Microreactor and method for evaluating mixing performance of microreactor

Abstract

The present invention provides a microreactor and a method for evaluating mixing performance of a microreactor, which are effective for suppressing deterioration in controllability of mixing time and reaction time, and for suppressing damage due to shearing to a component contained in a fluid, and in which the equivalence of mixing performance for each individual is secured at a high level. The microreactor (1) mixes a fluid introduced from one inlet (107) and a fluid introduced from the other inlet (108). The flow path through which the fluids flow has a structure in which a part downstream of a merging section (106) is linearly extended. The pressure loss from the merging section (106) to the outlet (109) is greater than the pressure loss from the one inlet (107) to the merging section (106) and the pressure loss from the other inlet (108) to the merging section (106). The method for evaluating the mixing performance measures the pressure loss from the inlet (107) to the outlet (109) and the pressure loss from the inlet (108) to the outlet (109), and evaluates the mixing performance of each individual on the basis of the correlation between the measured pressure loss and a predetermined mixing performance.

Description

Microreactor and method for evaluating the mixing performance of the microreactor

[0001] The present invention relates to a microreactor used in a process of mixing or reacting fluids, and a method for evaluating the mixing performance of the microreactor.

[0002] In recent years, the use of microreactors has been increasing in the fields of bio-related products and the manufacturing of pharmaceuticals and chemical products. Microreactors are flow-type reactors with microchannels on the order of μm, and are used for mixing and reacting fluids. Microreactors are fabricated using microfabrication techniques such as molding and lithography. Removable and single-use types of microreactors are also being considered.

[0003] In a microreactor, the microchannels act as reaction sites, allowing for rapid mixing of fluids through molecular diffusion. Furthermore, compared to the batch process using conventional large reactors, the effect of surface area relative to fluid volume is greater, resulting in higher efficiency in heat transfer and chemical reactions. Therefore, it may be possible to easily carry out reactions that are difficult to carry out using batch processes, such as reactions that may run away due to heat generation, reactions that require precise temperature control, and reactions that require rapid heating and cooling.

[0004] In the microchannels of a microreactor, the effect of the characteristic length on the volume and flow rate of the fluid is relatively greater than in the batch process. Therefore, even if the Reynolds number is the same as in the batch process, the shear rate of the fluid increases. Therefore, operations that require uniform mixing and particle size control, such as emulsification, nanoparticle generation, and antisolvent crystallization, may be easily performed using a microreactor.

[0005] Because of these characteristics, the use of microreactors is expected to shorten mixing and reaction times and improve reaction yields and production efficiency in various fields, including the production of biopharmaceuticals such as antibody drugs, nucleic acid drugs, and peptide drugs. Conventionally, various flow channel structures have been investigated for microreactors in order to improve the mixing performance of mixing fluids and increase the throughput of mixing and reactions.

[0006] Patent Document 1 describes a microchannel structure having a confluence where two or more fluids converge, in which the flow path length, flow path cross-sectional area, and flow path length / flow path cross-sectional area ratio of the inlet flow path are such that the pressure losses of each of the two or more fluids converging at the confluence are substantially equal (paragraph 0011).

[0007] Patent Document 2 describes a fluid mixing device equipped with a numbering-up mechanism that divides multiple types of fluids into individual flows and performs multiple mixings or reactions in parallel. This device has multiple annular flow paths that convert the multiple types of fluids into respective concentric annular flows. The device includes a rectifying section in which the multiple annular flow paths communicate with radially branched flow paths, a distribution section having multiple distribution flow paths that divide the multiple types of fluids after being rectified by the rectifying section, a confluence section having multiple confluence flow paths that merge the multiple types of fluids after being divided by the distribution section, and a mixing / reaction section that mixes or reacts the multiple types of fluids after being merged at the confluence section. The distribution flow paths are provided with a pressure loss increasing means (paragraph 0013).

[0008] Patent Document 3 describes a microchannel device including a microchannel through which a sample liquid is delivered. This device includes an inlet reservoir for holding the sample liquid to be introduced into the microchannel, an inlet provided on the sample introduction side of the microchannel and communicating with the inlet reservoir, an outlet provided on the sample discharge side of the microchannel, an open channel provided in communication with the outlet, which guides the sample liquid flowing out of the outlet in the direction of gravity and removes the sample liquid from the outlet, and whose side is open to the outside atmosphere, and an outlet reservoir provided in communication with the open channel for holding the sample liquid discharged from the open channel. The inlet is provided at a higher position in the direction of gravity than the outlet (paragraph 0009).

[0009] Japanese Patent Publication No. 2006-055770 Japanese Patent No. 4901260 Japanese Patent No. 5609648

[0010] In general, to improve the mixing performance of a microreactor, it is necessary to reduce the characteristic length of the microchannel, such as the width, depth, or diameter of the microchannel, or to provide the microchannel in a non-linear and complex structure. However, reducing the characteristic length of the microchannel or providing the microchannel in a non-linear and complex structure increases the pressure loss in the microchannel.

[0011] For example, an increase in pressure loss in a microchannel can cause a problem in that the pump used to introduce fluids into a microreactor is limited. When the same pump is used to introduce fluids in multiple processes involving mixing and reaction, a large pressure loss is added for a certain discharge pressure. The flow rate decreases for a certain discharge pressure, resulting in a decrease in the throughput per microreactor. While it is possible to use a pump with a high discharge pressure, such a pump is expensive, which leads to an increase in the overall cost of the process.

[0012] Furthermore, reducing the characteristic length of the microchannel increases the shear rate for a given flow rate, which can cause significant damage to components that are sensitive to shear forces, such as when mixing active pharmaceutical ingredients in biopharmaceuticals.

[0013] Furthermore, when microchannels are provided with nonlinear and complex structures, secondary flows are likely to occur at bends, corners, and other parts of the microchannels. The increased secondary flows cause problems such as poor control of the mixing and reaction times of fluids. Even when fluids are introduced into a microreactor under the same conditions or continuously, the time it takes for the components in the fluids to actually mix and react varies, making it impossible to obtain products with the same composition for each process.

[0014] Generally, microreactors are manufactured using microfabrication technology, making it difficult to ensure uniformity of the microchannels for each product. Due to limitations in processing precision, the dimensions of the microchannels (channel length, channel width, and channel depth) may vary within the range of processing precision, and minute irregularities, undulations, etc. may form on the inner surface of the microchannel. When the uniformity of the microchannels is low, it becomes difficult to ensure uniformity of the mixing performance for each individual microreactor. Ensuring uniformity of the mixing performance for each individual microreactor becomes more difficult as the representative length of the microchannel becomes smaller. When used for single-use applications, variations in the products cannot be ignored.

[0015] Therefore, an object of the present invention is to provide a microreactor and a method for evaluating the mixing performance of a microreactor that is effective in suppressing deterioration in controllability of mixing time and reaction time and suppressing shear damage to components contained in a fluid, and that ensures a high level of uniformity in mixing performance for each individual microreactor.

[0016] In order to solve the above problems, the microreactor of the present invention has two inlets through which fluids are introduced, a flow path through which the fluids are joined and flow, and an outlet through which the joined fluids are discharged, and mixes a first fluid introduced from one of the inlets with a second fluid introduced from the other of the inlets in the flow path and discharges the mixed fluid from the outlet, and is characterized in that the flow path has a structure in which a portion downstream from a confluence part where the first fluid and the second fluid join is extended linearly, and the pressure loss in the flow path from the confluence part to the outlet is greater than the pressure loss in the flow path from one of the inlets to the confluence part and the pressure loss in the flow path from the other inlet to the confluence part.

[0017] Furthermore, a method for evaluating the mixing performance of a microreactor according to the present invention is a method for evaluating the mixing performance of a microreactor for mixing fluids for each individual microreactor, wherein the microreactor has two inlets for introducing fluids, a flow path for joining the fluids and causing them to flow, and an outlet for discharging the joined fluids, a first fluid introduced from one of the inlets and a second fluid introduced from the other of the inlets are mixed in the flow path, and the mixed fluid is discharged from the outlet, and the flow path has a structure in which a portion downstream of a joining portion where the first fluid and the second fluid join is extended linearly. the pressure loss in the flow path from the confluence to the outlet is larger than the pressure loss in the flow path from one inlet to the confluence and the pressure loss in the flow path from the other inlet to the confluence; and at least one of the pressure loss in the flow path from one inlet to the outlet and the pressure loss in the flow path from the other inlet to the outlet is measured, and the mixing performance for each individual microreactor is evaluated based on a correlation between the measured pressure loss in the flow path and a mixing performance for mixing the first fluid and the second fluid that is determined in advance for the same type of microreactor.

[0018] According to the present invention, it is possible to provide a microreactor and a method for evaluating the mixing performance of a microreactor, which are effective in suppressing deterioration in controllability of mixing time and reaction time and suppressing damage to components contained in a fluid due to shear, and which ensure a high level of uniformity in the mixing performance of each individual microreactor.

[0019] FIG. 1 is a diagram showing an example of a microreactor according to an embodiment of the present invention; FIG. 2 is a diagram showing the relationship between the flow rate of all fluids fed to the microreactor and the pressure loss of the microreactor; FIG. 3 is a diagram showing the relationship between the flow rate of all fluids fed to the microreactor and the absorbance of the product by the Villermaux-Dushman reaction; FIG. 4 is a diagram showing the relationship between the pressure loss of the microreactor and the absorbance of the product by the Villermaux-Dushman reaction; FIG. 5 is a diagram showing an example of a pressure loss measurement system for a microreactor according to an embodiment of the present invention; and FIG. 6 is a flowchart showing a pressure loss measurement method for a microreactor according to an embodiment of the present invention.

[0020] Hereinafter, a microreactor and a method for evaluating the mixing performance of a microreactor according to an embodiment of the present invention will be described with reference to the drawings. Note that common components in the following drawings will be assigned the same reference numerals and redundant explanations will be omitted.

[0021] <First Embodiment> Fig. 1 is a diagram showing an example of a microreactor according to an embodiment of the present invention. As shown in Fig. 1, the microreactor 1 according to this embodiment has two inlets (107, 108) through which individual fluids are introduced from the outside, microchannels (103, 104) through which the individual fluids are introduced, a microchannel (105) through which the individually introduced fluids are joined and flowed, and an outlet 109 through which a product fluid generated by joining the fluids at a joining section 106 is discharged to the outside.

[0022] The microreactor 1 introduces individual fluids into microchannels (103, 104) and mixes or reacts the fluids in the microchannel (105) to produce a product fluid that is a mixture of the fluids or a product fluid that contains a product formed by the reaction of components contained in the fluids. The microreactor 1 can be used for operations that constitute a process for producing pharmaceuticals such as biopharmaceuticals, chemical products, etc., and for operations that mix fluids or operations that cause fluids to react with each other.

[0023] The microreactor 1 is formed by an upper plate 101 and a lower plate 102. Grooves are formed in the upper plate 101, and the lower plate 102 is placed on top of the upper plate 101 to cover the grooves, thereby forming microchannels (103, 104, 105). The grooves that become the microchannels (103, 104, 105) can be formed in either the upper plate 101 or the lower plate 102.

[0024] The lower plate 102 is provided with through-holes (107, 108, 109) at positions overlapping with the respective ends of the microchannels (103, 104, 105). The through-holes (107, 108, 109) are formed so that an upstream inlet 107, a downstream inlet 108, and an outlet 109 open on the surface opposite to the surface on which the grooves are formed.

[0025] The through-holes (107, 108, 109) can be formed with threads (not shown). The through-holes (107, 108, 109) can be connected to pipes such as tubes via fittings that screw into the threads. Pipes for introducing fluids into the microreactor 1 and pipes for discharging fluids to the outside are connected to the microreactor 1. Pipes such as tubes may be connected directly to the through-holes without using fittings.

[0026] The microchannels (103, 104, 105) are each formed with a junction 106 where fluids are joined together to initiate mixing or reaction. The microchannels (103, 104, 105) are each composed of an upstream inlet 107 leading to the junction 106, an downstream inlet 108 leading to the junction 106, and a mixing channel 105 leading to an outlet 109.

[0027] The upstream inlet flow channel 103 can be used to pass a fluid having a relatively high mixing ratio and a relatively high flow rate among the fluids to be mixed in the microreactor 1. The downstream inlet flow channel 104 can be used to pass a fluid having a relatively low mixing ratio and a relatively low flow rate among the fluids to be mixed in the microreactor 1.

[0028] A fluid introduced from the upstream inlet 107 flows through the upstream introduction channel 103 and reaches the confluence 106. A fluid introduced from the downstream inlet 108 flows through the downstream introduction channel 104 and reaches the confluence 106. The fluid introduced from the upstream inlet 107 and the fluid introduced from the downstream inlet 108 meet at the confluence 106, and mixing and reaction between the fluids begins. The combined fluids continue mixing and reaction while flowing through the mixing channel 105 and beyond. After flowing through the mixing channel 105, the combined fluid is discharged to the outside from the outlet 109.

[0029] The flow path length of the upstream inlet flow path 103 from the upstream inlet 107 to the junction 106 is set longer than the flow path length of the downstream inlet flow path 104 from the downstream inlet 108 to the junction 106. Furthermore, the flow path volume of the upstream inlet flow path 103 from the upstream inlet 107 to the junction 106 is set larger than the flow path volume of the downstream inlet flow path 104 from the downstream inlet 108 to the junction 106. For example, the upstream inlet flow path 103 is set to have a flow path length and flow path volume larger than those of the downstream inlet flow path 104 provided with the same flow path width and flow path depth.

[0030] With this structure, when the mixing ratio is biased toward one fluid and the fluids are controlled to flow at significantly different rates, it is possible to reduce the difference in timing at which the fluids arrive at the confluence 106. By synchronizing the timing at which the fluids arrive at the confluence 106, it is possible to produce a product fluid with a high mixing rate and reaction rate between the fluids.

[0031] The upstream inlet flow path 103 is structured so that it branches into two symmetrical branch flow paths 103a and 103b at an intermediate portion and then merges with each other at a junction 106. The downstream inlet flow path 104 is structured so that it merges with the junction 106 between the two branch flow paths 103a and 103b. The junction 106 is structured so that fluids introduced from a total of three paths flow in from the same side on the same plane, merge, and then flow to opposite sides.

[0032] With this structure, the fluids merging from the downstream inlet flow channel 104 begin mixing while sandwiched between the fluids merging from the two upstream inlet flow channels 103. This increases the area of ​​the interface where the fluids come into contact, improving the efficiency of mixing the fluids. Furthermore, the connection from the upstream inlet flow channel 103 to the mixing flow channel 105 is at an acute angle, while the connection from the downstream inlet flow channel 104 to the mixing flow channel 105 is linear, making it difficult for bends, corners, or other irregularities to form in the flow channels, thereby suppressing the generation of secondary flows. The reduction in secondary flows suppresses a decrease in the controllability of the mixing time and reaction time of the fluids.

[0033] The microchannels (103, 104, 105) are provided in a structure in which the downstream portion of the confluence 106 extends linearly. That is, the mixing channel 105, which mixes or reacts fluids with each other, does not have any curved or bent portions in the section from the confluence 106 to the terminal end where the outlet 109 is formed, and is composed only of linear channels. It is preferable that the mixing channel 105 does not have any corners or angles that would cause secondary flows, and has only a substantially linear inner wall surface.

[0034] With this structure, pressure loss in the microchannels (103, 104, 105) is minimized. Since a large pressure loss is unlikely to occur for a certain discharge pressure and the flow rate is unlikely to decrease for a certain discharge pressure, a high flow rate of fluid can be made to flow by using a pump with an appropriate discharge pressure. Therefore, a high level of mixing and reaction throughput per microreactor can be ensured. Since there is no need to use an expensive pump with a high discharge pressure, the overall processing cost can be reduced.

[0035] Furthermore, with this structure, the pressure loss in the mixing channel 105 is more likely to reflect differences in the processing accuracy of each individual microreactor. The pressure loss in each individual mixing channel 105 is more likely to be affected by the processing accuracy of the inner wall surface of the mixing channel 105, rather than the structure of the mixing channel 105. Therefore, even if there are individual differences in the mixing performance of the microreactor due to differences in processing accuracy, within the range of the allowable processing accuracy of the microchannel, it is possible to more accurately select the individual microreactors by their mixing performance based on the pressure loss.

[0036] The microreactor 1 is provided in a structure in which the pressure loss in the mixing channel 105 from the confluence 106 to the outlet 109 is larger than the pressure loss in the upstream inlet channel 103 from the upstream inlet 107 to the confluence 106 and the pressure loss in the downstream inlet channel 104 from the downstream inlet 108 to the confluence 106. The ratio of the pressure loss in the upstream inlet channel 103 or the pressure loss in the downstream inlet channel 104 to the pressure loss in the mixing channel 105 is designed to be larger on the mixing channel 105 side than 1:1.

[0037] With this structure, the overall pressure loss for each individual microreactor 1 depends on the pressure loss in the mixing channel 105. The larger the pressure loss in the mixing channel 105, the more dominant the pressure loss in the mixing channel 105 becomes in the entire fine channels (103, 104, 105) of the microreactor 1. Therefore, a higher flow rate can be ensured under a predetermined discharge pressure of the pump used, thereby ensuring the required mixing performance. Furthermore, the pressure loss in the entire microreactor 1 and the pressure loss in the mixing channel 105 can be approximately considered to be substantially equal.

[0038] The pressure loss in the mixing channel 105 is a parameter that influences the mixing performance of the microreactor 1. Because the mixing channel 105 is usually located inside the microreactor 1, it is difficult to measure the pressure loss in the mixing channel 105 individually, and it is difficult to quantitatively evaluate the mixing performance of each individual microreactor. In contrast, the larger the pressure loss in the mixing channel 105 is relative to the pressure loss in the upstream inlet channel 103 and the downstream inlet channel 104, the more dominant the pressure loss in the mixing channel 105 becomes in the entire microreactor 1.

[0039] Therefore, it becomes possible to estimate the pressure loss in the mixing channel 105 based on the pressure loss in the entire microreactor 1 and to evaluate with high accuracy the mixing performance of each individual microreactor 1. Even if there are individual differences in mixing performance due to differences in processing accuracy within the range of allowable processing accuracy of the microchannel among multiple microreactors of the same type that have the same microchannel structure, it becomes possible to select with high accuracy those microreactors whose mixing performance meets the required requirements based on the measurement results of the pressure loss in the entire microreactor 1.

[0040] The ratio of the pressure loss in the upstream inlet channel 103 and the downstream inlet channel 104 to the pressure loss in the mixing channel 105 is preferably designed to be greater than 3:7 on the mixing channel 105 side, and more preferably greater than 2:8 on the mixing channel 105 side. The relatively greater the pressure loss in the mixing channel 105, the more dominant the pressure loss in the mixing channel 105 becomes throughout the microreactor 1. Therefore, higher mixing performance can be ensured under a specified discharge pressure of the pump used. Furthermore, it becomes possible to select individuals whose mixing performance satisfies the required level with higher accuracy.

[0041] The microchannels (103, 104, 105) preferably have a channel width, channel depth, and channel diameter of 2 mm or less. The channel width, channel depth, and channel diameter are more preferably 1.8 mm or less, even more preferably 1.6 mm or less, even more preferably 1.4 mm or less, and even more preferably 1.2 mm or less. The channel width, channel depth, and channel diameter vary depending on the purpose of the treatment, but are preferably 10 μm or more, more preferably 100 μm or more. With such channels, the effects of the microreaction field, such as surface effects and improved heat transfer coefficients, can be effectively obtained.

[0042] The upstream inlet flow channel 103 immediately before the confluence 106, the downstream inlet flow channel 104 immediately before the confluence 106, the confluence 106, and the mixing flow channel 105 preferably have a flow channel width, flow channel depth, and flow channel diameter of 10 μm or more and 2 mm or less. Such a flow channel allows fluids to be mixed uniformly and quickly by molecular diffusion in a flow that is primarily laminar. This reduces the likelihood of secondary flow occurring and improves mixing performance through molecular diffusion, thereby improving controllability of the fluid mixing time and reaction time.

[0043] The flow path length of the mixing flow path 105 from the confluence 106 to the outlet 109 is preferably designed to be equal to or longer than the flow path length of the upstream inlet flow path 103 from the upstream inlet 107 to the confluence 106 and the flow path length of the downstream inlet flow path 104 from the downstream inlet 108 to the confluence 106. With such a structure, when the cross-sectional areas of the respective flow paths are equal to each other, the pressure loss of the mixing flow path 105 tends to become dominant in the entire microreactor 1.

[0044] The ratio of the flow path length of the upstream introduction flow path 103 from the upstream inlet 107 to the confluence 106 to the flow path length of the mixing flow path 105 from the confluence 106 to the outlet 109 is preferably designed so that the mixing flow path 105 side is longer than 1:1, more preferably so that the mixing flow path 105 side is longer than 1:1.2, and even more preferably so that the mixing flow path 105 side is longer than 1:1.5.

[0045] The ratio of the flow path length of the downstream introduction flow path 104 from the downstream inlet 108 to the confluence 106 to the flow path length of the mixing flow path 105 from the confluence 106 to the outlet 109 is preferably designed so that the mixing flow path 105 side is longer than 1:1, more preferably so that the mixing flow path 105 side is longer than 1:3, and even more preferably so that the mixing flow path 105 side is longer than 1:6.

[0046] The flow rate ratios of the fluids introduced into the microreactor 1 may be different from each other or may be equal to each other. When the flow rate ratio is biased toward one fluid, it is preferable to flow a fluid at a relatively high flow rate from the upstream inlet 107 to the upstream inlet channel 103, and it is preferable to flow a fluid at a relatively low flow rate from the downstream inlet 108 to the downstream inlet channel 104.

[0047] The mixing of the fluids in the microreactor 1 may be a form in which the fluids are mixed uniformly, or a form in which the fluids are mixed non-uniformly. Examples of a form in which the fluids are mixed non-uniformly include a form in which multiple phases, such as an emulsion state, are formed.

[0048] In FIG. 1 , the microreactor 1 includes an upstream inlet flow channel 103 that is symmetrical with respect to an extension of the mixing flow channel 105, and a downstream inlet flow channel 104 that is on an extension of the mixing flow channel 105. The flow channel lengths to the confluence 106 are different, but the mixing flow channel 105 has a structure that extends linearly. As long as the structure is such that the pressure loss of the mixing flow channel 105 is larger than the pressure loss of the upstream inlet flow channel 103 and the pressure loss of the downstream inlet flow channel 104, the microreactor 1 can be provided with a microchannel of any suitable structure.

[0049] The microchannels can be provided in a Y-shaped structure, a T-shaped structure, a structure in which multilayer flows are formed and merged, or the like. In the microreactor 1, the flow channel volumes before the fluids merge may be different from each other or may be the same. All of the flow channels in the microreactor 1 do not necessarily have to be microchannels. The flow channel width and flow channel depth of some of the flow channels in the microreactor 1 can be changed as appropriate depending on the purpose of the processing, the type of fluid, the type of reaction, etc.

[0050] 2A is a diagram showing the relationship between the flow rate of all fluids fed to the microreactor and the pressure loss of the microreactor. FIG. 2B is a diagram showing the relationship between the flow rate of all fluids fed to the microreactor and the absorbance of the product of the Villermaux-Dushman reaction. FIG. 2C is a diagram showing the relationship between the pressure loss of the microreactor and the absorbance of the product of the Villermaux-Dushman reaction. In FIGS. 2A, 2B, and 2C, the results of microreactor A, which has a relatively low pressure loss within the range of acceptable processing accuracy when processing a microchannel, are compared with the results of microreactor B, which has a relatively high pressure loss within the range of acceptable processing accuracy when processing a microchannel.

[0051] 2A, 2B, and 2C, the microreactor A with a relatively low pressure loss and the microreactor B with a relatively high pressure loss were the same types of microreactors used, in which the mixing channel 105 was provided in a structure extending linearly as shown in FIG. 1, and the pressure loss of the mixing channel 105 was larger than the pressure loss of the upstream inlet channel 103 and the pressure loss of the downstream inlet channel 104.

[0052] 2A shows the results of determining the pressure loss throughout the microreactor by changing the total flow rate of the fluid introduced from the upstream inlet 107 and the downstream inlet 108. Pure water was used as the fluid. Pure water was introduced from the upstream inlet 107 and the downstream inlet 108 using syringe pumps so that the flow rates were equal. Pressure sensors were installed upstream of the upstream inlet 107 and the downstream inlet 108 to measure the inlet pressure. The open pressure outside the microreactor was also measured as the outlet pressure. The difference between the inlet pressure and the outlet pressure was determined as the pressure loss throughout the microreactor.

[0053] As shown in Figure 2A, the pressure drop in microreactor B was greater than that in microreactor A across the entire range of change in flow rate of all fluids. It is assumed that mixing and reactions occur in a flow that is primarily laminar in a microreactor. However, even between microreactors of the same design, variations in the dimensions and inner surface condition of the microchannels due to differences in processing accuracy can occur within the allowable processing accuracy of the microchannels, resulting in differences in pressure drop between individual microreactors. Depending on the differences in pressure drop, individual differences can occur in the mixing performance of mixing fluids and the processing capacity of mixing and reactions for a given discharge pressure and flow rate.

[0054] In processes involving the mixing or reaction of fluids, the same type of process is often carried out in different individual microreactors. Individual differences in the mixing performance of microreactors can cause variations in the composition and quality of the products produced. To suppress such variations, it is necessary to ensure the equivalence of the mixing performance of the microreactors used among multiple microreactors of the same type, each with the same microchannel structure within the allowable processing accuracy. This requires selection to align the mixing performance of microreactors used for multiple processes of the same type.

[0055] The mixing performance of a microreactor for mixing fluids is likely to be affected mainly by variations in the dimensions and the condition of the inner surface of the mixing channel 105, which are caused by differences in the processing accuracy of the mixing channel 105 after the fluids join, and is easily affected by the pressure loss in the mixing channel 105. However, because the mixing channel 105 is located inside the microreactor, it is difficult to measure the pressure loss of the mixing channel 105 individually. Therefore, a method is desired that can evaluate the mixing performance of each individual microreactor based on the pressure loss in the entire microreactor, which is practical to measure.

[0056] 2B shows the results of measuring the absorbance of triiodide ions, a product of the Villermaux-Dushman reaction, while changing the total flow rate of the fluids introduced from the upstream inlet 107 and downstream inlet 108. Pure water was used as the solvent constituting the fluid. The Villermaux-Dushman method is known as a method for evaluating the mixing performance of a microreactor when two fluids are mixed at a 1:1 volume ratio (W. Ehrfeld et al., Ind. Eng. Chem. Res., 38, 1075-1082 (1999)).

[0057] In the Villermaux-Dushman method, an aqueous solution of a strong acid, a strong base, and an oxidation-reduction agent (KI, KIO) ３ The solution is mixed with a buffer solution containing acetic acid, and the absorbance of triiodide ions, which are the product of the Villermaux-Dushman reaction, is measured. When an aqueous solution of acetic acid is used as the buffer solution, the competitive reactions represented by the following formulas (1) and (2) are utilized. ３ COO － +H ＋ ⇔ CH ３ COOH...(1) 5I － +IO ３ － +6H ＋ ⇔ 3I ２ +3H ２ O...(2)

[0058] Equation (1) and equation (2) are both reactions in a buffer solution. Both involve the reaction of protons (H ＋) is consumed, and the reaction proceeds by mixing an acid. Since formula (1) is a neutralization reaction, the reaction rate is higher than formula (2), and it proceeds rapidly. Formula (2) is an oxidation-reduction reaction. The molecular iodine (I ２ ) is converted to triiodide ions (I) by the equilibrium reaction represented by the following equation (3): ３ － ) is produced. ２ +I － ⇔ I ３ － ...(3)

[0059] Therefore, in the Villermaux-Dushman method, the higher the mixing performance of the microreactor, the more difficult it is for the reaction of formula (2) to occur compared to formula (1), and the more difficult it is for molecular iodine (I ２ ) and triiodide ion (I ３ － The amount of triiodide ion (I ３ － ) shows an absorption maximum around a wavelength of 352 nm. Therefore, the higher the mixing performance of the microreactor, the lower the absorbance of the fluid discharged from the microreactor at a wavelength around 352 nm. Therefore, the lower the absorbance of the product of the Villermaux-Dushman reaction using the microreactor, the higher the mixing performance of the microreactor can be evaluated.

[0060] In the test shown in Figure 2B, a 0.1374 mol / L hydrochloric acid solution was prepared as the strong acid solution. A 1.33 mol / L sodium acetate solution with 0.0319 mol / L potassium iodide dissolved therein and a 1.33 mol / L sodium acetate solution with 0.00635 mol / L potassium iodate dissolved therein were prepared as buffer solutions. The two types of buffer solutions were mixed to form a mixed aqueous solution immediately before being sent to the microreactor.

[0061] Mixing of reactants in the Villermaux-Dushman reaction in the microreactor was carried out at room temperature. The hydrochloric acid aqueous solution was introduced from the downstream inlet 108. The mixed aqueous solution was introduced from the upstream inlet 107. These fluids were introduced into the microreactor at equal flow rates using a syringe pump. The product fluid produced in the microreactor was collected, and the absorbance of ultraviolet light at a wavelength of 352 nm was measured using a spectrophotometer.

[0062] As shown in Figure 2B, for both microreactor A, which has a relatively low pressure drop, and microreactor B, which has a relatively high pressure drop, the absorbance of triiodide ions, the product of the Villermaux-Dushman reaction, decreased as the total fluid flow rate increased, resulting in improved mixing performance of the microreactor. In both microreactors, the absorbance converged to a substantially constant value when the total fluid flow rate was 10 mL / min or higher. This convergence was due to reaching the detection limit of the spectrophotometer.

[0063] Figure 2C shows the relationship between the pressure drop across the microreactor shown in Figure 2A and the absorbance measurement results of triiodide ions, which are the product of the Villermaux-Dushman reaction, plotted against the pressure drop across the microreactor.

[0064] 2C, for both microreactor A, which has a relatively low pressure drop, and microreactor B, which has a relatively high pressure drop, the absorbance of triiodide ions decreased as the pressure drop increased, and the mixing performance of the microreactor improved. For both microreactors, the results were plotted on approximately the same curve within the range of variation in the pressure drop measurement results and the absorbance measurement results.

[0065] When a microreactor is designed to have a predetermined structure, it can be said that, within the expected range of processing accuracy, a strong correlation can be obtained between the pressure loss in the entire microreactor and the measurement results of the absorbance of the product of the Villermaux-Dushman reaction using the microreactor. In other words, it can be said that a strong correlation can be obtained between the pressure loss in the entire microreactor and the mixing performance of each individual microreactor involving the mixing channel 105.

[0066] This result is obtained because the mixing channel 105 of the microreactor is configured to extend linearly, and is configured so that the pressure loss in the mixing channel 105 is greater than the pressure loss in the upstream inlet channel 103 and the pressure loss in the downstream inlet channel 104. This configuration makes it possible to quantitatively estimate the mixing performance of the microreactor based on the pressure loss throughout the microreactor. Among microreactors of the same type within the range of allowable processing accuracy, individual differences in mixing performance due to variations in the dimensions of the microchannels and the condition of the inner surfaces of the microchannels can be evaluated, and the appropriateness of the individual to be used and the appropriateness of the application for which the individual is to be used can be confirmed.

[0067] Mixing and reaction processes in the microreactor 1 are preferably carried out primarily in laminar flow. When the mixing channel 105 is configured to have a linearly extended structure and the channel width and channel depth of the mixing channel 105 are set to 10 μm or more and 2 mm or less, the Reynolds number in the mixing channel 105 becomes 2300 or less. Under these conditions, the fluid flow can be considered laminar. In mixing and reactions under laminar flow, secondary flows are reduced, and mass transfer due to molecular diffusion becomes dominant. This improves controllability of the fluid mixing time and reaction time. In addition, components that are sensitive to shear forces are less susceptible to shear damage.

[0068] Generally, the pressure loss of a viscous fluid in laminar flow in a circular pipe is expressed by the Hagen-Poiseuille equation (4): ΔP=32 μLv / d ２... (4) In equation (4), ΔP is the pressure loss of the fluid (Pa), μ is the viscosity coefficient of the fluid (Pa·s), L is the length of the circular pipe (m), v is the average flow velocity of the fluid at the flow path cross section of the circular pipe (m / s), and d is the diameter of the circular pipe (m).

[0069] According to Equation (4), in a perfectly laminar flow, the pressure loss for a given channel width and channel depth depends on the average flow velocity of the fluid, i.e., the flow rate of the fluid introduced into the conduit. However, in an actual conduit, secondary flows occur at bends, corners, and other parts, resulting in pressure loss. For this reason, it is necessary to provide the mixing channel 105 with a linearly extending structure. If such a structure minimizes pressure loss due to secondary flows, pressure loss due to friction depending on the processing accuracy of each individual microreactor becomes dominant. Furthermore, a high level of fluid throughput per microreactor can be ensured by using a discharge pressure that matches the pump's performance.

[0070] The mixing performance of each individual microreactor can be quantitatively evaluated using the pressure loss throughout the microreactor and the absorbance of the product when the Villermaux-Dushman reaction solution is flowed as indicators. Compared to pressure loss, product absorbance is less dependent on the measurement system and is useful for understanding the actual mixing state. For example, a state in which the absorbance of the product from the Villermaux-Dushman reaction is 0.1 or less can be defined as a state in which mixing performance is good. Based on Figure 2C, a state in which the product absorbance is 0.1 or less can be considered equivalent to a state in which the overall pressure loss is approximately 50 to 55 kPa or more. Based on Figure 2A, the overall pressure loss is approximately 50 to 55 kPa or more when the total fluid flow rate is approximately 5 mL / min or more.

[0071] Therefore, by using the same type of microreactor in which the mixing flow path 105 is provided in a structure that extends linearly and the pressure loss in the mixing flow path 105 is larger than the pressure loss in the upstream inlet flow path 103 and the pressure loss in the downstream inlet flow path 104, and by determining in advance the relationship between the flow rates of all fluids and the pressure loss in the entire microreactor and performing flow rate control with the flow rate at which the required mixing performance is obtained as the lower limit, it is possible to reduce processing variations due to individual differences in the microreactor.

[0072] According to the microreactor of this embodiment, the mixing channel 105 is provided in a linearly extending structure, and is provided in a structure in which the pressure loss in the mixing channel 105 is greater than the pressure loss in the upstream inlet channel 103 and the downstream inlet channel 104. This makes it possible to evaluate the mixing performance of the microreactor with high accuracy based on the measurement results of the pressure loss throughout the microreactor. When multiple microreactors of the same type, each having equivalent microchannel structures processed within an acceptable processing accuracy range for the intended use, are used for the same type of process in which fluids are mixed or reacted, even if there are individual differences between the microreactors due to variations in the dimensions of the microchannels and the condition of the inner surfaces of the microchannels within the acceptable processing accuracy range, it is possible to ensure the equality of the mixing performance between the individual microreactors, thereby making it less likely that variations in the products will occur.

[0073] Furthermore, since the mixing channel 105 is provided in a linearly extended structure, secondary flows are less likely to occur, which can prevent a decrease in controllability of the mixing time and reaction time of the fluids. Furthermore, when performing appropriate mixing and reaction, the representative length of the microchannel is less likely to be limited, making it easier to ensure the channel width, channel depth, and channel diameter, which can suppress the shear rate for a predetermined flow rate and reduce shear damage to components that are sensitive to shear forces.

[0074] Furthermore, since the mixing channel 105 is provided in a linearly extended structure, pressure loss in the mixing channel 105 and the entire microreactor is minimized, and therefore, by using a pump with an appropriate discharge pressure, it is possible to ensure a high level of fluid processing volume per microreactor.Since fluids can be mixed appropriately while reducing the performance requirements for the pumps used, the overall cost of processing using the microreactor can be reduced.

[0075] Therefore, it is possible to provide a microreactor that is effective in suppressing deterioration in controllability of mixing time and reaction time, and in suppressing shear damage to components contained in the fluid, and that easily ensures the fluid processing volume per unit and ensures a high level of uniformity in mixing performance for each individual unit. Processing using a microreactor makes it possible to efficiently produce products with little variation in composition and quality.

[0076] Furthermore, since the mixing performance of a microreactor can be evaluated with high accuracy based on the pressure drop across the entire microreactor, when multiple microreactors of the same type, each with equivalent microchannel structures fabricated within the range of processing accuracy acceptable for the intended use, are used for the same type of process of mixing or reacting fluids, it becomes possible to select and use a microreactor with equivalent mixing performance from among the multiple microreactors of the same type.When evaluating the mixing performance, the measurement results of the pressure drop across the entire microreactor can be used, making it easy to perform multiple measurements.

[0077] 3 is a diagram showing an example of a pressure loss measurement system for a microreactor according to an embodiment of the present invention. As shown in Fig. 3, the pressure loss measurement system 3 includes a microreactor 1, a first container 301, a second container 302, a recovery container 303, a first pump 304, a second pump 305, a first pressure sensor 306, a second pressure sensor 307, a first switching valve 308, a second switching valve 309, a control unit 310, an analysis unit 311, a connection unit 312, a signal line 313, etc.

[0078] The pressure loss measurement system 3 is a system that measures the pressure loss of the microreactor. The pressure loss measurement system 3 measures the pressure loss from the upstream inlet 107 to the outlet 109 and the pressure loss from the downstream inlet 108 to the outlet 109. These measurements allow the pressure loss in the entire microreactor 1 to be measured for each individual microreactor 1. When the pressure loss in the mixing channel 105 is dominant in the entire microreactor 1, it becomes possible to evaluate the mixing performance of each individual microreactor and to select the individual microreactors by mixing performance based on the pressure loss.

[0079] The microreactor 1 to be measured is connected to a first container 301 in which a first fluid is prepared for measuring the pressure loss from the upstream inlet 107 to the outlet 109, a second container 302 in which a second fluid is prepared for measuring the pressure loss from the downstream inlet 108 to the outlet 109, a recovery container 303 for recovering the fluid discharged from the outlet 109, a pump for sending at least one of the first fluid and the second fluid to the upstream inlet 107 or the downstream inlet 108, and a pressure sensor for measuring the pressure of the fluid upstream of the upstream inlet 107 or the downstream inlet 108 via a connection part 312 that forms a pipe.

[0080] As the pressure loss of the microreactor, at least one of the pressure loss from the upstream inlet 107 to the outlet 109 and the pressure loss from the downstream inlet 108 to the junction 106 can be measured. The larger the pressure loss in the mixing channel 105 is relative to the pressure loss in the upstream inlet channel 103 and the pressure loss in the downstream inlet channel 104, the more dominant the pressure loss in the mixing channel 105 becomes in the pressure loss in the entire microreactor 1, and therefore, a highly accurate evaluation can be performed based on the measurement of at least one of the pressure losses.

[0081] As the pump, at least one of a first pump 304 that sends the first fluid to the upstream inlet 107 and a second pump 305 that sends the second fluid to the downstream inlet 108 can be connected. However, by connecting both the first pump 304 and the second pump 305, the pressure loss in the mixing channel 105 becomes the pressure loss caused by the mixed fluid obtained by mixing the first fluid and the second fluid, and the pressure loss in the mixing channel 105 becomes more dominant in the entire microreactor 1, allowing for more accurate evaluation.

[0082] As the pressure sensor, at least one of a first pressure sensor 306 that is installed upstream of the upstream inlet 107 and measures the pressure from that installation position on the flow path to the outlet 109 or downstream of the outlet 109, and a second pressure sensor 307 that is installed upstream of the downstream inlet 108 and measures the pressure from that installation position on the flow path to the outlet 109 or downstream of the outlet 109 can be connected. However, when measuring only one pressure, it is preferable to connect the first pressure sensor 306 that measures the upstream side where the fine flow path is longer, from the viewpoint of obtaining information about the fine flow path. As the pressure sensor, a combination of a sensor that measures the absolute pressure upstream of the upstream inlet 107 or the downstream inlet 108 and a sensor that measures the absolute pressure at the outlet 109 or downstream of the outlet 109 may be used.

[0083] At least one of a first switching valve 308 that can freely open and close the flow path between the first container 301 and the upstream inlet 107, and a second switching valve 309 that can freely open and close the flow path between the second container 302 and the downstream inlet 108 can be connected to the flow path in which the pump and pressure sensor are installed.

[0084] When measuring the pressure loss of the microreactor, at least one of the following operations is performed: a first fluid prepared in a first container 301 is sent to an upstream inlet 107 by a first pump 304, the pressure from the upstream side of the upstream inlet 107 to the outlet 109 or downstream side of the outlet 109 is measured by a first pressure sensor 306, and the first fluid discharged from the outlet 109 is then recovered in a recovery container 303; a second fluid prepared in a second container 302 is sent to a downstream inlet 108 by a second pump 305, the pressure from the upstream side of the downstream inlet 108 to the outlet 109 or downstream side of the outlet 109 is measured by a second pressure sensor 307, and the second fluid discharged from the outlet 109 is then recovered in a recovery container 303.

[0085] In addition, at least one of the following operations is performed: an operation to determine the pressure loss in the upstream introduction flow path 103 and the mixing flow path 105 from the upstream inlet 107 to the outlet 109 based on the pressure measurement results from the upstream side of the upstream inlet 107 to the outlet 109 or downstream side of the outlet 109 measured by the first pressure sensor 306 and a reference pressure outside the micro flow path (103, 104, 105); and an operation to determine the pressure loss in the downstream introduction flow path 104 and the mixing flow path 105 from the downstream inlet 108 to the outlet 109 based on the pressure measurement results from the upstream side of the downstream inlet 108 to the outlet 109 or downstream side of the outlet 109 measured by the second pressure sensor 307 and a reference pressure outside the micro flow path (103, 104, 105).

[0086] A method for determining the pressure loss may be to calculate the difference between the absolute pressure upstream of the upstream inlet 107 or the downstream inlet 108 and the absolute pressure at the outlet 109 or the absolute pressure downstream of the outlet 109. As the absolute pressure at the outlet 109 or the absolute pressure downstream of the outlet 109, the open pressure outside the pressure loss measurement system 3 or inside the collection container 303 can be measured as the reference pressure outside the microchannels (103, 104, 105).

[0087] A first pressure sensor 306 is connected to the upstream inlet 107 of the microreactor 1 via a connection part 312. A first switching valve 308 is connected to the first pressure sensor 306 via the connection part 312. A three-way valve capable of switching flow paths can be used as the first switching valve 308. A first container 301 is connected to one port of the first switching valve 308 via the connection part 312. A first pump 304 is connected to the other port of the first switching valve 308 via the connection part 312.

[0088] The first container 301 contains a first fluid for measuring the pressure loss throughout the microreactor 1. The first fluid is used to measure the pressure loss caused by the first fluid from the upstream inlet 107 to the outlet 109. As the first pump 304, for example, a syringe pump can be used.

[0089] The first fluid prepared in the first container 301 is sucked by the first pump 304 and then discharged toward the microreactor 1. The first fluid is introduced into the upstream inlet 107 via the first pressure sensor 306. The first pressure sensor 306 is installed upstream of the upstream inlet 107, and measures the pressure from the installation position on the flow path to the outlet 109 or downstream of the outlet 109.

[0090] A second pressure sensor 307 is connected to the downstream inlet 108 of the microreactor 1 via a connection part 312. A second switching valve 309 is connected to the second pressure sensor 307 via the connection part 312. A three-way valve capable of switching flow paths can be used as the second switching valve 309. A second container 302 is connected to one port of the second switching valve 309 via the connection part 312. A second pump 305 is connected to the other port of the second switching valve 309 via the connection part 312.

[0091] The second container 302 contains a second fluid for measuring the pressure loss throughout the microreactor 1. The second fluid is used to measure the pressure loss caused by the second fluid from the downstream inlet 108 to the outlet 109. As the second pump 305, for example, a syringe pump can be used.

[0092] The second fluid prepared in the second container 302 is sucked by the second pump 305 and then discharged toward the microreactor 1. The second fluid is introduced into the downstream inlet 108 via the second pressure sensor 307. The second pressure sensor 307 is installed upstream of the downstream inlet 108, and measures the pressure from the installation position on the flow path to the outlet 109 or downstream of the outlet 109.

[0093] A collection container 303 is connected to the outlet 109 of the microreactor 1 via a connection part 312. The product fluid produced in the microreactor 1 is discharged from the outlet 109 of the microreactor 1 and flows into the collection container 303 to be collected. Note that the product fluid produced in the microreactor 1 can also be collected by flowing directly from the outlet 109 into the collection container 303 without going through the connection part 312.

[0094] The connection part 312 that connects the microreactor 1 and the first pressure sensor 306 can be formed by, for example, a tube made of resin or the like, a fitting that detachably connects the tube and the microreactor 1, and another fitting that detachably connects the tube and the first pressure sensor 306. Alternatively, it can be formed by a fitting that directly connects the microreactor 1 and the first pressure sensor 306.

[0095] By making the length of the connection part 312 connecting the microreactor 1 and the first pressure sensor 306 sufficiently short or making the inner diameter thereof sufficiently larger than the fine flow paths (103, 104, 105) of the microreactor 1, it is possible to ignore the pressure loss at the connection part 312 connecting the microreactor 1 and the first pressure sensor 306 with respect to the pressure loss in the entire microreactor 1. In other words, the pressure value measured by the first pressure sensor 306 can be considered as the pressure loss in the entire microreactor 1, not including the pressure loss at the connection part 312 connecting the microreactor 1 and the first pressure sensor 306.

[0096] The control unit 310 controls the operations of the first pump 304, the second pump 305, the first switching valve 308, and the second switching valve 309. The control unit 310 controls the activation and deactivation of the first pump 304 and the second pump 305, as well as the discharge pressure. The control unit 310 also controls the opening and closing of the first switching valve 308 and the second switching valve 309, as well as the switching of the flow paths. The control unit 310 is configured with a sequence controller, a programmable controller, etc.

[0097] The analysis unit 311 calculates pressure loss and evaluates the mixing performance of the microreactor based on the pressure measurement results from the first pressure sensor 306 and the second pressure sensor 307. The analysis unit 311 also inputs operation signals for controlling the operation of the pressure loss measurement system 3 and outputs detection results and measurement results of the control status. The analysis unit 311 is configured, for example, by a personal computer equipped with a calculation unit, a storage device, input means, output means, communication means, etc.

[0098] The analysis unit 311 receives measurement signals indicating the pressure measurement results from the first pressure sensor 306 and the second pressure sensor 307, and calculates the difference between the measured inlet pressure and the separately measured outlet pressure to calculate the pressure loss. The analysis unit 311 also sets the flow rates of the first fluid and the second fluid, determines the magnitude of the inlet pressure, and determines the feasibility of a lower limit value for pressure loss depending on the intended use.

[0099] The connection part 312 that connects the microreactor 1 and the second pressure sensor 307 can be formed by, for example, a tube made of resin or the like, a fitting that detachably connects the tube and the microreactor 1, and another fitting that detachably connects the tube and the second pressure sensor 307. Alternatively, it can be formed by a fitting that directly connects the microreactor 1 and the first pressure sensor 306.

[0100] By making the length of the connection part 312 connecting the microreactor 1 and the second pressure sensor 307 sufficiently short or making the inner diameter thereof sufficiently larger than the fine flow paths (103, 104, 105) of the microreactor 1, it is possible to ignore the pressure loss at the connection part 312 connecting the microreactor 1 and the second pressure sensor 307 with respect to the pressure loss in the entire microreactor 1. In other words, the pressure value measured by the second pressure sensor 307 can be considered as the pressure loss in the entire microreactor 1, not including the pressure loss at the connection part 312 connecting the microreactor 1 and the second pressure sensor 307.

[0101] The connection part 312 that connects the microreactor 1 and the collection container 303 can be formed by, for example, a tube made of resin or the like, a fitting that detachably connects the tube and the microreactor 1, and another fitting that detachably connects the tube and the collection container 303. Alternatively, it can be formed by a fitting that directly connects the microreactor 1 and the collection container 303.

[0102] The pressure loss at the connection part 312 connecting the microreactor 1 and the collection container 303 can be ignored by making the length of the connection part 312 connecting the microreactor 1 and the collection container 303 sufficiently short or making the inner diameter thereof sufficiently larger than the fine flow paths (103, 104, 105) of the microreactor 1. That is, the pressure values ​​measured by the first pressure sensor 306 and the second pressure sensor 307 can be considered as the pressure loss in the entire microreactor 1, not including the pressure loss at the connection part 312 connecting the microreactor 1 and the collection container 303.

[0103] The connection part 312 that connects the first pressure sensor 306 and the first switching valve 308 can be formed, for example, by a tube made of resin or the like, a fitting that detachably connects the tube and the first pressure sensor 306, and another fitting that detachably connects the tube and the first switching valve 308. Alternatively, the connection part 312 can be formed by a fitting that directly connects the first pressure sensor 306 and the first switching valve 308.

[0104] The connection part 312 that connects the second pressure sensor 307 and the second switching valve 309 can be formed, for example, by a tube made of resin or the like, a fitting that detachably connects the tube and the second pressure sensor 307, and another fitting that detachably connects the tube and the second switching valve 309. Alternatively, it can be formed by a fitting that directly connects the second pressure sensor 307 and the second switching valve 309.

[0105] The connection part 312 that connects the first switching valve 308 and the first container 301 can be formed, for example, by a tube made of resin or the like, a fitting that detachably connects the tube and the first switching valve 308, and another fitting that detachably connects the tube and the first container 301. Alternatively, the connection part 312 can be formed by a fitting that directly connects the first switching valve 308 and the first container 301.

[0106] The connection part 312 that connects the second switching valve 309 and the second container 302 can be formed, for example, by a tube made of resin or the like, a fitting that detachably connects the tube and the second switching valve 309, and another fitting that detachably connects the tube and the second container 302. Alternatively, it can be formed by a fitting that directly connects the second switching valve 309 and the second container 302.

[0107] The connection part 312 connecting the first switching valve 308 and the first pump 304 can be formed, for example, by a tube made of resin or the like, a fitting that detachably connects the tube and the first switching valve 308, and another fitting that detachably connects the tube and the first pump 304. Alternatively, the connection part 312 can be formed by a fitting that directly connects the first switching valve 308 and the first pump 304.

[0108] The connection part 312 connecting the second switching valve 309 and the second pump 305 can be formed by, for example, a tube made of resin or the like, a fitting that detachably connects the tube and the second switching valve 309, and another fitting that detachably connects the tube and the second pump 305. Alternatively, the connection part 312 can be formed by a fitting that directly connects the second switching valve 309 and the second pump 305.

[0109] The first fluid and the second fluid may be, for example, a Newtonian fluid such as water or alcohol. As the first fluid and the second fluid, it is preferable to use a fluid that does not adversely affect the material of the microreactor 1, is easy to remove from the microchannel after use, and is unlikely to affect the process using the microreactor 1. Specific examples of the first fluid and the second fluid include pure water, ethanol, and an aqueous ethanol solution such as disinfectant ethanol.

[0110] For example, a syringe pump, a tube pump, a plunger pump, a diaphragm pump, a screw pump, etc. can be used as the first pump 304 and the second pump 305. Furthermore, instead of using a pump, the fluid can be transferred manually using a syringe or the like, or by a method utilizing a hydraulic head difference.

[0111] When syringe pumps are used as the first pump 304 and the second pump 305, syringes in which the first fluid and the second fluid are prepared can be used as the first container 301 and the second container 302. In such a case, the first fluid and the second fluid can be introduced directly into the microreactor 1 from the syringes via the first pressure sensor 306 and the second pressure sensor 307 without using the first switching valve 308 and the second switching valve 309.

[0112] It is also possible to omit installation of one of the first pressure sensor 306 and the second pressure sensor 307. By installing the first pressure sensor 306 or the second pressure sensor 307, one of the pressure loss from the upstream inlet 107 to the outlet 109 and the pressure loss from the downstream inlet 108 to the outlet 109 can be calculated based on the measurement result of either pressure, thereby enabling quantitative evaluation of the mixing performance of each individual microreactor 1. However, from the viewpoint of performing an accurate evaluation, it is preferable to install both the first pressure sensor 306 and the second pressure sensor 307.

[0113] The microreactor 1, one or more of the first container 301, the second container 302, and the collection container 303, and the connection part 312 may be disposable products for single use. Single use can prevent contamination of components during mixing or reaction processes. Furthermore, even if the fluid contains a toxic or hazardous substance, the device can be post-processed together with the fluid, thereby reducing the risk of contact with the fluid during disposal and the post-processing costs.

[0114] As materials for the microreactor 1, the first container 301, the second container 302, the recovery container 303, the connection part 312, the liquid contact part of the pressure sensor, the liquid contact part of the switching valve, the liquid contact part of the pump, the pump syringe, the pump diaphragm, the tubes, and the fittings, any suitable material can be used depending on the type of fluid, etc., as long as it does not have an adverse effect on the first fluid, the second fluid, and the produced fluid and is unlikely to deteriorate due to these.

[0115] The materials of the microreactor 1, the first container 301, the second container 302, the recovery container 303, the connection part 312, the liquid-contacting part of the pressure sensor, the liquid-contacting part of the switching valve, the liquid-contacting part of the pump, the pump syringe, the pump diaphragm, the tubes, and the fittings may be the same for each installation location or may be different for each installation location in the pressure loss measurement system 3. The materials for each installation location can be selected appropriately depending on processability, flexibility, etc.

[0116] Examples of materials for the microreactor 1 include stainless steel, gold, glass, Hastelloy, ceramic, PE (polyethylene), PP (polypropylene), PMP (polymethylpentene), PDMS (polydimethylsiloxane), PC (polycarbonate), acrylic resin, and fluorine-based resins such as PTFE (polytetrafluoroethylene) and PFA (perfluoroalkoxyalkane).The material for the microreactor 1 may be lined with glass or the like, coated with nickel, gold, or the like, or may have an oxide film formed thereon.

[0117] Examples of materials for the connection part 312 include fluororesins such as PTFE (polytetrafluoroethylene) and PFA (perfluoroalkoxyalkane). Examples of materials for the liquid-contacting parts of the pressure sensor, the liquid-contacting parts of the switching valve, the liquid-contacting parts of the pump, the pump syringe, and the pump diaphragm include stainless steel, glass, PDMS (polydimethylsiloxane), PE (polyethylene), PP (polypropylene), silicone resin, and fluororesin.

[0118] The pressure loss measurement system 3 is preferably installed in a space where the temperature is adjusted within a predetermined range. By maintaining constant temperatures of the microreactor 1, the first container 301, and the second container 302, accurate pressure loss measurements can be performed. The temperatures of the microreactor 1, the first container 301, and the second container 302 can be adjusted by at least one of heating and cooling. As the temperature adjustment device, a heat exchanger using a heat medium, a constant temperature water bath using a heat medium, a Peltier temperature adjustment device, a mantle heater, or the like can be used. As the heat medium, water, ethylene glycol, a water / ethylene glycol mixture, or the like can be used.

[0119] Fig. 4 is a flowchart showing a method for evaluating the mixing performance of a microreactor according to an embodiment of the present invention. As shown in Fig. 4, the evaluation of the mixing performance of a microreactor can be carried out by connecting the microreactor 1 to be evaluated to the pressure loss measurement system 3 shown in Fig. 3 and measuring the pressure loss throughout the microreactor 1 for each individual microreactor.

[0120] The microreactor 1 to be evaluated is connected via a connection part 312 that forms piping to a first container 301 in which a first fluid is prepared for measuring the pressure loss caused by the first fluid from the upstream inlet 107 to the outlet 109, a second container 302 in which a second fluid is prepared for measuring the pressure loss caused by the second fluid from the downstream inlet 108 to the outlet 109, a recovery container 303 that recovers the fluid discharged from the outlet 109, a pump that sends at least one of the first fluid and the second fluid to the upstream inlet 107 or the downstream inlet 108, and a pressure sensor that measures the pressure of the fluid upstream of the upstream inlet 107 or the downstream inlet 108.

[0121] As the pressure loss of the microreactor, at least one of the pressure loss from the upstream inlet 107 to the outlet 109 and the pressure loss from the downstream inlet 108 to the outlet 109 can be measured. The larger the pressure loss in the mixing channel 105 is relative to the pressure loss in the upstream inlet channel 103 and the pressure loss in the downstream inlet channel 104, the more dominant the pressure loss in the mixing channel 105 becomes in the pressure loss in the entire microreactor 1, and therefore, a highly accurate evaluation can be performed based on the measurement of at least one of the pressure losses.

[0122] As the pump, at least one of a first pump 304 that sends the first fluid to the upstream inlet 107 and a second pump 305 that sends the second fluid to the downstream inlet 108 can be connected. However, by connecting both the first pump 304 and the second pump 305, the pressure loss in the mixing channel 105 becomes the pressure loss caused by the mixed fluid obtained by mixing the first fluid and the second fluid, and the pressure loss in the mixing channel 105 becomes more dominant in the entire microreactor 1, allowing for more accurate evaluation.

[0123] As the pressure sensor, at least one of a first pressure sensor 306 that is installed upstream of the upstream inlet 107 and measures the pressure from that installation position on the flow path to the outlet 109 or downstream of the outlet 109, and a second pressure sensor 307 that is installed upstream of the downstream inlet 108 and measures the pressure from that installation position on the flow path to the outlet 109 or downstream of the outlet 109 can be connected. However, when measuring only one pressure, it is preferable to connect the first pressure sensor 306 that measures the upstream side where the fine flow path is longer, from the viewpoint of obtaining information about the fine flow path. As the pressure sensor, a combination of a sensor that measures the absolute pressure upstream of the upstream inlet 107 or the downstream inlet 108 and a sensor that measures the absolute pressure at the outlet 109 or downstream of the outlet 109 may be used.

[0124] At least one of a first switching valve 308 that can freely open and close the flow path between the first container 301 and the upstream inlet 107, and a second switching valve 309 that can freely open and close the flow path between the second container 302 and the downstream inlet 108 can be connected to the flow path in which the pump and pressure sensor are installed.

[0125] When measuring the pressure loss of the microreactor, at least one of the following operations is performed: a first fluid prepared in a first container 301 is sent to an upstream inlet 107 by a first pump 304, the pressure from the upstream side of the upstream inlet 107 to the outlet 109 or downstream side of the outlet 109 is measured by a first pressure sensor 306, and the first fluid discharged from the outlet 109 is then recovered in a recovery container 303; a second fluid prepared in a second container 302 is sent to a downstream inlet 108 by a second pump 305, the pressure from the upstream side of the downstream inlet 108 to the outlet 109 or downstream side of the outlet 109 is measured by a second pressure sensor 307, and the second fluid discharged from the outlet 109 is then recovered in a recovery container 303.

[0126] In addition, at least one of the following operations is performed: an operation to determine the pressure loss in the upstream introduction flow path 103 and the mixing flow path 105 from the upstream inlet 107 to the outlet 109 based on the pressure measurement results from the upstream side of the upstream inlet 107 to the outlet 109 or downstream side of the outlet 109 measured by the first pressure sensor 306 and a reference pressure outside the micro flow path (103, 104, 105); and an operation to determine the pressure loss in the downstream introduction flow path 104 and the mixing flow path 105 from the downstream inlet 108 to the outlet 109 based on the pressure measurement results from the upstream side of the downstream inlet 108 to the outlet 109 or downstream side of the outlet 109 measured by the second pressure sensor 307 and a reference pressure outside the micro flow path (103, 104, 105).

[0127] In the evaluation method shown in FIG. 4, first, the microreactor 1 to be evaluated is connected to the pressure loss measurement system 3 (step 401).

[0128] Next, the flow rate of the fluid to be introduced into the microreactor 1 to be evaluated is set (step 402). Any flow rate value can be set for the upstream inlet 107 and the downstream inlet 108 within the range expected when the microreactor 1 to be evaluated is used.

[0129] Next, the pressure of the microreactor 1 to be evaluated at the set flow rate of the fluid is measured (step 403). The first pump 304 and the second pump 305 suck the fluid prepared in the first container 301 and the second container 302 and send it toward the upstream inlet 107 and the downstream inlet 108, and the pressure loss of the microreactor 1 is measured by the first pressure sensor 306 and the second pressure sensor 307.

[0130] Next, it is determined whether the pressure in the microreactor 1 to be evaluated at the set flow rate of the fluid exceeds a preset threshold value (step 404). If the liquid delivery flow rate is small, the pressure loss will be small and sufficient mixing performance will not be obtained. In addition, it will be difficult to accurately evaluate the mixing performance of the microreactor. On the other hand, if the liquid delivery flow rate is too large, the pressure will increase, exceeding the discharge pressure of the pump to be used in production and the pressure resistance of the tubes and fittings, making it unusable in practice. Therefore, a threshold value is set as the upper limit of the pressure.

[0131] The pressure threshold can be set in advance to a value that keeps the pressure loss throughout the microreactor 1 to be evaluated below a predetermined upper limit, depending on the upper limit of the pump discharge pressure, the pressure resistance of the tubes and fittings, the required processing volume of the microreactor 1 to be evaluated, the purpose of the processing using the microreactor 1 to be evaluated, the structure of the microreactor 1 to be evaluated, the composition of the fluid, etc.

[0132] If the result of the determination is that the pressure of the fluid introduced into the microreactor 1 to be evaluated does not exceed the threshold value (step 404; NO), the process returns to step 402. In this case, in step 402, the flow rate of the fluid introduced into the microreactor 1 to be evaluated is reset to a flow rate higher than the previous flow rate.

[0133] On the other hand, if the determination result shows that the pressure of the fluid introduced into the microreactor 1 to be evaluated exceeds the threshold value (step 404 ; YES), the process proceeds to step 405 .

[0134] Next, the microreactor 1 to be evaluated is removed from the pressure loss measurement system 3 (step 405).

[0135] Next, the fluid remaining inside the microreactor 1 to be evaluated is removed (step 406). A method of injecting gas into the microreactor 1 can be used to remove the fluid. Compressed air, nitrogen gas, or the like can be used as the gas. The microreactor 1 can be rotated at high speed, and the remaining fluid can be removed by centrifugal force from the upstream inlet 107 and downstream inlet 108 toward the outlet 109, or from the outlet 109 toward the upstream inlet 107 and downstream inlet 108.

[0136] Furthermore, before removing the microreactor 1 from the pressure loss measurement system 3, a gas such as air may be injected into the microreactor 1 by the first pump 304 or the second pump 305. By such an operation, the fluid remaining inside can be removed to a certain extent.

[0137] Next, it is determined whether the microreactor 1 to be evaluated, whose pressure has been measured, can achieve a lower limit of pressure loss according to the intended use (step 407). If the pressure loss falls below the lower limit, sufficient mixing performance cannot be obtained. Furthermore, it becomes difficult to accurately evaluate the mixing performance of the microreactor 1 and ensure uniformity of mixing performance for each individual microreactor. Therefore, selection is performed so that the pressure loss is equal to or greater than a predetermined lower limit. On the other hand, if the pressure loss is too large, it will exceed the discharge pressure of the pump to be used in production and the pressure resistance of the tubes and fittings, making it unusable in practice.

[0138] The lower limit of the pressure loss can be preset to any value depending on the shear rate of the fluid, the upper limit of the discharge pressure of the pump, the pressure resistance of the tubes and fittings, the required throughput of the microreactor 1 to be evaluated, the purpose of the process using the microreactor 1 to be evaluated, etc. The lower limit of the pressure loss can be set so that the absorbance of the product of the Villermaux-Dushman reaction is equal to or greater than a preset threshold value, so that the required mixing performance is ensured.

[0139] The mixing performance of each individual microreactor can be quantitatively measured as the absorbance of triiodide ions, which are the product of the Villermaux-Dushman reaction, by performing the Villermaux-Dushman reaction using the same type of microreactor with the same microchannel structure within the allowable processing accuracy. That is, the relationship between the absorbance of the product of the Villermaux-Dushman reaction and the degree of mixing or reaction between predetermined fluids can be determined in advance using the same type of microreactor with the same microchannel structure within the allowable processing accuracy.

[0140] It is possible to evaluate the mixing performance of each individual microreactor based on the correlation between the pressure loss measured by the pressure loss measurement system 3 and the mixing performance previously determined for the same type of microreactor with the same microchannel structure within the range of allowable processing accuracy. By using the absorbance of the product of the Villermaux-Dushman reaction as an index, it is possible to objectively evaluate the mixing performance of each individual microreactor.

[0141] As a result of the determination, if the lower limit of pressure loss according to the intended use can be realized (step 407; YES), the process proceeds to step 408. In this case, it can be determined that the microreactor 1 to be evaluated is a microreactor suited to the intended use (step 408). Thereafter, the process of measuring pressure loss and evaluating mixing performance is terminated.

[0142] On the other hand, if the result of the determination is that the lower limit of pressure loss corresponding to the intended use cannot be realized (step 407; NO), the process proceeds to step 409. In this case, it can be determined that the microreactor 1 being evaluated is not a microreactor suited to the intended use, and is suited to a different intended use (step 409). Thereafter, the process of measuring pressure loss and evaluating mixing performance is terminated.

[0143] When the mixing performance of such a microreactor is evaluated, at least one of the pressure loss between the upstream inlet 107 and the mixing channel 105 from the upstream inlet 107 to the outlet 109 and the pressure loss between the downstream inlet 108 and the outlet 109 and the mixing channel 105 is measured, and based on the correlation between the measured pressure loss between the upstream inlet 103 and the mixing channel 105 or the measured pressure loss between the downstream inlet 104 and the mixing channel 105 and the mixing performance previously determined for a microreactor of the same type having an equivalent microchannel structure within the range of allowable processing accuracy, a microreactor whose mixing performance has been evaluated for each individual microreactor can be obtained.

[0144] Whether or not the mixing performance of each individual microreactor has been evaluated can be confirmed by the display of the mixing performance of each individual microreactor, the display of the overall pressure loss for each individual microreactor, the display of the pressure loss in the mixing flow path 105 for each individual microreactor, and the fluid used for measuring the pressure loss remaining inside the microreactor.

[0145] The microreactors whose individual mixing performance has been evaluated can be used under conditions in which the flow rates of the first fluid introduced from the upstream inlet 107 and the second fluid introduced from the downstream inlet 108 are such that the pressure loss between the upstream inlet channel 103 and the mixing channel 105 from the upstream inlet 107 to the outlet 109, and the pressure loss between the downstream inlet channel 104 and the mixing channel 105 from the downstream inlet 108 to the outlet 109, are equal to or greater than a lower limit. The lower limit of the pressure loss can be set so that the absorbance of triiodide ions, which are products of the Villermaux-Dushman reaction, is equal to or greater than a predetermined threshold. The absorbance of the product of the Villermaux-Dushman reaction can be determined in advance using the same type of microreactor having an equivalent microchannel structure within an allowable processing accuracy range.

[0146] When the microreactor is used under these flow rate conditions, the pressure loss in the mixing channel 105 is equal to or greater than a predetermined lower limit, ensuring the minimum mixing performance required for the process. When multiple microreactors of the same type, each with the same microchannel structure, are used for multiple processes involving mixing and reaction, and even if there are individual differences in mixing performance due to differences in processing accuracy within the range of allowable processing accuracy among the multiple microreactors of the same type, the pressure loss in the mixing channel 105 is uniformed to equal to or greater than a predetermined lower limit. This reduces the effects of individual differences, preventing variations in the composition and quality of the products produced from individual microreactors.

[0147] According to the method for evaluating the mixing performance of a microreactor according to the present embodiment, it is possible to select individual microreactors that have the mixing performance required for the intended use, based on the pressure loss measured for the microreactor to be evaluated. When multiple microreactors of the same type, each having the same microchannel structure within the range of allowable processing accuracy, are used for the same type of process of mixing or reacting fluids, even if there are individual differences between the microreactors due to differences in processing accuracy, it is possible to ensure the equality of the mixing performance of each individual microreactor, thereby making it difficult for variations in the product to occur.

[0148] Although the embodiments and modifications of the present invention have been described above, the present invention is not limited to the above-described embodiments, and various modifications are possible within the scope of the present invention. For example, the present invention is not necessarily limited to those having all of the configurations of the above-described embodiments. It is also possible to replace part of the configuration of one embodiment with the configuration of another embodiment, add part of the configuration of one embodiment to another embodiment, or omit part of the configuration of one embodiment.

[0149] For example, in the Villermaux-Dushman reaction for evaluating the mixing performance of a microreactor, an aqueous solution of sulfuric acid other than hydrochloric acid may be used as the aqueous solution of a strong acid. Furthermore, an aqueous solution of boric acid other than acetic acid may be used as the buffer solution. Sodium hydroxide or the like may be used as the strong base. For measuring pressure loss, ethanol, an aqueous ethanol solution, or the like may be used instead of pure water.

[0150] Although the pressure loss measurement system 3 described above is configured to measure one microreactor, it may be configured to measure multiple microreactors. For example, the multiple microreactors can be connected in parallel between the first pressure sensor 306 and the second pressure sensor 307 and the collection container 303 via the connection portion 312.

[0151] The pressure loss measurement system 3 may also be provided with a mechanism for removing fluid from inside the microreactor 1. For example, a gas injection device for injecting compressed air, nitrogen gas, or the like into the microreactor 1 can be connected to the connection part 312 upstream of the upstream inlet 107 or the connection part 312 upstream of the downstream inlet 108. A device for rotating the microreactor 1 at high speed and removing liquid by centrifugal force can also be provided in the pressure loss measurement system 3.

[0152] REFERENCE SIGNS LIST 1 Microreactor 3 Pressure loss measurement system 101 Upper plate 102 Lower plate 103 Upstream inlet flow channel (microchannel) 104 Downstream inlet flow channel (microchannel) 105 Mixing flow channel (microchannel) 106 Confluence 107 Upstream inlet (through-hole) 108 Downstream inlet (through-hole) 109 Outlet (through-hole) 301 First container 302 Second container 303 Recovery container 304 First pump 305 Second pump 306 First pressure sensor 307 Second pressure sensor 308 First switching valve 309 Second switching valve 310 Control unit 311 Analysis unit 312 Connection unit 313 Signal line

Claims

1. A microreactor having two inlets through which fluids are introduced, a flow path through which the fluids are joined and flow, and an outlet through which the joined fluids are discharged, wherein a first fluid introduced from one of the inlets and a second fluid introduced from the other of the inlets are mixed in the flow path and the mixed fluid is discharged from the outlet, wherein the flow path has a structure in which a portion downstream from a junction where the first fluid and the second fluid join is extended in a straight line, and wherein the pressure loss in the flow path from the junction to the outlet is greater than the pressure loss in the flow path from one of the inlets to the junction and the pressure loss in the flow path from the other inlet to the junction.

2. A microreactor according to claim 1, wherein the length of the flow path from one of the inlets to the confluence is longer than the length of the flow path from the other of the inlets to the confluence.

3. A microreactor according to claim 2, wherein at least one of the pressure loss in the flow path from one of the inlets to the outlet and the pressure loss in the flow path from the other of the inlets to the outlet is measured, and the mixing performance of each individual microreactor is evaluated based on the correlation between the measured pressure loss in the flow path and the mixing performance for mixing the first fluid and the second fluid, which is determined in advance for a microreactor of the same type.

4. A microreactor according to claim 3, wherein the mixing performance of the first fluid and the second fluid is quantitatively measured as the absorbance of triiodide ions, which are products of the Villermaux-Dushman reaction, by carrying out the Villermaux-Dushman reaction using the same type of microreactor.

5. A microreactor according to any one of claims 1 to 4, wherein the pressure loss in the flow path is the pressure loss when pure water is introduced as the first fluid and the second fluid.

6. A microreactor according to any one of claims 1 to 4, wherein the microreactor is connected via piping to: a first container in which the first fluid is prepared; a second container in which the second fluid is prepared; a recovery container for recovering fluids discharged from the outlet; a pump for sending at least one of the first fluid and the second fluid to the inlet; and a pressure sensor for measuring the pressure of the fluids upstream of the inlet; a control unit for controlling the operation of the pump is connected via wiring to the pump; and an analysis unit for receiving the measurement results from the pressure sensor and measuring the pressure loss in the flow path is connected via wiring to the pressure sensor; and at least one of the pressure loss in the flow path from one inlet to the outlet when the first fluid is introduced and the pressure loss in the flow path from the other inlet to the outlet when the second fluid is introduced is measured.

7. A microreactor according to any one of claims 1 to 4, wherein the flow rate of the first fluid introduced from one of the inlets and the flow rate of the second fluid introduced from the other of the inlets are used under conditions such that the pressure loss in the flow path is equal to or greater than a lower limit value, and the lower limit value is set so that the absorbance of triiodide ions, which are products of the Villermaux-Dushman reaction, is equal to or less than a predetermined threshold value.

8. A method for evaluating the mixing performance of a microreactor for evaluating the mixing performance of mixing fluids for each individual microreactor, wherein the microreactor has two inlets into which fluids are introduced, a flow path through which the fluids are joined and flow, and an outlet through which the joined fluids are discharged, a first fluid introduced from one of the inlets and a second fluid introduced from the other of the inlets are mixed in the flow path, and the mixed fluid is discharged from the outlet, the flow path has a structure in which a portion downstream from a junction where the first fluid and the second fluid join is extended linearly, the pressure loss in the flow path from the junction to the outlet is greater than the pressure loss in the flow path from one of the inlets to the junction and the pressure loss in the flow path from the other inlet to the junction, and at least one of the pressure loss in the flow path from one of the inlets to the outlet and the pressure loss in the flow path from the other inlet to the outlet is measured, A method for evaluating the mixing performance of a microreactor, which evaluates the mixing performance of each individual microreactor based on a correlation between the measured pressure loss of the flow path and the mixing performance of mixing the first fluid and the second fluid, which is determined in advance for the same type of microreactor.

9. A method for evaluating the mixing performance of a microreactor according to claim 8, wherein the mixing performance of the first fluid and the second fluid is quantitatively measured as the absorbance of triiodide ions, which are products of the Villermaux-Dushman reaction, by carrying out the Villermaux-Dushman reaction using the same type of microreactor.

10. A method for evaluating the mixing performance of a microreactor according to claim 8 or claim 9, wherein the pressure loss in the flow path is the pressure loss when pure water is introduced as the first fluid and the second fluid.

11. A method for evaluating the mixing performance of a microreactor according to claim 8 or 9, wherein the microreactor is connected via piping to: a first container in which the first fluid is prepared; a second container in which the second fluid is prepared; a recovery container for recovering fluids discharged from the outlet; a pump for sending at least one of the first fluid and the second fluid to the inlet; and a pressure sensor for measuring the pressure of the fluids upstream of the inlet, and the method performs at least one of the following operations: sending the first fluid prepared in the first container to one of the inlets, measuring the pressure of the first fluid, and then recovering the first fluid discharged from the outlet in the recovery container; and sending the second fluid prepared in the second container to the other inlet, measuring the pressure of the second fluid, and then recovering the second fluid discharged from the outlet in the recovery container.

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