JP4615502B2 - Micro chemical reactor and channel substrate - Google Patents

Description

The present invention relates to a microchemical reaction apparatus having a novel structure in which microreactor apparatuses for performing various chemical operations are integrated, a channel substrate used therefor, and a method for manufacturing the same.

The microreactor device uses a small amount of sample solution for the reaction, the reaction proceeds quickly, and the obtained reaction result is highly accurate. For example, in the field of medical analysis and environmental analysis that require high sensitivity, It is attracting attention in the field of biochemistry where selective separation and identification of trace molecules are required.
As such a microreactor device, for example, a plurality of independent reaction chambers, injection ports, and discharge ports are formed on the surface of a Si substrate by anisotropic etching, and fine concave grooves communicating with these are formed. There has been proposed a biochemical reaction microreactor having a structure in which a flat plate made of glass material is arranged on top of a reaction chamber, an injection port, and an exhaust port to form a microchannel connecting them (see Patent Document 1). reference).

The microreactor device is a single plate-like body as a whole. The reagent is supplied from a through hole connecting the injection port and the back surface of the substrate, and the reaction product, the residual liquid of the reagent, and the like are discharged from the through hole connecting the discharge port and the back surface of the substrate. In the meantime, reagents and the like flow through the microchannel.
Further, the surface of the quartz glass substrate is irradiated with a CO ₂ laser to form a groove having a predetermined size and shape and a planar pattern, and a quartz glass cover body is disposed on the groove to seal the groove. Thus, a microchannel structure having a structure in which a microchannel is formed has been proposed.

In the case of this structure, a small hole for sample injection and a small hole for discharge are formed at a predetermined position of the cover body, and the sample is injected from the small hole for injection into a predetermined position (end part) of the microchannel, and for discharge. It is discharged from the small hole.
All of these prior art microreactor devices are designed to perform one type of chemical operation, such as a particular reaction operation, and the sample is supplied from the top or bottom surface of the substrate. It has a structure.

Further, a micro device having a laminated structure in which a plurality of plate-like micro reactor devices for performing a specific chemical operation are stacked has been proposed, for example, as a heat exchanger, a reactor, and a mixer (see Non-Patent Document 1). ).
Such an apparatus having a laminated structure is said to exhibit high productivity as compared with a case where the unit microreactor apparatus constituting the apparatus is operated alone. However, these devices having a laminated structure have only a function of performing a specific chemical operation.

By the way, when a chemical reaction is considered, it includes mixing a fluid sample for reaction, performing a controlled heat treatment on the mixed sample to accelerate the reaction, and separating reaction products and by-products. In other words, it is an accumulation of a series of basic operations such as detecting reaction products.
In any of these operations, a predetermined sample is supplied to a chemical reaction field (reaction system) to advance a chemical reaction, and finally, a process required in the process of separating reaction products. This operation includes, for example, sample supply, mixing, reaction, separation (or extraction), detection (measurement), etc. Also, regarding reaction processing, measurement of reaction state, promotion of reaction, reaction system There are processing operations such as process control such as heating and cooling.

In the following description, the above-described processing operations required for realizing a chemical reaction are collectively referred to as a chemical operation.
From this point of view, a sample mixing area, reaction area, separation area, reaction product detection area, etc. are sequentially formed on a single substrate from the sample supply section to the discharge section. An integrated microreactor device with a structure connected with each other is conceived.

  As such an integrated microreactor device, for example, in the field of DNA analysis, a place where a sample is mixed on a substrate of several centimeters square, a place where the reaction of the mixed sample proceeds, a place where a reaction product is separated / extracted, a reaction generation There is known a μTAS (Micro Total Analytical System) having a structure in which each chemical operation is integrated in one substrate by forming a part for detecting an object and connecting them with a microchannel.

However, in the case of such an integrated type microreactor apparatus, it is considerably difficult to manufacture in a plane a region for performing various chemical operations in a small substrate.
Even if a small-sized microreactor device is obtained by incorporating all the regions into one substrate, sample supply to the device, separation of reaction products, connection to another device, etc. Therefore, since ordinary piping, joint means, etc. are used, the dead space is increased and the entire apparatus is increased in size and the advantage that the shape is small is reduced.

  In such an integrated microreactor device, the area of each chemical operation incorporated in the substrate and the structure of the microchannel are designed on the premise of a chemical operation under a specific condition relating to a specific reaction system. For example, if the microchannel structure or the flow path length needs to be changed due to the change of the sample in the reaction system, or if the chemical operation conditions need to be changed, it is impossible to cope with it. In such a case, it is eventually necessary to remanufacture a new device at a high cost under a new design standard. That is, this apparatus has a problem that the degree of freedom in changing the reaction system is poor.

Further, in the case of this integrated microreactor apparatus, for example, process control of the reaction system such as heating control and cooling control can be performed on the entire apparatus. However, it is virtually impossible to implement process control for each chemical operation, each requiring specific conditions, independently for each area of chemical operation.
On the other hand, when a microreactor device is manufactured, a substrate in which microchannels having a predetermined dimension and shape are formed in a predetermined plane pattern and a region for performing a certain chemical operation is formed (hereinafter referred to as a channel substrate). Must be manufactured.

Conventionally, as a channel substrate, for example, a glass (quartz glass) substrate, a Si substrate, a substrate made of various resins, and the like are used, but various methods are available for manufacturing microchannels corresponding to the type of substrate material. Has been applied.
For example, by applying a LIGA technology combining X-ray lithography and electroplating to the surface of a raw substrate, or applying a semiconductor process technology combining ultraviolet lithography and etching technology, After the concave groove for the microchannel is formed, a flat plate is disposed and fixed therein, thereby sealing the concave groove to form a microchannel.

In addition, when forming a microchannel on a resin substrate, for example, a raw substrate made of an ultraviolet curable resin is prepared, and on its surface, an optical modeling method for performing exposure and development processing using ultraviolet rays is applied. A microchannel is formed by engraving a concave groove for a microchannel on the substrate and then sealing it.
Furthermore, after engraving the groove for the microchannel on the surface of the unprocessed substrate by directly applying a laser processing method or an ion beam processing method that irradiates a laser beam or an ion beam with a predetermined scanning pattern, The microchannel is formed by sealing it with a flat plate.

However, these methods have the problem that the equipment and devices used are expensive, the conditions are severely set, and the manufacturing process is complicated, so that the manufactured channel substrate is expensive.
In particular, for example, when a finer structure is selectively added to the surface of the formed microchannel, the process for that purpose becomes more complicated.
JP 10-337173 A JP 2000-298109 A Chem. Tech., (1998). 27. pp124-126

The basic object of the present invention is to solve the problems in the conventional integrated microreactor device described above.
That is, in the present invention, even if a channel substrate that does not necessarily require planar integration of chemical operation regions necessary for the reaction system is used, the function as an integrated microreactor device is exhibited as a whole, The purpose of the present invention is to provide an integrated microchemical reaction apparatus and an auxiliary unit connected to the integrated microchemical reaction apparatus that are easy and have a large degree of freedom in changing reaction systems and that can also control individual processes for individual chemical operations. To do.

  Further, in the present invention, a channel substrate having a novel structure that is incorporated in the above-described microchemical reaction apparatus and performs a predetermined chemical operation, and a method for manufacturing the same with a high productivity compared to the conventional method are provided. For the purpose of provision.

In order to achieve the above object, in the present invention,
A substrate body, and a channel extending from one end surface to the other end surface inside the substrate body and having at least one opening on each of the one end surface and the other end surface of the substrate body; There is provided a chemical reaction channel substrate having a protruding portion protruding in a region surrounding the opening on at least one of the one end surface and the other end surface.
Furthermore, the chemical reaction channel substrate, and a frame-like body having a through hole for accommodating at least one chemical reaction channel substrate by projecting the protruding portion of the chemical reaction channel substrate to the outside. A microchemical reaction device is provided.

  This micro chemical reaction apparatus has a structure in which various chemical operation units that exhibit different functions are detachably connected. Therefore, for example, when the reaction system needs to be changed, the chemical operation unit that needs to be changed is replaced with another chemical operation unit that is compatible with the new reaction system, or is newly connected and added to the apparatus. Can cope with such a situation.

Further, since the chemical operation units are directly and hermetically connected with each other without using a conventional joint means, a dead space associated with the conventional connection does not occur.
Further, by connecting an auxiliary unit having a sensor means or the like to the chemical operation unit, it is possible to accelerate, measure, control, etc. the chemical operation that proceeds in the chemical operation unit.

In the channel substrate of the present invention, since an optical waveguide is formed across the microchannel through which the sample is sent, the state of the sample being sent is optically measured by introducing, for example, laser light. Alternatively, the chemical operation can be activated by supplying light energy such as ultraviolet light, visible light, and infrared light to the sample.
In addition, since the microchannel of the channel substrate is formed with a chemical operation promoting portion that is in charge of the channel substrate, the microchannel can exhibit a function more than the function of the sample flow channel. .

  Since this channel substrate uses a glass material as a material, it can be molded, and as a result, even if the microchannel to be formed has a complicated shape, it is easy to manufacture and the manufacturing cost is also low. It will be cheaper.

An example of the microchemical reaction apparatus of the present invention is shown in FIG. 1 as an exploded perspective view.
This apparatus includes a supply unit U ₁ that performs a chemical operation of supplying a sample to the apparatus, a mixing unit U ₂ that performs a chemical operation of mixing the supplied sample, and an operation unit U ₃ that performs a reaction operation of the mixed sample. The reaction unit and the flow unit U ₄ that performs the chemical operation for flowing the reaction product and other waste liquid are kept in airtight state at the respective end surfaces and are detachably connected in series. ing. Then, the side portion of the operation unit U _3, described later auxiliary unit u is connected.

In FIG. 1, the reaction unit is composed of the mixing unit U ₂ and the operation unit U ₃ , but both units U ₂ and U ₃ are not necessarily required. For example, the structure of each channel board installed in each unit U ₂ , U ₃ is formed on one board and installed in either unit, so that mixing and operation can be performed in one unit. Yes, you can omit one of the units.

In this apparatus, the supply line 1a connected to the supply unit U _1, 1b, 3 kinds of sample supplied to the supply unit U ₁ from 1c is flowed sent to the mixing unit U ₂ are mixed here, mixed The sample is sent to the operating unit U ₃ where a predetermined chemical reaction takes place and then sent to the sending unit U ₄ where it is split into reaction products and waste liquid, each connected to the sending unit U ₄ . The discharged liquid lines 2a and 2b are discharged out of the apparatus.

Here, each chemical operation unit is constituted by at least one channel substrate and a frame-like body that encloses and supports the channel substrate. The example U _A shown in FIG.
The unit U _A, upon the assembly, first, a laminated structure having a five channel substrate 3 of each other's end faces 3a end surface 3A and stacked with aligned (3b) (3B). When laminating each channel substrate, for example, a method in which each channel substrate is bonded and integrated with an adhesive, a method in which the channel substrates are integrated by thermocompression bonding, a method in which an appropriate jig is used with reference to the end face, and the like. Can be applied.

In the figure, an example in which five channel substrates are stacked is shown, but the number of stacked channel substrates is not limited to five, and may be any number. The size of the end face of the laminated structure is preferably 100 mm × 100 mm or less. This is because the flatness of the end face can be sufficiently obtained. The channel substrate used during assembly of the unit U _A may be one.

Here, an example of the channel substrate is shown in FIG. 4 which is a cross-sectional view taken along line IV-IV in FIGS. The channel substrate has a thickness of about 0.3 to 3 mm, a width of about 3 to 100 mm, and a length of about 10 to 100 mm.
In the channel substrate 3, a hollow microchannel 5 extending in a predetermined plane pattern from one end surface 3a to the other end surface 3b is formed in the above-described square plate-shaped substrate body 4. One plate-like body.

Therefore, in the case of this channel substrate 3, both end portions 5a and 5b of the microchannel, which is a sample flow path, are opened at the end surfaces 3a and 3b of the substrate body 4, respectively, for example, one is the sample inlet and the other is the sample. Functions as an outlet.
For example, the width and depth of the microchannel 5 are about 0.05 to several mm, and the cross-sectional shape is substantially square or rectangular, but semicircular or circular cross-sectional shapes are also possible.

As a material constituting the substrate body 4, a glass material, Si, resin, or the like can be used as in the conventional case. For example, when the operation unit U ₃ shown in FIG. It is preferable that
The planar pattern of the microchannel 5 in the channel substrate 3 and the overall flow path length, its cross-sectional shape, its surface structure, etc. are appropriately designed in relation to the chemical operation realized by the chemical operation unit in which the channel substrate is incorporated. do it. The microchannel 5 is designed in consideration of the form of the sample (for example, gas, liquid, solid, viscous body).

In the case of the channel substrate shown in FIG. 3, the end 5a (5b) of the microchannel 5 and the other region B are on the same plane, and the end surface 3a (3b) of the channel substrate forms a flat plane as a whole. is doing.
The end face of the channel substrate in the present invention is not limited to the above-described embodiment. For example, as shown in FIG. 5, the peripheral region A of the end portion 5a (5b) of the microchannel is defined with respect to the region B. The end surface 3a (3b) may be formed by projecting the entire region A.

In the present invention, the end face of the channel substrate is defined as including the embodiment shown in FIG.
Returning to FIG. 2 again, when the assembly of the units U _A, frame-shaped body 6 is used. This frame-like body 6 has a through hole 6c having substantially the same size and shape as the cross section of the laminated structure of the channel substrate (cross section in the direction perpendicular to the extending direction of the microchannel), and the length of the laminated structure of the channel substrate. Have substantially equal lengths. Then, the laminated structure is inserted and arranged in the through hole 6c of the frame-like body 6 in a state where both end faces 6a, 6b of the frame-like body 6 are aligned with both end faces 3A (3B) of the laminated structure. For example, the laminated structure is fixed to the frame using an adhesive.

In this way, the unit assembled U _A, as shown in FIG. 2, the laminated structure of the channel substrate, the frame-like body in a state of being encapsulated its side-top, the lower surface in the frame body 6 6, the end surface 3A (3B) of the laminated structure and the end surface 6a (6b) of the frame-like body 6 face the same direction.
Therefore, within this unit U _A, though traveling towards microchannels 5 of each channel substrate 3 which opens at both end faces from one end face 3A on the other end surface 3B, flow sending samples for the units U _A A flow path is formed.

_A plurality of (four in the figure) positioning pin holes 6d, which will be described later, are provided on the end surfaces 6a and 6b of the frame 6 in the unit UA.
It shows another example unit U _B in FIG.
In this unit, the frame-like body 6 has a divided structure of a lower member 6A having a groove 6e and a pressing plate 6B, and the already described channel substrate laminated structure is arranged in the groove 6e, and the pressing plate is placed thereon. 6B is arranged, and the lower member 6A and the pressing plate 6B are screwed or bonded, for example, and the laminated structure is supported by the frame-like body 6.

FIG. 7 shows still another example unit U _C.
The unit U _C, in units U _A shown in FIG. 2, the opening 6f is formed on one side or both sides of the frame-shaped body 6. A plurality of (four in the figure) positioning pin holes 6d, which will be described later, are also provided around the opening 6f.
Therefore, the side surface of the channel substrate 3 (or its laminated structure) supported by the frame 6 is exposed from the opening 6f.

This type of unit U _C is a unit suitable for use as the operation unit U ₃ shown in FIG. 1, for example. That is, as will be described later, an auxiliary unit u described later is connected to the opening 6f using the positioning pin hole 6d, and auxiliary means provided in the auxiliary unit, for example, laser light irradiation means for heating the object is driven. This is because it is possible to assemble a reaction system that increases the efficiency of the intended reaction by heating the sample fed into the microchannel 5 of each channel substrate 3.

Showing still another example unit U _D in FIG.
The unit U _D is stacked structure of the channel substrate 3 is frame-shaped body 6C at both ends, a chemical operation unit of the supported types through 6D. Therefore, if the unit U _D, the channel substrate 3 (or a laminated structure), portions other than both ends are supported frame body 6C, in 6D is in a state of out naked. For the structure of the unit U _D, it is possible to observe the end 5a of the microchannel 5, portions other than 5b from above and below. In other words, the reaction state of the sample can be observed from above and below.

The above-described units U _A , U _B , U _C , and U _D are all examples in which microchannels are two-dimensionally arranged on the end surfaces of each unit by using a laminated structure of a plurality of channel substrates. However, the unit of the present invention is not limited to this mode. For example, the unit U _D ′ having the structure shown in FIG. 9 may be used.
This unit U _D ′ is a type of chemical operation unit in which the channel substrate 3 is one in the unit U _D shown in FIG. 8 and both ends thereof are supported by the frame-like bodies 6C and 6D. Therefore, the microchannels 5 in the unit U _D ′ are arranged one-dimensionally in the width direction.

  Each of these chemical operation units is provided with a plurality (four in the figure) of pin holes 6d at predetermined positions on the end face of the frame-like body. The pin holes 6d cause the opening end surfaces of the microchannels 5 in the channel substrate 3 (or the laminated structure) supported by the respective units to be displaced in the plane when the units are connected to the end surfaces. It is a means for positioning the units relative to each other so that they are correctly connected.

In the case of units U _C in FIG. 7, the pin hole 6d to the sides of the frame-shaped body is formed, which is the auxiliary unit u shown in FIG. 1 in the opening 6f of side It is provided to connect the positions accurately.
These chemical operation units are connected to each other at their end faces, and the microchemical reaction apparatus illustrated in FIG. 1 is assembled.

In that case, the microchannels of the respective units are correctly connected without causing in-plane positional deviation at the opening end surfaces of the respective units, and a connecting flow path from the supply unit U ₁ to the flow sending unit U ₄ is formed, and At the same time, it is necessary to ensure an airtight state in the connection portion of the channel substrate (or its laminated structure).
When the airtight state of the connection portion is not ensured, the sample leaks at the connection portion. In addition, if each microchannel is connected with an in-plane misalignment, the flow of the sample may be disturbed due to the step of the flow path generated at the connection, or the flow resistance may increase, resulting in This is because the result of the chemical operation in the unit deviates from the set target value. In any case, when the above two conditions are not satisfied, the microchemical reaction device does not operate according to the design standard.

In order to realize the above-described problem, in the present invention, first, the following processing is performed for maintaining the airtight state in the connecting portion of the unit.
The first treatment is to perform precision grinding / polishing on both end faces of each channel substrate (or its laminated structure).
This will be described below with reference to the drawings.

Now, as shown in FIG. 10, the end face of the channel substrate 3 1, 2, 3 · · · n-number of the micro-channels 5 _1, 5 _2, 5 ₃ open end of · · · 5 _n is not exposed A region surrounded by the width t from the periphery of each opening end is A ₁ , A ₂ , A ₃ ... _An , and the other end face is a region B.
Here, the reason why the areas A ₁ , A ₂ , A ₃ ... _An are assumed is that, when the channel substrate 3 is connected to this area regardless of the area B, reliable airtightness between the microchannels is obtained. This is because it is considered to be a region that substantially contributes to realizing the state body.

When the end face state is defined as described above, in the present invention, precision grinding and polishing are performed so as to satisfy the following conditions.
First, there all the end faces of the region _{A 1, A 2, A 3} ··· A n coplanar, and that protrudes from the end face of the end face on the same plane or area B of the area B It is. The region A _1, A _2, A ₃ flatness of the surface of the · · · A _n is 1μm or less, preferably 0.5μm or less, and whose surface roughness is 100nm or less, preferably becomes 10nm or less It is that you are. Furthermore, the width t is in the range of 10 μm to 1 mm.

For example, as shown in FIG. 11, regions A _1, A _2, A ₃ when all · · · A _n does not exist on the same plane, only if one of the areas A ₁ is area B Even if it protrudes more, it is impossible to realize an airtight state at the time of connection. Further, as shown in FIG. 12, even if the areas A ₁ , A ₂ , A ₃ ... _An are all on the same plane, a part of the area B is part of the areas A ₁ , A ₂ , if protrudes from a ₃ ··· a _n, it is impossible to realize an airtight state at the time of connection even if the.

On the other hand, as shown in FIG. 13, when the areas A ₁ , A ₂ , A ₃ ... _An and the area B are all on the same plane, or as shown in FIG. ₁ , A ₂ , A ₃ ... _An are all on the same plane and protrude from the region B, the argument, flatness, surface roughness, and t value are the above values. As long as it is satisfied, a completely airtight connection can be formed.

Further, as shown in FIG. 15, the areas A ₁ , A ₂ , A ₃ ... _An are all on the same plane, and as long as they protrude from the area B, the areas B are recessed or bordered. Even in the case where part sagging occurs, it is possible to connect in an airtight state.
In the case of a channel substrate (or a laminated structure thereof) that has been subjected to this precision grinding / polishing treatment, even when a water pressure of 20 to 100 MPa is applied as a pump pressure in the microchannel in a state where the end surfaces are pressed and connected to each other. , No leakage at the connection. That is, a high level of airtightness is maintained.

Since there is piping resistance, the pressure that actually acts on the connecting portion is smaller than the pump pressure.
By the way, in the case of a unit using a channel substrate (or a laminated structure thereof) that has been subjected to this processing, it is necessary to make its end face slightly protrude from the end face of the frame-like body during assembly. If the end face of the channel board (or its laminated structure) is recessed from the end face of the frame-like body, the end faces of the channel board (or its laminated structure) will not contact each other even if the units are connected. is there.

However, such a state may collide with an end surface portion of the channel substrate (or a laminated structure thereof) when connecting the units, and cause damage to the portion.
In consideration of such a problem, it is preferable that the following second process is performed in the present invention.
That is, in the second process, both end surfaces of the already assembled unit itself are precision ground and polished.

In that case, at least the flatness and the surface roughness of the end face of the channel substrate (or its laminated structure) are maintained at the same level as in the case of the first treatment described above.
By performing the second process, in the unit after the process, the end face of the channel substrate (or its laminated structure) and the end face of the frame-like body are flush with each other.
However, strictly speaking, in the case of this second process, a minute step of the order of several tens to several hundreds of nanometers occurs at the boundary between the channel substrate (or its laminated structure) and the frame. Therefore, if the units are connected as they are, the airtight state of the unit connection portion is deteriorated as compared with the case of the first processing. Nevertheless, an airtight state can be realized even when a water pressure of 20 to 70 MPa is applied as the pump pressure.

Therefore, the second treatment can realize a significant reduction in the number of assembling steps, although the airtight state is slightly deteriorated compared to the first treatment that requires assembly of the unit after precision grinding / polishing. Moreover, it is excellent in the point that the damage of an end surface part can be eliminated reliably.
The above-described precision grinding / polishing is performed using a grindstone. In that case, the polishing operation is advanced step by step from polishing using a small number of grindstones to polishing using a grindstone having a large number. . For example, the both ends of a channel substrate (or its laminated structure or assembled unit) are ground with a rough rotating grindstone, and the ground surface is, for example, ultrasonically cleaned and then dried, and then, for example, cerium oxide, magnesium oxide, silicon carbide Alternatively, the above-described ground surface is polished using a rotating grindstone partially mixed with silica or the like, or free abrasive grains such as cerium oxide or colloidal silica.

In this process, the number of grindstones, the grain size of the abrasive grains, etc. are appropriately selected according to the type of glass material constituting the channel substrate and the size of the substrate, and the number of times of polishing is increased or decreased. By appropriately selecting the conditions, the flatness and surface roughness of the final finished end face can be set to the above-described values.
Note that the second treatment described above can be performed only by precision grinding. In that case, a 1000 or more grindstone is used. The surface roughness is slightly deteriorated, but the flatness is improved. Therefore, when the grinding area is large, the resin does not react with the supply sample (for example, polyimide resin, polyimide amide resin, etc.), or rubber (for example, , Viton rubber, silicone rubber, etc.) is advantageous in that leakage is suppressed.

Next, the alignment at the end face connection between the units will be described with reference to the case of FIG. 1 where the end face connection between the mixing unit U ₂ and the operation unit U ₃ is taken as an example.
The mixing unit U ₂ the unit U _A type, operating unit U ₃ shown in FIG. 2 is a type of unit U _C shown in FIG.
In any unit, as shown in FIG. 16, the end surface 3A of the laminated structure of the channel substrates protrudes from the end surface 6a of the frame-like body 6 at the end surface, and the end surface 3A has been described above. Precision grinding (second treatment) is performed. By causing the end face 3A of the laminated structure to protrude from the end face of the frame-like body 6, when the units are connected, only the end face 3A of the laminated structure abuts each other, so that the supply caused by the increase in the overall connection surface pressure The problem of sample leakage can be solved.

In consideration of the above, the protruding amount of the end face 3A is set to 100 μm or less, preferably 1 to 10 μm.
Both end surfaces 6a of the frame body 6 of the mixing unit U _2, the 6b, 4 pieces of positioning pin holes 6d having a predetermined diameter and depth is formed, also at both ends of the frame-shaped body of the operating unit U ₃ even surface, likewise four positioning pin hole at a position facing the positioning pin hole of the mixing unit U ₂ is formed.

The fitting pin 7 having a diameter that can be inserted into and removed from the pin hole 6d and having a length slightly shorter than the total depth of the two pin holes, as indicated by the arrow in FIG. After insertion into the respective pin holes 6d formed in the opposing end surface of the U ₂ and the operation unit U _3, to press along the one of the units in the flow direction of the microchannel 5 on the other unit. The fitting pin 7 may be integrally formed with the mixing unit U ₂ or the operation unit U ₃ .

The fitting pin 7 is set to a diameter smaller by 0.1 to 2.0 μm than the pin hole 6d.
By setting the diameter of the fitting pin to the above-mentioned value, as shown in FIG. 17, the positional deviation between the unit U ₂ and the unit U ₃ is minimized at the place where the fitting pin 7 is fitted. It is relaxed and high-precision alignment can be realized.
Further, even when one unit is pressed along the flow direction of the microchannel after the pin is fitted, even if a twist occurs and an opening occurs between the end faces of the unit as shown in FIG. The amount of opening is reduced, so that leakage is effectively prevented. In addition, since the fitting pin is shorter than the total depth of the two pin holes, the end surface of the mixing unit U _{2 and} the end surface of the operation unit U ₃ are securely in contact with each other while ensuring the airtight state described above. Connected airtight. The position accuracy of the fitting pin between the corresponding units is set to ± 5 μm or less, preferably ± 0.5 μm.

However, even if the respective pin holes 6d on the opposing end surfaces of the mixing unit U ₂ and the operation unit U ₃ are not positioned relative to each other, the micro of the channel substrate (or its laminated structure) with respect to the pin holes of the mixing unit U ₂ the position coordinates of the channel, when the position coordinates of the microchannel of the channel substrate for the pin hole of the operating unit U ₃ (or a lamination structure) are different from each other, open end face of the microchannel position Families in the plane Wake up. As a result, even if the airtight state at the connection part between the units is ensured, an apparatus in which the connection channel of the microchannel is not correctly formed is assembled.

In the present invention, such a problem can be solved by using the following chemical operation unit.
FIG. 19 shows one example U _A ′, and FIG. 20 shows another example U _A ″.
In the case of the chemical operation unit U _A ′ in FIG. 19, a plurality ( Two inverted V-shaped rails 6g and 6g are integrally formed. A position opposite to the inverted V-shaped rails 6g and 6g is formed on the lower surface of the channel substrate 3 (or its laminated structure) inserted and disposed in the through hole 6c along the flow direction of the microchannel. V-grooves 3c and 3c having a shape and size with high accuracy and a negative-positive relationship with the inverted V-shaped rail are engraved.

The V-shaped groove 3c and the inverted V-shaped rail 6g are engaged, and the channel substrate 3 (or a laminated structure thereof) is fixed in the through hole 6c using, for example, an adhesive, whereby the chemical operation unit U _A ′ is configured. Has been.
In this way, the channel substrate 3 (or its laminated structure) and the frame-like body 6 are fixed with high accuracy by engaging the V-shaped groove 3c and the inverted V-shaped rail 6g with the positioning pins described above. Can do.

In that case, it is necessary to make the outer dimension of the channel substrate 3 (or its laminated structure) smaller than the dimension of the through hole of the frame-like body 6. Specifically, the clearance between the two is set to 5 to 20 μm.
When the both are bonded and fixed, the above-described clearance is filled with an adhesive, and as shown in FIG. 21, an adhesive layer is interposed between the two. By interposing this adhesive layer, deformation of the channel substrate 3 (or its laminated structure) due to external stress is alleviated.

When all of the supply unit U ₁ to the flow unit U ₄ have the above-described structure, when pin holes are formed on the end surfaces of the respective units, the channel substrate 3 ( Alternatively, if a predetermined position (for example, a specific corner portion of a specific microchannel) of the laminated structure is used as a positioning reference, pin holes in all the units are formed with a common position coordinate.

In other words, if the corresponding pin holes of each unit are matched, the open end faces of the microchannels 5 in the channel substrate 3 (or the laminated structure) of each unit are connected without causing any positional displacement. Become.
The chemical operation unit U _A ″ in FIG. 20 has a V-shaped groove 6h formed in place of the inverted V-shaped rail of the unit U _A ′, and the V-shaped groove 6h on the lower surface of the channel substrate 3 (or a laminated structure thereof). For example, a V-shaped groove 3d having the same shape as that of the V-shaped groove 6h is formed at a position opposite to the V-shaped groove 6h, and a positioning pin 7A is inserted into a space formed by two types of V-shaped grooves. Or the laminated structure) and the frame-like body 6 are aligned.

This unit U _A "also exhibits the same function as the unit U _A '.
By exercising such means, if the mixing unit U ₂ and the operation unit U ₃ are connected to the end face using pin holes and pins, the opening end face of the microchannel of each unit will be almost displaced in the plane. Are connected correctly, and a connecting flow path is formed through the mixing unit U ₂ and the operation unit U ₃ .

  At this time, in consideration of the fact that the cross-sectional dimension of the microchannel 5 is in the range of several tens of μm to several hundreds of μm as described above, in the present invention, the accuracy with respect to the positioning reference described above is 5 μm. Hereinafter, it is preferably set to 0.5 μm or less. If the pin hole positioning accuracy is the above set value, the cross-section of the microchannel is extremely large compared to this misalignment even if a misalignment occurs in the plane between the microchannels when the units are connected. Therefore, inconvenient phenomena such as disturbance in the flow state of the sample in the connected flow path formed and stagnation of the sample at the connection portion do not occur. Note that the accuracy of the positioning reference is set to 1/20 to 1/10 of the length of one side of the microchannel.

  For example, a channel substrate and a frame-like body are both made of transparent glass, and the pin hole positioning accuracy is set to 0.5 μm, and a unit that has been subjected to precision polishing of the end face by the second treatment described above is connected. Then, when colored water was sent to the connecting channel at a pump water pressure of 20 to 70 MPa and the channel was observed under a microscope, phenomena such as stagnation at the connection and mixing of colored water from other connecting channels were observed. I couldn't.

Then, after separating each unit and reconnecting it 10 times, a test similar to the above was carried out, but no mixing of colored water into the connection channel or stagnation in the connection portion was observed. .
Here, a description will be given of a connector member suitable for use in supplying a sample to the microchemical reaction apparatus of the present invention and collecting a reaction product and a drainage liquid.

There are two types of connector members: a sample supply connector member and a recovery connector member. The former is disposed on the most upstream side of the microchemical reaction apparatus, and the latter is disposed at the end of the entire apparatus. .
For example, according to the apparatus shown in FIG. 1, the supply connector member corresponds to the supply unit U ₁ connected to the mixing unit U ₂ , and the recovery connector member is connected to the operation unit U _3. and which corresponds to the flow sending unit U _4.

Here, FIG. 22 shows an example C of the connector member.
The connector member A includes a main body 12 made of, for example, a glass material or a resin, a plurality of microtubes 13 and a connector 14 connected to a branch ferrule (not shown).
One end surface 12a of the main body 12 is a connection end surface with a chemical operation unit to be connected (for example, the mixing unit U _{2 in} FIG. 1), and there are a plurality of (four in the figure) positioning positions already described. The pin hole 6d is formed, and the end face thereof is in a state in which an airtight state can be secured when connected to the target chemical operation unit by performing the above-described precision grinding and polishing.

The main body 12 has a plurality of through holes arranged from the connection end surface 12a to the other end surface corresponding to the arrangement of the opening portions of the microchannels exposed on the connection end surface of the chemical operation unit to be connected. 15 is formed. On the other end face side of the main body 12, each through-hole 15 and each microtube 13 are connected by a connector 14.
In addition, the number of the through-holes 15 is designed suitably by the connection structure with the chemical operation unit connected. For example, in FIG. 22, a total of 16 holes of 4 rows × 4 rows of through holes 15 are formed, which corresponds to the number of chemical operation units to be connected or supplied (not shown). This is because. For this reason, if the number of chemical operation units supplied or fed is four, a total of four holes of 4 rows × 1 row may be formed as the through holes 15.

In this manner, the connector member C is formed with a plurality of sample supply paths having a connecting flow path of the microtube 13 ← → connector 14 ← → through hole 15 ← → connection end face 12a.
Here, the diameter of the through hole 15 is larger than the opening of the microchannel exposed on the connection end face of the chemical operation unit to be connected. This is to ensure an airtight state by accommodating the opening of the microchannel within the diameter of the through hole 15 when the connector member and the chemical operation unit are connected to the end face.

For example, when the connection end surface of the microchannel in the chemical operation unit to be connected is formed in the protruding region A as shown in FIG. 5, the diameter of the through hole in the connection end surface of the connector member C is The size is set so as to include the above-described region A.
However, if the diameter of the through hole 15 is made too large, the flow of the sample is disturbed at the connecting portion. Therefore, the diameter of the through hole is preferably about 5 to 10 μm larger than the opening of the microchannel.

Another connector member D is shown in FIG.
The main body 12 of the connector member D has a plurality of (four in the figure) positioning pin holes 6d formed on the connection end surface 12a, and a cavity 16 is formed by cutting the central portion to reach the other end surface. Has been. On the other end surface side of the main body 12, the cavity 16 and a SUS tube 17 are connected by a connector 14. The tube 17 is not particularly limited as long as it is not broken by the pressure received from the sample to be sent, such as aluminum, copper, resin, etc., other than SUS.

The size of the cavity 16 described above is such that it can include all of the openings of the microchannels exposed on the connection end face of the chemical operation unit to be connected. The connector member C shown in FIG. The same as in the case of the through hole.
This connector member D is mainly used in the following manner.
First, one end face (upstream end face) has, for example, one sample inlet, the other end face (downstream end face) has a plurality of sample injection ports, and a plurality of branching from the sample inlet. It is used by being connected to the one end face of the chemical operation unit composed of a channel substrate having a sample supply channel.

That is, the sample supplied from the tube 17 is filled in the cavity 16 and then supplied into the unit from one sample inlet of the chemical operation unit.
Conversely, it can also be used to join the samples flowing out from the microchannels of the chemical operation unit by connecting to the downstream end face of the chemical operation unit.
24 shows a pin-pin hole for positioning the unit U ₂ and unit U ₃ shown in FIG. 1 and the connector members C and C (corresponding to unit U ₁ and unit U ₄ in FIG. 1) to each other. 1 shows a microchemical reaction apparatus assembled by pressing the end face using a connecting clip 18 having a spring function in the longitudinal direction (flow path direction).

In this apparatus, for example, the connection portion between the connector member C and the unit U _{2 or} the connection portion between the unit U ₃ and the connector member C is formed in an arrangement corresponding to the arrangement of the microchannels as shown in FIG. If a sealing film in which holes corresponding to the holes and the positioning pin holes are formed is interposed, a further fluid-tight state is secured.
When the connector member connected to the unit U ₃ is the member D as shown in FIG. 23, a seal film as shown in FIG. 26 may be interposed.

Next, the channel substrate and the auxiliary unit of the present invention will be described. First, the channel substrate will be described.
An example A ₁ of the channel substrate of the present invention shown in FIG. 27.
In the channel substrate A ₁ , a microchannel 5 having a Y-shaped planar pattern extends from one end face 3 a to the other end face 3 b in the substrate body 4. An optical waveguide 9 connecting one side end surface 3e of the substrate body 4 to the microchannel 5 is formed. That is, the substrate body 4 as a whole is made of a glass material and has translucency, and the portion of the optical waveguide 9 described above is a core portion having a higher refractive index than the other portions.

In this channel substrate, for example, different types of samples are fed from the two sample inlets 5a and 5a ′ opened to one end surface 3a, the sample is mixed at the junction 5c, and the mixed sample is mixed with the other end surface 3b. a substrate for performing a mixing operation of the sample that flow sending from the opening to the sample outlet 5b microchannels of another channel substrate, incorporated for example in the mixing unit U ₂ in the apparatus of FIG.

Then, for example, a laser beam irradiation unit which is an auxiliary unit described later is attached to the side end surface of the substrate body, and the laser beam is incident from the end surface 9a of the optical waveguide 9 and used.
The mixed sample obtained at the junction 5 c is heated by laser light emitted from the other end surface 9 b of the optical waveguide 9. The laser beam used at this time may be a laser beam having a wavelength that can be absorbed by the sample being sent.

  The above-described optical waveguide 9 can be formed at a desired location on the substrate body 4 by various methods. For example, it is preferable to form the optical waveguide 9 using a hemtosecond laser beam having a pulse width on the order of hemtoseconds. According to this method, after the microchannel is formed in the substrate body, it is possible to form an optical waveguide that is accurately positioned at an arbitrary position of the substrate body, and it can be partially formed. is there.

  When the optical waveguide 9 is formed by this hemtosecond laser, first, as shown in FIG. 28, the substrate body 4 on which the microchannel 5 is already formed is prepared. Then, the power of hemtosecond laser light oscillated from a Ti: sapphire laser is adjusted with an ND filter, and the lens is used to adjust the depth of the microchannel 5 in the substrate body, specifically the height direction of the side surface of the microchannel. The focal point of the laser beam is focused on the depth of the central part of the substrate, and in this state, a planar pattern of the optical waveguide 9 to be formed in the plane of the substrate body is drawn. For example, in the case of FIG. 27, the irradiation position of the laser beam may be linearly shifted from the position of the side end face 3e of the main substrate 4 to the position of the already formed microchannel 5.

At the irradiation position of the laser beam, a certain kind of glass defect is generated by the laser beam energy introduced at the focal point, and the refractive index of the portion is increased. Therefore, by scanning the laser beam, the portion after scanning is converted into a core portion having a high refractive index, and an optical waveguide having a target pattern is formed in the substrate body.
In that case, the size of the cross section of the optical waveguide can be adjusted by adjusting the power density of the laser beam and the degree of aperture of the beam focus to control the introduction energy.

Of course, it is necessary to change depending on the material of the substrate body. For example, when a Ti: sapphire laser is used, the incident energy is 1 to 100 μJ, preferably 10 to 50 μJ, the pulse width is 50 to 1000 hemtoseconds, Preferably, the optical waveguide 9 can be formed with 100 to 300 hemtoseconds and a pulse period of 1 to 1000 Hz.
It shows another channel substrate A ₂ in FIG. 29.

In the case of this channel substrate A ₂ , the optical waveguide 9 is formed from one side end surface 3 c to the other side end surface 3 f of the substrate body 4 across the microchannel 5. In the figure, the number of optical waveguides 9 is one, but this number may be arbitrary. The channel substrate A ₂ can also perform the sample mixing operation.
In the case of this channel substrate, an auxiliary unit, for example, an optical fiber array unit (not shown), which will be described later, is arranged coaxially with the optical waveguide 9 on the side end surface 3e of the substrate body, and at the same time, the other side end surface 3f is also auxiliary. For example, a light receiving element as a unit can be arranged coaxially with the optical waveguide 9 for use.

  For example, when laser light for measurement is incident on the optical waveguide 9 from the optical fiber array unit, the laser light passes through the mixed sample sent to the microchannel 5 and is received by the light receiving element. At that time, the reaction state in the mixed sample is measured by irradiating a laser beam having a wavelength corresponding to the specific absorption wavelength of the target synthetic substance and measuring the intensity change of the laser beam, for example. Can do.

It should be noted that the integration of the optical waveguide and the microchannel as described above can be applied not only to the microchemical reaction apparatus of the present invention but also to a conventional microreactor apparatus.
Next, the auxiliary unit u will be described.
For the apparatus shown in FIG. 1, the opening 6f of the side of the operation unit U _3, auxiliary unit u is connected.

In addition, an auxiliary | assistant unit here is a module provided with the means for assisting the chemical operation which progresses in each chemical operation unit. Specifically, means for measuring and detecting the results of the chemical operations within the respective chemical manipulation unit (e.g., an optical fiber array and the light-receiving element as described with respect to the substrate A ₂ in FIG. 29), the sample in the chemical operations unit heating Means for (or cooling) (for example, the laser light irradiation unit described with reference to the substrate A _{1 in} FIG. 27), and a unit provided with means for controlling the progress of the chemical reaction.

In the case of the apparatus of FIG. 1, a laser beam irradiation unit for heating the sample to increase the reaction rate is exemplified as an auxiliary unit, and the channel substrate in the operation unit U ₃ is the substrate A ₁ of FIG. Thus, the board | substrate with which the optical waveguide 9 is formed from the side end surface 3e to the microchannel 5 is illustrated.
FIG. 30 shows an example of a connection state between the laser light irradiation unit and the operation unit U ₃ .

In FIG. 30, the pin hole described above is also formed in the front end face 10a of the unit u. The unit u is positioned and connected to the side of the operation unit U ₃ using the pin 7 between the pin hole 6d of the operation unit. This coupling, the front end surface 10a of the unit u is exposed into the opening 6f of the operating unit U _3, sides facing the stacked structure of the channel substrate 3 (5 sheets of the stack).

In the unit u, five optical fibers 10b are wired from the rear end portion to the front end face 10a. In that case, each optical fiber 10b is wired so that each tip 10c is coaxially opposed to the end surface 9a of the optical waveguide 9 exposed to the side end surface 3e of each microchannel substrate 3 in the laminated structure.
In addition, as an optical waveguide of such a laser beam irradiation unit, for example, a 5-core tape used for wiring of an optical cable can be used.

In the case of this unit u, laser light having a predetermined wavelength is incident on an optical fiber 10b connected to a laser light source (not shown), and the incident laser light is emitted from the front end surface 10a of the unit u from the tip 10c of each optical fiber. .
The emitted laser light is incident on the end face 9a of the optical waveguide 9 exposed to the side end face 3e of each channel substrate 3, propagates through each optical waveguide to the microchannel 5, and is emitted there. The sample fed to the microchannel 5 is heated and activated by absorbing the laser beam.

Thus, the unit u functions as a unit that assists the progress of the chemical operation (promotes the chemical reaction) in the operation unit U _{3 by} the action of the heating means (laser light irradiation means) provided therein.
In this case, the wavelength used for the laser light incident on the optical waveguide of each channel substrate can be changed independently, so that the heating temperature corresponds to the type of sample being sent to the microchannel of each channel substrate. Can be changed respectively. That is, a great degree of freedom can be exhibited even when the reaction system is changed.

In this case, the wavelength that the sample absorbs is selected as the wavelength of the laser beam used.
The above description is a case where a laser beam irradiation unit is used as an auxiliary unit and is connected to the operation unit U _3. However, the auxiliary unit is not limited to this unit, and the connection target is also the operation unit U. It is not limited to _three . This is explained below.
Prior to this description, the channel substrate of the present invention will be described again.

Figure 31 shows an example A ₃ of another channel substrate of the present invention.
In the channel substrate A ₃ , the microchannel 5 is formed in a predetermined plane pattern (Y-shaped pattern in the drawing) in the substrate body 4, and the groove 11 is engraved on the upper surface 3 g of the substrate body 4. Therefore, the substrate A ₃ can perform the sample mixing operation like the substrate A ₁ and the substrate A ₂ .

  The groove portion 11 does not directly intersect with the microchannel 5 but is formed at a location downstream of the junction 5c of the microchannel in a direction orthogonal to the flow path direction, and one end portion of the substrate body 4 It is opened in conformity with one side end face 3e. An energizing path 11a made of, for example, a conductive material is wired on the surface of the groove portion 11, and both ends 11b and 11b are positioned in the vicinity of the opening end of the groove portion as a power feeding portion.

  The wiring of the current path 11a is formed by applying a sputtering method or a CVD method using, for example, carbon or SiC, or after applying a mixed paste of those fine powders, an adhesive, or a solvent. Baking or forming by applying sputtering or vapor deposition using Pt or W, or applying a mixed paste of these metal fine powders and an adhesive or solvent with a predetermined line width and baking It can be realized by doing.

In the case of this channel substrate A ₃ , when power is supplied to the power supply portions 11 b and 11 b, the energization path 11 a generates resistance and functions as a heater portion.
The amount of heat generated in the heater part transfers heat to the substrate body located between the groove part 11 and the microchannel 5 to reach the microchannel 5 located directly below the groove part, and heats the mixed sample being sent. At this time, the temperature of the sample being sent in the microchannel can be changed by changing the power supplied to the energization path 11a. Note that power can be controlled by suppressing current and voltage.

By laminating the channel substrate A ₃ and supporting the laminated structure with a frame-like body, for example, the mixing unit U ₂ shown in FIG. 1 can be assembled.
Then, an opening is formed as a unit U _C in FIG. 7 on the side of the unit U _2, whereas, manufactured auxiliary units u which includes a plurality of adjustment means of the energization amount, the terminal of the adjusting means the power supply portion 11b of the channel substrate a _3, the auxiliary unit u while connected to 11b, FIG. 30R> 0 with in the same way as for the laser beam irradiation unit side of said mixing unit U ₂ shown By operating each adjusting means in connection with the opening, the sample in each channel substrate A ₃ can be individually heated independently in this mixing unit U ₂ .

At this time, if a thermocouple is further arranged on the channel substrate A ₃ and a temperature control means is added to the auxiliary unit u, the sample temperature can be controlled. In this case, the auxiliary unit u includes temperature control means in addition to the heating means.
By the way, the above-mentioned conventional stacked microreactor apparatus is entirely accommodated in a thermostatic chamber, and thus temperature control of the entire apparatus is realized. However, it is difficult to control the temperature of each channel substrate, and it is impossible to realize a steep temperature distribution in one channel substrate.

However, in the case of the apparatus of the present invention that operates by connecting the auxiliary units described above, the temperature control of each channel substrate A ₃ can be performed with an accuracy of ± 0.5 ° C. at a target temperature of 200 ° C., for example. Since only the portion immediately below the groove 11 is locally heated in the single channel substrate A ₃ , it is possible to realize a steep temperature distribution in the channel substrate. For example, the part which becomes 1/2 of the maximum temperature can be set to a width within 2 to 3 times the heating part.

Note that the auxiliary unit u is not limited to the microchemical reaction apparatus of the present invention, and can be connected to a conventional type microreactor apparatus.
Further shows examples A ₄ another channel substrate in Fig. 32.
The channel substrate A ₄ is a channel substrate in which a microchannel having a Y-shaped planar pattern is formed in the substrate body 4 and the sample mixing operation can be performed efficiently.

In this channel substrate A ₄ , a plurality (three in the figure) of fine convex portions 5 e are formed on the flow channel wall surface 5 d of the confluence microchannel located on the downstream side of the confluence 5 c. The part has an uneven surface. In this case, the degree of unevenness is appropriately set such as nm order, μm order, or sub-mm order.
In addition, this convex part 5e may be formed in one wall surface like a figure, and may be formed in another wall surface or all the wall surfaces. Moreover, it is preferable that the convex part 5e is formed in the position close | similar to the junction 5c among the flow paths of the junction microchannel 5C.

In the case of this channel substrate A ₄ , the two types of samples that have flowed into the microchannel 5 from the end surface openings 5 a and 5 a ′ merge, the flow is disturbed by the action of the convex portions 5 e of the wall surface 5 d, and mixing is promoted.
Therefore, in the channel substrate A ₄ , the sample mixing operation proceeds efficiently, and the convex portion 5 e functions as a chemical operation promoting portion with respect to the mixing operation that is a chemical operation of the channel substrate A ₄ .

Example A ₅ of another channel substrate having a chemical operations promoting portion described above is shown in FIG 433.
In this channel substrate A ₅ , a coating film 5 f as a chemical operation promoting portion described later is formed on the wall surface 5 d of the confluence microchannel.
In addition, the formation location of this coating film 5f is not limited to the wall surface of a confluence | merging microchannel, It forms in the appropriate location in the flow path of the microchannel 5 in relation to the chemical operation implement | achieved with a channel board | substrate. Also good.

As the coating film 5f, for example, a catalyst (for example, a metal catalyst such as Pt, Cu, Ag, or Ni or a photocatalyst such as TiO ₂ ) is applied in order to accelerate the reaction rate of the sample sent to the microchannel. There is a coating film. Coating in this case acts as an accelerator of the reaction process in this channel substrate A _A.
In addition, a coating film made of a light or electromagnetic wave absorber or reflector can be employed. For example, a coating film 5f made of a material that absorbs near-infrared to infrared wavelength light such as SiC, amorphous carbon, and diamond-like carbon (DLC) can be used.

In this case, the coating film generates heat due to absorption of light or electromagnetic waves, or functions as an acceleration unit for heating operation on the sample being fed by supplying the introduced energy to the sample by reflection and causing the sample to absorb the energy. .
Furthermore, the coating film 5f may be a coating film made of a heat conductor such as SiC, Si ₃ N ₄ , amorphous carbon, DLC, or Al ₂ O ₃ . The reflective coating film may be a metal film such as Al, Au, Ag, Ni, or Pt, or a multilayer reflective film such as TiO ₂ , Ta ₂ O ₅ and SiO ₂ .

The coating film in this case also functions as a heating operation promoting part for the sample being fed.
The channel substrate of the present invention is not limited to A _{1 to} A _A exemplified above, and a combined chemical operation can be realized by appropriately combining them.
For example, by incorporating an operation promoting portion of the uneven surface and the substrate A _A heater and the substrate A ₄ of the optical waveguide and the substrate A ₃ of the substrate A _1, the sample that flowed sent on one channel in the substrate It is possible to integrate a highly efficient mixing operation, an operation for increasing the reactivity of a sample, a highly efficient and steep heating operation and its control operation.

Further, by incorporating, for example, pressure sensor means, valve means, dynamic mixer means, pump means, etc. into the substrate body, more complex functions can be integrated.
Then, a chemical operation unit is assembled using this channel substrate (or its laminated structure), and means corresponding to the function of each channel substrate (for example, power supply means, light irradiation means, signal input / output means, measurement means) Etc.) is connected to produce a microchemical reaction apparatus capable of controlling the chemical operation of individual channel substrates in the chemical operation unit.

The channel substrate described above can be manufactured as follows.
First, as shown in FIG. 34, a first glass substrate 19A manufactured by a method described later is prepared. On one surface of the first glass substrate 19A, there is formed a groove 19a having a planar pattern of microchannels to be formed and extending from one end surface to the other end surface.

  Next, as shown in FIG. 35, the first glass substrate 19A is disposed on the lower mold 20a, and further, a flat plate-shaped second glass substrate 19B is disposed on the surface on the concave groove side. The substrate is heated and pressed with the upper mold 20b and the lower mold 20a. As a result, the contact portions of the first glass substrate 19A and the second glass substrate 19B are joined and the two substrates are integrated, and the upper opening of the concave groove is hermetically sealed by the second glass substrate 19B. The microchannel 5 is formed.

  The temperature applied during the hot press is preferably 5 to 150 ° C. lower than the softening point of the glass substrate used. If the temperature is less than the softening point minus 150 ° C., the glass substrate is insufficiently softened and it is difficult to form microchannels. If the softening point is minus 5 ° C. or higher, the glass substrate is excessively softened, the concave groove is deformed in the pressurizing direction, and a microchannel that retains the original shape cannot be formed. This is because the mold cannot be released due to close contact.

Moreover, it is preferable that the applied pressure applied at the time of hot-pressing exists in the range of 50-300 g / mm < ² >. This is because it is difficult to form microchannels on the glass substrate when the pressing force is smaller than 50 g / mm ² , and when the pressing force is larger than 300 g / mm ^{2, the} mold and the glass substrate are brought into close contact with each other and cannot be released. .
Regarding the manufacture of the first glass substrate 19A, a flat glass substrate is first placed on the lower mold. This glass substrate is usually a flat plate chip having a width of about several mm to 100 mm, a length of about several mm to 100 mm, and a thickness of 0.1 mm to several mm.

Then, as shown in FIG. 36, a mold surface mold 19A ′ having a projection shape 19a ′ having a negative-positive relationship with the shape of the concave groove 19a is prepared, and at least the glass substrate has its softening point In the state heated to a temperature lower by 5 to 150 ° C., the mold surface of the mold is pressed against the surface of the glass substrate, and then gradually cooled, and then the mold is released.
The mold surface of the mold is transferred to the glass substrate, and a concave groove having the same shape as the shape of the microchannel to be formed is formed, thereby obtaining the first glass substrate.

At this time, if irregularities are formed on the mold surface of the mold, for example, the first glass substrate for the substrate A ₄ shown in FIG. 32 can be obtained.
As the material for the mold, for example, amorphous carbon (or glassy carbon) or SiC, or those obtained by applying Si coating or DLC coating to them are suitable. This is because they are less likely to be fused with the glass material to be molded, and are easy to release, so that the molding cycle can be shortened.

Incidentally, after preparing the first glass substrate as described above, by applying the catalyst to the predetermined portion of the groove, to be the first glass substrate for the substrate A ₅ shown in FIG. 33 for example it can.
In this channel substrate manufacturing method, the first glass substrate and the second glass substrate are joined by a hot-pressing technique, so the time required for joining is short. However, in order to remove thermal deformation and thermal distortion of the obtained channel substrate, it is necessary to cool slowly after bonding. For this reason, the entire production time is limited by this slow cooling step, and therefore high productivity cannot be expected.

Considering this, it is preferable to manufacture with the following apparatus. An example of this apparatus is shown in FIG. 37 as a schematic diagram.
In this apparatus, a glass substrate stock unit 100, a glass substrate supply unit 110, a hot press unit 120, a substrate transport unit 130, and a cradle 140 are arranged in series in this order. This is an apparatus in which the joining process and the slow cooling process are continuously performed using separate apparatuses.

First, the first glass substrate 101 and the second glass substrate 102 described above are arranged in the stock unit 100. A transport robot 111 is installed in the supply unit 110, and the glass substrate 102 is set on the glass substrate 101 by the transport robot 111, and both are supplied to the hot press unit 120.
A substrate holder 121 and a transfer robot 122 are installed in the hot press unit 120. A set of glass substrates 123 supplied to the substrate holder 121 by the transfer robot 111 is positioned after the glass substrates are positioned. And heated to a predetermined temperature and pressed into a channel substrate.

  The channel substrate after the hot press is transferred to the transfer unit 130 by the transfer robot 122. The transport unit 130 includes a transport conveyor 131 that travels in a furnace having a temperature gradient in which the hot press unit side is at a high temperature. The channel substrate 3 transported to the transport conveyor 131 by the transport robot 122 is Then, it moves from the high temperature region to the low temperature region, is gradually cooled in the process, and is accommodated in the cradle 140.

According to this apparatus, the manufacture of the channel substrate can be continuously performed, and the time from joining to product completion can be shortened to 1/2 to 1/10 as compared with the prior art.
Next, another example of the connector member will be described with reference to FIGS. 38 and 39. FIG.
FIG. 38 shows an example of the connector member E, which is used for supply / merging / branching, but is not limited to this, and may be used as needed.

  This connector member E is composed of, for example, an array part 200 made of glass material or resin, and a connector part 202, and a plurality of microtubes 13 connected to the branch ferrule are inserted into the array part 200 and the connector part 202, Alignment is fixed. The connector member C shown in FIG. 22 is inserted with a total of 16 microtubes of 4 rows × 4 rows, but the connector member E shown in FIG. 38 is a total of 4 microarrays of 4 rows × 1 row. The tube 13 is inserted.

  The microtube 13 is inserted so that the position of the tip thereof is from the rear end surface 202 b of the connector unit 202 to the end surface 200 a of the array unit 200. In other words, the microtube 13 may be installed such that the tip thereof is positioned on the same plane as the end surface 200 a of the array unit 200, or may be installed so as to be positioned on the same plane as the end surface 202 a of the connector unit 202. May be.

The number of microtubes 13 is not particularly limited, and the number may be determined as necessary. Further, holes corresponding to the number of microtubes 13 are formed in the array unit 200 and the connector unit 202.
The end surface 200a of the array unit 200 has a structure capable of ensuring an airtight state when connected to the target chemical operation unit by performing precision grinding and polishing. Furthermore, the array portion 202 is formed with a positioning pin hole 6d, and has a connector structure capable of precise positioning with the target chemical operation unit. The array unit 200 and the connector unit 202 may be formed integrally or separately. However, in the case of separate molding, the end surface 202a of the connector unit 202 is subjected to precision grinding / polishing in the same manner as the end surface 200a of the array unit 200 to ensure an airtight state between the array unit 200 and the connector unit 202.

Next, an example of the connector member F will be described with reference to FIG. The connector member F is used for merging / branching, but is not limited thereto and may be used for supply.
The material of the connector member F is the same as that of the connector member E. A different structure between the connector member F and the connector member E is that the tip of the flow pipe 204 is arranged so as to be positioned on the end surface 200 a of the array unit 200. The connector member E has a structure in which the microtube 13 is inserted.

  Further, the structure different from the connector member D shown in FIG. 23 is that the front end of the flow pipe 204 is arranged so as to be flush with the end face 200a without forming the cavity 16. In the connector member D of FIG. 23, the size of the cavity 16 is large enough to include all the openings of the channel substrate exposed on the connection end surface of the chemical operation unit to be connected. In the same manner, the flow opening 204a located at the tip of the flow pipe 204 is sized to include all the openings of the channel substrate.

  In addition, in FIG. 39, although the example which has the one flow pipe 204 was shown, the number is not limited to this, A plurality of 4 rows x 1 row like the connector member E may be sufficient. Further, the size of the flow opening 204a is not necessarily required to include all the openings of the channel substrate, and may be designed to an appropriate size as necessary. Further, in FIG. 39, the cross-sectional shape of the flow pipe 204 is a round shape, but the shape is not limited to this, and may be a polygonal cross-section.

  The connector member F has a structure in which an end surface 200a of the array part 200 is subjected to precision grinding / polishing in the same manner as the connector member E, so that an airtight state can be secured when connected to the target chemical operation unit. Note that it is preferable that the end surface of the flow opening 204 a of the flow pipe 204 is precision ground and polished simultaneously with the end surface 200 a of the array unit 200. By doing so, the angles of the end surface 200a of the array unit 200 and the flow opening 204a of the flow pipe 204 are aligned on the same plane, so that the chemical operation unit to be connected can be connected in a more airtight state. It becomes.

  The flow feed pipe 204 may be anywhere as long as the flow feed opening 204 a is located from the rear end face 202 b of the connector part 202 to the end face 200 a of the array part 200 as in the case of the connector member E. Further, like the connector member E, the array part 200 is formed with positioning pin holes 6d, and has a connector structure that can be precisely positioned with the target chemical operation unit. As a main aspect, the sample supplied from the feed pipe 204 is supplied into the unit from the sample inlet of one chemical operation unit (not shown) connected to the connector member F.

Next, a connector connection structure will be described with reference to FIGS.
FIG. 40 shows an example of a connector connection structure. FIG. 40 shows an example of a connector connection structure in which the connection end surface is perpendicular to the flow direction. FIG. 41 shows an example of a structure in which the connecting end faces are connected at an arbitrary angle with respect to the flow direction. In each of the connector connection structures shown in FIGS. 40 and 41, the connection end faces are precision ground and polished as in the connector members E and F described in FIGS. Further, the micro chemical reaction apparatus is configured by connecting the end faces using positioning pin-pin holes to each other and assembling the whole by pressing in the longitudinal direction (flow path direction) with a coupling clip 18 having a spring function.

  In this way, the flow of the sample, or the mixing / reaction state can be controlled by making the connecting end face perpendicular to the flow direction or at an arbitrary angle. For example, when it is desired to maintain a laminar flow state when mixing and reacting two samples, the vertical structure shown in FIG. 40 is used. In this connector connection structure, the sample can be fed without changing the flow state of the sample. In order to mix and react two samples better, a connector connection structure in which connection end faces shown in FIG. 41R> 1 are connected at an arbitrary angle may be used. In this structure, the flow state of the sample tends to stay on the connection end surface depending on the angle of the connection end surface. For this reason, mixing and reaction proceed more in the staying part.

  When the connector connection structure shown in FIG. 41 is used, a connector member G as shown in FIG. 42 in which the connection end surface is formed at an arbitrary angle may be used. The connector member G shown in FIG. 42 is formed so that the connection end surface forms an arbitrary angle. The connector member G shown in FIG. 42 is obtained by precision grinding and polishing so that the end faces of the connector members E and F shown in FIGS. 38 and 39 are at an arbitrary angle with respect to the flow direction.

  In addition, in the connector connection structure shown in FIGS. 40 and 41, regardless of the material of the connector, it is possible to perform good connection between the connectors or between the connector and the target chemical operation unit. For example, when the connector or chemical operation unit is made of a different material, such as resin, ceramic, or metal, the position of the positioning pin hole is accurately formed, and the connection end face is precisely ground and polished. If this is the case, it is possible to connect the dissimilar materials with a structure that ensures an airtight state.

Next, an example of a structure for fixing the supply or flow part to the microchemical reaction apparatus will be described with reference to FIG. 43R> 3 to FIG.
First, the supply (feed) portion fixing structure P shown in FIG. 43 includes a guide pipe 300 and a microtube 302 inserted into the guide pipe 300, and the microtube 302 is one end of the guide pipe 300. It is fixed by the part 300a.

  The microtube 302 is fixed to the inner peripheral surface of the end portion 300a of the guide pipe 300 with an adhesive such as epoxy or silicone, or solder. In the case of fixing with solder, at least the inner surface of the end portion 300a of the guide pipe 300 is metallized as necessary. If the outer surface of the end portion 300a of the guide pipe 300 is metallized, the guide pipe 300 can be fixed to other parts using solder. FIG. 43 shows an example in which there is one microtube 302, but the number is not particularly limited. The number of the microtubes 302 is appropriately selected as necessary. The guide pipe 300 is preferably made of a metal such as copper, aluminum, or SUS. This is because the pressure resistance against the pressure received from the sample to be sent is excellent. The metallization described above is performed as necessary depending on the metal material used.

  The supply (flow) portion fixing structure Q shown in FIGS. 44 and 45 is another embodiment of FIG. In this embodiment, a guide jig 304 as shown in FIG. 44 is fitted into the end 300 a on the fixed side of the guide pipe 300, and the microtube 302 is inserted into the alignment hole formed in the guide jig 304. It is the composition which makes it. The microtube 302 and the guide jig 304, and the guide jig 304 and the guide pipe 300 are bonded with an adhesive, solder, or the like, respectively, to form a sealing structure. In addition, when fixing using a solder, metalization is performed as needed like the fixing structure P of FIG.

Next, an adjustment mechanism 400 that controls the mixing ratio, concentration, and flow rate of the sample fed from the feed pipe will be described with reference to FIG.
The adjustment mechanism 400 of FIG. 46 includes a unit L for supplying the A sample and an N unit for supplying the B sample as supply units, and a unit M for mixing the A sample and the B sample. Yes. From the unit L and the unit N, four micro tubes for supplying the A and B samples to the unit M are arranged. The microtubes from the unit L to the unit M have four bending rates and lengths changed, and the microtubes from the unit N to the unit M are arranged with the same four bending rates and lengths. Yes.

In the adjustment mechanism 400 having such a configuration, the samples A and B supplied from the units L and N are mixed by the unit M and sent from the unit M to the outside. Note that four microtubes are arranged on the flow side of the unit M, and the mixed sample can be simultaneously fed to four locations.
In the adjusting mechanism 400, the concentration of the mixed sample sent from the four ports of the unit M is changed. This is because the flow rate of the A sample supplied from the unit L to the unit M is changed for each microtube. In order to adjust the flow rate of the sample supplied to the unit M, the length of the microtube, the installation bending rate, the feed pressure, or the inner diameter of the tube may be set for each tube. In any structure, since the flow rate of the sample changes, for example, when a plurality of samples are mixed, the mixing ratio can be changed.

  The adjusting mechanism 400 of FIG. 46 shows an example in which the length and bending rate of the microtube are changed for each tube. 46, since the flow rate of the A sample is controlled and the flow rate of the B sample is constant, the supply (flow) amount of the B sample does not change for each microtube. For this reason, when the A sample and the B sample are mixed in the unit M, the mixing ratio is different in the four mixing steps. As a result, in the unit M shown in FIG. 46, mixed samples having different concentrations are sent from the four output ports.

The microchemical reaction apparatus of the present invention has a structure in which chemical operation units for performing chemical operations are connected in an airtight and detachable manner. It can be used as a novel microreactor device in which the chemical operations are integrated.
Then, by incorporating the channel substrate of the present invention that exhibits various functions into the chemical operation unit, and connecting the auxiliary unit of the present invention having means corresponding to the function to the chemical operation unit, various chemical operations can be performed. Promotion and control are also possible.

  In addition, since the channel substrate of the present invention is manufactured by applying a glass forming method, even a channel substrate having a complicatedly shaped microchannel or the like is easier and less productive than before. Can be manufactured.

It is a disassembled perspective view which shows one example of the microchemical reaction apparatus of this invention. Is a perspective view showing an example U _A chemical operations unit of the present invention. It is a top view which shows an example of a channel board | substrate. It is sectional drawing which follows the IV-IV line of FIG. It is a fragmentary top view which shows another example of a channel board | substrate. Another example U _B chemical operations unit of the present invention is a perspective view showing. It is a perspective view showing another example U _C chemical operations unit of the present invention. It is a perspective view showing still another example U _d chemical operations unit of the present invention. It is a perspective view which shows the other example _Ud 'of the chemical operation unit of this invention. It is a front view which shows the end surface of a channel board | substrate. It is a fragmentary top view which shows an example of the end surface of a channel board | substrate. It is a fragmentary top view which shows another example of the end surface of a channel board | substrate. It is a fragmentary top view which shows another example of the end surface of a channel board | substrate. It is a fragmentary top view which shows the other example of the end surface of a channel board | substrate. It is a fragmentary top view which shows another example of the end surface of a channel board | substrate. It is a perspective view which shows another example of the chemical operation unit of this invention. It is a partially cutaway sectional view showing a state of connecting the unit U ₂ and the unit U ₃ via a pin. It is a partially cutaway sectional view showing another connection state of the unit U ₂ and the unit U _3. Is a perspective view showing an example U _A 'chemical operations unit of the present invention. Another example U _A "chemical operations unit of the present invention is a perspective view showing. It is a fragmentary perspective view which shows the state which bonded the laminated structure of the channel board | substrate to the frame-shaped body. It is a perspective view which shows one example C of the connector member used with the apparatus of this invention. It is a perspective view which shows the other example D of a connector member. It is a perspective view which shows one example of the assembled microchemical reaction apparatus of this invention. It is a perspective view which shows a sealing film. It is a perspective view which shows another sealing film. Is a perspective view showing an example A ₁ of the channel substrate of the present invention. It is a schematic diagram which shows the state which forms an optical waveguide in a channel board | substrate with a hemtosecond laser. Another example A ₂ of the channel substrate of the present invention is a perspective view showing. It is a schematic view showing a state in which coupling the auxiliary unit u in chemical operations unit U _3. Another example A ₃ channels substrate of the present invention is a perspective view showing. Is a perspective view showing still another example A ₄ channel substrate of the present invention. It is a perspective view showing another example A ₅ channel substrate of the present invention. It is a perspective view which shows one example of the 1st glass substrate used for manufacture of the channel substrate of this invention. It is a schematic diagram which shows the state which hot-presses a 1st glass substrate and a 2nd glass substrate. It is a perspective view which shows an example of the metal mold | die used for manufacture of a 1st glass substrate. It is the schematic of the example of an apparatus which manufactures the channel board | substrate of this invention continuously. It is a perspective view which shows the other example E of a connector member. It is a perspective view which shows the other example F of a connector member. It is a perspective view which shows an example of the connector connection structure of the microchemical reaction apparatus of this invention. It is a perspective view which shows the other example of the connector connection structure of a microchemical reaction apparatus. It is a perspective view which shows the other example F of a connector member. It is a perspective view which shows an example of the structure of the supply to a microchemical reaction apparatus, or a flow part. It is a perspective view which shows an example of the jig | tool used for the supply to a microchemical reaction apparatus or a flow part. It is a perspective view which shows the other example of the structure of the supply to a micro chemical reaction apparatus, or a flow part. It is the schematic which shows an example of the adjustment mechanism which controls the flow volume of a sample.

Explanation of symbols

U ₁ , U ₂ , U ₃ , U ₄ , U _A , U _B , U _C , U _D , U _A ', U _A "chemical operation unit u auxiliary unit A ₁ , A ₂ , A ₃ , A ₄ , A ₅ channel substrate 3 channel substrate 3a, 3b end surface 3c of channel substrate 3 reverse V-shaped groove 3d V-shaped groove 3e, 3f side end surface 3g of channel substrate 3 surface of channel substrate 3 base body 5 base body 5 microchannels 5a, 5b End face opening 5c Junction point 5d Microchannel wall surface 5e Protruding part 5f Coating film 6 Frame-like body 6a, 6b End face 6c of frame-like body 6d Through hole 6d Positioning pin hole 6e Groove 6f Opening part 6g Rail 6h V-shaped groove 7, 7A pin 8 adhesive layer 9 optical waveguide 9a end face 10a of optical waveguide 9 front end face 10b of auxiliary unit u optical fiber 10c tip 11 of optical fiber 10b groove 11a conducting path 11b conducting path 11a Feeder 12 Main body 12a of connector members C and D Connection end face 13 of connector members C and D Micro tube 14 Connector 15 Through hole 16 Cavity 17 Tube 18 Bonding clip 19A First glass substrate 19a Groove 19B Second glass substrate 19A 'Mold 19a' protrusion shape

Claims (8)

A chemistry that is installed in or between processing units of a microchemical reactor equipped with a plurality of processing units, and sends the sample to each processing unit by pressing the end faces of each other and connecting the end faces. A reaction channel substrate,
The channel substrate for chemical reaction is
A substrate body;
A channel extending from one end face to the other end face inside the substrate body and having at least one opening on each of the one end face and the other end face of the substrate body;
A projecting portion projecting in a region surrounding the opening on at least one end surface of the one end surface and the other end surface, the projecting tip portion being processed into a flat surface and being connected to the end surface ;
A channel substrate for chemical reaction, comprising: The flatness of the tip surface of the protrusion is 1 μm or less.
The channel substrate for chemical reaction according to claim 1. The surface roughness of the tip surface of the protrusion is 100 nm or less.
The channel substrate for chemical reaction according to claim 1 or 2. The width of the protrusion around the opening is in the range of 10 μm to 1 mm.
The channel substrate for chemical reaction according to any one of claims 1 to 3, wherein: A plurality of the openings and the protrusions are formed on the end surface, and the tip surfaces of the protrusions are on the same plane.
The channel substrate for chemical reaction according to any one of claims 1 to 4, wherein the channel substrate is for chemical reaction. The height of the protrusion is in the range of 0.3 mm to 3.0 mm, and the width is in the range of 3 mm to 10 mm.
The channel substrate for chemical reaction according to any one of claims 1 to 5, wherein the channel substrate is for chemical reaction. A channel substrate for chemical reaction according to any one of claims 1 to 6,
A frame-like body having a through hole for accommodating at least one chemical reaction channel substrate by projecting the protruding portion of the chemical reaction channel substrate to the outside;
A microchemical reaction device comprising: In the through hole, a plurality of the chemical reaction channel substrates are stacked and stored,
The microchemical reaction device according to claim 7.

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