JP2009156778A - Microchip and manufacturing method therefor - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a microchip which excels in productivity and has a structure, capable of easily determining groove collapse and in which a fine channel circuit pattern is formed in a substrate. <P>SOLUTION: At least a first substrate, having a substrate surface provided with grooves, is pasted to a second substrate to form the microchip, and the microchip has a fluid circuit made of the grooves and a first substrate-side surface of the second substrate. In the first substrate, the surface provided with the grooves is provided with a collapse-measuring part for measuring groove destructions due to the pasting of the first substrate and the second substrate. The collapse-measuring part is provided with at least both a reference groove, having a depth which is equal to or deeper than the shallowest groove forming the fluid circuit in the thickness direction of the first substrate and a protrusion part in the shape of a pyramid, a cone, or a triangular prism mounted to the inside of the reference groove and having a measuring surface sloped in the direction of the surface of the second substrate. <P>COPYRIGHT: (C)2009,JPO&INPIT

Description

  The present invention relates to a microchip provided with a crush measurement unit on a substrate, and a method for manufacturing the microchip.

  In recent years, the importance of detecting, detecting or quantifying biological substances such as DNA (Deoxyribo Nucleic Acid), enzymes, antigens, antibodies, proteins, viruses and cells, and chemical substances in fields such as medicine, health, food, and drug discovery There have been proposed various biochips and microchemical chips (hereinafter collectively referred to as microchips) that can be easily measured.

  The microchip has a fluid circuit therein, and the fluid circuit processes, for example, a sample to be examined and analyzed (for example, blood) or a liquid reagent for reacting with the sample. Each part such as a liquid reagent holding chamber to be held, a mixing chamber for mixing the sample and the liquid reagent, a detection part for analyzing and / or inspecting the mixed liquid, and a fine flow path (several number) appropriately connecting these parts The width is about 100 μm). A microchip having such a fluid circuit can perform a series of experiments and analysis operations performed in a laboratory in a chip of several centimeters square and several millimeters in thickness. It has many advantages such as low cost, high reaction speed, high throughput testing, and the ability to obtain test results immediately at the site where the sample was taken, suitable for biochemical testing such as blood testing It is used for.

  By the way, a microchip is usually manufactured by bonding a substrate on which a recess (groove) constituting a fluid circuit is formed and a flat substrate. Conventionally, welding by light (for example, laser beam) irradiation has been used for bonding two substrates made of thermoplastic resin (for example, Patent Document 1). In this welding by light irradiation, one of the two thermoplastic resin substrates is a light-transmitting substrate and the other is a light-absorbing substrate. Irradiate light. When the temperature of the bonded surface exceeds the melting point due to light irradiation, the substrates are melted and the two substrates are bonded.

However, when bonding substrates made of plastic or the like by so-called thermocompression using welding by irradiation with light (for example, laser light), the grooves are crushed due to melting or compression of the substrates. Since this crushing of the groove affects the shape of the fluid circuit of the substrate, it has been necessary to quantify the crushing of the groove within a permissible range. Conventionally, methods for quantifying crushing include optical observation by cross-section cutting or a method using a reflected light path difference by a laser, but cutting of a product or a large-scale apparatus is required.
Japanese Examined Patent Publication No. 62-49850

  The present invention has been made in order to solve the above-mentioned problems, and its object is to have a structure capable of easily quantifying the crushing of the groove with good productivity and a fine flow path on the substrate. To provide a microchip on which a circuit pattern is formed.

  Another object of the present invention is to provide a method of manufacturing a microchip that has good productivity and can quickly and easily determine crushing of grooves.

  The present invention relates to a fluid circuit comprising at least a first substrate having a groove provided on a substrate surface and a second substrate, and comprising a groove and a first substrate side surface of the second substrate. The first substrate includes a crush measurement unit for measuring crushing of the groove due to the bonding between the first substrate and the second substrate on the surface provided with the groove, The measurement unit is installed at least inside a reference groove provided at a depth equal to or greater than the shallowest groove forming the fluid circuit in the thickness direction of the first substrate, and is provided on the surface of the second substrate. The present invention relates to a microchip including a pyramidal, conical, or triangular prism-shaped convex portion having a measurement surface inclined in the direction.

  In the microchip of the present invention, the microchip further includes a box that is provided on the bottom surface inside the reference groove and has a reference surface perpendicular to the thickness direction of the first substrate, and the convex portion is provided on the reference surface. It is preferable.

  In the microchip of the present invention, it is preferable that the vertex of the convex portion or one side of the convex portion has the same height as the surface of the first substrate where the groove is provided and in the thickness direction of the first substrate.

  In the microchip of the present invention, the length in the thickness direction from the surface of the first substrate on which the groove is provided to the surface of the reference surface is the bottom surface of the reference groove from the surface on which the groove of the first substrate is provided. It is preferable that it is ½ or less of the length in the thickness direction.

  In the microchip of the present invention, the first substrate is preferably a black substrate.

  The present invention is also the above-described microchip manufacturing method, wherein at least the first substrate and the second substrate are bonded together using laser light, and the protrusions of the crush measurement unit are crushed. The present invention relates to a method for manufacturing a microchip, comprising a step of measuring a dimension of a portion with an image sensor.

  According to the structure of the microchip of the present invention, substrates can be bonded with high productivity, and even when a fine channel pattern is formed on the substrate, deformation of the channel pattern is suppressed. be able to.

  Further, according to the microchip manufacturing method of the present invention, it is possible to quickly and easily quantify crushing, and in mass production of microchips, an image sensor or a simple non-defective product by visual inspection without observing a cross section by cutting. Can be determined.

  The present invention relates to an optical measurement microchip having a fluid circuit therein. The microchip for optical measurement according to the present invention is formed on the surface of the first substrate by laminating the second substrate on at least the surface of the first substrate having grooves formed on the surface of the substrate. A fluid circuit is constituted by the groove and the bonding surface of the second substrate. The size of the microchip is not particularly limited, but can be, for example, about several cm in length and width and about several mm to 1 cm in thickness. The microchip according to the present invention further includes a third substrate. The first substrate is provided with grooves on both surfaces, and the third substrate is bonded to the groove and the first substrate side of the third substrate. There may be a form having a fluid circuit composed of a surface. Further, in the microchip of the present invention, there is no particular limitation on the shape of the detection unit or the like in a known microchip.

  The fluid circuit may have other parts in addition to the detection unit. Other sites are not particularly limited, but a liquid reagent holding unit for holding a liquid reagent in a known microchip, a sample injected into the liquid reagent and the fluid circuit (or in the sample) (Hereinafter, also referred to simply as “specimen”), each measuring section for measuring, and a mixing section for mixing the weighed liquid reagent and the sample. Further parts may be provided as necessary. An object (analyte) to be examined / analyzed using a microchip having such a part in a fluid circuit is typically a mixed liquid in which a specimen and a liquid reagent are mixed. Here, the liquid reagent is a reagent that processes a sample to be tested or analyzed using a microchip, or is mixed or reacted with the sample. Usually, a fluid circuit is used in advance before using the microchip. It is built in the liquid reagent holding part.

  Each part in the fluid circuit is configured to measure a sample or a liquid reagent, mix the sample and the liquid reagent, introduce the obtained mixed liquid (analyte) into the detection unit, and mix the sample by applying an external centrifugal force. The liquid (subject) is arranged at an appropriate position so that it can be sequentially examined and analyzed, and is connected via a fine fluid circuit (hereinafter sometimes simply referred to as a fluid circuit). Yes. Application of centrifugal force to the microchip is typically performed by placing the microchip on a device (centrifuge) that can apply centrifugal force thereto.

  Hereinafter, embodiments of the present invention will be described with reference to the drawings. In the following drawings, the same or corresponding parts are denoted by the same reference numerals, and description thereof will not be repeated. In addition, dimensional relationships such as length, size, and width in the drawings are changed as appropriate for clarity and simplification of the drawings, and do not represent actual dimensions.

  FIG. 1 is a schematic plan view showing an example of a first substrate of a microchip according to the present invention. Hereinafter, a description will be given based on FIG.

  The present invention relates to a fluid circuit comprising at least a first substrate having a groove provided on a substrate surface and a second substrate, and comprising a groove and a first substrate side surface of the second substrate. The first substrate includes a crush measurement unit 10 for measuring crushing of the groove due to the bonding between the first substrate and the second substrate on the surface where the groove is provided. . In FIG. 1, the crushing measurement unit 10 is formed on the left side toward the left side, but the crushing measurement unit 10 can be located anywhere on the first substrate unless the fluid circuit setting pattern on the first substrate is deformed. 10 may be formed. The crushing measurement unit 10 is installed at least inside a reference groove provided at a depth equal to or greater than the shallowest groove forming the fluid circuit in the thickness direction of the first substrate, and the second groove And a convex portion having a pyramid shape, a conical shape, or a triangular prism shape having a measurement surface inclined in the direction of the surface of the substrate.

  In the microchip of the present invention, the first substrate is provided with a groove on both surfaces, and may include a third substrate that is bonded to a surface opposite to the surface of the first substrate that is bonded to the second substrate. . Hereinafter, the shape and operation of the crush measurement unit 10 formed on the surface of the first substrate will be described in detail by taking a specific embodiment as an example.

<First Embodiment>
FIG. 2 is an enlarged schematic plan view of a crush measurement unit in the microchip of the present embodiment. FIG. 3 is a cross-sectional view taken along line III-III in FIG. 4 is a cross-sectional view taken along line IV-IV in FIG. In the present embodiment, “upward in the thickness direction” means the direction on the second substrate 2 side in the thickness direction, and “downward in the thickness direction” means a direction opposite to the second substrate 2 in the thickness direction. Shall. Further, the depth of the groove means the length in the thickness direction from the surface of the first substrate 1 where the groove is provided.

  Hereinafter, the structure of the crush measurement part of this embodiment is demonstrated based on FIGS. As described above, the microchip of the present embodiment includes at least the first substrate 1 provided with grooves on the substrate surface. And the 1st board | substrate 1 is a figure for measuring the crushing of the groove | channel for forming the fluid circuit by bonding of the 1st board | substrate 1 and the 2nd board | substrate on the surface in which the groove | channel was provided in FIG. 4 is provided. The crushing measurement part has at least the reference groove 5 and the convex part 3. The reference groove 5 is a groove provided at a depth equal to or greater than the shallowest groove forming the fluid circuit in the thickness direction of the first substrate. This is because the depth of the groove forming the fluid circuit varies depending on the location of the pattern, so that the shallowest groove forming the fluid circuit can be measured so that the degree of collapse of the shallowest groove can be measured. It is necessary to provide the above depth. Specifically, the depth A has a depth equal to or greater than the depth of the shallowest groove for forming the fluid circuit. And the convex part 3 is the inside of the reference | standard groove | channel 5, and is a pyramid shape, a cone shape, or a triangular prism shape which has a measurement surface inclined in the direction of the surface of the 2nd board | substrate 2, In this embodiment It is a triangular prism. The measurement surface is a wall surface forming the convex portion 3, and “gradient in the direction of the surface of the second substrate 2” means that the convex portion 3 forms a taper shape in the direction of the second substrate 2. That's fine. And the depth B will show the depth of the convex part 3. FIG.

  And in this embodiment, it is further provided with the box which is installed in the bottom face inside the reference | standard groove | channel 5, and has the reference plane 4 perpendicular | vertical to the thickness direction of a 1st board | substrate. And the convex part 3 is installed on this reference plane 4. The bottom surface inside the reference groove 5 is a surface that forms the bottom of the reference groove 5 in the thickness direction of the first substrate 1, and the bottom surface is a surface perpendicular to the thickness direction of the first substrate 1. It is preferable that Further, in this embodiment, the box has a rectangular parallelepiped shape, but may be, for example, a cylindrical shape or a prismatic shape such as a triangular prism or a pentagonal prism, and has a reference surface 4. If there is, it will not be specifically limited. And in this embodiment, in order to provide this box, although the convex part is not directly formed in the bottom face of the reference groove 5, you may form the convex part 3 in the bottom face of the reference groove 5, for example.

  Moreover, it is preferable that the vertex in the convex part 3 or the one side in a convex part is the same height as the surface of the 1st board | substrate 1, and the thickness direction of a 1st board | substrate. This is because the crushing condition of the groove can be easily measured in the operation described later. In the present embodiment, one side of the convex portion 3 is set to be the same height as the surface of the first substrate 1 and the thickness direction of the first substrate 1.

  The length in the thickness direction from the surface of the first substrate 1 to the surface of the reference surface 4 is ½ or less of the length in the thickness direction from the surface of the first substrate 1 to the bottom surface of the reference groove 5. Preferably there is. This is because it is easy to calculate the degree of crushing of the grooves forming the fluid circuit in the operation described later. In the present embodiment, for example, when the depth of the shallowest groove forming the fluid circuit is 0.3 mm, the depth A is set to about 0.3 mm and the depth B is set to about 0.15 mm. The length C of the convex portion in the longitudinal direction can be set to about 2 mm. Moreover, it is preferable that the 1st board | substrate 1 with which the crushing measurement part was formed is a black board | substrate, and it is further more preferable that the 2nd board | substrate 2 is a transparent substrate.

  Here, FIG. 5 is a schematic plan view for explaining the operation of the crushing measurement unit in bonding the microchip of the present embodiment to the second substrate. 6 is a cross-sectional view taken along line VI-VI in FIG.

  Hereinafter, the operation of the crushing measurement unit when the first substrate and the second substrate of the microchip of the present embodiment are bonded together will be described with reference to FIGS. 5, 6, and 3. When the first substrate 1 and the second substrate 2 are bonded to each other, if the first substrate 1 is melted or compressed, the convex portion 3 is also compressed at the same time. At this time, the bonding between the first substrate 1 and the second substrate can be performed by a known method such as thermocompression bonding using a laser beam or the like. As described above, in the present embodiment, when the first substrate 1 is a black substrate and the second substrate 2 is a transparent substrate, the convex portion 3 when the collapse measuring portion is viewed from the top surface direction is the first substrate 1. It is possible to easily measure the length e in the longitudinal direction in the black portion formed by being compressed by the two substrates 2. The length e can be measured visually. For example, the length e can be measured quickly and easily by determining the position of the crushing measurement unit with an image sensor or the like. . In the image sensor, a crushed portion can be measured using the difference in reflectance, and can be measured more easily than visually confirmed.

  In this way, the length e of the black portion formed by compressing the convex portion 3 having the measurement surface and the length C in the longitudinal direction of the convex portion is compressed by the length d in the thickness direction. Can be calculated. Since the length d corresponds to the crushing condition of the groove forming the fluid circuit, the crushing condition of the groove forming the fluid circuit can be determined at the same time by measuring the length C and the length e. Can also be measured.

  In the present embodiment, a box having a reference surface 4 is further provided. The depth B from the surface of the first substrate 1 provided with the grooves forming the fluid circuit to the reference surface 4 may be set as an allowable upper limit of crushing of the grooves where the microchip does not substantially function. Specifically, preferably, the depth B is preferably ½ or less of the depth A. This is because it is easy to calculate the degree of crushing of the grooves forming the fluid circuit. For example, when the crushing measurement part is viewed from the upper surface direction, when the portion provided with the box inside the reference groove 5 and the convex part 3 is a black part formed by being compressed, This is because it can be easily determined that the microchip cannot be used.

  In the present embodiment, the convex portion 3 is provided with a triangular prism shape. However, when the convex portion 3 is conical, for example, the convex portion 3 having a measurement surface is compressed and formed. By measuring the radius or diameter of the black portion and measuring the radius or diameter of the bottom surface of the convex portion 3, the degree of collapse can be calculated. In this invention, it can apply by combining the shape of a convex part and the measuring method of the crushed part as an optimal thing suitably.

  Further, as described above, in the present embodiment, since the first substrate 1 is a black substrate, irregular reflection can be prevented when thermocompression bonding is performed with laser light.

  As described above, by using the structure of the present invention, it is possible to quickly and easily measure the degree of crushing that occurs when the first substrate 1 and the second substrate 2 are bonded together without destroying the microchip. Can be quantified.

<Second Embodiment>
FIG. 7 is a schematic cross-sectional view in which a crushing measurement unit in the microchip of the present embodiment is enlarged.

  Hereinafter, the structure of the crush measurement part of this embodiment is demonstrated based on FIG. As described above, the microchip of the present embodiment includes at least the first substrate 1 provided with grooves on the substrate surface. And the 1st board | substrate 1 has the crushing measurement part for measuring the crushing of the groove | channel for forming the fluid circuit by bonding of the 1st board | substrate 1 and the 2nd board | substrate on the surface in which the groove | channel was provided. I have. The crushing measurement part has at least the reference groove 5 and the convex part 3.

  In the present embodiment, the shape of the convex portion 3 is different from that of the first embodiment. The measurement surface as the wall surface forming the convex portion 3 is inclined in the direction of the surface of the second substrate 2, but its shape is different from that of the first embodiment. However, since the convex part 3 forms the taper shape in the direction of the 2nd board | substrate 2, the effect is the same as what was mentioned above.

<Third Embodiment>
In the microchip manufacturing method in the present embodiment, the first substrate and the second substrate of the microchip described above are used. And after manufacturing about the 1st substrate and the 2nd substrate by a publicly known method, the process of pasting together using the laser beam of the 1st substrate and the 2nd substrate, and the convex part of a crushing measurement part Measuring the dimensions of the collapsed portion of the image with an image sensor.

  That is, in the manufacturing method, by providing the step of measuring the size of the collapsed portion of the convex portion of the collapse measuring unit with an image sensor, it is possible to quickly and easily quantify the degree of collapse of the groove forming the fluid circuit. In mass production of microchips, simple non-defective / defective products can be determined without observing a cross section by cutting.

  It should be understood that the embodiments and examples disclosed herein are illustrative and non-restrictive in every respect. The scope of the present invention is defined by the terms of the claims, rather than the description above, and is intended to include any modifications within the scope and meaning equivalent to the terms of the claims.

It is a typical top view showing an example of the 1st substrate of the microchip concerning the present invention. It is the typical top view to which the crushing measurement part in the microchip of a 1st embodiment was expanded. It is sectional drawing along the III-III line in FIG. It is sectional drawing along the IV-IV line in FIG. It is a typical top view for demonstrating operation | movement of the crushing measurement part in bonding with the 2nd board | substrate of the microchip of 1st Embodiment. It is sectional drawing along the VI-VI line in FIG. It is the typical sectional view which expanded the crushing measurement part in the microchip of a 2nd embodiment.

Explanation of symbols

  DESCRIPTION OF SYMBOLS 1 1st board | substrate, 2nd board | substrate, 3 convex part, 4 reference plane, 5 reference | standard groove | channel, 10 squashing measurement part.

Claims (6)

A fluid circuit comprising at least a first substrate having a groove provided on the substrate surface and a second substrate, and comprising the groove and the first substrate side surface of the second substrate. A microchip having
The first substrate includes a crush measurement unit for measuring crushing of the groove due to the bonding between the first substrate and the second substrate on the surface provided with the groove,
The crush measurement unit is at least
A reference groove provided at a depth equal to or greater than the shallowest groove forming the fluid circuit in the thickness direction of the first substrate;
A microchip provided with a pyramid-like, conical or triangular prism-shaped convex part installed in the reference groove and having a measurement surface inclined in the direction of the surface of the second substrate. A box which is installed on the bottom surface inside the reference groove and has a reference surface perpendicular to the thickness direction of the first substrate;
The microchip according to claim 1, wherein the convex portion is provided on the reference surface.   The vertex in the said convex part or one side in the said convex part is the same height as the surface where the said groove | channel of the said 1st board | substrate was provided, and the thickness direction of the said 1st board | substrate. Microchip.   The length in the thickness direction from the surface of the first substrate on which the groove is provided to the surface of the reference surface is the thickness from the surface of the first substrate on which the groove is provided to the bottom surface of the reference groove. The microchip according to claim 2 or 3, wherein the microchip is not more than 1/2 of the length in the direction.   The microchip according to claim 1, wherein the first substrate is a black substrate. A method of manufacturing a microchip according to any one of claims 1 to 5,
at least,
Bonding the first substrate and the second substrate using laser light;
Measuring the size of the collapsed portion of the convex portion of the collapse measuring unit with an image sensor;
A method of manufacturing a microchip comprising:

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