Micro flow channel device and test system

Abstract

To provide a technique of improving accuracy of measuring a temperature in a micro flow channel device.SOLUTION: A micro flow channel device includes a first flow channel part having a first liquid reservoir which reserves a sample, a first partition valve which partitions the first liquid reservoir, and a temperature sensor, where the first partition valve includes: a fixed valve part which is fixed to the first flow channel part, and blocks a flow channel of a part of the first flow channel part; and a movable valve part which moves from a residual flow channel portion formed by excluding the partial flow channel from the first flow channel part to form an opening part, the fixed valve part has an insertion part which fixes the temperature sensor, the temperature sensor is a linear sensor having at least one measuring point, and a first measuring point of the temperature sensor is arranged for the first liquid reservoir by the insertion part provided for the fixed valve part.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a microfluidic device and a test system. [Background technology]

[0002] A microfluidic chip is a component with tiny channels formed on a substrate such as a glass substrate, and is a device that enables the mixing and distribution of liquids and particles in the liquids flowing through the channels. Microfluidic chips have the advantage of not requiring the preparation of large amounts of test samples, and are used in applications such as chemical reactions, genetic testing, and drug discovery.

[0003] To understand phenomena occurring within a flow channel, precise temperature control of the solvent in the flow channel is required. For example, Patent Document 1 addresses the problem of conventional microfluidic technology: "Conventional temperature sensors are typically relatively large, so they can only detect temperatures within a relatively large area of ​​a microfluidic chip and cannot accurately monitor the temperature of microdroplets as they move across a microfluidic substrate." The invention, "a microfluidic substrate, a method for manufacturing the same, a microfluidic chip, and a control method," discloses the following: "The microfluidic chip includes a microfluidic substrate including a first substrate, a microdroplet driver provided on the first substrate, and a temperature detector. The microdroplet driver includes a first electrode layer having a plurality of control electrodes, each of which is configured as part of a drive unit that drives the microdroplets to move along a predetermined path on the microfluidic substrate. The temperature detector includes at least one temperature sensor. The at least one temperature sensor is provided at a position corresponding to the plurality of control electrodes, and each temperature sensor is configured to detect the temperature at a position associated with one of the plurality of control electrodes." Specifically, Patent Document 1 describes forming an N-type layer of amorphous silicon doped with phosphorus and an N-type layer of amorphous silicon doped with boron on a microfluidic substrate, then performing a patterning process to form multiple PN junctions, and measuring the voltage at the PN junctions to detect the temperature. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] Special Publication No. 2020-531239 Summary of the Invention [Problem to be solved by the invention]

[0005] In Patent Document 1, the locations where temperature is detected are limited to locations where PN junctions are formed, making it difficult to accurately measure temperature in locations where no PN junctions are present. Also, if PN junctions are to be placed at each location where temperature is to be measured, the microchannel device must be designed according to the application scenario, which is costly. Therefore, an object of the present invention is to provide a technique for improving the accuracy of measuring the temperature in a microchannel device. [Means for solving the problem]

[0006] In order to solve the above-mentioned problems, one representative microchannel device of the present invention is a microchannel device including a first channel section having a first liquid reservoir section for storing a sample, a first partition valve that partitions the first liquid reservoir section, and a temperature sensor, wherein the first partition valve includes a fixed valve section that is fixed to the first channel section and blocks a part of the channel of the first channel section, and a movable valve section that moves from a part of the channel of the first channel section excluding the part of the channel to form an opening, the fixed valve section has an insertion section that fixes the temperature sensor, the temperature sensor is a linear sensor having at least one measurement point, and the first measurement point of the temperature sensor is positioned in the first channel section by the insertion section provided on the fixed valve section. [Effects of the Invention]

[0007] According to the present invention, it is possible to improve the accuracy of measuring the temperature in a microchannel device. Problems, configurations, and effects other than those described above will become apparent from the following description of the preferred embodiment of the invention. [Brief explanation of the drawings]

[0008] [Figure 1] FIG. 1 is a diagram showing an example of the configuration of a microchannel device. [Figure 2] FIG. 2 is a diagram illustrating an example of the configuration of the partition valve. [Figure 3] FIG. 3 is a diagram showing a schematic configuration of the block portion 100a and the block portion 100b. [Figure 4] FIG. 4 is a diagram showing another example of the joint structure. [Figure 5] Figure 5 is a table showing the materials used for the housing and their advantages and disadvantages. [Figure 6] FIG. 6 is a diagram showing an example of a beer production process. [Figure 7] FIG. 7 is a diagram showing an example of a test system using a microfluidic device. [Figure 8] FIG. 8 is a diagram showing an example of the decomposition reaction of maltose. [Figure 9] FIG. 9 is a flowchart showing a method for controlling the test system. [Figure 10] FIG. 10 is a diagram showing an example of a temperature pattern in a general mashing process. [Figure 11] FIG. 11 is a diagram showing an example of a test system using a microfluidic device. [Figure 12] FIG. 12 is a flowchart showing a method for controlling the test system. [Figure 13] FIG. 13 is a diagram for explaining a control method of the partition valve. [Figure 14] FIG. 14 is a diagram showing an example of the set time when the temperature pattern of FIG. 10 is applied to a test system. [Figure 15] FIG. 15 is a diagram showing a schematic diagram of a case where the temperature pattern of FIG. 14 is applied to a test system. [Figure 16] FIG. 16 is a diagram showing an example of the configuration of a test system when yeast is added. [Figure 17] FIG. 17 is a diagram showing another example of the configuration of the yeast addition port and the aeration port. [Figure 18] FIG. 18 is a diagram showing an example of a combination of microchannel devices when treating one type of wort with a plurality of temperature patterns. [Figure 19] FIG. 19 is a diagram showing an example of a combination 360 of microfluidic devices when performing a process of adding a plurality of yeasts. [Figure 20] FIG. 20 is a diagram showing an example of a test system configured by combining the microchannel devices shown in FIGS. [Figure 21] FIG. 21 is a diagram showing an example of a test when the test system is used. [Figure 22] FIG. 22 is a diagram showing an example of the configuration of a microfluidic device when performing a process for determining the state of maltose. [Figure 23] FIG. 23 is a diagram showing an example of a test system configured by combining the microchannel devices shown in FIGS. [Figure 24] FIG. 24 is a diagram showing an example of the set time when a test system is used. [Figure 25] FIG. 25 is a diagram showing an example of a configuration in which a test system is applied to a manufacturing line. DETAILED DESCRIPTION OF THE INVENTION

[0009] Hereinafter, an embodiment of the present invention will be described with reference to the drawings. Note that the present invention is not limited to this embodiment. In addition, in the description of the drawings, the same parts are designated by the same reference numerals.

[0010] When there are multiple components with the same or similar functions, they may be described using the same reference numeral with different subscripts. When there is no need to distinguish between these multiple components, the subscripts may be omitted. Furthermore, in order to facilitate understanding of the invention, the position, size, shape, range, etc. of each component shown in the drawings may not represent the actual position, size, shape, range, etc. Therefore, the present invention is not necessarily limited to the position, size, shape, range, etc. disclosed in the drawings. Furthermore, the length in the vertical direction may be referred to as the “height.” Furthermore, when the flow path structure is placed, the portion located at the lower side in the vertical direction may be referred to as the “bottom.”

[0011] [First embodiment] (Example of a microfluidic device configuration) A microchannel device according to a first embodiment will be described with reference to FIGS. 1 to 5. FIG. 1 is a diagram showing an example of the configuration of a microchannel device 100. FIG. 1(a) is a schematic cross-sectional view of the microchannel device 100 taken along a cross section including a channel section, and FIG. 1(b) shows a block section included in the microchannel device 100. FIG. 1(a) shows the microchannel device 100 placed on a horizontal surface, with the negative z-axis direction indicating the direction of gravity (vertical direction). The microchannel device 100 includes a first channel section (channel section 1a) having a first liquid reservoir section (liquid reservoir section 11a) for storing a sample, a first partition valve (partition valve 13a) that partitions the first liquid reservoir section, and a temperature sensor 30. The first partition valve (partition valve 13a) is fixed to the first channel section (channel section 1a) and has a fixed valve section 13b that blocks a part of the channel of the first channel section (channel section 1a). fi and a movable valve unit 13 that moves from the remaining part of the first microchannel portion (channel portion 1a) except for the part of the channel and forms an opening. mo The fixed valve portion 13 fi The temperature sensor 30 is fixed to the insertion portion 13. inThe temperature sensor 30 is a linear sensor having at least one measurement point, and the first measurement point of the temperature sensor 30 is disposed in the first liquid reservoir (liquid reservoir 11a). A specific description will be given below. Note that the following description will be given mainly using the block portion 100a as an example, but it can also be applied to other block portions.

[0012] (Block section) As shown in FIG. 1(b), the microchannel device 100 includes a block portion 100a (channel portion (first channel portion) 1a, partition valve (first partition valve) 13a, and housing portion (first housing portion) 20a), a block portion 100b (channel portion (second channel portion) 1b, partition valve (second partition valve) 13b, and housing portion (second housing portion) 20b), a block portion 100c (channel portion (third channel portion) 1c, partition valve (third partition valve) 13c, and housing portion (third housing portion) 20c), and a block portion 100d (channel portion (fourth channel portion) 1d, partition valve (fourth partition valve) 13d, and housing portion (fourth housing portion) 20d). While the present disclosure will be described with four block portions, the present disclosure is not limited to this. It is also possible to add other block structures using a joint structure (described later) to set the length of the channel 10 depending on the processing to be performed on the sample.

[0013] The microchannel device 100 has a channel 10 formed in a housing 20, and the channel 10 includes channel portions 1a to 1d. Channel portion 1a includes a liquid reservoir portion 11a and an inclined portion 12a connected to the liquid reservoir portion 11a. The liquid reservoir portion 11a and the inclined portion 12a are separated by a partition valve 13a. When the direction of sample movement in the microchannel device 100 (the positive direction of the x-axis) is defined as the movement direction, the inclined portion 12a has a shape that extends vertically downward toward the movement direction. Similarly, channel portion 1b includes liquid reservoir portion 11b and inclined portion 12b, channel portion 1c includes liquid reservoir portion 11c and inclined portion 12c, and channel portion 1d includes liquid reservoir portion 11d and inclined portion 12d. To make it easier to distinguish between the flow path sections, for example, the boundary between the inclined portion 12a of flow path section 1a and the liquid reservoir portion 11b of flow path section 1b is shown with a solid line, but in reality, there is nothing at the boundary that would hinder the movement of the sample. The boundaries between the other flow path sections are also shown with solid lines. The structure of the housing section will be described later. Furthermore, while the liquid reservoir portion is shown with a square cross section, it is sufficient that it has a structure that allows the sample to be stored. For example, it may have a structure in which the flow area expands in the y-axis direction and a structure with a depression in the negative z-axis direction.

[0014] To explain the flow path section in relation to the housing 20, flow path section 1a is a flow path formed inside housing section 20a and separated from the outside by housing section 20a. Housing section 20a may be composed of a single member or may be composed of multiple members. Similarly, flow path section 1b is a flow path separated from the outside by housing section 20b, flow path section 1c is a flow path separated from the outside by housing section 20c, and flow path section 1d is a flow path separated from the outside by housing section 20d. Housing 20 includes housing sections 20a to 20d. Housing sections 20a to 20d may have a common configuration, or each block section may have a different configuration.

[0015] The temperature sensor 30 is a linear sensor having multiple measurement points (measurement units 30a to 30e) and is capable of measuring the temperature of the sample in the liquid reservoirs 11a to 11e. The measurement units 30a to 30e are formed on the linear main body of the temperature sensor 30 at intervals corresponding to the intervals between the liquid reservoirs 11a to 11e. Here, a case will be described in which the temperature sensor 30 is inserted into the microchannel device 100 from the positive side of the x-axis, but the present disclosure is not limited to this case. The temperature sensor 30 can also be placed in the microchannel device 100 from the negative side of the x-axis.

[0016] (Partition valve) Next, the partition valve will be described with reference to Fig. 2. Fig. 2 is a diagram showing an example of the configuration of the partition valve. The partition valve 13a is a fixed valve portion 13 fi and movable valve section 13 mo The fixed valve portion 13 fi Insert 13 in The insertion portion 13 is formed. in The insertion portion 13 has a shape that allows the temperature sensor 30 to pass through, and has a structure that blocks the flow of the sample when the temperature sensor 30 is placed. in The insertion portion 13 has a check valve structure, and when forming the microchannel device 100, the temperature sensor 30 can be inserted from the negative x-axis direction and fixed. in After the temperature sensor 30 is placed on the sample, it is possible to prevent the sample from moving in the positive direction of the x-axis. As shown in FIG. 1(a), the temperature sensor 30 is placed so that it tilts in the negative direction of the z-axis as it moves in the positive direction of the x-axis. The insertion part 13 is provided so that the temperature sensor 30 as a whole can easily tilt. in is a fixed valve part 13 fiIt is desirable that the temperature sensor 30 is formed at a position below (in the negative z-axis direction) the partition valve 13a. Furthermore, since the sample accumulates on the partition valve 13a side, it is desirable that the measurement unit 30a be positioned close to the partition valve 13a so that the measurement point of the temperature sensor 30 is in sufficient contact with the sample. The temperature sensor 30 and the inclined structure will be described in detail later. The following explanation will be given using the partition valve 13a as an example, but the other partition valves 13b to 13e also have the same configuration as the partition valve 13a.

[0017] FIG. 2(a) shows the state in which the partition valve 13a is closed (closed state). The flow path portion 1a is indicated by a dashed line. The fixed valve portion 13 fi and the movable valve portion 13 mo have roughly the same area, and the fixed valve portion 13 fi and the movable valve portion 13 mo When these are integrated together, they function as a shielding portion having an area larger than the cross section of the flow path portion 1a. fi and the movable valve portion 13 mo blocks the sample present in flow path section 1a from moving to flow path section 1b on the downstream side.

[0018] On the other hand, FIG. 2(b) shows a state in which the partition valve 13a is open (open state). fi Since the movable valve unit 13 is fixed to the flow path portion 1a, its position does not change and it blocks a part of the flow path of the flow path portion 1a. mo has moved from the remaining part of the flow path of the flow path portion 1a, and an opening op that connects the flow path portion 1a to the downstream flow path portion 1b is formed at the location of the partition valve 13a.

[0019] Such a fixed valve portion 13 fi and movable valve section 13 mo By combining these to form the partition valve 13a, it becomes possible to control the movement of the sample in the flow channel 10 without changing the position of the temperature sensor 30. mo For example, a solenoid valve can be applied to the valve, and the solenoid valve can be switched between an open state and a closed state by a drive mechanism.

[0020] The temperature sensor 30 is inserted into the insert 13 of the partition valves 13a to 13e. in The temperature sensor 30 is disposed in the flow channel 10 of the microchannel device 100 by the connector 15. The temperature sensor 30 has a plurality of measurement points and can measure the temperatures at the liquid reservoirs 11a, 11b, 11c, and 11d. The measured values ​​of the temperature sensor 30 are output via the connector 15 to a measuring instrument, which will be described later.

[0021] A sample introduced into the microchannel device 100 is introduced into the channel section 1a and is stored in the liquid reservoir section 11a while the channel section 1a is blocked by the partition valve 13a, which will be described later. The measurement point of the temperature sensor 30 is located in the channel section 1a, and the temperature of the sample in the liquid reservoir section 11a is measured. After a predetermined process is performed and the partition valve 13a is opened, the sample flows through the inclined section 12a to the channel section 1b, which is located on the vertically downward (negative z-axis) side of the channel section 1a. Similarly, the sample is stored in the channel section 1b to the channel section 1d, and the predetermined process is performed on the sample.

[0022] (Temperature sensor) The temperature sensor 30 can be, for example, an FBG (Fiber Bragg Grating) sensor or an MP (Multi-Point) sensor. An FBG sensor is a sensor in which a diffraction grating structure with a variable refractive index is formed in the core portion of an optical fiber. In the case of an FBG sensor, the measurement units 30a to 30e correspond to the portion of the optical fiber in which the diffraction grating structure is formed. Temperature can be measured by detecting changes in the refractive index in the diffraction grating structure caused by temperature changes. An MP sensor is a sensor in which multiple thermocouples are bundled together to form a tubular structure, enabling temperature measurement at multiple locations. Both the FBG sensor and the MP sensor have a linear shape.

[0023] The position of the diffraction grating structure or the thermocouple must correspond to the measurement position of the temperature sensor 30, so it must be formed at a predetermined position on the temperature sensor. Furthermore, because distortion of both the FBG sensor and the MP sensor affects the measurement results, it is necessary to suppress distortion of the temperature sensor 30 within a predetermined range when they are placed in the microfluidic device 100. As shown in FIG. 1(a), in the microfluidic device 100, the angle between the inclined portion 12a and the inclined portion 12d and the line extending in the x-axis direction is defined as θ1, and the angle between the temperature sensor 30 and the line extending in the x-axis direction is defined as θ2. Furthermore, the length from the inclined portion 12a to the inclined portion 12d (equal to the length of the flow channel surface extending in the negative z-axis direction at an angle θ1 from the positive x-axis direction) is defined as a, and the length from the liquid reservoir 11a to the liquid reservoir 11d (length in the x-axis direction) is defined as b. Furthermore, the length of the temperature sensor 30 between the partition valves is defined as r. In this case, the relationship shown in Equation (1) holds. The measurement point of the temperature sensor 30 is set so as to satisfy the relationship of formula (1), and the inclination angle of the flow channel in the microchannel device 100 is formed. Note that in the present disclosure, the case is described in which the inclined portions 12a to 12d have the same length and inclination angle, and the liquid reservoir portions 11a to 11d have the same length.

number

[0024] By utilizing a temperature sensor with multiple measurement points in this way, it becomes possible to measure the temperature at multiple locations, and it becomes possible to control the sample temperature within a specified range using multiple liquid reservoirs.

[0025] (joint structure) Next, the joint structure of the microchannel device will be described with reference to Figures 3 and 4. Figure 3 is a diagram showing a schematic configuration of block portion 100a and block portion 100b. Figure 3(a) shows a schematic cross-sectional view of the block portion, and Figure 3(b) shows a perspective view of the block portion. To facilitate understanding, the joint structure between block portion 100a and block portion 100b is shown in particular, and a description of the other structures will be omitted.

[0026] The housing portion 20a of the block portion 100a has a first joint portion 20a1 formed around the inclined portion 12a. The housing portion 20b of the block portion 100b has a second joint portion 20b2 that fits into the first joint portion 20a1. By fitting the first joint portion 20a1 and the second joint portion 20b2 together, the block portion 100a and the block portion 100b are joined, connecting the flow path portion 1a and the flow path portion 1b. While the first joint portion 20a1 has a convex shape and the second joint portion 20b2 has a concave shape, and an insertion-type joint structure has been described, the present disclosure is not limited to this. The joint structure may be a butt-type, or a structure in which the joint is sealed with a flange-like member in addition to the two block portions may be used.

[0027] Figure 4 shows another example of a joint structure. If the flow paths are not joined properly at the joint, there is a risk of sample leakage from the flow path. Figure 4(a) shows a more preferable case from the viewpoint of preventing leakage, and Figure 4(b) shows a structure for comparison with Figure 4(a).

[0028] FIG. 4(a) shows the case where the block part 100x (liquid reservoir part 11xa, inclined part 12xa, casing part 20x, first joint part 20x1) and the block part 100xx (liquid reservoir part 11xxa, casing part 20xx, second joint part 20xx2) are joined. In the state before joining shown in FIG. 4(a)(1), the liquid reservoir part 11xxa is positioned vertically downward (in the negative z-axis direction) from the liquid reservoir part 11xa. When comparing the vertically downward part (bottom) of the liquid reservoir part 11xxa and the liquid reservoir part 11xa, they are separated by a length (height) h1 in the vertical direction. In the joined state shown in FIG. 4(a)(2), when the first joint portion 20x1 and the second joint portion 20xx2 are fitted together, the liquid reservoir portion 11xa is connected to the liquid reservoir portion 11xxa via the inclined portion 12xa. 4(b) shows a case where block portion 100y (liquid reservoir portion 11ya) and block portion 100yy (liquid reservoir portion 11yya) are joined together. Liquid reservoir portion 11ya and liquid reservoir portion 11yya have the same bottom position in the vertical direction and are arranged at the same position (height).

[0029] Here, if it were possible to form the liquid pools 11ya and 11yya at almost the same height in the vertical direction as shown in Figure 4(b), sample leakage would not occur, but in reality, forming them at the same height with precision would be costly. In contrast, when the liquid reservoirs are connected via the inclined portion 12xa as shown in Figure 4(a), the sample moves downstream at an increased speed due to the inclination of the inclined portion 12xa, thereby shortening the period of time the sample remains at the joint, and as a result, the condition in which leakage from the joint may occur can be quickly eliminated.

[0030] (Housing configuration) Next, the configuration of the housing 20 will be described with reference to Fig. 5. Fig. 5 is a table showing materials used for the housing 20 and their advantages and disadvantages. Note that the following description will focus on the housing 20, and will also cover the case where the housing sections 20a to 20e have the same configuration as the housing 20.

[0031] The main materials used for the housing 20 include PDMS (Polydimethylsiloxane), glass, and cyclic olefin resins (COC (Cyclic Olefin Copolymer), COP (Cyclic Olefin Polymer), etc.).

[0032] The advantages of PDMS are that it is relatively easy to prototype and that the cost of the PDMS component (e.g., per sheet) is low.The disadvantages are that water evaporation occurs, protein adsorption occurs, PCR (Polymerase Chain Reaction) is inhibited, and mechanical strength is weak. The advantages of glass include high corrosion resistance, heat resistance, good processing precision, and durability, while the disadvantages include the high cost per glass sheet, the high cost of prototypes and custom products, and the possibility of breakage. The advantages of cyclic olefin resins (COC, COP, etc.) include the ability to mass-produce them at low cost when molding devices, their suitability for disposable applications, higher dimensional stability than PDMS, high water vapor barrier properties, rigidity, and low autofluorescence.

[0033] When the temperature used in the microchannel device 100 is 100° C. or less, any material can be used, but it is preferable to use glass, which poses few problems in terms of processing precision of joint structures and heat resistance.

[0034] (Method for producing a microfluidic device) Next, a method for fabricating a microchannel device using glass will be described. The method for fabricating a microchannel device can be any of photolithography, inkjet printing, printing, etching, transfer printing, molding, or a combination of these methods, but is not limited to these methods.

[0035] Specifically, a resist coating process is performed first. Next, a glass substrate is prepared as the substrate for forming the bottom of the housing 20. A photosensitive composition is then coated onto the glass substrate and prebaked. The photosensitive resin contains a photoinitiator, a polymerizable monomer, and an appropriate solvent, and is patterned by utilizing the property that the photopolymerization reaction proceeds when irradiated with appropriate light, making the resin alkali-insoluble. Spin coating, dip coating, die coating, and other methods are typically used to apply this photosensitive resin. However, any method is not limited to these, as long as it can be applied to a substrate approximately 40 to 60 cm square with a uniform film thickness. Furthermore, prebaking is preferably performed by heating at a temperature of 50 to 120°C for approximately 1 to 5 minutes.

[0036] Next, an exposure step is performed. In the exposure step, the photosensitive composition coated on the glass substrate is exposed to light through a photomask. A typical high-pressure mercury lamp or the like is used as the light source.

[0037] Next, a development step is carried out. An alkaline aqueous solution is used as the developer. Examples of alkaline aqueous developers include an aqueous sodium carbonate solution, an aqueous sodium bicarbonate solution, or a mixture of these, and further, an aqueous solution to which an appropriate surfactant or the like has been added is used. After development, the substrate is washed with water and dried to obtain a flow path pattern of any single color.

[0038] Next, the lid formation process is carried out. The fabricated flow channel pattern has an open top (positive z-axis direction), so a lid is attached to form a small enclosed space. An acrylic resin substrate (hereinafter referred to as "acrylic substrate") can be used as the lid substrate. The glass and acrylic substrates are placed face-to-face and bonded together. Bonding methods include adhesives, press bonding with surface modification, thermal fusion bonding, and ultrasonic bonding. The method is determined by the compatibility and resistance of the substrates and materials used. Here, a bonding method using surface modification is used, where the glass and acrylic substrates are irradiated with ultraviolet light or plasma to render the surfaces hydrophilic, and then bonded together under heat and pressure to create a sealed flow channel device.

[0039] In the exposure step, it is possible to give a slope to the flow path by using a so-called gray-tone mask (half-tone mask) that has a semi-light-shielding portion, and thus the slope portion 121 can be formed.

[0040] (Actions and Effects) In the microchannel device 100, the temperature sensor 30 can be inserted into the channel 10, and a measurement point can be placed at a predetermined position such as a liquid reservoir. Since the temperature measurement position can be set at a desired position in the microchannel device, the accuracy of temperature measurement in the microchannel device 100 can be improved. Furthermore, by adding or removing blocks, the length of the channel 10 can be changed depending on the treatment to be performed on the sample. In this case, the temperature sensor 30 can also be placed in the channel after the channel is formed. Since it is not necessary to create a device for each treatment to be performed on the sample, it is possible to reduce costs when using a microchannel device.

[0041] [Second embodiment] In the second embodiment, a case where the microchannel device is applied to beer production will be described. In the following description, components that are the same as or equivalent to those in the first embodiment will be given the same reference numerals, and their description will be simplified or omitted.

[0042] (Problems in the beer production process) A typical beer production process will be described with reference to Fig. 6. Fig. 6 is a diagram showing an example of the beer production process. The beer production process is roughly divided into malt production (step S1), mashing (step S2), and fermentation (step S3). First, in malt production (step S1), beer barley is sorted and selected through a sorting machine, then placed in a steeping tank where it is washed and given the water needed for germination. After steeping, the barley is transferred to a germination device where it is germinated while being ventilated and the humidity and temperature are controlled. The germinated barley is then roasted, rooted, and refined to produce malt. Next, in the mashing step (step S2), malt crushed in a malt mill is mixed with water and auxiliary ingredients (rice, corn, cornstarch, etc.) to make wort. Hops are added to the filtered wort, which is then boiled and cooled to produce cold wort. In the fermentation step (step S3), yeast is added to the cooled wort to ferment it. The fermentation is then carried out, followed by storage and filtration. Further, depending on the subsequent steps, finished beer is produced.

[0043] During the mashing process (step S2), the starch contained in the malt and other ingredients is converted into sugars by the action of amylase, an enzyme contained in malt. Amylases are classified as α-amylase and β-amylase, with α-amylase and β-amylase being most active at approximately 73°C and 63°C, respectively. α-amylase randomly cleaves the starch chains to produce oligosaccharides, while β-amylase cleaves the sugar chains of starch and oligosaccharides two at a time from the end to produce maltose. If the saccharification process is gradually brought to a final temperature of, for example, 75°C, the inactivation of β-amylase cannot be adequately controlled, resulting in inadequate degradation of oligosaccharides. Oligosaccharides are not degraded by the yeast added during the subsequent fermentation process (step S3), which affects the flavor of the beer.

[0044] In addition, alcohol is produced by adding yeast in the fermentation (step S3). Yeast grows by supplying oxygen (aeration), but if the supply of oxygen is too little or too much, there is a risk that the appropriate amount of alcohol will not be produced.

[0045] Regarding brewing and fermentation, it is necessary to set the appropriate production conditions by measuring the set temperature and the products. Traditionally, when developing a new beer, a trial production was carried out using large amounts of malt and wort. If the appropriate production conditions cannot be found, there is a risk that a large amount of malt and wort will be wasted.

[0046] In contrast, it is desirable to first conduct tests using a small amount of material to determine production conditions and then expand the scale of production. In the second embodiment, we first consider configuring a system for testing saccharification and fermentation using a microfluidic device, and then transitioning to a full-scale production process using the conditions set there and the data obtained. In other words, this method involves first using a microfluidic device to create various profiles reflecting the characteristics of the wort and yeast, and then incorporating these into the full-scale production process. When using a microfluidic device, it is possible to virtually perform the production process using a small amount of wort, and it is expected that heating time will be shortened, making it possible to obtain test results in a short time. Furthermore, it is possible to configure production processes in parallel for multiple production conditions as needed, making it easy to compare production conditions.

[0047] (First application example of a microfluidic device) A first application example in which a microchannel device is used in a beer production process will be described with reference to Figures 7 to 9. Figure 7 is a diagram showing an example of a test system using a microchannel device.

[0048] The test system 200A includes a microchannel device 100A, a heater 40, a cooler 41, thermostats 441 and 442, a measuring instrument 50, and a control device 60. In the microchannel device 100A, the liquid reservoir 111 and the liquid reservoir 112 are connected by the joint structure shown in the first embodiment.

[0049] Temperature sensor 30 is disposed in microchannel device 100A by partition valves 131 and 132. Furthermore, measurement unit 301 is disposed in liquid reservoir 111, and measurement unit 302 is disposed in liquid reservoir 112. Therefore, temperature sensor 30 can measure the temperatures in liquid reservoir 111 and liquid reservoir 112. Data acquired by temperature sensor 30 is sent to measuring instrument 50.

[0050] The liquid reservoir 111 is in a state where it is heated by a heater 40, and the heater 40 is controlled by a thermostat 441. Similarly, the liquid reservoir 112 is in a state where it is cooled by a cooler 41, and the cooler 41 is controlled by a thermostat 442.

[0051] The liquid reservoir 112 is provided with an electrochemical sensor 43 and an enzyme 45. The electrochemical sensor 43 measures the state of the sample (wort) in the liquid reservoir 112. The electrochemical sensor 43 may be, for example, a chip-shaped sensor equipped with multiple electrodes (such as the IC chip 11 disclosed in Japanese Patent Application Laid-Open No. 2013-92437). Maltase and glucose oxidase are used as the enzyme 45. FIG. 8 shows an example of the decomposition reaction of maltose. Maltase decomposes maltose to generate glucose. Glucose oxidase generates hydrogen peroxide from glucose. The state of maltose can be determined by measuring the hydrogen peroxide generated by the electrochemical sensor 43. The hydrogen peroxide reacts with peroxidase in the presence of ADHP (10-acetyl-3,7-dihydroxiphenoxazine) to generate resorufin. Detection of fluorescence generated from resorufin may be applied to the present disclosure to measure the state of wort.

[0052] The control device 60 controls the partition valves 131 and 132 to switch between an open state and a closed state. The control device 60 can also obtain temperatures based on data obtained by the measuring instrument 50 and control the temperatures in the liquid reservoirs 111 and 112 by controlling the thermostats 441 and 442.

[0053] FIG. 9 is a flowchart showing a control method for the test system 200A. First, in step S10, the temperatures of the heater 40 and the cooler 41 are set. Because saccharification in the mashing process occurs in the liquid reservoir 111, a temperature pattern is set for the heater 40 that specifies the activation temperature for α-amylase, the activation temperature for β-amylase, the temperatures at which α-amylase and β-amylase are inactivated, and the duration for which these temperatures are maintained. Furthermore, a temperature pattern is set for the cooler 41 that specifies the temperature and cooling time appropriate for determining the state of maltose. The temperature and time according to these temperature patterns are set in the control device 60.

[0054] Next, after wort is introduced into the liquid reservoir 111, the temperature of the liquid reservoir 111 is controlled. In step S11, the temperature of the liquid reservoir 111 is detected. The thermostat 441 is operated to control the temperature of the liquid reservoir 111 in accordance with the temperature pattern. Saccharification is allowed to proceed in the wort stored in the liquid reservoir 111.

[0055] Next, in step S12, the partition valve 131 is controlled according to the temperature pattern. After saccharification according to the temperature pattern is performed, the control device 60 switches the partition valve 131 to an open state. The wort is filtered by the filter 42 and then moves to the liquid reservoir 112.

[0056] Next, in step S13, the detection value of the electrochemical sensor 43 is acquired. The state of maltose is determined from the acquired detection value, and the degree of saccharification is evaluated. Note that, since the measurement accuracy of the electrochemical sensor 43 can be improved when the wort is highly clear, the filtration rating of the filter 42 may be set according to the purpose of analysis.

[0057] (Actions and Effects) It is possible to compare saccharification through multiple mashing processes by changing the composition of the ingredients used (malt, water, auxiliary ingredients, etc.), the temperature pattern settings, etc. Also, since the temperature of the liquid reservoir where saccharification is taking place can be measured directly, highly accurate temperature control is possible. Although it may be possible to use near-infrared light to obtain the temperature of the microchannel device from the outside, the necessary equipment would be costly and this method would not be suitable for a test system using a microchannel device.

[0058] (Second application example of microfluidic device) Next, a second application example in which the microchannel device is applied to a beer production process will be described with reference to Figures 10 to 13. Figure 10 is a diagram showing an example of a temperature pattern in a general brewing process. The temperature pattern in Figure 10 is applied to temperature control of a storage tank that stores wort, and can also be applied to test system 200A that uses the microchannel device in Figure 7, for example.

[0059] In period pp, the temperature is set to 50°C, and the wort undergoes a protein rest. In period p1, the temperature is set to 63°C, and β-amylase is most active. In period p2, the temperature is set to 70°C, and β-amylase is close to losing its activity, while α-amylase is activated. In period p3, the temperature is set to 63°C, and β-amylase is most active. In period p4, the temperature is set to 73°C, and α-amylase is most active. In period p5, the temperature is set to 80°C, and α-amylase is inactivated.

[0060] Generally, when using one reservoir to achieve the temperature pattern shown in Figure 10, precise temperature control of the heater is required. When conducting tests with variations in the set temperature and duration, it is necessary to consider the heating time and cooling time in addition to heater control, making the test more difficult.

[0061] In contrast, in the second application example, we propose a method in which the temperature is set for each reservoir, and when the temperature needs to be changed, the wort is transferred to another reservoir.The temperature pattern is achieved simply by opening and closing the valves between the reservoirs, without controlling the heater temperature.

[0062] 11 is a diagram showing an example of a test system 200B using the microchannel device 100B. The test system 200B includes the microchannel device 100B and a heater 40. p1 From heater 40 p5 and cooler 41 ap and thermostat 44 p1 From 44 ap The microchannel device 100B includes a liquid reservoir 11, a measuring instrument 50, and a control device 60. p1 and liquid pool 11 p2 The inclined portion 12 is connected to the joint structure. p1 The other liquid reservoirs 11 are connected via the p3 Dry liquid pool 11 ap are also connected in the same way.

[0063] The temperature sensor 30 is connected to the compartment valve 13 p1 Partition valve 13 ap The temperature sensor 30 is arranged in the microchannel device 100B by the liquid reservoirs 11p1 to 11ap. The liquid reservoirs 11p1 to 11ap are also arranged with the measuring units 30p1 to 30ap, respectively. p1 Dry liquid pool 11 ap The temperature inside the container can be measured. The data acquired by the temperature sensor 30 is sent to the measuring instrument 50.

[0064] Liquid pool 11 p1 Heater 40 p1 The heater 40 is in a heated state. p1 Thermostat 44 p1 The temperatures of other liquid reservoirs, thermostats, and coolers are controlled in the same manner.

[0065] The control device 60 controls the partition valve 13 p1 Partition valve 13 ap The control device 60 also acquires the temperature measured by the measuring device 50 and controls the thermostat 44 to switch between an open state and a closed state. p1 From thermostat 44 apIt is also possible to control the temperature in the liquid reservoirs 111 and 112 by controlling the temperature.

[0066] 12 is a flowchart showing a control method for the test system 200B. p1 From 11 p5 The wort introduced into the test system 200B is collected in the liquid reservoir 11. p1 The period p1 of the temperature pattern has passed, and the liquid pool 11 p2 After the temperature pattern period p2 has elapsed, the liquid pool 11 p3 After the temperature pattern period p3 has elapsed, the liquid pool 11 p4 After the temperature pattern period p4 has elapsed, the liquid pool 11 p5 The temperature pattern is controlled so that period p5 of the temperature pattern passes.

[0067] First, in step S10, the heater 40 p1 From heater 40 p5 and cooler 41 ap In the second application example, a case where the temperature pattern in Fig. 10 is adopted will be described, but the present disclosure can also be applied to cases where other temperature patterns are used.

[0068] Next, in step S11b, the temperature of the liquid reservoir is detected. The control device 60 controls the thermostat to control the temperature of the liquid reservoir. p1 At 63°C, the liquid pool 11 p2 At 70°C, the liquid pool 11 p3 At 63°C, the liquid pool 11 p4 At 73°C, the liquid pool 11 p5 The temperature is controlled to 80°C. ap For example, in order to grasp the state of maltose, the temperature is set to 30°C.

[0069] Next, in step S12b, the partition valve is controlled according to the temperature pattern. Figure 13 is a diagram illustrating a method for controlling the partition valve. Figure 13(a) shows the case of period p1, Figure 13(b) shows the case of period p2, Figure 13(c) shows the case of period p3, Figure 13(d) shows the case of period p4, and Figure 13(e) shows the case of period p5. Figure 13(d) shows the case where the state of maltose is grasped after the control of the temperature pattern has been completed.

[0070] As shown in FIG. 13(a), during the period p1, the liquid pool 11 p1 After the period p1 has elapsed, the control device 60 closes the compartment valve 13 p1 is opened, and the liquid reservoir 11 p2 The wort is transferred to

[0071] Similarly, after the time period p2 has elapsed, the control device 60 closes the compartment valve 13. p2 is opened, and the liquid reservoir 11 p3 After the period p3 has elapsed, the control device 60 closes the compartment valve 13. p3 is opened, and the liquid reservoir 11 p4 After the period p4 has elapsed, the control device 60 closes the compartment valve 13. p4 is opened, and the liquid reservoir 11 p5 After all temperature patterns have been performed, the compartment valve 13 p5 is opened, and the liquid reservoir 11 ap The wort is transferred to

[0072] Subsequently, in step S13 of FIG. 12, the detection value of the electrochemical sensor 43 is acquired.

[0073] (Actions and Effects) The temperature setting for each reservoir is fixed, and the wort is passed between reservoirs, allowing the wort to be treated according to a temperature pattern. This makes it possible to perform tests while minimizing the burden on the control device 60.

[0074] In addition, when a temperature pattern in which the temperature is gradually increased during the mashing process is generally adopted, there is a risk that α-amylase and β-amylase may be inactivated before proper saccharification has occurred, making it difficult to efficiently produce maltose. For example, if β-amylase is activated at 63°C to finely cleave the sugar chains, and then α-amylase is activated at 73°C, it is thought that the action of α-amylase may not be fully exerted.

[0075] In contrast, in the present disclosure, rather than simply raising the temperature, it is possible to create a detailed and effective temperature profile for the brewing process by trial and error, raising and lowering the temperature for a portion of the period. By developing these temperature profiles during production, beer can be produced efficiently.

[0076] (Third application example of microfluidic device) Next, a third application example of the microchannel device will be described with reference to Figures 14 and 15. In order to set appropriate production conditions in beer production, it is necessary to perform tests using multiple temperature patterns and compare them. In the third application example, a method is shown in which multiple temperature patterns are continuously tested using the same test system 200B of the second application example.

[0077] 14 is a diagram showing an example of a set time when the temperature pattern of FIG. 10 is applied to the test system 200B. p1 Dry liquid pool 11 ap The temperature pattern α includes a table showing the time for storing wort at each temperature and a time chart showing the liquid reservoir used at each elapsed time. p1 The time is 10, the liquid pool is 11 p2 The time is 10, the liquid pool is 11p3 The time is 10, the liquid pool is 11 p4 The time is 10, the liquid pool is 11 p5 The time is 10, the liquid pool is 11 ap The time is set to 10. As shown in the time chart, the series of processes ends when the elapsed time reaches 60. Similarly, a total of five temperature patterns are shown, from temperature pattern β to temperature pattern γ.

[0078] Figure 15 is a diagram schematically illustrating a case where the temperature pattern of Figure 14 is applied to test system 200B. In Figure 15, the wort corresponding to temperature pattern α to temperature pattern ε, respectively, is indicated by symbols α to ε. Figure 15(a) corresponds to the case where elapsed time is 10, and Figure 15(b) corresponds to the case where elapsed time is 20. Figures from Figure 15(c) onwards also correspond to elapsed time in a similar manner, and Figure 15(p) corresponds to the case where elapsed time is 160.

[0079] In FIG. 15(a) (elapsed time 10), the liquid pool 11 p1 Next, in FIG. 15(b) (elapsed time 20), the partition valve 13p1 is switched to the open state, and the wort with the temperature pattern α is stored in the liquid reservoir 11. p2 The liquid is moved to the liquid pool 11. p1 The wort of temperature pattern β is stored in the reservoir. After the elapsed time 20, the state of the partition valve is switched to transfer the wort between the reservoirs as shown in the time chart of Figure 14, thereby performing processing corresponding to each temperature pattern.

[0080] (Actions and Effects) Since multiple temperature patterns can be performed consecutively in the same test system, temperature pattern testing can be performed quickly.

[0081] (Fourth application example of microfluidic device) Next, a fourth application example of the microfluidic device will be described with reference to Figures 16 and 17. In the first and third application examples, the state of maltose was analyzed using an electrochemical sensor 43 to evaluate the brewing process. In contrast, when yeast is added, it is possible to test up to the fermentation process, and a rough estimate of the compatibility between the wort and yeast can be obtained before proceeding to the production process.

[0082] Figure 16 is a diagram showing an example of the configuration of test system 200C when yeast is added. Test system 200C differs from test system 200B in Figure 11 in that it is provided with a yeast addition port 46 and an aeration port 47. In the following description, components that are the same as or equivalent to those in test system 200B of the second application example described above are given the same reference numerals, and their description will be simplified or omitted.

[0083] The yeast addition port 46 is located in the liquid reservoir 11 ap The aeration port 47 is a passage through which the yeast passes when it is introduced into the liquid reservoir 11. ap The yeast added through the yeast addition port 46 breaks down maltose into glucose, and then produces alcohol. There are various possible temperature settings for adding yeast, but here we will use the liquid reservoir 11. ap The temperature is generally considered to be 5°C.

[0084] Furthermore, by controlling the oxygen supplied through the aeration port 47, the state of the yeast can be changed, making it possible to analyze the compatibility between the wort and the yeast and the degree of aeration. Although the yeast addition port 46 and the aeration port 47 are provided separately in the above description, the present disclosure is not limited to this case. For example, if the yeast addition process and the aeration process do not need to be performed in parallel, a common inlet for yeast addition and aeration may be provided.

[0085] The type of sensor 48 can be selected depending on the object to be detected, such as alcohol or carbon dioxide.

[0086] 17A and 17B are diagrams showing other examples of the configuration of the yeast addition port and the aeration port. FIG. 17A shows a cross section of the micro-channel device 100Ca as viewed from above (the positive z-axis direction), and FIG. 17B shows a cross section of the micro-channel device 100Ca cut along a plane parallel to the x-axis direction. The yeast addition port 46a and the aeration port 47a are formed on the upper side (the positive z-axis direction) of the micro-channel device 100Ca. When the micro-channel device 100Ca has a top cover, the yeast addition port 46a and the aeration port 47a can be formed by drilling holes in the top cover.

[0087] Regarding yeast, when primarily using dry yeast, it is added directly through the yeast addition port 46a. Regarding aeration, oxygen can be injected through the aeration port 47a after the yeast is added, or an oxygen stone can be added through the aeration port 47a. The oxygen stone is composed of calcium peroxide, and CaO₂ reacts with water (H₂O) to produce calcium hydroxide (Ca(OH)₂) and oxygen (½O₂). The generation of calcium hydroxide along with oxygen shifts the pH in the flow path toward alkaline. Therefore, for example, by attaching an ISFET (ion-sensitive field-effect transistor) 70 to the bottom of the flow path and placing a reference electrode 71 within the flow path, the amount of oxygen supplied can be monitored by changes in pH. The ISFET 70 can be constructed, for example, by three-dimensionally processing a silicon substrate to create a probe shape, and then forming a field-effect transistor (FET) sensor at the tip of the probe. The entire surface is then covered with a highly water-resistant Si3N4 film (approximately 1,000 Å thick), and an ion-sensitive film, mainly made of Al2O3 or Ta2O5, is formed on top of that, thereby completing the ISFET 70.

[0088] (Actions and Effects) By adding yeast, it becomes possible to detect the amount of alcohol, and the fermentation process can also be analyzed using a test system that uses a microfluidic device.

[0089] (Fifth application example of microfluidic device) 18 to 21, a case will be described in which, in the fifth application example, in addition to variations in temperature patterns, yeast types are also tested to comprehensively test the production conditions. In this case, the tests can be performed by arranging microfluidic devices in parallel.

[0090] FIG. 18 is a diagram showing an example of a combination 350 of micro-channel devices when processing one type of wort with a plurality of temperature patterns. The channel 301 of the micro-channel device 300 has a structure in which one channel branches into three channels as it moves in the direction of movement of the wort (the positive direction of the x-axis). The micro-channel device 310a also has a liquid reservoir 11 p1 Dry liquid pool 11 p5 The microchannel device 310a has the liquid reservoir portion 11 from the microchannel device 100B of FIG. ap The micro-channel device 310b and the micro-channel device 310c have the same configuration as the micro-channel device 310a, except for the portion indicated by the arrows.

[0091] The micro-channel device 300 has a first joint 302 at the branched portion of the channel 301. The micro-channel device 310a has a second joint 311 on the minus x-axis side. By fitting the first joint 302 and the second joint 311 together, the channel 301 of the micro-channel device 300 and the liquid reservoir 11 of the micro-channel device 310a can be connected. p1are connected. Here, for example, by forming joint channel section 303 formed inside first joint section 302 as a channel that slopes vertically downward toward the positive x-axis direction, it is possible to control the movement of wort in microchannel device 310a. When providing a slope, the arrangement and structure of each microchannel device in the z-axis direction are adjusted so that the entire microchannel device combination 350 forms a slope. Three microchannel devices 310a to 310c are connected to microchannel device 300 by a joint structure.

[0092] As another example of moving the wort, the micro-channel device 300 may be formed as a tubular channel that generates capillary action, allowing the wort in the micro-channel device 300 to move to the downstream micro-channel device 310a by capillary action. In this case, by adjusting the structure (e.g., adjusting the cross-sectional area of ​​the channel) between the channel in the micro-channel device 300, the channel connected to the upstream side of the micro-channel device 300, and the channel connected to the downstream side of the micro-channel device 300, it becomes possible to move the wort by utilizing capillary action. Furthermore, by subjecting the joint channel portion 303 of the first joint portion 302 to a hydrophilic treatment, the movement of the wort can be facilitated.

[0093] Heater 40 p1 The three microfluidic device 310 liquid reservoirs 11 p1 Heater 40 p1 From 40 p5 The temperature of each thermostat is 44 p1 From 44 p5 and is controlled by a control device 60, which will be described later. p2 From heater 40 p5 In addition, although sharing a heater among the microchannel devices 310 is effective in simplifying the system configuration, if the temperature pattern is to be changed among the microchannel devices 310, it is also possible to provide separate heaters.

[0094] 19 is a diagram showing an example of a combination 360 of microchannel devices for performing a process of adding a plurality of yeasts. The microchannel device (branched channel section) 320 has an inlet 321 for introducing a sample. i a flow channel 321 through which the sample moves, and two or more outlets 321 through which the sample is discharged. v1 From 321 v3 and the inlet 321 i from the outlet 321 v1 From 321 v3 When the direction toward the outlet is the sample movement direction (x-axis positive direction), the flow path portion leading to each of the two or more outlets forms joint flow path portions 3231 to 3233 having a shape that extends vertically downward as it moves toward the movement direction, and has third joint portions 3221 to 3223 formed around the joint flow path portions. Also, microfluidic device (sensor flow path portion) 330a to 330c includes second joint portion 331 that fits into third joint portions 3221 to 3223, and liquid reservoir portion 11 in which the sample moving from joint flow path portions 3231 to 3233 is stored. ap and the liquid pool portion 11 ap and a sensor 48 disposed at

[0095] Specifically, the flow channel 321 of the microchannel device 320 has a structure in which one flow channel branches into three flow channels in the direction of movement of the sample (wort) (positive direction of the x-axis). ap The liquid reservoir portion 11 ap An enzyme 45, a yeast addition port 46, an aeration port 47, and a sensor 48 are arranged in the microchannel device 330. The microchannel device 330 is a microchannel device 300 having a liquid reservoir 11 from the microchannel device 100C of FIG. ap The micro-channel device 330b and the micro-channel device 330c have the same configuration as the micro-channel device 330a.

[0096] The micro-channel device 320 has a first joint 322 at the branched portion of the channel 321. The channel disposed within the first joint 322 is a joint channel portion 323 formed as an inclined channel. The micro-channel device 330a also has a second joint portion 311 on the negative x-axis side. By fitting the first joint portion 322 and the second joint portion 331 together, the channel 321 of the micro-channel device 320 and the liquid reservoir portion 11 of the micro-channel device 330 are inclined relative to each other. ap is connected to the micro-channel device 320. Three micro-channel devices 330a to 330c are connected to the micro-channel device 320 by joint structures. The channels of the micro-channel device 320 may have a shape that slopes vertically downward as it moves in the positive direction of the x-axis. As shown in FIG. 20 described below, the wort that has been processed according to the temperature pattern passes through the micro-channel device 320, and it is therefore necessary to quickly move the wort to the downstream micro-channel device 330a before its state changes.

[0097] Although the microchannel device (branched channel section) 320 has an inclined channel in the above description, the present disclosure is not limited to this case. For example, the microchannel device 320 may have a tubular channel that generates capillary action. The wort flows through the inlet 321 by capillary action. i The gas is introduced from the flow path 321, moves through the flow path 321, and exits the outlet 321. v1 From 321 v3 It is also possible to make the wort flow easily by subjecting the joint flow passage portions 3231 to 3233 to a hydrophilic treatment.

[0098] cooler 41 ap The three microfluidic device 330 liquid reservoirs 11 ap Cooling device 41 ap The temperature of each thermostat is 44 apand controlled by a control device 60, which will be described later. Although using a common cooler among the microchannel devices 330a to 330c is effective in simplifying the system configuration, if the temperature patterns are to be changed among the microchannel devices 330a to 330c, it is also possible to provide separate coolers.

[0099] Figure 20 is a diagram showing an example of a test system configured by combining the microchannel devices shown in Figures 18 and 19. Test system 200D has microchannel device 600, microchannel device combinations 3501 to 3503, and microchannel device combinations 3601 to 3609. Microchannel device combinations 3501 to 3503 correspond to microchannel device combination 350 shown in Figure 18, and microchannel device combinations 3601 to 3609 correspond to microchannel device combination 360 shown in Figure 19. Note that thermostats are provided corresponding to the multiple heaters and coolers, but are shown for brevity as thermostat 44.

[0100] Similar to microchannel devices 300 and 320, microchannel device 600 has a structure in which one channel branches into three channels as the sample (wort) moves in the positive x-axis direction. For example, microchannel device 600, microchannel device 300, microchannel device 310a, microchannel device 320, and microchannel device 330a are each connected by a joint structure. The channels included in the joint structure form joint channel sections, allowing the wort to move in response to the opening and closing of the partition valves. Furthermore, as shown in particular in temperature sensor 301, a temperature sensor is inserted from microchannel device 310a to microchannel device 330a, with a measurement point positioned at the liquid reservoir on the channel. Other microchannel device combinations 3502 and 3503, and 3602 to 3609 have similar configurations.

[0101] To facilitate understanding of the overall picture of test system 200D, the flow path between microchannel device 600 and microchannel device combination 3501 is shown in a simplified form with a dashed line extending in a direction tilted from the x-axis direction, and the flow path between microchannel device combination 3501 and combination 3601 is also shown in a simplified form with a dashed line extending in a direction tilted from the x-axis direction. The flow paths between other microchannel devices are similarly shown with dashed lines. In practice, sufficient spacing is maintained between the microchannel devices to prevent the flow paths from tilting from the x-axis direction and to prevent excessive bending load from being applied to temperature sensor 301. For example, microchannel devices 600, 300, and 320 each have three flow paths, but in reality, the spacing between the flow paths is greater than shown in the figure.

[0102] Note that in order to prevent excessive bending load from being applied to temperature sensor 301, branching portions of channel 321 of microchannel device 320 may be curved. Also, separate temperature sensors may be used for microchannel device combinations 3501 to 3503 (microchannel devices 310a to 310i) and microchannel device combinations 3601 to 3609 (microchannel devices 330a to 330aa). In this case, inlets for introducing the temperature sensors are formed downstream of microchannel devices 310a to 310i.

[0103] Furthermore, for test system 200D, it is possible to apply either a method of providing a flow path with a vertically downward inclination or a method of utilizing capillary action as a method of moving the wort.

[0104] The measuring instrument 50 can measure the temperature of the liquid reservoir included in the test system 200D via the sensor switch 52. The test system 200D shown in Fig. 20 includes 27 temperature sensors, and the connection of the measuring instrument 50 is switched by the sensor switch 52. Although the test system 200D shown in Fig. 20 includes 27 temperature sensors, if the number of temperature sensors is increased, the structure may be such that sensor switches are applied according to the number of temperature sensors to acquire data.

[0105] The control device 60 controls the temperature of the liquid reservoir based on the temperature measured by the thermostat 44 and the measuring device 50, and switches the on-off valve between an open state and a closed state. v1 From 321 v3 The results measured by the sensors 48 in the microfluidic device 330 connected to each of the sensors are obtained.

[0106] 21 is a diagram showing an example of a test using the test system 200D. The control device 60 switches between the open state and the closed state of the partition valve to direct the wort into the liquid reservoir 11. ap The test is controlled so that the liquid is stored in the reservoir for a predetermined period of time. During the test, it is possible to change conditions from two perspectives: the storage time in the reservoir (temperature pattern) and the enzyme to be added. Here, it is shown that the temperature pattern is changed between microchannel device 310a and microchannel device 310c, and the enzyme to be added is changed from enzyme A to enzyme C between microchannel devices 330a and 330i. In this way, it is possible to analyze the difference in the amount of alcohol detected depending on the difference in temperature pattern and the difference in yeast.

[0107] (Sixth application example of microfluidic device) 22 to 24, the sixth application example differs from the fifth embodiment in that the state of the wort is monitored without adding yeast. In the following description, the same or equivalent components as those in the fourth application example described above are designated by the same reference numerals, and their description will be simplified or omitted.

[0108] 22 is a diagram showing an example of the configuration of the microchannel device 340 when performing a process for determining the state of maltose. ap The liquid reservoir portion 11 ap An electrochemical sensor 43 and an enzyme 45 are disposed on the microchannel device 340. The microchannel device 340 has a first joint 322 on the negative x-axis side. The microchannel device 340 is connected to the microchannel device 100B in FIG. 11 by the liquid reservoir 11. ap It has the same structure as an extracted portion of the above.

[0109] Figure 23 is a diagram showing an example of a test system 200E configured by combining the microchannel devices shown in Figure 18 and Figure 22. In the fourth embodiment, a combination of microchannel devices 3601 to 3609 was used as shown in test system 200D in Figure 20, but in test system 200E in Figure 23, microchannel devices 3401 to 3409 shown in Figure 22 are applied instead.

[0110] FIG. 24 is a diagram showing an example of the set time when the test system 200E is used. By applying the set time shown in FIG. 24, it is possible to carry out a test in which the retention time (temperature pattern) in the liquid reservoir is changed, and it becomes possible to grasp the state of maltose. In addition, it is also possible to change the retention time for each liquid reservoir by controlling the open and closed states of the partition valves. Specifically, the set time shown in FIG. 24 can be applied to, for example, the combination 3601 of the microchannel device 310a and the microchannel device 310b. For the microchannel device 310a, the liquid reservoir 11 p1 From 11 p4 The temperature is controlled over time in the liquid reservoir 11 p5 In addition, the liquid reservoir 11 of the combination 3601 of micro-channel devices (micro-channel devices 330a to 330c) connected downstream of the micro-channel device 310a is deactivated. ap Cooling is performed in the liquid reservoir 11. p1From 11 p5 and 11 ap The standard retention time in the liquid pool 11 is set to 10. p1 From 11 p4 When creating variations in which the storage time is changed to 20 in any of the microchannel devices 330a to 330c, 11 temperature patterns, temperature patterns 1 to 11, are shown in Figure 24. If different types of yeast are used in the microchannel devices 330a to 330c, 11 x 3 = 33 different tests can be performed. It is assumed that the temperature time management is the same for the liquid reservoirs of the microchannel devices 330a to 330c.

[0111] Applying a method similar to the temperature time management described above, for example, by setting the reference retention time for microchannel device 310b to 5 and for microchannel device 310c to 7, it becomes possible to realize 33 x 3 = 99 different tests. Furthermore, when this method is applied to the combination of microchannel devices 3502 and 3503, it becomes possible to realize 33 x 3 = 99 different tests.

[0112] Furthermore, if it were possible to control the temperature of each microchannel device 330a to 330c (i.e., if it were possible to control the temperature independently for each microchannel device 330a to 330aa), it would be possible to perform 99 x 3 = 297 different tests.

[0113] (Actions and Effects of Application Examples 5 and 6) When testing under multiple conditions, such as temperature patterns and types of yeast, using test systems 200D and 200E makes it possible to perform the tests simultaneously, thereby shortening the time required for the tests.

[0114] (Seventh application example of microfluidic device) Next, in a seventh application example, a case where the test system is applied to a production line will be described with reference to Fig. 25. Fig. 25 is a diagram showing an example of a configuration where the test system is applied to a production line.

[0115] As an example of a production line, a brewing tank 500 in which wort is brewed is taken. A test system 200F applied to the brewing tank 500 has a microfluidic device 400, a thermometer 405, a pump 406, and a control device 460. The microfluidic device 400 has a liquid reservoir 401, a flow path 402, and an electrochemical sensor 403. For example, data obtained from the electrochemical sensor 403 and the thermometer 405 is acquired by the control device 460, and the pump 406 can be controlled by the control device 460.

[0116] The wort in the mashing tank 500 is introduced into the microchannel device 400 by a pump 406. The temperature of the wort is measured by a thermometer 405, while the liquid reservoir 401 is cooled to, for example, 30°C, which is set to a temperature suitable for determining the state of maltose. The wort used for measurement in the microchannel device 400 is returned to the mashing tank 500 again.

[0117] Generally, in the case of craft beer, a brewing tank 500 with a volume of 20 liters to 500 liters is used. Assuming that the shape of the channel of the microchannel device 400 is 5 mm in height, 5 mm in width, and 200 mm in length, and that the wort passes through the microchannel device 400 at a flow rate of 0.2 m / s, then the flow rate of 5×10 -2 liters of wort passes through the microfluidic device 400. This amount corresponds to 0.05% of the wort in the brewing tank 500, for example, if the amount of wort in the brewing tank 500 is 100 liters. When the test system 200F is used, the amount of wort required for measurement can be reduced.

[0118] Although the case where the test system 200F is applied has been described, the present disclosure is not limited to this case. It is also possible to apply the test systems 200A to 200E to the preparation tank 500 according to the purpose of the test.

[0119] (Actions and Effects) Furthermore, the amount of wort required for measurement in the microchannel device 400 can be kept small compared to the amount of wort stored in the production line (brewing tank 500). Even when wort is extracted for measurement in the microchannel device 400 and then returned to the brewing tank 500, the brewing process is not affected. Therefore, it is possible to grasp the state of maltose in the production process in real time.

[0120] Although the embodiments 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 gist of the present invention.

[0121] For example, this disclosure has been described as being applied to beer production, with wort being used as the sample for the test system, but in the case of wine production, for example, yeast is added to grapes, so the test systems shown in the fourth and fifth application examples can be applied. It can also be applied to drug development.

[0122] The following are examples of possible embodiments of the present invention, but the present invention is not limited to these. (Aspect 1) A microchannel device including a first channel portion having a first liquid reservoir portion for storing a sample, a first partition valve for partitioning the first liquid reservoir portion, and a temperature sensor, The first compartment valve is a fixed valve portion fixed to the first flow path portion and blocking a part of the flow path of the first flow path portion; a movable valve portion that moves from a portion of the first flow path portion other than the part of the flow path to form an opening, the fixed valve portion has an insertion portion for fixing the temperature sensor, The microchannel device, wherein the temperature sensor is a linear sensor having at least one measurement point, and a first measurement point of the temperature sensor is disposed in the first liquid reservoir. (Aspect 2) the microchannel device further includes a first housing portion in which the first channel portion is formed and a second housing portion in which a second channel portion is formed; the first flow path portion is partitioned by the first partition valve and includes a first inclined portion connected to the first liquid reservoir portion; the first housing portion has a first joint portion formed around the first inclined portion, the second housing portion has a second joint portion that fits into the first joint portion, the second flow path section has a second liquid reservoir section that stores the sample, By fitting the first joint portion and the second joint portion together, the first flow path portion and the second flow path portion are connected to each other, 2. The microchannel device according to aspect 1, wherein the second measurement point of the temperature sensor is disposed in the second liquid reservoir. (Aspect 3) When the direction in which the sample moves is defined as the movement direction, the first inclined portion has a shape that extends vertically downward toward the movement direction, the second liquid reservoir is disposed at a position vertically downward from the first liquid reservoir, The microchannel device according to aspect 1 or 2, wherein when the first fitting portion and the second fitting portion are fitted together, the first liquid reservoir portion is connected to the second liquid reservoir portion via the first inclined portion. (Aspect 4) Aspect 4. The microfluidic device according to any one of Aspects 1 to 3, wherein the temperature sensor is a Fiber Bragg Grating (FBG) sensor or a Multi-Point (MP) sensor. (Aspect 5) Aspect 5. The microchannel device according to any one of Aspects 1 to 4, wherein the movable valve portion is an electromagnetic valve. (Aspect 6) 6. The microchannel device according to any one of aspects 1 to 5, wherein the second channel section further includes an electrochemical sensor that measures a state of the sample in the second liquid reservoir section. (Aspect 7) The second flow path portion is a yeast addition port which is a passage through which yeast passes to be introduced into the second liquid reservoir; The microchannel device according to any one of aspects 1 to 6, further comprising an aeration port that is a passage through which oxygen passes before being introduced into the second liquid reservoir. (Aspect 8) a first branch flow path section having an inlet for introducing a sample, a flow path through which the sample moves, two or more outlets from which the sample is discharged, and a third joint section formed around the joint flow path section, wherein when the direction from the inlet to the outlet is the direction of movement of the sample, flow path portions leading to each of the two or more outlets form a joint flow path section having a shape that extends vertically downward as they move in the direction of movement of the sample, and a sensor flow path section including a second joint section that fits into the third joint section, a liquid reservoir section in which the sample moving from the joint flow path section is stored, and a sensor disposed in the liquid reservoir section; a control device that acquires the results measured by the sensors in the sensor flow path sections connected to each of the two or more outlets. (Aspect 9) The sample that has migrated from the first flow path section is introduced into the inlet, the first flow path section includes a first liquid reservoir section for storing the sample, a first partition valve for partitioning the first liquid reservoir section, a temperature sensor, and a heater for setting the temperature of the first liquid reservoir section; The first compartment valve is a fixed valve portion fixed to the first flow path portion and blocking a part of the flow path of the first flow path portion; a movable valve portion that moves from a portion of the first flow path portion other than the part of the flow path to form an opening, the fixed valve portion has an insertion portion for fixing the temperature sensor, the temperature sensor is a linear sensor having at least one measurement point, and a first measurement point of the temperature sensor is disposed in the first liquid reservoir; Aspect 10. The testing system according to aspect 9, wherein the control device switches the first partition valve between an open state and a closed state, and controls the sample to be stored in the first liquid reservoir for a predetermined time. (Aspect 10) 10. The test system of claim 8 or claim 9, wherein the sample is wort. [Explanation of symbols]

[0123] 1a to 1d: flow path section, 10: flow path, 11a~11e, 11 p1 ~11 p5 , 11 ap , 11 xa , 11 xxa , 11 ya , 11 yya , 111, 112: liquid pool, 12a~12d, 12 p1 ~12 p5 , 12 xa , 121: Inclined part, 13a~13e, 13 p1 ~13 p5 , 131: Compartment valve, 13 in : Insertion part, 15: connector portion, 20: housing, 20a to 20e: housing portion, 20a1, 20x1: 1st joint part, 20b2, 20xx2: 2nd joint part, 30, 301: temperature sensor, 30a~30e, 30 p1 ~30 p5 , 30 ap , 301, 302: Measuring section 40, 40p1 to 40p5: Heater 41, 41 ap :Cooler, 42: filter, 43: electrochemical sensor, 44, 44 p1 ~44 p5 , 44 ap , 441, 442: Thermostat 45: Enzyme, 46: Yeast addition port, 47: Aeration port, 48: Sensor, 50: Measuring instrument, 52: Sensor switch, 60: Control device, 100, 100A to 100C: Microfluidic device, 100a~100d, 100x, 100xx, 100y, 100yy: Block section, 200A~200F: Test system, 300, 310, 310a to 301c: microfluidic device; 301: Channel, 302: First joint portion, 303: Joint flow path portion, 311: Second joint portion, 320: Microfluidic device, 321: Fluid, 321 i : Entrance, 321 v1 ~321 v3 :Discharge port, 3221~3223: Third joint part, 3231~3233: Joint flow path part, 330, 330a to 330c: microchannel device, 331: second joint part, 340, 3401-3049: Microfluidic devices; 350, 3501-3503, 360, 3601-3609: combinations of microfluidic devices; 400: microchannel device, 401: liquid reservoir, 402: channel, 403: electrochemical sensor, 405: thermometer, 406: pump, 460: control device, 500: preparation tank, 600: Microfluidic device

Claims

1. A microchannel device including a first channel portion having a first reservoir portion for storing a sample, a first partition valve for partitioning the first reservoir portion, and a temperature sensor, The first compartment valve is a fixed valve portion fixed to the first flow path portion and blocking a part of the flow path of the first flow path portion; a movable valve portion that moves from a portion of the first flow path portion other than the part of the flow path to form an opening, the fixed valve portion has an insertion portion for fixing the temperature sensor, A microchannel device, wherein the temperature sensor is a linear sensor having at least one measurement point, and a first measurement point of the temperature sensor is disposed in the first liquid reservoir portion.

2. the microchannel device further includes a first housing portion in which the first channel portion is formed and a second housing portion in which a second channel portion is formed; the first flow path portion is partitioned by the first partition valve and includes a first inclined portion connected to the first liquid reservoir portion; the first housing portion has a first joint portion formed around the first inclined portion, the second housing portion has a second joint portion that fits into the first joint portion, the second flow path section has a second liquid reservoir section that stores the sample, The first joint portion and the second joint portion are fitted together to connect the first flow path portion and the second flow path portion, The microchannel device according to claim 1 , wherein the second measurement point of the temperature sensor is disposed in the second liquid reservoir.

3. When the direction in which the sample moves is defined as the movement direction, the first inclined portion has a shape that extends vertically downward toward the movement direction, the second liquid reservoir is disposed at a position vertically downward from the first liquid reservoir, The microchannel device according to claim 2 , wherein when the first joint and the second joint are fitted together, the first liquid reservoir is connected to the second liquid reservoir via the first inclined portion.

4. 2. The microfluidic device according to claim 1, wherein the temperature sensor is a Fiber Bragg Grating (FBG) sensor or a Multi-Point (MP) sensor.

5. The microchannel device according to claim 1 , wherein the movable valve portion is an electromagnetic valve.

6. The microchannel device according to claim 2 , wherein the second channel portion further comprises an electrochemical sensor that measures a state of the sample in the second liquid reservoir portion.

7. The second flow path portion is a yeast addition port which is a passage through which yeast passes to be introduced into the second liquid reservoir; The microchannel device according to claim 2 , further comprising an aeration port which is a passage through which oxygen passes to be introduced into the second liquid reservoir.

8. a first branch flow path section including an inlet for introducing a sample, a flow path through which the sample moves, two or more outlets from which the sample is discharged, and a third joint section formed around the joint flow path section, the joint flow path section having a shape such that, when the direction from the inlet to the outlet is the direction of movement of the sample, flow path portions leading to each of the two or more outlets extend vertically downward as they move in the direction of movement of the sample; a sensor flow path section including a second joint section that fits into the third joint section, a liquid reservoir section in which the sample moving from the joint flow path section is stored, and a sensor disposed in the liquid reservoir section; a control device that acquires the results measured by the sensors in the sensor flow path sections connected to each of the two or more outlets.

9. The sample that has migrated from the first flow path section is introduced into the inlet, the first flow path section includes a first liquid reservoir section for storing the sample, a first partition valve for partitioning the first liquid reservoir section, a temperature sensor, and a heater for setting the temperature of the first liquid reservoir section; The first compartment valve is a fixed valve portion fixed to the first flow path portion and blocking a part of the flow path of the first flow path portion; a movable valve portion that moves from a portion of the first flow path portion other than the part of the flow path to form an opening, the fixed valve portion has an insertion portion for fixing the temperature sensor, the temperature sensor is a linear sensor having at least one measurement point, and a first measurement point of the temperature sensor is disposed in the first liquid reservoir; 9. The testing system according to claim 8, wherein the control device controls the first partition valve to switch between an open state and a closed state, so as to retain the sample in the first liquid reservoir for a predetermined time.

10. 9. The test system of claim 8, wherein the sample is wort.

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