JP2005279493A - Microreactor and production method of the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To make a microreactor composed of a chemically resistant fluoro polymer possible to carry out optical measurement of transmittance in visible light wavelength, absorption, light emission, phosphorescence, and fluorescence. <P>SOLUTION: An amorphous fluoro resin layer 102 with a thickness, for example, about 30 μm is formed on a glass substrate 101; a resist pattern 103 having groove parts 103a penetrating the layer thereunder is formed on the amorphous fluoro resin layer 102; and the amorphous fluoro resin layer 102 is selectively etched using the resist pattern 103 as a mask to form grooves 102a in the amorphous fluoro resin layer 102. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a microreactor, which is a fine reactor composed of a flow path having a micron-order dimension, and a method for manufacturing the same.

In recent years, a method using a microreactor has attracted attention as an efficient manufacturing means that suppresses the generation of by-products in the manufacture of medical drugs or chemicals, or in the manufacture of materials for drug manufacturing (Non-patent Document 1). reference).
A microreactor is a fine reactor equipped with a channel with a tube diameter (width / height) of several microns to several hundreds of microns. Raw materials, samples, reagents, etc. are supplied from an inlet provided on one side of the channel. And the produced substance or by-product is taken out from the outlet provided in the other side of the flow path.

  In the microreactor, since the ratio of the surface area to the volume of the region where the reaction is performed is larger than that of a normal reactor, high thermal conductivity is obtained between the region where the reaction is performed and the outside. Accordingly, the reaction heat generated in the microreactor is easily diffused to the surroundings and is easily cooled from the outside, so that the temperature control in the microreactor is easy. Due to this characteristic, in the synthesis and analysis using a microreactor, the influence of secondary products due to reaction heat is excluded, and the intended chemical reaction is caused more selectively.

Some medical drugs or chemicals currently manufactured require complex and multi-stage chemical reactions and are manufactured using very large plants. Since the microreactor can cause only an intended chemical reaction, even a chemical that undergoes the complicated manufacturing process as described above can be efficiently manufactured.
In addition, manufacturing using a microreactor from the research and development stage of chemicals has the characteristic that various conditions once determined do not need to be changed greatly during mass production.

  In addition, a micro total analysis system, which is an analysis system using a microreactor, improves the reaction rate by reducing the reaction volume, and enables many analyzes to be performed in a shorter time. In addition, in this system, by increasing the efficiency of the chemical reaction, it is possible to execute various analyzes at once even with a small amount of sample.

  In the analysis of chemical reactions, in order to obtain more accurate and more information, many measuring means such as measurement of heat of reaction, analysis of products, measurement of light absorption or emission intensity, measurement of electrical characteristics, etc. are used. By using a microreactor with a small heat of reaction, it is possible to minimize the influence of an extra reaction on the measurement target and measure only the reaction of interest with high sensitivity. For this reason, in an analysis system using a microreactor, it is possible to analyze with a small amount of sample.

  Currently, LSI manufacturing technology such as lithography technology and etching technology is mainly used to form the flow path and reaction space constituting the microreactor. In addition to glass and quartz, materials such as corrosion-resistant metal, titanium, ceramics, and Teflon (registered trademark) are used for the flow path of the microreactor in addition to glass and quartz.

  In particular, in terms of excellent chemical resistance, by forming a flow path with a fluoride polymer typified by Teflon (registered trademark), it has high durability against acids, alkalis and organic solvents, and can be handled in a microreactor. There is an advantage that a variety of medicines are available.

The applicant has not yet found prior art documents related to the present invention by the time of filing other than the prior art documents specified by the prior art document information described in this specification.
Kiichi Sato, et.al., "Integuretion of Chemical and Biochemical Analysis System into a Glass Microchip", Analytical Science, vol.19, pp.15-22, (2003).

However, Teflon (registered trademark), which is commonly used in general, has a low transmittance with respect to light, and has a problem that it cannot measure transmittance and measure light emission / phosphorescence / fluorescence characteristics.
By observing the phenomenon in the visible light region, it is possible to obtain information for evaluating and controlling the chemical reaction in the microphone reactor. However, the above-mentioned conventional fluoride polymers have low light transmission and optical properties. It is not suitable for general observation.

  The present invention has been made to solve the above problems, and is a microreactor composed of a fluorine-based polymer having excellent chemical resistance. It can transmit and absorb light from the ultraviolet region to the infrared region. The purpose is to enable optical measurement of light emission, phosphorescence, fluorescence, and the like.

The microreactor according to the present invention includes a first fluororesin layer made of an amorphous fluororesin, a second fluororesin layer made of an amorphous fluororesin formed by bonding to the second fluororesin layer, The first fluororesin layer is provided with at least a flow path formed of a recess formed on the bonding surface side with the second fluororesin layer and a through hole formed in the second fluororesin layer and communicating with the flow path.
According to this microreactor, the first and second fluororesin layers are transparent members that transmit light in a wide wavelength band from the ultraviolet region to the infrared region.

In the microreactor, a first substrate made of a transparent material on which a first fluororesin layer is formed, a second substrate made of a transparent material on which a second fluororesin layer is formed, and a through-hole formed in the second substrate. You may make it provide the opening part connected.
Moreover, the recessed part of the 1st fluororesin layer may be formed along the groove | channel provided in the 1st board | substrate.

  Further, in the above microreactor, the amorphous fluororesin may be any material as long as it is composed of a fluorinated polysiloxane polymer. For example, CYTOP (manufactured by Asahi Glass Co., Ltd.) can be used as the fluorinated polysiloxane polymer. .

  In the microreactor manufacturing method of the present invention, first, a first fluororesin layer made of an amorphous fluororesin is formed on a first substrate made of a transparent material, and a flow path made of a recess is formed in the first fluororesin layer. To do. On the other hand, a second fluororesin layer made of an amorphous fluororesin is formed on a second substrate made of a transparent material, a through hole is formed at a predetermined location of the second fluororesin layer, and a through hole is formed in the second substrate. An opening communicating with the is formed. After these, the surface of the first fluororesin layer in which the flow path is formed and the surface of the second fluororesin layer in which the through hole is formed are joined.

In the microreactor manufacturing method, a groove is formed in the first substrate, and an amorphous fluororesin film is formed on the first substrate on which the groove is formed, thereby forming a flow path by a recess along the groove. You may make it form the made 1st fluororesin layer.
Further, at least a part of the first substrate may be removed, or at least a part of the second substrate may be removed.

  As described above, according to the present invention, the flow path forming part of the microreactor is made of amorphous fluororesin, so that the region where the reaction occurs can be optically observed from the outside, and fluorine having excellent chemical resistance. A microreactor composed of a polymer, which has the excellent effect of enabling optical measurement of light transmission, absorption, emission, phosphorescence, fluorescence, etc. in a wide wavelength range from the ultraviolet to the infrared. .

Hereinafter, embodiments of the present invention will be described with reference to the drawings.
FIG. 1 is a process diagram showing an example of a method for manufacturing a microreactor according to an embodiment of the present invention. First, as shown in FIG. 1A, an amorphous fluororesin layer 102 having a thickness of, for example, about 30 μm is formed on a glass substrate 101. The amorphous fluororesin layer 102 is formed by, for example, applying a coating solution in which a fluorinated polysiloxane polymer is dissolved in a fluorine-containing solvent onto the glass substrate 101 to form a coating film, and then removing the solvent in the coating film by air drying or the like. After removal, it can be formed by curing. As the solvent, for example, Fluorinert FC72 (manufactured by Sumitomo 3M Limited) can be used.

The curing may be photocuring by light irradiation or heat curing by heating.
For the photocured film, for example, an appropriate amount of a photopolymerization initiator such as benzyldimethyl ketal, 1-hydroxycyclohexyl phenyl ketone, benzophenone, or acetophenone is blended in the coating solution, and the coating film coated with this coating solution is irradiated with ultraviolet rays. It is obtained by. A film by thermosetting can be obtained by adding a platinum catalyst such as platinum chloride to a coating solution and heating the coating film coated with this coating solution at a temperature of about 100 to 200 ° C.
Therefore, the amorphous fluororesin layer 102 is composed of a fluorinated polysiloxane polymer. As the fluorinated polysiloxane polymer, for example, CYTOP manufactured by Asahi Glass Co., Ltd. may be used.

  Next, as shown in FIG. 1B, a resist pattern 103 having a groove 103 a penetrating in the lower layer is formed on the amorphous fluororesin layer 102. As illustrated in the plan view of FIG. 1B ', the resist pattern 103 is formed by combining two flow paths into one. FIG. 1B schematically shows a cross section taken along the line BB ′ of FIG.

  The resist pattern 103 can be formed by a known lithography technique using ultraviolet light or electron beam as a light source. The width of the groove may be about 30 μm, for example. Since the flow path of the microreactor is formed with a tube diameter of about several μm to several hundred μm, the resist pattern 103 may be formed by a photolithography technique using ultraviolet light as a light source.

  Next, the amorphous fluororesin layer 102 is selectively etched using the resist pattern 103 as a mask, so that a groove 102a is formed in the amorphous fluororesin layer 102 as shown in FIG. . For example, the groove 102a can be formed by a dry etching method using a fluorine-based gas or a mixed gas in which oxygen is added thereto. The groove 102 a is, for example, a recess having a depth of about 20 μm and formed without penetrating the amorphous fluororesin layer 102.

  After forming the groove 102a in the amorphous fluororesin layer 102, the resist pattern 103 is removed, and the amorphous substrate having the groove 102a serving as a flow path on the glass substrate 101 as shown in FIG. It is assumed that the porous fluororesin layer 102 is formed. For example, the resist pattern 103 can be removed by dissolving the resist pattern 103 in an organic solvent.

  Note that a groove (a channel made of a recess) may be formed in the amorphous fluororesin layer 102 by a mask pattern made of silicon dioxide. First, a silicon dioxide film is formed on the amorphous fluororesin layer 102, a resist pattern is formed on the silicon dioxide film, and the silicon dioxide film is etched using the resist pattern as a mask to form a mask pattern. Next, a groove is formed in the amorphous fluororesin layer 102 using the mask pattern as a mask. Thereafter, the mask pattern made of silicon dioxide may be removed using, for example, hydrofluoric acid. The resist pattern can be removed together with the removal of the mask pattern.

  On the other hand, as shown in FIG. 1F, another glass substrate 111 is prepared, and an amorphous fluororesin layer 112 having a film thickness of about 20 μm is formed on the glass substrate 111 as described above. To do. Next, as shown in FIG. 1 (f), an opening 111 a and a through hole 112 a are formed so as to penetrate the glass substrate 111 and the amorphous fluororesin layer 112. The opening 111a is formed to be wider than the through hole 112a. The openings 111a and 112a are disposed at the end of the flow path of the microreactor.

  Next, as shown in FIG. 1G, the glass substrate 101 and the glass substrate 111 are bonded to each other with the surfaces on which the amorphous fluororesin layer is formed facing each other to form the microreactor 121. State. FIG. 1G schematically shows a cross section taken along line GG ′ of FIG. For example, the surfaces of the amorphous fluororesin layer 102 and the amorphous fluororesin layer 112 can be bonded to each other by thermocompression bonding at a temperature of about 200 to 300 ° C.

  As shown in the plan view of FIG. 1 (g ′), the glass substrate 101 and the glass substrate 111 are bonded together so that the openings 111a and 112a are arranged at the end of the flow path formed by the groove 102a. State. The microreactor 121 includes, for example, a sample introduction port 104 into which a sample is introduced, and a reagent introduction port 105 into which a reagent is introduced. The sample introduction port 104 communicates with the sample channel 114, and the reagent introduction port 105 is a reagent. It communicates with the flow path 115.

Further, the sample channel 114 and the reagent channel 115 are merged near the center of the microreactor 121 and integrated into one reaction channel 116. In addition, the reaction channel 116 communicates with the discharge port 106.
In the microreactor 121, for example, the sample liquid is introduced from the sample introduction port 104, the reagent liquid is introduced from the reagent introduction port 105, and the sample liquid flowing through the sample flow path 114 and the reagent liquid flowing through the reagent flow path 115 are reacted. It is mixed in the passage 116 and discharged from the discharge port 106.

  According to the microreactor 121, the optical state of the chemical reaction between the sample liquid and the reagent liquid mixed in the reaction channel 116 can be observed through the amorphous fluororesin layer 102 and the glass substrate 101. It is. The amorphous fluororesin layer is a transparent material that transmits light in a wavelength range of about 200 to 2000 nm and a wide wavelength range from ultraviolet to infrared, and is suitable for a microreactor that performs optical measurement. Note that the optical state can be observed through the amorphous fluororesin layer 112 and the glass substrate 111.

  In addition, by forming the opening 111a larger than the through hole 112a, it is possible to connect the pipe connected to the sample introduction port 104, the reagent introduction port 105, etc. by directly contacting the amorphous fluororesin layer 112. Become. If each pipe is directly connected to the amorphous fluororesin layer 112, the sample solution or the like can be flowed to the microreactor 121 without contacting the glass substrate 111.

  If sufficient strength is obtained by the amorphous fluororesin layers 102 and 112, the glass substrates 101 and 111 are removed, and only from the amorphous fluororesin layers 102 and 112, as shown in FIG. The microreactor 122 may be configured. Moreover, you may make it remove the area | region corresponding to the reaction flow path 116 of a glass substrate.

  With the above-described configuration, the reaction flow path 116 portion of the microreactor 122 is free of glass, and the optical characteristics (light transmission characteristics) can be further improved. For example, when CYTOP is used as the fluorinated polysiloxane polymer, CYTOP has a transmittance of 95% (in the case of a film thickness of 200 μm) from the ultraviolet light region to the infrared light region. The light transmission characteristics can be further improved. Note that a quartz substrate may be used instead of the glass substrate.

Next, a configuration example of a micro total analysis system (μ-TAS) using the microreactor 122 will be described with reference to a perspective view of FIG.
In the system shown in FIG. 2, first, the sample is introduced into the sample introduction port 104 through the sample introduction pipe 201, the reagent is introduced into the reagent introduction port 105 through the reagent introduction pipe 202, mixed in the reaction channel 116, and the discharge port 106. To the discharge pipe 203.

  The light from the light source 205 formed by the aperture 204 is collected by the lens 206, passes through the reaction channel 116 through the amorphous fluororesin layer 112, and the light that has passed through the reaction channel 116 is The light passes through the amorphous fluororesin layer 102, is focused on the lens 206, and enters the light detection unit 207. The incident light is photoelectrically converted into a predetermined electrical signal on the detection surface of the light detection unit 207, and the converted signal is processed by the analysis processing unit 208.

  For example, the spectral characteristics of the sample solution in which the reagent solution is mixed in the reaction channel 116 can be measured with the system shown in FIG. As the light source, wavelengths from the infrared region to the ultraviolet region can be used. Further, not only transmission and absorption but also light emission such as phosphorescence and fluorescence may be measured. As described above, the amorphous fluororesin layers 102 and 112 constituting the microreactor 122 are transparent materials that transmit light in a wide wavelength band from the ultraviolet region to the infrared region. Optical measurement at can be performed.

Next, an example of a method for manufacturing another microreactor according to the embodiment of the present invention will be described.
For example, an amorphous fluororesin layer having a thickness of about 30 μm is formed on a substrate such as glass or quartz. An amorphous fluororesin layer can be formed by applying a coating solution obtained by dissolving a fluorinated polysiloxane polymer in a fluorine-containing solvent to a substrate and removing the solvent. Next, desired grooves are formed in the amorphous fluororesin layer by known laser processing. The formed groove becomes a channel of the microreactor.

In addition, after applying a coating solution in which a fluorinated polysiloxane polymer is dissolved in a fluorine-containing solvent to form a coating film, a mold having a convex pattern serving as a flow path is heated to apply the convex pattern portion to the coating film. An amorphous fluororesin layer in which a channel having a desired shape is engraved may be formed while contacting and volatilizing and removing the solvent of the coating film.
The groove serving as the flow path is the same as that of the embodiment shown in FIG. 1, and is formed without penetrating the amorphous fluororesin layer.

  Thereafter, the formed flow path or the through-hole capable of obtaining the microreactor 121 (FIG. 1) by the same process as described with reference to FIGS. It is desirable that the size and the position are determined in consideration of the positional deviation. When flowing a liquid having a property of chemically reacting with glass or quartz to the microreactor, it is better to remove the substrate when the liquid is in an environment where it contacts the substrate.

  Next, an example of a method for manufacturing another microreactor according to the embodiment of the present invention will be described. First, as shown in FIG. 3A, a resist pattern 302 having a groove 302a penetrating in a lower layer is formed on a glass substrate 301. The resist pattern 302 can be formed by a known lithography technique using ultraviolet rays or electron beams as a light source. The width of the groove may be about 30 μm, for example. Since the flow path of the microreactor is formed with a tube diameter of about several μm to several hundred μm, the resist pattern 302 may be formed by a photolithography technique using ultraviolet light as a light source.

  Next, the glass substrate 301 is selectively etched using the resist pattern 302 as a mask, so that a groove 301a is formed in the glass substrate 301 as shown in FIG. For example, the groove 301a can be formed by a dry etching method using a fluorine-based gas or a mixed gas in which oxygen is added thereto.

After forming the groove 301 a in the glass substrate 301, the resist pattern 302 is removed, and the groove 301 a serving as a flow path is formed on the glass substrate 301. For example, the resist pattern 302 can be removed by dissolving the resist pattern 302 in an organic solvent.
Note that the glass substrate 301 may be processed by wet etching using a fluorine-based etching solution. Further, the groove 302a may be formed directly on the glass substrate 301 by a laser processing method. Similarly, the groove 302a may be formed directly on the glass substrate 301 with high-pressure water.

  Next, an amorphous fluororesin layer 303 having a thickness of, for example, about 2 μm is formed on the glass substrate 301. The amorphous fluororesin layer 303 is formed by, for example, applying a coating solution in which a fluorinated polysiloxane polymer is dissolved in a fluorine-containing solvent onto the glass substrate 301 to form a coating film, and then removing the solvent in the coating film by air drying or the like. After removal, it can be formed by curing. The formation of the amorphous fluororesin layer 303 is almost the same as that of the embodiment shown in FIG.

Further, an amorphous fluororesin material is disposed opposite to the glass substrate 301, the vapor of the amorphous fluororesin material is generated by a laser ablation method, and the generated vapor is brought into contact with the glass substrate 301. It is good also as the state in which the quality fluororesin layer 303 was formed.
As described above, as shown in FIG. 3C, the amorphous fluororesin layer 303 is in a state in which the recess 303 a is formed along the groove 301 a provided in the glass substrate 302. .

On the other hand, as shown in FIG. 3D, another glass substrate 311 is prepared, and an amorphous fluororesin layer 312 having a thickness of about 2 μm is formed on the glass substrate 311 in the same manner as described above. To do. The amorphous fluororesin layer 312 may be formed by a laser ablation method as described above.
Next, as illustrated in FIG. 3E, an opening 311 a and a through hole 312 a are formed so as to penetrate the glass substrate 311 and the amorphous fluororesin layer 312. The opening 311a is formed wider than the through hole 312a. The opening 311a and the through hole 312a are disposed at the end of the flow path of the microreactor.

Next, as shown in FIG. 3F, the glass substrate 301 and the glass substrate 311 are bonded to each other with the surfaces on which the amorphous fluororesin layer is formed facing each other, whereby the microreactor 321 is formed. State. For example, the surfaces of the amorphous fluororesin layer 303 and the amorphous fluororesin layer 312 can be bonded to each other by thermocompression bonding at a temperature of about 200 to 300 ° C. As a result, the channel of the microreactor is formed by the recess 303a of the amorphous fluororesin layer 303.
The microreactor 321 manufactured as described above can also be used similarly to the microreactor 122.

  In the above description, the sample channel and the reagent channel merge with the reaction channel. However, it goes without saying that the present invention is not limited to this. A microreactor in which three or more channels merge into one channel may be used. Moreover, the microreactor which two flow paths merge once and branch into two different flow paths may be sufficient. The above-described present invention can be applied to various types of microreactors.

It is process drawing which shows the example of the manufacturing method of the microreactor in embodiment of this invention. 1 is a perspective view showing a configuration example of a micro total analysis system (μ-TAS) using a microreactor 122. FIG. It is process drawing which shows the example of the manufacturing method of the other microreactor in embodiment of this invention.

Explanation of symbols

DESCRIPTION OF SYMBOLS 101 ... Glass substrate, 102 ... Amorphous fluororesin layer, 102a ... Groove, 103 ... Resist pattern, 103a ... Groove part, 104 ... Sample introduction port, 105 ... Reagent introduction port, 106 ... Discharge port, 111 ... Glass substrate, 111a DESCRIPTION OF SYMBOLS ... Opening part, 112 ... Amorphous fluororesin layer, 112a ... Through-hole, 114 ... Sample flow path, 115 ... Reagent flow path, 116 ... Reaction flow path, 121, 122 ... Microreactor.

Claims (9)

A first fluororesin layer made of an amorphous fluororesin;
A second fluororesin layer made of an amorphous fluororesin formed by bonding to the second fluororesin layer;
A flow path formed of a recess formed on a side of the first fluororesin layer bonded to the second fluororesin layer;
A microreactor comprising: a through hole formed in the second fluororesin layer and communicating with the flow path. The microreactor according to claim 1, wherein
A first substrate made of a transparent material on which the first fluororesin layer is formed;
A second substrate made of a transparent material on which the second fluororesin layer is formed;
A microreactor comprising: an opening communicating with the through hole formed in the second substrate. The microreactor according to claim 2, wherein
The concave part of the first fluororesin layer is formed along a groove provided in the first substrate. The microreactor according to any one of claims 1 to 3,
The microreactor, wherein the amorphous fluororesin is composed of a fluorinated polysiloxane polymer. The microreactor according to claim 4, wherein
The microreactor that the fluorinated polysiloxane polymer is Cytop. Forming a first fluororesin layer made of an amorphous fluororesin on a first substrate made of a transparent material;
Forming a flow path comprising a recess in the first fluororesin layer;
Forming a second fluororesin layer made of an amorphous fluororesin on a second substrate made of a transparent material;
Forming a through hole at a predetermined location of the second fluororesin layer;
Forming an opening communicating with the through hole in the second substrate;
A method of manufacturing a microreactor comprising: joining at least a surface of the first fluororesin layer in which the flow path is formed and a surface of the second fluororesin layer in which the through hole is formed. In the manufacturing method of the micro reactor of Claim 6,
Forming a groove in the first substrate;
Forming an amorphous fluororesin film on the first substrate in which the groove is formed, thereby forming the first fluororesin layer in which the flow path is formed by a recess along the groove; A method of manufacturing a microreactor comprising: In the manufacturing method of the micro reactor of Claim 6 or 7,
A method of manufacturing a microreactor comprising a step of removing at least a part of the first substrate. In the manufacturing method of the micro reactor of any one of Claims 6-8,
A method of manufacturing a microreactor comprising a step of removing at least a part of the second substrate.

Images