WO2017179353A1 - マイクロリアクタ、化成品製造システム及びマイクロリアクタの製造方法 - Google Patents
マイクロリアクタ、化成品製造システム及びマイクロリアクタの製造方法 Download PDFInfo
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- WO2017179353A1 WO2017179353A1 PCT/JP2017/010021 JP2017010021W WO2017179353A1 WO 2017179353 A1 WO2017179353 A1 WO 2017179353A1 JP 2017010021 W JP2017010021 W JP 2017010021W WO 2017179353 A1 WO2017179353 A1 WO 2017179353A1
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
- B81B1/00—Devices without movable or flexible elements, e.g. microcapillary devices
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81B—MICROSTRUCTURAL DEVICES OR SYSTEMS, e.g. MICROMECHANICAL DEVICES
- B81B7/00—Microstructural systems; Auxiliary parts of microstructural devices or systems
- B81B7/02—Microstructural systems; Auxiliary parts of microstructural devices or systems containing distinct electrical or optical devices of particular relevance for their function, e.g. microelectro-mechanical systems [MEMS]
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B81—MICROSTRUCTURAL TECHNOLOGY
- B81C—PROCESSES OR APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OR TREATMENT OF MICROSTRUCTURAL DEVICES OR SYSTEMS
- B81C3/00—Assembling of devices or systems from individually processed components
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00801—Means to assemble
- B01J2219/00804—Plurality of plates
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00801—Means to assemble
- B01J2219/00804—Plurality of plates
- B01J2219/00808—Sealing means
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00819—Materials of construction
- B01J2219/00833—Plastic
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00851—Additional features
- B01J2219/00858—Aspects relating to the size of the reactor
- B01J2219/0086—Dimensions of the flow channels
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00889—Mixing
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00891—Feeding or evacuation
- B01J2219/00894—More than two inlets
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/00891—Feeding or evacuation
- B01J2219/00896—Changing inlet or outlet cross-section, e.g. pressure-drop compensation
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J2219/00781—Aspects relating to microreactors
- B01J2219/0095—Control aspects
- B01J2219/00952—Sensing operations
- B01J2219/00954—Measured properties
- B01J2219/00959—Flow
Definitions
- the present invention relates to a technology of a microreactor for mixing raw materials, a chemical product manufacturing system, and a manufacturing method of a microreactor.
- microreactors which mix fluids in microchannels made by microfabrication technology, in the field of chemical synthesis such as biotechnology, medicine, pharmaceuticals, and chemical products. It has been broken.
- the characteristics of the synthesis reaction in the microreactor include the following points. That is, as the size of the reaction field in the microreactor decreases, the fluid rapidly mixes by molecular diffusion. As a result, the effect of the surface area on the volume of the fluid is relatively increased, and the effect of heat transfer on the volume of the fluid is relatively increased. Therefore, compared with a normal batch reaction, an improvement in production efficiency is expected by shortening the reaction time and improving the yield.
- the microreactor is a closed system and provides a small reaction field, it is suitable for handling highly corrosive substances and dangerous synthetic reactions. Even if the amount of production per microreactor is small, the same product can be produced in large quantities by multiplying the microreactor by N, that is, numbering up.
- cross-contamination due to the introduction of foreign substances from the outside is often not preferable, although the corrosiveness of the material to be handled is relatively low.
- resin such as PDMS (polydimethylsiloxane), ABS resin, PC (polycarbonate) as a material, the microreactor is used as a single use (disposable). Yes.
- Patent Document 1 states that “a two or more kinds of fluids that have flowed in are independently supplied to the joining region, and these fluids are discharged from the joining region, and each fluid that has flowed into the microdevice. And a discharge channel for discharging the merged fluid from the merge region to the outside of the microdevice.
- the supply channel for supplying at least one kind of fluid has a plurality of subchannels. These subchannels merge into the same merge region, and at least one fluid of at least one central axis of the plurality of subchannels and other types of fluids other than the fluid supplied by the subchannels.
- These sub-channels so that at least one central axis of the supply channel or sub-channel supplying the Yan'neru and supply channels are formed, characterized in that is "micro devices and merging method of fluid has been described (see claim 1).
- Patent Document 2 states that “at least one type of organic pigment solution in which an organic pigment is dissolved and at least one type of pH adjuster is used in a non-laminar flow state in a microchannel.
- the organic pigment fine particles are precipitated by changing the hydrogen ion index (pH) of the organic pigment solution in the distribution process in the road, and the intersection of the organic pigment solution and the pH adjuster when the solutions merge together.
- Patent Document 3 states that “an introduction member, a first member connected to the introduction member, a second member connected to the first member, a third member connected to the second member, and the third member”. And a lead-out member connected to the dispersion member, the disperse phase inflow passage through which the first liquid flows through the introduction member and the first member in the lamination direction, A continuous-phase inflow channel provided between the first member and the second member, through which the second liquid that does not dissolve with the first liquid flows, and penetrates the second member in the stacking direction; A mixing channel that forms a sheath flow in which a mixed liquid flows inside with the first liquid flowing in from the dispersed phase inflow channel inside and the second liquid flowing in from the continuous phase inflow channel is outside; An enlarged mixed flow that penetrates the third member and the outlet member in the stacking direction and has a wider channel width than the mixed channel Among the channels, the dispersed-phase inflow channel, the mixing channel, and the expansion mixing channel are provided so as to be coaxial, and the mixing channel and the expansion
- the volume (internal volume) of each raw material from the introduction of two types of raw materials to the merging is substantially the same. If it does in this way, when the flow rate ratio (volume ratio) of two types of raw materials is largely biased, more raw material on the high flow rate side flows. Therefore, at the start of production of the chemical product, there arises a problem that the raw material on the high flow rate side flows into the flow path of the raw material on the low flow rate side.
- the present invention has been made in view of such a background, and an object of the present invention is to realize good mixing in mixing raw materials having different flow rates.
- the present invention includes a plurality of flow paths through which a plurality of raw materials having different flow rates respectively flow, and the flow path has a low It is characterized by being branched and joined so as to join the flow path of the raw material of the flow rate.
- 1 is an external view of a microreactor according to a first embodiment. It is a figure which shows the mode of the mixing in the flow path for residence. It is a schematic diagram of the chemical product manufacturing system which concerns on 1st Embodiment. It is an external view which shows the microreactor to which the microreactor for adjustment was connected. It is a side view for showing a manufacturing method of a micro reactor concerning a 1st embodiment. It is an external view of the microreactor which concerns on 2nd Embodiment. It is a figure which shows the detailed structure of an orifice. It is an external view of the microreactor which concerns on 3rd Embodiment.
- FIG. 1 is an external view of the microreactor according to the first embodiment.
- the microreactor 101 of FIG. 1 has a high flow rate side flow channel 102, a low flow rate side flow channel 103, a retention flow channel 104, a high flow rate side introduction port 105, a low flow rate side introduction port 106, and a discharge port 107.
- the high flow rate side raw material (high flow rate raw material) is introduced from the high flow rate side introduction port 105, the high flow rate side flow path 102 (flow of the high flow rate raw material) indicated by a one-dot chain line. Road).
- a low flow rate raw material (low flow rate raw material) is introduced from the low flow rate side inlet 106 and flows through a low flow rate flow path 103 (low flow rate raw material flow path) indicated by a broken line.
- the branch point 111a as the high flow rate side flow channel 102 is branched into two, a branch flow channel 102a and a branch flow channel 102b indicated by a one-dot chain line, the high flow rate side raw material is also branched into two.
- the raw material on the high flow rate side joins so as to sandwich the raw material on the low flow rate side.
- the high flow rate raw material and the low flow rate side raw material are mixed.
- a mixture of the raw material on the high flow rate side and the raw material on the low flow rate side is referred to as a mixture.
- the mixture finally flows through the retention flow path 104 indicated by a two-dot chain line and is discharged from the discharge port 107.
- the retention flow path 104 becomes a reaction field.
- the retention flow path 104 is a mixing field.
- the high flow side channel 102 is branched into two, the branch channel 102a and the branch channel 102b, so that the internal volume (internal volume) of the high flow side channel 102 is low. It is larger than the volume in the flow path 103.
- the ratio of the volume in the channel of the high flow rate side channel 102 and the volume in the channel of the low flow rate side channel 103 is close to the flow rate ratio (volume ratio) of the two types of raw materials. Not exclusively. It is desirable that the volume in the channel of the high flow rate side channel 102 and the volume in the channel of the low flow rate side channel 103 have the same or close values of pressure loss when the two kinds of raw materials flow. .
- the cross-sectional areas of the high flow side channel 102, the branch channels 102a and 102b, the low flow side channel 103, and the retention channel 104 are the same from the viewpoint of the manufacturing method of the microreactor 101 described later in FIG. It is desirable (the cross-sectional area of the high-flow-side channel 102 ⁇ the cross-sectional area of the branch channels 102 a and 102 b ⁇ the cross-sectional area of the low-flow-side channel 103 ⁇ the cross-sectional area of the retention channel 104).
- the cross-sectional area of the raw material on the high flow rate side in the retention flow path 104 becomes smaller than the cross-sectional area of the branch flow paths 102a and 102b, and the low flow rate in the retention flow path 104
- the cross-sectional area of the raw material on the side is smaller than the cross-sectional area of the low flow rate side channel 103.
- the high flow rate side raw material flowing from the high flow rate side flow channel 102 and the low flow rate side raw material flowing from the low flow rate side flow channel 103 are well mixed.
- a pump 204 see FIG.
- each raw material can flow into the retention flow path 104 even if the branch flow paths 102 a and 102 b and the low flow rate flow path 103 have the same cross-sectional area.
- the length of the high flow side channel 102 and the branch channels 102 a and 102 b are configured to be longer than the low flow side channel 103.
- the volume in the flow channel of 102 is larger than the volume in the flow channel of the low flow rate flow path 103, the present invention is not limited to this.
- the flow volume inside the high flow rate side flow channel 102 is larger than the flow volume inside the low flow rate side flow channel 103. It may be made to become.
- the flow volume in the high flow rate flow channel 102 is larger than the flow volume in the low flow rate flow channel 103. You may do it.
- the pressure loss in the flow path of the high flow rate side flow path 102 is substantially equal to the pressure loss in the flow path of the low flow rate side flow path 103.
- the high flow side inlet 105, the low flow side inlet 106, and the discharge port 107 are formed with screw holes for fitting connection (not shown). By using the fitting (not shown), a high flow rate is obtained.
- a tube 213 (see FIG. 3) can be connected to the side inlet 105, the low flow side inlet 106, and the outlet 107.
- the microreactor 101 includes two plates, an upper plate 108 and a lower plate 109.
- the upper plate 108 includes a high flow rate flow channel 102, branch flow channels 102a and 102b, and a low flow rate flow channel. 103, a retention channel 104 is formed.
- the lower plate 109 has a high flow rate inlet 105, a low flow rate inlet 106, and a discharge port 107.
- the upper plate 108 and the lower plate 109 are integrated by welding. The welding method will be described later.
- the representative diameters of the high flow side channel 102, the low flow side channel 103, and the retention channel 104 in the microreactor 101 are 2 mm or less.
- the typical diameter of the channel is preferably in the range of several tens of ⁇ m to 1 mm in order to quickly mix two kinds of raw materials by molecular diffusion.
- the two types of raw materials may be mixed uniformly or may not be mixed and become non-uniform (so-called emulsified state).
- the high flow rate side material merges with the low flow rate side raw material from another direction at the junction 111b, thereby realizing good mixing.
- the interfacial area 112 of the two types of raw materials (the high flow rate side raw material 603 and the low flow rate side raw material 602) is twice the interfacial area determined by the flow rate ratio (volume ratio).
- the mixing efficiency can be improved without a very fine structure. Note that the techniques described in Patent Documents 1 to 3 do not consider that the raw materials have different flow rate ratios (flow rates).
- the branch flow path 102a and the branch flow path 102b join the low flow rate side flow path 103 at the junction 111b at the same time, so that the high flow rate side as shown in FIG.
- the raw materials 603 merge so as to sandwich the raw material 602 on the low flow rate side.
- the interfacial area 112 of the two types of raw materials is twice the interfacial area determined by the flow rate ratio (volume ratio), and the mixing efficiency can be improved without having a very fine structure.
- the high-flow-rate raw material 603 and the low-flow-rate raw material 602 are described as being not mixed. Actually, the raw material 603 on the high flow rate side and the raw material 602 on the low flow rate side are in a mixed state.
- the flow volume in the high flow rate flow path 102 is made larger than the flow volume in the low flow rate flow path 103 by branching the raw material on the high flow rate side into two. growing. Thereby, it is possible to prevent the high flow rate side raw material from flowing into the low flow rate side flow path 103 at the start of the production of the chemical product. That is, if the flow volume in the high flow rate flow path 102 and the flow volume in the low flow rate flow path 103 are the same, the flow rate of the raw material on the high flow rate side is faster. 111b is reached. Then, the raw material on the high flow rate side that has reached the confluence 111b first flows into the low flow rate flow path 103, that is, it flows backward.
- the time required for the high flow rate side raw material to reach the confluence 111b is lengthened by making the volume in the flow rate side flow channel 102 larger than the flow volume in the low flow rate side flow channel 103. To do. Thereby, the raw material on the high flow rate side and the raw material on the low flow rate side can reach the confluence 111b almost simultaneously.
- the volume of the flow path (the high flow rate flow path 102, the branch flow paths 102a and 102b) through which the high flow rate raw material flows is equal to the flow rate of the flow path (the low flow rate flow path 103) through which the low flow rate raw material flows.
- One point of this embodiment is to make it larger than the volume in the road.
- FIG. 3 is a schematic diagram of the chemical product manufacturing system according to the first embodiment. 3 includes a high flow rate side raw material container 201, a first low flow rate side raw material container 202, a second low flow rate side raw material container 203, a pump 204 (204a to 204c), a product container 205, a disposal A physical container 206 is provided. Furthermore, the chemical product manufacturing system 200 includes a switching valve 207, a check valve 208, a thermostatic chamber 209 (209a, 209b), a weight sensor 210, a pressure sensor 211, a temperature sensor 212, a tube 213 (213a to 213e), and a microreactor 101. (101A, 101B). Here, the microreactor 101A and the microreactor 101B have the same structure as the microreactor 101 shown in FIG.
- the chemical product manufacturing system 200 is connected to a computer (not shown).
- the computer acquires information from each weight sensor 210, each pressure sensor 211, each temperature sensor 212, and the like.
- the computer controls the pumps 204 (204a to 204c), the switching valve 207, the heater in the thermostat 209, and the like based on the acquired information.
- the thermostatic chamber 209 is for holding the mixture obtained in each raw material and the microreactor 101 at an optimum temperature for the reaction, and holds the microreactor 101.
- the tube 213 has a loop 221 (221a to 221e). The thermostat 209 and the loop 221 will be described later.
- the high flow rate side raw material and the first low flow rate side raw material are respectively supplied from the high flow rate side raw material container 201 and the first low flow rate side raw material container 202 by the pumps 204 (204 a and 204 b), respectively. It is introduced into the first microreactor 101A through the tubes 213a and 213b. In the first microreactor 101A, the high-flow-rate raw material and the first low-flow-rate raw material are mixed to obtain a first mixture.
- the second low flow rate side raw material is introduced from the second low flow rate side raw material container 203 into the second microreactor 101B through the tube 213c by the pump 204c.
- the first mixture obtained in the first microreactor 101A is introduced into the second microreactor 101B through the tube 213d.
- the second microreactor 101B the first mixture and the second raw material on the low flow rate side are mixed, and the obtained second mixture passes through the tube 213e and passes through the switching valve 207 to the product container 205.
- the waste is collected in the waste container 206.
- the raw material on the high flow rate side and the raw material on the first low flow rate side are respectively introduced to a position before being introduced into the first microreactor 101A.
- the second raw material on the low flow rate side is introduced just before the second microreactor 101B.
- introduction of the high flow rate side raw material and the first low flow rate side raw material into the microreactor 101A is started.
- the introduction of the second low-flow-rate side raw material into the microreactor 101B is started. . Note that stopping the raw materials and the mixture before the microreactors 101A and 101B is performed by stopping the pump 204.
- the check valve 208 is installed immediately before the second low flow rate raw material side is introduced into the second microreactor 101B.
- the air inside the first microreactor 101A and the tube 213d becomes the second microreactor 101B.
- the check valve 208 may be installed immediately before the high-flow-rate raw material and the first low-flow-rate raw material are introduced into the first microreactor 101A.
- the high flow rate side raw material side introduction flow channel (the high flow rate side flow channel 102 and the branch flow channel 102a in the microreactor 101A) due to capillary action or the like. , 102b (FIG. 1)
- the raw material on the first low flow rate side can be prevented from flowing.
- a high flow rate is introduced into the first low flow rate side raw material side introduction flow channel (low flow rate flow channel 103 (FIG. 1) in the microreactor 101A). The raw material on the side can also be prevented from flowing.
- the weight sensor 210 measures the weights of the high flow rate side raw material container 201, the first low flow rate side raw material container 202, and the second low flow rate side raw material container 203.
- a computer grasps the amount introduced by the pump 204 (204a to 204c) for each of the high flow rate raw material, the first low flow rate side raw material, and the second low flow rate side raw material. Yes.
- a computer obtains a time series of weight data from the weight sensor 210 and combines it with time data (not shown), whereby a high flow rate raw material, a first low flow rate side raw material, and a second low flow rate side. The flow rate data of each raw material may be calculated.
- the flow rate sensor (not shown) is installed to measure the flow rate, and the density of the high flow rate side raw material, the first low flow rate side raw material and the second low flow rate side raw material,
- the computer can also replace the weight sensor 210 by calculating a change in weight based on the time series data and the time data.
- the pressure (in the chemical product manufacturing system 200 of the high flow rate raw material, the first low flow rate side raw material, and the second low flow rate side raw material in the tube 213 ( The discharge pressure is measured by the pressure sensor 211.
- the high flow rate flow path 102, the low flow rate flow path 103, the retention flow path 104 (FIG. 1), the tube 213 in the microreactor 101 are clogged due to the precipitation of substances contained in the raw material or an unexpected increase in viscosity. Can be detected.
- the maximum pressure allowed by the chemical product manufacturing system 200 is determined in advance, and the computer can acquire time-series data of pressure data from the pressure sensor 211 and stop the operation of the pump 204 when the maximum pressure is reached. It is.
- the pressure sensor 211 a relief valve or the like that detects a certain pressure value and releases the pressure can be substituted.
- the temperatures of the two microreactors 101A and 101B are adjusted by the thermostats 209a and 209b, respectively, and the temperatures thereof are measured by the temperature sensors 212, respectively.
- the raw material introduced into each of the microreactors 101A and 101B can be mixed at a predetermined temperature.
- the computer acquires time-series data of temperature data from the temperature sensor 212, and adjusts the temperature in the thermostatic chamber 209 by turning on and off a heater (not shown) or a cooler (not shown) so as to satisfy the set temperature. .
- the necessary length of the loops 221a, 221b, and 221c may be adjusted by the thermostatic chamber 209.
- the raw material introduced into the microreactor 101 can be mixed more accurately at a predetermined temperature.
- the reaction proceeds on the downstream side of the microreactor 101 if the residence time in the residence flow path 104 (see FIG. 1) is shorter than the reaction time. It will be.
- the lengths of the tubes 213d and 213e may be adjusted so as to ensure an appropriate residence time. Then, depending on the flow rate of the mixed liquid, the thermal conductivity, the reaction heat, the thickness and the thermal conductivity of the tube 213, the necessary length in the loops 221d and 221e out of the tubes 213d and 213e on the downstream side of the microreactor 101. By controlling the temperature in the constant temperature baths 209a and 209b, the reaction can proceed more accurately at a predetermined temperature.
- the representative diameter of not only the flow path in the microreactor 101 but also the flow path of the tube 213 (213d, 213e) on the downstream side of the microreactor 101 is 2 mm or less.
- the high flow rate raw material, the first low flow rate side raw material, and the second low flow rate side raw material are respectively introduced by the pump 204.
- the pump 204 for example, a tube pump, a syringe pump, a manual syringe, a plunger pump, a diaphragm pump, a screw pump, or the like can be used.
- a liquid feeding means using a water head difference may be used instead of the pump 204.
- the temperature adjusting means of the thermostatic chamber 209 can use a fluid such as water, a water-ethanol mixed solvent, ethylene glycol, a Peltier, a mantle heater, or the like.
- a fluid such as water, a water-ethanol mixed solvent, ethylene glycol, a Peltier, a mantle heater, or the like.
- the thermostatic chamber 209 is not necessarily required depending on the heat controllability between the reaction heat and the microreactor 101.
- the material of the liquid contact part in the microreactor 101, the high flow rate side raw material container 201, the first low flow rate side raw material container 202, the second low flow rate side raw material container 203, etc. does not adversely affect the mixing or the subsequent reaction. If it is. And the material of this liquid-contact part can be suitably changed according to the kind of the raw material of the high flow rate side, the 1st low flow rate side raw material, and the 2nd low flow rate side raw material.
- the pump 204, the tube 213, the fitting (not shown) for connecting the microreactor 101 and the tube 213, and the material of the liquid contact portion in the tube 213, etc. are those that do not adversely affect the mixing and subsequent reaction. Good.
- this liquid-contact part can be suitably changed according to the kind of the raw material of the high flow rate side, the 1st low flow rate side raw material, and the 2nd low flow rate side raw material.
- the raw material of the high flow rate side the 1st low flow rate side raw material
- the 2nd low flow rate side raw material for example, stainless steel, silicon, gold, glass, hastelloy, silicone resin, PP (polypropylene), TPX (methyl pentene polymer), PE (polyethylene), fluorine resin, or the like having high chemical resistance can be used.
- a glass lining, a metal surface coated with nickel or gold, a silicon surface oxidized, or the like having improved corrosion resistance may be used.
- various resins such as a silicone resin, PP (polypropylene), and a fluorine resin are used as the material of the tube 213 and the syringe that are in contact with the pump 204. Can do. Furthermore, various resins are also applied to the high flow rate side raw material container 201, the first low flow rate side raw material container 202, the second low flow rate side raw material container 203, the tube 213, and the fitting (not shown) for connecting the microreactor 101 and the tube 213. You may make it use. By doing in this way, it is possible to make only the liquid contact part of the chemical product manufacturing system 200 single use (disposable). Note that it is not necessary to use the same material for all the wetted parts, and the material can be appropriately changed according to the processability of the microreactor 101, the flexibility of the tube 213, and the like.
- the chemical product manufacturing system 200 shown in FIG. 3 is for mixing three types of raw materials in two stages: a high flow rate side raw material, a first low flow rate side raw material, and a second low flow rate side raw material.
- Two microreactors 101 are mounted.
- the configuration relating to the second raw material on the low flow rate side may be omitted from the chemical product manufacturing system 200.
- three types of raw materials are mixed in two stages, there may be only one type of raw material on the low flow rate side, and only one microreactor 101 of this embodiment is required.
- the microreactor that mixes different flow ratios is the microreactor 101 according to the present embodiment, and the microreactor that mixes the mixture and the remaining one type of raw material is generally used (this embodiment).
- the flow path shape in a general microreactor may be a Y-shape, a T-shape, or a shape that forms a multilayer flow as long as two types of raw materials are mixed rapidly.
- a general microreactor (not the one in the present embodiment) is arranged at the front stage, and the microreactor 101 according to the present embodiment is arranged at the rear stage.
- the chemical product manufacturing system of FIG. 200 may be expanded to form a chemical product manufacturing system 200 in which n microreactors 101 of this embodiment are mounted.
- n + 1 types of raw materials are mixed in n stages, if the number of the low flow rate side raw materials is m (m is 2 or less) and m microreactors 101 of this embodiment are to be mounted, the remaining n ⁇
- the shape of the flow path of m general (not in this embodiment) microreactors is a shape that forms a Y-shape, a T-shape, or a multi-layer flow if two types of raw materials are rapidly mixed. But you can.
- a general microreactor other than the microreactor 101 may be a microreactor having a flow path for mixing three or more kinds of raw materials.
- the raw materials may be mixed uniformly or may not be mixed and become non-uniform (so-called emulsified state).
- the chemical product manufacturing system 200 having the effect of the microreactor 101 can be realized. Further, by connecting a plurality of microreactors 101, it is possible to mix and react raw materials of a type that can be mixed by one microreactor 101.
- FIG. 4 is an external view showing a microreactor to which an adjustment microreactor is connected.
- the residence time in the residence flow path 104 is short relative to the reaction time, the downstream side of the microreactor 101 (after leaving the microreactor 101) )
- the reaction proceeds.
- the retention channel 104 needs to be lengthened in order to secure the residence time in the channel of the microreactor 101. Therefore, the microreactor 101 becomes huge. Therefore, in order to secure the reaction time, an adjustment microreactor 301 as shown in FIG. 4 is prepared.
- the adjustment microreactor 301 in FIG. 4 includes a retention channel 304, a mixture inlet 302, and a reactant outlet 303.
- the discharge port 107 of the microreactor 101 and the mixture introduction port 302 of the adjustment microreactor 301 are connected to each other by a tube 213.
- the mixture obtained in the microreactor 101 passes through the discharge port 107 and the tube 213. Then, the mixture is introduced into the retention flow path 304 of the adjustment microreactor 301 through the mixture introduction port 302. In addition to the retention flow path 104 of the microreactor 101, the mixture reaction is also performed in the retention flow path 304 of the adjustment microreactor 301. The reactant obtained as a result is discharged from the reactant outlet 303.
- the pump 204 (see FIG. 3) can be continuously operated, and the reaction time of the mixture can be adjusted by using the time during which the mixture is flowing in the retention flow paths 104 and 304 as the reaction time.
- the pump 204 may be stopped once after the mixture fills the retention channels 104 and 304 and the tube 213. Then, when a predetermined time has elapsed after the pump 204 is stopped, the mixture may be recovered from the reactant discharge port 303 by operating the pump 204 again.
- the time obtained by adding the time during which the pump 204 is stopped and the time during which the mixture flows in the retention flow paths 104 and 304 and the tube 213 can be used as the reaction time of the mixture.
- the adjustment microreactor 301 is composed of two plates, an upper plate 308 and a lower plate 309.
- a retention channel 304 is formed in the upper plate 308, and a mixture inlet 302 and a reactant outlet 303 are formed in the lower plate 309.
- the upper plate 308 and the lower plate 309 are integrated by welding according to the method described later in FIG.
- the representative diameter of the retention channel 304 in the adjustment microreactor 301 is 2 mm or less. Further, in the adjustment microreactor 301, the mixture flowing in the retention flow path 304 may be mixed uniformly or non-mixed (so-called emulsified state).
- the material of the adjustment microreactor 301 can be changed as appropriate according to the type of the mixture as long as it does not adversely affect the mixing and subsequent reaction.
- the material of the adjustment microreactor 301 a material having improved corrosion resistance such as a glass lining, a metal surface coated with nickel or gold, or a silicon surface oxidized may be used. .
- the retention flow path 304 in the adjustment microreactor 301 has a longer residence time of the mixture by increasing the volume in the flow path than the retention flow path 104.
- FIG. 5 is a side view for illustrating the method for manufacturing the microreactor according to the first embodiment.
- the material of the microreactor 101 is methyl tempen polymer or polyethylene.
- the microreactor 101 is composed of two plates, the upper plate 108 and the lower plate 109. Each flow path (high flow rate flow path 102, branch flow paths 102a and 102b, low flow rate flow path 103, retention flow path 104) is formed on the upper plate 108, but is formed on the lower plate 109. May be.
- the upper plate 108 is preferably made of white TPX (methyl pentene polymer) or PE (polyethylene).
- the lower plate 109 is made of colored (for example, black) TPX (methyl pentene polymer) or PE (polyethylene).
- TPX methyl pentene polymer
- PE polyethylene
- the microreactor 101 that can be incinerated at low cost can be manufactured. That is, the microreactor 101 usable for single use can be created.
- the upper plate 108 and the lower plate 109 are overlapped so as to form a flow path (a high flow rate flow path 102, branch flow paths 102a and 102b, a low flow rate flow path 103, and a retention flow path 104) on the inner side. .
- the laser beam 401 is irradiated on the entire surface of the upper plate 108 from above the upper plate 108 (on the upper plate 108 side), whereby portions other than the flow path are welded, and the microreactor 101 is formed.
- the channel width in each channel (the high-flow-side channel 102, the branch channels 102a and 102b, the low-flow-side channel 103, and the retention channel 104) is the same, and the channel depth in each channel By making the same, it is possible to reduce the possibility that the flow path is buried when welding.
- the microreactor 101 and the chemical product manufacturing system 200 with high manufacturing efficiency and safety can be provided.
- the microreactor 101 having the effect of the first embodiment can be easily manufactured by the manufacturing method shown in FIG.
- the upper plate 108 and the lower plate 109 can be integrated by such a manufacturing method.
- FIG. 6 is an external view of the microreactor according to the second embodiment.
- the same components as those in FIG. A microreactor 101a in FIG. 6 includes two orifices 502 (502a and 502b) and two sudden expansion portions 503 (503a and 503b) in the microreactor 101 in FIG.
- the raw material on the high flow rate side is introduced into the high flow rate side flow path 102 from the high flow rate side introduction port 105. Further, the raw material on the low flow rate side is introduced into the low flow rate flow path 103 from the low flow rate introduction port 106.
- the raw material on the high flow rate side is branched into two at the branch point 111a as the high flow rate side flow channel 102 is branched into two, the branch flow channel 102a and the branch flow channel 102b, and then the first embodiment.
- the raw material on the low flow rate side is joined at the joining point 111b (see FIG. 7) to form a mixture.
- this mixture is introduced into the first orifice 502a, it is finally introduced into the retention channel 104 through the first sudden expansion portion 503a, the second orifice 502b, and the second sudden expansion portion 503b. Is done. As a result, the obtained mixture is discharged from the discharge port 107.
- the microreactor 101a includes an upper plate 108 and a lower plate 109.
- the upper plate 108 includes a high flow rate flow channel 102, branch flow channels 102a and 102b, a low flow rate flow channel 103, a retention flow channel 104, an orifice 502 (502a and 502b), and a sudden expansion portion 503 (503a and 503b). Is formed.
- the lower plate 109 is formed with a high flow rate inlet 105, a low flow rate inlet 106 and a discharge port 107.
- FIG. 7 shows the detailed structure of the orifice.
- FIG. 7 shows the configuration of the orifice 502a in FIG. 6, the configuration of the orifice 502b is the same.
- the same components as those of FIG. As shown in FIG. 7, the orifice 502a has a narrower channel than the upstream channel.
- a sudden enlargement portion 503a is disposed downstream of the orifice 502a.
- the high flow rate side channel 102 (branch channels 102a and 102b), the low flow rate side channel 103, the retention channel 104, the orifices 502a and 502b, and the rapid expansion portion 503a.
- 503b preferably has a representative diameter of 2 mm or less.
- the typical diameter of the channel is preferably in the range of several tens of ⁇ m to 1 mm in order to quickly mix the raw materials by molecular diffusion.
- the orifice 502 causes the low-flow-rate raw material with a small amount to be present in a small amount in the high-flow-rate raw material with a large amount, resulting in a so-called emulsified state.
- the area where the raw material on the low flow rate side comes into contact with the raw material on the high flow rate side is increased, and a good reaction is promoted.
- the reaction can be promoted by bringing raw materials having low mixing properties into an emulsified state.
- FIG. 8 is an external view of the microreactor according to the third embodiment.
- the microreactor 101b of FIG. 8 includes a high flow side channel 102, a branch channel 102Z1, branch channels 102A1 to 102D1, channels A1 to D1, a low flow side channel 103, a retention channel 104, and a high flow side inlet. 105, a low flow side introduction port 106, and a discharge port 107. As shown in FIG.
- the raw material on the high flow rate side is introduced from the high flow rate inlet 105 into the high flow channel 102. Further, the low flow rate side raw material is introduced into the low flow rate side flow path 103 from the low flow rate side introduction port 106. Then, the high flow rate side channel 102 is branched into four channels of branch channels 102A1 to 102D1. Along with this, the raw material on the high flow rate side is branched into four, and at the confluences 701 to 704, the raw material or mixture on the low flow rate side is joined stepwise to form a final mixture. Thereafter, the mixture is introduced into the retention channel 104, and the obtained mixture is discharged from the discharge port 107.
- the flow path from the high flow rate inlet 105 to the branch point 700 is referred to as a high flow rate flow path 102.
- the flow path from the bending point 700a to the confluence 701 be the branch flow path 102A1.
- a flow path from the branch point 700b to the junction point 702 is referred to as a branch flow path 102B1.
- a flow path from the branch point 700c to the junction point 703 is defined as a branch flow path 102C1.
- a flow path from the bending point 700d to the merge point 704 is defined as a branch flow path 102D1.
- the flow path from the bending point 700a to the bending point 700d be the branch flow path 102Z1.
- a flow path from the confluence 701 to the confluence 702 is a flow path A1
- a flow path from the confluence 702 to the confluence 703 is a flow path B1.
- a flow path from the junction point 703 to the junction point 704 is a flow path C1
- a flow path from the junction point 704 to the discharge port 107 is a flow path D1.
- the channel D1 is the retention channel 104.
- the microreactor 101b is composed of two plates, an upper plate 108 and a lower plate 109.
- the upper plate 108 is formed with a high flow side channel 102, a branch channel 102Z1, branch channels 102A1 to 102D1, channels A1 to D1, a low flow side channel 103, and a stay channel 104.
- the lower plate 109 is formed with a high flow rate inlet 105, a low flow rate inlet 106, and a discharge port 107.
- the upper plate 108 and the lower plate 109 are welded and integrated by the manufacturing method shown in FIG.
- the flow paths having the same cross-sectional area merge at the merge points 701 to 704 of the branched raw material on the high flow rate side, and the cross-sectional area of the flow path does not change even after the merge.
- the high flow rate side flow channel 102 is branched into four branch flow channels 102A1 to 102D1 via the branch flow channel 102Z1, but each time the flow is merged, the cross-sectional area of each branch flow channel 102A1 to 102D1 is halved. .
- the mixing volume ratio of the raw material on the high flow rate side and the raw material on the low flow rate side is 15: 1 is shown as an example, but other mixing volume ratios may be used. The same applies to the fourth to sixth embodiments.
- a section 801 is defined from the branch point 700 to the first junction 701, and a section 802 is defined from the junction 701 to the next junction 702.
- a section 803 is defined as a section 803 from the confluence 702 to the next confluence 703, and a section 804 is defined from the confluence 703 to the next confluence 704.
- the cross-sectional area of the low flow rate side flow path 103 is 1, it is desirable that the cross-sectional area of the branch flow path 102D1 in the section 801 is 8. In addition, it is desirable that the cross-sectional area of the branch channel 102D1 in the section 802 is 4.
- the cross-sectional area of the branch flow path 102D1 in the section 803 is desirably 2, and the cross-sectional area of the branch flow path 102D1 in the section 804 is desirably 1.
- the cross-sectional area of the low flow rate side flow path 103 is 1, it is desirable that the cross-sectional area of the branch flow path 102C1 in the section 801 is 4.
- the cross-sectional area of the branch flow path 102C1 in the section 802 is desirably 2
- the cross-sectional area of the branch flow path 102C1 in the section 803 is desirably 1.
- the cross-sectional area of the low flow side flow path 103 is 1, the cross-sectional area of the branch flow path 102B1 in the section 801 is desirably 2, and the cross-sectional area of the branch flow path 102B1 in the section 802 is 1 Is desirable. Further, when the cross-sectional area of the low-flow-side channel 103 is 1, it is desirable that the cross-sectional area of the branch channel 102A1 in the section 801 is 1. Thus, in the third embodiment, it is desirable to halve the cross-sectional area of each of the branch flow paths 102B1 to 102D1 for each of the sections 801 to 804. However, it is not necessary to strictly set the cross-sectional area to the value described above. Note that the cross-sectional areas of the flow path from the high flow rate inlet 105 to the branch point 700 (the high flow rate flow path 102) and the branch flow path 102Z1 may be any value.
- the cross-sectional areas of the flow paths to be merged at the merge points 701 to 704 can be made the same.
- the closer the flow rate ratio the easier the mixing. Therefore, the cross-sectional areas of the merging target flow paths at the merging points 701 to 704 are the same, and the cross-sectional areas of the branch flow paths 102B1 to 102D1 are set to the sections 801 to 801. By halving every 804, the pressure loss in the flow path at each of the junctions 701 to 704 can be made uniform.
- each branch flow channel 102A1 to 102D1 is proportional to the cross-sectional area in the section 801
- the flow channel C1 has the same cross-sectional area as the low flow rate side flow channel 103 and flows therethrough.
- the flow rate of the mixture is 8, which is the total flow rate of the low flow rate side channel 103 + the branch channel 102A1 + the branch channel 102B1 + the branch channel 102C1, where the flow rate through the low flow side channel 103 is 1.
- the flow rate flowing through the branch flow channel 102D1 is 8, and the sectional area of the section 804 is the same as that of the low flow rate flow channel 103. Accordingly, the branch flow path 102D1 and the flow path C1 in the section 804 have the same flow rate and the same cross-sectional area, and therefore the pressure loss is the same. The same applies to the other junctions 701 to 703.
- the cross-sectional area of the flow path B1 is the same cross-sectional area as that of the low flow rate side flow path 103, and the flow rate is the sum of the low flow rate side flow path 103 + the branch flow path 102A1 + the branch flow path 102B1.
- the flow rate is 4.
- the flow rate of the branch flow path 102C1 in the section 803 is 4, and the cross-sectional area of the branch flow path 102C1 is the same as that of the low flow rate side flow path 103. Therefore, in the section 803, the pressure loss in the flow path B1 and the branch flow path 102C1 is the same.
- the flow rate of the branch flow channel 102D1 is 8, and the cross-sectional area in the section 803 is twice that of the low flow rate flow channel 103. From this, in the section 803, the pressure loss in the branch channel 102D1 is the same as the pressure loss in the channel B1 and the branch channel 102C1. The same applies to the other sections 801, 802, and 804.
- the microreactor 101b can make the pressure loss in each of the flow paths A1 to D1 and each of the branch flow paths 102A1 to 102D1 uniform for each section 801 to 804.
- the branch points 701 to 704 the raw material on the low flow rate side, the raw material on the high flow rate side, and the mixture can merge at substantially the same time. Thereby, favorable mixing can be realized.
- the microreactor 101b has the same effect as the microreactor 101 according to the first embodiment.
- FIG. 9 it is described that the raw material 603 on the high flow rate side and the raw material 602 on the low flow rate side are not mixed. Actually, the raw material 603 on the high flow rate side and the raw material 602 on the low flow rate side are in a mixed state.
- the high flow rate side raw material 603 and the low flow rate side raw material 602 from the branch flow path 102A1 adjoin each other.
- the raw material 602 on the low flow rate side and the raw material 603 on the high flow rate side are adjacent to each other.
- the raw material 603 on the high flow rate side from the branch flow path 102B1 joins the flow path A1 from the right side of the drawing.
- the raw material 603 on the high flow rate side merges on the right side of the page with respect to the state of the flow path A1.
- the raw material on the high flow rate side from the branch channel 102C1 joins the channel B1 from the right side of the drawing.
- the raw material 603 on the high flow rate side joins on the right side of the page with respect to the state of the flow path B1.
- the raw material on the high flow rate side from the branch flow path 102D1 joins the flow path C1 from the right side of the drawing.
- the raw material 603 on the high flow rate side merges on the right side of the page with respect to the state of the flow path C1.
- the raw material 603 on the high flow rate side and the raw material 602 on the low flow rate side are not mixed in order to facilitate understanding of the state of merging.
- the raw material 603 on the high flow rate side and the raw material 602 on the low flow rate side are in a mixed state. If the raw material 603 on the high flow rate side and the raw material 602 on the low flow rate side are not mixed, it can be said that the raw material 603 on the high flow rate side merges from the right side of the paper surface of the raw material 602 on the low flow rate side.
- the total of the volume in the channel of the high flow rate side channel 102, the volume in the channel of the branch channels 102A1 to 102D1, and the volume in the channel of the channels A1 to D1 and the volume in the channel of the low flow rate side channel 103 The ratio is desirably close to the flow rate ratio (volume ratio) of the two types of raw materials. Further, the total pressure loss in the flow path of the high flow rate side flow path 102, the branch flow paths 102A1 to 102D1, and the flow paths A1 to D1 may be substantially equal to the pressure loss in the flow path of the low flow rate side flow path 103. desirable.
- the microreactor 101b by dividing the high flow rate flow path 102 into four, the total volume in the flow path of the raw material on the high flow rate side becomes larger than the volume in the flow path of the low flow rate flow path 103. . For this reason, as in the first embodiment, it is possible to prevent the raw material on the high flow rate side from flowing into the low flow channel 103 at the start of the production of the compound.
- the microreactor 101b by mixing the raw material 603 on the high flow rate side in a stepwise manner, good mixing can be achieved even when the flow rate ratio between the low flow rate raw material and the high flow rate side raw material is greatly different. Is possible.
- the target mixture is obtained in the flow path D1, but since the flow path D1 is short, only the raw materials are mixed in the microreactor 101b, and the reaction is performed at the discharge port 107 of the microreactor 101b. It is desirable to perform in the connected adjustment microreactor 301 (FIG. 4) or the like.
- the flow paths 102 of the high flow rate side, the branch flow paths 102A1 to 102D1, the flow paths A1 to D1, the low flow rate side flow path 103, and the retention flow path 104 are set.
- the representative diameter is desirably 2 mm or less.
- the typical diameter of the channel is preferably in the range of several tens of ⁇ m to 1 mm in order to quickly mix the raw materials by molecular diffusion.
- the two types of raw materials may be mixed uniformly or may not be mixed and become non-uniform (so-called emulsified state).
- the high-flow-side channel 102 is branched into four.
- the micro-reactor 101b may be branched into three or more than five according to the flow rate ratio (volume ratio) of the two types of raw materials. May be.
- FIG. 10 is an external view of a microreactor according to the fourth embodiment.
- the microreactor 101c in FIG. 10 is different from the microreactor 101b in FIG. 6 in the arrangement of the branch flow paths of the high flow rate side flow path 102.
- the microreactor 101c of FIG. 10 includes a high flow side channel 102, a branch channel 102Z2, branch channels 102A2 to 102D2, channels A2 to D2, a low flow side channel 103, a retention channel 104, and a high flow side inlet. 105, a low flow side introduction port 106, and a discharge port 107.
- the raw material on the high flow rate side is introduced into the high flow rate channel 102 from the high flow rate introduction port 105.
- the low flow rate side raw material is introduced into the low flow rate side flow path 103 from the low flow rate side introduction port 106.
- the high flow rate side flow channel 102 is branched into four flow channels 102A2 to 102D2.
- the raw material on the high flow rate side is branched into four, and the raw material on the high flow rate side is stepwise joined with the raw material or mixture on the low flow rate side, whereby a final mixture is generated. Thereafter, the mixture is finally introduced into the retention channel 104, and the obtained mixture is discharged from the discharge port 107.
- the flow path from the high flow rate inlet 105 to the branch point 710 is referred to as a high flow rate flow path 102.
- the flow path from the bending point 710a to the confluence 714 be the branch flow path 102A2.
- a flow path from the branch point 710b to the junction point 712 is referred to as a branch flow path 102B2.
- a flow path from the branch point 710c to the junction point 711 is defined as a branch flow path 102C2.
- a flow path from the bending point 710d to the confluence 713 is defined as a branch flow path 102D2.
- the flow path from the bending point 710a to the bending point 710d be the branch flow path 102Z2.
- the channel D2 is the retention channel 104.
- the microreactor 101c is composed of two plates, an upper plate 108 and a lower plate 109.
- the upper plate 108 is formed with a high flow side channel 102, a branch channel 102Z2, branch channels 102A2 to 102D2, channels A2 to D2, a low flow side channel 103, and a stay channel 104.
- the lower plate 109 is formed with a high flow rate inlet 105, a low flow rate inlet 106, and a discharge port 107.
- the upper plate 108 and the lower plate 109 are welded and integrated by the manufacturing method shown in FIG.
- the flow paths having the same cross-sectional area merge at the junctions 711 to 714 of the branched high flow rate side raw material, and the cross-sectional area of the flow path does not change even after the merge.
- the high flow rate flow channel 102 is branched into four branched flow channels 102A2 to 102D2 via the branched flow channel 102Z2, but each time the flow flows, the cross sectional area of each of the branched flow channels 102A2 to 102D2 is halved. . This will be described in detail below.
- a section 811 is a section from the branch point 710 to the first junction 711
- a section 812 is a section from the junction 711 to the next junction 712.
- a section 813 is defined as a section 813 from the junction point 712 to the next junction point 713
- a section 814 is defined from the junction point 713 to the next junction point 714.
- the cross-sectional area of the low flow rate side flow path 103 is 1, it is desirable that the cross-sectional area of the branch flow path 102A2 in the section 811 is 8. In addition, it is desirable that the cross-sectional area of the branch flow path 102A2 in the section 812 is 4. Furthermore, the cross-sectional area of the branch flow path 102A2 in the section 813 is desirably 2, and the cross-sectional area of the branch flow path 102A2 in the section 814 is desirably 1.
- the cross-sectional area of the low flow rate side flow path 103 is 1, it is desirable that the cross-sectional area of the branch flow path 102D2 in the section 811 is 4.
- the cross-sectional area of the branch flow path 102D2 is desirably 2
- the cross-sectional area of the branch flow path 102D2 in the section 813 is desirably 1.
- the cross-sectional area of the low flow side flow path 103 is 1, the cross-sectional area of the branch flow path 102B2 in the section 811 is desirably 2, and the cross-sectional area of the branch flow path 102B2 in the section 812 is 1. Is desirable. Further, when the cross-sectional area of the low-flow-side channel 103 is 1, it is desirable that the cross-sectional area of the branch channel 102C2 in the section 811 is 1. Thus, in the fourth embodiment, it is desirable to halve the cross-sectional areas of the respective branch flow paths 102A2, 102B2, and 102D2 for each of the sections 811 to 814. However, it is not necessary to strictly set the cross-sectional area to the value described above. Note that the cross-sectional area of the flow path (high flow side flow path 102) from the high flow rate introduction port 105 to the branch point 710 and the branch flow path 102Z2 may be any value.
- the cross-sectional areas of the flow paths to be merged at the respective merge points 711 to 714 can be made the same.
- the closer the flow rate ratio the easier the mixing. Therefore, by setting the cross-sectional areas of the flow paths to be merged at the merge points 711 to 714 to be the same, the pressure loss in the flow paths at the merge points 711 to 714 is the same. Can be aligned. The reason why the pressure losses in the flow paths at the respective junctions 711 to 714 can be made uniform has already been described in the third embodiment, and thus the description thereof is omitted here. Thereby, favorable mixing can be realized.
- the volume in the flow channel 102 is larger than the volume in the low flow side channel 103.
- the microreactor 101c can obtain the same effect as the microreactor 101 shown in FIG.
- FIG. 11 shows that the raw material 603 on the high flow rate side and the raw material 602 on the low flow rate side are not mixed. Actually, the raw material 603 on the high flow rate side and the raw material 602 on the low flow rate side are in a mixed state.
- the high flow rate side raw material 603 and the low flow rate side raw material 602 from the branch flow path 102C2 adjoin each other.
- the raw material 602 on the low flow rate side and the raw material 603 on the high flow rate side are adjacent to each other.
- the raw material 603 on the high flow rate side of the branch flow path 102B2 joins the flow path A2 from the left side of the drawing.
- the raw material 603 on the high flow rate side merges on the left side of the page with respect to the state of the flow path A2.
- the raw material on the high flow rate side of the branch channel 102D2 joins the channel B2 from the right side of the drawing.
- the raw material 603 on the high flow rate side merges on the right side of the page with respect to the state of the flow path B2.
- the raw material on the high flow rate side of the branch flow path 102A2 joins the flow path C2 from the left side of the drawing.
- the high flow rate side raw material 603 merges on the left side of the drawing with respect to the state of the flow path C2.
- the raw material 603 on the high flow rate side and the raw material 602 on the low flow rate side are not actually separated (mixed). However, in FIG. It is described that the raw material 603 and the raw material 602 on the low flow rate side are not mixed. If the raw material 603 on the high flow rate side and the raw material 602 on the low flow rate side do not mix, it can be said that the raw material 603 on the high flow rate side alternately joins the raw material 602 on the low flow rate side from the left and right direction of the drawing.
- the total of the volume in the channel of the high flow rate side channel 102, the volume in the channel of the branch channels 102A2 to 102D2, and the volume in the channel of the channels A2 to D2 and the volume in the channel of the low flow rate side channel 103 The ratio is preferably close to the flow rate ratio (volume ratio) of the two types of raw materials. Further, the total pressure loss in the high flow side channel 102, the branch flow channels 102A2 to 102D2, and the flow channels A2 to D2 may be substantially equal to the pressure loss in the low flow side channel 103. desirable.
- the microreactor 101c by mixing the raw material 603 on the high flow rate side in a stepwise manner, good mixing can be achieved even when the flow rate ratio between the low flow rate raw material and the high flow rate side raw material is greatly different. Is possible.
- the target mixture is obtained in the flow path D2, but since the flow path D2 is short, only the raw materials are mixed in the microreactor 101c, and the reaction is performed at the outlet 107 of the microreactor 101c. It is desirable to perform in the connected adjustment microreactor 301 (FIG. 4) or the like.
- the flow path 102 In order to perform mixing well, in the microreactor 101c, the flow path 102, the branch flow paths 102A2 to 102D2, the flow paths A2 to D2, the low flow side path 103, and the retention flow path 104 of the flow path 104 are used.
- the representative diameter is desirably 2 mm or less.
- the typical diameter of the channel is preferably in the range of several tens of ⁇ m to 1 mm in order to quickly mix the raw materials by molecular diffusion.
- the two types of raw materials may be mixed uniformly or may not be mixed and become non-uniform (so-called emulsified state).
- the microreactor 101c by dividing the high flow rate side flow channel 102 into four, the total volume in the flow rate of the high flow rate side raw material becomes larger than the volume in the flow rate of the low flow rate side flow channel 103. . For this reason, as in the first embodiment, it is possible to prevent the raw material on the high flow rate side from flowing into the low flow channel 103 at the start of the production of the compound.
- the low flow side raw material is merged stepwise from the left and right sides of the paper, so the interface area between the two types of raw materials is the same as the conventional microreactor ( Compared with the microreactor which is not the one of the present embodiment, the mixing efficiency can be improved even if the microstructure is not so small. Furthermore, in the microreactor 101c, as shown in FIG. 11, since the raw material 603 on the high flow rate side alternately joins from the left and right direction on the paper surface, the mixing efficiency can be improved as compared with the microreactor 101b (see FIG. 8).
- the high-flow-side channel 102 is branched into four.
- the micro-reactor 101c may be branched into three or more than five according to the flow rate ratio (volume ratio) of the two types of raw materials. May be.
- FIG. 12 is an external view of the microreactor according to the fifth embodiment
- FIG. 13 is an exploded view of the microreactor according to the fifth embodiment. 12 and 13, the same components as those in FIG. 1 are denoted by the same reference numerals and description thereof is omitted.
- the raw material on the high flow rate side is introduced into the high flow rate channel 102 from the high flow rate introduction port 105.
- the low flow rate side raw material is introduced into the low flow rate side flow path 103 from the low flow rate side introduction port 106.
- the high flow rate side flow channel 102 is branched into four branch flow channels 102A3 to 102D3
- the high flow rate side raw material is branched into four.
- the raw material on the high flow rate side is stepwise merged with the raw material or mixture on the low flow rate side in the flow paths A3 to D3 to form a final mixture.
- the mixture is finally introduced into the retention channel 104 and discharged from the outlet 107.
- the cross-sectional area of the high flow rate flow channel 102 decreases each time it branches.
- the high flow rate side flow passage 102 is defined from the high flow rate side introduction port 105 to the bending point 734.
- a branch flow path 102A3 is defined from the branch point 731 to the junction point 741
- a branch flow path 102B3 is defined from the branch point 732 to the junction point 742.
- a branch flow path 102C3 is defined from the branch point 733 to the merge point 743
- a branch flow path 102D3 is defined from the bending point 734 to the merge point 744.
- a flow path A3 is defined from the junction point 741 to the merge point 742, and a flow path B3 is defined from the junction point 742 to the merge point 743.
- a flow path C3 is defined from the junction 743 to the merge point 744, and a flow path D3 is defined from the merge point 744 to the discharge port 107.
- the flow path D3 is also the retention flow path 104.
- the microreactor 101d is composed of two plates, an upper plate 108d and a lower plate 109d.
- the upper plate 108d is formed with a high flow side channel 102, branch channels 102A3 and 102C3, and channels A3 and C3.
- the lower plate 109d is formed with a low flow rate flow path 103, branch flow paths 102B3 and 102D3, and flow paths B3 and D3 (retention flow path 104).
- the lower plate 109d is formed with a high flow rate inlet 105, a low flow rate inlet 106, and a discharge port 107.
- the upper plate 108d and the lower plate 109d are manufactured by the manufacturing method shown in FIG. , Integrated by welding.
- each of the flow paths A3 to D3 flow paths having the same cross-sectional area merge together, and the cross-sectional area of the flow path after merging does not change.
- the cross section of the high flow side channel 102 is halved every time it is branched. That is, when the cross-sectional area of the low flow rate side flow path 103 is 1, the cross sectional area of the high flow rate side flow path 102 is 8 before branching to the branch flow path 102A3, 4 before branching to the branch flow path 102B3, It is desirable that 2 before branching to the branch channel 102C3 and 1 for the branch channel 102D3.
- the cross-sectional areas of the branch flow paths 102A3 to 102D3 and the flow paths A3 to D3 are desirably the same as those of the low flow rate side flow path 103.
- the flow rate in the branch flow paths 102A3 to 102D3 and the flow rate in the low flow rate side flow path 103 can be made the same, and the pressure loss in the branch flow paths 102A3 to 102D3 and the low flow rate side flow path 103 is achieved.
- the internal volume of the high flow side channel 102, the internal volume of the branch channels 102A3 to 102D3, and the internal volume of the channels A3 to D3. Is larger than the volume in the flow path of the low flow rate flow path 103.
- the cross-sectional area does not have to be halved every time it is strictly branched.
- the total of the volume in the flow path 102, the volume in the flow paths 102A3 to 102D3, and the volume in the flow paths A3 to D3 and the volume in the low flow path 103 The volume ratio is preferably close to the flow rate ratio (volume ratio) of the two types of raw materials. Furthermore, the pressure loss in the flow path of the raw material on the high flow rate side (the high flow rate flow path 102, the branch flow paths 102A3 to 102D3, the flow path A3 to D3) It is desirable that they are approximately equal. The same applies to a sixth embodiment described later.
- FIG. 14 is a schematic diagram of each flow path in the microreactor 101d
- FIG. 15 is a diagram showing a state of mixing in the flow paths A3 to D3 when viewed from the upstream side of the flow path.
- the flow path formed in the upper plate 108d is indicated by a solid line
- the flow path formed in the lower plate 109d is indicated by a broken line.
- the same components as those in FIG. 12 are denoted by the same reference numerals, and description thereof is omitted.
- the change of the cross-sectional area of the high flow volume side flow path 102 is not specified.
- the high-flow-rate raw material 603 and the low-flow-rate raw material 602 are mixed.
- the raw material 602 on the low flow rate side is described as not being mixed.
- the raw material 603 on the high flow rate side from the branch flow path 102A3 formed in the upper plate 108d and the lower plate 109d are formed.
- the low flow rate side raw material 602 from the low flow rate side flow channel 103 joins.
- the high flow rate raw material 603 is passed through the upper side of the paper, and the low flow rate side raw material 602 is passed through the upper plate 108d on the lower side of the paper.
- the high flow rate side raw material 603 from the branch flow path 102B3 formed in the lower plate 109d is transferred to the upper plate 108d. It merges with the mixture from the formed flow path A3.
- the lower plate 109d flows through the mixture in the upper flow path A3 with the raw material 603 on the high flow rate side adjacent from the lower side of the drawing. .
- the raw material on the high flow rate side from the branch flow path 102C3 formed in the upper plate 108d is formed in the lower plate 109d.
- the mixture in the lower channel B3 flows through the upper plate 108d in a state where the raw material 603 on the high flow rate side is adjacent from above in the drawing. .
- the raw material on the high flow rate side from the branch flow path 103D3 formed in the lower plate 109d is formed in the upper plate 108d.
- the high flow rate raw material 603 is adjacent to the upper flow path C3 from the lower side in the drawing. Flow through plate 109d.
- the raw material 603 on the high flow rate side and the raw material 602 on the low flow rate side are actually mixed.
- FIG. It is described that the raw material 603 on the flow rate side and the raw material 602 on the low flow rate side are not mixed. If the raw material 603 on the high flow rate side and the raw material 602 on the low flow rate side do not mix, it can be said that the raw material 603 on the high flow rate side merges so as to sandwich the raw material 602 on the low flow rate side from above and below in the drawing.
- the merging direction is different from that of the microreactor 101b (FIG. 8) and the microreactor 101c (FIG. 10), but the raw material 603 on the high flow rate side is alternately changed stepwise from the vertical direction on the paper surface. Therefore, more efficient mixing than the microreactor 101b and the microreactor 101c becomes possible.
- the representative diameter of the flow paths A3 to C3 and D3 (retention flow path 104) in the microreactor 101d be 2 mm or less.
- the typical diameter of the channel is preferably in the range of several tens of ⁇ m to 1 mm in order to quickly mix the raw materials by molecular diffusion.
- the two kinds of raw materials may be mixed uniformly or may not be mixed and become non-uniform (so-called emulsified state).
- the high flow rate flow path 102 is branched into four, but may be branched into three according to the flow ratio (volume ratio) of the two types of raw materials. Moreover, you may branch into five or more. In general, it is desirable to increase the number of branches of the high flow rate side channel 102 as the flow rate ratio (volume ratio) of the two types of raw materials increases.
- FIG. 16 is an external view of a microreactor according to the sixth embodiment
- FIG. 17 is an exploded view of the microreactor according to the sixth embodiment. 16 and 17, the same components as those in FIG. 1 are denoted by the same reference numerals and description thereof is omitted.
- the microreactor 101e shown in FIG. 16 differs from the microreactor 101d shown in FIG. 12 in the direction of the flow path after each of the junctions 761 to 764. As shown in FIG.
- the microreactor 101e includes a high flow side channel 102, a low flow side channel 103, a retention channel 104, a high flow side inlet 105, a low flow side inlet 106, and a discharge port 107. It is composed of
- the high flow rate side raw material is introduced into the high flow rate side flow path 102 from the high flow rate side introduction port 105.
- the low flow rate side raw material is introduced into the low flow rate side flow path 103 from the low flow rate side introduction port 106.
- the high flow rate side flow path 102 is branched into four branch flow paths 102A4 to 102D4. Then, the raw material on the high flow rate side gradually merges with the raw material or mixture on the low flow rate side in the flow paths A4 to D4 to form a final mixture.
- the mixture is finally introduced into the retention channel 104 and discharged from the outlet 107.
- the cross-sectional area of the high flow rate flow channel 102 decreases each time it branches.
- the high flow rate flow path 102 is defined from the high flow rate introduction port 105 to the bending point 754.
- a branch flow path 102A4 is defined from the branch point 751 to the merge point 761
- a branch flow path 102B4 is defined from the branch point 752 to the merge point 762.
- a branch flow path 102C4 is defined from the branch point 753 to the junction point 763
- a branch flow path 102D4 is defined from the bending point 754 to the junction point 764.
- a flow path A4 is defined as the flow path A4 from the junction point 761 to the merge point 762, and a flow path B4 is defined from the junction point 762 to the merge point 763.
- the flow path C4 is defined from the junction 763 to the merge point 764, and the flow path D4 is defined from the merge point 764 to the discharge port 107.
- the channel D4 is also a staying channel 104.
- the microreactor 101e is composed of two plates, an upper plate 108e and a lower plate 109e.
- a high flow rate side channel 102, branch channels 102A4 and 102C4, and channels A4 and C4 are formed in the upper plate 108e.
- the lower plate 109e is formed with a low flow rate flow path 103, branch flow paths 102B4 and 102D4, and flow paths B4 and D4 (retention flow path 104).
- the lower plate 109e is formed with a high flow rate inlet 105, a low flow rate inlet 106, and a discharge port 107.
- the upper plate 108e and the lower plate 109e are manufactured by the manufacturing method shown in FIG. , Welded and integrated.
- channels having the same cross-sectional area are merged in each of the channels A4 to D4, and the cross-sectional area of the channel after merging does not change.
- the cross-sectional area becomes half. That is, when the cross-sectional area of the low flow rate side flow path 103 is 1, the cross section area of the high flow rate side flow path 102 is 8 before branching to the branch flow path 102A4, 4 before branching to the branch flow path 102B4, It is desirable that 2 before branching to the branch channel 102C4 and 1 for the branch channel 102D4.
- the cross-sectional areas of the branch flow paths 102A4 to 102D4 and the flow paths A4 to D4 are preferably the same as those of the low flow rate side flow path 103.
- the flow rate in the branch flow paths 102A4 to 102D4 and the flow rate in the low flow rate side flow path 103 can be made the same, and the pressure loss in the branch flow paths 102A4 to 102D4 and the low flow rate side flow path 103 is achieved.
- branching of the high flow side channel 102, the internal volume of the high flow side channel 102, the internal volume of the branch channels 102A4 to 102D4, and the internal volume of the channels A4 to D4. Is larger than the volume in the flow path of the low flow rate flow path 103.
- the cross-sectional area does not have to be halved every time it is strictly branched.
- the total volume in the flow path 102, the volume in the flow paths 102A4 to 102D4, the volume in the flow paths A4 to D4, and the volume in the low flow path 103 The volume ratio is preferably close to the flow rate ratio (volume ratio) of the two types of raw materials. Further, the pressure loss in the flow path of the raw material on the high flow rate side (the high flow rate flow path 102, the branch flow paths 102A4 to 102D4, the flow path A4 to D4) It is desirable that they are approximately equal.
- the flow paths A4 to D4 move in the direction of the extension line of the branch flow paths 102A4 to 102D4 by a predetermined distance after joining, and then move in the direction of the discharge port 107.
- the microreactor 101e has a smoother flow of the mixture after each merging than the microreactor 101d shown in FIG.
- FIG. 18 is a schematic diagram of each flow path in the microreactor 101e
- FIG. 19 is a diagram showing a state of mixing in the flow paths A4 to D4 when viewed from the upstream side of the flow path.
- the flow path formed in the upper plate 108e is indicated by a solid line
- the flow path formed in the lower plate 109e is indicated by a broken line.
- the same components as those in FIG. the cross-sectional area of each flow path is not specified.
- the raw material 603 on the high flow rate side from the branch flow path 102A4 formed in the upper plate 108e and the lower plate 109e are formed.
- the raw material 602 on the low flow rate side of the low flow rate flow path 103 adjacent to each other merges.
- the high flow rate raw material 603 is adjacent to the upper side of the paper and the low flow rate raw material 602 is adjacent to the lower side of the paper.
- the raw material 603 on the high flow rate side from the branch flow path 102B4 formed in the lower plate 109e is transferred to the upper plate 108e. It merges with the mixture from the formed flow path A4. Accordingly, as shown in FIG. 19, in the flow path B4, the lower plate 109e flows through the mixture in the upper flow path A4 in a state where the raw material 603 on the high flow rate side is adjacent from the lower side of the drawing. .
- the raw material on the high flow rate side from the branch flow path 102C4 formed in the upper plate 108e is formed in the lower plate 109e. It joins the mixture in the flow path B4.
- the upper plate 108e flows through the mixture in the lower flow path B4 with the raw material 603 on the high flow rate side adjacent from above in the drawing. .
- the raw material 603 on the high flow rate side and the raw material 602 on the low flow rate side are actually mixed.
- FIG. It is described that the raw material 603 on the flow rate side and the raw material 602 on the low flow rate side are not mixed. If the raw material 603 on the high flow rate side and the raw material 602 on the low flow rate side do not mix, it can be said that the raw material 603 on the high flow rate side merges so as to sandwich the raw material 602 on the low flow rate side from above and below in the drawing.
- the representative diameters of the flow paths A4 to C4 and D4 (retention flow path 104) in the microreactor 101e be 2 mm or less.
- the typical diameter of the channel is preferably in the range of several tens of ⁇ m to 1 mm in order to quickly mix the raw materials by molecular diffusion.
- the two types of raw materials may be mixed uniformly or may not be mixed and become non-uniform (so-called emulsified state).
- the high flow rate flow path 102 is branched into four, but may be branched into three according to the flow ratio (volume ratio) of the two types of raw materials. Moreover, you may branch into five or more. In general, it is desirable to increase the number of branches of the high flow rate side channel 102 as the flow rate ratio (volume ratio) of the two types of raw materials increases.
- the flow paths A4 to D4 move to the discharge port 107 after moving in the extension line direction of the branch flow paths 102A4 to 102D4 by a predetermined distance after joining. is doing.
- the microreactor 101e can smoothly flow the mixture after each merging than the microreactor 101d shown in FIG.
- each flow path is formed on the upper plate 108, but may be formed on the lower plate 109d.
- the high flow side channel 102, the branch channels 102A3 and 102C3, and the channels A3 and C3 are formed in the upper plate 108d, and the low flow side channel 103, the branch channels 102B3 and 102D3,
- the paths B3 and D3 are formed in the lower plate 109d, but the reverse may be possible.
- microreactors 101A and 101B shown in FIG. 3 have the same structure as the microreactor 101 shown in FIG. 1, the microreactor 101a shown in FIG. 6, the microreactor 101b shown in FIG. 8, the microreactor 101c shown in FIG. The microreactor 101d shown in FIG. 12 and the microreactor 101e shown in FIG. 16 may be used. Further, the microreactors 101A and 101B shown in FIG. 3 may be connected to the adjustment microreactor 301 shown in FIG.
- raw materials having two kinds of flow rates are used, but three or more kinds of raw materials may be used.
- the raw material on the high flow rate side may sequentially join so as to sandwich the raw material with the lowest flow rate.
- the flow volume in the flow path may be increased as the flow rate becomes higher.
- microreactors 101, 101a to 101e are used for the production of antibody drug conjugates (ADC) drugs or for on-demand type drug production apparatuses.
- ADC antibody drug conjugates
- the present invention is not limited to the above-described embodiment, and includes various modifications.
- the above-described embodiment has been described in detail for easy understanding of the present invention, and is not necessarily limited to having all the configurations described.
- a part of the configuration of a certain embodiment can be replaced with the configuration of another embodiment, and the configuration of another embodiment can be added to the configuration of a certain embodiment.
- control lines and information lines indicate what is considered necessary for the explanation, and not all the control lines and information lines on the product are necessarily shown. In practice, it can be considered that almost all configurations are connected to each other.
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Abstract
Description
マイクロリアクタにおける合成反応の特徴として、以下の点がある。すなわち、マイクロリアクタにおける反応場のサイズの低下に伴い、分子拡散により流体が迅速混合する。その結果、流体の体積に対する表面積の効果が相対的に大きくなるとともに、流体の体積に対する熱伝達の効果が相対的に大きくなる。従って、通常のバッチ反応に比べ、反応時間の短縮や収率の向上による製造効率の向上が期待されている。
そして、材質としてPDMS(ポリジメチルシロキサン)、ABS樹脂、PC(ポリカーボネート)等の樹脂を用いることにより、材料、成型加工も含めたコストが安くなるため、マイクロリアクタはシングルユース(使い捨て)として使われている。
第1の手法として、2種類の原料をそれぞれ複数に分岐し、放射状に交互に導入できるようにし、中心に向かって多層流を形成して合流するものが知られている(例えば、特許文献1及び特許文献2参照)。
その他の解決手段については実施形態中において記載する。
以下、図1~図5を用いて、第1実施形態について説明する。
図1は、第1実施形態に係るマイクロリアクタの外観図である。
図1のマイクロリアクタ101は、高流量側流路102、低流量側流路103、滞留用流路104、高流量側導入口105、低流量側導入口106及び排出口107を有している。
ここで、高流量側流路102の流路内体積と低流量側流路103の流路内体積の比は、2種類の原料の流量比(体積比)に近いことが望ましいが、これに限らない。高流量側流路102の流路内体積と低流量側流路103の流路内体積は、2種類の原料が流れる際の圧力損失が等しい、又は、近い値となるようにすることが望ましい。
なお、特許文献1~3に記載の技術では、原料が異なる流量比(流量)を有することについては考慮していない。
なお、図2において、合流する様子をわかりやすくするために、高流量側の原料603と低流量側の原料602は混合していないようなイメージで記載している。実際には、高流量側の原料603と低流量側の原料602とは混合した状態となっている。
つまり、高流量側流路102の流路内体積と、低流量側流路103の流路内体積とを同じとすると、高流量側の原料の方が、流速が速いので、先に合流点111bに到達してしまう。すると、先に合流点111bに到達した高流量側の原料が低流量側流路103に流れ込む、すなわち、逆流をしてしまう。
図3の化成品製造システム200は、高流量側原料容器201、第1低流量側原料容器202、第2低流量側原料容器203、ポンプ204(204a~204c)、生成物用容器205、廃棄物用容器206を有している。さらに、化成品製造システム200は、切り替え用バルブ207、逆止弁208、恒温槽209(209a,209b)、重量センサ210、圧力センサ211、温度センサ212、チューブ213(213a~213e)及びマイクロリアクタ101(101A,101B)を有している。ここで、マイクロリアクタ101A及びマイクロリアクタ101Bは、図1に示すマイクロリアクタ101と同じ構造を有している。
また、1つめのマイクロリアクタ101Aで得られた第1の混合物が、2つめのマイクロリアクタ101Bに導入される手前まで導入されたら、マイクロリアクタ101Bへの第2の低流量側の原料の導入が開始される。
なお、マイクロリアクタ101A,101Bの手前で、各原料及び混合物を止めることは、ポンプ204を停止することで行われる。
同様に、ポンプ204、チューブ213、マイクロリアクタ101とチューブ213を接続するフィッティング(不図示)や、チューブ213等における接液部の材質は、混合やその後の反応に悪い影響を与えないものであればよい。そして、この接液部の材質は、高流量側の原料、第1の低流量側の原料及び第2の低流量側の原料の種類に応じて適宜変更することができる。例えば、耐薬品性の高い、ステンレス、シリコン、金、ガラス、ハステロイ、シリコーン樹脂、PP(ポリプロピレン)、TPX(メチルテンペンポリマ)、PE(ポリエチレン)、フッ素系樹脂等を用いることができる。また、グラスライニングや、金属の表面にニッケルや金等のコーティングをしたものや、シリコンの表面を酸化させたもの等、耐食性を向上させたものが用いられてもよい。
また、3種類の原料を2段階で混合するが、低流量側の原料が1種類のみであり、本実施形態のマイクロリアクタ101が1つあればよい場合がある。例えば、3種類のうち、2種類は流量比に差があるが、流量比に差がある原料の混合物の流量と、残り1種類の原料の流量とがほぼ同じである場合である。このような場合、2つのマイクロリアクタ101のうち、異なる流量比を混合するマイクロリアクタは本実施形態に係るマイクロリアクタ101とし、混合物と、残り1種類の原料を混合するマイクロリアクタを、一般的な(本実施形態のものではない)マイクロリアクタとすることができる。このとき、一般的なマイクロリアクタにおける流路形状は、2種類の原料が迅速に混合するのであれば、Y字型やT字型、多層流を形成する形状でもよい。
前記したように、マイクロリアクタ101に導入された原料が混合して反応する場合、滞留用流路104に滞留する時間が反応時間に対して短いと、マイクロリアクタ101の下流側(マイクロリアクタ101から出た後)で反応が進行することになる。反応時間が長い場合、マイクロリアクタ101の流路内で滞留時間を確保しようとすると、滞留用流路104を長くする必要がある。そのため、マイクロリアクタ101が巨大化してしまう。そこで、反応時間を確保するために、図4に示すような調整用マイクロリアクタ301が用意される。
なお、滞留用流路304が下側プレート309に形成されていてもよい。
図5では、マイクロリアクタ101の材質がメチルテンペンポリマもしくはポリエチレンであるものとする。
前記したように、マイクロリアクタ101は、上側プレート108及び下側プレート109の2枚のプレートから構成されている。各流路(高流量側流路102、分岐流路102a,102b、低流量側流路103、滞留用流路104)は、上側プレート108に形成されているが、下側プレート109に形成されてもよい。上側プレート108は白色のTPX(メチルテンペンポリマ)もしくはPE(ポリエチレン)で作製されることが望ましい。また、下側プレート109が有色(例えば黒色)のTPX(メチルテンペンポリマ)もしくはPE(ポリエチレン)で作製されることが望ましい。このように、上側プレート108及び下側プレート109をTPXや、PEのような樹脂製とすることで、安価かつ焼却可能なマイクロリアクタ101を作製することができる。つまり、シングルユースで使用可能なマイクロリアクタ101を作成することができる。上側プレート108及び下側プレート109は、内側に流路(高流量側流路102、分岐流路102a,102b、低流量側流路103、滞留用流路104)を形成するように重ね合わせられる。そして、上側プレート108の上方(上側プレート108側)からレーザ光401が、上側プレート108の全面に照射されることにより、流路以外の部分が溶着し、マイクロリアクタ101が形成される。
ここで、高流量側流路102、分岐流路102a,102b、低流量側流路103及び滞留用流路104の断面積は同じとすることが望ましい。特に各流路(高流量側流路102、分岐流路102a,102b、低流量側流路103、滞留用流路104)での流路幅を同じとし、各流路での流路深さを同じとすることにより、溶着する際に流路が埋まってしまう可能性を低くすることができる。
また、図5に示す製造方法により、第1実施形態における効果を有するマイクロリアクタ101を容易に製造することができる。
また、このような製造方法により、上側プレート108及び下側プレート109を一体化することができる。これにより、各流路(高流量側流路102、分岐流路102a,102b、低流量側流路103、滞留用流路104)からの漏れや、外部からの異物の混入を防止することができ、腐食性の高い物質や、取扱いに注意を要する合成反応を取り扱う場合や、クロスコンタミネーション(交差汚染)が生じるおそれのある場合においても、安全性や、安定性の高い化成品の製造を行うことができる。
以下、図6を用いて、第2実施形態について説明する。
図6は、第2実施形態に係るマイクロリアクタの外観図である。なお、図6において、図1と同様の構成については同一の符号を付して説明を省略する。
図6のマイクロリアクタ101aは、図1のマイクロリアクタ101に、2つのオリフィス502(502a,502b)、及び、2つの急拡大部503(503a,503b)を有している。
図7では、図6のオリフィス502aの構成を示しているが、オリフィス502bの構成も同様である。図7において、図6と同様の構成については同一の符号を付して説明を省略する。
図7に示すように、オリフィス502aでは、その上流の流路より狭い流路となっている。そして、オリフィス502aの下流では、急拡大部503aが配置されている。
以下、図8及び図9を参照して、第3実施形態について説明する。
図8は、第3実施形態に係るマイクロリアクタの外観図である。なお、図8において、図1と同様の構成要素については、同一の符号を付して説明を省略する。
図8のマイクロリアクタ101bは、高流量側流路102、分岐流路102Z1、分岐流路102A1~102D1、流路A1~D1、低流量側流路103、滞留用流路104、高流量側導入口105、低流量側導入口106、排出口107から構成されている。
図8に示すように、マイクロリアクタ101bにおいて、高流量側の原料は、高流量側導入口105から高流量側流路102に導入される。また、低流量側原料は、低流量側導入口106から低流量側流路103に導入される。そして、高流量側流路102は分岐流路102A1~102D1の4つに分岐する。これに伴い、高流量側の原料は4つに分岐され、合流点701~704において、低流量側の原料もしくは混合物と段階的に合流することで、最終的な混合物となる。その後、混合物は、滞留用流路104に導入され、得られた混合物は排出口107から排出される。
以下、このことを詳細に説明する。
なお、ここでは、高流量側の原料と、低流量側の原料との混合体積比が15:1である場合を例として示しているが、これ以外の混合体積比でもよい。第4~第6実施形態においても同様である。
また、低流量側流路103の断面積を1とした場合、区間801における分岐流路102A1の断面積は1であることが望ましい。
このように、第3実施形態では、各分岐流路102B1~102D1の断面積を区間801~804ごとに半分にしていくことが望ましい。ただし、断面積を厳密に前記した値とする必要はない。なお、高流量側導入口105から分岐点700までの流路(高流量側流路102)及び分岐流路102Z1の断面積はどのような値でもよい。
例えば、各分岐流路102A1~102D1の流量は、区間801における断面積に比例するものと仮定すると、流路C1は、低流量側流路103と同じ断面積を有し、そこを通流する混合物の流量は、低流量側流路103を通流する流量を1とすると、低流量側流路103+分岐流路102A1+分岐流路102B1+分岐流路102C1の合計流量である8となる。一方、分岐流路102D1に流れる流量は8であり、区間804において、その断面積は低流量側流路103と同じ断面積となっている。従って、区間804における分岐流路102D1と、流路C1とでは、同じ流量、同じ断面積となるため、圧力損失が同じとなる。その他の合流点701~703も同様である。
これにより、良好な混合を実現することができる。
なお、マイクロリアクタ101bにおいて、目的とする混合物は、流路D1で得られるが、流路D1は長さが短いため、マイクロリアクタ101bでは原料の混合のみを行い、反応は、マイクロリアクタ101bの排出口107に接続されている調整用マイクロリアクタ301(図4)等で行われることが望ましい。
以下、図10及び図11を参照して、第4実施形態について説明する。
図10は、第4実施形態に係るマイクロリアクタの外観図である。なお、図10において図1と同様の構成要素については同一の符号を付して説明を省略する。
図10のマイクロリアクタ101cは、図6のマイクロリアクタ101bに対し、高流量側流路102の分岐流路の並びが異なるものである。
図10のマイクロリアクタ101cは、高流量側流路102、分岐流路102Z2、分岐流路102A2~102D2、流路A2~D2、低流量側流路103、滞留用流路104、高流量側導入口105、低流量側導入口106、排出口107から構成されている。
以下、このことを詳細に説明する。
また、低流量側流路103の断面積を1とした場合、区間811における分岐流路102C2の断面積は1であることが望ましい。
このように、第4実施形態では、各分岐流路102A2、102B2,102D2の断面積を区間811~814ごとに半分にしていくことが望ましい。ただし、断面積を厳密に前記した値とする必要はない。なお、高流量側導入口105から分岐点710までの流路(高流量側流路102)及び分岐流路102Z2の断面積はどのような値でもよい。
なお、マイクロリアクタ101cにおいて、目的とする混合物は、流路D2で得られるが、流路D2は長さが短いため、マイクロリアクタ101cでは原料の混合のみを行い、反応は、マイクロリアクタ101cの排出口107に接続されている調整用マイクロリアクタ301(図4)等で行われることが望ましい。
さらに、マイクロリアクタ101cでは、図11に示すように、紙面左右方向から交互に高流量側の原料603が合流するため、マイクロリアクタ101b(図8参照)よりも混合効率を向上させることができる。
以下、図12~図15を参照して、第5実施形態について説明する。
図12は、第5実施形態に係るマイクロリアクタの外観図であり、図13は、第5実施形態に係るマイクロリアクタの分解図である。なお、図12、図13において、図1と同様の構成については、同一の符号を付して説明を省略する。
また、高流量側流路102は、分岐する毎にその断面積が小さくなっている。
そして、上側プレート108d及び下側プレート109dは、図5に示す製造方法によって、溶着により一体化されている。
また、このような高流量側流路102の分岐により、高流量側流路102の流路内体積、分岐流路102A3~102D3の流路内体積、及び流路A3~D3の流路内体積の合計は、低流量側流路103の流路内体積より大きくなっている。なお、断面積は、厳密に分岐される毎に半分としなくてもよい。
図14は、マイクロリアクタ101dにおける各流路の模式図であり、図15は、流路の上流側から見たときの流路A3~D3における混合の様子を示す図である。なお、図14において、上側プレート108dに形成されている流路を実線で示し、下側プレート109dに形成されている流路を破線で示す。なお、図14において、図12と同様の構成については同一の符号を付し、説明を省略する。また、図14において、高流量側流路102の断面積の変化を明示していない。
また、実際には、高流量側の原料603と低流量側の原料602とは混合するが、これまでと同様、合流する様子をわかりやすくするために、図15において、高流量側の原料603と低流量側の原料602は混合していないように記載している。
以下、図16~図19を参照して、第6実施形態について説明する。
図16は、第6実施形態に係るマイクロリアクタの外観図であり、図17は、第6実施形態に係るマイクロリアクタの分解図である。なお、図16、図17において、図1と同様の構成については、同一の符号を付して説明を省略する。
図16に示すマイクロリアクタ101eは、図12に示すマイクロリアクタ101dと比較し、各合流点761~764後の流路の方向が異なるものである。
そして、図16に示すように、マイクロリアクタ101eは、高流量側流路102、低流量側流路103、滞留用流路104、高流量側導入口105、低流量側導入口106、排出口107から構成されている。
また、高流量側流路102は、分岐する毎にその断面積が小さくなっている。
そして、上側プレート108e及び下側プレート109eは、図5に示す製造方法によって、溶着され、一体化されている。
また、このような高流量側流路102の分岐により、高流量側流路102の流路内体積、分岐流路102A4~102D4の流路内体積、及び流路A4~D4の流路内体積の合計は、低流量側流路103の流路内体積より大きくなっている。なお、断面積は、厳密に分岐される毎に半分としなくてもよい。
図18は、マイクロリアクタ101eにおける各流路の模式図であり、図19は、流路の上流側から見たときの流路A4~D4における混合の様子を示す図である。なお、図18において、上側プレート108eに形成されている流路を実線で示し、下側プレート109eに形成されている流路を破線で示す。また、図18において、図16と同様の構成については、同一の符号を付して説明を省略する。なお、図18において、各流路の断面積は明示していない。
これにより、図19に示すように、流路B4では、上側の流路A4内の混合物に対して、紙面下方から高流量側の原料603が隣り合った状態で下側プレート109eを通流する。
また、第5実施形態において、高流量側流路102、分岐流路102A3,102C3、流路A3,C3が上側プレート108dに形成され、低流量側流路103、分岐流路102B3,102D3、流路B3,D3(滞留用流路104)が、下側プレート109dに形成されているが、逆でもよい。第6実施形態も同様である。
102 高流量側流路(高流量の原料の流路)
102a,102b,102A1~102A4,102B1~102B4,102C1~102C4,102D1~102D4 分岐流路
103 低流量側流路(低流量の原料の流路)
104 滞留用流路
105 高流量側導入口
106 低流量側導入口
107 排出口
108,108d,108e 上側プレート
109,109d,109e 下側プレート
111b,701~704,711~714,741~744,761~764 合流点
111a,700,700b,700c,710,710b,710c,731~733,751~753 分岐点
200 化成品製造システム
201 高流量側原料容器
202 第1低流量側原料容器
203 第2低流量側原料容器
204,204a~204c ポンプ
205 生成物用容器
206 廃棄物用容器
207 切り替え用バルブ
208 逆止弁
209,209a,209b 恒温槽
210 重量センサ
211 圧力センサ
212 温度センサ
213,213a~213e チューブ
221,221a~221e ループ
603 高流量側の原料
602 低流量側の原料
700a,700d,710a,710d 屈曲点
801~804,811~814 区間
A1~A4,B1~B4,C1~C4,D1~D4 流路
Claims (15)
- 流量が異なる複数の原料がそれぞれ通流する複数の流路を備え、
前記流路は、高流量の原料の流路が複数に分岐した後、低流量の原料の流路に合流するように、分岐・合流されている
ことを特徴とするマイクロリアクタ。 - 請求項1に記載のマイクロリアクタにおいて、
各原料が最終的に合流するまでの各原料の流路の内容積について、前記高流量の原料の流路の内容積が、前記低流量の原料の流路の内容積より大きい
ことを特徴とするマイクロリアクタ。 - 請求項1に記載のマイクロリアクタにおいて、
複数に分岐した高流量の原料と、低流量の原料とが同時に合流する
ことを特徴とするマイクロリアクタ。 - 請求項3に記載のマイクロリアクタにおいて、
前記高流量の原料と、前記低流量の原料とが合流する際、前記低流量の原料の両側から前記高流量の原料が合流する
ことを特徴とするマイクロリアクタ。 - 請求項1に記載のマイクロリアクタにおいて、
前記高流量の原料の流路と、前記低流量の原料の流路との合流点の後段に、少なくとも1つのオリフィスを有する
ことを特徴とするマイクロリアクタ。 - 請求項1に記載のマイクロリアクタにおいて、
複数に分岐した高流量の原料が、段階的に、低流量の原料に合流するよう前記流路が形成されている
ことを特徴とするマイクロリアクタ。 - 請求項6に記載のマイクロリアクタにおいて、
前記高流量の原料は、前記低流量の原料に対して、異なる方向から交互に合流するよう前記流路が形成されている
ことを特徴とするマイクロリアクタ。 - 請求項7に記載のマイクロリアクタにおいて、
前記マイクロリアクタは、2枚のプレートから構成され、
それぞれのプレートに前記流路が形成されており、
前記高流量の原料は、前記低流量の原料に対して、前記2枚のプレートそれぞれの方向から、交互に合流するよう前記流路が形成されている
ことを特徴とするマイクロリアクタ。 - 請求項1に記載のマイクロリアクタにおいて、
各原料が最後に合流した後の下流側に滞留用流路が設けられる
ことを特徴とするマイクロリアクタ。 - 請求項9に記載のマイクロリアクタにおいて、
前記マイクロリアクタの下流側に、前記滞留用流路のみを有するマイクロリアクタが接続される
ことを特徴とするマイクロリアクタ。 - 請求項1に記載のマイクロリアクタにおいて、
前記マイクロリアクタの材質がメチルテンペンポリマもしくはポリエチレンである
ことを特徴とするマイクロリアクタ。 - 請求項1に記載のマイクロリアクタにおいて、
前記流路の代表径が2mm以下である
ことを特徴とするマイクロリアクタ。 - 流量が異なる複数の原料がそれぞれ通流する複数の流路を備え、
前記流路は、高流量の原料の流路が複数に分岐した後、低流量の原料の流路に合流するように、分岐・合流されているマイクロリアクタを少なくとも1つ有するとともに、
それぞれの前記マイクロリアクタに原料を送るためのポンプを有する
ことを特徴とする化成品製造システム。 - 流量が異なる複数の原料がそれぞれ通流する複数の流路を備え、
前記流路は、高流量の原料の流路が複数に分岐した後、低流量の原料の流路に合流するように、分岐・合流されているマイクロリアクタが、2枚のプレートから構成され、前記2枚のプレートのうち、少なくとも一方に前記流路が形成されているマイクロリアクタの製造方法において、
前記流路が前記2枚のプレートにおける対合面に位置するよう、前記2枚のプレートが溶着される
ことを特徴とするマイクロリアクタの製造方法。 - 請求項14に記載のマイクロリアクタの製造方法において、
前記2枚のプレートそれぞれの材質は、メチルテンペンポリマもしくはポリエチレンで構成されており
互いに一方の面が接するように対置されている前記2枚のプレートに対して、レーザが照射されることにより、前記2枚のプレートが溶着する
ことを特徴とするマイクロリアクタの製造方法。
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| WO2019049547A1 (ja) * | 2017-09-06 | 2019-03-14 | 株式会社日立製作所 | マイクロリアクタシステム |
| WO2020075817A1 (ja) | 2018-10-10 | 2020-04-16 | 武田薬品工業株式会社 | 抗体薬物複合体の製造方法 |
| US20230082190A1 (en) * | 2020-03-24 | 2023-03-16 | Hitachi Plant Services Co., Ltd. | Microreactor system |
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| CN111974324A (zh) * | 2020-09-17 | 2020-11-24 | 苏州昊帆生物股份有限公司 | 乙硫氨酯的连续制备装置及制备乙硫氨酯的方法 |
| TW202528741A (zh) * | 2023-10-10 | 2025-07-16 | 日商大賽璐股份有限公司 | 微流體系統、使用微流體系統之處理方法及聚合物的製造方法 |
| JP2025133373A (ja) * | 2024-03-01 | 2025-09-11 | 株式会社日立プラントサービス | マイクロリアクタおよびマイクロリアクタの混合性能の評価方法 |
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| WO2019049547A1 (ja) * | 2017-09-06 | 2019-03-14 | 株式会社日立製作所 | マイクロリアクタシステム |
| JP2019042713A (ja) * | 2017-09-06 | 2019-03-22 | 株式会社日立製作所 | マイクロリアクタシステム |
| US10987649B2 (en) | 2017-09-06 | 2021-04-27 | Hitachi Plant Services Co., Ltd. | Microreactor system |
| WO2020075817A1 (ja) | 2018-10-10 | 2020-04-16 | 武田薬品工業株式会社 | 抗体薬物複合体の製造方法 |
| CN112839676A (zh) * | 2018-10-10 | 2021-05-25 | 武田药品工业株式会社 | 制造抗体药物偶联物的方法 |
| JPWO2020075817A1 (ja) * | 2018-10-10 | 2021-09-02 | 武田薬品工業株式会社 | 抗体薬物複合体の製造方法 |
| EP3865151A4 (en) * | 2018-10-10 | 2022-11-16 | Takeda Pharmaceutical Company Limited | METHOD FOR PRODUCING AN ANTIBODY-DRUG CONJUGATE |
| JP7364584B2 (ja) | 2018-10-10 | 2023-10-18 | 武田薬品工業株式会社 | 抗体薬物複合体の製造方法 |
| CN112839676B (zh) * | 2018-10-10 | 2024-10-25 | 武田药品工业株式会社 | 制造抗体药物偶联物的方法 |
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| US11857941B2 (en) * | 2020-03-24 | 2024-01-02 | Hitachi Plant Services Co., Ltd. | Microreactor system |
Also Published As
| Publication number | Publication date |
|---|---|
| SG11201809014XA (en) | 2018-11-29 |
| CN109070041A (zh) | 2018-12-21 |
| US20190118156A1 (en) | 2019-04-25 |
| JP2017189729A (ja) | 2017-10-19 |
| JP6924556B2 (ja) | 2021-08-25 |
| EP3444027B1 (en) | 2025-05-28 |
| EP3444027A1 (en) | 2019-02-20 |
| EP3444027A4 (en) | 2019-12-18 |
| US10464039B2 (en) | 2019-11-05 |
| CN109070041B (zh) | 2021-08-24 |
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