JP2006021156A - Microreactor and manufacturing method therefor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a microreactor in which a fluid in a flow passage is heated efficiently and the temperature of the fluid is controlled quickly with high precision and to provide a method for manufacturing the microreactor. <P>SOLUTION: The microreactor is provided with flow passage forming members 10, 12 in each of which the flow passage is formed. A metallic electrical wire 30 for a heater and metallic electrical wires 40A, 40B for a temperature sensor are arranged in a specified area of the surface of an inner wall surrounding the flow passage. A heat insulating layer 18 having the insulating property higher than those of the flow passage forming members 10, 12 is interposed between the metallic electrical wire 30 for the heater and the inner wall surface of the flow passage so that the heat to be generated by the metallic electrical wire 30 for the heater is restrained from being transmitted to the sides of the flow passage forming members. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a microreactor for causing an efficient chemical reaction in a limited space in the fields of medical treatment, biochemistry, analytical chemistry, and the like.

Conventionally, what was described in patent document 1 as a micro reactor as mentioned above is known. The microreactor includes a flow channel plate and a bottom plate, and is configured such that a fluid flow channel having a reaction chamber is formed inside by superimposing them. Furthermore, a heating device is provided on the lower surface of the bottom plate, and the temperature of the fluid in the fluid flow path is maintained at a desired temperature suitable for reaction by the heating. Specifically, the heating device described in the document has a structure in which a sheet-like heater and a temperature sensor are incorporated in an insulating film made of polyimide formed on the lower surface of the bottom plate.
JP 2004-33907 A

  In the microreactor described in Patent Document 1, a heating device is attached to the outside of the bottom plate, and heat is applied to the fluid flow path through the bottom plate, so that the heater in the heating device operates. And a substantial response delay between the actual fluid temperature change in the reaction chamber is expected. Therefore, it is difficult to realize quick and highly accurate temperature control. Moreover, in order to heat the fluid, first, the bottom plate having a relatively large heat capacity must be heated, and it is difficult to prevent heat dissipation to the outside of the reactor.

  As means for solving the above-mentioned problems, the present invention provides a flow path forming member that forms a fluid flow path inside, and a heater formed in a specific region on an inner wall surface that surrounds the fluid flow path. A metal wiring for the temperature sensor and a metal wiring for the temperature sensor, and a heat insulating layer having a higher heat insulating property than the flow path forming member is interposed between the metal wiring for the heater and the inner wall surface of the fluid flow path. Is a microreactor.

  According to this configuration, the metal wiring for the heater and the temperature sensor are respectively incorporated in the fluid flow path, and heat is directly applied to the fluid in the fluid flow path by energization of the heater metal wiring, and Since the temperature of the fluid is directly detected by the metal wire for the temperature sensor, it is possible to realize quick and highly accurate control of the fluid temperature. Further, since the fluid is directly heated in the fluid flow path, the thermal efficiency is dramatically improved as compared with the case where the fluid is heated from the outside of the reactor.

  In addition, since a heat insulating layer having a higher heat insulating property than the flow path forming member is interposed between the heater metal wiring and the inner wall surface of the fluid flow path, the presence of the heat insulating layer allows the heater wiring to be separated from the heater wiring. It is suppressed that the generated heat is transmitted to the flow path forming member side, thereby further improving the thermal efficiency and the responsiveness of temperature control.

  The heat insulating layer only needs to be interposed at least between the metal wiring for the heater and the wiring surface, and it does not matter whether the heat insulating layer is present between the metal wiring for the temperature sensor and the wiring surface.

  As this heat insulating layer, those composed of a porous film excellent in heat insulating properties are preferable, and a porous film made of silica airgel is particularly preferable.

  Further, when the heat insulating layer is constituted by the porous film, the heat insulating layer is covered with a waterproof film having higher hydrophobicity than the material constituting the heat insulating layer, and the metal for the heater is formed on the waterproof film. By adopting a configuration in which the wiring is arranged, it is possible to effectively prevent, for example, an aqueous solution from penetrating into the porous film and causing a change in fluid behavior or a structural destruction.

  The flow path forming member has a wiring surface, a wiring substrate on which the heat insulating layer and each metal wiring are disposed, and a facing surface facing the wiring surface of the wiring substrate, A flow path base material in which a flow path forming recess having a shape surrounding the metal wiring is recessed from the facing surface, and the wiring surface of the wiring base material and the facing surface of the flow path base material are overlapped with each other. Accordingly, a fluid flow path for storing the metal wiring for the heater and the metal wiring for the temperature sensor is formed by the wiring surface of the wiring base and the flow path forming recess of the flow path base. What has been done is preferred.

  According to this configuration, a thin wiring structure can be obtained simply by overlapping the wiring surface of the wiring base material on which the heat insulating layer and the metal wiring are formed in advance and the facing surface of the flow path base material on which the flow path forming recess is formed. Can be easily obtained.

  For the metal wiring, for example, a metal plate punched out or a wire material may be used. However, by forming the metal wiring with a metal pattern formed along the facing surface of the wiring substrate, the metal wiring is extremely thin. The wiring structure can be obtained.

  In this case, if the metal pattern has an electrode connected to an external circuit at an end thereof, and this electrode protrudes outward from the flow path base material and is exposed to the outside of the flow path forming member, the By using the electrodes, the metal wiring built in the fluid flow path and the external circuit can be easily connected.

  The present invention also includes a flow path forming member that forms a fluid flow path therein, a metal wiring for a heater and a metal wiring for a temperature sensor formed in a specific region on an inner wall surface surrounding the fluid flow path. And, a method of manufacturing a microreactor in which a heat insulating layer having a higher heat insulating property than the flow path forming member is interposed between the metal wiring for the heater and the inner wall surface of the fluid flow path, A step of manufacturing a wiring base material having a planar wiring surface, a step of forming a heat insulating layer having a higher heat insulating property than the wiring base material on the wiring surface of the wiring base material, A flow path base material having a step of forming a metal wiring and a facing surface facing the wiring surface of the wiring base material, the flow path forming concave portion having a shape surrounding the metal wiring from the facing surface is manufactured. Do not oppose the wiring surface of the wiring substrate and the facing surface of the flow path substrate. By superimposing the Luo both flow path forming member in which a step of forming a fluid flow path for storing each of said metal wiring and the flow path forming recess of the wiring surface and the channel base of the wiring substrate.

  According to this method, the heat insulating layer and the metal wiring can be easily formed on the wiring substrate with the wiring surface open. And the fluid flow path in which the said metal wiring was integrated can be easily formed only by overlapping the opposing surface of a flow-path base material on the wiring surface.

  Here, when the step of forming the heat insulating layer is a step of forming a porous film on the wiring surface, after the step, a waterproof film covering the heat insulating layer is formed on the heat insulating layer, and then the waterproofing is performed. If the step of forming the metal wiring on the film is performed, the porous film can be protected from the fluid in the fluid flow path by the waterproof film.

  As described above, according to the present invention, the fluid in the fluid flow path can be efficiently heated, and the temperature control can be performed more quickly and accurately.

  A preferred embodiment of the present invention will be described with reference to the drawings.

  The illustrated microreactor includes a flat wiring substrate 10 corresponding to a wiring substrate and a flow channel substrate 12 stacked thereon as a flow channel forming member. These substrates 10 and 12 are preferably formed of a ceramic material excellent in insulation and durability, but the specific material is not particularly limited.

  Among these substrates 10 and 12, the upper surface of the wiring substrate 10 is a wiring surface 14, and the lower surface of the flow path substrate 12 is a facing surface 16 that faces the wiring surface 14. A heat insulating layer 18 is formed on the wiring surface 14 of the wiring substrate 10, while a flow path forming recess 20 that is recessed upward from the facing surface 16 is formed in the flow path substrate 12.

  The flow path forming recess 20 forms a fluid flow path with the wiring surface 14 of the wiring board 10 and extends in a specific direction in the drawing. Specifically, the flow path forming recess 20 according to this embodiment includes a wide main passage portion 22 that forms a reaction chamber, a small fluid inlet passage portion 23 that extends from one end of the main passage portion 22, and A cylindrical fluid inlet port 24 formed at the end of the fluid inlet passage 23, a small fluid outlet passage 25 extending from the other end of the main passage 22, and the fluid outlet passage 25 It is comprised with the column-shaped fluid outlet port 26 formed in the edge part.

  On the other hand, the wiring board 10 is provided with a fluid inlet hole 27 and a fluid outlet hole 28 penetrating in the thickness direction including the heat insulating layer 18. The fluid inlet hole 27 is provided at a position corresponding to the fluid inlet port 24, and the fluid outlet hole 28 is provided at a position corresponding to the fluid outlet port 26.

  The heat insulating layer 18 is formed over substantially the entire area of the wiring surface 14. The heat insulating layer 18 is more preferably excellent in heat insulating properties and insulating properties, and specifically, a porous film formed of silica airgel or the like is preferable. Moreover, application of resin materials such as silicone rubber is also possible.

When the porous membrane as described above is employed, it is more preferable to cover the surface with a waterproof membrane having a higher hydrophobicity than the porous membrane. Such a waterproof film can be formed, for example, by forming a thin film made of SiO ₂ , SiN or the like on the heat insulating layer by a sputtering method or a CVD method. In addition, application of fluororesin etc. is also possible.

  And the pattern which comprises metal wiring is formed on this heat insulation layer 18 (When the surface of the said heat insulation layer 18 is covered with the waterproof film). Specifically, the heater metal pattern 30 is formed at a substantially intermediate portion in the longitudinal direction of the fluid flow path, and the temperature sensor metal patterns are respectively positioned on the upstream side and the downstream side of the heater metal pattern 30. 40A and 40B are formed.

  The heater metal pattern 30 includes a heater portion 32 incorporated in the main passage portion 22, connection portions 34 and 36 extending in the same direction from one end of the flow passage width direction from both ends of the heater portion 32, and each connection portion. The electrodes 34 and 36 are integrally formed with rectangular electrodes 37 and 38 formed at the ends thereof. The heater part 32 and the connecting parts 34 and 36 are formed with a small width, and the heater part 32 is formed in a finely meandering shape in order to increase the resistance.

  On the other hand, the temperature sensor metal patterns 40A and 40B include a sensor part 42 incorporated in the main passage part 22, and connection parts 44 extending in opposite directions from both ends of the sensor part 42 to both sides in the channel width direction. 46 and rectangular electrodes 47 and 48 formed at end portions of the respective connection portions 44 and 46 are integrally provided. The sensor part 42 and the connection parts 44 and 46 are formed with a small width, and the sensor part 42 is formed in a finely meandering shape in order to increase resistance.

  Cutout portions 49 for exposing the electrodes 37, 38, 47, 48 to the outside of the substrate are formed at both sides in the width direction at the intermediate position in the longitudinal direction of the flow path base material 12. As shown in FIG. 2, a temperature controller 50 as shown in FIG. 2 is connected to the electrodes 37 and 38 of the heater metal pattern 30 among the electrodes, and the electrode of the upstream temperature sensor metal pattern 40A. The upstream temperature measuring device 52A is connected to 47, 48, and the downstream temperature measuring device 52B is connected to the electrodes 47, 48 of the downstream temperature sensor metal pattern 40B.

  Each of the temperature measuring devices 52A and 52B causes a current to flow between the electrodes 47 and 48 of the temperature sensor metal patterns 40A and 40B, measures the resistance value, and based on the resistance value, in each of the metal patterns 40A and 40B. The temperature of the sensor unit 42 is calculated.

  The temperature adjuster 50 causes a current to flow between the electrodes 37 and 38 of the heater metal pattern 30 to generate heat in the high-resistance heater 32, and based on the temperature calculated by the downstream temperature measuring device 52B. Energization control of the heater metal pattern 30 is performed so that the temperature approaches a preset target temperature. Further, the difference between the temperature measurement values output from the upstream temperature measuring device 52A and the downstream temperature measuring device 52B is monitored, and the difference does not match the current energization state of the heater metal pattern 30 (for example, the heater In the case where the difference in the temperature measurement value hardly occurs even though the metal pattern 30 is energized), a warning signal is output as the heater operation is defective.

  Further, an auxiliary heater 56 for keeping the substrate 10 at a predetermined temperature is attached to the lower surface of the wiring substrate 10. The auxiliary heater 56 has a medium flow path 58 for flowing a heating medium along the lower surface of the wiring board 10, and the temperature of the wiring board 10 is maintained at a predetermined temperature by supplying and discharging the medium. It has come to droop.

  Next, a preferred example of a method for producing this microreactor will be described. However, the microreactor according to the present invention is not limited to the one manufactured by the method shown below.

1) Substrate manufacturing process The wiring substrate 10 and the flow path substrate 12 are manufactured. These substrates 10 and 12 are more preferably formed of a ceramic material having high insulation and durability as described above. Specifically, the flow path substrate 12 is preferably formed of quartz or glass having low thermal conductivity and high transparency (that is, high internal visibility), and the wiring substrate 10 has relatively high thermal conductivity. It is preferable to mold with silicon or the like that can be easily bonded to the quartz or glass.

2) Heat insulation layer forming step A heat insulation layer 18 is formed on the wiring surface 14 of the wiring board 10. The heat insulating layer 18 may be formed over substantially the entire area of the wiring surface 14 as shown in the figure, but it is sufficient that it is interposed between the heater metal pattern 30 and the wiring surface 14 at least in the fluid flow path. For example, the heat insulating layer 18 may be locally formed in a shape corresponding to the shape of the pattern 30.

  A specific method for forming the heat insulating layer 18 can be appropriately set according to the material and the like. For example, in the case of applying a porous film made of silica aerogel, it is preferable to form the heat insulating layer 18 by the following procedure.

  2-1) Tetramethoxysilane (TMOS) is used as a raw material, and the solution is spin-coated on the wiring substrate 10.

  2-2) Holding the wiring board 10 in a container filled with ammonia water vapor at room temperature for a predetermined time to promote gelation of the solution to form a wet gel.

  2-3) The substrate is immersed in ethanol to replace methanol, water, and ammonia in the gel with ethanol.

  2-4) The produced membrane is kept in a high-pressure vessel while being immersed in ethanol, and is supercritically dried by passing supercritical carbon dioxide or the like.

  The heat insulating layer made of the porous film thus obtained is excellent in heat insulating properties but very sensitive to moisture adsorption, so that the surface can be coated with a waterproof film as described above. More preferred.

  In addition, after the heat insulating layer 18 is formed, the fluid inlet hole 27 and the fluid outlet hole 28 penetrating the heat insulating layer 18 and the wiring board 10 are formed.

3) Wiring process The heater metal pattern 30 and the temperature sensor metal patterns 40A and 40B are formed on the heat insulating layer 18. In order to form these patterns, for example, if a masking board having a through-hole having a shape corresponding to the shape of the pattern is placed on the heat insulating layer 18 and platinum or the like is deposited, a thin film pattern is formed. Good. In addition, a method such as pattern formation by printing or sticking of a thin metal plate punched in advance in a predetermined shape may be used. However, an extremely thin metal wiring can be efficiently formed by performing the film formation by the vapor deposition method as described above.

  In addition, the process of manufacturing the flow path substrate 12 in the “1) substrate manufacturing process”, “2) heat insulating layer forming process”, and “3) wiring process” are performed in parallel, for example, before and after. You may do it. Further, the auxiliary heater 56 may be attached at any stage.

4) Substrate superposition process Both substrates 10 and 12 are joined so that the facing surface 16 of the flow path substrate 12 is superimposed on the heat insulating layer 18 of the wiring substrate 10 on which the metal patterns 30, 40A, and 40B are arranged. . By this bonding, a fluid flow path surrounded by the wiring surface 14 of the wiring board 10 on which the heat insulating layer 18 is formed and the flow path forming recess 20 of the flow path substrate 12 is formed, and in the fluid flow path The heater portion 32 of the heater metal pattern 30 and the temperature sensor portion 42 of the temperature sensor metal patterns 40A and 40B are built.

  In the microreactor thus obtained, the fluid introduced from the fluid inlet hole 27 flows into the fluid inlet port 24, the fluid inlet passage portion 23, the main passage portion 22, and the fluid outlet passage portion 25 of the flow path forming recess 20. And through the fluid outlet port 26 and out of the fluid outlet hole 28.

  At this time, the temperature of the fluid is detected by the sensor portions 42 of the temperature sensor metal patterns 40A and 40B coming into contact with the fluid, and the energization of the heater portion 32 is controlled based on the detected temperature. The fluid is heated to the target temperature. At this time, the sensor unit 42 and the heater unit 32 are in direct contact with the fluid, and the heat conduction between the heater unit 32 and the sensor unit 42 and the wiring board 10 due to the presence of the heat insulating layer 18 having heat insulating properties. Therefore, rapid and highly accurate temperature control becomes possible, and a significant improvement in thermal efficiency can be expected.

  Furthermore, it is possible to keep the entire wiring board 10 at a suitable temperature by flowing a heating medium through the medium passage 58 of the auxiliary heater 56 as necessary.

A quartz substrate having a thickness of 1.0 mm is used as the channel substrate 12, and a channel having a depth of 90 μm is formed on the quartz substrate using photolithography. The shape of the main passage portion 22 in this flow path is 100 μm wide and 30 mm long. On the other hand, a 0.7 mm thick silicon substrate is used as the wiring substrate 10, and a 5 μm thick heat insulating layer 18 made of a silica airgel film is formed on the wiring surface 14, and a SiO ₂ thickness of 1000 μm on the surface thereof. A waterproof film of about 1 μm is formed. Then, after forming metal patterns 30, 40A and 40B having a thickness of 0.02 μm and a width of 100 μm on the heat insulating layer 18 by platinum vapor deposition, both substrates 10 and 12 are bonded together by hydrofluoric acid bonding to form a fluid flow path. .

  With respect to this structure, the temperature change after 1 second has elapsed after the start of heating at an initial temperature of 20 ° C. was obtained by simulation and compared with that without the heat insulating layer 18. In addition, the length of the heater portion 32 is 30 mm, the amount of heat released is 1.13 W, and water flows through the fluid flow path at a flow rate of 10 mm / s.

  FIGS. 6A and 6B show the simulation results. As shown in the figure, in the case without the heat insulation layer, the fluid temperature rises only to about 23 ° C. and the wiring board is heated to a temperature substantially equal to the fluid temperature, whereas the heat insulation layer In the case where a silica airgel film having a thickness of 0.5 μm is formed, the fluid temperature (temperature at the center position) rises quickly to about 29 ° C., while the wiring board temperature hardly rises (21 ° C.). It was. This result clearly shows that the microreactor according to the present invention has high warming response and excellent thermal efficiency.

  And since it has such an excellent temperature control characteristic, the microreactor according to the present invention can be applied to various fields. An example of its use is shown below.

  Use Example 1: PCR treatment for carrying out a DNA amplification reaction is as follows: “In the first stage (94 to 96 ° C.), the target double-stranded DNA is thermally denatured to form a single strand, and the second stage (55 to 60 The primer is annealed to single-stranded DNA at a temperature of 0 ° C.), and amplification is carried out by repeating a temperature cycle of “promoting the extension reaction at the third stage (72 to 74 ° C.)”. In order to reproduce in the microreactor shown in FIG. 1, the entire reactor is kept at 55 ° C. by the auxiliary heater 56 and then the 73 ° C. heating period and the 95 ° C. heating period are locally applied by energizing the heater metal pattern 30. Or the temperature may be continuously changed.

  Example of use 2: When conducting linear electrophoresis of proteins, as a pretreatment, a protein sample and a treatment solution are mixed and heated to a certain temperature to change the protein into a form that can be analyzed. Cost. In order to reproduce this process, it is necessary to send a protein sample and a processing solution in a microreactor and perform a three-stage process such as merging, mixing, and heating. The local heating temperature control mechanism of the vessel is very suitable.

1 is a perspective view of a microreactor according to an embodiment of the present invention. It is a top view of the said micro reactor. It is the sectional view on the AA line of FIG. FIG. 3 is a sectional view taken along line B-B in FIG. 2. It is CC sectional view taken on the line of FIG. (A) is a graph showing the results of a simulation of the fluid temperature rise associated with heater operation in each of the microreactor and the microreactor having no heat insulation layer, and (b) shows the heater operation in each microreactor. It is a graph which shows the result of having performed the simulation about the accompanying wiring board temperature rise.

Explanation of symbols

DESCRIPTION OF SYMBOLS 10 Wiring board 12 Flow path board 14 Wiring surface 16 Opposing surface 18 Heat insulation layer 20 Flow path formation recessed part 30 Heater metal pattern 32 Heater part 37,38 Heater metal pattern electrode 40A, 40B Temperature sensor metal pattern 42 Sensor part 47 , 48 Metal pattern electrode for temperature sensor

Claims (9)

  A flow path forming member for forming a fluid flow path therein, a metal wiring for a heater and a metal wiring for a temperature sensor formed in a specific region on an inner wall surface surrounding the fluid flow path, and the heater A microreactor, wherein a heat insulating layer having a higher heat insulating property than the flow path forming member is interposed between a metal wiring for use and an inner wall surface of the fluid flow path.   2. The microreactor according to claim 1, wherein the flow path forming member has a wiring surface on which the heat insulating layer and each metal wiring are arranged, and the wiring surface of the wiring substrate. And a flow path base material in which a flow path forming recess having a shape surrounding the metal wiring is recessed from the facing surface, the wiring surface of the wiring base material and the flow path base material Fluid that stores the metal wiring for the heater and the metal wiring for the temperature sensor between the wiring surface of the wiring base material and the flow path forming recess of the flow path base material by being overlapped with the opposing surface facing each other A microreactor characterized in that a flow path is formed.   3. The microreactor according to claim 1 or 2, wherein the heat insulating layer is constituted by a porous film.   4. The microreactor according to claim 3, wherein the heat insulating layer is composed of a porous film made of silica aerogel.   5. The microreactor according to claim 3, wherein a surface of the heat insulating layer is covered with a waterproof film having a higher hydrophobicity than a material constituting the heat insulating layer, and the metal wiring is disposed on the waterproof film. A microreactor characterized by that.   6. The microreactor according to claim 1, wherein the metal wiring is composed of a metal pattern formed on the heat insulating layer.   7. The microreactor according to claim 6, wherein the metal pattern has an electrode connected to an external circuit at an end thereof, and the electrode protrudes outward from the flow path base material and is exposed to the outside of the flow path forming member. A microreactor characterized by being configured to do so.   A flow path forming member for forming a fluid flow path therein, a metal wiring for a heater and a metal wiring for a temperature sensor formed in a specific region on an inner wall surface surrounding the fluid flow path, and the heater A method of manufacturing a microreactor in which a heat insulating layer having a higher heat insulating property than the flow path forming member is interposed between a metal wiring for use and an inner wall surface of the fluid flow path. Manufacturing a wiring base material having a step, forming a heat insulating layer having a higher heat insulating property than the wiring base material on the wiring surface of the wiring base material, and forming each metal wiring on the heat insulating layer A step of manufacturing a flow path base material having a facing surface facing the wiring surface of the wiring base material, and having a recessed flow path forming recess having a shape surrounding the metal wiring from the facing surface; Both flow paths are formed while facing the wiring surface of the base material and the facing surface of the flow path base material Forming a fluid flow path for storing each of the metal wirings by superimposing materials on the wiring surface of the wiring base material and the flow path forming recess of the flow path base material. Manufacturing method.   9. The method of manufacturing a microreactor according to claim 8, wherein the step of forming the heat insulating layer is a step of forming a porous film on the wiring surface, and after that step, the heat insulating layer is covered on the heat insulating layer. A method for producing a microreactor, comprising: forming a metal film on the waterproof film after forming the waterproof film.

Images