JPWO2006043642A1 - Fluid reaction device - Google Patents

Abstract

Provided is a fluid reaction apparatus suitable as a practical mass production means capable of mixing a plurality of fluids using a micro space and performing various chemical reaction operations efficiently. This fluid reaction apparatus is a fluid reaction apparatus in which a plurality of fluids A and B are introduced into a reaction flow path 62 having a micro reaction space and reacted. This apparatus includes an introduction section 2 for individually introducing fluids used for reaction, a flat mixed substrate 40 having mixing channels 56, 57, and 58 for mixing and mixing fluids, and a plurality of transport pipes for fluids. Fluid transporting means 16A, 16B transporting toward the mixing flow path via 21A, 21B, flow rate control means 20 for controlling the flow rate of the fluid, temperature control means 7 for controlling the temperature of the reaction flow path 62, It has the derivation | leading-out part 104 which derives | leads-out the substance after reaction, and the operation control means 6 which controls these operation | movement.

Description

  The present invention relates to a fluid reaction apparatus for reacting fluids in a minute space. For example, the present invention relates to a microreactor that performs reactions such as continuous synthesis of drugs, genes, and proteins in a minute space.

  As conventional batch-type organic synthesis reactors, colbens, beakers, test tubes and the like are used in laboratories, and reaction kettles exceeding a few hundred liters are widely used in chemical production lines. In these reaction containers, for example, in a reaction with an explosion risk, a technique such as extremely reducing the mixing speed or extremely reducing the reaction temperature to minus is taken.

  In the case of a reaction with a slow reaction time, in the conventional continuous flow method, the reaction is advanced by passing through a capillary pipe having an inner diameter of about 1 to 5 mm. However, it takes time to conduct heat from the outer circumference of the pipe to the center. Further, since the diffusion time of the reaction intermediate also becomes long, it is insufficient in terms of high selectivity and high yield.

  In recent years, there has been a movement to perform these organic synthesis reactions and biochemical reactions in a micro space of several tens to several hundreds of microns. That is, when analysis or chemical synthesis is performed, it is reported that the reaction occurs in a so-called micro reaction state by setting the mutual reaction distance of the mixed portion of the raw material fluid to 1 μm to 500 μm. Advantages of using a microreaction state, such as making the mixing part or reaction part into a microspace, are that the ratio of the surface area to the volume of the fluid is large, the mass transfer distance is shortened and the diffusion time is shortened (why Then, the diffusion time between materials is proportional to the square of the mutual distance (Fick's law), so the diffusion time is shortened.For example, if the reaction mutual distance between two substances in a regular batch reactor with a diameter of 1000 mm is 10 mm If the reaction of microreactors with mutual distances of 500 μm, 100 μm, and 10 μm occurs simultaneously with diffusion, the reaction time will be 400 times, 10,000 times, and 1 million times faster than the batch reactor, respectively) Reduction of heat, heat transfer and transfer are quick, material transfer is performed efficiently, and the supply of the substance can catch up with fast reactions. But allowing at ordinary temperature, it is possible to continuously synthesis flame reactants according to the microreactor. In addition, in a conventional batch reaction kettle, the reaction rate may be increased to increase the reaction rate, but in the case of a microreactor, the reaction rate is fast, so that the reaction is possible even at room temperature. Furthermore, in batch reactors, the concentration (molar ratio) of the mixing portion is non-uniform, and unnecessary intermediate products are likely to be generated. In the microreactor, the concentration of the mixing portion is easily uniformed, so unnecessary intermediate products are generated. In addition, a high yield and a highly selective reaction can be obtained at the same time. The possibility of creating reactions that produce only the necessary components has also emerged if microspace is used.

  However, none of the reactors that perform mixing and reaction in this microspace have left the laboratory area at present, and none can be used in the chemical production line. For example, there is no storage container installation space for manually storing the fluid used for operating each device, there is no collection container installation space for containing the reaction-terminated substance, and substances that can be recovered from the recovery port are required and unnecessary substances. There are many functions that have only the functions used at the laboratory level, such as no separation function, no safety measures, and no monitoring mechanism. Even if they are mixed in a micro space, the space for later reaction time is only to move the fluid through the tube piping with an inner diameter of 1 mm or more, and the reaction must be controlled uniformly. Was unsuitable.

  In recent years, a microreactor has been developed as a fluid reaction apparatus for reacting a liquid such as a reagent. When this microreactor is viewed from the standpoint of a liquid feeding system for flowing liquid, when the inner diameter of the flow path becomes small, the Reynolds number becomes small and the liquid flow becomes a laminar flow. In order to rapidly mix the liquid in the laminar flow region, it is effective to make the inner diameter of the flow path as small as possible. This is because in the laminar flow region, molecular diffusion becomes a rate-limiting factor, and the liquid diffusion time is proportional to the square of the width of the flow path.

  In addition, in a fluid reaction apparatus that reacts fluids in a minute space, there is still a need to study practical implementation of the microchannel structure as a central element for mixing in the apparatus. This includes the case where a micro space is pursued by making full use of production technology, and the formation of complicated flow paths by repeating processes such as film formation and etching, resulting in higher manufacturing costs and flow path cleaning. There are cases where disadvantages as a microreactor associated with the manufacturing process are improved, such as maintenance is not easy.

    Conventionally used organic synthesis reactors include colbens, beakers, test tubes and the like in research laboratories, and reaction pots of over several hundred liters in chemical production lines. In these reaction containers, for example, in a reaction with an explosion risk, a technique such as extremely reducing the mixing speed or extremely reducing the reaction temperature to minus is taken.

  Also, in the case of a reaction with a slow reaction time, the reaction has been progressed by passing through a capillary pipe having an inner diameter of about 1 to 5 mm. However, it takes time to conduct heat from the outer periphery of the pipe to the center, and the reaction intermediate. Since the diffusion time of the film becomes long, it is insufficient in terms of high selectivity and high yield.

  In recent years, there has been a movement to perform these organic synthesis reactions and biochemical reactions in a micro space of several tens to several hundreds of microns. By making the mixing part and the reaction part into a micro space, the ratio of the surface area to the volume of the fluid is increased, the mass transfer distance is shortened and the diffusion time is shortened, the volume of the fluid is reduced, the heat transfer, Since the transfer is quick and the substance is transferred efficiently, even the fast reaction can catch up with the substance supply, and even explosive reactions are possible at room temperature, and the reaction is high yield and high selectivity. Also became possible. The possibility of creating reactions that produce only the necessary components has also emerged if microspace is used.

    However, none of the reactors that perform mixing and reaction in this microspace have left the laboratory area at present, and none can be used in the chemical production line. For example, there is no storage container installation space for manually storing the fluid used for operating each device, there is no collection container installation space for containing the reaction-terminated substance, and substances that can be recovered from the recovery port are required and unnecessary substances. In many cases, there were no functions for separation, no safety measures, no monitoring mechanism, and so on. Even if they are mixed in a micro space, the space for later reaction time is only suitable for moving the fluid through the tube piping with an inner diameter of 1 mm or more and is not suitable for reactions where the temperature must be uniformly controlled. Met.

    In the laminar flow region, if there is a liquid concentration difference in the flow direction of the flow path, the liquid will be mixed non-uniformly. If the mixing of the liquid becomes uneven, the substance produced by the reaction further reacts with the stock solution to produce a by-product, resulting in a decrease in yield. Therefore, the flow rate of each liquid before mixing needs to be kept constant. However, since the liquid is usually transferred to the micro flow path by a gear pump, a piston pump, or the like, the liquid is influenced by the pump, and the pulsation is generated in the liquid flow. Therefore, an attempt has been made to introduce a mass flow controller in order to keep the flow rate of the liquid flowing through the microchannel constant.

  FIG. 39 is a schematic diagram showing a flow rate measuring unit of a general mass flow controller. As shown in FIG. 39, a temperature adjustment mechanism 3002 is provided in the flow path 3001, and an upstream first temperature sensor 3003 and a downstream second temperature sensor 3004 are disposed on the downstream side thereof. ing. The temperature adjustment mechanism 3002 is controlled by the temperature control unit 3005 and heats the liquid flowing through the flow path 3001 at a predetermined temperature change rate. The second temperature sensor 3004 is connected to the temperature difference measuring device 3006, and the temperature change at the position of the second temperature sensor 3004 is recorded in the temperature difference measuring device 3006.

  FIG. 40 is a graph showing the temperature distribution of the flow path. In FIG. 40, the position of the first temperature sensor 3003 is represented by P1, and the position of the second temperature sensor 3004 is represented by P2. Reference sign D1 represents the temperature distribution when the liquid is not flowing, and reference sign D2 represents the temperature distribution when the liquid is flowing. As shown in FIG. 40, when the liquid flows in the flow path 3001, the temperature curve indicating the temperature distribution shifts to the downstream side. For this reason, a temperature difference ΔT occurs at P2 between when the liquid is not flowing and when the liquid is flowing. Therefore, if the specific heat and specific gravity of the liquid are known in advance, the flow rate can be obtained from the temperature difference ΔT. Such a flow meter for obtaining a flow rate from a temperature difference is generally called a thermal flow meter.

  In a general mass flow controller, the flow rate adjustment valve is controlled by the output of the flow meter.

  In order to sufficiently react a liquid having a slow reaction rate in the micro channel, it is necessary to secure a reaction time by lengthening the channel. For this reason, it is necessary to pump the liquid at a high pressure. However, since the conventional mass flow controller has been developed based on the mechanism of a mass flow controller for gas, the upper limit of the allowable pressure is as low as 0.5 MPa or less, so that it can be used for a microreactor that requires high pressure. There were difficulties. In particular, when a micro flow path is used, the reaction product is expected to increase the pressure on the downstream side of the mass flow controller, and there is a possibility that accurate flow rate measurement may not be performed due to liquid leakage. Therefore, the flow rate adjusting device used in the microreactor is required to have a performance and high pressure response capable of performing accurate flow rate measurement even when the liquid pressure fluctuates.

  However, since the conventional thermal flow meter obtains the flow rate from the temperature difference, the measurement of the flow rate is affected by the specific heat and specific gravity of the liquid. For this reason, it is necessary to correct the flow rate in consideration of specific heat and specific gravity for each type of liquid. Further, in the conventional thermal flow meter, the temperature difference varies depending on the viscosity of the liquid in addition to the specific heat and specific gravity, so that the viscosity of the liquid also affects the flow rate measurement. The influence of the viscosity on the flow rate will be described with reference to FIG.

  FIG. 41 is a diagram showing the flow velocity distribution of the liquid flowing through the microchannel. In FIG. 41, symbol V1 represents a flow velocity distribution of a liquid having a low viscosity, and symbol V2 represents a flow velocity distribution of a liquid having a high viscosity. As shown in FIG. 41, the average flow velocities of the two liquids are equal to each other, but the shape of the flow velocity distribution is different due to the difference in viscosity. That is, even if the flow rate (average flow rate) is the same between the case of a liquid having a high viscosity and the case of a liquid having a low viscosity, a difference occurs in the flow rate in the vicinity of the inner surface of the flow path 3001. A difference occurs in the temperature measured by the temperature sensor 3007 provided on the outer surface. Therefore, in order to accurately measure the flow rate, it is necessary to check the viscosity of the liquid in advance and correct the flow rate based on the viscosity. As described above, in the conventional thermal flow meter, it is necessary to correct the flow rate based on the physical properties of the liquid, such as the specific heat, specific gravity, and viscosity of the liquid. Was necessary.

  Thus, it can be seen that there is a problem that the flowmeter is not chemical-free in the conventional mass flow controller of the liquid feeding system.

  In a fluid reaction device that reacts fluids in a minute space, for example, in order to discharge a chemical solution continuously at a constant flow rate, a plunger pump device or a motor-type pump device can be used as described above.

  Although it is preferable that the pump itself has low pulsation, the plunger pump, for example, forms a pump chamber by partitioning the space in the cylinder, and the pump chamber is provided with a suction pipe and a discharge pipe via a suction valve and a discharge valve, respectively. The partition plate is connected and reciprocated by a predetermined driving means. During suction, the suction valve is opened and the discharge valve is closed, and the partition plate is moved in the direction of expansion of the pump chamber. During discharge, the suction valve is closed, the discharge valve is opened, and the partition plate is contracted by the pump chamber. Move in the direction you want. With one plunger pump, intermittent operation is performed as shown in FIG.

  Therefore, when continuous operation is required, one in which two plunger pumps are installed in parallel is used. In this apparatus, as shown in FIG. 105 (b), the switching of discharge is simply switched at a cycle of 180 degrees. However, in such a conventional double plunger pump, discharge is temporarily interrupted during switching, and pulsation occurs. In order to make up for this drawback, there is one that attaches a motor to each plunger and performs coordinated control, but the whole becomes large and the system becomes complicated. There is also a triple system that suppresses pulsation, but the size of the main body becomes large.

  For example, in a conventional double plunger pump, a groove cam is used as a drive transmission means. However, it is difficult to process and accuracy is difficult, and it is necessary to reduce backlash when switching between forward and reverse. There are some disadvantages. On the other hand, since an open cam such as an end face cam can only move in one direction, it is necessary to use a spring that biases the plunger toward the cam. However, in this case, when the plunger is pushed out, the spring needs to have a resistance against the urging force, so that the motor load is increased.

  Further, in the plunger pump, when switching between suction and discharge, the flow state and the operation of the valve body are likely to be unstable, and as a result, pulsation may occur.

  In this way, even when looking at the pump in the plan, there is still a need for further improvement in sending the liquid so that pressure pulsation does not occur.

  From the standpoint of quality assurance in which a reaction occurs in a microreactor and produces a predetermined reactant, when using a microreactor device that reacts in a continuous flow field in a pharmaceutical production line, quality control based on the idea of GMP and FDA Is required. The basic idea of GMP is to guarantee quality reproducibility, and the quality must be uniform within a lot. In conventional batch processing, the quality in the reaction kettle should have been uniform, but in a continuous flow microreactor, it remains uniform regardless of the point of liquid flowing out by reacting from moment to moment. It has become necessary. Uniform state means that the product produced by the reaction is of course required to be uniform with no change over time, such as by-products, unreacted raw materials, other impurities, and components eluted from the piping. Is done. In addition, instead of sampling and collecting the liquid offline, a means for analyzing in real time multiple components of the liquid in the main pipe through which the liquid flows is required. Furthermore, the US FDA has proposed PAT (Process Analytical Technology) as a way of analysis for each process, promoting the construction of a pharmaceutical production line based on that, and discussing the necessity of in-line analysis for each process.

  In order to analyze a multi-component in these liquids in-line in real time, it is necessary to have a wide wavelength region to be measured and to be able to cope with a wide variety of molecular structures of the object to be measured. In addition, because there are areas that are good and weak in the ultraviolet, infrared, and far infrared areas, combining each of these wavelength areas can supplement each other's weak areas, and the substance to be measured This is effective when there is a wide variety of molecular structures.

  In the development stage of pharmaceuticals, there is an operation of finding a reaction that may be called so-called screening by changing various conditions such as the type, concentration, temperature, and flow rate of the reagent. In order to optimize the synthesis route even after candidate drugs have been narrowed down, the same reaction must be repeated under the same conditions with the same reagent, and each time it must be analyzed and evaluated offline. Even in this case, if there is an inline multi-type analyzer, it is not necessary to sample and collect each time, and the analysis result can be output in a very short time.

  The present invention has been made in view of the above circumstances, and by utilizing the characteristics of the reaction in the micro space, a plurality of fluids can be mixed, various chemical reaction operations can be performed efficiently, and at low cost. An object of the present invention is to provide a fluid reaction apparatus that can be manufactured, is easy to maintain, and is suitable as a practical mass production means.

  As one object for realizing a microreactor required in the present invention, a flow rate adjusting device capable of accurately measuring and adjusting the flow rate of a fluid without depending on the specific gravity, specific heat, viscosity, and pressure fluctuation of the fluid. Is provided.

  Another object of the present invention is to provide a liquid feeding device capable of continuous operation with pulsation suppressed in a fluid reaction device that reacts fluids in a minute space.

  Furthermore, a microreactor channel structure is specifically provided for realizing mixing and reaction with high yield and selectivity.

  Another object of the present invention is to provide an analysis system that can output an analysis result in a short time without requiring screening by offline analysis.

  Another object of the present invention is to provide an overall configuration of a convenient microreactor device.

  The present invention includes, but is not limited to, the following inventions.

  (1) In a fluid reaction device that introduces and reacts a plurality of fluids into a reaction channel having a micro reaction space, an introduction unit that individually introduces fluids used for the reaction, and a mixing channel that joins and mixes the fluids Fluid transport means for transporting fluid toward the mixing flow path via a plurality of transport pipes, flow control means for controlling the flow rate of the fluid, temperature control means for controlling the temperature of the reaction flow path, A fluid reaction apparatus comprising: a deriving unit for deriving a substance after reaction from a recovery port; and an operation control means for controlling these operations.

  (2) A fluid reaction apparatus further comprising a flat mixed substrate, wherein the mixing flow path for combining the fluids to mix is provided in the flat mixed substrate, (1) The fluid reaction apparatus as described.

  (3) The fluid reaction apparatus according to (2), wherein an installation space for installing a storage container for individually storing fluids used for the reaction is provided.

  (4) The fluid reaction apparatus according to (2) or (3), wherein an installation space is provided in which a plurality of collection containers for collecting the substance after reaction from the lead-out part can be installed.

  (5) The fluid reaction apparatus according to any one of (2) to (4), wherein a channel having a channel width of 500 μm or less exists in the micro reaction space.

  (6) The introduced fluid is a gas or a liquid, and the substance after the reaction is either a gas, a liquid or a solid, or a mixture thereof, and the introduced fluid is a continuous flow. The fluid reaction device according to any one of (2) to (5).

  (7) The fluid reaction apparatus according to any one of (2) to (6), wherein the fluid transport means includes pressure generation means or electrical dielectric force interaction means.

  (8) The fluid transporting means is a plunger pump device in which a pair of plunger pumps are connected in parallel, and a cam mechanism that interlocks the plungers of the plunger pumps so as to alternately advance, and the plungers A plunger pump device comprising: a fluid pressure device that presses toward the cam mechanism when retreating; and a control unit that controls an operation of the fluid pressure device according to an operation cycle of the plunger. The fluid reaction device according to any one of 2) to (7).

  (9) The fluid reaction device according to (8), wherein the control unit of the plunger pump device stops pressing by the fluid pressure device when each plunger moves forward.

  (10) The pair of plunger pumps respectively perform a speed increasing process and a speed reducing process at the initial stage and the final stage of the discharge operation, and the timing is set so that one speed increasing process and the other speed reducing process overlap each other. The fluid reaction device according to (8), characterized in that

  (11) The fluid reaction device according to (8), wherein each of the plunger pumps performs a certain stop process between forward movement and backward movement.

  (12) The fluid transporting means is a plunger pump device, each having a separate driving device, and a pair of plunger pumps connected in parallel between the liquid source and the microreactor channel, and in the microreactor channel A control unit that alternately discharges the installed flow meter and the pair of plunger pumps at a constant predetermined feed rate, and the control unit measures the flow meter when the plunger pump is discharging. The fluid reaction device according to any one of (2) to (7), which is a plunger pump device that adjusts the feed speed at a predetermined timing based on a value.

  (13) The plunger pump device includes a pressure sensor installed in the microreactor flow path, and the control unit finely adjusts the feed rate based on an output value of the pressure sensor. (12) The fluid reaction apparatus according to (12).

  (14) The control unit of the plunger pump device performs a speed increasing process and a speed reducing process for each of the pair of plunger pumps at an initial stage and a final stage of the discharge operation, and one speed increasing process and the other speed reducing process are mutually The fluid reaction apparatus according to (12) or (13), wherein the flow control is performed while maintaining a constant flow rate so as to overlap.

  (15) The fluid reaction device according to (14), wherein the feed speed is finely adjusted only for one plunger pump during the switching control.

  (16) The control unit of the plunger pump device controls the plunger pump to perform a certain stopping process between forward and backward movements, according to any one of (12) to (15), Fluid reaction device.

  (17) The plunger pump device includes a position sensor that detects a position of a plunger of the plunger pump, and the control unit controls a feed rate based on an output of the position sensor. The fluid reaction device according to any one of to (16).

  (18) The flow rate control means includes a sensor unit that measures the volume of the fluid passing therethrough, and a passage amount control unit that controls a passage area through which the fluid passes based on measurement information of the sensor unit. (2) The fluid reaction device according to any one of (17).

  (19) The flow rate control device is a flow rate adjustment device that adjusts the flow rate of the fluid flowing through the flow path, and a temperature control mechanism that heats or cools the fluid flowing through the flow path, and a first measurement of the flow path The flow rate of the fluid flowing in the flow path is calculated from the time difference between the time when the fluid temperature at the point changes and the time when the fluid temperature changes at the second measurement point downstream of the first measurement point. Flow rate measuring unit, a downstream temperature sensor for measuring the temperature of the fluid passing through the second measurement point, a control valve provided on the downstream side of the downstream temperature sensor, and the flow rate measuring unit. A flow rate adjusting device comprising: a control unit that controls the control valve so that the flow rate of the fluid becomes constant based on the flow rate of the flow rate, wherein the flow rate adjustment device is any one of (2) to (18). Fluid reaction device.

  (20) The flow rate measuring unit of the flow rate adjusting device is configured to change a fluid based on a time difference between two corresponding points on a temperature curve indicating a temperature change of the fluid at the first measurement point and the second measurement point. The fluid reaction device according to (19), characterized in that the flow rate of is calculated.

  (21) The fluid reaction device according to (19) or (20), further comprising an upstream temperature sensor for measuring the temperature of the fluid passing through the first measurement point.

  (22) The upstream temperature sensor of the flow rate adjusting device includes a sensor holder that contacts a fluid flowing through the flow path, and a thermistor inserted into the sensor holder to a position close to the flow path. The fluid reaction device according to (21), characterized in that

  (23) The downstream temperature sensor of the flow rate adjusting device includes a sensor holder that contacts a fluid flowing through the flow path, and a thermistor inserted into the sensor holder to a position close to the flow path. The fluid reaction device according to any one of (19) to (22), characterized in that it is characterized.

  (24) Any one of (19) to (23), further comprising an environmental temperature control mechanism that keeps the temperature of a space including at least the first measurement point and the second measurement point constant. The fluid reaction device according to claim 1.

  (25) The temperature control mechanism of the flow rate adjusting device includes a Peltier element, a Seebeck element, an electromagnetic wave generator, or a resistance heating wire, according to any one of (19) to (24). Fluid reaction device.

  (26) The temperature adjustment mechanism of the flow rate adjusting device includes a structure having a cylindrical part in which holes forming the flow path are formed, a heat transfer part that transfers heat to the cylindrical part, and transmission of the structure. The fluid reaction device according to any one of (19) to (25), further comprising: a temperature adjustment member that heats or cools the heat section.

  (27) The control valve of the flow rate adjusting device includes a valve for adjusting the flow rate and a drive source for driving the valve, and the drive source is a piezoelectric element, an electromagnet, a servo motor, or a stepping motor. (19) The fluid reaction device according to any one of (19) to (26).

  (28) The control valve of the flow rate adjusting device includes a valve for adjusting the flow rate and a drive source for driving the valve, and the drive source has a structure in which a plurality of piezoelectric elements are stacked. (19) The fluid reaction device according to any one of (19) to (27).

  (29) The fluid reaction device according to any one of (19) to (28), wherein the pressure of the fluid passing through the control valve is 1 MPa to 10 MPa.

  (30) The fluid reaction device according to any one of (19) to (29), wherein a flow rate of the fluid passing through the control valve is 0.01 to 10 L / h.

  (31) The fluid reaction device according to any one of (19) to (30), wherein the flow path of the flow rate adjusting device is formed of a corrosion-resistant material.

  (32) The material of the flow control device is stainless steel, titanium, polyether ether ketone, polytetrafluoroethylene, or polychlorotrifluoroethylene, (19) to (31) The fluid reaction device according to any one of the above.

  (33) The flow rate control means is arranged at a temperature adjustment mechanism for adjusting the temperature of the fluid flowing through the flow path for a short time at a predetermined temperature adjustment position, and at a temperature measurement position downstream of the temperature adjustment position of the flow path. A flow rate measuring device including at least one main temperature sensor, wherein the flow of temperature-controlled fluid is determined based on a temperature change at a temperature measurement position observed by the main temperature sensor, and based on the determination result In the flow rate measuring device for calculating the flow rate, a sub temperature sensor is installed at a position upstream of the temperature control position of the flow path, and the temperature measurement value of the main temperature sensor is corrected by the measurement value of the sub temperature sensor. The fluid reaction device according to any one of (2) to (18), wherein the fluid reaction device is characterized by the following.

  (34) The fluid reaction device according to (33), wherein the correction of the flow rate measuring device is performed by obtaining a difference between a measurement value of the main temperature sensor and a measurement value of the sub temperature sensor. .

  (35) The at least two main temperature sensors are provided at different temperature measurement positions, and the flow rate is calculated based on a time difference between passages at these temperature measurement positions. (33) or (34) Fluid reaction device.

  (36) The fluid according to (33) or (34), wherein the flow rate is calculated based on a time difference between when the temperature adjustment mechanism performs temperature adjustment and when passing through the temperature measurement position. Reactor.

  (37) The fluid reaction device according to any one of (33) to (36), wherein the time point when the temperature measurement value after the correction reaches the extreme value is determined as the passage of the temperature-controlled fluid.

  (38) The sub-temperature sensor of the flow rate measuring device is at a position substantially symmetrical to the temperature measurement position with respect to the temperature adjustment position, according to any one of (33) to (37), Fluid reaction device.

  (39) The fluid reaction device according to any one of (33) to (38), wherein the position of the sub temperature sensor is adjustable along the flow path.

  (40) The fluid reaction device according to any one of (33) to (39), wherein the measured value of the main temperature sensor or the sub temperature sensor is converted from analog to digital, and taken into a digital circuit for processing. .

  (41) The temperature control mechanism of the flow rate measuring device includes a Peltier element, a Seebeck element, an electromagnetic wave generator, a resistance heating wire, a thermistor, or a platinum resistor, (33) to (40) The fluid reaction device according to any one of the above.

  (42) The fluid reaction apparatus according to any one of (2) to (41), wherein a plurality of the mixed substrates are provided.

  (43) In any one of (2) to (42), the reaction channel is formed on a reaction substrate provided separately from the mixed substrate in order to advance the reaction of the fluid after mixing. Fluid reaction device.

  (44) The fluid reaction apparatus according to (43), wherein a plurality of the reaction substrates are provided.

  (45) A first flow path selection switching valve is provided between the fluid transporting means and the mixing substrate, and a second flow path selection switching valve is provided between the mixing substrate and the substance recovery port. The fluid reaction device according to any one of (2) to (44), wherein

  (46) The fluid reaction device according to (45), wherein the first flow path selection switching valve and the second flow path selection switching valve are automatic valves that are operated by an electric operation or a pneumatic operation.

  (47) After the fluid introduced into the mixing channel is mixed, a filling detection means for judging that the fluid is filled in the mixing channel or / and the reaction channel is provided. It is possible to control to stop the transportation means or switch the flow path selection switching valve so that the fluid stays in the mixing flow path and / or the reaction flow path for a certain time to adapt to the reaction end time (2) -The fluid reaction device according to any one of (46).

  (48) The fullness detection means is a fluid presence / absence sensor that detects a fluid that has started to exit from the substance recovery port, or a fluid presence / absence sensor that detects the presence / absence of fluid in the transport pipe after the mixing reaction ( 47).

  (49) Any one of (2) to (48), wherein the mixing channel and the reaction channel are individually provided with temperature measuring sensors, and the temperature can be individually controlled. A fluid reaction device according to claim 1.

  (50) The fluid reaction apparatus according to any one of (2) to (49), wherein at least a part of the mixed substrate and the reaction substrate are stacked.

  (51) (2) to (2) characterized by comprising backwashing means for switching the flow path selection switching valve to feed the fluid in the direction opposite to the normal flow direction in the mixing flow path and the reaction flow path. 50) The fluid reaction apparatus according to any one of the above.

  (52) The fluid reaction apparatus according to (51), wherein the backwashing means has a single piston pump as a pressure feeding means.

  (53) The first flow path selection switching valve includes one or more of a nitrogen gas supply line, a pure water supply line, an organic solvent supply line, an acid supply line, a hydrogen water supply line, and an ozone water supply line. It is connected, The fluid reaction apparatus in any one of (45)-(52) characterized by the above-mentioned.

  (54) The second flow path selection switching valve includes one or more of a nitrogen gas supply line, a pure water supply line, an organic solvent supply line, an acid supply line, a hydrogen water supply line, and an ozone water supply line. It is connected, The fluid reaction apparatus in any one of (45)-(53) characterized by the above-mentioned.

  (55) The installation space of the lead-out portion is provided with a table capable of holding two or more recovery containers and a table moving mechanism, according to any one of (4) to (54), Fluid reaction device.

  (56) The fluid reaction device according to (55), wherein the table moving mechanism is a rotating mechanism or a reciprocating mechanism.

  (57) The fluid reaction apparatus according to any one of (2) to (56), wherein yield measuring means for measuring the yield of the substance after the reaction is provided.

  (58) The fluid reaction apparatus according to (57), wherein the yield measuring means is ultraviolet absorption, infrared spectroscopy, or near infrared spectroscopy.

(59) The yield measuring means includes a light source unit having a plurality of light sources having different wavelengths, a casing constituting a flow cell for circulating the liquid to be measured, a plurality of light emitting units adjacent to the liquid to be measured and light reception in the flow cell. And a spectroscopic unit having a spectroscope that individually performs spectroscopy of each wavelength obtained from the light receiving unit, and a control unit that arithmetically controls and outputs spectroscopic information of the liquid to be measured obtained by the spectroscope The fluid reaction device according to (57), wherein the fluid reaction device is a multispectral analyzer.

  (60) The light source unit of the multispectral analyzer has a light source that covers at least two wavelength regions of ultraviolet light, visible light, near infrared light, infrared light, and far infrared light. The fluid reaction device according to (59), characterized in that

  (61) The fluid reaction device according to (59) or (60), wherein a plurality of the flow cells of the multispectral analyzer are formed, and a light emitting portion and a light receiving portion are respectively arranged in each flow cell.

  (62) The fluid reaction apparatus according to any one of (59) to (61), wherein the casing of the multispectral analyzer is configured to form a plurality of flow cells therein by a partition. .

  (63) The casing of the multispectral analyzer is configured to form one flow cell therein, and a plurality of the casings can be detachably mounted on a substrate (59). ) To (62).

  (64) The fluid reaction device according to any one of (59) to (63), wherein the light source in the visible region to the near-infrared region is shared by one light source and guided to different light receiving units. .

  (65) The fluid reaction device according to any one of (59) to (64), wherein a distance between the light emitting unit and the light receiving unit is adjustable.

  (66) The fluid reaction device according to any one of (59) to (65), further comprising a spectroscopic analysis device on the downstream side of the reaction region.

  (67) A fluid mixing device used in a fluid reaction device for reacting a plurality of fluids in a flow path including a micro reaction space, wherein a plurality of flat base materials are joined, and the plurality of fluids are separated from respective header spaces. A plurality of liquid separation flows configured to be continuously supplied to and mixed with the merge space, the header spaces of the fluids provided on different surfaces of the base material, and the header spaces and the merge space to communicate with each other. A fluid mixing apparatus characterized in that the channel is formed such that liquid separation channels from different header spaces open alternately at the inflow portion of the merge space.

  (68) The fluid mixing according to (67), wherein each of the header spaces is formed in a concentric arc shape on the different surfaces, and the merging space is disposed substantially on the center of these arcs. apparatus.

  (69) The header spaces are formed on the front and back surfaces of the base material, the merge space is formed on one surface of the base material, and the liquid separation flow path communicating with the header space on the other surface is the base. The fluid mixing device according to (67) or (68), wherein the fluid mixing device is provided so as to penetrate the material.

  (70) The fluid mixing device according to (67) or (69), wherein the plurality of liquid separation channels communicating the header spaces and the merge space are formed to extend in parallel to each other. .

  (71) A fluid mixing device used in a fluid reaction device for reacting a plurality of fluids in a flow path including a micro reaction space, wherein a plurality of flat base materials are joined, and the plurality of fluids are separated from respective header spaces. The header space is provided along the surface of the base material, and the joint space is provided so that the fluid flows in the plate thickness direction of the base material. A plurality of liquid separation channels that communicate between the header space and the merge space are formed such that the liquid separation channels from different header spaces are alternately opened at the inflow portion of the merge space. Mixing device.

  (72) The header space is provided on both sides of the merge space on the surface of the base material, and the liquid separation channels from different header spaces are opened at positions shifted from each other in the inflow portion of the merge space. (71) The fluid mixing device according to (71).

  (73) The header spaces of the respective fluids are provided on different surfaces of the base material, at least one of the separation flow paths is provided through the base material, and the separation flow paths from different header spaces are joined to each other. The fluid mixing device according to (71), wherein the fluid mixing devices are formed so as to face each other on opposite sides of the space and alternately adjacent to each other on the same side of the merging space.

  (74) The confluence space is formed to be bent so that the fluid flows along the surface of the base material after the fluid flows in the plate thickness direction of the base material (71) to ( 73) The fluid mixing apparatus according to any one of 73).

  (75) having a mixing channel that continuously supplies and mixes a plurality of fluids into a space including a channel width portion of 500 μm or less formed on a flat substrate, and from the confluence of the plurality of fluids A fluid mixing apparatus, wherein columnar obstacles having a diameter of 50 μm or less are arranged at equal intervals over a length of 5 mm or more along the flow.

  (76) The fluid mixing apparatus according to (75), wherein the columnar obstacle includes a plurality of columns of columns arranged alternately in the flow direction at different intervals.

  (77) The fluid mixing apparatus according to (75) or (76), wherein a plurality of the columnar obstacles are arranged in a staggered manner in the flow direction.

  (78) The fluid mixing device according to any one of (67) to (77), which has a portion where the width of the channel gradually decreases and a portion where the width gradually increases after the merge.

  (79) The fluid mixing device according to any one of (67) to (78), wherein the width dimension and the depth dimension of the flow path are alternately reduced and enlarged after joining.

  (80) The fluid mixing device according to any one of (67) to (79), wherein the fluid mixing device has a flat portion whose width direction dimension is larger than the depth direction dimension after joining.

  (81) The members forming the flow path are hard glass such as SUS316, SUS304, Ti, quartz glass, Pyrex glass (registered trademark), PEEK (polyetheretherketone), PE (polyethylene), PVC (polyvinylchloride), PDMS (polydimethylsiloxane) The fluid mixing according to any one of (67) to (80), characterized in that it comprises one or more of Si, PTFE (polytetrafluoroethylene), PCTFE (polychlorotrifluoroethylene), and PFA (perfluoroalkoxylalkane) apparatus.

  (82) The material of a part or all of the inner wall of the flow path is Au, Ag, Pt, Pd, Ni, Cu, Ru, Zr, Ta, Nb or a compound containing these metals ( 67) to (80).

  (83) The fluid mixing apparatus according to any one of (67) to (82), wherein the base material is a rectangle having a size of at least one side exceeding 150 mm.

  (84) The fluid mixing apparatus according to any one of (67) to (83), wherein the plurality of fluid inlets and the outlet of the single fluid after mixing are present on the opposite surface of the substrate.

  (85) In any one of (67) to (84), a mixed reaction substrate is provided in the same substrate, and a preliminary temperature adjusting unit that raises or lowers the temperature of the fluid toward the reaction temperature is provided. Fluid mixing device.

  (86) A manifold portion in which a plurality of first flow paths communicating with the first fluid source and a plurality of second flow paths communicating with the second fluid source are respectively formed in the mixing flow path; A manifold space adjacent to the manifold portion, the manifold portion having an open end surface facing the merge space, and the openings of the first flow channel and the second flow channel are the open end surfaces. The fluid reaction device according to (1), wherein the fluid reaction device is arranged three-dimensionally so as to be alternately adjacent to each other.

  (87) The manifold portion is configured by laminating plate-like elements in which grooves constituting the first flow path and the second flow path are alternately formed, so that the first flow path is formed on the opening end surface. The fluid reaction device according to (85), wherein the second flow paths are arranged in a staggered manner.

  (88) The fluid reaction device according to (86) or (87), wherein a maximum width dimension in a section of the opening of the first flow path and the second flow path is 3000 μm or less.

  (89) A mixing promoting object for bypassing the flow mixing from the first flow path and the second flow path is provided in the merge space or the downstream side thereof (86) to (88) The fluid reaction device according to any one of the above.

  (90) The fluid reaction apparatus according to (89), wherein a substance having a catalytic action is provided on a surface of the mixing promoting object.

  (91) A representative dimension of the mixing promoting object is in a range of 0.1 to 10 times a minimum width dimension of individual flows from the first flow path and the second flow path immediately before the mixing promoting object. The fluid reaction device according to (89) or (90), characterized in that it exists.

  (92) The fluid reaction device according to any one of (86) to (91), wherein a throttle portion or a fluid lens in which a flow path cross section gradually decreases is provided downstream of the merge space. .

  (93) The minimum width of the virtual cross section of each flow from the first flow path and the second flow path is 500 μm or less in the downstream portion of the throttle portion or the fluid lens. (92) The fluid reactor.

  (94) The fluid reaction device according to (92) or (93), wherein the opening end surface and the throttle portion or the fluid lens have substantially similar flow path cross sections.

  (95) The fluid reaction device according to any one of (86) to (94), wherein a plurality of the manifold portions are arranged so that respective opening end faces are opposed to each other in the merge space.

  (96) A heat exchanger that heats or cools the fluid flowing in the first flow path, the second flow path, the merge space and / or the downstream side thereof is provided (86) to (95) The fluid reaction device according to any one of the above.

  (97) The heat exchanger is configured by laminating plate-like elements in which grooves constituting the heated fluid channel and / or the heat medium channel are stacked (96) The fluid reaction apparatus according to 1.

  (98) The heated fluid flow path of the heat exchanger that heats or cools the fluid flowing downstream of the merge space is a delay loop for adjusting the synthesis reaction time, and heat exchange is performed by changing the delay loop pattern or the number of stacked layers. The fluid reaction device according to (96) or (97), wherein the residence time in the inside is adjustable.

  (99) The fluid reaction apparatus according to any one of (96) to (98), wherein a fluid that does not contaminate the heated fluid even if mixed in the heated fluid is used as the heat medium of the heat exchanger. .

  (100) The fluid reaction device according to any one of (2) to (66), wherein the fluid mixing device according to any one of (67) to (85) is used as the mixing substrate.

  (101) The peripheral members forming the flow path of the reaction substrate are hard glass such as SUS316, SUS304, Ti, quartz glass, Pyrex glass (registered trademark), PEEK, PE, PVC, PDMS, Si, PTFE, PCTFE The fluid reaction apparatus according to any one of (2) to (66) and (100), wherein the fluid reaction apparatus includes one or more of the following.

  (102) A part or all of the material of the inner wall of the flow path of the reaction substrate contains one or more of Au, Ag, Pt, Pd, Ni, Cu, Ru, Zr, Ta, and Nb or a metal thereof. The fluid reaction device according to any one of (2) to (66), (100), and (101), which is a compound.

  (103) The mixed substrate and / or the reaction substrate are accommodated in a temperature adjustment case having a heat medium flow path. (2) to (66) and (100) to (102) The fluid reaction device according to any one of the above.

  (104) The fluid reaction apparatus according to (103), characterized in that a temperature measuring means is provided in the heat medium fluid flow path.

  (105) The fluid reaction device according to (102) or (103), wherein the heat medium flow path has a plurality of branch flow paths along front and back surfaces of the mixed substrate and / or reaction substrate.

  (106) The temperature adjustment case has a case main body and a lid, and the heat medium flow path is formed so as to communicate with them, (103) to (105), Fluid reaction device.

  (107) A plurality of throttle holes provided in the first header of the case body into which the thermal fluid flows are directly connected to the second header of the lid, and the second header includes the mixed substrate and / or reaction. (2) The fluid reaction apparatus as set forth in (106), characterized in that a second restriction hole is provided that is directly connected to a plurality of branch flow paths that form a flow parallel to the front and back surfaces of the substrate.

  (108) The fluid reaction device according to any one of (48) to (107), wherein a material of the temperature adjustment case is any one of Ti, Al, SUS304, and SUS316.

  (109) The temperature control means includes a temperature adjustment medium holding mechanism that surrounds the mixed substrate or the reaction substrate and adjusts the temperature of the mixed fluid, a temperature adjustment medium held by the holding mechanism, a temperature measurement sensor, and a temperature adjustment medium. The fluid reaction apparatus according to any one of (2) to (66) and (100) to (108), further comprising a heat transfer amount adjusting unit that adjusts a heat transfer amount between the liquid and the mixed reaction fluid.

  (110) The fluid reaction apparatus according to (109), wherein any one or more of silicon oil, fluorine oil, alcohol, liquid nitrogen, electric resistance heating wire, and Peltier element is used as the temperature adjusting medium.

  (111) The fluid reaction apparatus according to (109) or (110), wherein the heat transfer amount adjusting means is any one of a pump flow rate adjustment, a flow rate adjustment valve, and an electric quantity.

  (112) The fluid reaction device according to any one of (109) to (111), wherein the temperature adjusting medium holding mechanism is covered with a heat insulating member.

  (113) The fluid reaction apparatus according to (112), wherein the heat insulating member is silicon rubber.

  (114) The fluid according to any one of (2) to (66) and (100) to (113), characterized by comprising separation and extraction means for separating a necessary substance and an unnecessary substance in a substance after reaction. Reactor.

  (115) The fluid reaction apparatus according to any one of (2) to (66) and (100) to (114), comprising a powder dissolver for liquefying and dissolving a powder raw material.

  (116) (2) to (66) and (100) to (115) are characterized in that a part or the entire region of the fluid reaction device is isolated from the outside of the device and is set to a negative pressure from the pressure outside the device. The fluid reaction device according to any one of the above.

  (117) (2) to (66), (100) to (100) including a liquid storage pan for storing a liquid leaked at a lower portion of the fluid reaction device and a liquid leakage sensor for detecting the leaked liquid. 116) The fluid reaction device according to any one of

  (118) In any one of (2) to (66) and (100) to (117), the operation control means includes a display mechanism for displaying a flow rate of the fluid and a reaction temperature. The fluid reaction apparatus as described.

  According to the present invention, there is provided a fluid reaction apparatus suitable for practical use as a mass production means capable of mixing a plurality of fluids using a micro space and efficiently performing various chemical reaction operations. Can do.

  ADVANTAGE OF THE INVENTION According to this invention, the mixing apparatus which has a mixing flow path which makes a fine flow path alternately adjoin and flows into a merge space is easily manufactured by simple structure.

  According to the present invention, by disposing and arranging fine columnar obstacles along the flow from the confluence of the fluid in the mixing channel, the mixing device using the micro channel can be easily configured with a simple configuration. Manufactured.

  According to the present invention, an automated operation indispensable for a mass production apparatus is possible. In addition, it is possible to provide safety measures indispensable for the chemical production line.

  According to the present invention, the ratio of the interface between fluids can be improved, efficient mixing and reaction can be performed, and the structure can be easily manufactured at low cost, and maintenance is easy. A microreactor can be provided.

  According to the present invention, it is possible to provide a flow rate measuring device that measures an accurate flow rate without being affected by physical properties such as specific gravity, specific heat, and viscosity of a fluid, and a flow rate adjustment device that can maintain a desired flow rate. Can do.

ADVANTAGE OF THE INVENTION According to this invention, the liquid feeding apparatus which can perform the continuous operation which suppressed the pulsation can be provided.
According to the present invention, it is possible to obtain analysis results in a short time without the need for screening by off-line analysis.

It is a figure which shows the whole liquid flow of the fluid reaction apparatus of embodiment of this invention. It is a perspective view which shows the structure of the whole fluid reaction apparatus of FIG. It is (a) top view and (b) front view which show the whole structure of the fluid reaction apparatus of FIG. It is a figure which shows the structure of the supply part for raw materials. It is a figure which shows a mass flow controller. It is a figure which shows other embodiment of a massflow controller. It is (a) top view and (b) sectional view showing composition of a mixed substrate. It is a figure which expands and shows the mixing part of a mixing board | substrate. It is (a) top view and (b) sectional view showing composition of a reaction substrate. The other structure of a reaction substrate is shown, (a) is a longitudinal cross-sectional view along a flow path, (b) is a bb arrow line view in (a), (c) is still another structure. It is a cross-sectional view shown. It is a perspective view which shows the structure of a process block. 1 shows a structure in which processing blocks are overlaid, (a) a plan sectional view of a temperature adjustment case, (b) a side sectional view, (c) a diagram showing an enlarged main part of (a), (d) It is a figure which expands and shows the principal part of (b). It is a figure which shows the structure of the production | generation fluid storage part of other embodiment. (A) And (b) is a figure which shows the other structure of the mixing part. (A) thru | or (c) is a figure which shows the further another structure of a mixing part. (A) And (b) is a figure which shows the further another structure of a mixing part. (A) thru | or (c) is a figure which shows the further another structure of a mixing part. (A) And (b) is a figure which shows the further another structure of a mixing part. (A) Top view which shows the other structure of a mixing channel, (b) It is a figure which expands and shows the principal part of (a). It is a top view which shows other structure of a mixing flow path. It is a flowchart of the process part in other embodiment of this invention. It is a flowchart of the process part in further another embodiment of this invention. It is a flowchart of the process part in further another embodiment of this invention. It is a flowchart of the process part in further another embodiment of this invention. It is a perspective view which shows the structure of the process part of embodiment of FIG. It is a perspective view which shows the structure of the raw material storage part of other embodiment of this invention. It is a figure which shows the whole structure of the compound manufacturing system using the microreactor of embodiment of this invention. It is a top view which shows the structure of a mixing and reaction part. (A) Front view of first heat exchange element constituting preheating block, (b) Front view of first heat exchange element and second heat exchange element overlapping, (c) First heat It is sectional drawing of an exchange element. It is a figure which shows the flow of the raw material solution in a preheating block. It is a figure which shows the flow of the heat medium in a preheating block. It is a top view which shows the structure of a mixing block. It is a perspective view which decomposes | disassembles and shows the structure of a manifold. It is a figure which shows a manifold and merge space typically. (A) It is sectional drawing which shows the cover plate of the exit side of a reaction block, (b) Similarly front view, (c) The front view which shows the cover plate of the inlet side, (d) It is sectional drawing. (A) Front view of first heat exchange element constituting reaction block, (b) Front view of first heat exchange element and second heat exchange element overlapping, (c) First heat It is sectional drawing of an exchange element. It is a figure which shows typically the manifold and merge space of other embodiment of this invention. It is a figure which shows typically the manifold and merge space of other embodiment of this invention. It is a figure which shows typically the manifold and merge space of other embodiment of this invention. It is a figure which shows typically the manifold and merge space of other embodiment of this invention. It is a figure which shows typically the manifold and merge space of other embodiment of this invention. It is a figure which shows typically the manifold and merge space of other embodiment of this invention. It is a figure which shows typically the manifold and merge space of other embodiment of this invention. It is a figure which shows typically the manifold and merge space of other embodiment of this invention. It is a schematic diagram which shows the flow volume measurement part of a general mass flow controller. It is a graph which shows the temperature distribution of a flow path. It is a figure which shows the flow-velocity distribution of the fluid which flows through a microchannel. It is a figure for demonstrating the principle by which the flow volume of a fluid is measured. It is a schematic diagram which shows the flow volume adjustment apparatus which concerns on the 1st Embodiment of this invention. FIG. 44 is a cross-sectional view showing another configuration example of the temperature adjustment mechanism and the upstream temperature sensor shown in FIG. 43. 45 (a) is a cross-sectional view taken along the line VII-VII in FIG. 44, and FIG. 45 (b) is a cross-sectional view showing another configuration example of the structure shown in FIG. 45 (a). 44 is an enlarged view showing another configuration example of the control valve shown in FIG. 43. FIG. It is a schematic diagram which shows the flow volume adjustment apparatus which concerns on the 2nd Embodiment of this invention. It is a schematic diagram which shows the flow volume adjustment apparatus which concerns on the 3rd Embodiment of this invention. It is a figure for demonstrating the principle by which the flow volume of a fluid is measured. FIG. 49 is a perspective view of the spool shown in FIG. 48. It is a schematic diagram which shows the flow volume adjustment apparatus which concerns on the 4th Embodiment of this invention. It is a schematic diagram which shows the whole fluid reaction apparatus. FIG. 53 is a perspective view showing an overall configuration of the fluid reaction device of FIG. 52. 54 (a) is a plan view showing the overall configuration of the fluid reaction device of FIG. 52, and FIG. 54 (b) is a front view. FIG. 55A is a plan view showing the configuration of the mixing section, and FIG. 55B is a cross-sectional view. It is a figure which expands and shows the confluence | merging part of a mixing part. FIG. 57A is a plan view showing the structure of the reaction section, and FIG. 57B is a cross-sectional view. 58 (a) is a longitudinal sectional view showing another configuration of the reaction section, FIG. 58 (b) is a sectional view taken along the line XVIII-XVIII in FIG. 58 (a), and FIG. 58 (c) is still another configuration of the reaction section. FIG. It is a perspective view which shows the structure of a temperature adjustment case. 60 (a) is a plan sectional view of the processing section, FIG. 60 (b) is a side sectional view, FIG. 60 (c) is a partially enlarged view of FIG. 60 (a), and FIG. 60 (d) is FIG. FIG. It is a figure which shows the other structure of a product storage part. FIG. 62A is a plan view showing another configuration of the merging portion, and FIG. 62B is an enlarged view showing the main part of FIG. 62A. It is a top view which shows other structure of a confluence | merging part. It is a schematic diagram which shows the other structure of a fluid reaction apparatus. It is a schematic diagram which shows the other structure of a fluid reaction apparatus. It is a schematic diagram which shows the other structure of a fluid reaction apparatus. It is a schematic diagram which shows the other structure of a fluid reaction apparatus. FIG. 68 is a perspective view illustrating a configuration of a processing unit in FIG. 67. It is a schematic diagram which shows the other structure of a fluid reaction apparatus. It is a schematic diagram which shows the flow volume measurement part of a general mass flow controller. It is a graph which shows the temperature distribution of a flow path. It is a figure which shows the flow-velocity distribution of the fluid which flows through a microchannel. It is a figure for demonstrating the principle by which the flow volume of a fluid is measured. It is a schematic diagram which shows the flow volume adjustment apparatus which concerns on the 1st Embodiment of this invention. It is a figure which shows the structure of a difference detection circuit. FIG. 75 is an enlarged view showing another configuration example of the control valve shown in FIG. 74. It is a schematic diagram which shows the flow volume adjustment apparatus which concerns on the 2nd Embodiment of this invention. It is a figure for demonstrating the principle by which the flow volume of a fluid is measured. It is a schematic diagram which shows the flow volume adjustment apparatus which concerns on the 3rd Embodiment of this invention. It is a figure for demonstrating the principle by which the flow volume of a fluid is measured. FIG. 80 is a perspective view of the spool shown in FIG. 79. It is a schematic diagram which shows the flow volume adjustment apparatus which concerns on the 4th Embodiment of this invention. It is a schematic diagram which shows the whole fluid reaction apparatus. It is a perspective view which shows the structure of the whole fluid reaction apparatus of FIG. FIG. 85 (a) is a plan view showing the overall structure of the fluid reaction device of FIG. 83, and FIG. 85 (b) is a front view. FIG. 86A is a plan view showing the configuration of the mixing section, and FIG. 86B is a cross-sectional view. It is a figure which expands and shows the confluence | merging part of a mixing part. 88 (a) is a plan view showing the structure of the reaction part, and FIG. 88 (b) is a cross-sectional view. 89A is a longitudinal sectional view showing another configuration of the reaction unit, FIG. 89B is a cross-sectional view taken along line XVIII-XVIII in FIG. 89A, and FIG. 89C is still another configuration of the reaction unit. FIG. It is a perspective view which shows the structure of a temperature adjustment case. 91 (a) is a plan sectional view of the processing section, FIG. 91 (b) is a side sectional view, FIG. 91 (c) is a partially enlarged view of FIG. 91 (a), and FIG. 91 (d) is FIG. 91 (b). FIG. It is a figure which shows the other structure of a product storage part. FIG. 93 (a) is a plan view showing another configuration of the merging portion, and FIG. 93 (b) is an enlarged view showing the main part of FIG. 93 (a). It is a top view which shows other structure of a confluence | merging part. It is a schematic diagram which shows the other structure of a fluid reaction apparatus. It is a schematic diagram which shows the other structure of a fluid reaction apparatus. It is a schematic diagram which shows the other structure of a fluid reaction apparatus. It is a schematic diagram which shows the other structure of a fluid reaction apparatus. FIG. 99 is a perspective view showing a configuration of a processing unit in FIG. 98. It is a schematic diagram which shows the other structure of a fluid reaction apparatus. BRIEF DESCRIPTION OF THE DRAWINGS (a) Whole view which shows the plunger pump apparatus of 1st Embodiment of this invention, (b) It is a figure which shows the principal part. It is a figure explaining operation | movement of each part of one plunger pump. It is a figure which shows operation | movement of the plunger pump apparatus of 1st Embodiment. It is a figure which shows the plunger pump apparatus of 2nd Embodiment of this invention. (A), (b) is a figure explaining operation | movement of the conventional plunger pump, respectively. It is a figure which shows the plunger pump apparatus of one Embodiment of this invention. It is a figure which shows the connection of a plunger pump apparatus and a microreactor. It is a graph which shows the pattern of the feed rate of one plunger pump. It is a graph which shows the pattern of the feed rate of the whole plunger pump apparatus. It is a flowchart explaining adjustment operation | movement of a feed rate. It is a graph explaining control of feed speed. It is a graph explaining the control action in other embodiments. It is a schematic diagram which shows the whole fluid reaction apparatus. It is a perspective view which shows the structure of the whole fluid reaction apparatus of FIG. 115 (a) is a plan view showing the overall configuration of the fluid reaction apparatus of FIG. 8, and FIG. 115 (b) is a front view. FIG. 116 (a) is a plan view showing the configuration of the mixing section, and FIG. 116 (b) is a cross-sectional view. It is a figure which expands and shows the confluence | merging part of a mixing part. 118 (a) is a plan view showing the structure of the reaction section, and FIG. 118 (b) is a cross-sectional view. 119 (a) is a longitudinal sectional view showing another configuration of the reaction unit, FIG. 119 (b) is a cross-sectional view taken along line XVIII-XVIII in FIG. 119 (a), and FIG. 119 (c) is still another configuration of the reaction unit. FIG. It is a perspective view which shows the structure of a temperature adjustment case. 121 (a) is a plan sectional view of the processing section, FIG. 121 (b) is a side sectional view, FIG. 121 (c) is a partially enlarged view of FIG. 121 (a), and FIG. 121 (d) is FIG. 121 (b). FIG. It is a figure which shows the other structure of a product storage part. FIG. 123 (a) is a plan view showing another configuration of the merging portion, and FIG. 123 (b) is an enlarged view showing the main part of FIG. 123 (a). It is a top view which shows other structure of a confluence | merging part. It is a schematic diagram which shows the other structure of a fluid reaction apparatus. It is a schematic diagram which shows the other structure of a fluid reaction apparatus. It is a schematic diagram which shows the other structure of a fluid reaction apparatus. It is a schematic diagram which shows the other structure of a fluid reaction apparatus. It is a perspective view which shows the structure of the process part of FIG. It is a schematic diagram which shows the other structure of a fluid reaction apparatus. It is a figure which shows typically the structure of the multi-spectral-analysis apparatus of one embodiment of this invention. It is a figure which shows the example of reaction analyzed with this apparatus. It is a figure which shows typically the structure of other embodiment of the multispectral-analysis apparatus of this invention. It is a figure which shows typically the structure of other embodiment of the multispectral-analysis apparatus of this invention. It is a figure which shows typically the structure of other embodiment of the multispectral-analysis apparatus of this invention. It is a figure which shows typically the structure of other embodiment of the multispectral-analysis apparatus of this invention. It is a figure which shows the structure of the modification of embodiment of FIG. It is a figure which shows the structure of the other modification of embodiment of FIG. (A) And (b) is a figure which shows typically the usage condition of the multispectral-analysis apparatus of one Embodiment of this invention. It is a schematic diagram which shows the whole fluid reaction apparatus. It is a perspective view which shows the structure of the whole fluid reaction apparatus of FIG. 142 (a) is a plan view showing the overall configuration of the fluid reaction apparatus of FIG. 140, and FIG. 142 (b) is a front view. FIG. 143 (a) is a plan view showing the configuration of the mixing section, and FIG. 143 (b) is a sectional view. It is a figure which expands and shows the confluence | merging part of a mixing part. FIG. 145 (a) is a plan view showing the structure of the reaction section, and FIG. 145 (b) is a cross-sectional view. 146 (a) is a longitudinal sectional view showing another configuration of the reaction unit, FIG. 146 (b) is a sectional view taken along line XVIII-XVIII in FIG. 146 (a), and FIG. 146 (c) is still another configuration of the reaction unit. FIG. It is a perspective view which shows the structure of a temperature adjustment case. 148 (a) is a plan sectional view of the processing unit, FIG. 148 (b) is a side sectional view, FIG. 148 (c) is a partially enlarged view of FIG. 148 (a), and FIG. 148 (d) is FIG. FIG. It is a figure which shows the other structure of a product storage part. FIG. 150 (a) is a plan view showing another configuration of the merging portion, and FIG. 150 (b) is an enlarged view showing the main part of FIG. 150 (a). It is a top view which shows other structure of a confluence | merging part. It is a schematic diagram which shows the other structure of a fluid reaction apparatus. It is a schematic diagram which shows the other structure of a fluid reaction apparatus. It is a schematic diagram which shows the other structure of a fluid reaction apparatus. It is a schematic diagram which shows the other structure of a fluid reaction apparatus. FIG. 156 is a perspective view illustrating a configuration of a processing unit in FIG. 155. It is a schematic diagram which shows the other structure of a fluid reaction apparatus.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Raw material storage part (raw material container installation space); 2 Liquid distribution part (introduction part); 3 Processing part; 4 Generation fluid storage part (recovery container installation space); 5 Temperature control piping chamber; 6 Operation control means (Operation control part) 7) Heat medium controller (temperature adjusting means); 10A, 10B raw material storage container; 12 cleaning liquid container; 14 nitrogen gas pressure source; 16A, 16B, 16C pump; 20 mass flow controller; 20a, 20b flow rate sensor; Pipe; 24A, 24B Pressure measuring sensor in flow path; 26A, 26B Flow path selection switching valve; 28 Backwash pump; 32 Flow path selection switching valve; 40, 40a, 40b, 40c Mixed substrate; 42, 42a, 42b, 42c Reaction substrate; 46 Temperature adjustment case; 48 Preheating channel; 50, 51 Outlet channel; 52, 52a, 52b, 52c, 52d, 52e, 5 f Mixing part; 54, 54a, 54b, 54c, 54d Header part; 55, 55a, 55b, 55c, 55d Header part; 56, 56a, 56b, 56c, 56d Separation flow path; 57, 57a, 57b, 57c, 57d Separation channel; 58, 58a, 58b, 58c, 58d, 58e, 58f Merge space; 62 Reaction channel; 72 Case body; 74 Lid; 82 Heat exchanger; 84 Heat medium inlet; 90 communication path; 92 heat medium flow path; 98 flow path; 100 communication pipe; 102 outflow port; 104, 104a recovery pipe (outlet part); 106 heat exchanger; 108, 108a recovery container; 110 substance recovery port; Optical fluid detection sensor; 111b Liquid level detection sensor; 112 Rotary table; 114 Actuator; 116, 118, 120, 122, 120, 12 a, 122b, 122c temperature sensor; 124 obstacle; 126 yield evaluator; 128, 128a, 128b separation extraction substrate; 130 hydrophobic wall; 132 hydrophilic wall; 134 separation channel; 170 flow monitor; 154, 156 Partition; 158, 160, 162 Cover; 164 Exhaust port; A, B Raw material solution;
2001a, 2001b Raw material supply section; 2002 Mixing / reaction section; 2020a, 2020b Preheating block; 2040, 2040A, 2040B Mixing block; 2041a, 2041b Raw material inflow path; 2044A, 2044B Manifold element; 2046 Manifold; Parallel separation flow path; 2053 Open end face; 2054a, 2054b jet outlet; 2060 Reaction block; 2065 Restriction part; 2068 Reaction flow path; 2071 Inline sensor; 2072-2074 Mixing acceleration object; La, Lb Raw material solution; ratio;
3001 Flow path; 3002 Temperature control mechanism; 3003 Upstream temperature sensor; 3004 Downstream temperature sensor; 3005 Temperature control unit; 3006 Temperature difference measuring device; 3007 Temperature sensor; 3009 Time difference measurement unit; 3010 Flow rate measurement unit; 3013 Structure; 3013a Through hole; 3013b Cylindrical part; 3013c Heat transfer part; 3014 Fixing plate; 3016 Seal member; 3017 Temperature control member; 3019 Seal member; 3020 Control valve; 3021 Piston; 3022 Piezoelectric element; 3025 Magnetic body; 3026 Electromagnet; 3027 Sealing member; 3030 Control unit; 3032 Amplifier; 3033 Comparator; 3034 Piston drive circuit; 3035 Spool drive circuit; 3041 Poppet; 3042 Shaft; 3044 Servo motor; 3047 Sealing member; 3048 Poppet drive circuit; 3101 Raw material storage part; 3102 Liquid distribution part; 3103 Processing part; 3104 Product storage part; 3105 Piping chamber; 3106 Operation control means ( 3107 Heat medium controller (temperature adjusting means); 3110A, 3110B storage container; 3112 cleaning liquid container; 3114 pressure source; 3116A, 3116B, 3116C pump; 3121A, 3121B transport pipe; 3124A, 3124B pressure sensor; 3126B flow path switching valve; 3130 backwash pump; 3132 flow path switching valve; 3140, 3140a, 3140b, 3140c mixing section; 3142, 3142a, 3142b, 3142c reaction section; 3148A, 3148B Preheating flow path; 3150A, 3150B Outlet flow path; 3152, 3152a, 3152b Merge part; 3154, 3155 Header part; 3156, 3157 Separation flow path; 3158, 3158a, 3158b Merge space; 3172 Case body; 3174 Lid; 3182 Heat exchanger; 3184 Heat medium inlet; 3188 Supply pipe; 3190 Communication passage; 3192 Heat medium passage; 3198 Flow passage; 3200 Communication passage; 3202 Outlet; 3206 Heat exchanger; 3208, 3208a Recovery container; 3210 Recovery port; 3211a Optical fluid detection sensor; 3211b Liquid level detection sensor; 3212 Rotary table; 3214 Actuator; 3216, 3218, 3220, 322 , 3222a, 3222b, 3222c Temperature sensor; 3224 Obstacle; 3226 Yield evaluator; 3228, 3228a, 3228b Separation and extraction unit; 3230 Hydrophobic wall surface; 3232 Hydrophilic wall surface; 3234 Separation channel; 3270 Flow rate monitor; 3254, 3256 partition; 3258, 3260, 3262 cover; 3264 exhaust port; 3300A, 3300B flow control device;
4001 flow path; 4002 temperature control mechanism; 4003 first main temperature sensor; 4003a first sub temperature sensor; 4004 second main temperature sensor; 4004a second sub temperature sensor; 4005 temperature control unit; 4008A, 4008B Difference detection circuit; 4008C Bridge circuit; 4007 Temperature sensor; 4009 Time difference measurement unit; 4010 Flow rate measurement unit; 4012 Case body; 4013 Structure; 4013a Through hole; 4013b Cylindrical part; 4013c Heat transfer unit; 4016 Seal member; 4017 Temperature control member; 4019 Seal member; 4020 Control valve; 4021 Piston; 4022 Piezoelectric element; 4023 Piston chamber; 4024 Spool; 4025 Magnetic body; 4026 Electromagnet; 4027 Seal member; 2 Amplifier; 4033 Comparator; 4034 Piston drive circuit; 4035 Spool drive circuit; 4041 Poppet; 4042 Shaft; 4043 Shaft guide; 4044, 4046 Gear; 4045 Servo motor; 4047 Seal member; 4048 Poppet drive circuit; 4102 Liquid distribution unit; 4103 Processing unit; 4104 Product storage unit; 4105 Piping chamber; 4106 Operation control means (operation control unit); 4107 Heat medium controller (temperature adjustment means); 4110A, 4110B storage container; 4112 Cleaning liquid container; Pressure source; 4116A, 4116B, 4116C pump; 4121A, 4121B transport pipe; 4124A, 4124B pressure sensor; 4126A, 4126B flow path switching valve; 4130 backwash pump; 4132 flow path switching valve; 140, 4140a, 4140b, 4140c Mixing section; 4142, 4142a, 4142b, 4142c Reaction section; 4146 Temperature adjustment case; 4148A, 4148B Preheating channel; 4150A, 4150B Outlet channel; 4152, 4152a, 4152b Merge section; 4155 Header part; 4156, 4157 Separation flow path; 4158, 4158a, 4158b Merge space; 4162 Reaction flow path; 4172 Case body; 4174 Lid; 4182 Heat exchanger; 4184 Heat medium inlet; 4188 Liquid supply pipe; 4192 Heat path; 4198 Flow path; 4200 Communication path; 4202 Outlet; 4204, 4204a Recovery pipe (outlet); 4206 Heat exchanger; 4208, 4208a Recovery container; 4210 Recovery port; 4211a Optical Body detection sensor; 4211b liquid level detection sensor; 4212 rotary table; 4214 actuator; 4216, 4218, 4220, 4222, 4222a, 4222b, 4222c temperature sensor; 4224 obstacle; 4226 yield evaluator; 4228, 4228a, 4228b Part: 4230 hydrophobic wall; 4232 hydrophilic wall; 4234 separation channel; 4270 flow monitor; 4272 temperature monitor; 4254, 4256 partition wall; 4258, 4260, 4262 cover; 4264 exhaust port; 4300A, 4300B flow controller;
5010 Plunger pump; 5012 Cylinder; 5014 Plunger; 5016 Bulkhead; 5022 Piston; 5024 Rod; 5026 Pump chamber; 5028 Buffer chamber; 5030 Discharge port; 5032 Suction port; 5034, 5036 Check valve; 5050 Cam mechanism; 5054 Motor; 5056A End face cam; 5058 Roller (cam follower); 5060 Air cylinder (fluid pressure device); 5062 Pressure plate; 5064 Pressure air chamber; 5068 Air control valve; 5070 Pressure air source; 5072 Drain; 5080 Controller; ;
6001 Plunger pump device; 6002 Microreactor; 6010 Plunger pump; 6012 Cylinder; 6014 Plunger; 6016 Piston; 6017 Pump chamber; 6018 Rod; 6019 Drive device; 6020 Motor; 6022 Feed screw; 6024 Nut; 6026 Linear scale; 6030 Discharge port; 6032 Suction port; 6034 Check valve; 6036 Discharge line; 6038 Fluid tank; 6040 Supply line; 6042 Raw material receiving port; 6044 Introduction flow path; 6046 Flow meter; 6048 Pressure sensor; 6050 Mixing / reaction unit; 6102 processing unit; 6104 product storage unit; 6105 piping chamber; 6107 heat medium controller; 6110 storage container; 6110A, 6110 A storage container; 6110A, 6110B storage container; 6112 Cleaning liquid container; 6114 Pressure source; 6116A, 6116B, 6116C Plunger pump; 6121A, 6121B Transport pipe; 6122A, 122B Relief valve; 6126A, 6126B Channel switching valve; 6126A Channel switching valve; 6126A, 6126B Channel switching valve; 6130 Backwash pump; 6132 Channel switching valve; 6134 Waste liquid port; 6136 Waste liquid container; 6136 Waste liquid storage container; 6140a mixing unit; 6140a mixing unit; 6140b mixing unit; 6140a mixing unit; 6140b mixing unit; 6140c mixing unit; 6140c mixing unit; 6142a reaction part; 6142a reaction part; 6142a reaction part; 6142a reaction part; 6142a reaction part; 6142b reaction part; 6142a reaction part; 6142b reaction part; 6142b reaction part; 6144 reaction part; 6144a upper plate; 6144c lower plate; 6144b middle plate; 6144d, 6144e base material; 6146 each temperature adjustment case; 6146 temperature adjustment case; 6147A, 6147B inflow port; 6148A, 6148B preheating flow path; 6150A, 6150B outlet channel; 6150A outlet channel; 6150B outlet channel; 6150A, 6150B outlet channel; 6152 merging part; 6152a merging part; 6152b merging part; 6154, 6155 header part; 6155 6156, 6157 Separation channel; 6156 Separation channel; 6156, 6157 Separation channel; 6157 Separation channel; 6157a Communication hole; 6158 Confluence space for a certain period of time; 6158 Junction space; 6158b Merge space; 6159 Opening surface; 6160 Outflow port; 6162 Reaction channel; 6162, 6163 Reaction channel; 6162 Reaction channel; 6162b Meandering part; 6162a, 6162c Connecting part; 6163c Reaction channel; 6163c Reaction channel; Portion; 6163b Portion; 6164 Inlet port; 6165 Outlet port; 6170 Space; 6172 Case body; 6174 Lid; 6176 Groove; 6178 Supply path; 6179 Opening; 6180 Drain path; 6182 Heat exchanger; 6190 Communication path; 6192 Heat medium flow path; 61 94 bolt; 6195 nut; 6196 spacer; 6198 flow path; 6200 communication path; 6202 outlet; 6204 recovery pipe; 6204, 6204a recovery pipe; 6206 heat exchanger; 6208 recovery container; 6208, 6208a recovery container; 6211a Optical fluid detection sensor; 6211b Liquid level detection sensor; 6212 Rotary table; 6214 Actuator; 6216, 6218 Temperature sensor; 6220 Temperature sensor; 6220, 6222a, 6222b, 6222c Temperature sensor; 6222 Temperature sensor; 6224 Each obstacle; Obstacle; 6226 inline yield evaluator; 6228 separation and extraction unit; 6228a separation and extraction unit; 6228b separation and extraction unit; 6228a separation and extraction unit; 6228b separation and extraction unit; 6228a separation and extraction 6228b Separation and extraction unit; 6230 Hydrophobic wall surface; 6232 Hydrophilic wall surface; 6234 Separation flow path; 6234a Discharge port; 6234b Discharge port; 6236 Silicon member; 6240 Inlet port; 6240 Powder dissolver; 6242 Raw material inlet port; 6246 agitator; 6249 piping; 6250 pan; 6250 code; 6252 code; 6252 code; 6254, 6256 partition wall; 6258, 6260, 6262 cover; 6264 code; 6270 flow rate monitor; 6272 temperature monitor;
7001 Multispectral analyzer; 7010 Casing; 7014 Flow cell; 7016 Internal space; 7018 Partition; 7020 Light emitting part; 7022 Light receiving part; 7024 Light source part; 7024a-7024g Light source; 7026 Optical fiber; 7028 Spectroscopy part: 7028a-7028g Spectroscope; 7028a Ultraviolet spectrometer; 7028b Visible light spectrometer; 7028c-7028e Near-infrared spectrometer; 7028f Infrared spectrometer; 7028g Far-infrared spectrometer; 7030 AD converter; 7032 Control unit; 7034 Display; 7036 Storage device; 7040 Branching flow path; 7042 Flow control valve; 7044 On-off valve; 7046 Casing; 7047 Substrate; 7048 Flow path; 7050 Joint part; 7052 Light emitting case; 7054 Light receiving case; 58 Mixing and reaction section; 7060 Micro quench section; 7062 Three-way switching valve; 7064 Product storage line; 7066 Spare tank; 7068 Spare line; 7101 Raw material storage section; 7102 Liquid distribution section; 7103 Treatment section; 7104 Product storage section; 7105 Piping chamber; 7107 Heat medium controller; 7110 Storage container; 7110A, 7110B Storage container; 7110 Storage container; 7110A, 7110B Storage container; 7112 Cleaning liquid container; 7114 Pressure source; 7121B transport pipe; 7122A, 7122B relief valve; 7124A, 7124B pressure measurement sensor; 7125 interface; 7126A, 7126B flow path switching valve; 7126A flow path switching valve; 7126A, 7126B flow 7130 Backwashing pump; 7134 Waste liquid outlet; 7136 Waste liquid container; 7136 Waste liquid storage container; 7140 Mixing part; 7140a Mixing part; 7140, 7140a Mixing part; 7140a Mixing part; 7140b Mixing part; 7140a mixing unit; 7140b mixing unit; 7140c mixing unit; 7140 mixing unit; 7142 reaction unit; 7142a reaction unit; 7142b reaction unit; 7142 reaction unit; 7142a, 7142b, 7142c reaction unit; 7142a reaction unit; 7142b reaction unit 7142 reaction part; 7142a reaction part; 7142b reaction part; 7142a reaction part; 7142b reaction part; 7142b reaction part; 7144a upper plate; 7144c lower plate; 7144b middle plate; 7144d, 7144e base material; 146 Temperature adjustment case; 7147A, 7147B Inflow port; 7148A, 7148B Preheating channel; 7148 port; 7150A, 7150B outlet channel; 7150A outlet channel; 7150B outlet channel; 7150A, 7150B outlet channel; 7152a Merge portion; 7152b Merge portion; 7154, 7155 Header portion; 7155 Header portion; 7156, 7157 Separation channel; 7156 Separation channel; 7156, 7157 Separation channel; 7157 Separation channel; 7158 Joint space; 7158 Merge space; 7158a Merge space; 7158b Merge space; 7159 Open surface; 7160 Outflow port; 7162 Reaction channel; 7162, 7163 Reaction channel; 7162 Reaction channel; 7162b Meandering part; Contact 7163 Reaction channel; 7163c Reaction channel; 7163a part; 7163b part; 7164 Inlet port; 7165 Outlet port; 7170 Space; 7172 Case body; 7174 Lid; 7176 Groove; 7178 Supply line; 7179 Opening; 7182 Heat exchanger; 7188 Supply pipe; 7190 Communication path; 7192 Heat medium path; 7194 Bolt; 7195 Nut; 7196 Spacer; 7198 Flow path; 7200 Communication path; 7202 Outlet; 7204 Recovery pipe; 7204, 7204a 7206 Heat exchanger; 7208 Recovery container; 7208, 7208a Recovery container; 7210 Recovery port; 7211a Optical fluid detection sensor; 7211b Liquid level detection sensor; 7212 Rotary table; 7214 Actuator; 7216, 7218 7220 temperature sensor; 7220, 7222a, 7222b, 7222c temperature sensor; 7222 temperature sensor; 7224 obstacles; 7224 obstacles; 7226 inline yield evaluator; 7228 separation and extraction unit; 7228a separation and extraction unit; 7228b separation and extraction 7228a Separation and extraction unit; 7228b Separation and extraction unit; 7228b Separation and extraction unit; 7230 Hydrophobic wall surface; 7232 Hydrophilic wall surface; 7234 Separation channel; 7234a Discharge port; 7234b Discharge port; 7236 Silicon member; 7240 Powder dissolver; 7242 Raw material inlet; 7244 Heater; 7246 Stirrer; 7249 Piping; 7250 Pan; 7250 Code; 7252 Code; 7254, 7256 Bulkhead; 7258, 7260, 7262 Cover; 64 code; 7270 flow rate monitor; 7272 temperature monitor; 7300A, 7300B flow rate adjustment device

Fluid reactor The present invention relates to a fluid reaction device for reacting the fluid with each other in very small spaces.

  The present invention for achieving the above-described object includes, but is not limited to, the following inventions.

  (1) In a fluid reaction device that introduces and reacts a plurality of fluids into a reaction channel having a micro reaction space, an introduction unit that individually introduces fluids used for the reaction, and a mixing channel that joins and mixes the fluids A plate-like mixed substrate having fluid, fluid transporting means for transporting fluid toward the mixing flow path via a plurality of transport pipes, flow rate control means for controlling the flow rate of fluid, and temperature of the reaction flow path A fluid reaction apparatus comprising temperature control means for controlling, a derivation section for deriving a substance after reaction, and operation control means for controlling these operations.

  According to the invention described in (1), a microreactor is provided as a practical mass production means, and the present invention can reliably and continuously perform a high yield reaction in a microspace. In the liquid-liquid reaction, the Reynolds number in a microspace of the tens to hundreds of μm class is small, the flow becomes laminar, and mixing by molecular diffusion becomes the rate-limiting step. In other words, in a micro space of several hundred μm or less, mixing using laminar flow diffusion is more efficient than conventional mechanical stirring mixing. Since the mixing part where the fluid is mixed is a micro space, the diffusion time is shortened and uniform mixing is achieved in a short time. For example, even in an explosive reaction, the reaction is performed at an extremely low temperature of minus 50 ° C. Productivity is increased because it is no longer necessary and the yield increases with safety. Even when the reaction is complicated and the reaction time is long, a high yield can be obtained by increasing the reaction rate or selectively reacting by using a micro space.

  Further, by performing mixing on a flat mixed substrate, the contact area with the heat medium fluid can be increased and the heat transfer rate to the reaction fluid can be increased. Therefore, it is possible to improve the temperature uniformity over the entire reaction fluid and improve the accuracy of temperature control. The process used can be widely applied from the laboratory level to the chemical production line, from organic synthesis, inorganic synthesis, catalytic reaction to bio-based biochemical synthesis and fine particle production.

  The condition of the flow path in the mixed substrate needs to make the diffusion distance small, that is, to have a micro dimension from the relationship between the diffusion time and the diffusion distance that can be estimated from Fick's law. It is preferable to increase the area of the two-liquid interface after merging by providing a plurality of merging points or placing obstacles such as porous frit and pillars in the channel after merging.

  When a plurality of merge points are provided in parallel, it is desirable that a time difference is not generated as much as possible in the merge points. In addition, the flow path width after merging is gradually reduced to 100 μm or less, and if possible, to 40 μm or less, the width of the two liquids in the merged flow is forcibly reduced, and diffusion mixing is forcibly shortened. It is desirable to do it. This greatly shortens the mixing time, allows explosive reactions even at room temperature, simplifies the reaction route in organic synthesis reactions, and reduces wasteful reactions. Production is extremely reduced, and the amount of raw material used is reduced, which is advantageous in terms of running cost.

  (2) In the invention described in (1), an installation space for installing a storage container for individually storing fluids used for the reaction is provided.

  (3) In the invention according to (1) or (2), a fluid reaction apparatus characterized in that an installation space is provided in which a plurality of recovery containers for recovering a substance after reaction from the lead-out part can be installed. .

  (4) The fluid reaction device according to any one of (1) to (3), wherein a channel having a channel width of 500 μm or less exists in the micro reaction space.

  (5) In the invention according to any one of (1) to (4), the fluid to be introduced is a gas or a liquid, and the substance after the reaction is either a gas, a liquid or a solid, or a mixture thereof. The fluid reaction apparatus is characterized in that the introduced fluid is a continuous flow.

  (6) The fluid reaction apparatus according to any one of (1) to (5), wherein the fluid transporting means includes a pressure generating means or an electric dielectric force interaction means.

  (7) In the invention according to any one of (1) to (6), the flow rate control means includes a sensor unit that measures a volume of the passing fluid, and a passage area through which the fluid passes based on measurement information of the sensor unit. A fluid reaction apparatus comprising a passage amount control unit for controlling.

  (8) The fluid reaction apparatus according to any one of (1) to (7), wherein a plurality of the mixed substrates are provided.

  (9) In the invention according to any one of (1) to (8), in order to advance the reaction of the fluid after mixing, the reaction flow path is formed on a reaction substrate provided separately from the mixing substrate. A fluid reaction device characterized by the above.

  (10) The fluid reaction apparatus according to the item (9), wherein a plurality of the reaction substrates are provided.

  (11) In the invention according to any one of (1) to (11), a first flow path selection switching valve is provided between the fluid transporting means and the mixing substrate, and between the mixing substrate and the substance recovery port. A fluid reaction apparatus characterized by comprising a second flow path selection switching valve.

  (12) The fluid reaction according to the invention described in (11), wherein the first flow path selection switching valve and the second flow path selection switching valve are automatic valves operated by an electric operation or a pneumatic operation. apparatus.

  (13) In the invention according to any one of (1) to (12), after the fluid introduced into the mixing channel is mixed, the mixing channel or / and the reaction channel are filled with fluid. A filling detection means for judging, and when the fluid is filled, the fluid transportation means is stopped or the first channel selection switching valve is switched, and the mixing channel or / and reaction for a certain time to adapt the fluid to the reaction end time. A fluid reaction apparatus characterized in that it can be controlled to remain in a flow path.

  (14) In the invention according to (13), the fullness detection means is a fluid presence sensor for detecting a fluid that has started to come out from the substance recovery port, or a fluid presence or absence for detecting the presence or absence of a fluid in the transport pipe after the mixing reaction. A fluid reaction device characterized by being a sensor.

  (15) In the invention according to any one of (1) to (14), a temperature measurement sensor is individually provided in the mixing channel and the reaction channel, and the temperature can be individually controlled. A fluid reaction device characterized by the above.

  (16) The fluid reaction device according to any one of (1) to (15), wherein at least a part of the mixed substrate and the reaction substrate are stacked.

  (17) In the invention according to any one of (1) to (16), the second flow path selection switching valve is switched to reverse the direction of normal flow in the mixing flow path and the reaction flow path. A fluid reaction apparatus comprising backwashing means for feeding a fluid into the apparatus.

  (18) In the invention according to (17), the backwashing means includes a single piston pump as a pressure feeding means.

  (19) In the invention according to any one of (11) to (18), the first flow path selection switching valve includes a nitrogen gas supply line, a pure water supply line, an organic solvent supply line, an acid supply line, hydrogen A fluid reaction apparatus connected to any one or more of a water supply line and an ozone water supply line.

  (20) In the invention according to any one of (11) to (19), the second flow path selection switching valve includes a nitrogen gas supply line, a pure water supply line, an organic solvent supply line, an acid supply line, hydrogen A fluid reaction apparatus connected to any one or more of a water supply line and an ozone water supply line.

  (21) In the invention according to any one of (3) to (20), a table capable of holding two or more recovery containers and a table moving mechanism are provided in the installation space of the lead-out portion. Fluid reaction device.

  (22) In the invention described in (21), the table moving mechanism is a rotating mechanism or a reciprocating mechanism.

  (23) The fluid reaction apparatus according to any one of (1) to (22), further comprising yield measuring means for measuring the yield of the substance after the reaction.

  (24) The fluid reaction apparatus according to (23), wherein the yield measuring means is ultraviolet absorption, infrared spectroscopy, or near infrared spectroscopy.

  (25) A fluid mixing device used in a fluid reaction device for reacting a plurality of fluids in a flow path including a micro reaction space, wherein a plurality of flat base materials are joined, and the plurality of fluids are separated from each header space. A plurality of liquid separation flows configured to be continuously supplied to and mixed with the merge space, the header spaces of the fluids provided on different surfaces of the base material, and the header spaces and the merge space to communicate with each other. A fluid mixing apparatus characterized in that the channel is formed such that liquid separation channels from different header spaces open alternately at the inflow portion of the merge space.

  According to the invention described in (25), the mixing having the mixing flow path for processing the predetermined flow paths on the surface of the base material and joining them so that the fine flow paths are alternately adjacent to each other and flow into the merge space The device is easily manufactured with a simple configuration.

  (26) In the invention described in (25), each of the header spaces is formed in a concentric arc shape on the different surfaces, and the merging space is arranged substantially at the center of these arcs. Fluid mixing device.

  (27) In the invention described in (25) or (26), the header space is formed on each of the front and back surfaces of the base material, the merge space is formed on one surface of the base material, and on the other surface A fluid mixing device, wherein a separation flow path communicating with the header space is provided through the base material.

  (28) In the invention described in (25) or (27), the plurality of liquid separation channels communicating the header spaces and the merge space are formed to extend in parallel to each other. Fluid mixing device.

  According to the invention described in (28), since the plurality of liquid separation channels are formed to extend in parallel to each other, they are not concentrated on the side of the merged space and can be easily designed and manufactured.

  (29) A fluid mixing device used in a fluid reaction device for reacting a plurality of fluids in a flow path including a micro reaction space, wherein a plurality of flat base materials are joined, and the plurality of fluids are separated from respective header spaces. The header space is provided along the surface of the base material, and the joint space is provided so that the fluid flows in the plate thickness direction of the base material. A plurality of liquid separation channels that communicate between the header space and the merge space are formed such that the liquid separation channels from different header spaces are alternately opened at the inflow portion of the merge space. Mixing equipment.

  According to the invention described in (29), since the merging space is provided so that the fluid flows in the plate thickness direction of the base material, the merging space does not occupy the plate surface of the base material, and the header space and the plurality of parts are separated. The liquid flow path can be freely arranged on the plate surface of the substrate.

  (30) In the invention described in (29), the header spaces are provided on both sides of the merge space on the surface of the base material, and liquid separation channels from different header spaces are mutually connected at the inflow portion of the merge space. A fluid mixing device, wherein the fluid mixing device is opened at a shifted position.

  According to the invention described in (30), fluids from different header spaces flow into positions shifted from each other while facing each other at the inflow portion of the merge space, and form alternately adjacent flows with a swirl flow, Increase the area of the interface.

  (31) In the invention according to (29), the header space of each fluid is provided on a different surface of the base material, and at least one of the separation flow paths is provided through the base material, The fluid mixing device is characterized in that the liquid separation channels are formed so as to face each other on the opposite sides of the merge space and alternately adjacent to each other on the same side of the merge space.

  According to the invention as described in (31), the flow which adjoins by turns into two layers becomes a layered flow arranged in three layers, and increases the area of the interface.

  (32) In the invention according to any one of (29) to (31), the merging space is bent so that the fluid flows along the substrate after flowing in the plate thickness direction of the substrate. A fluid mixing device formed.

  According to the invention described in (32), the merge space is formed to be bent so that the fluid flows along the surface of the substrate after flowing in the plate thickness direction of the substrate. Increase in dimensions is suppressed.

  (33) having a mixing channel for continuously supplying and mixing a plurality of fluids to a space including a channel width portion of 500 μm or less formed on a flat substrate, and from the confluence of the plurality of fluids A fluid mixing apparatus, wherein columnar obstacles having a diameter of 50 μm or less are arranged at equal intervals over a length of 5 mm or more along the flow.

  According to the invention described in (33), by mixing and arranging minute columnar obstacles along the flow from the confluence of fluids in the mixing flow path, the mixing device using the micro flow path can be simplified. It is easily manufactured with a simple structure.

  (34) The fluid mixing apparatus according to the invention described in (33), wherein the columnar obstacle is configured such that a plurality of columns are alternately arranged in the flow direction at different intervals.

  (35) In the invention according to (33) or (34), a plurality of the columnar obstacles are arranged in a staggered manner in the flow direction.

  (36) The fluid mixing device according to any one of (25) to (35), wherein the fluid mixing device has a portion in which the width of the flow path gradually decreases and a portion in which the width gradually increases after joining. It is preferable that the surface of the flow path that gradually decreases is on the same plane as the surface where a plurality of fluids merge.

  (37) The fluid mixing device according to any one of (25) to (36), wherein the width dimension and the depth dimension of the flow path are alternately reduced and enlarged after joining. The minimum dimension is preferably 100 μm or less.

  (38) In the invention according to any one of (25) to (37), the fluid mixing device has a flat portion in which the width direction dimension of the flow path is larger than the depth direction dimension after joining. .

  (39) In the invention according to any one of (25) to (38), the member forming the flow path is made of hard glass such as SUS316, SUS304, Ti, quartz glass, Pyrex glass (registered trademark), PEEK (polyetheretherketone) ), PE (polyethylene), PVC (polyvinylchloride), PDMS (polydimethylsiloxane), Si, PTFE (polytetrafluoroethylene), PCTFE (polychlorotrifluoroethylene), and PFA (perfluoroalkoxylalkane). Fluid mixing device. From these materials, preferable materials are selected in consideration of chemical resistance, pressure resistance, and thermal conductivity. The material of the wetted part of the mixed / reacted substrate material is preferably one that has little elution from the surface, can be modified with a surface catalyst, has a certain degree of chemical resistance, and can withstand a wide temperature range of −40 to 150 ° C.

  (40) In the invention according to any one of (25) to (38), a part or all of the material of the inner wall of the flow path is made of Au, Ag, Pt, Pd, Ni, Cu, Ru, Zr, Ta, A fluid mixing apparatus characterized by being a compound containing Nb or a metal thereof.

  (41) The fluid mixing apparatus according to any one of (25) to (40), wherein the base material is a rectangle having a size of at least one side exceeding 150 mm.

  (42) The fluid according to any one of (25) to (41), wherein the plurality of fluid inlets and the outlet of the single fluid after mixing are present on the opposite surface of the substrate. Mixing equipment.

  (43) In the invention described in any one of (25) to (42), the mixed reaction substrate is provided in the same substrate, and a preliminary temperature adjusting unit is provided for increasing or decreasing the temperature of the fluid toward the reaction temperature. A fluid mixing device.

  (44) The fluid reaction device according to any one of (1) to (24), wherein the fluid mixing device according to any one of (25) to (43) is used as the mixing substrate.

  (45) In the invention according to any one of (1) to (24) and (44), the peripheral members forming the flow path of the reaction substrate are SUS316, SUS304, Ti, quartz glass, Pyrex glass (registered trademark). A fluid reaction apparatus characterized by comprising one or more of hard glass such as PEEK, PE, PVC, PDMS, Si, PTFE, and PCTFE.

  (46) In the invention according to any one of (1) to (24), (44), and (45), a part or all of the material of the inner wall of the flow path of the reaction substrate is Au, Ag, Pt, Pd , Ni, Cu, Ru, Zr, Ta, Nb, or a compound containing one or more of these metals, or a fluid reaction apparatus characterized by the above.

  (47) In the invention according to any one of (1) to (24) and (44) to (46), the mixed substrate and / or reaction substrate is accommodated in a temperature adjustment case having a heat medium flow path. A fluid reaction apparatus characterized by being provided. Accordingly, the heat medium flow path creates a uniform flow along the entire area of the mixed substrate and / or the reaction substrate, and adjusts the reaction region to a uniform temperature.

  (48) The fluid reaction device according to the item (47), wherein a temperature measuring means is provided in the heat medium fluid flow path.

  (49) In the invention described in (46) or (47), the heat medium flow path has a plurality of branch flow paths along the front and back surfaces of the mixed substrate and / or reaction substrate. Reactor.

  (50) In the invention according to any one of (47) to (49), the temperature adjustment case has a case main body and a lid, and the heat medium flow path is formed so as to connect them. A fluid reaction device characterized by the above.

  (51) In the invention according to (50), the plurality of throttle holes provided in the first header of the case body into which the thermal fluid flows are directly connected to the second header of the lid portion, and the second header Is provided with a second throttle hole that is directly connected to a plurality of branch channels that form a flow parallel to the front and back surfaces of the mixed substrate and / or reaction substrate.

  (52) The fluid reaction device according to any one of (47) to (51), wherein the material of the temperature adjustment case is Ti, Al, SUS304, or SUS316.

  (53) In the invention according to any one of (1) to (24) and (44) to (52), the temperature control means surrounds the fluid mixed substrate or the reaction substrate and adjusts the temperature of the mixed fluid. A fluid comprising: an adjustment medium holding mechanism; a temperature adjustment medium held by the holding mechanism; a temperature measurement sensor; and a heat transfer amount adjusting means for adjusting a heat transfer amount between the temperature adjustment medium and the mixed reaction fluid. Reactor.

  (54) In the invention described in (53), any one or more of silicon oil, fluorine oil, alcohol, liquid nitrogen, electric resistance heating wire, and Peltier element is used as the temperature adjusting medium. Reactor. Silicon oil can perform temperature control in a wide range of, for example, −40 to 150 ° C. with one fluid. Or, if importance is given to the high temperature side, fluorinated oil is desirable, and if it is on the low temperature side, alcohol based is desirable.

  (55) The fluid reaction device according to (53) or (54), wherein the heat transfer amount adjusting means is any one of a pump flow rate adjustment, a flow rate adjustment valve, and an electric quantity.

  (56) The fluid reaction device according to any one of (53) to (55), wherein the temperature adjusting medium holding mechanism is covered with a heat insulating member.

  (57) The fluid reaction device according to (56), wherein the heat insulating member is silicon rubber.

  (58) The invention according to any one of (1) to (24) and (44) to (57), characterized in that it comprises a separation and extraction means for separating necessary and unnecessary substances in the post-reaction substance. A fluid reaction device.

  (59) The fluid according to any one of (1) to (24) and (44) to (58), comprising a powder dissolver for liquefying and dissolving the powder raw material. Reactor.

  (60) In the invention according to any one of (1) to (24) and (44) to (59), a part or all of the inside of the fluid reaction device is isolated from the outside of the device and is more negative than the pressure outside the device. A fluid reaction apparatus characterized by having a pressure of

  (61) In the invention according to any one of (1) to (24) and (44) to (60), a liquid storage pan for storing liquid leaked at a lower portion of the fluid reaction device, and detecting the leaked liquid A fluid reaction apparatus comprising a leak sensor.

  (62) In the invention according to any one of (1) to (24) and (44) to (61), the operation control unit including the operation control means attached to the fluid reaction device includes a fluid flow rate and a reaction. A fluid reaction apparatus comprising a display mechanism for displaying temperature.

  A microreaction apparatus according to an embodiment of the present invention will be described below with reference to the drawings.

  1 to 3 show an embodiment of the fluid reaction apparatus of the present invention, which is an apparatus for reacting after mixing two liquids. As shown in FIG. 2 or FIG. 3, the apparatus according to this embodiment is installed in a single installation space as a unit. In this embodiment, the installation space is rectangular and is partitioned into four regions along the longitudinal direction.

  A first region on one end side is a raw material storage unit (raw material container installation space) 1 in which a plurality of raw material storage containers 10A and 10B for storing a raw material fluid and its ancillary facilities are installed, and a second region adjacent thereto is The liquid distribution unit 2 is provided with a pump for supplying fluid from the raw material storage containers 10A and 10B to the processing unit 3, a switching valve for setting a flow path, and the like. A third region adjacent to the second region is a processing unit 3 that performs a predetermined process on the fed raw material fluid, and a fourth region on the other end side is a fluid obtained as a result of the processing. A generated fluid storage unit (recovery container installation space) 4 for storing (generated fluid) by deriving from the deriving unit. Further, an operation control unit 6 which is a computer for controlling the operation of each unit and a heat medium controller 7 for adjusting the temperature of the processing unit 3 are provided. In this embodiment, the operation control unit 6 and the heat medium controller 7 are provided separately from the reaction apparatus, but may be integrated as a matter of course. As shown in FIG. 2, a temperature adjusting piping chamber 5 is formed in the lower floor portion of the second to fourth regions, and here, a heating medium for heating or cooling is sent to the processing substrates 40 and 42 described later. Piping is provided.

  Thus, by arranging each facility from the upstream side to the downstream side, the flow of fluid can be made smooth and the entire apparatus can be compactly integrated. In this embodiment, the arrangement of the equipment is linear, but for example, if the whole is a space close to a square, each equipment may be configured such that the flow of fluid forms a loop. Such a partition is a rough one, and each facility can be appropriately arranged in order to effectively utilize the vacant space in the design.

  A plurality (six in this embodiment) of storage containers 10 </ b> A and 10 </ b> B are installed in the raw material storage unit 1. Of course, the necessary number of storage containers 10A and 10B may be used. By storing the same fluid in the two storage containers 10A and 10B and using them alternately, the processing can be continuously performed. As a fluid source from the outside, a cleaning liquid container 12 containing an organic solvent such as acetone for line cleaning, hydrochloric acid, pure water, or a nitrogen gas pressure source 14 for purging may be placed in the raw material reservoir 1. . Further, a waste liquid container 36 may be placed.

  The liquid distribution section (introduction section) 2 is provided with raw material pumps 16A and 16B connected to the raw material storage containers 10A and 10B via fluid inlets and their associated facilities. In this embodiment, since the discharge amount of each raw material pump 16A, 16B is managed by the number of revolutions of the motors 18A, 18B driving the raw material pumps 16A, 16B, the raw material pumps 16A, 16B have pressure generating means and flow rate. It also serves as an adjustment means. The raw material pumps 16A and 16B in FIG. Examples of other pressure generating means and flow rate adjusting means are shown in FIGS.

  The pressure generating means and the flow rate adjusting means may be configured separately. In FIG. 4, liquid is pumped by sending pressure gas from the nitrogen gas pressure source 14 to the storage containers 10A and 10B, and the flow rate is adjusted by the mass flow controller 20 provided at the outlet. The mass flow controller 20 is a hot wire type sensor unit and a piezoelectric type controller unit, but may be other flow rate adjusting means having a sensor unit for measuring the flow rate and a controller unit for controlling the flow rate. The sensor unit may be an ultrasonic piezoelectric element type flow sensor 20a as shown in FIG. 5A or a differential pressure type flow sensor 20b as shown in FIG. 5B, for example. The controller unit may be a controller 20d using a piezoelectric piezoelectric element spool shown in FIG. 5A or 5B, or a controller 20c using a magnetic levitation spool as shown in FIG.

  As ancillary equipment of the liquid distribution unit 2, relief valves 22A and 22B, flow path pressure measurement sensors 24A and 24B, flow path selection switching valve 26A disposed in the transport pipes 21A and 21B downstream of the raw material pumps 16A and 16B. , 26B and backwash pump 28 are provided. The flow path selection switching valves 26A and 26B are connected to the cleaning liquid container 12 and the nitrogen gas pressure source 14 for purging, in addition to the normal line. The backwash pump 28 is used when the inside of the flow path is blocked with a product. The pump 28 discharges an organic solvent, hydrochloric acid, pure water, and the like from the cleaning liquid container 12 and is connected to a downstream outlet of a reaction substrate, which will be described later, via a flow path selection switching valve 32. The cleaning liquid flows in the opposite direction to the normal path, and is put into the waste liquid storage container 36 from the waste liquid port 34 through the flow path selection switching valves 26A and 26B from the inlet of the mixed substrate 40. The pump 28 is preferably a single-piston pump so that the generated pressure is high and the product can be moved by pulsating force. As the organic solvent, acetone, ethanol, methanol, or the like is used, and nitric acid, phosphoric acid, or an organic acid may be used instead of hydrochloric acid. An introduction port 140 for infrastructure water or the like in FIG. 1 is an introduction port when pure water or hydrogen water supply equipment is provided as factory equipment, and a cleaning liquid container placed in the installation space (raw material storage part) 1 of the container 10. 12 can be used for washing instead of the washing liquid in the inside. Hydrogen water is used as a catalyst with Pd, Ni, etc. Ozone water is used for oxidizing cleaning. Moreover, a raw material solution can also be received from this inlet 140 via piping from an external raw material tank.

  In this example, the processing unit 3 includes two processing substrates, that is, a mixed substrate 40 and a reaction substrate 42 as shown in FIGS. 7 and 9. The mixed substrate 40 and the reaction substrate 42 are plate-like members configured by joining two or more pieces obtained by processing a groove having a predetermined shape on at least one surface of a thin plate-like base material 44, A channel is formed inside by a groove on the surface of the substrate 44. The shape and dimensions of the flow path are designed according to the reaction process of the processing to be performed. Further, the material of the base material 44 is also selected in accordance with the processing as described later, and designed to have a thickness necessary to withstand the working pressure. These processing substrates 40 and 42 are accommodated and used in a temperature adjustment case 46 as shown in FIG.

  FIG. 7 shows a mixed substrate 40 for performing preheating (preliminary temperature adjustment) and mixing processing, and an upper plate 44a, a middle plate 44b, and a lower plate 44c, which are three thin plate-like base materials, are joined. Thus, a mixed substrate 40 having a total thickness of 5 mm is formed. All the grooves forming the flow path are formed in the intermediate plate 44b. In the figure, the solid line indicates the groove formed on the upper surface of the intermediate plate 44b, and the chain line indicates the groove formed on the lower surface of the intermediate plate 44b. . That is, the two inflow ports 47 formed through the upper plate 44a communicate with the two preheating channels 48 formed on the upper surface of the middle plate 44b. Each of these preheating channels 48 branches and expands in the middle, and merges again and communicates with the outlet channels 50 and 51 and further with the mixing unit 52. One outlet channel 50 is formed on the upper surface of the middle plate 44b, and the other outlet channel 51 is formed on the lower surface of the middle plate 44b.

  As shown in an enlarged view in FIG. 8, the mixing portion 52 includes header portions 54 and 55 formed as arc-shaped grooves communicating with the outlet channels 50 and 51 respectively on the upper and lower surfaces of the intermediate plate 44 b, and the header portion 54. , 55 and a plurality of liquid separation channels 56, 57 extending toward the center of the arc, and a merge space 58 formed such that the front and back radial channels merge. The separation flow paths 56 and 57 and the merge space 58 are formed on the upper surface of the intermediate plate 44b, and the separation flow paths 56 and 57 are alternately arranged to communicate with the header portions 54 and 55, respectively. The liquid separation flow path 57 communicating with the header section 55 on the lower surface side is communicated with a communication hole 57a that penetrates the intermediate plate 44b. The merge space 58 is formed so that the width gradually decreases toward the outlet side at the other end, and opens to the outflow port 60 formed through the middle plate 44b and the lower plate 44c on the other end side. .

  In the example shown in the figure, five liquid separation channels 56 for liquid A and four liquid separation channels 57 for liquid B are alternately arranged on the inlet side opening surface 59 of the merge space 58. The outflowing A liquid and B liquid gradually reduce the width of the flow path in an alternating layered and striped flow. In this case, the flow reaches 40 μm, and both liquids are forcibly mixed. The width gradually increases thereafter, and a steady flow rate can be obtained.

  FIGS. 9A and 9B show a reaction substrate 42. In this example, two substrates 44 are joined to form a total reaction substrate 42 of 5 mm. In the reaction substrate 42, the reaction flow path 62 is meandered to provide a long flow path efficiently. The reaction channel 62 is formed such that the connecting portions 62a and 62c connected to the inlet port 64 and the outlet port 65 are narrow and the central meandering portion 62b is wide. Therefore, it is squeezed at the entrance / exit part and flows rapidly, avoiding the adhesion of by-products, and flows gently at the center part, so that the heating and reaction time can be increased.

  FIGS. 10A and 10B show another example of the reaction substrate 42a having a portion 63a where the width of the shape of the flow path gradually decreases and a portion 63b where the width gradually increases. In this embodiment, a reaction channel 63 is formed between the base materials 44d and 44e so that the width dimension increases or decreases in the range from the maximum a to the minimum b. The depth may be increased or decreased according to the increase or decrease of the width dimension. In this example, the depth changes from the maximum c to the minimum d so that the cross-sectional area of the flow path is constant.

  FIG. 10C shows a cross section of the reaction flow path 63c in the reaction substrate 42b of another embodiment. The reaction channel 63c has a flat shape with a width e larger than the depth f and has a wide heat transfer surface that intersects the direction of heat transfer from the thermal catalyst (indicated by an arrow). Heat is effectively transferred to the fluid.

  In addition, it is effective in order to accelerate | stimulate reaction to arrange | position an appropriate catalyst in the merge space 58 and the reaction flow path 62. FIG. Such a catalyst is selected depending on the type of reaction. As for the arrangement method, for example, it can be applied to the inner surface of the channel, or can be arranged as an obstacle of the channel as described later.

  The material forming at least the flow path of the base material 44 forming these substrates 40 and 42 is, for example, hard glass such as SUS316, SUS304, Ti, quartz glass, Pyrex glass (registered trademark), PEEK (polyetheretherketone), PE (Polyethylene), PVC (polyvinylchloride), PDMS (polydimethylsiloxane), Si, PTFE (polytetrafluoroethylene), PCTFE (polychlorotrifluoroethylene), PFA (perfluoroalkoxylalkane), chemical resistance, pressure resistance, thermal conductivity, heat resistance, etc. A preferable one is selected in consideration. The material of the wetted part of the mixed substrate 40 and the reaction substrate 42 is one that has little elution from the surface, can be modified with a surface catalyst, has a certain degree of chemical resistance, and can withstand a wide temperature range of −40 to 150 ° C. desirable.

  FIG. 11 shows a configuration of the processing block. The temperature adjustment case 46 includes a case main body 72 in which a space 70 for accommodating the processing substrates 40 and 42 is formed, and a lid portion 74 covering the case main body 72. In these, grooves 76 constituting a plurality of parallel heat medium flow paths are formed so as to open to the inner surface. A liquid supply path 78 and a drainage path 80 (see FIG. 12A) communicating with the grooves 76 are formed in the case main body 72. The liquid supply path 78 and the drainage path 80 are respectively connected to the liquid supply pipes. And connected to the heat medium controller 7 via a return pipe. These liquid supply path 78 and drainage path 80 are also communicated with each other through the opening on the lid 74 side to be joined. As described above, in this example, the processing substrates 40 and 42 are heated (or cooled) in a state of being completely accommodated in the temperature adjustment case 46, and the heat medium fluid is directly applied to the front and back surfaces of the mixed substrate 40 or the reaction substrate 42. In contact.

  The heat medium controller 7 includes a control mechanism for correcting the medium temperature and a transport pump for transporting the heat medium. The heat medium fluid passes through the individual heat exchangers 82 and then reaches the heat medium inlet 84 of the temperature adjustment case 46 of the mixed substrate 40 or the reaction substrate 42 via the heat medium pipe. The heat exchanger 82 can change individual temperatures of the heat medium, for example, by changing the amount of city water for cooling.

  12 (a) to 12 (d) show other examples of the temperature adjustment case 46. Here, the heat medium flow path is formed inside each of the case main body 72 and the lid portion 74. FIG. . As shown in FIG. 12 (c), the liquid supply path 78 has a double pipe structure in which the tip of the liquid supply pipe 88 is inserted, and communicates with the heat medium flow path 92 through the thin communication path 90. is doing. The drainage side has the same configuration. As shown in FIG. 12 (b), the mixed substrate 40 and the reaction substrate 42 are laminated and bonded via bolts 94, nuts 95, and spacers 96.

  FIG. 12B shows a supply / discharge path of the raw material solution to the processing substrates 40 and 42 accommodated in the temperature adjustment case 46. That is, each solution flows into and out of the mixed substrate 40 through the flow passage 98 formed through the temperature adjustment case 46. In addition, the processing substrates 40, 42 are circulated from the mixed substrate 40 to the reaction substrate 42, for example, via the connecting pipe 100 that communicates the flow path 98 of the temperature adjustment case 46. FIG. 12D illustrates the structure of the inflow portion and the outflow portion of the liquid to the reaction substrate 42. In order to direct the flow of the liquid from the upper direction to the lower direction, the liquid substrate of the processing substrates 40 and 42 is usually formed on the upper surface and the outlet is formed on the lower surface.

  In the embodiment shown in FIG. 1, the outlet 102 of the reaction substrate 42 is connected to the product fluid reservoir 4 via a recovery pipe 104. In the product fluid storage unit 4, a recovery container 108 is provided on the downstream side of the cooling heat exchanger 106, the flow path selection switching valve 32, and the like. The product fluid reservoir 4 in which the recovery container 108 is placed is isolated so as not to be affected by temperature or the like from other regions and to block toxic gas that may be generated from the product fluid.

  FIG. 13 shows another embodiment of the product fluid storage unit 4, and a plurality of collection containers 108 are held on the turntable 112. In the case of FIG. 13, there are two collection containers 108, and the actuator 114 that moves the rotary table 112 is a 180-degree rotary actuator. Of course, the number of collection containers 108 and the type of actuator 114 can be selected as appropriate. For example, the operation control unit 6 determines the replacement time of the recovery container 108 by the liquid level detection sensor 111b that detects the liquid level of the recovery container 108, stops the liquid flow by the flow path selection switching valve 32, and the substance recovery port 110. This is confirmed by the optical fluid detection sensor 111a provided downstream of the actuator 114, and the actuator 114 is operated.

  A process of producing a product such as a chemical solution using the fluid reaction apparatus configured as described above will be described. The processes that can be automated are basically automatically controlled by the operation control unit 6.

  First, the raw material solutions A and B required in the raw material storage unit 1 are prepared in the storage containers 10A and 10B. A necessary mixed substrate 40 and reaction substrate 42 are selected as processing substrates and installed in the processing unit 3. The temperature of the heat medium is set by the heat medium controller 7, the amount of city water in the heat exchanger 82 is adjusted to adjust the temperature of each heat medium path, and the temperature adjustment case 46 of the mixed substrate 40 and the reaction substrate 42. These are circulated and maintained at a predetermined temperature. The temperature control is managed by the temperature sensors 116 and 118 provided at the entrance to the temperature adjustment case 46. The temperature is controlled while flowing pure water for cleaning or the like in the flow path in the processing substrates 40 and 42. The measurement can be performed accurately by measuring and feeding back with the temperature sensors 120 and 122 at the outlet of the mixed substrate 40.

  After the temperature is adjusted and the cleaning of the flow path is completed, the flow path selection switching valve 32 is switched, and the raw material storage containers 10A and 10B to the pumps 16A and 16B, the mixed substrate 40, the reaction substrate 42, the outlet 102, and the recovery port 110 are switched. Then, the processing flow path to the recovery container 108 is configured, and the pumps 16A and 16B are operated to feed the raw material solutions A and B at a predetermined flow rate, respectively. The flow path selection valve 32 is an automatic valve operated by an actuator, and these operations can be automatically operated.

  In the mixed substrate 40, the solution is preheated to a predetermined temperature in the preheating unit, and then merged and mixed in the mixing unit 52. At this time, each liquid flows from the header portions 54 and 55 via the separation flow paths 56 and 57 into the merging space 58 from the alternately arranged processing, and the cross section decreases further toward the downstream. The flow is mixed regularly and mixed quickly according to Fick's law. In that state, when it flows into the reaction channel 62 of the reaction substrate 42 maintained at the reaction temperature, the reaction proceeds rapidly without being restricted by mass transfer or heat conduction. Therefore, it is sufficiently practical as a mass production means, and it is not necessary to carry out an explosive reaction with a high reaction rate at a low temperature. In this example, since the reaction channel 62 is formed to be sufficiently wide as compared with the mixing channel, even when the reaction rate is low, the reaction can be performed with sufficient time, resulting in a high yield. Obtainable.

  The obtained product is sent from the outlet 102 of the reaction channel 62 to the heat exchanger 106 via the recovery pipe 104, cooled here, and flows into the recovery container 108 from the recovery port 110. When the raw material storage containers 10A and 10B are emptied or the recovery container 108 is full, continuous operation is possible by switching the flow path selection switching valves 26A and 26B and replacing them with other containers. . In addition, when reaction takes time, it is also possible to carry out batch operation by confining the liquid in the mixed substrate 40 and the reaction substrate 42 for a certain period of time. Since the flow path selection valves 26A and 26B are also automatic valves, these operations can be automatically operated.

  In the batch operation method, the pumps 16A and 16B in FIG. 1 may be temporarily stopped, or the flow path selection switching valves 26A and 26B may be switched to stop the flow into the processing unit 3. This eliminates the need to increase the length of the reaction channel 62 even when the reaction time is long. In batch operation, it is preferable to perform operation control using a fullness detection means for determining that the fluid is filled in the mixing channel or / and the reaction channel. For example, an optical fluid detection sensor 111a as shown in FIG. 13 is used. Accordingly, when it is determined that the fluid is filled in the mixing channel or / and the reaction channel, the fluid transporting unit is stopped or the first channel selection switching valve is switched to adapt the fluid to the reaction end time. It is allowed to stay in the mixing channel or / and the reaction channel for a certain time.

  FIG. 14 (a) shows a mixing portion 52a according to another embodiment. The two header portions 54a and 55a are not circular but extend linearly in the width direction, and the front end side of the merge space 58a. That is, the width W on the side facing the header portion 54a is set to be substantially the same as the width of the header portion 54a. The liquid separation channels 56a and 57a extend in parallel to each other and are formed so as to communicate the header portion and the merge space. The merge space 58 is formed in a trapezoidal shape in plan view so that the width gradually decreases toward the outlet side of the other end, and the outflow formed through the middle plate 44b and the lower plate 44c on the other end side. The port 60 is open. The width w on the exit side is selected so that the reduction ratio (r = w / W) becomes an appropriate value according to the processing target.

  As in the previous embodiment, the header portions 54a and 55a are formed separately on the upper and lower surfaces of the intermediate plate 44b, and the one header portion 55a and the liquid separation flow path 57a are connected to the communication hole 57x penetrating the intermediate plate 44b. Are in communication with each other.

  In this embodiment, there are advantages that the manufacturing process is easier and the shift to the scale-up model is easier than the embodiment of FIG. In the case of FIG. 8, the first point is that the liquid separation flow paths 56 a and 57 a are close to each other in the vicinity of the merge space 58 a, so that manufacture of this part is more difficult than other parts. This is because there is no such problem in the embodiment.

  The second point is related to the first point and will be described below. For example, when a reaction apparatus including a mixing unit is used for manufacturing a pharmaceutical product, the apparatus is used not only in a development stage but also in a production stage. If we move from the development stage to the production stage, the mixing section must also support scale-up. For example, if the initial flow rate is 0.1 L / h, the preclinical level is 1 L / h, the pilot plant level is 50 L / h, and the production plant level is 100 to 200 L / h. For example, a scale-up of about 1000 times is required. In the mixing section, the width of the flow path is a factor that affects the basic performance of the apparatus and basically does not change, so the number of liquid separation flow paths is increased.

  In the case of FIG. 8, as described above, the part where the liquid separation channels 56 and 57 gather becomes a manufacturing bottleneck. Therefore, if the minimum dimension between the grooves in this portion is predetermined, the width on the header portion side increases as the number increases, and as a result, the size (chip size) of the device increases. In the embodiment of FIG. 14A, the width W only increases as shown in FIG. 14B in proportion to the processing amount, that is, in proportion to the processing amount.

  Further, in the case of FIG. 8, since the merging angle changes with the scale-up, the manufacturing process becomes complicated. In some cases, as a result of the change in the merging angle, the same performance as the development stage may not be obtained in the production stage after the scale-up. On the other hand, it is obvious that there is no such problem in the embodiment of FIG.

  FIG. 15 shows a mixing unit 52b according to still another embodiment. The two header parts 54b and 55b are formed in a U shape in a plan view, and the two side branch parts 54x and 55x have the same center. They are arranged symmetrically with respect to the line. In this example, the merge space 58b is a space extending downward. From the side branch portions 54x and 55x of the two header portions 54b and 55b, the liquid separation flow paths 56b and 57b extend in parallel toward the center line, respectively, and open to the merge space 58b. The liquid separation channels 56b and 57b from the different header portions 54b and 55b are arranged so as to be alternately adjacent to each other on the same side and open at positions facing each other on the opposite side in the merge space 58b. The merge space 58b extends vertically in the lowermost base material 44d, but the shape, dimensions, and the like are the same as in the previous embodiment.

  In the embodiment of FIG. 15, the flow from the liquid separation flow paths 56b and 57b forms a flow that is alternately adjacent in a plane, but in this embodiment, it is arranged three-dimensionally in two layers. Laminar flow. Therefore, the area of the interface with the adjacent flow is increased, and mixing by diffusion is further promoted. Further, since the opposing flows collide with each other, the flow becomes finer, and the mixing effect is enhanced by the effect of increasing the area of the interface. This embodiment has the advantage of easy transition to the scale-up model, as in the case of FIG.

  FIG. 16 shows a mixing portion 52c according to still another embodiment. The mixing space 58c is formed of an orthogonal portion 58x extending downward and a parallel portion 58y extending along the plate surface. In FIG. 15, since the total length of the mixing space 58b extends in the vertical direction, that is, in the thickness direction of the mixing substrate 40 and the base material 44, the overall size increases, or conversely, the length of the mixing space 58b. This causes the problem of being restricted. Moreover, it is not easy in manufacturing to form a space in the thickness direction. In this embodiment, since the mixing space 58c is formed by the orthogonal portion 58x extending downward and the parallel portion 58y extending along the plate surface, the increase in the plate thickness is slight, and the manufacturing process is processed to the flat plate surface. Then, it can be handled in the same process as the other part of overlapping.

  FIG. 17 shows a mixing unit 52d of still another embodiment. As shown in FIG. 17A, the two header units 54d and 55d are separately arranged on both sides of the mixing space 58d. In addition, the mixing space 58d is formed to extend along the plate surface after once extending downward, as shown in FIG. The liquid separation flow paths 56d and 57d from the different header portions 54d and 55d are opposed to each other in the mixing space 58d and open while being shifted from each other. The flow from the liquid separation flow paths 56d and 57d forms a flow alternately adjacent in a plane, and a mixing space 58d while forming a swirling flow between the adjacent flows as shown in FIG. Descend. The swirl flow in this case can also increase the area of the interface between the two liquids and enhance the mixing effect.

  FIG. 18 shows a modification of the mixing portion of FIG. 17, and the two header portions 54d and 55d are formed on the same side surface of the base member 44b. Since the mixing space 58c has the orthogonal portion 58x extending downward, the two header portions 54d and 55d can be formed on both sides of the same surface as the mixing space 58c, and the liquid separation channels 56d and 57d interfere with each other. It is because it can be made to open alternately, without doing.

  FIG. 19 shows another embodiment of the mixing part 52e in the mixed substrate 40. The obstacle 124 is arranged at a constant distance a over a predetermined distance L in the merge space 58e that merges in a Y-shape. Is. In this example, the columnar obstacles 124 having a diameter of 50 μm or less are arranged in five rows from the merging point over L = 5 mm. Each obstacle 124 is arranged in a staggered manner so that adjacent ones are shifted by half the pitch in the flow direction. As a result, the interface meanders, so that the interface area between the two fluids can be increased. In the mixing unit 52f of FIG. 20, the obstacles 124 are arranged in a line in the merge space 58f, and the interface area can be increased similarly. This is suitable for use in a narrower merge space 58f.

  FIG. 21 shows another embodiment of the liquid flow of the processing unit 3 of the fluid reaction device. This is because, in the processing section 3 of FIG. 1, two systems R1, R2 are provided in the combination of the mixed substrate 40 → the reaction substrate 42, and further, the raw material solutions A, B are used by using the flow path selection switching valves 26A, 26B of the liquid distribution section 2. Can be supplied to any system R1, R2. In this embodiment, the amount of processing can be increased as necessary by using two systems, but there are various other usage methods. For example, in the case where the reaction product easily deposits solid particles and is easily clogged in the middle of the piping, one system is used as a reserve. Further, the above-described batch operation can be continuously performed by alternately switching the line 1 with the flow path selection switching valves 26A and 26B. Of course, three or more such lines can be provided in parallel as appropriate. Also in this case, the flow path selection valve switching valves 26A and 26B can be automatically operated.

  FIG. 22 shows an example in which a plurality of reaction substrates are arranged in series in the processing unit 3. In this example, individual temperature sensors 120, 122a, 122b, and 122c are provided on a total of four processing substrates, that is, the mixed substrate 40 and the three reaction substrates 42a, 42b, and 42c. It is possible to control the temperature of 42b and 42c independently. The configuration of the processing unit 3 of this embodiment is suitable for a reaction in which the reaction time and the reaction temperature are to be changed boldly and instantaneously, such as a biochemical reaction. For example, a reaction such as 100 ° C. for the reaction substrate 42a and −20 ° C. for the reaction substrate 42b is possible in this system.

  FIG. 23 shows an embodiment in which a plurality of mixed substrates 40 are provided in the processing unit 3. In this embodiment, a second mixed substrate 40a is provided downstream of the mixed substrate 40 and the reaction substrate 42 for mixing and reacting the A liquid and the B liquid. Here, the third raw material solution transported from the pump 16C is provided. Alternatively, it is combined with the C liquid which is a reactant and mixed. The temperatures of these two mixed substrates 40, 40a and one reaction substrate 42 are individually controlled. The liquid C may be a reaction terminator.

  In this embodiment, an in-line yield evaluator 126 is directly connected to the outlet 102 downstream of the second mixed substrate 40a. Thereby, the yield of the result of the chemical reaction can be confirmed in real time and can be immediately fed back to the process parameters. As the in-line yield evaluator 126, there are methods such as infrared spectroscopy, near infrared spectroscopy, and ultraviolet absorption as methods that can be measured without separating the measurement object.

  In this embodiment, a separation / extraction means 128 is further provided for separating unnecessary substances and necessary substances from the reaction product. In the illustrated example, as the separation and extraction means 128, a separation channel 134 formed by a hydrophobic wall surface 130 that allows only hydrophobic molecules in the substance to pass through and a hydrophilic wall surface 132 that allows only hydrophilic molecules in the substance to pass through, respectively. Branched into The separated substances are recovered in the recovery containers 108 and 108a via the recovery pipes 104 and 104a, respectively. As the separation and extraction means 128, it is also possible to use a membrane or a porous frit that can adsorb only a hydrophobic substance.

  FIG. 24 shows an embodiment for carrying out a continuous reaction process by repeating mixing / reaction and separation / extraction. Unnecessary substances after the liquid A and the liquid B react are discharged from the discharge port 134a, and unnecessary substances in the second reaction to which the liquid C is added are discharged from the discharge port 134b. The D liquid as the fourth liquid may be a reaction terminator or another raw material solution. Finally, an inline yield evaluator 126 may be provided.

  FIG. 25A shows a configuration in which the circuit of FIG. 24 is stacked. The fluid flows from top to bottom. Each block in the figure is configured such that a mixed substrate 40a, a reaction substrate 42a, a separation / extraction substrate 128a, a mixing substrate 40b, a reaction substrate 42b, a separation / extraction substrate 128b, and a mixing substrate 40c are accommodated in a temperature adjustment case 46, respectively. Further, they are laminated by bolts 94, nuts 95 and spacers 96. As shown in FIG. 9, the movement of the liquid between the substrates is performed in the communication passage 100. The temperature control accuracy is improved by interposing air between the blocks so as not to be affected by the heat of other blocks by utilizing the heat insulation of the air. As shown in FIG. 25 (b), it is preferable to cover each block with a heat insulating material such as a silicon member 136 that is clean and contains bubbles.

  The fluid introduced into the fluid reaction apparatus of the present invention is liquid, gas, and the substance to be recovered is liquid, gas, solid or a mixture thereof. However, when the introduced substance is a solid such as powder, the raw material in FIG. It is also possible to install a powder dissolver in the space of the storage unit 1. FIG. 26 shows an embodiment of the raw material reservoir 1 when the liquid A is a solution obtained by dissolving powder and the liquid B is originally liquid. The raw material powder and the solvent are introduced from the raw material inlet 142 of the powder dissolver 140. In this embodiment, the raw material powder is dissolved by heating by the heater 144 and stirring by the stirrer 146, and the mixed raw material 40 and the reaction substrate 42 are pumped by the pump 16A from the pipe drawn into the outlet 148. It comes to send to.

  In FIG. 2, reference numeral 150 denotes a liquid storage pan provided at the lower part of the apparatus, and 152 denotes a liquid leakage sensor installed on the liquid storage pan 150. Further, in this example of the apparatus, the liquid distribution unit 2, the processing unit 3, and the generated fluid storage unit 4 are partitioned by partition walls 154 and 156, and covers 158, 160, and 162 are attached to the respective rooms so that they can be connected to the outside of the apparatus. Isolated. Reference numeral 164 denotes an exhaust port, which is connected to an exhaust fan and prevents the toxic gas in the apparatus from leaking outside by making the pressure in the apparatus negative from the outside of the apparatus.

  Further, as shown in FIG. 1, the operation controller 6 is equipped with a flow rate monitor 170 and a temperature monitor 172 that can monitor the flow rate and reaction temperature of the fluid that are particularly important in the operation within the fluid reaction device.

  As described above, some circuit configurations of the fluid reaction apparatus of the present invention have been described along the embodiments. However, the present invention is not limited to these embodiments, and various modifications can be made in accordance with the spirit of the invention. Is possible. That is, the number of processing substrates connected in series or in parallel is determined to an appropriate number of 1 or more according to the processing to be performed and the production amount. For example, the processing substrates may be joined sequentially into a frame having slits. In this embodiment, the processing substrate is disposed horizontally, but may be disposed obliquely or vertically.

Microreactor The present invention further relates to a microreactor that can be used in the fluid reaction apparatus and the fluid mixing apparatus of the present invention.

  The present invention for achieving the above-described object includes, but is not limited to, the following inventions.

  (1) A manifold section in which a plurality of first flow paths communicating with the first fluid source and a plurality of second flow paths communicating with the second fluid source are respectively formed, and adjacent to the manifold section The manifold portion has an opening end face facing the joining space, and the openings of the first flow path and the second flow path are three-dimensionally adjacent to each other at the opening end face. A microreactor characterized in that the microreactor is arranged.

  According to the invention described in (1), the flow (collective flow) flowing out from the opening end face of the manifold portion into the merge space is alternately adjacent to the respective flows (element flows) of the first fluid and the second fluid. The flow of one fluid is surrounded by the flow of the other fluid. Therefore, the ratio of the interfaces between these fluids is, for example, twice that of a flow parallel in a plane, and a mixing effect due to greater interdiffusion can be obtained.

  (2) In the invention described in (1), the manifold portion is formed by stacking plate-like elements in which grooves constituting the first flow path and the second flow path are alternately formed. A microreactor characterized in that the first flow path and the second flow path are arranged in a staggered pattern on the open end face.

  According to the invention described in (2), it is possible to easily construct a manifold section that creates a three-dimensional collective flow in which element flows are alternately adjacent.

  (3) The microreactor according to the invention described in (1) or (2), wherein a maximum width dimension in a section of the opening of the first flow path and the second flow path is 3000 μm or less.

  According to the invention described in (3), even if solid matter is mixed into the first flow path and the second flow path, the mixing can be promoted without being blocked, and the throttle portion or the fluid is provided downstream. By providing the lens, the condition of the micro reaction state can be formed.

  (4) In the invention according to any one of (1) to (3), an accelerating object that bypasses the flow mixing from the first flow path and the second flow path is provided in the merge space or downstream thereof. A microreactor characterized by being provided.

  According to the invention described in (4), since the interface is curved when the collective flow bypasses the mixing promoting object, the ratio of the interface is further increased to promote mixing, and the flow path cross section is also reduced. , Can promote micro reaction.

  (5) The microreactor according to the invention described in (4), wherein a substance having a catalytic action is provided on a surface of the mixing promoting object.

  According to the invention described in (5), the required reaction is promoted by the catalytic action of the substance.

  (6) In the invention described in (4) or (5), the representative dimension of the mixing promoting object is an individual flow from the first flow path and the second flow path immediately before the mixing promoting object. A microreactor characterized by being in the range of 0.1 to 10 times the minimum width.

  If the size of the mixing promoting object is too small compared to the minimum width (representative dimension) of the element flow, the mixing promoting object becomes a mere porous object and sufficient mixing cannot be expected, and if it is too large, it flows in a staggered manner. However, since the elemental flow of the different fluids flowing in a lump form, sufficient mixing cannot be obtained.

  (7) In the invention according to any one of (1) to (6), a throttle portion or a fluid lens in which a flow path cross section gradually decreases is provided downstream of the merging space. Microreactor.

  According to the invention described in (7), when the collective flow passes through the constricted portion or the fluid lens, the cross-sectional dimension gradually decreases, and the representative dimension decreases while maintaining the element flow. Therefore, the microreaction conditions are enhanced and the ratio of interfaces depending on the element flow dimensions is greatly improved.

  (8) In the invention described in (7), the minimum width of the virtual cross section of each flow from the first flow path and the second flow path is 500 μm or less at the downstream portion of the throttle portion or the fluid lens. A microreactor characterized by

  According to the invention described in (8), the micro reaction condition can be configured in the element flow without using a physical micro-sized flow path.

  (9) The microreactor according to the invention described in (7) or (8), wherein the opening end face and the throttle portion or the fluid lens have substantially similar flow path cross sections.

  According to the invention described in (9), since the shape does not change when passing through the aperture portion or the fluid lens, it is easy to reduce the representative dimension while maintaining the element flow.

  (10) The microreactor according to any one of (1) to (9), wherein a plurality of the manifold portions are arranged so that respective opening end faces are opposed to each other in the merge space.

  According to the invention described in (10), it is possible to further collide the collective flows from the manifold portion, and obtain further mixing promoting action by turbulent flow.

  (11) In the invention according to any one of (1) to (10), heat for heating or cooling the fluid flowing in the first flow path, the second flow path, the merge space and / or the downstream side thereof. A microreactor provided with an exchanger. Thereby, the temperature control with respect to explosive reaction and difficult reaction can be performed precisely, and the effect of a micro reaction can be heightened.

  (12) In the invention described in (11), the heat exchanger is configured by laminating plate-like elements in which grooves constituting the heated fluid flow path and / or the heat medium flow path are formed. A microreactor characterized by having Thereby, it is possible to adjust the heat exchange amount and the heat exchange pattern suitable for the target reaction by appropriately selecting the elements to be laminated or by changing the number of laminated layers.

  (13) In the invention described in (11) or (12), a heated fluid channel of a heat exchanger that heats or cools a fluid flowing downstream of the merge space is a delay loop for adjusting a synthesis reaction time, A microreactor characterized in that the residence time in heat exchange can be adjusted by changing the delay loop pattern or the number of stacked layers.

  (14) In the invention according to any one of (11) to (13), a fluid that does not contaminate the heated fluid is used as the heat medium of the heat exchanger even if mixed into the heated fluid. Microreactor. As the fluid that does not contaminate the heated fluid even if mixed into the heated fluid, the heated fluid itself or a solution having a composition close to this is preferable.

  Embodiments of the present invention will be described below with reference to the drawings.

  FIG. 27 is a diagram showing an overall configuration of a compound production system using the microreactor of the present invention. This compound production system includes two raw material supply parts 2001a and 2001b for supplying raw material solutions La and Lb, respectively, and a mixing / reaction part for mixing and reacting the raw material solutions La and Lb from these raw material supply parts 2001a and 2001b. 2002, a storage tank 2003 for temporarily storing the reaction product, and a purification tank 2004 for further concentrating and purifying the product.

  In this embodiment, each of the two raw material supply units 2001a and 2001b has dissolution tanks 2011a and 2011b in which raw materials such as powder are used as solutions of a predetermined concentration, and reservoirs 2012a and 2012b that store the resulting solutions. In addition, on the downstream side of the reservoirs 2012a and 2012b, raw material transfer pipes 2014a and 2014b communicating with the mixing / reaction unit 2002 via fluid transfer pumps 2013a and 2013b are provided, respectively. In the dissolution tanks 2011a and 2011b, a heat retaining jacket 2015 and a stirrer 2016 are provided as necessary.

  The storage tank 2003 for temporarily storing the reaction product is provided as necessary. In this embodiment, the storage tank 2003 is configured as a sealed container including a heat insulation jacket 2015 and a stirrer 2016, and has a predetermined sensor. . In this embodiment, the refining tank 2004 concentrates the synthesized fluid in a vacuum atmosphere, and a vacuum pump 2017 and a recovery container 2018 are provided in addition to the heat retaining jacket 2015 and the stirrer 2016.

  Moreover, each part of the said structure is provided with the on-off valve, the flow control valve, the flowmeter, various sensors, the washing | cleaning fluid circuit, etc. as needed. As a sensor, a temperature sensor (indicated by T in the figure), a flow sensor (indicated by F in the figure), a pressure sensor (indicated by Ps in the figure), a liquid level sensor (indicated by L in the figure), a pH sensor (in the figure) and the like). Further, a control device (not shown) for controlling each part individually and / or as a whole is provided.

  In this embodiment, as shown in FIG. 28, the mixing / reaction unit 2 includes two preheating blocks 2020a and 2020b for preheating the raw material solutions La and Lb and two heated raw material solutions La and Lb, respectively. It has a mixing block 2040 that joins in a state of being trickled, and a reaction block 2060 that guides the joined fluid to a reaction channel further reduced in diameter and reacts by heating. Each of these blocks is a manifold constructed by stacking and joining flat plates in which flow paths through which the raw material solutions La and Lb and the heat mediums Ma and Mb flow are formed in a groove shape.

  As shown in FIG. 29 (a), the preheating blocks 2020a and 2020b include a plate-like first heat exchange element 2022 in which a plurality of parallel solution flow paths 2021 for flowing the raw material solutions La and Lb are formed, and FIG. As shown in (b), the plate-like second heat exchange element 2024 formed with a plurality of parallel heat medium flow paths 2023 through which the heat mediums Ma and Mb flow are connected to the flow paths 2021 and 2023 with each other. The layers are alternately stacked so as to be orthogonal to each other. The preheating blocks 2020a and 2020b are covered with cover plates 2025A and 2025B on the front and back, and are joined using a fastener such as a bolt, a seal member, or an adhesive. Each of the heat exchange elements 2022 and 2024 is provided with through holes 2026 and 2027 in the vicinity of both ends of the flow path, which individually communicate with the solution flow path 2021 and the heat medium flow path 2023 and at the solution inflow ports of the cover plates 2025A and 2025B. 2028A, the solution outflow port 2028B, the heat medium inflow port 2029A, and the heat medium outflow port 2029B communicate with each other.

  As shown in FIG. 30, the raw material solutions La and Lb flow in series through the flow paths of the heat exchange elements 2022 and 2024, and the heat media Ma and Mb flow through the heat exchange elements 2022 and 2024 as shown in FIG. The heat exchange is performed through the heat exchange elements 2022 and 2024 here. These heat exchange elements 2022 and 2024 use a material having good heat conductivity suitable for heat exchange, while the cover plates 2025A and 2025B are formed using a material having low heat conductivity.

  As shown in FIG. 32, the mixing block 2040 has a plurality of plate-like manifold elements in a frame body 2043 formed of a plurality of members in which two raw material inflow channels 2041a and 2041b and one merging portion 2042 are formed. A manifold 2046 configured by stacking 2044A and 2044B and front and back cover plates 2045a and 2045b is accommodated. The raw material inflow paths 2041a and 2041b are connected to solution outflow ports 2028B of the preheating blocks 2020a and 2020b, respectively, and the confluence 2042 is connected to an inlet 2061 of a reaction block 2060 described later, as shown in FIG. A merge space 2047 is configured.

  As shown in FIG. 33, in each manifold element 2044A, 2044B, a plurality of through liquid supply holes 2048a, 2048b communicating with the respective raw material inflow passages 2041a, 2041b when stacked are arranged along rows whose positions are different in the width direction. Has been. The cover plates 2045a and 2045b are formed with through holes 2049a and 2049b connected to only one of the through liquid supply holes 2048a and 2048b, which are respectively connected to the header portions 2050a and 2050b formed in the frame body 2043. It communicates with the raw material inflow channels 2041a and 2041b. Manifold elements 2044A and 2044B are formed with liquid separation flow paths 2051a and 2051b extending from these penetrating liquid supply holes 2048a and 2048b toward substantially the center of one side edge. These liquid separation channels 2051a and 2051b are formed so as to have a rectangular cross section so that the ones communicating with the raw material inflow channels 2041a and 2041b are alternately arranged, and in a predetermined length portion near the side edge portion. Parallel liquid separation flow paths 2052a and 2052b are parallel to each other. The parallel liquid separation channels 2052a and 2052b are opened on the side surfaces of the manifold elements 2044A and 2044B.

  As shown in FIG. 33, adjacent manifold elements 2044A and 2044B are arranged such that the liquid separation flow paths 2051a and 2051b (parallel liquid separation flow paths 2052a and 2052b) at the corresponding positions communicate with the different raw material inflow paths 2041a and 2041b. It is configured. That is, the manifold element 2044A has a separation flow path 2051a (parallel separation flow path 2052a) communicating with the raw material inflow path 2041a at the upper end in FIG. 33, whereas the manifold element 2044B has a raw material inflow path 2041b at the upper end. There is a liquid separation flow path 2051b (parallel liquid separation flow path 2052b) communicating with. Therefore, as shown in FIG. 34, on the opening end face 2053 of the manifold 2046, the jet outlets 2054a and 2054b of the parallel liquid separation channels 2052a and 2052b communicating with the different raw material inflow channels 2041a and 2041b are arranged in a lattice pattern. It is open.

  The reaction block 2060 is configured by alternately laminating plate-like heat exchange elements 2063 and 2064 as shown in FIG. 36 between two cover plates 2062A and 2062B shown in FIG. 35, and is configured as a heat exchanger. Is basically the same as the previous preheating blocks 2020a and 2020b. That is, plate-like heat exchange elements 2063 and 2064 each formed with a plurality of parallel solution flow paths and heat medium flow paths through which the combined solution Lm and the heat medium Mc flow are alternately arranged so that the respective flow paths are orthogonal to each other. The front and back surfaces are covered with cover plates 2062A and 2062B, and are joined using a fastener such as a bolt, a seal member, or an adhesive. Each heat exchange element 2063, 2064 is provided with a through hole in the vicinity of both ends of the flow path, which individually communicate with the solution flow path and the heat medium flow path and communicate with the ports of the cover plates 2062A, 2062B. The solution and the heat medium joined to the flow path are circulated.

  The inflow side cover plates 2062A and 2062B are provided with inflow ports 2061 having the same diameter as the joining portion 2042 of the mixing block 2040 and opening so as to communicate therewith. A throttle part (fluid lens) 2065 having a gradually decreasing cross-sectional dimension is provided on the downstream side of the inflow port 2061, and the tip side thereof is heated via the communication channel 2066 and the through channel 2067 of the cover plate 2062A. The exchange element 2063 communicates with the reaction channel 2068. As shown in FIG. 36 (a), the reaction channel 2068 is a solution of the preheating blocks 2020a and 2020b in that a plurality of parallel channels 2069 formed by grooves are connected in series to the surface of the heat exchange element 2063. Different from the flow path 2021. Since the flow of the heat medium flow path 2070 and the heat medium Mc is the same as that in FIG. 31, the description thereof is omitted.

  In this embodiment, as shown in FIG. 34, the diaphragm 2065 has a similar cross section. That is, the cross-sectional dimension is reduced without changing the cross-sectional shape as a square. As a result, the cross-sectional dimensions of the individual solution flows (referred to as “element flows”) that flow out of the opening of the mixing block 2040 and are assumed to exist in a state before being mixed and completely mixed are uniformly reduced. be able to.

For example, in the case of the above embodiment, if the cross-sectional dimension of the flow path in the mixing block 2040 is 100 μm × 100 μm and the number of flow paths in parallel for one manifold element 2044A, 2044B is 10, the merge section 42 The cross-sectional dimension of is about 1 mm × 1 mm. When the cross-sectional dimension reduction ratio (ρ = (S1 / S2) ^1/2 ) in the throttle portion 2065 is 1/10, the dimension of the reaction channel 2068 after the throttle portion 2065 is 0.1 mm × 0.1 mm, and the reaction channel The cross-sectional dimension of the “element flow” of the raw material solutions La and Lb in 2068 is 10 μm × 10 μm. Note that S1 and S2 are cross-sectional areas before and after the aperture 2065, respectively. The width w of this “element flow” is calculated as the product of the width W of the flow path in the mixing block 40 and the cross-sectional dimension reduction ratio ρ when the throttle portion 2065 changes in a similar manner.

w = W × ρ
The condition that the reaction in the merged flow is a micro reaction is not necessarily a physical flow path width problem, but under a certain condition, it is a virtual “element flow” width problem as described above. That is, by sufficiently reducing the width of the “element flow”, the interface ratio is increased to promote mixing, and the reaction rate can be improved in accordance with Fick's law. In order to obtain such an effect, it is preferable that the minimum value wmin of the width in the cross section of the element flow is 500 μm or less. In the above example, the virtual minimum width wmin is 10 μm, which sufficiently satisfies this condition.

  In the mixing block 2040 and the reaction block 2060 described above, the temperature conditions are strictly controlled. That is, in each block, the temperature of the heat medium is measured by temperature sensors provided at the inlet and outlet of the flow path, and the temperature of the solution passing through this is also measured by each sensor. These measured values are input to the control device, and feedback control is performed so that the reaction is performed under optimum conditions.

  In the above, as a method of forming a groove serving as a flow path in the element, an appropriate method is employed according to the dimensions and materials such as machining and etching. In this embodiment, the preheating block, the mixing block 2040, and the reaction block 2060 are configured by combining plate-like elements, respectively, so that they can be completely disassembled and cleaned, It is also suitable for pharmaceutical manufacturing with high precision. In addition, since there is no pipe for transferring the solution between the preheating blocks 2020a and 2020b, the mixing block 2040, and the reaction block 2060, heat loss is extremely small and highly accurate temperature control is possible.

  In addition, the devices constituting the above-described parts can be easily installed and operated by making them into units by appropriately arranging them on a base provided with a flow path by machining or etching, for example. Cost can also be reduced. A plurality of such bases can be stacked to form a three-dimensional structure, and these can be constructed by piping, further saving space. Furthermore, each device may be integrally processed on a base to form a one-chip shape. It is desirable to provide a control system that controls the process of each part as necessary.

  In order to enable precise temperature control, a sandwich structure may be used by enclosing with a flat plate provided with heat exchange on both sides of a flat pipe portion provided with a mixer and a reactor. Also, a flexible device configuration can be realized by using a minimum configuration base provided with one or more devices and peripheral piping as a unit, and connecting a plurality of them together. Alternatively, a continuous multistage synthesis reaction may be performed by combining a plurality of such unitized or chipped continuous synthesis systems and batch separation / purification systems.

  It is preferable that both of the raw material fluids are liquid, but it is of course possible to use gases. In addition, mixing can be performed in the mixing block 2040 with one as a gas and the other as a liquid. If microbubbles generated at this time are used, a high mixing action can be obtained. The material constituting the flow path or the material of the surface coating of the flow path is appropriately performed for the purpose of imparting heat conduction uniformity, catalyst support, chemical resistance, biosafety, etc. to the corresponding part. It is also possible to coat.

  Hereinafter, a method for producing a compound such as a pharmaceutical using the compound production system configured as described above will be described. The raw material solutions La and Lb prepared in the dissolution tanks 2011a and 2011b in the raw material supply units 2001a and 2001b are stored in the reservoirs 2012a and 2012b. In the mixing / reaction unit 2002, the heating medium is flowed to set the heating (or cooling) temperature in the preheating blocks 2020a and 2020b and the reaction block 2060 to, for example, about −80 ° C. to + 200 ° C., and each temperature is measured by a sensor. It is held at that value by control based on the value.

  By the operation of the fluid transfer pumps 2013a and 2013b, the raw material solutions La and Lb are pumped to the preheating blocks 2020a and 2020b, branch and flow into the heat medium flow path 2023 of each heat exchange element 2063 and 2064, where heat exchange is performed efficiently. To reach a predetermined temperature. The preheated raw material solutions La and Lb respectively flow into the two solution inflow ports 2028A of the mixing block 2040, and pass through the through holes 2049a and 2049b of the cover plates 2045a and 2045b from the raw material inflow passages 2041a and 2041b of the frame body 2043. Via the flow passages 2051a and 2051b of the manifold elements 2044A and 2044B, and further through the parallel liquid separation passages 2052a and 2052b, the jets 2054a opening in a lattice shape on the opening end face 2053 of the manifold 2046. , 2054b to the merging portion 2042 to form a collective flow. Here, since the periphery of one solution flow is covered with another solution, it is necessary for mutual diffusion between the two types of solutions even in the case of a collective flow in which a laminar flow is maintained under the conditions of the microreaction. A sufficient interface can be provided. In addition, since the cross-sectional dimension of the merging portion 2042 is relatively large in millimeters, even if solid matter is generated immediately after merging, the solid portion is not immediately clogged as long as it disappears up to the throttle portion 2065.

  The collective flow composed of the raw material solutions La and Lb further flows from the merging portion 2042 into the throttle portion 2065, and the cross-sectional dimension of the “element flow” of the raw material solutions La and Lb in the reaction channel 2068 further decreases. As a result, the ratio of the interface in the merged flow is further increased, and interdiffusion at the interface is promoted and mixing is promoted. When this flows into the reaction channel 2068 and reaches the reaction temperature, the reaction proceeds promptly.

  The product synthesized by the reaction in this manner is discharged from the reaction block 2060 and stored in the storage tank 2003 under predetermined conditions. Further, the product is concentrated in a downstream purification tank 2004 under a vacuum atmosphere and recovered in the recovery container 2018. An in-line sensor 2071 for evaluating the properties of the synthetic substance can be arranged downstream of the reaction block 2060, and the operating conditions can be feedback controlled based on the measured values. In the illustrated example, a pH meter is used as a sensor, but an appropriate one can be selected according to the product.

  In the above embodiment, even if the dimension of the flow path in the mixing block 2040 is set to 1 mm × 1 mm, for example, the confluence portion becomes 10 mm × 10 mm, and the cross-sectional dimension reduction ratio is 1/10. The dimension of the reaction channel 2068 below the throttle unit 2065 is 1 mm × 1 mm. If a laminar flow is maintained in the collective flow in the reaction channel 2068, the virtual minimum width wmin of the flow in the reaction channel 2068 is 100 μm, which substantially satisfies the conditions of the micro reaction space. Therefore, according to this embodiment, it is possible to realize a micro reaction space of 100 μm class only with an element having a size of mm that can be easily processed. In this way, when the cross-sectional dimension is reduced by the throttle portion, the maximum size of the flow path in the mixing block 2040 is set to 1000 μm or more and 3000 μm or less, so that clogging can be prevented even if solid matter enters.

  In the above-described embodiment, the preheating blocks 2020a and 2020b, the mixing block 2040, and the reaction block 2060 are configured by combining plate-like elements, respectively, so that they can be completely disassembled and cleaned. Yes, it is also suitable for pharmaceutical production with high precision against impurities.

  FIG. 37A to FIG. 37D show an embodiment in which a mixing promoting object is provided instead of the constricting part 2065 in the joining part 2042 of the mixing block 2040. In FIG. 37A, a fine spherical mixing promoting object 2072 is arranged in the merging portion 2042 so as to substantially correspond to the opening of the flow path of the mixing block 2040. By arranging the spherical mixing promoting object 2072 at a predetermined length along the flow path, the collective flow flowing out from the jets 2054a and 2054b is diverted along these, so that the interface between the element flows is The ratio can be improved.

  If the size of the mixing promoting body 2072 is too small compared to the representative length of the element flow, the mixing promoting body 2072 becomes a mere porous body, and sufficient mixing cannot be expected. As a result, the elements flow together and flow, so that sufficient mixing cannot be obtained. The representative length of the optimum mixing promoting body 2072 is desirably 0.1 to 10 times the maximum width of the element flow. Note that the smaller the maximum width of the element flow, the faster the mixing can be expected. At least 800 μm or less, preferably 10 μm or less is preferable.

  As the mixing promoting object, various shapes can be appropriately employed, and these can be appropriately combined. Some examples are shown in FIGS. 37B to 37D. FIG. 37B shows a plurality of mesh-like mixing promoting objects 2073 in which columnar bodies are assembled in a grid, and FIG. 37C shows a mesh-like mixing promoting object 2074 in which parallel columnar bodies are arranged in parallel. In FIG. 37D, a spherical mixing promoting object 2072 is arranged between two mesh-like mixing promoting objects 2073.

  The reaction can be promoted by fixing an appropriate catalyst on the surfaces of the mixing promoting objects 2072 to 2074. In these embodiments using the mixing promoting objects 2072 to 2074, the reaction proceeds in a relatively wide space, so that there is an advantage that the flow path is not easily blocked even when a solid reaction product is generated. In addition, when mixing is insufficient only with the mixing promoting objects 2072 to 2074, it may be used together with the throttle unit 2065. In FIG. 37E, a spherical mixing promoting object 2072 is provided on the downstream side of the throttle unit 2065, and in FIG. 37F, a throttle unit 2065 is provided on the downstream side of the spherical mixing promoting object 2072.

  FIG. 38A shows a configuration of a microreactor according to another embodiment of the present invention, in which a set of mixing blocks 2040A and 2040B having the same structure are arranged to face each other. These mixing blocks 2040A and 2040B are supplied with the raw material solutions La and Lb from the raw material supply units 2001a and 2001b, but are arranged so that different raw material solutions La and Lb flow out from the opposed outlets 2054a and 2054b. To do. Thereby, mixing is promoted by colliding each element flow and forming a jet. The shape of the merging portion 2042A is configured to draw the merging solution in a direction orthogonal to the collision surface. For example, the merging portion 2042A may be configured to be drawn out from its peripheral portion in the tangential direction as a disk-shaped space.

  In this embodiment, since the mixing can be promoted with the wide confluence 2042A without using the restriction 2065, blockage of the flow path can be avoided even when a solid product is generated by the reaction. There are advantages. Of course, depending on the case, as shown in FIG. 38B, it may be used together with the diaphragm 2065, or may be used together with the mixing promoting object 2072 (not shown).

  In these embodiments, the mixing blocks 2040 are opposed to each other from a direction of 180 degrees, but may be opposed to each other at an angle smaller than 180 degrees to form a Y-shaped combined flow path. In the above embodiment, two kinds of fluids are mixed, but it goes without saying that it is suitable for mixing two or more kinds of fluids simultaneously. Moreover, since the temperature of the two mixing blocks 40 can be set differently, it is also suitable when mixing fluids having different stable temperature conditions.

Flow Control Device The present invention further relates to a flow control device that can be used in the fluid reaction device and the fluid mixing device of the present invention.

  In order to achieve the above-described object, one aspect of the present invention is a flow rate adjusting device that adjusts the flow rate of a fluid that flows through a flow path, the temperature adjustment mechanism that heats or cools the fluid that flows through the flow path, From the time difference between the time when the temperature of the fluid at the first measurement point of the flow path changes and the time when the temperature of the fluid at the second measurement point downstream of the first measurement point changes, A flow rate measurement unit that calculates the flow rate of the fluid flowing through, a downstream temperature sensor that measures the temperature of the fluid that passes through the second measurement point, and a control valve provided on the downstream side of the downstream temperature sensor; And a control unit that controls the control valve so that the flow rate of the fluid becomes constant based on the flow rate obtained by the flow rate measurement unit.

  The principle of measuring the fluid flow rate according to the present invention will be described with reference to FIG. In FIG. 42, the vertical axis represents temperature and the horizontal axis represents time. First, the fluid is heated by the temperature control mechanism, and the temperature of the fluid is increased at a predetermined rate of change as indicated by reference numeral T1. At this time, if the fluid is flowing in the flow path, the temperature of the fluid at the first measurement point changes as indicated by reference numeral C1. Furthermore, at the second measurement point located on the downstream side of the first measurement point, the temperature of the fluid changes as indicated by reference numeral C2. In this case, the time difference between the peak of the temperature curve C1 and the peak of the temperature curve C2 is Δt. And the flow volume of the fluid can be calculated | required from the following formula | equation.

Flow rate = distance between first measurement point and second measurement point × channel cross-sectional area ÷ time difference Δt
When fluids having different specific gravities, specific heats, and viscosities flow, the temperature of the fluid at the first measurement point changes as indicated by reference numeral C1 ', and the temperature at the second measurement point changes as indicated by reference numeral C2'. Change. The time difference between the peak of the temperature curve C1 ′ and the peak of the temperature curve C2 ′ is Δt. That is, the time difference between the temperature curve C1 and the temperature curve C2 and the time difference between the temperature curve C1 ′ and the temperature curve C2 ′ are the same. This is because the time difference between the temperature curve on the upstream side and the temperature curve on the downstream side depends only on the flow rate under the condition that the average flow velocity of the fluid is the same even if the specific gravity, specific heat, and viscosity of the fluid are different. For example, as shown in FIG. 41, even if the viscosity of the fluid changes, only the maximum flow rate changes, and the average flow rate (ie, flow rate) does not change. Therefore, if the time difference between the temperature curves appearing at the two measurement points is measured, the flow rate can be accurately measured without being affected by the physical properties of the fluid.

  When the flow rate is as small as 0.01 to 10 L / h, further 0.01 to 2 L / h, the inner diameter of the flow path is as small as 2 mm or less and the Reynolds number is small, so that the fluid flow becomes a laminar flow. Therefore, the curve indicating the flow velocity distribution in the flow path is not disturbed and the shape thereof is stable, thereby enabling the flow rate measurement based on the time difference of the temperature change. This makes it unnecessary to know the physical properties such as specific heat, specific gravity, and viscosity of the reagent in advance, even when testing with various reagents. Can be obtained.

  Examples of fluids used in the present invention include reagents, organic solvents, biochemical substances and the like. For example, in the development stage of pharmaceuticals, so-called screening is performed in which a number of reagents are used and tests are performed while various conditions such as concentration, solvent, and temperature are changed. In this screening, it is required to measure an accurate volume regardless of the physical properties of the reagent. According to the present invention, an accurate volume (flow rate) of a reagent can be obtained regardless of the type of reagent, and thus a preferable development environment can be provided.

  In a preferred aspect of the present invention, the flow rate measurement unit is configured to determine the flow rate of the fluid based on a time difference between two corresponding points on a temperature curve indicating a temperature change of the fluid at the first measurement point and the second measurement point. The flow rate is calculated.

  In the example shown in FIG. 42, the time difference when the peaks of the two temperature curves appear is measured, but the present invention is not limited to this. For example, the time difference at the time of rising of the temperature curve may be obtained, or the time difference at a time point deviated from the peak by a predetermined time may be obtained. Thus, in the present invention, the time difference between two points corresponding to each other on the temperature curve is measured.

  In a preferred aspect of the present invention, an upstream temperature sensor for measuring the temperature of the fluid passing through the first measurement point is further provided. The upstream temperature sensor may include a sensor holder that contacts a fluid flowing through the flow path, and a thermistor inserted into the sensor holder up to a position close to the flow path. Furthermore, the downstream temperature sensor may include a sensor holder that contacts the fluid flowing through the flow path, and a thermistor inserted into the sensor holder to a position close to the flow path.

  In a preferred aspect of the present invention, there is further provided an environmental temperature control mechanism for maintaining a constant temperature in a space including at least the first measurement point and the second measurement point.

  The temperature measurement of the fluid flowing through the minute flow path is easily affected by disturbance, and there is a possibility that accurate flow rate measurement cannot be performed. According to the present invention, disturbances can be blocked by actively keeping the temperature at the first measurement point and the second measurement point constant. Therefore, the flow rate of the fluid can be accurately measured.

  In a preferred aspect of the present invention, the temperature control mechanism includes a Peltier element, a Seebeck element, an electromagnetic wave generator, or a resistance heating wire.

  The temperature adjustment mechanism is not limited to the heating unit, and a cooling unit may be used. In addition, the temperature control mechanism is configured to heat or cool the structure having a cylindrical portion in which holes forming the flow path are formed and a heat transfer portion that transfers heat to the cylindrical portion, and the heat transfer portion of the structure. And a temperature control member.

  In a preferred aspect of the present invention, the control valve includes a valve that adjusts a flow rate and a drive source that drives the valve, and the drive source includes a piezoelectric element, an electromagnet, a servo motor, or a stepping motor. It is characterized by having.

  According to the present invention, by using a drive source with good responsiveness, it is possible to quickly drive the valve based on the actual flow rate measured by the flow rate measurement unit and keep the flow rate constant.

  In a preferred aspect of the present invention, the control valve has a valve for adjusting a flow rate and a drive source for driving the valve, and the drive source has a structure in which a plurality of piezoelectric elements are stacked. It is characterized by.

  According to the present invention, even when a high-pressure fluid flows, the flow rate can be kept constant without being affected by high pressure or pressure fluctuation.

  In a preferred aspect of the present invention, the pressure of the fluid passing through the control valve is 1 MPa to 10 MPa.

  In a preferred aspect of the present invention, the flow rate of the fluid passing through the control valve is 0.01 to 10 L / h.

  In a preferred aspect of the present invention, the flow path is formed of a corrosion-resistant material.

  In a preferred aspect of the present invention, the material is stainless steel, titanium, polyetheretherketone, polytetrafluoroethylene, or polychlorotrifluoroethylene.

  Another aspect of the present invention is a fluid reaction characterized by comprising a plurality of containers for storing fluids, a mixing unit for mixing fluids, a reaction unit for reacting the mixed fluids, and the flow rate adjusting device. Device.

  Hereinafter, a flow control device according to an embodiment of the present invention will be described with reference to the drawings. FIG. 43 is a schematic view showing a flow rate adjusting device according to the first embodiment of the present invention. As shown in FIG. 43, the flow rate adjustment device of this embodiment includes a flow rate measurement unit 3010 that measures the flow rate of the liquid (fluid) flowing through the flow path 3001, a control valve 3020 that adjusts the flow rate of the liquid, and a flow rate measurement unit. The control unit 3030 basically controls the control valve 3020 based on the flow rate measured by 3010.

  The flow rate measurement unit 3010 includes a temperature adjustment mechanism 3002 that heats the liquid flowing through the flow path 3001 at a predetermined cycle, and an upstream temperature sensor 3003 and a downstream temperature sensor 3004 that measure the temperature of the liquid flowing through the flow path 3001. ing. The temperature adjustment mechanism 3002 is provided so as to surround the wall portion of the flow path 3001 and heats the liquid via the wall portion of the flow path 3001. The temperature adjustment mechanism 3002 is connected to a temperature control unit 3005 and heats the liquid at an optimal temperature increase rate. Note that as the temperature adjustment mechanism 3002, a Peltier element, Seebeck element, electromagnetic wave generator, resistance heater, or the like is preferably used. Further, the temperature adjustment mechanism 3002 may change the temperature of the liquid by cooling the liquid.

  The upstream temperature sensor 3003 is disposed at the first measurement point P1 of the flow path 3001, and measures the temperature of the liquid passing through the first measurement point P1. The downstream temperature sensor 3004 is disposed at the second measurement point P2 of the flow path 1, and measures the temperature of the liquid that passes through the second measurement point P2. The flow rate measurement unit 3010 includes a time difference measurement unit 3009 that obtains the flow rate of the liquid based on the time difference during which the heated liquid passes through the two measurement points P1 and P2.

  The upstream temperature sensor 3003 is located on the downstream side of the temperature adjustment mechanism 3002 and is disposed close to the temperature adjustment mechanism 3002. The downstream temperature sensor 3004 is located on the downstream side of the upstream temperature sensor 3003 and is arranged at a predetermined distance from the upstream temperature sensor 3003. Each of the upstream temperature sensor 3003 and the downstream temperature sensor 3004 is attached to the outer surface of the flow path 3001 and measures the temperature of the liquid through the wall portion of the flow path 3001. As the upstream temperature sensor 3003 and the downstream temperature sensor 3004, a thermistor thermometer or a thermocouple having excellent responsiveness is preferably used.

  The upstream temperature sensor 3003 and the downstream temperature sensor 3004 are connected to the time difference measuring unit 3009, and the outputs of the upstream temperature sensor 3003 and the downstream temperature sensor 3004 are sent to the time difference measuring unit 3009. The principle that the flow rate of the liquid is measured by the time difference measuring unit 3009 is as already described with reference to FIG. That is, when the temperature adjustment mechanism 3002 heats the liquid while the liquid is flowing, the heated liquid flows downstream, and the first measurement point P1 on the upstream side and the second measurement point P2 on the downstream side are changed to this. Pass in order. At this time, the temperature of the liquid at the first measurement point P1 is measured by the upstream temperature sensor 3003, and the temperature of the liquid at the second measurement point P2 is measured by the downstream temperature sensor 3004.

  The outputs of the upstream temperature sensor 3003 and the downstream temperature sensor 3004 are continuously sent to the time difference measuring unit 3009, where the peaks of the temperature curve C1 and the temperature curve C2 (see FIG. 42) are detected. The peak of the temperature curve can be detected using a known method. For example, a peak can be determined when the sign of the difference between the two measured values changes. Then, the difference between the time when the peak of the temperature curve C1 appears and the time when the peak of the temperature curve C2 appears is calculated, and the flow rate of the liquid flowing through the flow path 1 is obtained from the following equation.

Flow rate (L / h) = Distance between sensors (distance between the first measurement point P1 and the second measurement point P2) × cross-sectional area of the flow path 1 ÷ time difference The point to be compared when calculating the time difference is the temperature It is not limited to the peak of the curve. That is, the time difference between two corresponding points on the temperature curve may be obtained. For example, the time difference between the rises of the two temperature curves may be obtained.

  As shown in FIG. 43, the control valve 3020 is disposed on the downstream side of the flow rate measurement unit 3010. The control valve 3020 includes a piston (valve) 3021 disposed so as to face the liquid flow, and a piezoelectric element (drive source) 3022 that drives the piston 3021. A piezoelectric element (piezoelectric actuator) 3022 is fixed to the back surface of the piston 3021, and the piezoelectric element 3022 and the piston 3021 are integrally formed. The piston 3021 and the piezoelectric element 3022 are accommodated in the piston chamber 3023. A part of the flow path 3001 has a T-shaped path, and the piston 3021 is arranged so that the liquid flowing into the T-shaped path hits the front surface of the piston 3021. When a voltage is applied to the piezoelectric element 3022, the piezoelectric element 3022 expands and contracts, thereby moving the piston 3021 along the liquid flow direction to adjust the opening degree α of the piston 3021.

  A throttle portion 3001a is provided on the upstream side of the piston 3021. By narrowing the flow path 3001, the flow rate can be accurately adjusted by the piston 3021. The above-described piston chamber 3023 is formed in a bottomed cylindrical shape, and this piston chamber 3023 is liquid-tightly fixed to the outer surface of the flow path 3001. With such a configuration, even when the liquid leaks from the gap between the piston 3021 and the flow path 3001, the liquid is held inside the piston chamber 3023, so that leakage of the liquid to the outside is prevented.

  In the microreactor incorporating the flow control device according to the present embodiment, a reaction product is generated on the downstream side of the flow control device by reaction between reagents. In this case, depending on the type of the reaction product, the pressure of the liquid on the downstream side of the flow rate adjusting device may increase, and the liquid may leak from the flow path 1. According to the present embodiment, liquid leakage to the outside can be prevented by the bottomed cylindrical piston chamber 3023, so that accurate flow rate adjustment is possible.

  Next, the control unit 3030 will be described. The control unit 3030 includes an amplifier 3032 connected to the time difference measurement unit 3009, a comparison unit (PID control unit) 3033 that determines the opening of the piston 3021 for keeping the flow rate constant, and a piezoelectric element 3022 of the control valve 3020. And a piston drive circuit 3034 for generating a voltage to be applied. The amplifier 3032 amplifies the signal representing the liquid flow rate (actual flow rate) calculated by the time difference measurement unit 3009 and sends the amplified signal (actual flow rate) to the comparison unit 3033. A set flow rate (target value) is input in advance to the comparison unit 3033. The comparison unit 3033 compares the actual flow rate with the set flow rate, and calculates the opening degree of the piston 3021 for making the actual flow rate coincide with the set flow rate. To do. The opening degree of the piston 3021 calculated by the comparison unit 3033 is converted into a voltage by the piston drive circuit 3034. This voltage is applied to the piezoelectric element 3022, and the piston 3021 is driven by the piezoelectric element 3022. In this way, the control valve 3020 is controlled by the control unit 3030 so that the flow rate of the liquid passing through the control valve 3020 is always constant.

  In order to quickly reflect the measurement result of the flow rate measurement unit 3010 in the operation of the control valve 3020, the distance of the flow path 3001 between the flow rate measurement unit 3010 and the control valve 3020 is preferably as short as possible. That is, the distance between the downstream temperature sensor 3004 and the piston 3021 is preferably 10 to 100 mm, more preferably 10 to 50 mm, and still more preferably 10 to 20 mm. In addition, it is preferable to use a drive source (actuator) used for the control valve 3020 having excellent responsiveness such as a piezoelectric element. By doing in this way, the fluctuation | variation (pulsation) of the flow volume which flows through the flow path 3001 can be eliminated rapidly, and a fixed flow volume can be maintained.

  This flow control device is suitably used for a fluid reaction device (microreactor) that reacts two or more kinds of liquids. In general, the smaller the mixing space in which the liquid is mixed, the faster the liquid is mixed. The inner diameter of the flow path 3001 of the flow control device according to this embodiment is preferably 0.1 to 5 mm, more preferably 0.1 to 2 mm, and further preferably 0.1 to 1 mm. Moreover, when only a very small amount is used as the handling range, the minimum diameter can be set to 0.02 mm. In addition, when the width | variety (inner diameter) of a flow path becomes small, it will be necessary to transfer a liquid by a high voltage | pressure. In the present embodiment, the pressure of the liquid at the outlet of the flow rate adjustment device (downstream of the control valve 3020) is 1 MPa to 10 MPa, 2 MPa to 5 MPa, or 3 MPa to 4 MPa.

  Examples of liquids to be handled include reagents, organic solvents, and biochemical substances. Therefore, it is preferable that the material constituting the flow path 3001 has corrosion resistance. As described above, since the upstream temperature sensor 3003 and the downstream temperature sensor 3004 measure the temperature of the liquid through the wall portion of the flow path 3001, the material constituting the flow path 3001 is excellent in thermal conductivity. Those that can withstand a wide temperature range of −40 to 150 ° C. are preferable. Furthermore, the material constituting the flow path 3001 is preferably one that can withstand the high pressure of the liquid. Considering these points, preferable examples of the material constituting the flow path 3001 include stainless steel such as SUS316 or SUS304, hard glass such as Ti (titanium), quartz glass, or Pyrex (registered trademark) glass, PEEK (polyetheretherketone). , PE (polyethylene), PVC (polyvinylchloride), PDMS (polydimethylsiloxane), Si, PTFE (polytetrafluoroethylene), and PCTFE (polychlorotrifluoroethylene).

  When stainless steel or Ti is used, the wall thickness of the channel 3001 is preferably 0.01 to 0.1 mm. When resin such as PEEK, PTFE, PCTFE is used, the wall of the channel 3001 is used. The thickness of the part is preferably 0.5 to 1 mm. Considering thermal conductivity, it is preferable to use Ti having a small heat capacity. When resin is used, it is preferable to improve the thermal conductivity by locally reducing the thickness of the portion of the flow path 3001 to which the upstream temperature sensor 3003 and the downstream temperature sensor 3004 are attached.

  Note that the channel 3001 may be composed of a combination of a plurality of materials selected from the above materials. For example, a material having corrosion resistance may be used for the liquid contact portion of the channel 3001, and a pressure resistant material may be stacked on the outside thereof. Further, in order to accurately measure the temperature of the liquid, it is preferable to configure the flow path 3001 as follows. That is, a portion where the upstream temperature sensor 3003 and the downstream temperature sensor 3004 are provided is made of a material having high thermal conductivity, and a portion between the upstream temperature sensor 3003 and the downstream temperature sensor 3004 has low thermal conductivity. Consists of materials. According to such a configuration, the influence of the flow path 3001 on the temperature measurement can be reduced, and the heat of the temperature adjustment mechanism 3002 travels through the flow path 3001 and affects the measurement value of the downstream temperature sensor 3004. It can prevent giving.

  FIG. 44 is a cross-sectional view showing another configuration example of the temperature adjustment mechanism and the upstream temperature sensor. In the example shown in FIG. 44, a hole 300 is formed in a case main body 3012 made of a fluororesin such as PTFE or PCTFE to form a flow path 3001 extending in the longitudinal direction. The case body 3012 is formed with a recess 3012a by drilling in a direction perpendicular to the flow path 3001. A structure 3013 for heating the liquid flowing through the flow path 3001 is inserted into the recess 3012 a of the case body 3012.

  FIG. 45A is a sectional view taken along line VII-VII in FIG. As shown in FIGS. 44 and 45 (a), the structure 3013 includes a cylindrical portion 3013b in which a through-hole 3013a having a rectangular or circular cross section forming the flow path 3001 is formed at the tip portion, and a case body 3012. And a heat transfer portion 3013c located outside. The heat transfer part 3013c is provided at the end opposite to the end where the through hole 3013a is formed. In the example shown in FIG. 45 (a), the outside of the copper heat transfer portion 3013c is covered with a chemical-resistant titanium cylindrical portion 3013b, but the cylindrical portion 3013b and the heat transfer portion 3013c are the same. You may form integrally with material.

  The cylindrical portion 3013b is fixed to the case main body 3012 by fixing a fixing plate 3014 made of a heat insulating material such as PEEK to the case main body 3012 with a bolt 3015. Further, a seal member 3016 is disposed between the case main body 3012 and the cylindrical portion 3013b, and the seal member 3016 prevents liquid leakage.

  A temperature control member 3017 such as a heater or a Peltier element is attached to the heat transfer part 3013c of the structure 3013, and heat from the temperature control member 3017 is transferred to the cylindrical part 3013b via the heat transfer part 3013c. ing. Therefore, the heat from the temperature adjustment member 3017 is transmitted to the liquid passing through the through hole 3013a through the copper heat transfer portion 3013c and through the titanium cylindrical portion 3013b. In this manner, the liquid flowing through the flow path 3001 is heated by passing through the through hole 3013a of the structure 3013. Note that the copper heat transfer section 3013c and the temperature adjustment member 3017 do not directly contact the liquid. Note that when the liquid is cooled using a Peltier element or the like for the temperature adjustment member 3017, the heat flow is opposite to that described above.

  FIG. 45B is a cross-sectional view illustrating another configuration example of the structure described above. Although titanium has chemical resistance, its thermal conductivity is worse than that of copper. Therefore, in the example shown in FIG. 45B, the cylindrical portion 3013b and the heat transfer portion 3013c of the structure 3013 are integrally formed of a copper material. Yes. Further, the through hole 3013a is formed so that the cross section is circular. Parts exposed to the liquid, such as the inner surface of the through hole 3013a and the outer surface of the cylindrical portion 3013b, are plated with a material having chemical resistance. A seal member for preventing leakage of liquid is disposed between the cylindrical portion 3013b subjected to the plating process and the case main body. With such a configuration, heat from the temperature adjustment member is more efficiently transmitted to the liquid flowing through the through hole 3013a.

  As shown in FIG. 44, the upstream temperature sensor 3003 is inserted into a hole 3012b formed in a direction orthogonal to the flow path 3001, and includes a sensor holder 3003a made of a metal having chemical resistance such as titanium, And a thermistor 3003b inserted into the sensor holder 3003a up to a position close to the path 3001. A through-hole constituting the flow path 3001 may be provided at the tip of the sensor holder 3003a, similarly to the structure 3013 of the heating unit. The tip of the sensor holder 3003a is in contact with the liquid in the flow path 3001, but the thermistor 3003b is not in direct contact with the liquid flowing in the flow path 3001. The thermistor 3003b can detect the temperature of the liquid flowing through the flow path 3001. The sensor holder 3003a is fixed to the case main body 3012 by a bolt 3018. Further, a seal member 3019 is disposed between the case main body 3012 and the sensor holder 3003a, and the liquid leakage is prevented by the seal member 3019. Note that when the liquid is cooled using a Peltier element or the like for the temperature adjustment member 3017, the heat flow is opposite to that described above.

  In the above example, the sensor holder 3003a is formed of a metal having chemical resistance such as titanium. However, the sensor holder 3003a is formed of copper having good heat conductivity, and the portion that comes into contact with the liquid is resistant to the liquid. Plating may be performed with a material having chemical properties. With such a configuration, the temperature of the liquid flowing through the flow path 3001 can be detected efficiently. In FIG. 44, only the upstream temperature sensor 3003 has been described, but it is needless to say that the structure shown in FIG. 44 can also be applied to the downstream temperature sensor 3004.

  FIG. 46 is an enlarged view showing another configuration example of the control valve. As described above, the drive source that drives the piston 3021 is required to drive the piston 3021 against high-pressure liquid. In the configuration example shown in FIG. 46, two piezoelectric elements 3022 are stacked in order to increase the driving force. With such a configuration, even when the liquid is high pressure, the opening degree α of the piston 3021 can be accurately adjusted, and the flow rate can be kept constant. If necessary, three or more piezoelectric elements may be stacked.

  Next, a second embodiment of the present invention will be described with reference to FIG. FIG. 47 is a schematic diagram showing a flow rate adjusting device according to a second embodiment of the present invention. Note that the configuration of the present embodiment that is not particularly described is the same as the configuration of the first embodiment described above, and thus the redundant description thereof is omitted.

  As already described, since the flow rate measurement unit 3010 obtains the flow rate using the temperature change of the liquid, the accurate flow rate cannot be obtained if the temperature of the ambient atmosphere changes. Therefore, in this embodiment, the environmental temperature control mechanism 3011 is arranged in the flow rate measurement unit 3010 in order to stably measure the temperature of the liquid. This environmental temperature control mechanism 3011 includes a partition wall 3011a that hermetically accommodates the upstream temperature sensor 3003 and the downstream temperature sensor 3004, a temperature controller 3011b such as a Peltier element that adjusts the temperature of the internal space of the partition wall 3011a, and a partition wall 3011a. A temperature sensor 3011c for measuring the temperature of the internal space of the slab and a temperature controller 3011d for controlling the temperature controller 3011b based on a signal from the temperature sensor 3011c (actual temperature of the internal space). Note that the temperature controller 3005 described above may be used as the temperature controller 3011d.

  The partition wall 3011a is made of a heat insulating material. The temperature controller 3011b is connected to the temperature controller 3011d and is controlled by the temperature controller 3011d so as to keep the temperature of the internal space constant. According to the environmental temperature control mechanism 3011 configured as described above, the upstream temperature sensor 3003 (that is, the first measurement point P1), the downstream temperature sensor 3004 (the second measurement point P2), and the flow located therebetween. The temperature around the site of the path 3001 can be kept constant, and the thermal disturbance can be blocked. Therefore, the time difference measuring unit 3009 can perform accurate flow rate measurement, and as a result, the flow rate can be kept constant with high accuracy.

  Next, a third embodiment of the present invention will be described with reference to FIG. FIG. 48 is a schematic diagram showing a flow rate adjusting device according to a third embodiment of the present invention. Note that the configuration of the present embodiment that is not particularly described is the same as the configuration of the first embodiment described above, and thus the redundant description thereof is omitted.

  As shown in FIG. 48, in this embodiment, the upstream temperature sensor 3003 is omitted, and the time difference measuring unit 3009 is connected to the temperature adjustment mechanism 3002 and the downstream temperature sensor 3004. In the present embodiment, the first measurement point P1 is the position of the temperature adjustment mechanism 3002.

  Here, the principle by which the flow rate is measured by the flow rate measurement unit 3010 of this embodiment will be described with reference to FIG. The liquid flowing through the flow path 3001 is heated by the temperature adjustment mechanism 3002, and the heating start time t1 is recorded in the time difference measuring unit 3009. At this time, in the temperature adjustment mechanism 3002 (that is, the first measurement point P1), the temperature of the liquid rises at a predetermined rate of change as indicated by the temperature curve T3. The heated liquid flows through the flow path 3001 and eventually passes through the second measurement point P2. At this time, the temperature curve C3 is detected by the downstream temperature sensor 3004. Then, the time difference measuring unit 3009 obtains the time difference Δt between the rising point t1 of the temperature curve T3 and the rising point t2 of the temperature curve C3, and the liquid flow rate is calculated by the above-described equation. As in the example described with reference to FIG. 42, the time difference at which the peaks of the two temperature curves appear may be measured.

  As shown in FIG. 48, in the control valve 3020 of this embodiment, a cylindrical spool 3024 is used instead of the piston 3021. The spool 3024 is disposed on the T-shaped path of the flow path 3001, and the tip of the spool 3024 is slidably fitted in the flow path 3001. A magnetic body (eg, iron core) 3025 is attached to the end of the spool 3024, and an electromagnet 3026 is disposed around the magnetic body 3025. A seal member 3027 is disposed between the electromagnet 3026 and the flow path 3001, and liquid leakage is prevented by the seal member 3027. The magnetic body 3025 is driven by the electromagnetic force formed by the electromagnet 3026, whereby the spool 3024 moves along its axial direction. The control valve 3020 having such a configuration is called a solenoid valve (electromagnetic valve).

  FIG. 50 is a perspective view of the spool shown in FIG. As shown in FIG. 50, an obliquely extending groove 3024 a is formed on the side surface of the spool 3024. The groove 3024a has a triangular cross section, and the size of the cross section changes according to the axial position. That is, the cross section of the groove 3024a is the largest at the tip of the spool 3024, and gradually decreases as the cross-sectional position moves toward the opposite end. Since the liquid flows through the groove 3024a, the flow rate can be adjusted by moving the spool 3024 in the axial direction. In this case, the opening degree α of the spool (valve) 3024 can be expressed by the length of the groove 3024a protruding from the flow path 3001.

  The control unit 3030 of this embodiment includes a spool drive circuit 3035 instead of the piston drive circuit. The spool drive circuit 3035 converts the opening degree of the spool 3024 calculated by the comparison unit 3033 into a current, and the current is supplied to the electromagnet 3026 so that the spool 3024 moves. In this way, the control valve 3020 is controlled by the control unit 3030 so that the flow rate of the liquid passing through the control valve 3020 is always constant. It is preferable to use an electromagnet capable of generating a large electromagnetic force in order to make the flow rate constant accurately even when the liquid is high pressure.

  Next, a fourth embodiment of the present invention will be described with reference to FIG. FIG. 51 is a schematic diagram showing a flow rate adjusting device according to a fourth embodiment of the present invention. Note that the configuration of the present embodiment that is not particularly described is the same as the configuration of the first embodiment described above, and thus the redundant description thereof is omitted.

  As shown in FIG. 51, the control valve 3020 of the present embodiment includes an inverted triangular pyramid-shaped poppet 3041 instead of the piston 3021. The poppet 3041 is located at the T-shaped path of the flow path 3001 and is arranged so that the tip thereof faces the liquid flow. A shaft 3042 is integrally fixed to the poppet 3041, and this shaft 3042 is fitted to a bottomed cylindrical shaft guide 3043. A gear 3044 is provided on the outer peripheral surface of the shaft guide 3043, and the gear 3044 meshes with a gear 3046 connected to a servo motor 3045. The shaft 3042 is configured not to rotate by a rotation prevention mechanism (not shown) such as a key or a key groove. Note that the poppet 3041, the shaft 3042, and the shaft guide 3043 are aligned on the same axis.

  A seal member 3047 is disposed between the shaft guide 3043 and the flow path 3001 to prevent liquid from leaking from the flow path 3001. A male screw 3042a is formed on the outer peripheral surface of the shaft 3042, and a female screw (not shown) that meshes with the male screw 3042a is formed on the inner peripheral surface of the shaft guide 3043. With such a configuration, when the shaft guide 3043 is rotated by the servo motor 3045, the poppet 3041 moves in the vertical direction with respect to the opening of the T-shaped path, thereby adjusting the opening α of the poppet (valve) 3041. The A stepping motor may be used instead of the servo motor.

  The control unit 3030 of this embodiment includes a poppet drive circuit 3048 instead of the piston drive circuit. The poppet driving circuit 3048 converts the opening of the poppet 3041 calculated by the comparison unit 3033 into a current, and the current is supplied to the servo motor 3045 so that the poppet 3041 moves. In this way, similarly to the first embodiment, the control valve 3020 is controlled by the control unit 3030 so that the flow rate of the liquid passing through the control valve 3020 is always constant. Note that it is preferable to use a servo motor or a stepping motor capable of generating a large torque in order to make the flow rate constant accurately even when the liquid is high pressure.

  Note that the above-described embodiments can be combined as necessary. For example, the environmental temperature control mechanism 3011 according to the second embodiment may be incorporated in the third and fourth embodiments. Further, the flow rate adjusting device according to the above-described embodiment can measure and control not only liquid but also gas flow rate.

  Next, a fluid reaction device (microreactor) incorporating the above-described flow rate adjusting device according to an embodiment of the present invention will be described. FIG. 52 to FIG. 54 (b) are diagrams showing the overall configuration of a fluid reaction device incorporating a flow rate adjusting device according to an embodiment of the present invention. The fluid reaction apparatus described below is an apparatus used for mixing and reacting two or more kinds of liquids.

  As shown in FIG. 52, FIG. 53, FIG. 54 (a), and FIG. 54 (b), the entire fluid reaction device is installed in one installation space and packaged. In this configuration example, the installation space is rectangular and is divided into four regions along the longitudinal direction. That is, the first region on one end side is a raw material storage unit 3101 in which a plurality of storage containers 3110 (only two storage containers 3110A and 3110B are shown in FIG. 52) for storing the raw material liquid are installed, and adjacent thereto. The second region is a liquid distribution unit 3102 in which pumps 3116A and 3116B for transferring the raw material liquid in the storage container 3110 are installed. A third region adjacent to the second region is a processing unit 3103 having a mixing unit (mixing chip) 3140 for mixing the raw material liquid and a reaction unit (reaction chip) 3142 for reacting the mixed raw material liquid. . The fourth region on the other end side is a product storage unit (recovery container installation space) 3104 for deriving and storing a product obtained as a result of the processing.

  The fluid reaction apparatus also includes an operation control unit 3106 that is a computer that controls the operation of each unit, and a heat medium controller 3107 that adjusts the temperature of the processing unit 3103 by flowing a heat medium through the temperature adjustment case 3146. . As shown in FIG. 52, the operation control unit 3106 is equipped with a flow rate monitor 3270 and a temperature monitor 3272 that can monitor the flow rate and temperature of the liquid. In this configuration example, the operation control unit 3106 and the heat medium controller 3107 are separated from the fluid reaction device, but may be integrated as a matter of course. As shown in FIG. 53, a piping chamber 3105 is formed in the lower floor portion of the second to fourth regions, and piping for sending a heating medium for heating or cooling to the mixing unit 3140 and the reaction unit 3142 is provided here. Is provided.

  In this way, by arranging the respective parts from the upstream side to the downstream side, the flow of the liquid can be made smooth, and the entire apparatus can be made compact. In this configuration example, each part is arranged in a straight line. However, for example, if the entire space is close to a square, each part may be configured such that the liquid flow forms a loop.

  In FIG. 53, reference numeral 3250 denotes a liquid reservoir pan provided at the lower part of the apparatus, and reference numeral 3252 denotes a liquid leakage sensor installed on the liquid reservoir pan 3250. In this example of the apparatus, the liquid distribution unit 3102, the processing unit 3103, and the product storage unit 3104 are partitioned by partition walls 3254 and 3256, and covers 3258, 3260 and 3262 are attached to the respective units to isolate them from the outside of the apparatus. is doing. Reference numeral 3264 denotes an exhaust port, which is connected to an exhaust fan (not shown). And the toxic gas in the apparatus is prevented from leaking outside by making the pressure in the apparatus negative from the outside of the apparatus.

  In the raw material storage unit 3101 shown in FIG. 52, two storage containers 3110A and 3110B are installed, but three or more storage containers may be used as necessary. For example, the process can be continuously performed by storing the same liquid in two storage containers and using them alternately. Note that the raw material reservoir 3101 may be provided with a cleaning liquid container 3112 containing an organic solvent such as acetone for line cleaning, hydrochloric acid, pure water, or the like, or a pressure source 3114 filled with a purge nitrogen gas. Further, the waste liquid container 3136 may be placed in the raw material storage unit 3101.

  Pumps 3116A and 3116B connected to the storage containers 3110A and 3110B via the transport pipes 3121A and 3121B are installed in the liquid distribution unit (introduction unit) 3102. A centrifugal pump is used for the pumps 3116A and 3116B in FIG. Further, the liquid distribution unit 3102 includes flow rate adjusting devices 3300A and 3300B, relief valves 3122A and 3122B, pressure measurement sensors 3124A and 3124B, flow path switching valves 3126A and 3126B, and backwashing that are arranged downstream of the pumps 3116A and 3116B. A pump 3130 is included. The flow path switching valves 3126A and 3126B are connected to a cleaning liquid container 3112 and a pressure source 3114 in addition to the transport pipes 3121A and 3121B, respectively. The backwash pump 3130 is used when the flow path of the mixing unit 3140 or the reaction unit 3142 is blocked by the product. The backwash pump 3130 is connected to a cleaning liquid container 3112 that stores cleaning liquid, and is further connected to an outlet of the reaction unit 3142 via a flow path switching valve 3132. The cleaning liquid transferred by the backwash pump 3130 flows in reverse to the normal flow. That is, the cleaning liquid flows from the outlet of the reaction unit 3142 toward the inlet of the mixing unit 3140, passes through the flow path switching valves 3126 </ b> A and 3126 </ b> B, and enters the waste liquid storage container 3136 from the waste liquid port 3134 through a pipe (not shown).

  The backwash pump 3130 is preferably a single piston pump so that the discharge pressure is high and the product can be removed by causing pulsation in the cleaning liquid. As the cleaning liquid, an organic solvent, hydrochloric acid, nitric acid, phosphoric acid, organic acid, pure water, or the like is preferably used. Examples of the organic solvent include acetone, ethanol, methanol and the like. An introduction port 3240 shown in FIG. 52 is provided when pure water or hydrogen water is introduced from the outside, and can be used for cleaning instead of the cleaning liquid in the cleaning liquid container 3112.

  FIG. 55 shows a mixing unit 3140 for performing preheating (preliminary temperature adjustment) and mixing of the raw material liquid. The upper plate 3144a, the middle plate 3144b, and the lower plate 3144c, which are three thin plate-like base materials, are shown. A mixing portion 3140 having a total thickness of 5 mm is formed by bonding. Note that the flow paths described below are all grooves formed on the surface of the intermediate plate 3144b. Two inflow ports 3147A and 3147B formed through the upper plate 3144a communicate with two preheating channels 3148A and 3148B formed on the upper surface of the middle plate 3144b, respectively. These preheating flow paths 3148A and 3148B each branch in the middle and expand, and merge again. Further, the preheating channels 3148A and 3148B communicate with the outlet channels 3150A and 3150B, respectively, and these outlet channels 3150A and 3150B communicate with the junction 3152. The outlet channel 3150A is formed on the upper surface of the middle plate 3144b, and the outlet channel 3150B is formed on the lower surface of the middle plate 3144b.

  56 is an enlarged view of the merging portion shown in FIG. As shown in FIG. 56, the merging portion 3152 includes header portions 3154 and 3155 formed on the upper and lower surfaces of the middle plate 3144b as arc-shaped grooves that communicate with the outlet flow paths 3150A and 3150B, respectively, and the header portions 3154 and 3155. A plurality of liquid separation flow paths 3156 and 3157 extending toward the center of the arc and a merge space 3158 where these liquid separation flow paths 3156 and 3157 merge. Separation channels 3156 and 3157 and merge space 3158 are formed on the upper surface of intermediate plate 3144b, and separation channels 3156 and 3157 are arranged alternately. The header portion 3155 on the lower surface side and the liquid separation flow path 3157 communicate with each other through a communication hole 3157a penetrating the intermediate plate 3144b. The merge space 3158 is formed so that the width gradually decreases toward the downstream side, and communicates with an outflow port 3160 formed through the middle plate 3144b and the lower plate 3144c.

  In the example shown in FIG. 56, five separation channels 3156 and four separation channels 3157 are alternately arranged on the inlet side opening surface 3159 of the merge space 3158. The two types of liquids respectively flowing out from the separation flow paths 3156 and 3157 flow downstream while forming a stripe-shaped flow in the merge space 3158, and are forced as the flow path width of the merge space 3158 gradually decreases. Both liquids are mixed. In this example, the flow path width of the merge space 3158 finally reaches 40 μm. If the processing technology accuracy is increased, the flow path width can be reduced to 10 μm.

  FIG. 57 (a) is a plan view showing the reaction part shown in FIG. 52, and FIG. 57 (b) is a cross-sectional view of the reaction part shown in FIG. 57 (a). In this example, two base materials 3144d and 3144e are joined to form a reaction portion 3142 having a thickness of 5 mm. In this reaction part 3142, the reaction flow path 3162 meanders, and provides a long flow path efficiently. The reaction channel 3162 includes connecting portions 3162a and 3162c connected to the inlet port 3164 and the outlet port 3165, respectively, and a meandering portion 3162b communicating with the connecting portions 3162a and 3162c. The width of the connecting portions 3162a and 3162c is narrow. The meandering portion 3162b is formed wider. Therefore, the liquid flows rapidly in the entrance / exit portion to prevent adhesion of by-products, and flows gently in the meandering portion 3162b, so that the heating and reaction time can be increased.

  58 (a) and 58 (b) show another example of the structure of the reaction part having the part 3163a in which the width of the reaction channel gradually decreases and the part 3163b in which the width gradually increases. In the reaction portion 3142a, a reaction flow path 3163 is formed between the base materials 3144d and 3144e so that the width dimension increases or decreases in the range from the maximum a to the minimum b. The depth may be increased or decreased according to the increase or decrease of the width dimension. In this example, the depth changes from the maximum c to the minimum d so that the cross-sectional area of the reaction channel 3163 is constant.

  FIG. 58 (c) is a cross-sectional view showing another configuration example of the reaction channel. In this reaction part 3142b, the reaction flow path 3163c has a flat shape whose width e is larger than the depth f, and has a wide heat transfer surface intersecting the heat transfer direction (indicated by an arrow) from the thermal catalyst. Therefore, heat is effectively transferred to the liquid in the reaction channel 3163c. In addition, it is effective in order to accelerate | stimulate reaction to arrange | position a suitable catalyst in the confluence | merging space 3158 and the reaction flow path 3162, 3163. FIG. Such a catalyst is selected depending on the type of reaction. As for the arrangement method, for example, it can be applied to the inner surface of the channel, or can be arranged as an obstacle of the channel as described later.

  Examples of a material that forms at least the flow path of the mixing unit 3140 and the reaction unit 3142 include, for example, hard glass such as SUS316, SUS304, Ti, quartz glass, and Pyrex (registered trademark) glass, PEEK (polyetheretherketone), PE (polyethylene), Among PVC (polyvinylchloride), PDMS (Polydimethylsiloxane), Si, PTFE (polytetrafluoroethylene), and PCTFE (PolyChloroTriFluoroEthylene), a preferable one is selected in consideration of chemical resistance, pressure resistance, thermal conductivity, heat resistance, and the like. The material of the wetted part of the mixing part 3140 and the reaction part 3142 is preferably one that has little elution from the surface, can be modified with a surface catalyst, has a certain degree of chemical resistance, and can withstand a wide temperature range of −40 to 150 ° C. .

  FIG. 59 is a perspective view showing a configuration of a temperature adjustment case for adjusting the temperatures of the mixing unit and the reaction unit. In the following description, only the temperature adjustment case 3146 for adjusting the temperature of the reaction unit 3142 will be described, but the temperature adjustment case 3146 for the mixing unit 3140 also has the same configuration, and redundant description thereof is omitted. To do. The temperature adjustment case 3146 includes a case main body 3172 in which a space 3170 that accommodates the reaction portion 3142 is formed, and a lid portion 3174 that covers the space 3170. A groove 3176 constituting the medium flow path is formed. A liquid supply path 3178 and a drainage path 3180 (see FIG. 52) communicating with the groove 3176 are formed in the case main body 3172. The liquid supply path 3178 and the drainage path 3180 are connected to the heat medium controller 3107, respectively. Yes. The liquid supply path 3178 communicates with the groove 3176 of the lid 3174 via the opening 3179, and the drainage path 3180 also communicates with the groove 3176 of the lid 3174 via an opening (not shown). In this example, the heat medium flowing through the groove 3176 directly contacts the front and back surfaces of the reaction unit 3142, and the reaction unit 3142 is heated (or cooled) in a state of being completely accommodated in the temperature adjustment case 3146.

  Although not shown, the heat medium controller 3107 includes a control mechanism for controlling the temperature of the heat medium and a pump for transferring the heat medium. As shown in FIG. 52, the heat medium is supplied to the temperature adjustment case 3146 of the mixing unit 3140 and the reaction unit 3142 after passing through the heat exchanger 3182. The heat exchanger 3182 can change the temperature of the heat medium supplied to the mixing unit 3140 and the reaction unit 3142 independently by changing the amount of city water for cooling, for example.

  60 (a) to 60 (d) show another example of the temperature adjustment case 3146. Here, the heat medium flow path 3192 is formed inside each of the case main body 3172 and the lid portion 3174. FIG. Has been. As shown in FIG. 60 (c), the liquid supply path 3178 has a double pipe structure in which the tip of the liquid supply pipe 3188 is inserted, and communicates with the heat medium flow path 3192 through a thin communication path 3190. is doing. The drainage side has the same configuration. As shown in FIG. 60 (b), the temperature adjustment case 3146 that accommodates the mixing unit 3140 and the temperature adjustment case 3146 that accommodates the reaction unit 3142 are stacked and coupled via a bolt 3194, a nut 3195, and a spacer 3196. ing.

  FIG. 60B shows a path for supplying and discharging the liquid to and from the mixing unit 3140 and the reaction unit 3142 accommodated in the temperature adjustment case 3146. That is, each liquid flows into and out of the mixing unit 3140 through the flow passage 3198 formed through the temperature adjustment case 3146. Further, the liquid is circulated between the mixing unit 3140 and the reaction unit 3142 via a communication passage 3200 that communicates with the flow passage 3198 of the temperature adjustment case 3146. FIG. 60D illustrates the structure of the liquid inflow portion and the outflow portion of the reaction portion 3142. In order to direct the liquid flow downward, the liquid inlet of the mixing unit 3140 and the reaction unit 3142 is normally formed on the upper surface and the outlet is formed on the lower surface.

  As shown in FIG. 52, the outlet 3202 of the reaction unit 3142 is connected to the product storage unit 3104 via a recovery pipe 3204. The product storage unit 3104 is provided with a recovery container 3208 on the downstream side of the heat exchanger 3206 for cooling and the flow path switching valve 3132. The product storage unit 3104 in which the recovery container 3208 is placed is isolated so as not to be affected by temperature and the like from other regions, and to prevent toxic gas that may be generated from the product from leaking outside. .

  FIG. 61 shows another configuration example of the product storage unit 3104, and a plurality of collection containers 3208 are installed on the turntable 3212. In this example, there are two collection containers 3208, and the actuator 3214 for moving the rotary table 3212 is a 180-degree rotary actuator. Of course, the number of collection containers 3208 and the type of actuator 3214 can be selected as appropriate. The operation control unit 3106 shown in FIG. 52 determines the replacement timing of the recovery container 3208 based on a signal from the liquid level detection sensor 3211b that detects the liquid level of the recovery container 3208, and the flow path switching valve 3132 (see FIG. 52). The liquid flow is stopped, the stop of the liquid flow is confirmed by the optical fluid detection sensor 3211a provided downstream of the recovery port 3210, and the actuator 3214 is operated to move the other recovery container 3208 below the recovery port 3210.

  Next, a process of reacting a liquid (raw material liquid) such as a chemical solution with the fluid reaction apparatus configured as described above will be described. The operation of the fluid reaction apparatus is basically automatically controlled by the operation control unit 3106. First, in the raw material storage unit 3101, the storage containers 3110 </ b> A and 3110 </ b> B that store the raw material liquid are prepared. The temperature of the heat medium is set by the heat medium controller 3107, the amount of city water passing through the heat exchanger 3182 is adjusted to adjust the temperature of each heat medium, and the temperature adjustment case 3146 of the mixing unit 3140 and the reaction unit 3142. Heat medium is circulated to maintain a predetermined temperature. The temperature of the heat medium is measured by temperature sensors 3216 and 3218 provided at the inlet of the temperature adjustment case 3146.

  In this example, before supplying the raw material liquid to the processing unit 3103, a cleaning liquid such as pure water is flowed through the flow paths in the mixing unit 3140 and the reaction unit 3142 to perform cleaning in advance. While cleaning the flow path, the temperature of the cleaning liquid is measured by the temperature sensor 3220 at the outlet of the mixing unit 3140 and the temperature sensor 3222 at the outlet of the reaction unit 3142, and the temperature of the cleaning liquid is fed back to the heat medium controller 3107. In this way, the mixing unit 3140 and the reaction unit 3142 are adjusted to a predetermined temperature.

  After the temperature of the mixing unit 3140 and the reaction unit 3142 is adjusted and the cleaning of the flow path is completed, the flow path switching valve 3132 is switched, and the pumps 3116A and 3116B are driven to supply the raw material liquid in the storage containers 3110A and 3110B, respectively. Transport. The raw material liquid is adjusted to a predetermined flow rate by the flow rate adjusting devices 3300A and 3300B, and then reaches the recovery container 3208 through the mixing unit 3140, the reaction unit 3142, the outlet 3202, and the recovery port 3210. Note that the flow path switching valve 3132 is an automatic valve that is operated by an actuator, and this operation can also be performed automatically.

  In the mixing unit 3140, the raw material liquids are heated to a predetermined temperature in the preheating channels 3148 </ b> A and 3148 </ b> B (see FIG. 55), and then merged and mixed in the merging unit 3152. At that time, as shown in FIG. 56, the respective liquids flow into the merge space 3158 from the header portions 3154 and 3155 via the liquid separation flow paths 3156 and 3157. Since the cross section of the merge space 3158 gradually decreases toward the downstream, micro-sized flows are mixed regularly and mixed rapidly according to Fick's law. In that state, when it flows into the reaction channel 3162 of the reaction unit 3142 maintained at a predetermined temperature, the reaction proceeds rapidly without being restricted by mass transfer or heat conduction. Therefore, it is sufficiently practical as a mass production means, and it is not necessary to carry out an explosive reaction with a high reaction rate at a low temperature. Further, in this example, the width of the reaction channel 3162 is sufficiently wide compared to the width of the merge space 3158, so that even when the reaction rate is slow, the reaction can be performed over a sufficient period of time, resulting in a high yield. Obtainable.

  The obtained product is sent from the outlet 3202 of the reaction channel 3162 to the heat exchanger 3206 via the recovery pipe 3204, cooled here, and flows into the recovery container 3208 from the recovery port 3210. When the storage containers 3110A and 3110B are emptied or the collection container 3208 is full, the operation control unit 3106 stops the operation of the pumps 3116A and 3116B and ends the processing. In this case, in addition to the storage containers 3110A and 3110B, if an additional storage container is prepared in the raw material storage unit 3101 in advance, the flow path switching valves 3126A and 3126B are switched to continuously operate without stopping. Processing is possible. In addition, when reaction takes time, it is also possible to carry out batch operation by confining the liquid in the mixing unit 3140 and the reaction unit 3142 for a certain period of time. Since the flow path switching valves 3126A and 3126B are also automatic valves, these operations can be automatically operated.

  In the batch operation method, the pumps 3116A and 3116B may be temporarily stopped, or the flow switching valves 3126A and 3126B may be switched to stop the inflow of liquid into the processing unit 3103. This eliminates the need to increase the length of the reaction channel 3162 even when the reaction time of the liquid is long. During batch operation, it is preferable to perform operation control using a fullness detection means for detecting that the merge space 3158 and / or the reaction flow path 3162 is filled with liquid. For example, an optical fluid detection sensor as shown in FIG. 61 is used. As a result, when it is determined that the merge space 3158 and / or the reaction flow path 3162 is filled with the liquid, the pumps 3116A and 3116B are stopped or the first flow path switching valve is switched to adapt the liquid to the reaction termination time. It is allowed to stay in the merge space 3158 and / or the reaction flow path 3162 for a fixed time.

  In addition, according to the flow control devices 3300A and 3300B according to the present invention, the liquid flow rate can be accurately measured, so that the liquid supply amount can be obtained from the measured flow rate and the liquid supply time. Therefore, the operation control unit 3106 can adjust the production amount of the product based on the supply amount of the liquid, and can control the operation of the fluid reaction device. For example, the operation control unit 3106 may stop the operation of the pumps 3116A and 3116B or switch the flow path switching valves 3126A and 3126B when the liquid supply amount reaches a predetermined value. As described above, by incorporating the flow control device according to the present invention into the fluid reaction device, the operation control unit 3106 can control the operation of each part of the fluid reaction device based on the supply amount of the liquid.

  62 (a) and 62 (b) show another configuration example of the merging portion in the mixing portion 3140. FIG. The junction 3152a is configured by disposing an obstacle 3224 over a predetermined distance L at a constant interval a in a Y-shaped junction space 3158a. In this example, a columnar obstacle 3224 having a diameter of 50 μm or less was arranged from the merging point over L = 5 mm. As shown in FIG. 62 (b), the obstacles 3224 are arranged in a staggered manner so that adjacent ones are shifted by half the pitch in the flow direction. As a result, the interface 3125 between the liquid A and the liquid B meanders, so that the interface area (contact area) between the two liquids can be increased. In the merge portion 3152b shown in FIG. 63, a single row of obstacles 3224 is arranged in a zigzag along the flow direction at the center of the merge space 3158b, and the interface area can be similarly increased. This is suitable for use in the narrow merge space 3158b.

  FIG. 64 shows another configuration example of the processing unit 3103 of the fluid reaction device. 52 is provided with two systems R1 and R2 each having a combination of a mixing unit 3140 and a reaction unit 3142 in the processing unit 3103 in FIG. 52, and further using two types of flow path switching valves 3126A and 3126B in the liquid distribution unit 3102. The raw material liquid can be supplied to any of the systems R1 and R2. As described above, by using the two systems, the processing amount can be increased as necessary, but there are various other usage methods. For example, when the reaction product easily precipitates solid particles and is easily clogged in the middle of the piping, one system is used as a spare. Further, the batch operation described above can be continuously performed by alternately switching the transfer lines by the flow path switching valves 3126A and 3126B. Of course, three or more transfer lines can be provided in parallel as appropriate. Also in this case, the flow path switching valves 3126A and 3126B can be automatically operated.

  FIG. 65 shows an example in which a plurality of reaction units are arranged in series in the processing unit 3103. In this example, one mixing unit 3140 and three reaction units 3142a, 3142b, 3142c are connected in series, and temperature sensors 3220, 3222a, 3222b, 3222c are provided respectively. In this example, the temperature of the reaction units 3142a, 3142b, and 3142c can be independently controlled according to the stage of the reaction. This configuration is suitable for reactions that require a bold and instantaneous change in reaction time and reaction temperature, such as biochemical reactions. For example, in this system, the reaction can be performed at 100 ° C. in the reaction unit 3142a and at −20 ° C. in the reaction unit 3142b.

  FIG. 66 shows an example in which a plurality of mixing units are provided in the processing unit 3103. In this configuration example, a first mixing unit 3140 and a reaction unit 3142 for mixing and reacting liquid A and liquid B are provided, and a second mixing unit 3140a is provided downstream of the reaction unit 3142. In this mixing unit 3140a, the third raw material liquid or the C liquid which is the reactant transported from the pump 3116C is merged with the A liquid and the B liquid. The temperatures of these two mixing units 3140 and 3140a and one reaction unit 3142 are individually controlled. The liquid C may be a reaction terminator.

  In this configuration example, an inline yield evaluator 3226 is directly connected to the outlet 3202 of the second mixing unit 3140a. Thereby, the yield of the result of the chemical reaction can be confirmed in real time, and can be immediately fed back to the process parameters. The in-line yield evaluator 3226 includes methods such as infrared spectroscopy, near infrared spectroscopy, and ultraviolet absorption as methods that can be measured without separating the object to be measured.

  In this configuration example, a separation and extraction unit 3228 that further separates unnecessary substances and necessary substances from the reaction product is provided on the downstream side of the second mixing unit 3140a. As illustrated, the separation / extraction unit 3228 includes a Y-shaped separation channel 3234. The liquid from the second mixing unit 3140a is branched into two flows by the separation channel 3234, one in the channel formed by the hydrophobic wall 3230 that allows only the hydrophobic molecules in the material to pass through, and the other in the material It flows into the flow path formed from the hydrophilic wall surface 3232 through which only the hydrophilic molecules inside pass. The separated substances are collected in the collection containers 3208 and 3208a via the collection pipes 3204 and 3204a, respectively. As the separation / extraction unit 3228, a membrane or a porous frit capable of adsorbing only a hydrophobic substance may be used.

  FIG. 67 is a configuration example for continuous processing by repeating mixing / reaction and separation / extraction. That is, the mixing unit 3140a for processing the A liquid and the B liquid, the reaction unit 3142a, and the separation / extraction unit 3228a are arranged on the upstream side, and the mixing unit 3140b for processing the liquid extracted from the separation / extraction unit 3228a and the C liquid The unit 3142b and the separation / extraction unit 3228b are arranged on the downstream side. Unnecessary substances after the A liquid and B liquid have reacted are discharged out of the system from the discharge port 3234a of the separation and extraction unit 3228a, and unnecessary substances in the second reaction added with the C liquid are discharged from the discharge port 3234b of the separation and extraction unit 3228b. Be taken out of the system. Furthermore, a mixing unit 3140c that mixes the liquid extracted from the separation / extraction unit 3228b and the fourth liquid D is provided. Liquid D may be a reaction terminator or other raw material solution. An in-line yield evaluator 3226 may be provided on the downstream side of the mixing unit 3140c.

  FIG. 68A shows a configuration in which the respective parts in FIG. 67 are stacked. The liquid flows downward. The mixing unit 3140a, the reaction unit 3142a, the separation / extraction unit 3228a, the mixing unit 3140b, the reaction unit 3142b, the separation / extraction unit 3228b, and the mixing unit 3140c are accommodated in the temperature adjustment case 3146, respectively, and further, a bolt 3194, a nut 3195, and a spacer 3196. Are stacked at a predetermined interval. The movement of the liquid between each part is performed via the communication path 3200 (refer FIG.55 (b)). The accuracy of temperature control is improved by interposing air between each part so as not to be affected by the heat of other parts by utilizing the heat insulation of air. As shown in FIG. 68B, it is preferable to cover each temperature adjustment case 3146 with a heat insulating material such as a clean silicon member 3236 containing bubbles.

  The fluid introduced into the fluid reaction apparatus is liquid or gas, and the substance to be recovered is liquid, gas, solid or a mixture thereof. When the introduced substance is a solid such as powder, a powder dissolver can be installed in the raw material reservoir 3101. FIG. 69 shows a configuration example of the raw material reservoir 3101 in which one of the two raw material liquids is a solution in which powder is dissolved and the other is originally liquid. The raw material powder and the solvent are introduced from the raw material inlet 3242 of the powder dissolver 3240. In this example, the raw material powder is dissolved by heating by the heater 3244 and stirring by the stirrer 3246, and the generated raw material liquid is mixed by the pump 3116A from the pipe 3249 drawn into the take-out port 3148, by the mixing unit 3140 and the reaction unit 3142. It comes to send to.

  Thus, the flow control device according to the present invention can be suitably used for a fluid reaction device (microreactor) that mixes and reacts fluids in a minute space. The present invention is not limited to the embodiments described so far, and is not limited to the illustrated examples, and various modifications can be made without departing from the gist of the present invention.

Flow measuring device and the flow control device present invention further relates to a flow control device that can be used in the fluid reaction device and the fluid mixing system of the present invention.

  The present invention for achieving the above-described object includes, but is not limited to, the following inventions.

  (1) A temperature adjustment mechanism for adjusting the temperature of the fluid flowing through the flow path for a short time at a predetermined temperature adjustment position, and at least one main temperature sensor disposed at a temperature measurement position downstream of the temperature adjustment position of the flow path. A flow rate measuring device that determines when a temperature-controlled fluid passes based on a temperature change at a temperature measurement position observed by the main temperature sensor and calculates a flow rate based on the determination result. A sub-flow sensor is installed upstream of the temperature control position, and a temperature measurement value of the main temperature sensor is corrected by a measurement value of the sub-temperature sensor.

  In the invention described in (1), the temperature of the flow path that has not undergone a temperature change due to the movement of the fluid is measured by the sub-temperature sensor installed on the upstream side of the flow path. Therefore, by correcting the temperature measurement value of the main temperature sensor with the measurement value of the sub temperature sensor, it is possible to detect the temperature change of the fluid excluding the influence of disturbance. Therefore, it is possible to more accurately determine when the temperature-controlled fluid passes and to calculate the flow rate more accurately based on the determination result.

  The location of the sub temperature sensor is a place where the influence of disturbance (for example, the heat of the temperature control mechanism transmitted through the piping) at the measurement position of the main temperature sensor can be measured. The position is symmetrical to the temperature sensor or equidistant if it is a curved pipe. Therefore, when sub-temperature sensors are installed for a plurality of main temperature sensors, they are installed at positions corresponding to the sub-temperature sensors. Since this position is not necessarily an exact symmetrical position according to the situation at the site, an isothermal point when the flow rate is zero may be searched.

  The principle of measuring the fluid flow rate according to the present invention will be described with reference to FIG. In FIG. 73 (a), the vertical axis represents temperature and the horizontal axis represents time. First, a thermal load is applied to the fluid as indicated by reference numeral HL by the temperature control mechanism, and the temperature is increased at a predetermined rate of change. At this time, if the fluid is flowing in the flow path, temperature changes such as S1 and S2 are observed at the first measurement point P1 and the second measurement point P2, respectively. Assuming that the temperature changes due to heat conduction or the like passing through the pipes are s1 and s2, the actual temperature change of the fluid is the difference, that is, the portion indicated by a thin line in FIG. 73 (a). This is shown as curves ΔS1, ΔS2 in FIG. 73 (b). Since the peak portions of the curves ΔS1 and ΔS2 are considered to measure the temperature of the center point of the temperature-controlled liquid at the temperature adjustment position Ph, the time difference Δt is the time during which the fluid moves between P1 and P2. It is thought that it corresponds to. Therefore, the flow rate of the fluid can be obtained from the following equation.

Flow rate = distance between temperature measurement points (D) × channel cross-sectional area ÷ time difference (Δt)
Even if the specific gravity, specific heat, and viscosity of the fluid are different, the time difference between the upstream temperature curve and the downstream temperature curve depends only on the flow rate under the same average flow velocity of the fluid. The way does not change. For example, as shown in FIG. 72, even if the viscosity of the fluid changes, only the maximum flow rate changes and the average flow rate (that is, the flow rate) does not change. Therefore, if the time difference between the temperature curves appearing at the two measurement points is measured, the flow rate can be accurately measured without being affected by the physical properties of the fluid.

  When the flow rate is as small as 0.01 to 10 L / h, further 0.01 to 2 L / h, the inner diameter of the flow path is as small as 2 mm or less and the Reynolds number is small, so that the fluid flow becomes a laminar flow. Therefore, the curve indicating the flow velocity distribution in the flow path is not disturbed and the shape thereof is stable, thereby enabling the flow rate measurement based on the time difference of the temperature change. This makes it unnecessary to know the physical properties such as specific heat, specific gravity, and viscosity of the reagent in advance, even when testing with various reagents. Can be obtained.

  Examples of fluids used in the present invention include reagents, organic solvents, biochemical substances and the like. For example, in the development stage of pharmaceuticals, so-called screening is performed in which a number of reagents are used and tests are performed while various conditions such as concentration, solvent, and temperature are changed. In this screening, it is required to measure an accurate volume regardless of the physical properties of the reagent. According to the present invention, an accurate volume (flow rate) of a reagent can be obtained regardless of the type of reagent, and thus a preferable development environment can be provided.

  In the example shown in FIG. 73, the time difference when the peaks of the two temperature curves appear is measured, but the present invention is not limited to this. For example, the time difference at the time of rising of the temperature curve may be obtained, or the time difference at a time point deviated from the peak by a predetermined time may be obtained. Thus, in the present invention, the time difference between two points corresponding to each other on the temperature curve is measured.

  (2) In the invention described in (1), the correction is performed by obtaining a difference between a measurement value of the main temperature sensor and a measurement value of the sub temperature sensor. The method for obtaining the difference may be an analog method for directly obtaining an output difference as in the case of a bridge circuit, or a digital method in which a measurement signal is processed after analog / digital change.

  (3) In the invention described in (1) or (2), at least two main temperature sensors are provided at different temperature measurement positions, and a flow rate is calculated based on a time difference between passages at these temperature measurement positions. A flow measuring device characterized by the above.

  In the invention described in (3), the flow rate of the fluid is calculated based on the time difference between the two corresponding points on the temperature curve indicating the temperature change of the fluid at the first measurement point and the second measurement point. Can do. The correction by the sub temperature sensor may be performed on the main temperature sensor measurement values at both the first measurement point and the second measurement point, or may be performed only on the one having a larger influence of disturbance.

  (4) In the invention described in (1) or (2), the flow rate is calculated based on a time difference between the time when the temperature adjustment mechanism performs temperature adjustment and the passage at the temperature measurement position. Flow measurement device.

  (5) The flow rate measurement according to any one of (1) to (4), wherein the time point at which the corrected temperature measurement value reaches an extreme value is determined as the passage of the temperature control fluid. apparatus. This is because the time point at which the temperature measurement value reaches the minimum value (in the case of cooling) or the maximum value (in the case of heating) is considered to be the time when the part affected by the temperature control passes.

  (6) In the invention according to any one of (1) to (5), the sub-temperature sensor is located at a position substantially symmetrical to the temperature measurement position with respect to the temperature control position. apparatus.

  (7) The flow rate measuring device according to any one of (1) to (6), wherein the position of the sub temperature sensor is adjustable along the flow path.

  (8) The flow rate according to any one of (1) to (7), wherein the measured value of the main temperature sensor or the sub temperature sensor is converted from analog to digital and incorporated into a digital circuit for processing. measuring device.

  (9) In the invention according to any one of (1) to (8), the temperature adjustment mechanism includes a Peltier element, a Seebeck element, an electromagnetic wave generator, a resistance heating wire, a thermistor, or a platinum resistor. Flow rate measuring device. The temperature adjustment mechanism is not limited to the heating unit, and a cooling unit may be used.

  (10) The flow rate measuring device according to any one of (1) to (9), wherein the flow path is made of a corrosion-resistant material.

  (11) In the invention according to (10), the material is stainless steel, titanium, polyetheretherketone, polytetrafluoroethylene, or polychlorotrifluoroethylene.

  (12) A flow rate obtained by the flow rate measuring device according to any one of (1) to (11), a control valve provided in a downstream portion of the flow rate measuring device of the flow path, and the flow rate measuring unit. And a control unit that controls the control valve so that the flow rate of the fluid is constant.

  (13) In the invention described in (12), the control valve includes a valve that adjusts a flow rate and a drive source that drives the valve, and the drive source includes a piezoelectric element, an electromagnet, and a servo motor. Or a flow control device comprising a stepping motor. According to the present invention, by using a drive source with good responsiveness, it is possible to quickly drive the valve based on the actual flow rate measured by the flow rate measurement unit and keep the flow rate constant.

  (14) In the invention described in (12), the control valve has a valve for adjusting a flow rate and a drive source for driving the valve, and the drive source is formed by laminating a plurality of piezoelectric elements. A flow control device characterized by having a structure. According to the present invention, even when a high-pressure fluid flows, the flow rate can be kept constant without being affected by high pressure or pressure fluctuation.

  (15) The flow rate measuring device according to any one of (12) to (14), wherein the pressure of the fluid passing through the control valve is 1 MPa to 10 MPa.

  (16) In the invention according to any one of (12) to (15), the flow rate of the fluid passing through the control valve is 0.01 to 10 L / h.

  (17) A plurality of containers for storing fluid, a mixing unit for mixing the fluid, a reaction unit for reacting the mixed fluid, and the flow rate adjusting device according to any one of (12) to (16) are provided. A fluid reaction device.

  Hereinafter, a flow control device according to an embodiment of the present invention will be described with reference to the drawings. FIG. 74 is a schematic diagram showing a flow rate adjusting device according to the first embodiment of the present invention. As shown in FIG. 74, the flow rate adjusting device of the present embodiment includes a flow rate measuring unit 4010 that measures the flow rate of the liquid (fluid) flowing through the flow path 4001, a control valve 4020 that adjusts the flow rate of the liquid, and a flow rate measurement. The control unit 4030 basically controls the control valve 4020 based on the flow rate measured by the unit (flow rate measuring device) 4010.

  The flow rate measuring unit 4010 has a temperature adjustment mechanism 4002 that heats the liquid flowing through the flow path 4001 at a predetermined cycle, and a liquid at a first measurement point Pm1 downstream from the installation position (temperature adjustment position Ph) of the temperature adjustment mechanism 4002. A first main temperature sensor 4003 that measures the temperature of the liquid and a second main temperature sensor 4004 that measures the temperature of the liquid at a second measurement point Pm2 downstream from the first measurement point Pm1 are provided. . Further, sub temperature sensors 4003a and 4a are provided at upstream positions Ps1 and Ps2 that are symmetrical (equal distance) with respect to the main temperature sensor and the temperature control mechanism 4002, respectively. The distance between the temperature adjustment mechanism 4002 and the first main temperature sensor 4003 and the distance D between the first main temperature sensor 4003 and the second main temperature sensor 4004 are not particularly limited, but are 0.5 [mm] to 10 [mm] is preferred. The temperature adjustment mechanism 4002 is provided so as to surround the wall portion of the flow path 4001 and heats the liquid through the wall portion of the flow path 4001. The temperature adjustment mechanism 4002 is connected to the temperature control unit 4005 and heats the liquid at an optimal temperature increase rate. Note that, as the temperature adjustment mechanism 4002, a Peltier element, Seebeck element, electromagnetic wave generator, resistance heater, or the like is preferably used. The temperature adjustment mechanism 4002 may change the temperature of the liquid by cooling the liquid.

  The outputs of the first main temperature sensor 4003 and the first sub temperature sensor 4003a are input to the first difference detection circuit 8A, and similarly the outputs of the second main temperature sensor 4004 and the second sub temperature sensor 4004a. Is input to the second difference detection circuit 4008B. These difference detection circuits 4008A and 4008B are configured by, for example, a bridge circuit 4008C as shown in FIG. . The time difference measurement unit 4009 calculates the time during which the heated liquid passes through the two measurement points P1 and P2 from the change of each difference signal, and obtains the flow rate of the liquid, that is, the flow rate based on the difference.

  It is necessary to balance the outputs of the main temperature sensors 4003 and 4004 and the sub temperature sensors 4003a and 4004a at the beginning of the operation of the apparatus. This must be such that the differential output becomes zero in a state where no fluid flows through the flow path 4001 (zero flow velocity). This is performed by adjusting the resistances R1 and R2 of the bridge circuit 4008C in a state where the main temperature sensors 4003 and 4004 and the sub temperature sensors 4003a and 4004a are arranged at symmetrical positions, and the resistances R1 and R2 of the bridge circuit 4008C are There is a method of adjusting the main temperature sensors 4003 and 4004 and the sub-temperature sensors 4003a and 4004a by shifting the symmetrical relationship. The situation at the site is complex, and neither method is correct, and it may be selected appropriately according to the situation, or a combination of both may be performed.

  As a method for extracting the difference between the main temperature sensors 4003 and 4004 and the sub temperature sensors 4003a and 4004a, in addition to the analog method using the bridge circuit 4008C as described above, the temperature signal of each temperature sensor is analog / digital. A method may be used in which a difference is calculated by software after conversion and incorporation into a digital circuit. In this case, the input may be performed without passing through the bridge circuit, or digital processing may be performed after the peak detection after passing through the bridge circuit.

  Since the flow path 4001 is basically a closed system and may handle a liquid having high reactivity or harmful or dangerous to the environment, it is not preferable to form an opening. Therefore, in this example, the temperature adjustment mechanism 4002, the first main temperature sensor 4003, and the second main temperature sensor 4004 are all attached to the outer surface of the pipe 4001A constituting the flow path 4001. Each sub temperature sensor is similarly attached to the outer surface of the flow path 4001. Therefore, these temperature sensors 4003, 4003a, 4004, 4004a measure the temperature of the liquid via the wall portion of the flow path 4001. As the temperature sensors 4003, 4003a, 4004, 4004a, a thermistor type thermometer or a thermocouple having excellent responsiveness is preferably used. Of course, the temperature adjustment mechanism 4002 and the temperature sensors 4003, 4003a, 4004, 4004a may be embedded in the wall portion of the flow path 4001. In any case, it is preferable that the corresponding main temperature sensors 4003 and 4004 and the sub temperature sensors 4003a and 4004a adopt the same installation method.

  The principle that the flow rate of the liquid is measured by the time difference measuring unit 4009 is as described with reference to FIG. That is, when the temperature adjustment mechanism 4002 heats the liquid with a pulse load as shown in FIG. 73 while the liquid is flowing, the heated liquid flows downstream, and the first measurement point Pm1 and the second measurement point. It passes through Pm2 in this order. At this time, the temperature of the liquid at the first measurement point Pm1 is measured by the first main temperature sensor 4003, and the temperature of the liquid at the second measurement point P2 is measured by the second main temperature sensor 4004.

  Here, since these main temperature sensors 4003 and 4004 measure the temperature of the wall portion of the flow path, the heat from the temperature control mechanism 4002 is transferred to the fluid through the wall portion, and further the wall on the downstream side again. It is transmitted to the temperature sensor through the part. Therefore, while the amount of heat given by the temperature control mechanism 4002 passes through the wall portion twice, the pure fluid flows when the distance between the temperature detection portions increases due to heat conduction through the pipe 4001A and external influences. It becomes difficult to detect temperature changes. Therefore, in this embodiment, the sub-temperature sensors 4003a and 4004a are arranged at positions symmetrical to the temperature control mechanism 4002 for the main temperature sensors 4003 and 4004, and the influence of ambient temperature change and tube wall heat transfer is measured. . Then, by taking the difference between the temperature signals of the sub temperature sensors 4003a and 4004a and the main temperature sensors 4003 and 4004, the temperature change of the fluid itself in which the influence of the ambient temperature change and the tube wall heat transfer is canceled is measured. As a result, even if the amount of heat applied to the fluid is increased, the temperature change itself of the fluid can be accurately detected. Therefore, it is possible to increase the distance between the temperature detection positions and accurately detect the flow rate in a wide flow range. it can.

  That is, the output signals from the first main temperature sensor 4003 and the sub temperature sensor 4003a (S1 and s1 in FIG. 73A) are input to the difference detection circuit 4008A and the difference signal (ΔS1 in FIG. 73B). Are output, and the output signals of the second temperature sensor 4004 and the sub-temperature sensor 4004a (S2 and s2 in FIG. 73A) are input to the difference detection circuit 4008B and the difference signal (ΔS2 of FIG. 73B). ) Are output, and these outputs are continuously sent to the time difference measurement unit 4009. The time difference measuring unit 4009 monitors the changes of these outputs ΔS1, ΔS2, records the time when they reach the peak (rate of change = 0), calculates the time difference Δt, and uses the following formula: Convert to flow rate.

Flow rate = distance between temperature measurement points (D) x cross-sectional area of flow path / time difference (Δt)
Note that the measurement time difference Δt in FIG. 73A shows the case of the conventional method for comparison, and the time difference of the peak of the temperature measurement values of the main temperature sensors 4003 and 4004 is adopted.

  Here, the flow rate of the fluid is obtained based on the moving speed of the peak of the temperature change, but the time difference between the other two corresponding points of the temperature change curve may be obtained. For example, the time difference between the rises of the two temperature curves may be obtained.

  The above flow rate calculation method by the flow rate measuring unit 4010 may be manufactured by an analog circuit or digitally. In the case of performing digital processing, even if the signals of the temperature sensors 4003, 4003a, 4004, and 4004a are input after analog / digital conversion, the differential signals after passing through the difference detection circuits 4008A and 4008B are converted to analog / digital. An input method may be used.

  As shown in FIG. 74, the control valve 4020 is disposed on the downstream side of the flow rate measuring unit 4010. The control valve 4020 includes a piston (valve) 4021 disposed so as to face the liquid flow, and a piezoelectric element (drive source) 4022 that drives the piston 4021. A piezoelectric element (piezoelectric actuator) 4022 is fixed to the back surface of the piston 4021, and the piezoelectric element 4022 and the piston 4021 are integrally formed. The piston 4021 and the piezoelectric element 4022 are accommodated in the piston chamber 4023. A part of the flow path 4001 has a T-shaped path, and the piston 4021 is arranged so that the liquid flowing into the T-shaped path hits the front surface of the piston 4021. When a voltage is applied to the piezoelectric element 4022, the piezoelectric element 4022 expands and contracts, thereby moving the piston 4021 along the liquid flow direction to adjust the opening degree α of the piston 4021.

  A throttle 4001a is provided on the upstream side of the piston 4021. By narrowing down the flow path 4001, the flow rate can be accurately adjusted by the piston 4021. The above-described piston chamber 4023 is formed in a bottomed cylindrical shape, and this piston chamber 4023 is fixed to the outer surface of the flow path 4001 in a liquid-tight manner. With such a configuration, even when the liquid leaks from the gap between the piston 4021 and the flow path 4001, the liquid is held inside the piston chamber 4023, so that leakage of the liquid to the outside is prevented.

  In the microreactor incorporating the flow control device according to the present embodiment, a reaction product is generated on the downstream side of the flow control device by the reaction between the reagents. In this case, depending on the type of the reaction product, the pressure of the liquid on the downstream side of the flow control device may increase, and the liquid may leak from the flow path 4001. According to the present embodiment, liquid leakage to the outside can be prevented by the bottomed cylindrical piston chamber 4023, so that accurate flow rate adjustment is possible.

  Next, the control unit 4030 will be described. The control unit 4030 includes an amplifier 4032 connected to the time difference measurement unit 4009, a comparison unit (PID control unit) 4033 that determines the opening of the piston 4021 for keeping the flow rate constant, and a piezoelectric element 4022 of the control valve 4020. And a piston drive circuit 4034 for generating a voltage to be applied. The amplifier 4032 amplifies the signal representing the liquid flow rate (actual flow rate) calculated by the time difference measurement unit 4009 and sends the amplified signal (actual flow rate) to the comparison unit 4033. The set flow rate (target value) is input in advance to the comparison unit 4033. The comparison unit 4033 compares the actual flow rate with the set flow rate, and calculates the opening of the piston 4021 for matching the actual flow rate with the set flow rate. To do. The opening degree of the piston 4021 calculated by the comparison unit 4033 is converted into a voltage by the piston drive circuit 4034. This voltage is applied to the piezoelectric element 4022, and the piston 4021 is driven by the piezoelectric element 4022. In this way, the control valve 4020 is controlled by the control unit 4030 so that the flow rate of the liquid passing through the control valve 4020 is always constant.

  In order to quickly reflect the measurement result of the flow rate measurement unit 4010 in the operation of the control valve 4020, the distance of the flow path 4001 between the flow rate measurement unit 4010 and the control valve 4020 is preferably as short as possible. That is, the distance between the second main temperature sensor 4004 and the piston 4021 is preferably 10 to 100 mm, more preferably 10 to 50 mm, and still more preferably 10 to 20 mm. In addition, it is preferable to use a drive source (actuator) used for the control valve 4020 having excellent responsiveness such as a piezoelectric element. By doing in this way, the fluctuation | variation (pulsation) of the flow volume which flows through the flow path 4001 can be eliminated rapidly, and a fixed flow volume can be maintained.

  This flow control device is suitably used for a fluid reaction device (microreactor) that reacts two or more kinds of liquids. In general, the smaller the mixing space in which the liquid is mixed, the faster the liquid is mixed. The inner diameter of the flow path 4001 of the flow control device according to the present embodiment is preferably 0.1 to 5 mm, more preferably 0.1 to 2 mm, and still more preferably 0.1 to 1 mm. Moreover, when only a very small amount is used as the handling range, the minimum diameter can be set to 0.02 mm. In addition, when the width | variety (inner diameter) of a flow path becomes small, it will be necessary to transfer a liquid by a high voltage | pressure. In the present embodiment, the pressure of the liquid at the outlet of the flow rate adjusting device (downstream of the control valve 4020) is 1 MPa to 10 MPa, 2 MPa to 5 MPa, or 3 MPa to 4 MPa.

  Examples of liquids to be handled include reagents, organic solvents, and biochemical substances. Therefore, the material constituting the flow path 4001 is preferably one having corrosion resistance. Further, as described above, since the first main temperature sensor 4003 and the second main temperature sensor 4 measure the temperature of the liquid through the wall portion of the flow path 4001, the material constituting the flow path 4001 is heat. Those having excellent conductivity and withstanding a wide temperature range of −40 to 150 ° C. are preferable. Furthermore, it is preferable that the material constituting the flow path 4001 can withstand the high pressure of the liquid. Considering these points, preferable examples of the material constituting the flow path 4001 include hard glass such as SUS316, SUS304, Ti, quartz glass, and Pyrex (registered trademark) glass, PEEK (polyetheretherketone), PE (polyethylene), and PVC. Examples thereof include resins such as (polyvinylchloride), PDMS (Polydimethylsiloxane), Si, PTFE (polytetrafluoroethylene), PCTFE (Polychlorotrifluoroethylene), and PFA (perfluoroalkoxylalkane).

  When stainless steel or Ti is used, the wall thickness of the channel 4001 is preferably 0.01 to 0.1 mm. When resin such as PEEK, PTFE, PCTFE, or PFA is used, the channel 4001 is used. The wall thickness is preferably 0.1 to 1 mm. Considering thermal conductivity, it is preferable to use Ti having a small heat capacity. When resin is used, it is preferable to improve the thermal conductivity by locally reducing the thickness of the portion of the flow path 4001 to which the first main temperature sensor 4003 and the second main temperature sensor 4004 are attached.

  FIG. 76 is an enlarged view showing another configuration example of the control valve. As described above, the drive source that drives the piston 4021 is required to drive the piston 4021 against high-pressure liquid. In the configuration example shown in FIG. 76, two piezoelectric elements 4022 are stacked in order to increase the driving force. With such a configuration, even when the liquid is high pressure, the opening degree α of the piston 4021 can be accurately adjusted, and the flow rate can be kept constant. If necessary, three or more piezoelectric elements may be stacked.

  FIG. 77 shows a second embodiment of the present invention, which is a simplified version of the previous embodiment. Note that the configuration of the present embodiment that is not particularly described is the same as the configuration of the first embodiment described above, and therefore redundant description thereof is omitted.

  Here, only the sub temperature sensor 4003a corresponding to the first main temperature sensor 4003 is installed, and the corresponding sub temperature sensor is not provided for the second main temperature sensor 4004. The processing of the first main temperature sensor 4003 and the sub temperature sensor 4003a is input to the time difference measurement unit 4009 via the first difference detection circuit 4008A, and the output of the second sub temperature sensor is input to the time difference measurement unit 4009 as it is. ing. Therefore, the time difference measurement unit 4009 determines the peak for the first temperature measurement position Pm1 based on the difference (the temperature curve of ΔS1 shown in FIG. 78), but the second temperature measurement position Pm2 The peak is determined from the measured value of the sensor 4004.

  This is because the heat of the pipe 4001A etc. escapes to the outside due to the distance from the temperature control position Ph, and the influence on the measured value is reduced. In addition, since the temperature signal from the fluid is small at the second temperature measurement position Pm2, it is considered that the signal is easier to detect if the difference is not taken.

  By doing in this way, while ensuring the required detection accuracy, one temperature sensor and a difference detection circuit can be omitted, the configuration can be simplified, and the cost can be reduced. In addition, since the total length of the flow rate measuring unit 4010 and the length of the straight portion of the pipe 4001A can be reduced, the size of the device can be reduced, the degree of freedom in designing the device can be increased, and the like.

  Next, a third embodiment of the present invention will be described with reference to FIG. FIG. 79 is a schematic diagram showing a flow rate adjusting device according to a third embodiment of the present invention. As shown in FIG. 79, in this embodiment, the first main temperature sensor 4003, the first sub temperature sensor 4003a, and the first difference detection circuit 4008A are omitted, and the flow rate measurement unit 4010 The main temperature sensor 4004, the second sub temperature sensor 4004a, and the second difference detection circuit 4008B are connected to the time difference measuring unit 4009. In the present embodiment, the first measurement point Pm1 overlaps the position Ph of the temperature adjustment mechanism 4002.

  Here, the principle by which the flow rate is measured by the flow rate measurement unit 4010 of the present embodiment will be described with reference to FIG. The liquid flowing in the flow path 4001 is heated by receiving the heat load pulse HL from the temperature adjustment mechanism 4002 and starts to rise in temperature. As the heating pulse, a rectangular wave, a triangular wave, a sine wave or the like is appropriately used. The loading time of the thermal load pulse HL is 0.001 to 100 seconds, preferably 0.01 to 10 seconds, and more preferably 0.1 to 1 second. The heated liquid flows through the flow path 4001 and eventually passes through the second measurement point P2. At this time, the temperature curve ΔS2 is detected based on the difference between the second temperature sensor 4004 and the first side temperature sensor 4004a. Then, the peak is determined by the time difference measuring unit 4009, the time difference Δt with respect to the time of the representative point of the thermal load pulse HL is obtained, and the flow rate of the liquid is calculated by the above-described equation. In this example, the point on the rear end side of the pulse is used as the representative point of the heat load pulse HL. However, an appropriate point corresponding to the temperature rise of the fluid may be obtained experimentally and used.

  As shown in FIG. 79, in the control valve 4020 of the present embodiment, a cylindrical spool 4024 is used instead of the piston 4021. The spool 4024 is disposed on the T-shaped path of the flow path 4001, and the tip of the spool 4024 is slidably fitted in the flow path 4001. A magnetic body (eg, iron core) 4025 is attached to the end of the spool 4024, and an electromagnet 4026 is disposed around the magnetic body 4025. A seal member 4027 is disposed between the electromagnet 4026 and the flow path 4001, and liquid leakage is prevented by the seal member 4027. The magnetic body 4025 is driven by the electromagnetic force formed by the electromagnet 4026, whereby the spool 4024 moves along its axial direction. The control valve 4020 having such a configuration is called a solenoid valve (electromagnetic valve).

  81 is a perspective view of the spool shown in FIG. 79. FIG. As shown in FIG. 81, an obliquely extending groove 4024 a is formed on the side surface of the spool 4024. The groove 4024a has a triangular cross section, and the size of the cross section changes according to the axial position. That is, the cross section of the groove 4024a is the largest at the tip of the spool 4024, and gradually decreases as the cross-sectional position moves toward the opposite end. Since the liquid flows through the groove 4024a, the flow rate can be adjusted by moving the spool 4024 in the axial direction. In this case, the opening degree α of the spool (valve) 4024 can be expressed by the length of the groove 4024a protruding from the flow path 4001.

  The control unit 4030 of this embodiment includes a spool drive circuit 4035 instead of the piston drive circuit. The spool drive circuit 4035 converts the opening degree of the spool 4024 calculated by the comparison unit 4033 into a current, and the current is supplied to the electromagnet 4026 so that the spool 4024 moves. In this way, the control valve 4020 is controlled by the control unit 4030 so that the flow rate of the liquid passing through the control valve 4020 is always constant. It is preferable to use an electromagnet capable of generating a large electromagnetic force in order to make the flow rate constant accurately even when the liquid is high pressure.

  Next, a fourth embodiment of the present invention will be described with reference to FIG. FIG. 82 is a schematic diagram showing a flow rate adjusting device according to a fourth embodiment of the present invention. Note that the configuration of the present embodiment that is not particularly described is the same as the configuration of the first embodiment described above, and therefore redundant description thereof is omitted.

  As shown in FIG. 82, the control valve 4020 of the present embodiment includes an inverted triangular pyramid-shaped poppet 4041 instead of the piston 4021. The poppet 4041 is located at the T-shaped path of the flow path 4001 and is arranged so that the tip thereof faces the liquid flow. A shaft 4042 is integrally fixed to the poppet 4041, and the shaft 4042 is fitted to a bottomed cylindrical shaft guide 4043. A gear 4044 is provided on the outer peripheral surface of the shaft guide 4043, and the gear 4044 meshes with a gear 4046 connected to a servo motor 4045. The shaft 4042 is configured not to rotate by a rotation prevention mechanism (not shown) such as a key or a key groove. Note that the poppet 4041, the shaft 4042, and the shaft guide 4043 are aligned on the same axis.

  A seal member 4047 is disposed between the shaft guide 4043 and the flow path 4001 to prevent liquid from leaking from the flow path 4001. A male screw 4042a is formed on the outer peripheral surface of the shaft 4042, and a female screw (not shown) that meshes with the male screw 4042a is formed on the inner peripheral surface of the shaft guide 4043. With this configuration, when the shaft guide 4043 is rotated by the servo motor 4045, the poppet 4041 moves in the direction perpendicular to the opening of the T-junction, thereby adjusting the opening α of the poppet (valve) 4041. The A stepping motor may be used instead of the servo motor.

  The control unit 4030 of this embodiment includes a poppet drive circuit 4048 instead of the piston drive circuit. The poppet driving circuit 4048 converts the opening of the poppet 4041 calculated by the comparison unit 4033 into a current, and the current is supplied to the servo motor 4045 so that the poppet 4041 moves. In this manner, as in the first embodiment, the control valve 4020 is controlled by the control unit 4030 so that the flow rate of the liquid passing through the control valve 4020 is always constant. Note that it is preferable to use a servo motor or a stepping motor capable of generating a large torque in order to make the flow rate constant accurately even when the liquid is high pressure.

  Note that the above-described embodiments can be combined as necessary. For example, the environmental temperature control mechanism 4011 according to the second embodiment may be incorporated in the third and fourth embodiments. In addition, the flow rate adjusting device according to the above-described embodiment can measure and control not only liquid but also gas flow rate.

  Next, a fluid reaction device (microreactor) incorporating the above-described flow rate adjusting device according to an embodiment of the present invention will be described. FIG. 83 to FIG. 85 (b) are diagrams showing the overall configuration of a fluid reaction device incorporating a flow rate adjusting device according to an embodiment of the present invention. The fluid reaction apparatus described below is an apparatus used for mixing and reacting two or more kinds of liquids.

  As shown in FIG. 83, FIG. 84, FIG. 85 (a), and FIG. 85 (b), the entire fluid reaction device is installed in one installation space and packaged. In this configuration example, the installation space is rectangular and is divided into four regions along the longitudinal direction. That is, the first region on one end side is a raw material storage unit 4101 in which a plurality of storage containers 4110 (only two storage containers 4110A and 4110B are shown) for storing the raw material liquid are installed, and are adjacent thereto. The second region is a liquid distribution unit 4102 in which pumps 4116A and 4116B for transferring the raw material liquid in the storage container 4110 are installed. A third region adjacent to the second region is a processing unit 4103 having a mixing unit (mixing chip) 4140 for mixing the raw material liquid and a reaction unit (reaction chip) 4142 for reacting the mixed raw material liquid. . The fourth region on the other end side is a product storage unit (recovery container installation space) 4104 for deriving and storing a product obtained as a result of the processing.

  The fluid reaction apparatus also includes an operation control unit 4106 that is a computer that controls the operation of each unit, and a heat medium controller 4107 that adjusts the temperature of the processing unit 4103 by flowing a heat medium through the temperature adjustment case 4146. . Further, as shown in FIG. 83, the operation control unit 4106 is equipped with a flow rate monitor 4270 and a temperature monitor 4272 that can monitor the flow rate and temperature of the liquid. In this configuration example, the operation control unit 4106 and the heat medium controller 4107 are provided separately from the fluid reaction device, but may of course be integrated. As shown in FIG. 84, a pipe 4001A chamber 4105 is formed in the lower floor portion of the second to fourth regions, and a pipe for sending a heating medium for heating or cooling to the mixing unit 4140 and the reaction unit 4142 here. 4001A is provided.

  In this way, by arranging the respective parts from the upstream side to the downstream side, the flow of the liquid can be made smooth, and the entire apparatus can be made compact. In this configuration example, each part is arranged in a straight line. However, for example, if the entire space is close to a square, each part may be configured such that the liquid flow forms a loop.

  In FIG. 84, reference numeral 4250 denotes a liquid storage pan provided at the lower part of the apparatus, and reference numeral 4252 denotes a liquid leakage sensor installed on the liquid storage pan 4250. In this example of the apparatus, the liquid distribution unit 4102, the processing unit 4103, and the product storage unit 4104 are partitioned by partition walls 4254 and 4256, and covers 4258, 4260 and 4262 are attached to the respective parts to isolate them from the outside of the apparatus. is doing.

  Reference numeral 4264 denotes an exhaust port, which is connected to an exhaust fan (not shown). And the toxic gas in the apparatus is prevented from leaking outside by making the pressure in the apparatus negative from the outside of the apparatus.

  Although two storage containers 4110A and 4110B are installed in the raw material storage unit 4101 shown in FIG. 83, three or more storage containers may be used as necessary. For example, the process can be continuously performed by storing the same liquid in two storage containers and using them alternately. Note that the raw material reservoir 4101 may be provided with a cleaning liquid container 4112 containing an organic solvent such as acetone for line cleaning, hydrochloric acid, pure water, or the like, or a pressure source 4114 filled with a purge nitrogen gas. Further, the waste liquid container 4136 may be placed in the raw material storage unit 4101.

  Pumps 4116A and 4116B connected to storage containers 4110A and 4110B via transport pipes 4121A and 4121B are installed in the liquid distribution unit (introduction unit) 4102. A centrifugal pump is used for the pumps 4116A and 4116B in FIG. The liquid distribution unit 4102 includes flow rate adjusting devices 300A and 300B, relief valves 4122A and 4122B, pressure measurement sensors 4124A and 4124B, flow path switching valves 4126A and 4126B, and backwashing disposed downstream of the pumps 4116A and 4116B. A pump 4130 is included. The flow path switching valves 4126A and 4126B are connected to the cleaning liquid container 4112 and the pressure source 4114 in addition to the transport pipes 4121A and 4121B, respectively. The backwash pump 4130 is used when the flow path of the mixing unit 4140 or the reaction unit 4142 is blocked by the product. The backwash pump 4130 is connected to a cleaning liquid container 4112 that stores cleaning liquid, and is further connected to an outlet of the reaction unit 4142 via a flow path switching valve 4132. The cleaning liquid transferred by the backwash pump 4130 flows in the opposite direction to the normal flow. That is, the cleaning liquid flows from the outlet of the reaction unit 4142 toward the inlet of the mixing unit 4140, passes through the flow path switching valves 4126 </ b> A and 4126 </ b> B, and enters the waste liquid storage container 4136 from the waste liquid port 4134 through the pipe 4001 </ b> A (not shown).

  The backwash pump 4130 is preferably a single piston pump so that the discharge pressure is high and the product can be removed by causing pulsation in the cleaning liquid. As the cleaning liquid, an organic solvent, hydrochloric acid, nitric acid, phosphoric acid, organic acid, pure water, or the like is preferably used. Examples of the organic solvent include acetone, ethanol, methanol and the like. 83 is provided when pure water or hydrogen water is introduced from the outside, and can be used for cleaning instead of the cleaning liquid in the cleaning liquid container 4112.

  FIG. 86 shows a mixing unit 4140 for performing preliminary heating (preliminary temperature adjustment) and mixing of the raw material liquid. The upper plate 4144a, the middle plate 4144b, and the lower plate 4144c, which are three thin plate-like substrates, are shown. A mixing portion 4140 having a total thickness of 5 mm is formed by bonding. Note that the flow paths described below are grooves formed on the surface of the intermediate plate 4144b. Two inflow ports 4147A and 4147B formed through the upper plate 4144a communicate with two preheating channels 4148A and 4148B formed on the upper surface of the middle plate 4144b, respectively. These preheating channels 4148A and 4148B each branch in the middle and expand, and merge again. Further, the preheating channels 4148A and 4148B communicate with the outlet channels 4150A and 4150B, respectively, and these outlet channels 4150A and 4150B communicate with the junction 4152. The outlet channel 4150A is formed on the upper surface of the middle plate 4144b, and the outlet channel 4150B is formed on the lower surface of the middle plate 4144b.

  87 is an enlarged view of the merging portion shown in FIG. As shown in FIG. 87, the merging portion 4152 includes header portions 4154 and 4155 formed on the upper and lower surfaces of the middle plate 4144b as arc-shaped grooves that communicate with the outlet flow paths 4150A and 4150B, and the header portions 4154 and 4155, respectively. A plurality of liquid separation channels 4156, 4157 extending toward the center of the arc and a merge space 4158 where these liquid separation channels 4156, 4157 merge. The liquid separation channels 4156 and 4157 and the merge space 4158 are formed on the upper surface of the intermediate plate 4144b, and the liquid separation channels 4156 and 4157 are alternately arranged. The header portion 4155 on the lower surface side and the liquid separation channel 4157 communicate with each other through a communication hole 4157a penetrating the intermediate plate 4144b. The merge space 4158 is formed so that the width gradually decreases toward the downstream side, and communicates with an outflow port 4160 formed through the middle plate 4144b and the lower plate 4144c.

  In the example shown in FIG. 87, five separation flow paths 4156 and four separation flow paths 4157 are alternately arranged on the opening surface 4159 on the inlet side of the merge space 4158. The two types of liquids respectively flowing out from the separation flow paths 4156 and 4157 flow downstream while forming a striped flow in the merge space 4158, and are forced as the flow path width of the merge space 4158 gradually decreases. Both liquids are mixed. In this example, the flow path width of the merge space 4158 finally reaches 40 μm. If the processing technology accuracy is increased, the flow path width can be reduced to 10 μm.

  88 (a) is a plan view showing the reaction part shown in FIG. 83, and FIG. 88 (b) is a cross-sectional view of the reaction part shown in FIG. 88 (a). In this example, two base materials 4144d and 4144e are joined to form a reaction portion 4142 having a thickness of 5 mm. In this reaction part 4142, the reaction flow path 4162 meanders, and provides a long flow path efficiently. The reaction flow path 4162 has connecting portions 4162a and 4162c connected to the inlet port 4164 and the outlet port 4165, respectively, and a meandering portion 4162b communicating with the connecting portions 4162a and 4162c. The width of the connecting portions 4162a and 4162c is narrow. The meandering portion 4162b is formed wider. Accordingly, the liquid flows rapidly at the entrance / exit portion to prevent adhesion of by-products, and flows slowly at the meandering portion 4162b, so that the heating and reaction time can be increased.

  FIGS. 89 (a) and 89 (b) show another example of the structure of the reaction part having the part 4163a in which the width of the reaction channel gradually decreases and the part 4163b in which the width gradually increases. In the reaction part 4142a, a reaction channel 4163 is formed between the base materials 4144d and 4144e, the width dimension of which increases or decreases in the range from the maximum a to the minimum b. The depth may be increased or decreased according to the increase or decrease of the width dimension.

  In this example, the depth changes from the maximum c to the minimum d so that the cross-sectional area of the reaction channel 4163 is constant.

  FIG. 89 (c) is a cross-sectional view showing another configuration example of the reaction channel. In this reaction part 4142b, the reaction flow path 4163c has a flat shape whose width e is larger than the depth f, and has a wide heat transfer surface intersecting the heat transfer direction (indicated by the arrow) from the thermal catalyst. Therefore, heat is effectively transferred to the liquid in the reaction channel 4163c. In addition, it is effective in order to accelerate | stimulate reaction to arrange | position an appropriate catalyst in the confluence | merging space 4158 and the reaction flow paths 4162 and 4163. FIG. Such a catalyst is selected depending on the type of reaction. As for the arrangement method, for example, it can be applied to the inner surface of the channel, or can be arranged as an obstacle of the channel as described later.

  Examples of a material that forms at least the flow path of the mixing unit 4140 and the reaction unit 4142 include, for example, hard glass such as SUS316, SUS304, Ti, quartz glass, and Pyrex (registered trademark) glass, PEEK (polyetheretherketone), PE (polyethylene), From among PVC (polyvinylchloride), PDMS (polydimethylsiloxane), Si, PTFE (polytetrafluoroethylene), PCTFE (Polychlorotrifluoroethylene), and PFA (perfluoroalkoxylalkane), considering chemical resistance, pressure resistance, thermal conductivity, heat resistance, etc. Choose the preferred one. The material of the wetted part of the mixing part 4140 and the reaction part 4142 is preferably one that has little elution from the surface, can be modified with a surface catalyst, has a certain degree of chemical resistance, and can withstand a wide temperature range of −40 to 150 ° C. .

  FIG. 90 is a perspective view showing a configuration of a temperature adjustment case for adjusting the temperatures of the mixing unit and the reaction unit. In the following description, only the temperature adjustment case 4146 for adjusting the temperature of the reaction unit 4142 will be described, but the temperature adjustment case 4146 for the mixing unit 4140 has the same configuration, and redundant description thereof is omitted. To do. The temperature adjustment case 4146 includes a case main body 4172 in which a space 4170 that accommodates the reaction portion 4142 is formed, and a lid portion 4174 that covers the space 4170. A groove 4176 constituting the medium flow path is formed. A liquid supply path 4178 and a drainage path 4180 (see FIG. 83) communicating with the groove 4176 are formed in the case main body 4172. These liquid supply path 4178 and the drainage path 4180 are connected to the heat medium controller 4107, respectively. Yes. The liquid supply path 4178 communicates with the groove 4176 of the lid portion 4174 via the opening 4179, and the drainage path 4180 also communicates with the groove 4176 of the lid portion 4174 via an opening (not shown). In this example, the heat medium flowing through the groove 4176 is in direct contact with the front and back surfaces of the reaction unit 4142, and the reaction unit 4142 is heated (or cooled) in a state of being completely accommodated in the temperature adjustment case 4146.

  Although not shown, the heat medium controller 4107 includes a control mechanism for controlling the temperature of the heat medium and a pump for transferring the heat medium. As shown in FIG. 83, the heat medium is supplied to the temperature adjustment case 4146 of the mixing unit 4140 and the reaction unit 4142 after passing through the heat exchanger 4182. The heat exchanger 4182 can change the temperature of the heat medium supplied to the mixing unit 4140 and the reaction unit 4142 independently by changing the amount of city water for cooling, for example.

  91 (a) to 91 (d) show another example of the temperature adjustment case 4146. Here, the heat medium flow path 4192 is formed inside each of the case main body 4172 and the lid portion 4174. FIG. Has been. As shown in FIG. 91 (c), the liquid supply path 4178 has a double pipe structure in which the tip of the liquid supply pipe 4001A4188 is inserted, and communicates with the heat medium flow path 4192 through a thin communication path 4190. is doing. The drainage side has the same configuration. As shown in FIG. 91 (b), the temperature adjustment case 4146 that accommodates the mixing unit 4140 and the temperature adjustment case 4146 that accommodates the reaction unit 4142 are stacked and coupled via a bolt 4194, a nut 4195, and a spacer 4196. ing.

  FIG. 91 (b) shows a path for supplying and discharging the liquid to and from the mixing unit 4140 and the reaction unit 4142 accommodated in the temperature adjustment case 4146. That is, each liquid flows into and out of the mixing unit 4140 through the flow passage 4198 formed through the temperature adjustment case 4146. In addition, the liquid is circulated between the mixing unit 4140 and the reaction unit 4142 through a communication passage 4200 that communicates with the flow passage 4198 of the temperature adjustment case 4146. FIG. 91 (d) illustrates the structure of the inflow portion and the outflow portion of the liquid in the reaction portion 4142. In order to direct the liquid flow downward, the liquid inlet of the mixing unit 4140 and the reaction unit 4142 is normally formed on the upper surface and the outlet is formed on the lower surface.

  As shown in FIG. 83, the outlet 4202 of the reaction unit 4142 is connected to the product storage unit 4104 via a recovery pipe 4001A4204. The product storage unit 4104 is provided with a recovery container 4208 on the downstream side of the heat exchanger 4206 for cooling and the flow path switching valve 4132. The product storage unit 4104 in which the recovery container 4208 is placed is isolated so as not to be affected by temperature and the like from other regions, and to prevent toxic gas that may be generated from the product from leaking outside. .

  FIG. 92 shows another configuration example of the product storage unit 4104, and a plurality of collection containers 4208 are installed on the turntable 4212. In this example, two collection containers 4208 are provided, and the actuator 4214 for moving the rotary table 4212 is a 4180-degree rotary actuator. Of course, the number of collection containers 4208 and the type of actuator 4214 can be selected as appropriate. The operation control unit 4106 shown in FIG. 83 determines the replacement timing of the recovery container 4208 based on a signal from the liquid level detection sensor 4211b that detects the liquid level of the recovery container 4208, and the flow path switching valve 4132 (see FIG. 83). The liquid flow is stopped, the stop of the liquid flow is confirmed by the optical fluid detection sensor 4211a provided downstream of the recovery port 4210, and the actuator 4214 is operated to move the other recovery container 4208 below the recovery port 4210.

  Next, a process of reacting a liquid (raw material liquid) such as a chemical solution with the fluid reaction apparatus configured as described above will be described. The operation of the fluid reaction apparatus is basically automatically controlled by the operation control unit 4106. First, in the raw material storage unit 4101, the storage containers 4110 </ b> A and 4110 </ b> B storing the raw material liquid are prepared. The temperature of the heat medium is set by the heat medium controller 4107, the amount of city water passing through the heat exchanger 4182 is adjusted to adjust the temperature of each heat medium, and the temperature adjustment case 4146 of the mixing unit 4140 and the reaction unit 4142. Heat medium is circulated to maintain a predetermined temperature. The temperature of the heat medium is measured by temperature sensors 4216 and 4218 provided at the inlet of the temperature adjustment case 4146.

  In this example, before supplying the raw material liquid to the processing unit 4103, a cleaning liquid such as pure water is supplied to the flow paths in the mixing unit 4140 and the reaction unit 4142 to perform cleaning in advance. While cleaning the flow path, the temperature of the cleaning liquid is measured by the temperature sensor 4220 at the outlet of the mixing unit 4140 and the temperature sensor 4222 at the outlet of the reaction unit 4142, and the temperature of the cleaning liquid is fed back to the heat medium controller 4107. In this way, the mixing unit 4140 and the reaction unit 4142 are adjusted to a predetermined temperature.

  After the temperature of the mixing unit 4140 and the reaction unit 4142 is adjusted and the cleaning of the flow path is completed, the flow path switching valve 4132 is switched and the pumps 4116A and 4116B are driven to supply the raw material liquid in the storage containers 4110A and 4110B, respectively. Transport. The raw material liquid is adjusted to a predetermined flow rate by the flow rate adjusting devices 4300A and 4300B, and then reaches the recovery container 4208 via the mixing unit 4140, the reaction unit 4142, the outlet port 4202, and the recovery port 4210. The flow path switching valve 4132 is an automatic valve that is actuated by an actuator, and this operation can also be performed automatically.

  In the mixing unit 4140, the raw material liquids are heated to a predetermined temperature in the preheating channels 4148 </ b> A and 4148 </ b> B (see FIG. 86), and then merged and mixed in the joining unit 4152. At that time, as shown in FIG. 87, each liquid flows into the merge space 4158 from the header portions 4154 and 4155 via the liquid separation channels 4156 and 4157. Since the cross section of the merge space 4158 gradually decreases toward the downstream, micro-sized flows are regularly mixed and rapidly mixed according to Fick's law. In that state, when it flows into the reaction channel 4162 of the reaction unit 4142 maintained at a predetermined temperature, the reaction proceeds rapidly without being restricted by mass transfer or heat conduction. Therefore, it is sufficiently practical as a mass production means, and it is not necessary to carry out an explosive reaction with a high reaction rate at a low temperature. In this example, since the width of the reaction channel 4162 is sufficiently wide compared to the width of the merge space 4158, even when the reaction rate is slow, the reaction can be performed over a sufficient time, and a high yield can be obtained. Obtainable.

  The obtained product is sent from the outlet 4202 of the reaction channel 4162 to the heat exchanger 4206 via the recovery pipe 4001A4204, where it is cooled, and flows into the recovery container 4208 from the recovery port 4210. When the storage containers 4110A and 4110B are emptied or the collection container 4208 is full, the operation control unit 4106 stops the operation of the pumps 4116A and 4116B and ends the process. In this case, in addition to the storage containers 4110A and 4110B, if an additional storage container is prepared in the raw material storage unit 4101 in advance, the flow path switching valves 4126A and 4126B can be switched to perform continuous operation without stopping. Processing is possible. In addition, when reaction takes time, it is also possible to carry out batch operation by confining the liquid in the mixing unit 4140 and the reaction unit 4142 for a certain period of time. Since the flow path switching valves 4126A and 4126B are also automatic valves, these operations can be automatically operated.

  In the batch operation method, the pumps 4116A and 4116B may be temporarily stopped, or the flow switching valves 4126A and 4126B may be switched to stop the inflow of liquid into the processing unit 4103. This eliminates the need to increase the length of the reaction channel 4162 even when the liquid reaction time is long. In batch operation, it is preferable to perform operation control using a fullness detection means for detecting that the merge space 4158 and / or the reaction flow path 4162 is filled with liquid. For example, an optical fluid detection sensor as shown in FIG. 92 is used. Accordingly, when it is determined that the merge space 4158 and / or the reaction channel 4162 is filled with the liquid, the pumps 4116A and 4116B are stopped or the first channel switching valve is switched to adapt the liquid to the reaction termination time. It is retained in the merge space 4158 and / or the reaction flow path 4162 for a fixed time.

  In addition, according to the flow control devices 4300A and 4300B according to the present invention, the liquid flow rate can be accurately measured, so that the liquid supply amount can be obtained from the measured flow rate and the liquid supply time. Therefore, the operation control unit 4106 can adjust the production amount of the product based on the supply amount of the liquid, and can control the operation of the fluid reaction apparatus. For example, the operation control unit 4106 may stop the operation of the pumps 4116A and 4116B or switch the flow path switching valves 4126A and 4126B when the liquid supply amount reaches a predetermined value. As described above, by incorporating the flow control device according to the present invention in the fluid reaction device, the operation control unit 4106 can control the operation of each part of the fluid reaction device based on the supply amount of the liquid.

  FIG. 93A and FIG. 93B show another configuration example of the merging unit in the mixing unit 4140. This merging portion 4152a is configured such that obstacles 4224 are arranged at a constant interval a over a predetermined distance L in a Y-shaped merging space 4158a. In this example, a columnar obstacle 4224 having a diameter of 50 μm or less was arranged over L = 5 mm from the junction. As shown in FIG. 93 (b), the obstacles 4224 are arranged in a staggered manner so that adjacent ones are shifted by half the pitch in the flow direction. As a result, the interface 4125 between the liquid A and the liquid B meanders, so that the interface area (contact area) between the two liquids can be increased. In the merging portion 4152b shown in FIG. 94, a row of obstacles 4224 are arranged in a zigzag along the flow direction in the central portion of the merging space 4158b, and the interface area can be similarly increased. This is suitable for use in the narrow merge space 4158b.

  FIG. 95 shows another configuration example of the processing unit 4103 of the fluid reaction device. 83. In the processing unit 4103 of FIG. 83, two systems R1 and R2 each having a combination of a mixing unit 4140 and a reaction unit 4142 are provided, and two kinds of flow switching valves 4126A and 4126B of the liquid distribution unit 4102 are used. The raw material liquid can be supplied to any of the systems R1 and R2. As described above, by using the two systems, the processing amount can be increased as necessary, but there are various other usage methods. For example, when the reaction product easily precipitates solid particles and is easily clogged in the middle of the pipe 4001A, one system is used as a spare. Further, the batch operation described above can be continuously performed by alternately switching the transfer lines by the flow path switching valves 4126A and 4126B. Of course, three or more transfer lines can be provided in parallel as appropriate. Also in this case, the channel switching valves 4126A and 4126B can be automatically operated.

  FIG. 96 shows an example in which a plurality of reaction units are arranged in series in the processing unit 4103. In this example, one mixing unit 4140 and three reaction units 4142a, 4142b, and 4142c are connected in series, and temperature sensors 4220, 4222a, 4222b, and 4222c are provided respectively. In this example, the temperatures of the reaction units 4142a, 4142b, and 4142c can be independently controlled according to the reaction stage. This configuration is suitable for reactions that require a bold and instantaneous change in reaction time and reaction temperature, such as biochemical reactions. For example, in this system, the reaction can be performed at 100 ° C. in the reaction unit 4142a and at −20 ° C. in the reaction unit 4142b.

  FIG. 97 shows an example in which a plurality of mixing units are provided in the processing unit 4103. In this configuration example, a first mixing unit 4140 and a reaction unit 4142 for mixing and reacting the liquid A and the liquid B are provided, and a second mixing unit 4140a is provided on the downstream side of the reaction unit 4142. In the mixing unit 4140a, the third raw material liquid or the C liquid that is the reactant transported from the pump 4116C joins and mixes the A liquid and the B liquid. The temperatures of these two mixing units 4140 and 4140a and one reaction unit 4142 are individually controlled. The liquid C may be a reaction terminator.

  In this configuration example, the inline yield evaluator 4226 is directly connected to the outlet 4202 of the second mixing unit 4140a. Thereby, the yield of the result of the chemical reaction can be confirmed in real time, and can be immediately fed back to the process parameters. The in-line yield evaluator 4226 includes methods such as infrared spectroscopy, near-infrared spectroscopy, and ultraviolet absorption as methods that can be measured without separating the object to be measured.

  In this configuration example, a separation and extraction unit 4228 that separates unnecessary substances and necessary substances from the reaction products is further provided on the downstream side of the second mixing unit 4140a. As illustrated, the separation and extraction unit 4228 includes a Y-shaped separation channel 4234. The liquid from the second mixing unit 4140a is branched into two flows by the separation channel 4234, one in the channel formed by the hydrophobic wall 4230 that allows only the hydrophobic molecules in the material to pass through, and the other in the material It flows into a flow path formed from a hydrophilic wall surface 4232 that allows only the hydrophilic molecules inside to pass therethrough. The separated substances are recovered in the recovery containers 4208 and 4208a through the recovery pipes 4001A4204 and 4204a, respectively. As the separation / extraction unit 4228, it is possible to use a membrane or a porous frit that can adsorb only a hydrophobic substance.

  FIG. 98 is a configuration example for continuous processing by repeating mixing / reaction and separation / extraction. That is, a mixing unit 4140a that processes liquid A and liquid B, a reaction unit 4142a, and a separation / extraction unit 4228a are arranged on the upstream side, and a mixing unit 4140b that processes liquid extracted from the separation / extraction unit 4228a and liquid C and reaction The unit 4142b and the separation / extraction unit 4228b are arranged on the downstream side. Unnecessary substances after the A liquid and B liquid have reacted are discharged from the discharge port 4234a of the separation and extraction unit 4228a, and unnecessary substances in the second reaction to which the C liquid has been added are discharged from the discharge port 4234b of the separation and extraction unit 4228b. Be taken out of the system. Furthermore, a mixing unit 4140c that mixes the liquid extracted from the separation / extraction unit 4228b and the fourth liquid D is provided. Liquid D may be a reaction terminator or other raw material solution. An inline yield evaluator 4226 may be provided downstream of the mixing unit 4140c.

  FIG. 99 (a) shows a configuration in which the respective parts in FIG. 98 are stacked. The liquid flows downward. The mixing unit 4140a, the reaction unit 4142a, the separation / extraction unit 4228a, the mixing unit 4140b, the reaction unit 4142b, the separation / extraction unit 4228b, and the mixing unit 4140c are accommodated in the temperature adjustment case 4146, respectively, and further, a bolt 4194, a nut 4195, and a spacer 4196. Are stacked at a predetermined interval. The movement of the liquid between each part is performed via the communication path 4200 (refer FIG. 86 (b)). The accuracy of temperature control is improved by interposing air between each part so as not to be affected by the heat of other parts by utilizing the heat insulation of air. As shown in FIG. 99 (b), it is preferable to cover each temperature adjustment case 4146 with a heat insulating material such as a clean silicon member 4236 containing bubbles.

  The fluid introduced into the fluid reaction apparatus is liquid or gas, and the substance to be recovered is liquid, gas, solid or a mixture thereof. When the introduced substance is a solid such as a powder, a powder dissolver can be installed in the raw material reservoir 4101. FIG. 100 is a configuration example of the raw material storage unit 4101 in which one of the two raw material liquids is a solution in which powder is dissolved and the other is originally liquid. The raw material powder and the solvent are introduced from the raw material inlet 4242 of the powder dissolver 4240. In this example, the raw material powder is dissolved by heating by the heater 4244 and stirring by the stirrer 4246, and the generated raw material liquid is mixed by the pump 4116A from the pipe 4001A4249 drawn into the outlet 4148, and the mixing unit 4140 and the reaction unit 4142. It comes to send to.

  Thus, the flow control device according to the present invention can be suitably used for a fluid reaction device (microreactor) that mixes and reacts fluids in a minute space. The present invention is not limited to the embodiments described so far, and is not limited to the illustrated examples, and various modifications can be made without departing from the gist of the present invention.

Plunger Pump Device The present invention further relates to a plunger pump device that can be used in the fluid reaction device and the fluid mixing device of the present invention.

  The present invention for achieving the above-described object includes, but is not limited to, the following inventions.

  (1) A plunger pump device in which a pair of plunger pumps are connected in parallel, and a cam mechanism that interlocks the plungers of the plunger pumps so as to alternately advance, and the plungers A plunger pump device comprising: a fluid pressure device that presses toward the cam mechanism when retreating; and a control unit that controls the operation of the fluid pressure device in accordance with an operation cycle of the plunger.

  In the invention described in (1), since the cam mechanism advances the plunger of each plunger pump alternately, while the fluid pressure device presses each plunger toward the cam mechanism, the plunger is positioned by the cam mechanism. Move forward and backward to perform pump operation. Since the operation of the fluid pressure device is controlled by the control unit according to the operation cycle of the plunger, unnecessary interference with the cam mechanism can be eliminated.

  (2) In the invention described in (1), the control unit stops the pressing by the fluid pressure device when each plunger moves forward.

  In the invention described in (2), unnecessary interference between the cam mechanism and the fluid pressure device is eliminated when each plunger moves forward.

  (3) In the invention described in (1) or (2), the pair of plunger pumps respectively perform a speed increasing process and a speed reducing process at an initial stage and an end stage of a discharge operation, and one speed increasing process and the other speed reducing process. The plunger pump device is characterized in that the timing is set so as to overlap each other.

  In the invention described in (3), the total discharge amount of the pair of plunger pumps is kept constant.

  (4) The plunger pump device according to any one of (1) to (3), wherein each of the plunger pumps performs a fixed stopping process between forward movement and backward movement.

  In the invention described in (4), since each plunger pump performs a fixed stopping process between forward and backward movements, the next operation is started after the flow in each plunger pump and the valve operation are stabilized.

  Embodiments of the present invention will be described below with reference to the drawings.

  FIG. 101 is a diagram showing a dual plunger pump device according to an embodiment of the present invention, and is used, for example, for the purpose of continuously discharging a chemical solution into a microreactor at a constant flow rate. This plunger pump device includes a pair of plunger pumps 5010 having the same structure. Each plunger pump 5010 has a cylinder 5012, a plunger 5014 slidably provided in the cylinder 5012, and drive means for reciprocating these. A partition 5016 that divides this space into two is provided inside the cylinder 5012. Here, one (the right side in this figure) is a pump space 5018, and the other (the left side in this figure) is an actuator space 5020. Called.

  Each plunger 5014 includes a disk-shaped piston 5022 disposed in the pump space 5018 and a rod 5024 connected to the piston 5022. The rod 5024 passes through the partition wall 5016 and the end wall 5020a of the actuator space 5020. , Projecting outside the cylinder 5012. The pump space 5018 is partitioned into a pump chamber 5026 on the end side by a piston 5022 and a buffer chamber 5028 on the partition wall 5016 side, and a seal structure is provided between the piston 5022 and the inner wall of the cylinder 5012. The end wall 5026a of the pump chamber 5026 is provided with a discharge port 5030 and a suction port 5032, which are connected to a discharge line 5038 and a supply line 5042 connected to a fluid tank 5040 via check valves 5034 and 5036, respectively. ing. Thereby, the fluid such as the chemical solution is sucked into the pump chamber 5026 from the suction port 5032 by the backward movement of the plunger 5014 (moving to the right in FIG. 101), and by the forward movement of the plunger 5014 (moving to the left in FIG. 101). The ink is discharged from the discharge port 5030. The material of the wetted part including the plunger 5014 is preferably compatible with a corrosive or erodible chemical solution. For example, sapphire, ruby, alumina, ceramic, SUS, hastelloy, titanium Etc. are used as appropriate.

  This plunger pump device is provided with two types of drive means. The first driving means is a cam mechanism 5050 provided outside the cylinder 5012, and interlocks the plungers 5014 of the plunger pumps 5010 so as to advance alternately. The cam mechanism 5050 is provided at a drive motor 5054 for rotating the camshaft 5052 at a constant speed, a pair of plate cams 5056 installed integrally with the camshaft 5052, and an outer end portion of a rod 5024 of each plunger 5014. And a roller (cam follower) 5058. The plate cam 5056 has an outer shape of a predetermined shape, and the rod 5024 reciprocates in a predetermined displacement pattern by changing the contact position with the roller 5058 as it rotates.

  The second driving means is a fluid pressure device 5060 (air cylinder) formed in the actuator space 5020 of the cylinder 5012. That is, a pressure plate 5062 is provided at the center of each rod 5024, and a pressure air chamber 5064 is formed between the pressure plate 5062 and the partition wall 5016. The pressurized air chamber 5064 is provided with a port 5066 for introducing pressurized air, which is connected to a pressurized air source 5070 and a drain 5072 via an air control valve 5068 which is a solenoid valve. A space between the pressure plate 5062 and the end wall 5020a of the actuator space 5020 communicates with an external space through an opening 5074 near the end wall. Further, the buffer chamber 5028 communicates with the drain 5072 via the port 5076 near the partition wall 5016 and the air control valve 5068, so that even if fluid leaks from the gap between the piston 5022 and the inner wall of the cylinder 5012, it does not flow outside. It has become.

  In the first switching position in which the solenoid is in a non-excited state, the air control valve 5068 is connected to the drain 5072 in both the pressure air chamber 5064 and the buffer space as shown for the upper plunger pump 5010 in FIG. 5014 is in a neutral state. On the other hand, in the second switching position in which the solenoid is excited, the pressure air chamber 5064 is connected to the pressure air source 5070 and the buffer space is connected to the drain 5072 as shown for the lower plunger pump 5010 in FIG. It becomes a state. Accordingly, the plunger 5014 is pushed in the direction of enlarging the pump chamber 5026 (leftward in FIG. 101). As described above, the piston 5022, the pressure air chamber 5064, the solenoid valve, and the pressurized air source constitute an air cylinder 5060 that operates only in one direction. The air pressure of the pressure air source 5070 is set to about 3 to 5 kg / cm 2, for example.

  A control unit 5080 is provided to control these two driving units in conjunction with each other. The camshaft 5052 is provided with an encoder, and its output is input to the control unit 5080. Thereby, the rotational position information of the camshaft 5052, that is, the reciprocating position information of each plunger 5014 is input to the control unit 5080. The control unit 5080 controls the operation of the air cylinder 5060 by switching the solenoid of the air control valve 5068 on and off based on the reciprocating position information of the plunger 5014 given by the encoder 5082.

  Hereinafter, the operation of the plunger pump device configured as described above will be described.

  First, the operation of one plunger pump 5010 will be described. In FIG. 102, line A is a velocity diagram of the plunger 5014 when the camshaft 5052 is rotated at a constant rotational speed, the horizontal axis indicates the rotation angle of the camshaft 5052, and the vertical axis indicates the speed of the plunger 5014 (+ is Forward direction,-indicates backward direction). Since the discharge amount is proportional to the speed of the plunger 5014, the vertical axis also represents the discharge amount. The horizontal axis is also a time axis. Line B represents the pressing state of the plunger 5014 by the cam mechanism 5050, line C represents on / off of the air cylinder 5060, and line D represents volume change of the pump chamber 5026.

  In the range of 0-15 degrees of rotation angle, the contact surface of the plate cam 5056 advances at a constant acceleration while increasing the speed to a predetermined value (steady discharge speed), and thereafter in the range of 15-180 degrees. Advances at the discharge speed. During this time, since the air control valve 5068 is in the first switching position in a non-excited state, the plunger 5014 is neutral, and only the force from the plate cam 5056 acts on the plunger 5014 as shown by the line B. 5014 moves forward as shown by line A to perform a discharge operation. Further, in the range of the rotation angle of 180 to 195 degrees, the plunger 5014 decreases the speed to 0 at a constant ratio, and then the speed becomes 0 in the range of the rotation angle of 195 to 210 degrees and the discharge operation is stopped.

  When the rotation angle is between 0 and 210 degrees, as indicated by line C, the plunger 5014 is neutral, and the cam mechanism 5050 only needs to perform work for the plunger 5014 to perform the pump operation. As described above, the speed increasing process (rotation angle 0 to 15 degrees) and the deceleration process (rotation angles 180 to 195 degrees) are shifted by exactly 180 degrees in the discharge operation. Further, the entire discharging process is performed within a rotation angle range of 0 to 195 degrees.

  Next, in the range of a rotation angle of 210 to 225 degrees, the contact surface of the plate cam 5056 moves backward at a constant acceleration while increasing the speed to a predetermined value (steady suction speed). On the other hand, when the encoder 5082 detects a rotation angle of 210 degrees, the control unit 5080 excites the solenoid of the air control valve 5068, the air control valve 5068 becomes the second switching position, and the pressurized air is supplied to the pressure air chamber 5064. Sent. As a result, the air cylinder 5060 is activated, and the plunger 5014 is pressed toward the cam mechanism 5050 and moved by following the retreating plate cam 5056. Since the pressure of the air cylinder 5060 is set to a value sufficient for the plunger 5014 to perform a fluid suction operation, the plunger 5014 performs the suction operation. The rigidity of the cam mechanism 5050 and the driving force of the motor 5054 are set to withstand the pressing force of the air cylinder 5060, and the positioning function of the cam mechanism 5050 when the plunger 5014 is retracted is not impaired.

  Thereafter, in the range of the rotation angle 225 to 330 degrees, the plunger 5014 moves backward at the steady suction speed to perform the discharge operation. Further, in the range of the rotation angle of 330 to 345 degrees, the plunger 5014 decreases the speed to 0 at a constant ratio, and then the speed becomes 0 in the range of the rotation angle of 345 to 360 degrees, and the suction operation is stopped. As is clear from FIG. 101, the suction time is shorter than the discharge time, so the steady suction speed is greater than the steady discharge speed.

  In the above steps, a stop process is provided after the discharge operation (range of rotation angle 195 to 210 degrees) and after the suction operation (range of rotation angles 330 to 345 degrees), respectively. Accordingly, the check valve 5034, 5036 of the discharge port 5030 or the suction port 5032 is reliably closed, or the next suction or discharge operation starts after the flow has settled in this portion. Pulsation due to backflow or the like from the valves 5034 and 5036 is prevented.

  Next, the overall operation of the plunger pump device will be described with reference to FIG. In FIG. 103, the ratio of each process is exaggerated. The process is described for the plunger pump 5010 indicated by a solid line.

  The two plunger pumps 5010 are driven by two plate cams 5056 attached to a common cam shaft 5052 so that the phases are different by 180 degrees. That is, these operations are 180 degrees out of phase. The discharge amount of the entire plunger pump device is the sum of the plunger pumps 5010 connected in parallel, and is represented by a two-dot chain line in FIG. As described above, in the discharge operation, the speed increasing process (rotation angle 0 to 15 degrees) and the speed reducing process (rotation angle 180 to 195 degrees) are shifted by exactly 180 degrees, and the speed increasing rate and the speed reducing rate in these are equal. The sum of the discharge amounts of these plunger pumps 5010 is constant, so that no pulsation occurs when the operation is switched.

  Further, in this plunger pump device, since the plunger 5014 is always in contact with the cam mechanism 5050, the plunger 5014 is reliably positioned by the contact surface of the plate cam 5056. Therefore, the discharge amount is controlled with high accuracy, and pulsation can be suppressed also in this respect.

  In addition, since the second driving means capable of on / off operation is used to press the plunger 5014 against the cam mechanism 5050, the cam mechanism 5050 can be turned off when the cam mechanism 5050 is moved forward. The load on the mechanism 5050 can be reduced. Therefore, the cost of an actuator such as a motor 5054 that is a driving device of the cam mechanism 5050 is reduced, and friction at the contact portion of these members is reduced, thereby enabling a long life.

  FIG. 104 shows another embodiment of the present invention, in which the cam mechanism 5050A uses an end face cam 5056A instead of the plate cam 5056. Since this operation is basically the same as that of the above-described embodiment, description thereof is omitted.

  The present invention has been described in detail with specific examples. However, the present invention is not limited to the above contents, and various modifications and changes can be made without departing from the gist of the present invention. For example, the operating source of the fluid pressure device may be pressurized liquid instead of pressurized air.

Plunger Pump Device The present invention further relates to a plunger pump device that can be used in the fluid reaction device and the fluid mixing device of the present invention.

  The present invention for achieving the above-described object includes, but is not limited to, the following inventions.

  (1) Plunger pump device, each having a separate drive device, a pair of plunger pumps connected in parallel between the liquid source and the microreactor channel, and a flow meter installed in the microreactor channel A control unit that alternately discharges the pair of plunger pumps at a constant predetermined feed rate, and the control unit is configured to perform a predetermined operation based on a measurement value of the flow meter when the plunger pump is performing a discharge operation. The plunger pump device is characterized in that the feed rate is adjusted at the timing of

  In the invention described in (1), since the feed rate is adjusted at a predetermined timing based on the measured value of the flow meter when the plunger pump is performing a discharge operation, without using a complicated control means, The accuracy of the discharge amount of the plunger pump can be maintained. It is desirable to obtain the measured value by the flow meter as an average value for a predetermined time. The plunger pump may be adjusted individually, and in that case, the measurement is also performed individually.

  (2) The invention described in (1), further comprising a pressure sensor installed in the microreactor flow path, wherein the control unit finely adjusts the feed rate based on an output value of the pressure sensor. Plunger pump device.

  In the invention described in (2), since the feed rate is finely adjusted based on the output value of the pressure sensor installed in the microreactor flow path, pulsation due to various causes is suppressed.

  (3) In the invention according to (1) or (2), the control unit performs a speed increasing process and a speed decreasing process for each of the pair of plunger pumps at an initial stage and an end stage of a discharge operation, A plunger pump device that performs switching control with a constant flow rate so that the process and the other deceleration process overlap each other.

  In the invention described in (3), the transition from one plunger pump to the other plunger pump is performed with a constant flow rate.

  (4) In the invention described in (3), the plunger pump device is characterized in that the feed rate is finely adjusted only for one plunger pump during the switching control.

  (5) In the invention according to any one of (1) to (4), the control unit controls the plunger pump to perform a certain stopping process between forward and backward movements. Pump device.

  In the invention described in (5), since each plunger pump performs a fixed stopping process between the forward movement and the backward movement, the next operation is started after the flow in each plunger pump and the valve operation are stabilized.

  (6) In the invention according to any one of (1) to (5), a position sensor that detects a position of a plunger of the plunger pump is provided, and the control unit controls a feed rate based on an output of the position sensor. A plunger pump device characterized by:

  Embodiments of the present invention will be described below with reference to the drawings.

  FIG. 106 is a diagram showing a dual plunger pump apparatus according to an embodiment of the present invention, and is used, for example, for the purpose of continuously discharging a chemical solution at a constant flow rate into a microreactor. This plunger pump device 6001 is composed of a pair of plunger pumps 6010 having the same structure. Each plunger pump 6010 has a cylinder 6012, a plunger 6014 slidably provided in the cylinder 6012, a drive device 6019 for reciprocating these, and a control unit 6028 for controlling each part.

  Each plunger 6014 is constituted by a disk-like piston 6016 and a rod 6018 connected thereto, and forms a pump chamber 6017 before the end. The rod 6018 is connected to the driving device 6019 through the end wall. In this embodiment, the drive device 6019 has a feed screw 6022 that is rotationally driven by a motor 6020 and a nut 6024 that is screwed to the feed screw 6022, and the nut 6024 is fixed to the end of the rod 7018. A ball (bearing) is interposed between the feed screw 6022 and the nut 6024, and a smooth and highly accurate linear motion mechanism called a ball screw is configured. Further, a linear scale (position sensor) 6026 for detecting the position of the nut 6024 is provided, and its output is sent to the control unit 6028. The controller 6028 can feedback control the rotation of the motor 6020 based on this output, and can accurately control the position and feed rate of the plunger 6014.

  A seal structure is provided between the piston 6016 and the inner wall of the cylinder 6012. A discharge port 6030 and a suction port 6032 are provided on the end wall of the pump chamber 6017, and these are connected to a supply line 40 connected to a discharge line 6036 or a fluid tank 6038 via a check valve 6034, respectively. Thereby, fluid such as a chemical solution is sucked into the pump chamber from the suction port 6032 by the backward movement of the plunger 6014 (moving to the left in FIG. 106) and discharged by the forward movement of the plunger 6014 (moving to the right in FIG. 106). The ink is discharged from the port 6030. The material of the wetted part including the plunger 6014 is preferably compatible with a corrosive or erosive chemical solution, for example, sapphire, ruby, alumina, ceramic, SUS, hastelloy, titanium. Etc. are used as appropriate.

  As shown in FIG. 107, the discharge ports 6030 of the two plunger pumps 6010 merge and are connected to the raw material receiving port 6042 of the microreactor 6002. In this microreactor 6002, two raw material receiving ports 6042 are provided, and these merge at the mixing / reaction unit 50 via the introduction flow path 6044. The introduction flow path 6044 is provided with a flow meter 6046 and a pressure sensor 6048, respectively, and these outputs are input to the control unit 6028 and used for control as described later. In FIG. 107, the control unit 6028 is provided for each plunger pump device 6001, but of course, one control unit 6028 may be shared. Further, these control units 6028 may be connected to, for example, a control device of the microreactor 6002 for integrated control.

Hereinafter, the operation of the plunger pump device 6001 having such a configuration will be described. The control unit 6028 uses a combination of two control methods, that is, pattern control for controlling the plunger pump 6010 along a predetermined pattern, and feedback control for controlling the plunger pump 6010 based on the measured value of the sensor. Each of these controls the feed speed of the plunger 6014, but basically the pattern control is the main and the feedback control is the sub. Describing this conceptually, the overall control function F is represented by a pattern control function F1 (t) that is a function of time t and a feedback control function F2 (p) that is a function of measured pressure p.
F = F1 (t) [1 + F2 (p)] (Formula 1)
It is represented by That is, when there is no pressure fluctuation, only pattern control of F = F1 (t) is performed, and when there is a pressure fluctuation, it fluctuates at a ratio of F2 (p). How much F2 (p) contributes is determined by how the function is set, for example, it is preferably about 10% at the maximum.

  108 and 109 explain pattern control. FIG. 108 shows the operation of each plunger pump 6010, and line A is a velocity diagram when the plunger 6014 reciprocates once. The horizontal axis represents time as 360 degrees per cycle, and the vertical axis represents the speed of the plunger 6014 (+ is the forward direction, − is the backward direction). Since the discharge amount is proportional to the speed of the plunger 6014, the vertical axis also represents the discharge amount. A line B represents a change in volume of the pump chamber 6017. FIG. 109 shows a state in which the two plunger pumps 6010 are operating with a phase shifted by 180 degrees.

  As can be seen from these drawings, the two plunger pumps 6010 overlap each other so that one of them performs the speed increasing process and the other performs the speed reducing process at the beginning and the end of the discharge process. Thus, in this switching process, the plunger pump 6010 that performs the discharge operation is switched while the total flow rate is controlled to be constant. A short stop process is provided after the discharge operation and the suction operation of each plunger pump 6010. Therefore, the check valve 6034, 6036 of the discharge port 6030 or the suction port 6032 is securely closed, or the next suction or discharge operation starts after the flow has settled in this portion. Pulsation due to backflow or the like from the valves 6034 and 6036 is prevented.

In this pattern control, the steady feed speed Vc at the time of discharge is determined based on the required discharge amount and the following formula, and thereby the initial pattern function P (t) is set.

Flow rate L = plunger 6014 cross-sectional area S × plunger 6014 feed speed V (Formula 2)
However, the actual machine may differ from the calculation and may change with time. Therefore, an operation of adjusting the set value with the actually measured value is performed. This is not performed constantly but at an appropriate timing and frequency. This is because even if the feedback control is steadily performed, there is no effect because the response speed of the flow sensor is low, and it is considered that adjustment in a timely manner is sufficient from the characteristics of the plunger 6014. Although timing and frequency are arbitrary, for example, it is performed at start-up, performed every time a certain operation time elapses, or a combination thereof.

  This adjustment process will be described with reference to the flowchart of FIG. 110 and the graph showing the change of each measured value of FIG. 111A shows an example of a change in the measured value of the flow meter 6046 installed in the flow channel of the microreactor 6002, FIG. 111B shows an example of a change in the output value of the pressure sensor 6048, and FIG. 111C shows a plunger 6014. One example of the change in the feed speed is shown.

First, the control unit 6028 determines whether it is the timing of the adjustment work (step 1). This is performed, for example, by detecting the presence / absence of the command signal at the start or by detecting the presence / absence of a signal for notifying that the timer has been operated for a predetermined time. At that timing,
First, the flow rate when only the first plunger pump 6010 is discharging is measured (step 2). Here, an average flow rate for a predetermined time is calculated, not an instantaneous flow rate at a certain point in time. You may make it use the average value of the flow volume of one pump in several cycles instead of one cycle.

Next, a difference ΔL between the measured flow rate and the specified flow rate is calculated, and it is determined whether or not this is larger than a preset allowable upper limit value (step 3). As shown in FIG. 111 (a), when it is larger than the set upper limit value, an adjustment amount of the feed speed is calculated (step 4), and adjustment is performed based on the calculated value (step 5). Calculation of the adjustment amount ΔV uses the following expression based on Expression 2.

Feed rate adjustment amount ΔV = flow rate difference ΔL / plunger cross-sectional area S (Formula 3)
If ΔL is smaller than the allowable upper limit value in step 3, no adjustment is performed. Next, the measurement or adjustment operation is performed in the same manner for the second pump (steps 6 to 9), and the adjustment operation is completed. In this way, a new steady feed speed Vc is determined, and a new pattern function P (t) in which the gradient of the switching process is adjusted is determined along with this. Thereby, an accurate flow rate output in an actual machine can be achieved by a simple control method.

  In this embodiment, since adjustment is performed for each plunger pump 6010, even when there is a difference in the characteristics of the two plunger pumps 6010 and the flow path, it is possible to always perform liquid feeding with no flow rate fluctuation. If there is no difference for each plunger pump 6010, the two may be controlled by the same pattern function. In this case, step 6 to step 9 are omitted. In step 2, it is preferable that the flow rates of the discharge operations of the two pumps are measured and averaged to obtain a measured value.

  Next, the case where the feed rate is feedback controlled based on the measured value of the pressure sensor 6048 installed in the flow path of the microreactor 6002 will be described with reference to FIGS. 111 and 112. FIG. This is done by setting the control function for the overall feed rate as shown in Equation 1 below.

F = F1 (t) [1 + F2 (p)] (Formula 1)
The actual form of F (p) can be obtained, for example, by obtaining a PID control coefficient by using both experiments and theoretical analysis.

  The pressure varies depending on the length and shape of the flow path, but the pressure is constant if a constant flow rate is maintained. For this reason, since the change in pressure represents the flow rate fluctuation in the flow path, the flow rate fluctuation can be suppressed by feedback-controlling this. Further, since the response of the pressure sensor 6048 is faster and more accurate than the general flow meter 6046, it is suitable for suppressing fluctuations in the flow rate. In the switching process in which the two pumps operate, the control function of each pump is different in that one of P (t) is increased and the other is decreased, so that the total flow rate is maintained. The meaning of is the same.

  In the plunger pump device 6001 of this embodiment, the pulsation generated when the feed of the plunger 6014 is shifted due to a mechanical error, gas is mixed in the fluid, or the check valve operation becomes unstable is canceled. It is possible to control the discharge amount. For example, in FIG. 111 (b), case 1 shows pressure fluctuation during steady feeding, and case 6002 shows pressure fluctuation during steady feeding, and this is detected and the feed speed is shown as in FIG. By performing feedback control, pressure fluctuations are suppressed, and fluctuations in the discharge amount are also suppressed as shown in FIG.

  In the above-described embodiment, as shown in FIG. 112 (a), the pressure sensor 6048 is always used in both the steady discharge process in which one unit discharges and the switching process in which two units discharge. However, when the same control is simultaneously performed on the two plungers, there may be a problem that the control becomes unstable. Therefore, as shown in FIG. 112 (b), in the switching process, pressure feedback control may be performed on only one of the pumps. In this example, the pressure feedback control is performed for the pump in the speed increasing process in the switching process, but the reverse may be possible. Further, as shown in FIG. 112 (c), pressure feedback control may be performed only for the pump having the larger discharge amount.

  Next, a fluid reaction device (microreactor 6002) incorporating the above-described flow rate adjusting device according to an embodiment of the present invention will be described. FIG. 113 to FIG. 115 (b) are diagrams showing the overall configuration of a fluid reaction apparatus incorporating a flow rate adjusting device according to an embodiment of the present invention. The fluid reaction apparatus described below is an apparatus used for mixing and reacting two or more kinds of liquids.

  As shown in FIG. 113, FIG. 114, FIG. 115 (a), and FIG. 115 (b), the fluid reaction apparatus is entirely installed in one installation space and packaged. In this configuration example, the installation space is rectangular and is divided into four regions along the longitudinal direction. In other words, the first region on one end side is a raw material storage unit 6101 in which a plurality of storage containers 6110 (only two storage containers 6110A and 6110B are shown in FIG. 113) for storing the raw material liquid are installed, and are adjacent thereto. The second region is a liquid distribution unit 6102 in which double plunger pumps 6001A and 6001B for transferring the raw material liquid in the storage container 6110 are installed. A third region adjacent to the second region is a processing unit 6103 having a mixing unit (mixing chip) 6140 for mixing the raw material liquid and a reaction unit (reaction chip) 6142 for reacting the mixed raw material liquid. . The fourth region on the other end side is a product storage unit (recovery container installation space) 6104 for deriving and storing a product obtained as a result of the processing.

  The fluid reaction apparatus also includes an operation control unit 6106 that is a computer that controls the operation of each unit, and a heat medium controller 6107 that adjusts the temperature of the processing unit 6103 by flowing a heat medium through the temperature adjustment case 6146. . Further, as shown in FIG. 113, the operation control unit 6106 is equipped with a flow rate monitor 6270 and a temperature monitor 6272 that can monitor the flow rate and temperature of the liquid. In this configuration example, the operation control unit 6106 and the heat medium controller 6107 are provided separately from the fluid reaction device, but may of course be integrated. As shown in FIG. 114, a piping chamber 6105 is formed in the lower floor portion of the second to fourth regions, and piping for sending a heating medium for heating or cooling to the mixing unit 6140 and the reaction unit 6142 is provided here. Is provided.

  In this way, by arranging the respective parts from the upstream side to the downstream side, the flow of the liquid can be made smooth, and the entire apparatus can be made compact. In this configuration example, each part is arranged in a straight line. However, for example, if the entire space is close to a square, each part may be configured such that the liquid flow forms a loop.

  In FIG. 114, reference numeral 6250 denotes a liquid reservoir pan provided at the lower part of the apparatus, and reference numeral 6252 denotes a liquid leakage sensor installed on the liquid reservoir pan 6250. In this example of the apparatus, the liquid distribution unit 6102, the processing unit 6103, and the product storage unit 6104 are partitioned by partition walls 6254 and 6256, and covers 6258, 6260, and 6262 are attached to the respective parts to isolate them from the outside of the apparatus. is doing. Reference numeral 6264 denotes an exhaust port, which is connected to an exhaust fan (not shown). And the toxic gas in the apparatus is prevented from leaking outside by making the pressure in the apparatus negative from the outside of the apparatus.

  Although the two storage containers 6110A and 6110B are installed in the raw material storage unit 6101 shown in FIG. 113, three or more storage containers may be used as necessary. For example, the process can be continuously performed by storing the same liquid in two storage containers and using them alternately. Note that the raw material reservoir 6101 may be provided with a cleaning liquid container 6112 containing an organic solvent such as acetone for line cleaning, hydrochloric acid, pure water, or the like, or a pressure source 6114 filled with a purge nitrogen gas. Further, the waste liquid container 6136 may be placed in the raw material storage unit 6101.

  Pumps 6001A and 6001B connected to the storage containers 6110A and 6110B via transport pipes 6121A and 6121B are installed in the liquid distribution section (introduction section) 6102. In addition, the liquid distribution unit 6102 includes flow rate adjusting devices 6300A and 6300B, relief valves 6122A and 6122B, pressure measurement sensors 6124A and 6124B, flow path switching valves 6126A and 6126B, and the like arranged on the downstream side of the plunger pumps 6001A and 6001B. A washing pump 6130 is provided. The flow path switching valves 6126A and 6126B are connected to the cleaning liquid container 6112 and the pressure source 6114 in addition to the transport pipes 6121A and 6121B, respectively. The backwash pump 6130 is used when the flow path of the mixing unit 6140 or the reaction unit 6142 is blocked by the product. The backwash pump 6130 is connected to a cleaning liquid container 6112 that stores cleaning liquid, and is further connected to an outlet of the reaction unit 6142 via a flow path switching valve 6132. The cleaning liquid transferred by the backwash pump 6130 flows in reverse to the normal flow. That is, the cleaning liquid flows from the outlet of the reaction unit 6142 toward the inlet of the mixing unit 6140, passes through the flow path switching valves 6126 </ b> A and 6126 </ b> B, and enters the waste liquid storage container 6136 from the waste liquid port 6134 through a pipe (not shown).

  The backwash pump 6130 is preferably a single piston 16 type pump so that the discharge pressure is high and the product can be removed by causing pulsation in the cleaning liquid. As the cleaning liquid, an organic solvent, hydrochloric acid, nitric acid, phosphoric acid, organic acid, pure water, or the like is preferably used. Examples of the organic solvent include acetone, ethanol, methanol and the like. An introduction port 6240 shown in FIG. 113 is provided when pure water or hydrogen water is introduced from the outside, and can be used for cleaning instead of the cleaning liquid in the cleaning liquid container 6112.

  FIG. 116 shows a mixing unit 6140 for performing preliminary heating (preliminary temperature adjustment) and mixing of the raw material liquid. A mixing portion 6140 having a total thickness of 5 mm is formed by bonding. Note that the flow paths described below are all grooves formed on the surface of the intermediate plate 6144b. Two inflow ports 6147A and 6147B formed through the upper plate 6144a communicate with two preheating channels 6148A and 6148B formed on the upper surface of the middle plate 6144b, respectively. These preheating flow paths 6148A and 6148B each branch in the middle, expand, and merge again. Further, the preheating channels 6148A and 6148B communicate with the outlet channels 6150A and 6150B, respectively, and these outlet channels 6150A and 6150B communicate with the junction 6152. The outlet channel 6150A is formed on the upper surface of the middle plate 6144b, and the outlet channel 6150B is formed on the lower surface of the middle plate 6144b.

  117 is an enlarged view of the merging portion shown in FIG. As shown in FIG. 117, the merging portion 6152 includes header portions 6154 and 6155 formed on the upper and lower surfaces of the middle plate 6144b as arc-shaped grooves communicating with the outlet flow paths 6150A and 6150B, and the header portions 6154 and 6155, respectively. A plurality of liquid separation channels 6156, 6157 extending toward the center of the arc and a merge space 6158 where these liquid separation channels 6156, 6157 merge. The liquid separation channels 6156 and 6157 and the merge space 6158 are formed on the upper surface of the intermediate plate 6144b, and the liquid separation channels 6156 and 6157 are alternately arranged. The header portion 6155 on the lower surface side and the liquid separation channel 6157 communicate with each other through a communication hole 6157a penetrating the intermediate plate 6144b. The merge space 6158 is formed so that the width gradually decreases toward the downstream side, and communicates with an outflow port 6160 formed through the middle plate 6144b and the lower plate 6144c.

  In the example shown in FIG. 117, five separation flow paths 6156 and four separation flow paths 6157 are alternately arranged on the opening surface 6159 on the inlet side of the merge space 6158. The two types of liquids respectively flowing out from the separation flow channels 6156 and 6157 flow downstream while forming a striped flow in the merge space 6158, and are forced as the flow channel width of the merge space 6158 gradually decreases. Both liquids are mixed. In this example, the flow path width of the merge space 6158 finally reaches 40 μm. If the processing technology accuracy is increased, the flow path width can be reduced to 10 μm.

  118 (a) is a plan view showing the reaction part shown in FIG. 113, and FIG. 118 (b) is a cross-sectional view of the reaction part shown in FIG. 118 (a). In this example, two base materials 6144d and 6144e are joined to form a reaction portion 6142 having a thickness of 5 mm. In this reaction part 6142, the reaction flow path 6162 meanders, and provides a long flow path efficiently. The reaction flow path 6162 has connecting portions 6162a and 6162c connected to the inlet port 6164 and the outlet port 6165, respectively, and a meandering portion 6162b communicating with the connecting portions 6162a and 6162c. The width of the connecting portions 6162a and 6162c is narrow. The meandering portion 6162b is formed wider. Accordingly, the liquid flows rapidly at the inlet / outlet portion to prevent adhesion of by-products, and flows slowly at the meandering portion 6162b, so that the heating and reaction time can be increased.

  FIG. 119 (a) and FIG. 119 (b) show another configuration example of the reaction section having a portion 6163a where the width of the reaction channel gradually decreases and a portion 6163b where the width of the reaction channel gradually increases. In the reaction portion 6142a, a reaction flow path 6163 is formed between the base materials 6144d and 6144e, the width dimension of which increases or decreases in the range from the maximum a to the minimum b. The depth may be increased or decreased according to the increase or decrease of the width dimension. In this example, the depth changes from the maximum c to the minimum d so that the cross-sectional area of the reaction channel 6163 is constant.

  FIG. 119 (c) is a cross-sectional view showing another configuration example of the reaction channel. In the reaction section 6142b, the reaction flow path 6163c has a flat shape whose width e is larger than the depth f, and has a wide heat transfer surface intersecting the heat transfer direction (indicated by an arrow) from the thermal catalyst. Therefore, heat is effectively transferred to the liquid in the reaction channel 6163c. In addition, it is effective in order to accelerate | stimulate reaction to arrange | position an appropriate catalyst in the merge space 6158 and the reaction flow path 6162, 6163. Such a catalyst is selected depending on the type of reaction. As for the arrangement method, for example, it can be applied to the inner surface of the channel, or can be arranged as an obstacle of the channel as described later.

  Examples of a material that forms at least the flow path of the mixing unit 6140 and the reaction unit 6142 include, for example, hard glass such as SUS316, SUS304, Ti, quartz glass, and Pyrex (registered trademark) glass, PEEK (polyetheretherketone), PE (polyethylene), Among PVC (polyvinylchloride), PDMS (Polydimethylsiloxane), Si, PTFE (polytetrafluoroethylene), and PCTFE (PolyChloroTriFluoroEthylene), a preferable one is selected in consideration of chemical resistance, pressure resistance, thermal conductivity, heat resistance, and the like. The material of the wetted part of the mixing part 6140 and the reaction part 6142 is preferably one that has little elution from the surface, can be modified with a surface catalyst, has a certain degree of chemical resistance, and can withstand a wide temperature range of −40 to 150 ° C. .

  FIG. 120 is a perspective view showing a configuration of a temperature adjustment case for adjusting the temperatures of the mixing unit and the reaction unit. In the following description, only the temperature adjustment case 6146 for adjusting the temperature of the reaction unit 6142 will be described, but the temperature adjustment case 6146 for the mixing unit 6140 also has the same configuration, and redundant description thereof is omitted. To do. The temperature adjustment case 6146 includes a case main body 6172 in which a space 6170 that accommodates the reaction portion 6142 is formed, and a lid portion 6174 that covers the space 6170. A groove 6176 constituting the medium flow path is formed. A liquid supply path 6178 and a drainage path 6180 (see FIG. 113) communicating with the groove 6176 are formed in the case main body 6172, and these liquid supply path 6178 and drainage path 6180 are connected to the heat medium controller 6107, respectively. Yes. The liquid supply path 6178 communicates with the groove 6176 of the lid portion 6174 via the opening 6179, and the drainage path 6180 also communicates with the groove 6176 of the lid portion 6174 via an opening (not shown). In this example, the heat medium flowing through the groove 6176 directly contacts the front and back surfaces of the reaction unit 6142, and the reaction unit 6142 is heated (or cooled) in a state of being completely accommodated in the temperature adjustment case 6146.

  Although not shown, the heat medium controller 6107 includes a control mechanism for controlling the temperature of the heat medium and a pump for transferring the heat medium. As shown in FIG. 113, the heat medium is supplied to the temperature adjustment case 6146 of the mixing unit 6140 and the reaction unit 6142 after passing through the heat exchanger 6182. The heat exchanger 6182 can change the temperature of the heat medium supplied to the mixing unit 6140 and the reaction unit 6142 independently by changing the amount of city water for cooling, for example.

  121 (a) to 121 (d) show another example of the temperature adjustment case 6146. Here, the heat medium flow path 6192 is formed inside each of the case main body 6172 and the lid portion 6174. FIG. Has been. As shown in FIG. 121 (c), the liquid supply path 6178 has a double pipe structure in which the tip of the liquid supply pipe 6188 is inserted, and communicates with the heat medium flow path 6192 through a thin communication path 6190. is doing. The drainage side has the same configuration. As shown in FIG. 121 (b), the temperature adjustment case 6146 that accommodates the mixing portion 6140 and the temperature adjustment case 6146 that accommodates the reaction portion 6142 are stacked and coupled via a bolt 6194, a nut 6195, and a spacer 6196. ing.

  FIG. 121 (b) shows the supply / discharge paths of the liquid to / from the mixing unit 6140 and the reaction unit 6142 accommodated in the temperature adjustment case 6146. That is, each liquid flows into and out of the mixing unit 6140 through the flow passage 6198 formed through the temperature adjustment case 6146. Further, the liquid is circulated between the mixing unit 6140 and the reaction unit 6142 through a communication passage 6200 that communicates with the flow passage 6198 of the temperature adjustment case 6146. FIG. 121 (d) illustrates the structure of the inflow portion and the outflow portion of the liquid in the reaction portion 6142. In order to direct the liquid flow downward, the liquid inlet of the mixing unit 6140 and the reaction unit 6142 is normally formed on the upper surface and the outlet is formed on the lower surface.

  As shown in FIG. 113, the outlet 6202 of the reaction unit 6142 is connected to the product storage unit 6104 via a recovery pipe 6204. The product reservoir 6104 is provided with a recovery container 6208 on the downstream side of the heat exchanger 6206 for cooling and the flow path switching valve 6132. The product storage unit 6104 in which the recovery container 6208 is placed is isolated so as not to be affected by temperature and the like from other regions, and to prevent toxic gas that may be generated from the product from leaking outside. .

  FIG. 122 shows another configuration example of the product storage unit 6104, and a plurality of collection containers 6208 are installed on the turntable 6212. In this example, there are two collection containers 6208, and the actuator 6214 that moves the rotary table 6212 is a 180-degree rotary actuator. Of course, the number of collection containers 6208 and the type of actuator 6214 can be selected as appropriate. The operation control unit 6106 shown in FIG. 113 determines the replacement timing of the recovery container 6208 based on a signal from the liquid level detection sensor 6211b that detects the liquid level of the recovery container 6208, and the flow path switching valve 6132 (see FIG. 113). The liquid flow is stopped, the stop of the liquid flow is confirmed by the optical fluid detection sensor 6211a provided downstream of the recovery port 6210, and the actuator 6214 is operated to move the other recovery container 6208 below the recovery port 6210.

  Next, a process of reacting a liquid (raw material liquid) such as a chemical solution with the fluid reaction apparatus configured as described above will be described. The operation of the fluid reaction apparatus is basically automatically controlled by the operation control unit 6106. First, in the raw material storage part 6101, it prepares in the storage containers 6110A and 6110B which stored the raw material liquid. The temperature of the heat medium is set by the heat medium controller 6107, the amount of city water passing through the heat exchanger 6182 is adjusted to adjust the temperature of each heat medium, and the temperature adjustment case 6146 of the mixing unit 6140 and the reaction unit 6142 is adjusted. Heat medium is circulated to maintain a predetermined temperature. The temperature of the heat medium is measured by temperature sensors 6216 and 6218 provided at the inlet of the temperature adjustment case 6146.

  In this example, before supplying the raw material liquid to the processing unit 6103, a cleaning liquid such as pure water is supplied to the flow paths in the mixing unit 6140 and the reaction unit 6142 to perform cleaning in advance. While cleaning the flow path, the temperature of the cleaning liquid is measured by the temperature sensor 6220 at the outlet of the mixing unit 6140 and the temperature sensor 6222 at the outlet of the reaction unit 6142, and the temperature of the cleaning liquid is fed back to the heat medium controller 6107. In this way, the mixing unit 6140 and the reaction unit 6142 are adjusted to a predetermined temperature.

  After the temperature of the mixing unit 6140 and the reaction unit 6142 is adjusted and the cleaning of the flow path is completed, the flow path switching valve 6132 is switched and the plunger pumps 6001A and 6001B are driven to supply the raw material liquid in the storage containers 6110A and 6110B. Transfer each one. The raw material liquid is adjusted to a predetermined flow rate by the flow rate adjusting devices 6300A and 6300B, and then reaches the recovery container 6208 via the mixing unit 6140, the reaction unit 6142, the outlet port 6202, and the recovery port 6210. Note that the flow path switching valve 6132 is an automatic valve that is operated by an actuator, and this operation can also be performed automatically.

  In the mixing unit 6140, the raw material liquids are heated to a predetermined temperature in the preheating channels 6148 </ b> A and 6148 </ b> B (see FIG. 116), and then merged and mixed in the merging unit 6152. At that time, as shown in FIG. 117, each liquid flows into the merge space 6158 from the header portions 6154 and 6155 via the liquid separation channels 6156 and 6157. Since the cross section of the merge space 6158 gradually decreases toward the downstream, micro-sized flows are mixed regularly and mixed rapidly according to Fick's law. In that state, when it flows into the reaction flow path 6162 of the reaction unit 6142 maintained at a predetermined temperature, the reaction proceeds rapidly without being restricted by mass transfer or heat conduction. Therefore, it is sufficiently practical as a mass production means, and it is not necessary to carry out an explosive reaction with a high reaction rate at a low temperature. In this example, since the width of the reaction channel 6162 is sufficiently wide compared to the width of the merge space 6158, even when the reaction rate is slow, the reaction can be performed over a sufficient period of time, resulting in a high yield. Obtainable.

  The obtained product is sent from the outlet 202 of the reaction channel 6162 to the heat exchanger 6206 via the recovery pipe 6204, where it is cooled and flows into the recovery container 6208 from the recovery port 6210. When the storage containers 6110A and 6110B are emptied or the collection container 6208 is full, the operation control unit 6106 stops the operation of the plunger pumps 6001A and 6001B to end the processing. In this case, in addition to the storage containers 6110A and 6110B, if an additional storage container is prepared in the raw material storage unit 6101 in advance, the flow path switching valves 6126A and 6126B can be switched to continuously operate without stopping. Processing is possible. In addition, when reaction takes time, it is also possible to carry out batch operation by confining the liquid in the mixing unit 6140 and the reaction unit 6142 for a certain period of time. Since the flow path switching valves 6126A and 6126B are also automatic valves, these operations can be automatically operated.

  In the batch operation method, the plunger pumps 6001A and 6001B may be temporarily stopped, or the flow switching valves 6126A and 6126B may be switched to stop the inflow of liquid into the processing unit 6103. This eliminates the need to increase the length of the reaction channel 6162 even when the liquid reaction time is long. During batch operation, it is preferable to perform operation control using a fullness detection means for detecting that the merge space 6158 and / or the reaction flow path 6162 is filled with liquid. For example, an optical fluid detection sensor as shown in FIG. 122 is used. Thus, when it is determined that the merge space 6158 and / or the reaction flow path 6162 is filled with liquid, the plunger pumps 6001A and 6001B are stopped or the first flow path switching valve is switched to adapt the liquid to the reaction end time. It is made to stay in the merge space 6158 and / or the reaction channel 6162 for a certain period of time.

  123 (a) and 123 (b) show another configuration example of the merging unit in the mixing unit 6140. FIG. This merging portion 6152a is configured by arranging obstacles 6224 in a Y-shaped merging space 6158a at a predetermined interval a over a predetermined distance L. In this example, a columnar obstacle 6224 having a diameter of 50 μm or less was disposed over L = 5 mm from the junction. As shown in FIG. 123 (b), the obstacles 6224 are arranged in a staggered manner so that adjacent ones are displaced by half the pitch in the flow direction. As a result, the interface 6125 between the liquid A and the liquid B meanders, so that the interface area (contact area) between the two liquids can be increased. In the merging portion 6152b shown in FIG. 19, a row of obstacles 6224 are arranged in a zigzag along the flow direction at the center of the merging space 6158b, and the interface area can be similarly increased. This is suitable for use in the narrow merge space 6158b.

  FIG. 125 shows another configuration example of the processing unit 6103 of the fluid reaction device. In the processing unit 6103 of FIG. 113, two systems R1 and R2 each having a combination of a mixing unit 6140 and a reaction unit 6142 are provided, and two kinds of flow switching valves 6126A and 6126B of the liquid distribution unit 6102 are used. The raw material liquid can be supplied to any of the systems R1 and R2. As described above, by using the two systems, the processing amount can be increased as necessary, but there are various other usage methods. For example, when the reaction product easily precipitates solid particles and is easily clogged in the middle of the piping, one system is used as a spare. Further, the batch operation described above can be performed continuously by alternately switching the transfer lines by the flow path switching valves 6126A and 6126B. Of course, three or more transfer lines can be provided in parallel as appropriate. Also in this case, the flow path switching valves 6126A and 6126B can be automatically operated.

  FIG. 126 shows an example in which a plurality of reaction units are arranged in series in the processing unit 6103. In this example, one mixing unit 6140 and three reaction units 6142a, 6142b, 6142c are connected in series, and temperature sensors 6220, 6222a, 6222b, 6222c are respectively provided. In this example, the temperature of the reaction units 6142a, 6142b, 6142c can be independently controlled according to the stage of the reaction. This configuration is suitable for reactions that require a bold and instantaneous change in reaction time and reaction temperature, such as biochemical reactions. For example, in this system, the reaction can be performed at 100 ° C. in the reaction unit 6142a and at −20 ° C. in the reaction unit 6142b.

  FIG. 127 shows an example in which a plurality of mixing units are provided in the processing unit 6103. In this configuration example, a first mixing unit 6140 and a reaction unit 6142 for mixing and reacting liquid A and liquid B are provided, and a second mixing unit 6140a is provided on the downstream side of the reaction unit 6142. In the mixing section 6140a, the third raw material liquid or the C liquid as the reactant transported from the plunger pump 6116C joins and mixes the A liquid and the B liquid. The temperatures of these two mixing units 6140 and 6140a and one reaction unit 6142 are individually controlled. The liquid C may be a reaction terminator.

  In this configuration example, the in-line yield evaluator 226 is directly connected to the outlet 6202 of the second mixing unit 6140a. Thereby, the yield of the result of the chemical reaction can be confirmed in real time, and can be immediately fed back to the process parameters. The in-line yield evaluator 6226 includes methods such as infrared spectroscopy, near infrared spectroscopy, and ultraviolet absorption as methods that can be measured without separating the object to be measured.

  In this configuration example, a separation / extraction unit 6228 that separates unnecessary substances and necessary substances from the reaction products is further provided on the downstream side of the second mixing unit 6140a. As shown in the figure, the separation / extraction section 6228 has a Y-shaped separation flow path 6234. The liquid from the second mixing unit 6140a is branched into two flows by the separation channel 6234, one in the channel formed by the hydrophobic wall 6230 that allows only the hydrophobic molecules in the material to pass through, and the other in the material It flows into the flow path formed from the hydrophilic wall surface 6232 that allows only the hydrophilic molecules inside to pass therethrough. The separated substances are recovered in the recovery containers 6208 and 6208a via the recovery pipes 6204 and 6204a, respectively. As the separation / extraction unit 6228, it is possible to use a membrane or a porous frit that can adsorb only a hydrophobic substance.

  FIG. 128 shows a configuration example for continuous processing by repeating mixing / reaction and separation / extraction. That is, the mixing unit 6140a for processing the A liquid and the B liquid, the reaction unit 6142a, and the separation / extraction unit 6228a are arranged on the upstream side, and the mixing unit 6140b for processing the liquid extracted from the separation / extraction unit 6228a and the C liquid, the reaction The part 6142b and the separation / extraction part 6228b are arranged on the downstream side. Unnecessary substances after the liquid A and the liquid B have reacted are discharged from the outlet 6234a of the separation and extraction unit 6228a, and unnecessary substances in the second reaction to which the liquid C has been added are discharged from the discharge port 6234b of the separation and extraction unit 6228b. Be taken out of the system. Furthermore, a mixing unit 6140c that mixes the liquid extracted from the separation / extraction unit 6228b and the fourth liquid D is provided. Liquid D may be a reaction terminator or other raw material solution. An inline yield evaluator 6226 may be provided on the downstream side of the mixing unit 6140c.

  FIG. 129 (a) shows a configuration in which the respective parts in FIG. 23 are stacked. The liquid flows downward. The mixing unit 6140a, the reaction unit 6142a, the separation / extraction unit 6228a, the mixing unit 6140b, the reaction unit 6142b, the separation / extraction unit 6228b, and the mixing unit 6140c are accommodated in a temperature adjustment case 6146, respectively, and further, a bolt 6194, a nut 6195, and a spacer 6196. Are stacked at a predetermined interval. The movement of the liquid between each part is performed via the communication path 6200 (see FIG. 116 (b)). The accuracy of temperature control is improved by interposing air between each part so as not to be affected by the heat of other parts by utilizing the heat insulation of air. As shown in FIG. 129 (b), it is preferable to cover each temperature adjustment case 6146 with a heat insulating material such as a clean silicon member 6236 containing bubbles.

  The fluid introduced into the fluid reaction apparatus is liquid or gas, and the substance to be recovered is liquid, gas, solid or a mixture thereof. When the introduced substance is a solid such as powder, a powder dissolver can be installed in the raw material reservoir 6101. FIG. 130 is a configuration example of the raw material reservoir 6101 in which one of the two raw material liquids is a solution in which powder is dissolved and the other is originally liquid. The raw material powder and the solvent are introduced from the raw material inlet 6242 of the powder dissolver 6240. In this example, the raw material powder is dissolved by heating by the heater 6244 and stirring by the stirrer 246, and the generated raw material liquid is mixed by the plunger pump 6116A from the pipe 6249 drawn into the take-out port 6148, and the mixing unit 6140 and the reaction unit. 6142.

Multispectral apparatus The present invention further relates to a multispectral analysis apparatus that can be used in the fluid reaction apparatus and the fluid mixing apparatus of the present invention.

  The present invention for achieving the above-described object includes, but is not limited to, the following inventions.

  (1) A multispectral analyzer, which is a multispectral analyzer for evaluating organic synthesis reaction results at a pharmaceutical / pharmaceutical production line and a pharmaceutical development stage, comprising: a light source unit having a plurality of light sources having different wavelengths; A casing that constitutes a flow cell through which a measurement liquid is circulated, a plurality of light emitting units and light receiving units that are close to the liquid to be measured in the flow cell, and a spectroscopic unit that individually performs spectroscopy of each wavelength obtained from the light receiving unit And a controller for controlling and outputting the spectral information of the liquid to be measured obtained by the spectrometer.

  In the invention described in (1), a plurality of lights having different wavelength regions are emitted from the light source unit, received by different spectroscopes, and each wavelength of the spectrum that has passed through the liquid to be measured is individually performed. By combining such a plurality of pieces of analysis information, a highly accurate and leak-free analysis is performed.

  (2) In the invention described in (1), the light source unit covers at least two wavelength regions of ultraviolet light, visible light, near infrared light, infrared light, and far infrared light. A multispectral analysis apparatus comprising:

  In the invention described in (2), a combination of light sources covering at least two wavelength regions of ultraviolet light, visible light, near infrared light, infrared light, and far infrared light from the light source unit is combined. The analysis information according to the processing object and purpose can be obtained.

  (3) The invention according to (1) or (2), wherein a plurality of the flow cells are formed, and a light emitting unit and a light receiving unit are arranged in each flow cell, respectively.

  (4) The invention according to any one of (1) to (3), wherein the casing is configured to form a plurality of flow cells inside by a partition.

  (5) In the invention according to any one of (1) to (4), the casing is configured to form one flow cell therein, and a plurality of the casings can be detachably mounted on the substrate. A multispectral analyzer characterized by the fact that

  (6) The multispectral analysis according to any one of (1) to (5), wherein the light source from the visible region to the near-infrared region is shared by a single light source and guided to different light receiving units. apparatus.

  (7) The multispectral analyzer according to any one of (1) to (6), wherein a distance between the light emitting unit and the light receiving unit can be adjusted.

  (8) A microreactor comprising the multispectral analysis apparatus according to any one of (1) to (7) on a downstream side of a reaction region.

  Embodiments of the present invention will be described below with reference to the drawings.

  FIG. 131 schematically shows a multispectral analysis apparatus 7001 according to an embodiment of the present invention. For example, the multispectral analysis apparatus 7001 is configured in a casing 7010 constituted by a pair of substrates. As shown in FIG. 140 to be described later, the spectroscopic analyzer 7001 is used by being incorporated in a part of a member constituting a downstream portion of the microreactor.

  In the casing 7010, a plurality of flow cells 7014 connected to a flow path (flow path through which a reaction product flows) 7012 on the downstream side of the microreactor are formed. The flow cell 7014 is formed by partitioning a rectangular plate-like internal space 7016 as a whole by a plurality of partitions 7018, and a light emitting unit 7020 and a light receiving unit 7022 are arranged opposite to each other. In this embodiment, it is possible to reduce the size by accommodating a plurality of flow cells 7014 in the internal space 7016 in one casing 7010, and it is possible to improve the analysis accuracy by suppressing the flow rate variation. . The flow path in the flow cell 7014 is preferably shaped so that there is no stagnant flow or passage resistance as much as possible.

  The material constituting the casing 7010 is preferably one that has excellent thermal conductivity and can withstand a wide temperature range of −40 to 150 ° C. Further, the material constituting the flow path of the flow cell 7014 is preferably one that can withstand the high pressure of the liquid. Considering these points, preferable examples of the material constituting the flow path include SUS316, SUS304, Ti, quartz glass, Pyrex (registered trademark) glass and other hard glass, PEEK (polyetheretherketone), PE (polyethylene), PVC ( Examples thereof include resins such as polyvinylchloride), PDMS (Polydimethylsiloxane), Si, PTFE (polytetrafluoroethylene), PCTFE (Polychlorotrifluoroethylene), and PFA (perfluoroalkoxylalkane).

  A light source unit 7024 having a plurality of light sources 7024a to 7024g for outputting light of different wavelength ranges is installed at a predetermined location in the vicinity of the flow cell 7014, and each output light is guided to the light emitting unit 7020 by an optical fiber 7026. Yes. In this embodiment, the light source 7024a that outputs ultraviolet light is a deuterium lamp, the light sources 7024b to 7024e that output near infrared light from visible light are halogen lamps, and the infrared light is a nichrome infrared light source 7024f. is there. A single halogen lamp may cover from visible light to near infrared light. By doing so, the size of the apparatus can be made more compact.

  The light receiving unit 7022 is coupled by an optical fiber 7026 to a spectroscopic unit 7028 having spectroscopes 7028a to 7028g installed in the vicinity of the flow cell 7014. The spectroscopes 7028a to 7028g are constituted by, for example, CCD elements, and can measure the intensity by dividing the light received by each of the wavelength bands. In this embodiment, seven spectroscopes 7028a to 7028g are installed, and the wavelength ranges shared by the spectroscopes 7028a to 7028g are 200 to 400 nm (ultraviolet spectrometer 7028a), 400 to 700 nm (visible light spectrometer). 7028b), 700-1000 nm (first near infrared spectrometer 7028c), 1000-1700 nm (second near infrared spectrometer 7028d), 1700-2200 nm (third near infrared spectrometer 7028e), 2200-25000 nm (red) The outer spectroscope 7028f) and the wavelength region exceeding the wavelength of 25000 nm (far infrared spectroscope 7028g). It is not necessary to cover all of these combinations depending on the substance to be measured, and any combination of two or more appropriate numbers may be used.

  In this embodiment, the optical path between the light emitting unit 7020 and the light receiving unit 7022 is formed in the fluid flow direction, and can be set according to a predetermined optical path length regardless of the flow path width. Further, the adjustment of the optical path length for each section flow path can be performed by changing the protruding lengths of the light emitting unit 7020 and the light receiving unit 7022. For example, in the ultraviolet spectrometer 7028a, the sample solution is usually diluted and analyzed off-line. However, in the in-line measurement, since the concentration remains high, the optical path length is shortened to avoid unnecessary reactions. Measure (for example, 1 mm or less). Further, since the near-infrared spectrometers 7028c to 7028e have relatively low sensitivity, the optical path length is long (5 to 10 mm). As will be described later, in order to instantaneously simultaneously measure a plurality of components having a wide absorption wavelength, it is necessary to set the shape and dimensions of the flow cell 7014 in accordance with the pros and cons of each wavelength region.

  From each of the spectroscopes 7028a to 7028g, the light reception intensity for each preset wavelength region is output and input to the control unit 7032 via the AD converter 7030. The control unit 7032 calculates the transmittance (absorption rate) based on this data and the intensity distribution data for each wavelength region of each of the light sources 7024a to 7024g inputted in advance, and based on this, the target reaction is calculated. The production amount of the product (regular product) and the production amount of the reaction by-product are obtained, and as a result, the yield, conversion rate, and secondary solvent concentration are also obtained.

  Since reaction products and reaction by-products have been narrowed down in advance unless they are experimental, a combination of light sources 7024a to 7024g and spectroscopes 7028a to 7028g prepared for wavelength absorption corresponding to components to be generated is selected. Use it. In this case, even if there are a plurality of reaction by-products and the possibility of being generated is low, it is desirable to install them in order to clear GMP (Appropriate Manufacturing Standard) of FDA (US Food and Drug Administration), for example.

  On the other hand, in the development stage of pharmaceuticals, there is an operation of finding a reaction that may be referred to as so-called screening by changing various conditions such as reagent type, concentration, temperature, and flow rate. In this way, when it is impossible to predict what kind of reaction product is generated, light sources 7024a to 7024g and spectrometers 7028a to 7028g in all wavelength regions are installed in advance so that any product can be detected. After data is accumulated, take measures such as removing unnecessary ones or replacing them with appropriate ones.

  The control unit 7032 displays data such as the production amount, yield, and conversion rate of the reaction product and reaction by-product on the display 7034 and stores the data in the storage device 7036, and these data exceed a preset threshold value. If an alarm is issued, an alarm is issued by the alarm device 7038, and if the threshold is exceeded, the process is automatically stopped. Furthermore, the correlation between the above data and reaction conditions may be obtained in advance, and the reaction conditions of the microreactor, for example, reaction temperature, flow rate, pressure, etc. may be controlled based on the detection data.

  In general, in the spectroscopic analyzer 7001 using a single light source, the light is concentrated and distributed in a certain wavelength region, so the sensitivity in the peripheral region is lowered. In the multi-spectral analysis apparatus 7001, a plurality of light sources 7024a to 7024g and spectroscopes 7028a to 7028g having different wavelength ranges are provided, so that accurate data can be obtained over a wide wavelength range. Hereinafter, characteristics of the spectroscopes 7028a to 7028g and a combination method based on the characteristics will be described with reference to Table 131. Table 131 illustrates the absorption spectrum wavelength of each functional group, molecule, and the like.

The ultraviolet spectrometer 7028a is suitable for reading the absorption spectrum trends of all components and detecting changes in yield and impurity amount. The infrared spectrometer 7028f can cope with many organic functional groups of individual substances, but there are cases in which the intensity is too strong to cause interference substances. In that case, the near-infrared spectrometers 7028c to 7028e are substituted. In the case where the solvent is water, the infrared spectrometer 7028f may have water as an interfering substance. The visible light spectrometer 7028b is suitable for detecting colored substances such as chlorophyll and carotene. In this embodiment, the reason why the three near-infrared spectrometers 7028c to 7028e are used properly is that a portion having a weak measurement ability is not formed in the near-infrared region 700 to 2200 nm. This is to accurately read small shifts in the peak due to lengthening or subtle changes in coupling.

Hereinafter, a more specific reaction will be described with reference to FIG. The reaction in FIG. 132 (a) is an overreaction reaction performed in a solvent pyridine, and if a positive reaction is performed based on the microchannel effect, monobenzoylresorcinol is produced. However, the concentration imbalance in the microchannel is not improved. When it occurs, the reaction further proceeds to produce dibenzoyl resorcinol, which is a side reaction. The formation of functional groups such as benzene ring, CO, OH, etc. can be determined by measuring the absorption region, and the ratio of mono- and di-forms can be detected. Although the benzene ring can be measured with an infrared spectrometer 7028f, there is a possibility that the solvent pyridine may be detected as a background, and measurement may be impossible or it may be difficult to distinguish due to overlapping peaks. In that case, the near-infrared spectrometers 7028c to 7028e may be used.

  In the above case, the specific wavelength region where the difference in absorption intensity is sufficiently large between the number of benzoyl groups of 1 and 2 is, for example, near infrared spectrometers 7028c to 7028e or infrared spectrometer 7028f. If it exists in the area, it may be selected. Also in this case, the absorption spectrum of the whole reaction system liquid is monitored by the ultraviolet spectrometer 7028a, and when there is a change in the reaction, an alarm is issued or the process is stopped.

  In the reaction of FIG. 132 (b), benzyl phenylalanine is reacted with hydrogen gas in methanol and reduced to yield phenylalanine methyl ester. This is a deprotection reaction of the protecting group with catalytic hydrogen, and a Pd catalyst is used. If you read the ratio of NH2 and NH, you can see the reaction rate. Strong NH2 can be read by near infrared spectrometers 7028c to 7028e, and weak NH2 can be read by infrared spectrometer 7028f. Depending on the overlap of interfering substances, near infrared spectrometers 7028c to 7028e and infrared spectroscopy can be obtained. The container 7028f can be used properly. Of course, both components may be measured individually in their respective wavelength ranges. In this case as well, the absorption spectrum of the whole liquid is monitored by the ultraviolet spectrometer 7028a, and if there is a change in the reaction, an alarm is issued or the process is stopped.

  The reaction in FIG. 132 (c) is a hydrolysis reaction in which water is added to glycine anhydride and hydrochloric acid is used as a catalyst to turn into glycylglycine in one step of polypeptide synthesis. Since the reaction is in the presence of water in the product, avoid the infrared spectrometer 7028f, where water is likely to interfere with absorption, and use a weakly sensitive area in the near-infrared spectrometer 7028c to 7028e area that is not affected by water. And measure.

  FIG. 133 shows a modification of the embodiment of FIG. 131, in which the flow cells 7014 are individually formed in the casing 7010, and the fluid flow paths are branched and guided to the respective flow cells 7014. As a result, each flow cell 7014 is not affected by the other flow cells 7014 and the flow resistance is low, so that the fluid flow becomes more uniform. Further, as shown in the figure, a flow rate adjusting valve 7042 is individually installed in the branch flow path 7040 to the flow cell 7014, so that the flow rate can be adjusted to an appropriate flow rate according to the characteristics of the spectroscopes 7028a to 7028g.

  FIG. 134 shows a modification of the embodiment of FIG. 131, in which the flow cell 7014 is individually formed in the casing 7010, but an open / close valve 7044 is installed in each branch flow path 7040. As a result, only the opening / closing valve 7044 of the flow cell 7014 having the required wavelength is opened, and the unnecessary opening / closing valve 7044 of the flow cell 7014 is closed, thereby preventing the occurrence of excessive flow path resistance. In the embodiment of FIG. 135, the flow cells 7014 are connected in series. In this embodiment, since there is no need for a branch flow, there is an advantage that it is easy to handle if only the flow path resistance is taken into consideration.

  FIG. 136 shows the structure of a multispectral analysis apparatus 7001 according to another embodiment, and a plurality of casings 7046 constituting one flow cell 7014 are arranged on a substrate 7047. Each casing 7046 is formed of a transparent material such as quartz glass, and a flow path 7048 is formed therein. The flow path 7048 is opened at a side surface to form a joint portion 7050. Inside the casing 7046, a light emitting unit 7020 and a light receiving unit 7022 are placed with a flow path 7048 interposed therebetween, and these are connected to an external light source and a spectroscope (not shown) by an optical fiber 7026.

  In this case, the width of the flow path 7048 is the optical path length that the light traverses. The joint portion 7050 is connected to a microreactor or the like by piping. The material of the casing 7046 may be PCTFE, PTFE, or PEEK having chemical resistance. In this case, the light emitting portion 7020 and the light receiving portion 7022 are protected by quartz so as not to be in direct contact with liquid. In this embodiment, since the connection to the flow path 7048 is performed via the joint portion 7050, the connection can be freely changed. The flow of fluid to each flow cell 7014 may be a parallel branch or may be in series, and an on-off valve 7044 may be provided for each flow cell 7014 to selectively flow.

  FIG. 137 shows a modification of FIG. 136 in which a light emitting portion 7020 and a light receiving portion 7022 are projected into the flow path 7048 in order to set the optical path length short. In this case, in order to reduce stagnant flow and flow path resistance in the flow cell 7014, a tapered portion 7049a that gradually expands the diameter of the flow path 7048 is formed.

  FIG. 138 shows a modification of FIG. 136, and the optical path length can be freely adjusted in each of the casings 7046 arranged on the substrate 7047. A light emitting case 7052 and a light receiving case 7054 are arranged to face each other with a flow path 7048 in the flow cell 7014 interposed therebetween. Both the light emitting case 7052 and the light receiving case 7054 are made of quartz, and a light emitting unit 7020 is attached in the light emitting case 7052, and a light receiving unit 7022 is attached in the light receiving case 7054. At least one of the outer shapes of the light emitting case 7052 and the light receiving case 7054 is a screw, and is screwed into a fixing nut 7056 attached to the outer surface of the case 7046. Thereby, it is possible to freely adjust the length of the optical path length. The opposite side may be adjusted by fixing one side, or both sides may be adjustable. As a result, it is possible to freely adjust on-site individually from the sensitivity, molecular concentration, and solvent substance information of each wavelength region. Since a liquid with a high concentration is generally analyzed in-line, the optical path length is shorter than that in the off-line case, and is set to 10 mm to 0.5 mm, preferably 5 mm to 0.1 mm.

  FIG. 139 (a) shows an embodiment of how to use the multispectral analysis apparatus 7001 of the present invention, and rapid cooling is performed downstream of the mixing / reaction unit 7058 of the microreactor in order to stop the continuation of the reaction. A micro-quenching unit 7060 is installed. The micro quenching unit 7060 can have, for example, a water cooling jacket structure. In this embodiment, by installing a multi-spectral analyzer 7001 between the mixing / reaction unit 7058 and the micro-quenching unit 7060, the target product can be obtained by performing the micro-quenching after confirming the progress of the reaction. Can be manufactured stably.

  FIG. 139 (b) shows another embodiment of how to use the multispectral analysis apparatus 7001 of the present invention. A multispectral analysis apparatus 7001 is installed downstream of the mixing / reaction unit 7058 of the microreactor. Further, a three-way switching valve 7062 is installed on the downstream side. The three-way switching valve 7062 switches the line from the multispectral analyzer 7001 so as to be selectively connected to the normal product storage line 7064 and the spare line 7068 connected to the spare tank 7066. The output signal of the multispectral analyzer 7001 is sent to the control unit 7032, and when the control unit 7032 determines that there is an abnormality in the component, the three-way switching valve 7062 is switched to the spare tank 7066 side. Thereby, it can prevent that an abnormal component mixes in the product storage line 7064. FIG.

  Next, a fluid reaction apparatus (microreactor) incorporating the above-described multispectral analysis apparatus according to an embodiment of the present invention will be described. FIG. 140 to FIG. 142 (b) are diagrams showing the overall configuration of a fluid reaction device incorporating a flow rate adjusting device according to an embodiment of the present invention. The fluid reaction apparatus described below is an apparatus used for mixing and reacting two or more kinds of liquids.

  As shown in FIG. 140, FIG. 141, FIG. 142 (a), and FIG. 142 (b), the entire fluid reaction device is installed in one installation space and packaged. In this configuration example, the installation space is rectangular and is divided into four regions along the longitudinal direction.

  That is, the first region on one end side is a raw material storage portion 7101 in which a plurality of storage containers 7110 (only two storage containers 7110A and 7110B are shown in FIG. 140) for storing the raw material liquid are installed, and are adjacent thereto. The second region is a liquid distribution unit 7102 in which pumps 7116A and 7116B for transferring the raw material liquid in the storage container 7110 are installed. A third region adjacent to the second region is a processing unit 7103 having a mixing unit (mixing chip) 7140 for mixing the raw material liquid and a reaction unit (reaction chip) 7142 for reacting the mixed raw material liquid. . The fourth region on the other end side is a product storage unit (recovery container installation space) 7104 for deriving and storing a product obtained as a result of the processing.

  The fluid reaction apparatus also includes an operation control unit 7106 that is a computer that controls the operation of each unit, and a heat medium controller 7107 that adjusts the temperature of the processing unit 7103 by flowing a heat medium through the temperature adjustment case 7146. . Further, as shown in FIG. 140, the operation controller 7106 is equipped with a flow rate monitor 7270 and a temperature monitor 7272 that can monitor the flow rate and temperature of the liquid. In this configuration example, the operation control unit 7106 and the heat medium controller 7107 are provided separately from the fluid reaction device, but may of course be integrated. As shown in FIG. 141, a piping chamber 7105 is formed in the lower floor portion of the second to fourth regions, and piping for sending a heating medium for heating or cooling to the mixing unit 7140 and the reaction unit 7142 is provided here. Is provided. Although the operation control unit 7106 and the control unit 7032 of the multi-spectral analysis apparatus 7001 are separate, of course, they may be integrated.

  In this way, by arranging the respective parts from the upstream side to the downstream side, the flow of the liquid can be made smooth, and the entire apparatus can be made compact. In this configuration example, each part is arranged in a straight line. However, for example, if the entire space is close to a square, each part may be configured such that the liquid flow forms a loop.

  In FIG. 141, reference numeral 7250 denotes a liquid storage pan provided at the lower part of the apparatus, and reference numeral 7252 denotes a liquid leakage sensor installed on the liquid storage pan 7250. In this example of the apparatus, the liquid distribution unit 7102, the processing unit 7103, and the product storage unit 7104 are partitioned by partition walls 7254 and 7256, and covers 7258, 7260, and 7262 are attached to the respective parts to isolate them from the outside of the apparatus. is doing. Reference numeral 7264 denotes an exhaust port, which is connected to an exhaust fan (not shown). And the toxic gas in the apparatus is prevented from leaking outside by making the pressure in the apparatus negative from the outside of the apparatus.

  140 is provided with two storage containers 7110A and 7110B, but three or more storage containers may be used as necessary. For example, the process can be continuously performed by storing the same liquid in two storage containers and using them alternately. Note that the raw material storage unit 7101 may be provided with a cleaning liquid container 7112 containing an organic solvent such as acetone for line cleaning, hydrochloric acid, pure water, or the like, or a pressure source 7114 filled with a purge nitrogen gas. Further, the waste liquid container 7136 may be placed in the raw material reservoir 7101.

  Pumps 7116A and 7116B connected to the storage containers 7110A and 7110B via transport pipes 7121A and 7121B are installed in the liquid distribution unit (introduction unit) 7102. As the pumps 7116A and 7116B in FIG. 140, centrifugal pumps are used. Further, the liquid distribution unit 7102 includes flow rate adjusting devices 7300A and 7300B, relief valves 7122A and 7122B, pressure measurement sensors 7124A and 7124B, flow path switching valves 7126A and 7126B, and backwashing that are disposed downstream of the pumps 7116A and 7116B. A pump 7130 is included. The flow path switching valves 7126A and 7126B are connected to a cleaning liquid container 7112 and a pressure source 7114 in addition to the transport pipes 7121A and 7121B, respectively. The backwash pump 7130 is used when the flow path of the mixing unit 7140 or the reaction unit 7142 is blocked by the product. The backwash pump 7130 is connected to a cleaning liquid container 7112 that stores the cleaning liquid, and is further connected to the outlet of the reaction unit 7142 via a flow path switching valve 7132. The cleaning liquid transferred by the backwash pump 7130 flows in reverse to the normal flow. That is, the cleaning liquid flows from the outlet of the reaction unit 7142 toward the inlet of the mixing unit 7140, passes through the flow path switching valves 7126 </ b> A and 7126 </ b> B, and enters the waste liquid storage container 7136 from the waste liquid port 7134 through a pipe (not shown).

  The backwash pump 7130 is preferably a single piston 16 type pump so that the discharge pressure is high and the product can be removed by causing pulsation in the cleaning liquid. As the cleaning liquid, an organic solvent, hydrochloric acid, nitric acid, phosphoric acid, organic acid, pure water, or the like is preferably used. Examples of the organic solvent include acetone, ethanol, methanol and the like. An introduction port 7240 shown in FIG. 140 is provided when pure water or hydrogen water is introduced from the outside, and can be used for cleaning instead of the cleaning liquid in the cleaning liquid container 7112.

  FIG. 143 shows a mixing unit 7140 for preheating (preliminary temperature adjustment) and mixing of the raw material liquid. The upper plate 7144a, the middle plate 7144b, and the lower plate 7144c, which are three thin plate-like base materials, are shown. A mixing portion 7140 having a total thickness of 5 mm is formed by bonding. In addition, all the flow paths described below are grooves formed on the surface of the intermediate plate 7144b. Two inflow ports 7147A and 7147B formed through the upper plate 7144a communicate with two preheating channels 7148A and 7148B formed on the upper surface of the middle plate 7144b, respectively. These preheating flow paths 7148A and 7148B each branch in the middle, expand, and merge again. Further, the preheating channels 7148A and 7148B communicate with the outlet channels 7150A and 7150B, respectively, and these outlet channels 7150A and 7150B communicate with the junction 7152. The outlet channel 7150A is formed on the upper surface of the middle plate 7144b, and the outlet channel 7150B is formed on the lower surface of the middle plate 7144b.

  FIG. 144 is an enlarged view of the junction shown in FIG. As shown in FIG. 144, the merging portion 7152 includes header portions 7154 and 7155 formed on the upper and lower surfaces of the middle plate 7144b as arc-shaped grooves that communicate with the outlet flow paths 7150A and 7150B, and the header portions 7154 and 7155, respectively. A plurality of liquid separation channels 7156, 7157 extending toward the center of the arc and a merge space 7158 where these liquid separation channels 7156, 7157 merge. The liquid separation channels 7156 and 7157 and the merge space 7158 are formed on the upper surface of the intermediate plate 7144b, and the liquid separation channels 7156 and 7157 are alternately arranged. The header portion 7155 on the lower surface side and the liquid separation flow path 7157 communicate with each other through a communication hole 7157a penetrating the intermediate plate 7144b. The merge space 7158 is formed so that the width gradually decreases toward the downstream side, and communicates with an outflow port 7160 formed through the middle plate 7144b and the lower plate 7144c.

  In the example shown in FIG. 144, five separation channels 7156 and four separation channels 7157 are alternately arranged on the opening surface 7159 on the inlet side of the merge space 7158. The two kinds of liquids respectively flowing out from the separation flow paths 7156 and 7157 flow downstream while forming a stripe-like flow in the merge space 7158, and are forced as the flow path width of the merge space 7158 gradually decreases. Both liquids are mixed. In this example, the flow path width of the merge space 7158 finally reaches 40 μm. If the processing technology accuracy is increased, the flow path width can be reduced to 10 μm.

  FIG. 145 (a) is a plan view showing the reaction part shown in FIG. 140, and FIG. 145 (b) is a cross-sectional view of the reaction part shown in FIG. 145 (a). In this example, two base materials 7144d and 7144e are joined to form a reaction portion 7142 having a thickness of 5 mm. In this reaction part 7142, the reaction flow path 7162 meanders, and provides a long flow path efficiently. The reaction flow path 7162 has connecting portions 7162a and 7162c connected to the inlet port 7164 and the outlet port 7165, respectively, and a meandering portion 7162b communicating with the connecting portions 7162a and 7162c. The width of the connecting portions 7162a and 7162c is narrow. The meandering portion 7162b is formed wider. Therefore, the liquid flows rapidly at the entrance / exit part to prevent adhesion of by-products, and flows gently at the meandering part 7162b, so that the heating and reaction time can be increased.

  FIG. 146 (a) and FIG. 146 (b) show another example of the structure of the reaction part having the part 7163a in which the width of the reaction channel gradually decreases and the part 7163b in which the width gradually increases. In the reaction portion 7142a, a reaction flow path 7163 is formed between the base materials 7144d and 7144e so that the width dimension increases or decreases in the range from the maximum a to the minimum b. The depth may be increased or decreased according to the increase or decrease of the width dimension. In this example, the depth changes from the maximum c to the minimum d so that the cross-sectional area of the reaction channel 7163 is constant.

  FIG. 146 (c) is a cross-sectional view showing another configuration example of the reaction channel. In this reaction portion 7142b, the reaction flow path 7163c has a flat shape whose width e is larger than the depth f, and has a wide heat transfer surface that intersects the heat transfer direction (indicated by an arrow) from the thermal catalyst. Therefore, heat is effectively transferred to the liquid in the reaction channel 7163c. In addition, it is effective in order to accelerate | stimulate reaction to arrange | position an appropriate catalyst in the merge space 7158 and the reaction flow paths 7162, 7163. Such a catalyst is selected depending on the type of reaction. As for the arrangement method, for example, it can be applied to the inner surface of the channel, or can be arranged as an obstacle of the channel as described later.

  Examples of a material that forms at least the flow path of the mixing unit 7140 and the reaction unit 7142 include, for example, hard glass such as SUS316, SUS304, Ti, quartz glass, and Pyrex (registered trademark) glass, PEEK (polyetheretherketone), PE (polyethylene), Among PVC (polyvinylchloride), PDMS (Polydimethylsiloxane), Si, PTFE (polytetrafluoroethylene), and PCTFE (PolyChloroTriFluoroEthylene), a preferable one is selected in consideration of chemical resistance, pressure resistance, thermal conductivity, heat resistance, and the like. The material of the wetted part of the mixing part 7140 and the reaction part 7142 is preferably one that has little elution from the surface, can be modified with a surface catalyst, has a certain degree of chemical resistance, and can withstand a wide temperature range of −40 to 150 ° C. .

  FIG. 147 is a perspective view showing a configuration of a temperature adjustment case for adjusting the temperatures of the mixing unit and the reaction unit. In the following description, only the temperature adjustment case 7146 for adjusting the temperature of the reaction unit 7142 will be described, but the temperature adjustment case 7146 for the mixing unit 7140 also has the same configuration, and redundant description thereof is omitted. To do. The temperature adjustment case 7146 includes a case main body 7172 in which a space 7170 that accommodates the reaction portion 7142 is formed, and a lid portion 7174 that covers the space 7170. Grooves 7176 constituting the medium flow path are formed. A liquid supply path 7178 and a drainage path 7180 (see FIG. 140) communicating with the groove 7176 are formed in the case body 7172, and these liquid supply path 7178 and drainage path 7180 are connected to the heat medium controller 7107, respectively. Yes. The liquid supply path 7178 communicates with the groove 7176 of the lid portion 7174 via the opening 7179, and the drainage path 7180 also communicates with the groove 7176 of the lid portion 7174 via an opening (not shown). In this example, the heat medium flowing through the groove 7176 is in direct contact with the front and back surfaces of the reaction unit 7142, and the reaction unit 7142 is heated (or cooled) in a state of being completely accommodated in the temperature adjustment case 7146.

  Although not shown, the heat medium controller 7107 includes a control mechanism for controlling the temperature of the heat medium and a pump for transferring the heat medium. As shown in FIG. 140, the heat medium is supplied to the temperature adjustment case 7146 of the mixing unit 7140 and the reaction unit 7142 after passing through the heat exchanger 7182. The heat exchanger 7182 can change the temperature of the heat medium supplied to the mixing unit 7140 and the reaction unit 7142 independently by changing the amount of city water for cooling, for example.

  FIGS. 148 (a) to 148 (d) show another example of the temperature adjustment case 7146. Here, the heat medium flow path 7192 is formed inside each of the case main body 7172 and the lid portion 7174. FIG. Has been. As shown in FIG. 148 (c), the liquid supply path 7178 has a double pipe structure in which the tip of the liquid supply pipe 7188 is inserted, and communicates with the heat medium flow path 7192 through a thin communication path 7190. is doing. The drainage side has the same configuration. As shown in FIG. 148 (b), the temperature adjustment case 7146 that accommodates the mixing unit 7140 and the temperature adjustment case 7146 that accommodates the reaction unit 7142 are stacked and coupled via a bolt 7194, a nut 7195, and a spacer 7196. ing.

  FIG. 148 (b) shows a path for supplying and discharging liquid to / from the mixing unit 7140 and the reaction unit 7142 accommodated in the temperature adjustment case 7146. That is, each liquid flows into and out of the mixing unit 7140 through a flow passage 7198 formed through the temperature adjustment case 7146. In addition, the flow of the liquid between the mixing unit 7140 and the reaction unit 7142 is performed through the communication path 200 that communicates with the flow path 7198 of the temperature adjustment case 7146. FIG. 148 (d) illustrates the structure of the inflow portion and the outflow portion of the liquid in the reaction portion 7142. In order to direct the liquid flow downward, the liquid inlet of the mixing unit 7140 and the reaction unit 7142 is normally formed on the upper surface and the outlet is formed on the lower surface.

  As shown in FIG. 140, the outlet 202 of the reaction unit 7142 is connected to the product storage unit 7104 via the recovery pipe 204. The product storage unit 7104 is provided with a recovery container 7208 on the downstream side of the heat exchanger 7206 for cooling and the flow path switching valve 7132. The product storage unit 7104 in which the recovery container 7208 is placed is isolated so as not to be affected by temperature and the like from other regions, and to prevent toxic gas that may be generated from the product from leaking to the outside. .

  FIG. 149 shows another configuration example of the product storage unit 7104, and a plurality of collection containers 7208 are installed on the turntable 7212. In this example, the number of collection containers 7208 is two, and the actuator 7214 that moves the rotary table 7212 is a 180-degree rotary actuator. Of course, the number of collection containers 7208 and the type of actuator 7214 can be selected as appropriate. The operation control unit 7106 shown in FIG. 140 determines the replacement timing of the recovery container 7208 based on a signal from the liquid level detection sensor 7211b that detects the liquid level of the recovery container 7208, and the flow path switching valve 7132 (see FIG. 140). The liquid flow is stopped, the stop of the liquid flow is confirmed by the optical fluid detection sensor 7211a provided downstream of the recovery port 7210, and the actuator 7214 is operated to move the other recovery container 7208 below the recovery port 7210.

  Next, a process of reacting a liquid (raw material liquid) such as a chemical solution with the fluid reaction apparatus configured as described above will be described. The operation of the fluid reaction apparatus is basically automatically controlled by the operation control unit 7106. First, in the raw material storage part 7101, it prepares in the storage containers 7110A and 7110B which stored the raw material liquid. The temperature of the heat medium is set by the heat medium controller 7107, the amount of city water passing through the heat exchanger 7182 is adjusted to adjust the temperature of each heat medium, and the temperature adjustment case 7146 of the mixing unit 7140 and the reaction unit 7142 is adjusted. Heat medium is circulated to maintain a predetermined temperature. The temperature of the heat medium is measured by temperature sensors 7216 and 7218 provided at the inlet of the temperature adjustment case 7146.

  In this example, before supplying the raw material liquid to the processing unit 7103, a cleaning liquid such as pure water is supplied to the flow paths in the mixing unit 7140 and the reaction unit 7142 to perform cleaning in advance. While cleaning the flow path, the temperature of the cleaning liquid is measured by the temperature sensor 7220 at the outlet of the mixing unit 7140 and the temperature sensor 7222 at the outlet of the reaction unit 7142, and the temperature of the cleaning liquid is fed back to the heat medium controller 7107. In this way, the mixing unit 7140 and the reaction unit 7142 are adjusted to a predetermined temperature.

  After the temperature of the mixing unit 7140 and the reaction unit 7142 is adjusted and the cleaning of the flow path is completed, the flow path switching valve 7132 is switched and the pumps 7116A and 7116B are driven to supply the raw material liquid in the storage containers 7110A and 7110B, respectively. Transport. The raw material liquid is adjusted to a predetermined flow rate by the flow rate adjusting devices 7300A and 7300B, and then reaches the recovery container 7208 via the mixing unit 7140, the reaction unit 7142, the outlet port 7202, and the recovery port 7210. Note that the flow path switching valve 7132 is an automatic valve that is operated by an actuator, and this operation can also be performed automatically.

  In the mixing unit 7140, the raw material liquids are heated to a predetermined temperature in the preheating channels 7148 </ b> A and 7148 </ b> B (see FIG. 143), and then merged and mixed in the joining unit 7152. At that time, as shown in FIG. 144, the respective liquids flow into the merge space 7158 from the header portions 7154 and 7155 via the liquid separation channels 7156 and 7157. Since the cross section of the merge space 7158 gradually decreases toward the downstream, micro-sized flows are regularly mixed and rapidly mixed according to Fick's law. In that state, when it flows into the reaction channel 7162 of the reaction unit 7142 maintained at a predetermined temperature, the reaction proceeds quickly without being restricted by mass transfer or heat conduction. Therefore, it is sufficiently practical as a mass production means, and it is not necessary to carry out an explosive reaction with a high reaction rate at a low temperature. Further, in this example, the width of the reaction channel 7162 is sufficiently wide compared to the width of the merge space 7158, so that even when the reaction rate is slow, the reaction can be performed over a sufficient period of time, resulting in a high yield. Obtainable.

  The obtained product is sent from the outlet 7202 of the reaction flow path 7162 to the multi-spectral analysis apparatus 7001 via the recovery pipe 7204, and a plurality of lights having different wavelength regions are received by the different spectroscopic units 28 from the light source unit 7024. Then, the spectrum of each wavelength that has passed through the liquid to be measured is performed, the contained components are measured based on the result, and various measures as described are performed based on the result.

  The processing liquid that has passed through the multispectral analyzer 7001 is sent to the heat exchanger 7206 where it is cooled and flows into the recovery container 7208 through the recovery port 7210. When the storage containers 7110A and 7110B are emptied or the collection container 7208 is full, the operation control unit 7106 stops the operation of the pumps 7116A and 7116B and ends the process. In this case, in addition to the storage containers 7110A and 7110B, if an additional storage container is prepared in the raw material storage unit 7101 in advance, the flow switching valves 7126A and 7126B can be switched to continuously operate without stopping. Processing is possible. In addition, when reaction takes time, it is also possible to carry out batch operation by confining the liquid in the mixing unit 7140 and the reaction unit 7142 for a certain period of time. Since the flow path switching valves 7126A and 7126B are also automatic valves, these operations can be automatically operated.

  In the batch operation method, the pumps 7116A and 7116B may be temporarily stopped, or the flow switching valves 7126A and 7126B may be switched to stop the inflow of liquid into the processing unit 7103. This eliminates the need to increase the length of the reaction channel 7162 even when the liquid reaction time is long. In batch operation, it is preferable to perform operation control using a fullness detection means for detecting that the confluence space 7158 and / or the reaction flow path 7162 is filled with liquid. For example, an optical fluid detection sensor as shown in FIG. 149 is used. Accordingly, when it is determined that the merge space 7158 and / or the reaction flow path 7162 is filled with the liquid, the pumps 7116A and 7116B are stopped or the first flow path switching valve is switched to adapt the liquid to the reaction end time. It is retained in the merge space 7158 and / or the reaction flow path 7162 for a fixed time.

  FIG. 150A and FIG. 150B show another configuration example of the merging unit in the mixing unit 7140. The junction 7152a is configured by disposing an obstacle 7224 in a Y-shaped junction space 7158a at a predetermined interval a over a predetermined distance L. In this example, a columnar obstacle 7224 having a diameter of 50 μm or less was arranged over L = 5 mm from the junction. As shown in FIG. 150 (b), the obstacles 7224 are arranged in a staggered manner so that adjacent ones are shifted by half the pitch in the flow direction. As a result, the interface 7125 between the liquid A and the liquid B meanders, so that the interface area (contact area) between the two liquids can be increased. In the merge portion 7152b shown in FIG. 151, a row of obstacles 7224 are arranged in a zigzag along the flow direction at the center of the merge space 7158b, and the interface area can be similarly increased. This is suitable for use in the narrow merge space 7158b.

  FIG. 152 shows another configuration example of the processing unit 7103 of the fluid reaction device. In the processing unit 7103 of FIG. 10, two systems R1 and R2 each having a combination of a mixing unit 7140 and a reaction unit 7142 are provided, and two types of flow path switching valves 7126A and 7126B of the liquid distribution unit 7102 are used. The raw material liquid can be supplied to any of the systems R1 and R2. As described above, by using the two systems, the processing amount can be increased as necessary, but there are various other usage methods. For example, when the reaction product easily precipitates solid particles and is easily clogged in the middle of the piping, one system is used as a spare. Further, the batch operation described above can be continuously performed by alternately switching the transfer lines by the flow path switching valves 7126A and 7126B. Of course, three or more transfer lines can be provided in parallel as appropriate. Also in this case, the channel switching valves 7126A and 7126B can be automatically operated.

  FIG. 153 shows an example in which a plurality of reaction units are arranged in series in the processing unit 7103. In this example, one mixing unit 7140 and three reaction units 7142a, 7142b, 7142c are connected in series, and temperature sensors 7220, 7222a, 7222b, 7222c are provided respectively. In this example, the temperatures of the reaction units 7142a, 7142b, and 7142c can be independently controlled according to the stage of the reaction. This configuration is suitable for reactions that require a bold and instantaneous change in reaction time and reaction temperature, such as biochemical reactions. For example, in this system, the reaction can be performed at 100 ° C. in the reaction unit 7142a and at −20 ° C. in the reaction unit 7142b.

  FIG. 154 is an example in which a plurality of mixing units are provided in the processing unit 7103. In this configuration example, a first mixing unit 7140 and a reaction unit 7142 for mixing and reacting the liquid A and the liquid B are provided, and a second mixing unit 7140a is provided on the downstream side of the reaction unit 7142. In the mixing unit 7140a, the third raw material liquid or the C liquid which is the reactant transported from the pump 7116C is merged with the A liquid and the B liquid. The temperatures of these two mixing units 7140 and 7140a and one reaction unit 7142 are individually controlled. The liquid C may be a reaction terminator.

  In this configuration example, the inline yield evaluator 7226 is directly connected to the outlet 7202 of the second mixing unit 7140a. Thereby, the yield of the result of the chemical reaction can be confirmed in real time, and can be immediately fed back to the process parameters. As the inline yield evaluator 7226, there are methods such as infrared spectroscopy, near infrared spectroscopy, and ultraviolet absorption as methods that can be measured without separating the object to be measured.

  In this configuration example, a separation and extraction unit 7228 that further separates unnecessary substances and necessary substances from the reaction product is provided on the downstream side of the second mixing unit 7140a. As illustrated, the separation and extraction unit 7228 has a Y-shaped separation channel 7234. The liquid from the second mixing portion 7140a is branched into two flows by the separation channel 7234, one in the channel formed by the hydrophobic wall 7230 that allows only the hydrophobic molecules in the material to pass through, and the other in the material It flows into a flow path formed from a hydrophilic wall surface 7232 through which only the hydrophilic molecules inside pass. The separated substances are recovered in recovery containers 7208 and 7208a via recovery pipes 7204 and 7204a, respectively. As the separation / extraction unit 7228, it is possible to use a membrane or a porous frit that can adsorb only a hydrophobic substance.

  FIG. 155 is a configuration example for continuous processing by repeating mixing / reaction and separation / extraction. That is, the mixing unit 7140a for processing the liquid A and the liquid B, the reaction unit 7142a, and the separation / extraction unit 7228a are arranged on the upstream side, and the mixing unit 7140b for processing the liquid extracted from the separation / extraction unit 7228a and the liquid C The part 7142b and the separation / extraction part 7228b are arranged on the downstream side. Unnecessary substances after the A liquid and B liquid have reacted are discharged from the discharge port 7234a of the separation and extraction unit 7228a, and unnecessary substances in the second reaction to which the C liquid has been added are discharged from the discharge port 7234b of the separation and extraction unit 7228b. Be taken out of the system. Furthermore, a mixing unit 7140c that mixes the liquid extracted from the separation / extraction unit 7228b and the fourth liquid D is provided. Liquid D may be a reaction terminator or other raw material solution. An in-line yield evaluator 7226 may be provided on the downstream side of the mixing unit 7140c.

  FIG. 156 (a) shows a configuration in which the components shown in FIG. 155 are stacked. The liquid flows downward. The mixing unit 7140a, the reaction unit 7142a, the separation / extraction unit 7228a, the mixing unit 7140b, the reaction unit 7142b, the separation / extraction unit 7228b, and the mixing unit 7140c are housed in a temperature adjustment case 7146, respectively, and further, a bolt 7194, a nut 7195, and a spacer 7196. Are stacked at a predetermined interval. The movement of the liquid between each part is performed via the communication path 7200 (see FIG. 143 (b)). The accuracy of temperature control is improved by interposing air between each part so as not to be affected by the heat of other parts by utilizing the heat insulation of air. As shown in FIG. 156 (b), it is preferable to cover each temperature adjustment case 7146 with a heat insulating material such as a clean silicon member 7236 containing bubbles.

The fluid introduced into the fluid reaction apparatus is liquid or gas, and the substance to be recovered is liquid, gas, solid or a mixture thereof. When the introduced substance is a solid such as a powder, a powder dissolver can be installed in the raw material reservoir 7101. FIG. 157 is a configuration example of the raw material reservoir 7101 in which one of the two raw material liquids is a solution in which powder is dissolved and the other is originally liquid. Raw material powder and solvent are introduced from a raw material inlet 7242 of a powder dissolver 7240. In this example, the raw material powder is dissolved by heating with a heater 7244 and stirring with a stirrer 7246, and the generated raw material liquid is mixed by a pump 7116A from a pipe 7249 drawn into a takeout port 7148, with a mixing unit 7140 and a reaction unit 7142. It comes to send to.

Claims (118)

In a fluid reaction device that introduces a plurality of fluids into a reaction channel having a micro reaction space and reacts them,
An introduction part for individually introducing the fluid used for the reaction;
A mixing channel for combining and mixing fluids;
Fluid transporting means for transporting the fluid toward the mixing flow path via a plurality of transport pipes;
Flow rate control means for controlling the flow rate of the fluid;
Temperature control means for controlling the temperature of the reaction channel;
A deriving unit for deriving the substance after the reaction from the recovery port;
A fluid reaction apparatus comprising operation control means for controlling these operations.   2. The fluid reaction apparatus according to claim 1, further comprising a plate-shaped mixed substrate, wherein the mixing flow path for mixing and mixing the fluids is provided in the plate-shaped mixed substrate. Reactor.   3. The fluid reaction apparatus according to claim 2, further comprising an installation space for installing a storage container for individually storing fluids used for the reaction.   The fluid reaction apparatus according to claim 2 or 3, wherein an installation space is provided in which a plurality of collection containers for collecting the substance after reaction from the lead-out part can be installed.   5. The fluid reaction apparatus according to claim 2, wherein a channel having a channel width of 500 μm or less exists in the micro reaction space.   The introduced fluid is a gas or a liquid, and the substance after reaction is either a gas, a liquid or a solid, or a mixture thereof, and the introduced fluid is a continuous flow. The fluid reaction apparatus according to any one of claims 2 to 5.   The fluid reaction apparatus according to any one of claims 2 to 6, wherein the fluid transport means includes pressure generation means or electrical dielectric force interaction means. The fluid transport means is a plunger pump device in which a pair of plunger pumps are connected in parallel,
A cam mechanism that interlocks the plungers of the plunger pumps so as to advance alternately.
A fluid pressure device that presses each plunger toward the cam mechanism when the plunger is retracted;
The fluid reaction according to any one of claims 2 to 7, further comprising a control unit that controls the operation of the fluid pressure device in accordance with an operation cycle of the plunger. apparatus.   The fluid reaction device according to claim 8, wherein the control unit of the plunger pump device stops pressing by the fluid pressure device when each plunger moves forward.   The pair of plunger pumps respectively perform a speed increasing process and a speed reducing process at an initial stage and an end of a discharge operation, respectively, and timing is set so that one speed increasing process and the other speed reducing process overlap each other. The fluid reaction apparatus according to claim 8.   9. The fluid reaction apparatus according to claim 8, wherein each plunger pump performs a fixed stopping process between forward and backward movements. The fluid transport means is a plunger pump device, each having a separate drive device, and a pair of plunger pumps connected in parallel between the liquid source and the microreactor flow path;
A flow meter installed in the microreactor channel;
A controller that alternately discharges the pair of plunger pumps at a constant predetermined feed rate;
3. The plunger pump device according to claim 2, wherein the control unit adjusts the feed rate at a predetermined timing based on a measurement value of the flow meter when the plunger pump is performing a discharge operation. The fluid reaction device according to claim 7. The plunger pump device is
A pressure sensor installed in the microreactor channel;
The fluid reaction device according to claim 12, wherein the control unit finely adjusts the feed rate based on an output value of the pressure sensor.   The control unit of the plunger pump device performs a speed-up process and a speed-down process for each of the pair of plunger pumps at an initial stage and an end stage of the discharge operation so that one speed-up process and the other speed-down process overlap each other. 14. The fluid reaction apparatus according to claim 12, wherein the flow control is performed while the flow rate is constant.   The fluid reaction apparatus according to claim 14, wherein the feed speed is finely adjusted only for one plunger pump during the switching control.   The said control part of the said plunger pump apparatus controls so that the said plunger pump may perform a fixed stop process between advancing and reverse | retreating, The any one of Claims 12-15 characterized by the above-mentioned. Fluid reaction device.   The said plunger pump apparatus is provided with the position sensor which detects the position of the plunger of the said plunger pump, The said control part controls feed speed based on the output of this position sensor, The Claims 12- Claim characterized by the above-mentioned. The fluid reaction device according to any one of 16.   3. The flow rate control means includes a sensor unit for measuring a volume of a passing fluid, and a passage amount control unit for controlling a passage area through which the fluid passes based on measurement information of the sensor unit. The fluid reaction device according to claim 17. The flow rate control means is a flow rate adjustment device that adjusts the flow rate of the fluid flowing through the flow path,
A temperature control mechanism for heating or cooling the fluid flowing through the flow path;
From the time difference between the time when the temperature of the fluid at the first measurement point of the flow path changes and the time when the temperature of the fluid at the second measurement point downstream of the first measurement point changes, the flow path A flow rate measurement unit for calculating the flow rate of the fluid flowing in the interior,
A downstream temperature sensor for measuring the temperature of the fluid passing through the second measurement point;
A control valve provided on the downstream side of the downstream temperature sensor;
A flow rate adjusting device comprising: a control unit that controls the control valve so that the flow rate of the fluid becomes constant based on the flow rate obtained by the flow rate measurement unit. Item 19. The fluid reaction device according to any one of Items 18 above.   The flow rate measuring unit of the flow rate adjusting device adjusts the flow rate of the fluid based on a time difference between two corresponding points on a temperature curve indicating a temperature change of the fluid at the first measurement point and the second measurement point. The fluid reaction device according to claim 19, wherein the fluid reaction device is calculated.   21. The fluid reaction apparatus according to claim 19, further comprising an upstream temperature sensor for measuring a temperature of the fluid passing through the first measurement point.   The upstream temperature sensor of the flow rate adjusting device includes a sensor holder that contacts a fluid flowing in the flow path, and a thermistor inserted into the sensor holder to a position close to the flow path. The fluid reaction device according to claim 21.   The downstream temperature sensor of the flow rate adjusting device includes a sensor holder that contacts a fluid flowing through the flow path, and a thermistor inserted into the sensor holder to a position close to the flow path. The fluid reaction device according to any one of claims 19 to 22.   The environmental temperature control mechanism that keeps the temperature of a space including at least the first measurement point and the second measurement point constant is further provided. The fluid reaction apparatus according to 1.   The fluid reaction according to any one of claims 19 to 24, wherein the temperature control mechanism of the flow rate adjusting device includes a Peltier element, a Seebeck element, an electromagnetic wave generator, or a resistance heating wire. apparatus.   The temperature control mechanism of the flow rate adjusting device includes a structure having a cylindrical part in which holes forming the flow path are formed, a heat transfer part that transfers heat to the cylindrical part, and a heat transfer part of the structure. The fluid reaction device according to any one of claims 19 to 25, further comprising a temperature control member for heating or cooling.   The control valve of the flow rate adjusting device includes a valve that adjusts the flow rate and a drive source that drives the valve, and the drive source includes a piezoelectric element, an electromagnet, a servo motor, or a stepping motor. 27. The fluid reaction device according to any one of claims 19 to 26, wherein:   The control valve of the flow rate adjusting device includes a valve for adjusting a flow rate and a drive source for driving the valve, and the drive source has a structure in which a plurality of piezoelectric elements are stacked. The fluid reaction device according to any one of claims 19 to 27.   The fluid reaction device according to any one of claims 19 to 28, wherein the pressure of the fluid passing through the control valve is 1 MPa to 10 MPa.   30. The fluid reaction apparatus according to any one of claims 19 to 29, wherein a flow rate of the fluid passing through the control valve is 0.01 to 10 L / h.   The fluid reaction device according to any one of claims 19 to 30, wherein the flow path of the flow rate adjusting device is formed of a material having corrosion resistance.   32. Any one of claims 19 to 31, wherein the material of the flow control device is stainless steel, titanium, polyetheretherketone, polytetrafluoroethylene, or polychlorotrifluoroethylene. The fluid reaction device according to item. The flow rate control means is
A temperature control mechanism for controlling the temperature of the fluid flowing through the flow path for a short time at a predetermined temperature control position;
A flow rate measuring device including at least one main temperature sensor disposed at a temperature measurement position downstream of the temperature control position of the flow path,
In the flow rate measuring device that determines the passage of the temperature-controlled fluid based on the temperature change at the temperature measurement position observed by the main temperature sensor, and calculates the flow rate based on the determination result,
A sub temperature sensor is installed at a position upstream of the temperature control position of the flow path,
The fluid reaction device according to any one of claims 2 to 18, wherein the fluid reaction device is a flow rate measurement device that corrects a temperature measurement value of the main temperature sensor with a measurement value of the sub temperature sensor.   The fluid reaction device according to claim 33, wherein the correction of the flow rate measurement device is performed by obtaining a difference between a measurement value of the main temperature sensor and a measurement value of the sub temperature sensor.   35. The fluid reaction apparatus according to claim 33 or 34, wherein at least two main temperature sensors are provided at different temperature measurement positions, and a flow rate is calculated based on a time difference of passage at these temperature measurement positions. .   35. The fluid reaction device according to claim 33 or claim 34, wherein the flow rate is calculated based on a time difference between when the temperature adjustment mechanism performs temperature adjustment and when passing through the temperature measurement position.   37. The fluid reaction device according to any one of claims 33 to 36, wherein the time point at which the corrected temperature measurement value reaches an extreme value is determined as the passage of a temperature control fluid.   38. The sub-temperature sensor of the flow rate measuring device is at a position that is substantially symmetric to the temperature measurement position with respect to the temperature control position, according to any one of claims 33 to 37. Fluid reaction device.   The fluid reaction device according to any one of claims 33 to 38, wherein the position of the sub temperature sensor is adjustable along the flow path.   40. The fluid reaction apparatus according to any one of claims 33 to 39, wherein the measured value of the main temperature sensor or the sub temperature sensor is analog / digital converted and taken into a digital circuit for processing.   The temperature control mechanism of the flow rate measuring device includes a Peltier element, a Seebeck element, an electromagnetic wave generator, a resistance heating wire, a thermistor, or a platinum resistor, any one of claims 33 to 40. The fluid reaction device according to item.   The fluid reaction apparatus according to any one of claims 2 to 41, wherein a plurality of the mixed substrates are provided.   The reaction channel according to any one of claims 2 to 42, wherein the reaction channel is formed in a reaction substrate provided separately from the mixing substrate in order to advance the reaction of the fluid after mixing. Fluid reaction device.   44. The fluid reaction apparatus according to claim 43, wherein a plurality of the reaction substrates are provided.   A first channel selection switching valve is provided between the fluid transporting means and the mixed substrate, and a second channel selection switching valve is provided between the mixing substrate and the substance recovery port. The fluid reaction device according to any one of claims 2 to 44.   46. The fluid reaction apparatus according to claim 45, wherein the first flow path selection switching valve and the second flow path selection switching valve are automatic valves that are operated by electric operation or pneumatic operation.   After the fluid introduced into the mixing channel is mixed, it is provided with a filling detection means for judging that the mixing channel or / and the reaction channel is filled with the fluid. 2. The control according to claim 2, wherein the control is performed by stopping or switching the flow path selection switching valve so that the fluid is retained in the mixing flow path and / or the reaction flow path for a certain period of time adapted to the reaction end time. 46. The fluid reaction device according to any one of 46.   48. The fluid detection sensor according to claim 47, wherein the fullness detection means is a fluid presence / absence sensor that detects fluid that has started to come out from the substance recovery port, or a fluid presence / absence sensor that detects presence / absence of fluid in the transport pipe after the mixing reaction. The fluid reaction apparatus as described.   49. The temperature measurement sensor is provided separately for each of the mixing channel and the reaction channel, and the temperature can be individually controlled. The fluid reaction apparatus according to 1.   The fluid reaction apparatus according to any one of claims 2 to 49, wherein at least a part of the mixed substrate and the reaction substrate are stacked.   The backwashing means for switching the channel selection switching valve to feed the fluid in the direction opposite to the normal flow direction in the mixing channel and the reaction channel is provided. The fluid reaction apparatus according to any one of claims.   52. The fluid reaction apparatus according to claim 51, wherein the backwashing means has a single piston pump as pressure feeding means.   The first channel selection switching valve is connected to one or more of a nitrogen gas supply line, a pure water supply line, an organic solvent supply line, an acid supply line, a hydrogen water supply line, and an ozone water supply line. 53. The fluid reaction device according to any one of claims 45 to 52, wherein:   The second channel selection switching valve is connected to one or more of a nitrogen gas supply line, a pure water supply line, an organic solvent supply line, an acid supply line, a hydrogen water supply line, and an ozone water supply line. 54. The fluid reaction device according to any one of claims 45 to 53, wherein:   55. The fluid according to any one of claims 4 to 54, wherein a space for holding two or more recovery containers and a table moving mechanism are provided in an installation space of the lead-out portion. Reactor.   56. The fluid reaction device according to claim 55, wherein the table moving mechanism is a rotating mechanism or a reciprocating mechanism.   57. The fluid reaction apparatus according to any one of claims 2 to 56, further comprising yield measuring means for measuring a yield of the substance after the reaction.   58. The fluid reaction apparatus according to claim 57, wherein the yield measuring means is ultraviolet absorption, infrared spectroscopy, or near infrared spectroscopy. The yield measuring means is
A light source unit having a plurality of light sources having different wavelengths;
A casing constituting a flow cell for circulating the liquid to be measured;
In the flow cell, a plurality of light emitting units and light receiving units adjacent to the liquid to be measured,
A spectroscopic unit having a spectroscope that individually performs spectroscopy of each wavelength obtained from the light receiving unit;
58. The fluid reaction apparatus according to claim 57, further comprising: a control unit that arithmetically controls and outputs spectral information of the liquid to be measured obtained by the spectroscope.   The light source unit of the multispectral analyzer has a light source that covers at least two wavelength regions of ultraviolet light, visible light, near infrared light, infrared light, and far infrared light. 60. A fluid reaction device according to claim 59.   61. The fluid reaction apparatus according to claim 59, wherein a plurality of the flow cells of the multispectral analyzer are formed, and a light emitting unit and a light receiving unit are respectively disposed in each flow cell.   62. The fluid reaction apparatus according to any one of claims 59 to 61, wherein the casing of the multispectral analyzer is configured to form a plurality of flow cells therein by a partition.   The casing of the multi-spectral analyzer is configured to form one flow cell therein, and a plurality of the casings can be detachably mounted on a substrate. Item 63. The fluid reaction device according to any one of Item 62.   The fluid reaction device according to any one of claims 59 to 63, wherein a light source in a visible region to a near-infrared region is shared by a single light source and guided to different light receiving parts.   The fluid reaction device according to any one of claims 59 to 64, wherein a distance between the light emitting unit and the light receiving unit is adjustable.   The fluid reaction device according to any one of claims 59 to 65, further comprising a spectroscopic analysis device on a downstream side of the reaction region. A fluid mixing device used in a fluid reaction device for reacting a plurality of fluids in a flow path including a micro reaction space,
A plurality of flat base materials are joined, and a plurality of fluids are continuously supplied from each header space to the merge space to be mixed,
The header spaces of the respective fluids are provided on different surfaces of the base material, and a plurality of liquid separation channels that communicate the header spaces and the merge space are provided, and the separate flow channels from different header spaces are the merge spaces. A fluid mixing device, wherein the fluid mixing device is formed so as to open alternately at the inflow portion.   68. The fluid mixing apparatus according to claim 67, wherein each of the header spaces is formed in a concentric arc shape on the different surfaces, and the merge space is disposed substantially at the center of these arcs.   The header space is formed on each of the front and back surfaces of the base material, the merge space is formed on one surface of the base material, and a liquid separation channel communicating with the header space on the other surface penetrates the base material. 69. The fluid mixing apparatus according to claim 67 or claim 68, wherein the fluid mixing apparatus is provided as follows.   70. The fluid mixing apparatus according to claim 67 or 69, wherein the plurality of liquid separation flow paths that communicate with each of the header spaces and the merge space are formed to extend in parallel with each other. A fluid mixing device used in a fluid reaction device for reacting a plurality of fluids in a flow path including a micro reaction space,
A plurality of flat base materials are joined, and a plurality of fluids are continuously supplied from each header space to the merge space to be mixed,
The header space is provided along the surface of the base material, the joining space is provided so that fluid flows in the plate thickness direction of the base material, and a plurality of liquid separation flows each communicating the header space and the joining space. A fluid mixing apparatus characterized in that the channel is formed such that liquid separation channels from different header spaces open alternately at the inflow portion of the merge space.   The header space is provided on both sides of the merge space on the surface of the base material, and liquid separation channels from different header spaces are opened at positions shifted from each other in the inflow portion of the merge space. The fluid mixing apparatus according to claim 71.   The header space of each fluid is provided on a different surface of the base material, at least one of the separation flow paths is provided through the base material, and the separation flow paths from different header spaces are opposed to the merge space. 72. The fluid mixing device according to claim 71, wherein the fluid mixing device is formed so as to be opposed to each other on the same side and alternately adjacent to each other on the same side of the merging space.   The said joining space is bent and formed so that a fluid may flow along the surface of this base material after flowing in the plate | board thickness direction of the said base material of Claims 71-73 characterized by the above-mentioned. The fluid mixing apparatus according to any one of claims. Having a mixing channel for continuously supplying and mixing a plurality of fluids to a space including a channel width portion of 500 μm or less formed on a flat substrate;
A fluid mixing apparatus, wherein columnar obstacles having a diameter of 50 μm or less are arranged at equal intervals over a length of 5 mm or more along a flow from a confluence of the plurality of fluids.   76. The fluid mixing apparatus according to claim 75, wherein the columnar obstacle has a plurality of columns of columns arranged alternately in the flow direction with the intervals of the columns being shifted.   77. The fluid mixing apparatus according to claim 75 or 76, wherein a plurality of the columnar obstacles are arranged in a staggered manner in the flow direction.   The fluid mixing device according to any one of claims 67 to 77, wherein the fluid mixing device has a portion in which the width of the channel gradually decreases and a portion in which the width gradually increases after the merge.   The fluid mixing device according to any one of claims 67 to 78, wherein after the merging, the width dimension and the depth dimension of the flow path are alternately reduced and enlarged.   The fluid mixing device according to any one of claims 67 to 79, wherein the fluid mixing device has a flat portion in which a width direction dimension of the flow path is larger than a depth direction dimension after the merge.   The members forming the flow path are SUS316, SUS304, Ti, quartz glass, Pyrex glass (registered trademark) hard glass, PEEK (polyetheretherketone), PE (polyethylene), PVC (polyvinylchloride), PDMS (polydimethylsiloxane), Si, The fluid mixing device according to any one of claims 67 to 80, wherein the fluid mixing device includes one or more of PTFE (polytetrafluoroethylene), PCTFE (polychlorotrifluoroethylene), and PFA (perfluoroalkoxylalkane). .   A part or all of the material of the inner wall of the flow path is Au, Ag, Pt, Pd, Ni, Cu, Ru, Zr, Ta, Nb or a compound containing these metals. The fluid mixing apparatus according to any one of claims 80.   The fluid mixing device according to any one of claims 67 to 82, wherein the substrate has a rectangular shape with a size of at least one side exceeding 150 mm.   The fluid mixing apparatus according to any one of claims 67 to 83, wherein a plurality of fluid inlets and a single fluid outlet after mixing are present on an opposite surface of the substrate.   85. The preliminary reaction temperature adjusting unit for raising or lowering the temperature of the fluid toward the reaction temperature in the same substrate in the mixed reaction substrate is provided. Fluid mixing device. A manifold portion in which a plurality of first flow paths communicating with the first fluid source and a plurality of second flow paths communicating with the second fluid source are respectively formed in the mixing flow path;
A confluence space adjacent to the manifold portion,
The manifold portion has an open end surface facing the merge space,
2. The fluid reaction apparatus according to claim 1, wherein the openings of the first flow path and the second flow path are three-dimensionally arranged so as to be alternately adjacent to each other at the opening end surface.   The manifold portion is formed by laminating plate-like elements in which grooves constituting the first flow path and the second flow path are alternately formed, so that the first flow path and the second flow path are formed on the opening end surface. 86. The fluid reaction apparatus according to claim 85, wherein the flow paths are arranged in a staggered manner.   88. The fluid reaction apparatus according to claim 86, wherein a maximum width dimension in a section of the opening of the first channel and the second channel is 3000 [mu] m or less.   The mixing promoting object for bypassing the flow mixing from the first flow path and the second flow path is provided in the merging space or the downstream side thereof. The fluid reaction apparatus according to claim 1.   90. The fluid reaction apparatus according to claim 89, wherein a substance having a catalytic action is provided on a surface of the mixing promoting object.   The representative dimension of the mixing promoting object is within a range of 0.1 to 10 times the minimum width dimension of the individual flows from the first flow path and the second flow path immediately before the mixing promoting object. 92. A fluid reaction device according to claim 89 or claim 90.   92. The fluid reaction device according to any one of claims 86 to 91, wherein a throttle portion or a fluid lens in which a flow path cross section gradually decreases is provided on the downstream side of the merge space.   92. A minimum width of a virtual cross section of each flow from the first flow path and the second flow path is 500 μm or less in the downstream portion of the throttle portion or the fluid lens. The fluid reaction apparatus according to 1.   94. The fluid reaction device according to claim 92 or 93, wherein the opening end surface and the throttle portion or the fluid lens have substantially similar flow path cross sections.   95. The fluid reaction apparatus according to any one of claims 86 to 94, wherein a plurality of the manifold portions are arranged so that respective opening end faces are opposed to each other in the merge space.   The heat exchanger which heats or cools the fluid flowing through the first flow path, the second flow path, the merge space and / or the downstream side thereof is provided. The fluid reaction apparatus according to claim 1.   The said heat exchanger is comprised by laminating | stacking the plate-shaped element in which the groove | channel which comprises a to-be-heated fluid flow path and / or a heat-medium flow path was formed, It is characterized by the above-mentioned. Fluid reaction device.   The heated fluid flow path of the heat exchanger that heats or cools the fluid flowing downstream of the merging space is a delay loop for adjusting the synthesis reaction time, and stays in the heat exchange by changing the delay loop pattern or the number of stacked layers 98. The fluid reaction device according to claim 96 or 97, wherein the time is adjustable.   99. The fluid reaction apparatus according to any one of claims 96 to 98, wherein a fluid that does not contaminate the heated fluid even when mixed in the heated fluid is used as the heat medium of the heat exchanger.   The fluid reaction device according to any one of claims 2 to 66, wherein the fluid mixing device according to any one of claims 67 to 85 is used as the mixing substrate.   The peripheral member forming the flow path of the reaction substrate is one of hard glass such as SUS316, SUS304, Ti, quartz glass, Pyrex glass (registered trademark), PEEK, PE, PVC, PDMS, Si, PTFE, PCTFE or The fluid reaction device according to any one of claims 2 to 66 and claim 100, comprising a plurality.   A part or all of the material of the inner wall of the flow path of the reaction substrate is a compound containing one or more of Au, Ag, Pt, Pd, Ni, Cu, Ru, Zr, Ta, and Nb or a metal thereof. 102. The fluid reaction apparatus according to any one of claims 2 to 66, claim 100, and 101.   The mixed substrate and / or the reaction substrate are accommodated in a temperature adjustment case having a heat medium flow path, and any one of claims 2 to 66 and 100 to 102. The fluid reaction device according to item.   104. The fluid reaction apparatus according to claim 103, wherein temperature measuring means is provided in the heat medium fluid flow path.   104. The fluid reaction apparatus according to claim 102 or 103, wherein the heat medium flow path has a plurality of branch flow paths along front and back surfaces of the mixed substrate and / or reaction substrate.   The said temperature control case has a case main body and a cover part, and the said heat-medium flow path is formed so that these may be connected, The one of Claims 103-105 characterized by the above-mentioned. Fluid reaction device.   A plurality of throttle holes provided in the first header of the case main body into which the thermal fluid flows are directly connected to the second header of the lid, and the second header includes a surface of the mixed substrate and / or reaction substrate. 107. The fluid reaction apparatus according to claim 106, further comprising a second throttle hole that is directly connected to a plurality of branch flow paths that form a flow parallel to the back surface.   108. The fluid reaction device according to any one of claims 48 to 107, wherein a material of the temperature adjustment case is any one of Ti, Al, SUS304, and SUS316.   The temperature control means surrounds the mixed substrate or the reaction substrate and adjusts the temperature of the mixed fluid, a temperature adjustment medium holding mechanism that adjusts the temperature of the mixed fluid, a temperature adjustment medium held by the holding mechanism, a temperature measurement sensor, a temperature adjustment medium, and a mixed reaction The fluid reaction device according to any one of claims 2 to 66 and 100 to 108, further comprising heat transfer amount adjusting means for adjusting a heat transfer amount between fluids.   110. The fluid reaction apparatus according to claim 109, wherein one or more of silicon oil, fluorine oil, alcohol, liquid nitrogen, electric resistance heating wire, and Peltier element is used as the temperature adjusting medium.   The fluid reaction device according to claim 109 or 110, wherein the heat transfer amount adjusting means is any one of a pump flow rate adjustment, a flow rate adjustment valve, and an electric quantity.   The fluid reaction device according to any one of claims 109 to 111, wherein the temperature adjusting medium holding mechanism is covered with a heat insulating member.   113. The fluid reaction device according to claim 112, wherein the heat insulating member is silicon rubber.   The fluid reaction according to any one of claims 2 to 66 and 100 to 113, further comprising separation and extraction means for separating a necessary substance and an unnecessary substance in the post-reaction substance. apparatus.   The fluid reaction apparatus according to any one of claims 2 to 66 and 100 to 114, comprising a powder dissolver for liquefying and dissolving the powder raw material.   The part or the whole region in the fluid reaction device is isolated from the outside of the device, and is set to a negative pressure with respect to the pressure outside the device, any one of claims 2 to 66 and claim 100 to 115 2. The fluid reaction apparatus according to item 1.   The liquid storage pan for storing the liquid leaked in the lower part of the fluid reaction device, and the liquid leakage sensor for detecting the liquid leaked are provided. The fluid reaction apparatus according to any one of claims. The said operation control means is equipped with the display mechanism which displays the flow volume and reaction temperature of a fluid, The any one of Claims 2-66 and 100-117 characterized by the above-mentioned. Fluid reaction device.

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