, the discharge switching valve 26 is switched to the product container 28 side, The steady operation state shown in FIG. If the pressure does not decrease even after the cleaning operation has passed for a certain time, the control device 46 issues an alarm to that effect.

  The control device 46 constantly monitors the component by the component measuring device 24 for each line, and when this is determined to be an abnormal value, the discharge side is connected to the drain line regardless of whether the supply side is switched or not. To switch to. Thereby, contamination of the common discharge line 22 and the product container 28 due to an abnormality of a certain line can be prevented.

It is a block diagram which shows the structure of the microchemical reaction system of 1st Embodiment of this invention. It is a block diagram which shows the flow of the fluid when abnormality generate | occur | produces in the microchemical reaction system of FIG. It is a figure which shows the repair process of the line which abnormality generate | occur | produced in the microchemical reaction system of FIG. It is a block diagram which shows the structure of the microchemical reaction system of the modification of 1st Embodiment. It is a block diagram which shows the flow of the fluid when abnormality occurs in the microchemical reaction system of FIG. It is a block diagram which shows the structure of the micro chemical reaction system of the further another modification of 1st Embodiment, and the flow of the fluid at the time of steady operation. It is a block diagram which shows the flow of the fluid when abnormality occurs in the microchemical reaction system of FIG. It is a block diagram which shows the structure of the microchemical reaction system of 2nd Embodiment of this invention. It is a perspective view which shows the structure of the microreactor of the microchemical reaction system of embodiment of FIG. It is a block diagram which shows the flow of the fluid at the time of steady operation of the microchemical reaction system of FIG. It is a block diagram which shows the switching process when abnormality generate | occur | produces in the microchemical reaction system of FIG. It is a block diagram which shows the washing | cleaning process of the line which abnormality generate | occur | produced in the microchemical reaction system of FIG. It is a block diagram which shows the steady state return process of the line which abnormality generate | occur | produced in the microchemical reaction system of FIG.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Raw material supply part 2 Reaction part 3 Cleaning liquid supply part 10 Reaction line 10a Steady line 10b Reserve line 12 Microreactor 12 Mixing / reactor 14 Joint flow path 16a, 16b On-off valve 18 Fitting 20 Common supply line 22 Common discharge line 24 Component measurement Device 26 Discharge switching valve 28 Product container 30 Waste liquid container 31 Check valve 32, 34 Raw material liquid container 36, 38 Pump 40 Raw material supply valve (supply switching valve)
42 pressure sensor 44 flow sensor 46 control device 48 cleaning liquid container 50 cleaning liquid discharge container 52 waste liquid line 54 discharge switching valve 56 cleaning liquid supply line 58 cleaning liquid pump 60 cleaning liquid supply valve 62 vibration generating element 64 temperature adjusting element 66 microreactor base 68 temperature sensor

Claims (4)

A microchemical reaction system having a plurality of reaction lines installed in parallel, each having a raw material supply unit for supplying two or more raw materials and a microchemical chip for advancing the reaction by joining the two or more raw materials. There,
The reaction line has a stationary line that operates constantly and at least one auxiliary line;
Each of the steady lines is provided with state detecting means for detecting that the steady line is in an abnormal state,
A microchemical reaction system, characterized in that a supply switching valve is provided between the raw material supply unit and the plurality of reaction lines to flow the raw material to a spare line when a steady line becomes abnormal. .   The microchemical reaction system according to claim 1, wherein a cleaning liquid supply unit that supplies a cleaning liquid to the reaction line via a cleaning liquid supply switching valve is provided.   3. The microchemical system according to claim 2, wherein the microchemical chip is provided with one or both of a vibration generating element and a temperature adjusting element for improving the cleaning action of the cleaning liquid. The microchemical reaction system according to any one of claims 1 to 3, further comprising a control device that receives a signal from the state detection means to determine an abnormality and performs a switching operation of the supply switching valve. .

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