JP2011053091A - Bonding member and method of manufacturing the same - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a bonding member capable of performing more reliable sealing than before and precisely forming a channel and further effectively suppressing mixture of bubbles on a bonding interface, and to provide a method of manufacturing the bonding member. <P>SOLUTION: A silicone rubber sheet (sealing member) 14 is bonded to the surface 11a of a first base material 11 where the channel (groove section) 13 is formed on the surface 11a by a roller 15, thus adhering the surface 11a of the first base material 11 to the silicone rubber sheet 14. Then, a liquid resin 16 is applied between the silicone rubber sheet 14 and the flat surface 12a of the second base material 12, and the first and second base materials 11, 12 are pressurized while performing heating in that state. <P>COPYRIGHT: (C)2011,JPO&INPIT

Description

  The present invention relates to a joining member such as a biochip plate having a fine channel and a method for manufacturing the same.

  A biochip plate used for μ-TAS (Micro-Total Analysis Systems) or the like has a structure in which substrates having excellent transparency and low fluorescence are bonded together.

  One plate is provided with a groove constituting a flow path, and the other is a flat plate. A method using an adhesive and a method using thermocompression bonding are known for joining these plates.

  However, when bonding is performed using an adhesive, since the adhesive enters the fine channel formed in a groove shape, the fine channel is often blocked. In addition, even when the blockage does not occur, there is a problem that the flow rate is not stable because the size of the flow path varies depending on the location. On the other hand, if the application amount of the adhesive is reduced in order to avoid such a problem, the adhesion is insufficient and the sealing tends to be poor. Further, there is a problem that the transparent and colorless fluorescent agent does not exist, or even the low fluorescent adhesive causes the plate side to become cloudy due to the influence of the solvent or the like.

  Moreover, when joining between plates by thermocompression bonding, there existed a problem that joining took time and productivity was bad. Moreover, the pressure required for joining is high, and as a result, the fine flow path is crushed and a problem that a crack occurs in the plate is likely to occur. In addition, when an organic solvent was previously applied to the joint surface, fluorescence and light scattering generated from the plate were likely to increase.

International Publication No. 2008/050791 JP 2008-49311 A JP 2006-78414 A JP 2006-53094 A Japanese Patent Laid-Open No. 2008-8880

  Each of the above patent documents discloses an invention relating to a biochip plate (microchip plate).

  However, all the inventions described in Patent Documents 1 to 5 join both plates with an adhesive sheet or an adhesive.

  In addition, in the configuration in which a sheet is interposed between both plates, if bubbles are mixed in the joining interface, the refractive index changes there, and high-precision optical measurement cannot be performed. Control was an important issue.

  The invention described in Patent Document 5 discloses a process of applying an adhesive to the surface of the plate on which the groove is formed, and subsequently bonding a film lid. In Patent Document 5, the adhesive is applied so as not to enter the groove portion. However, it is difficult and difficult to apply the adhesive while avoiding the groove portion. Even if the adhesive can be applied while avoiding the groove, it is easy for the adhesive to protrude into the groove by pressurization, and as a result, it is difficult to control the adhesive so that it does not enter the groove.

  Therefore, the present invention is for solving the above-described conventional problems, and in particular, it is possible to form a reliable seal and flow path with high accuracy compared to the conventional technique, and to effectively suppress the bubble mixing at the joining interface. It aims at providing a joining member and its manufacturing method.

The present invention is a method for manufacturing a bonded member comprising a first base material and a second base material joined together, wherein at least the detection region is made light transmissive.
A step of closely attaching a light-transmitting sealing member to the groove forming surface of the first base material on which the concave groove portion is formed, and closing the opening on the groove forming surface side of the groove portion;
A step of applying pressure between the first base material and the second base material in a state where a light-transmitting liquid resin is applied between the second base material and the sealing member;
It is characterized by having.

  In the present invention, first, a light-transmissive sheet-like sealing member is brought into close contact with the groove forming surface on which the groove portion of the first base material is formed, for example, with a roller, thereby opening the groove portion on the groove forming surface side. Block. This state is shown in FIG. FIGS. 3A and 3B are comparative examples, where reference numeral 1 is a first base material and reference numeral 2 is a rubber sheet (sealing member). 3A, when pressure is applied to the flow path (groove portion) 3, the rubber sheet 2 is deformed as shown in FIG. 3B, and the flow path 3 is swollen or in the worst case, the rubber sheet 2 May be damaged. Therefore, the form of the comparative example shown in FIG. 3 cannot be applied to a μ-TAS or a microreactor that adjusts the flow rate with high accuracy.

  Therefore, the present invention brings the sealing member into close contact with the groove forming surface of the first base material, sandwiches the sealing member between the first base material and the second base material, Thus, for example, even if pressure is applied to the flow path (groove portion), the shape of the flow path can be prevented from being deformed.

  In addition, in the present invention, the sealing member can block the opening of the groove portion to achieve reliable sealing, and the groove portion is crushed and the size of the groove portion is changed as in the case of using an adhesive as in the prior art. There will be no inconvenience. In addition, when a pressure is applied between the first base material and the second base material by interposing a sealing member, it is possible to suppress problems such as cracks in the first base material and the second base material and crushing of the grooves. .

  Further, in the present invention, a light transmissive liquid resin is applied between the sealing member and the flat surface of the second base material, and the first base material and the second base material are pressurized in that state. The liquid resin fills the gap between the sealing member and the second base material and drives out the bubbles to the outside. In addition, the liquid resin can be applied while sliding between the sealing member and the second base material, and the first base material and the second base material can be aligned with high accuracy.

  In the present invention, it is preferable that the sealing member is formed by curing the liquid resin into a sheet shape. Moreover, it is preferable to use a two-component mixed addition reaction type silicone rubber material for the sealing member and the liquid resin, and pressurize between the first base material and the second base material while heating.

  As a result, a highly transparent and low fluorescent material can be realized, and a highly accurate optical measurement can be realized and a highly reliable joining member can be manufactured. Moreover, the cushioning property between the first base material and the second base material can be effectively increased, and when the first base material and the second base material are pressurized, the first base material and the second base material The occurrence of cracks and the like can be prevented more effectively.

  Moreover, in this invention, it is preferable to form the said 1st base material and the said 2nd base material by either among cycloolefin, glass, an acrylic resin, and PDMS. As a result, a highly transparent and low fluorescent material can be realized, and a highly accurate optical measurement can be realized and a highly reliable joining member can be manufactured.

Moreover, in this invention, it is preferable to carry out molecular adhesion between the said 1st base material and the said 2nd base material. Specifically, before bringing the sealing member into close contact with the groove forming surface of the first base material,
It is preferable to immerse at least one of the first base material, the second base material, and the sealing member in a polysilane compound solution shown in Chemical Formula 2 below to form a coating on the surface.

Here, a total of 2n Rs of R _{11 to} R _1n and R ₂₁ to _2n is either A or B shown below, and the molar ratio of A and B is between 40:60 and 60:40. It is.

A is a hydrocarbon having 2 to 5 carbon atoms in the main chain, and has one of the following structures:
_{CH 2 = C A · C B} · C C · C D · C E -
CH ₂ = C _A -X-C _B · C _C · C _{D-
CH 2 = C A · C B} -X-C C · C D -
CH ₂ = C _A · C _B · C _C -X-C _{D-
CH 2 = C A · C B} · C C · C D -X-
X is selected from any of —NH—, —S—, and —O—,
C _A -C _{E is, -CO -, - CH 2 -} , - C (CH 3) 2 -, - C (C 2 H 5) 2 -, - CH =, - CCH 3 =, - CC 2 H 5 =, -CCH ₃ (C ₂ H ₅ )-, and C _B to _CE may be blank.

B is a halogen or a hydrocarbon having 1 to 3 carbon atoms in the main chain,
X-C _A・ C _B・ C _C −
It has the structure of X is a halogen or alkoxy group, and C _{A to} C _C are selected from any one of —CO—, —CH ₂ —, —C (CH ₃ ) ₂ —, —CH═, —CCH ₃ =, and a blank. .

  Thereby, the adhesive strength between a 1st base material and a 2nd base material can be raised. In particular, since the bonding can be performed without using an adhesive, the flow path can be formed with a highly accurate dimension without collapsing the flow path as in the prior art.

  Moreover, the joining member in the present invention is provided in close contact with the first base material having a concave groove formed on the surface, the second base material, and the groove forming surface of the first base material. It has a sealing member that closes the opening on the groove forming surface side, and a light-transmitting cured resin layer interposed between the sealing member and the second base material, and at least the detection region is light-transmitting. It is characterized by this.

  Thereby, reliable sealing with respect to a groove part is possible, and the said groove part can be formed by a highly accurate dimension, without being crushed. Moreover, it can suppress appropriately that a bubble enters between a sealing member and a 2nd base material, can implement | achieve a highly accurate optical measurement, and can make it a highly reliable joining member.

  In the present invention, the sealing member and the cured resin layer are preferably formed of a two-component mixed addition reaction type silicone rubber material. As a result, high transparency and low fluorescence can be realized, and optical measurement can be performed more effectively and accurately.

  According to the present invention, the groove portion can be surely sealed, and the groove portion can be formed with a highly accurate dimension without being crushed. Moreover, it can suppress appropriately that a bubble enters between a sealing member and a 2nd base material, and can also perform alignment between a 1st base material and a 2nd base material easily.

It is process drawing which shows the manufacturing method of the biochip plate (joining member) of this embodiment, and each figure is the longitudinal cross-sectional view which cut | disconnected the biochip plate in the manufacturing process from the thickness direction. FIG. 1D is a partially enlarged longitudinal sectional view of a biochip plate showing an enlarged part of FIG. A longitudinal sectional view of a biochip plate as a comparative example,

  FIG. 1 is a process diagram showing a method for manufacturing a biochip plate (joining member) according to the present embodiment, and each figure is a cross-sectional view of the biochip plate in the manufacturing process cut from the thickness direction.

  The biochip plate 10 in this embodiment is applied to μ-TAS or the like. Basically, a minute amount of liquid that is a specimen is passed through the fine flow path 13 and the characteristics of the liquid are measured. For example, a light source is applied to a sample liquid that has flowed to the detection region (measurement region) of the biochip plate, and weak light such as fluorescence generated from the sample or near-field light is measured. Therefore, the biochip plate 10 is formed with high transparency and low fluorescence, and at least the detection region (portion including the flow path 13) is light transmissive.

  Hereinafter, with reference to FIG. 1, the manufacturing process of the biochip plate 10 in this embodiment is demonstrated.

  First, in the process of FIG. 1A, a concave flow path (groove portion) 13 is formed on the surface 11 a of the plate-like first base material 11.

  The depth dimension of the flow path 13 is about 10-500 micrometers. The flow path 13 can be formed by an etching technique or the like. Further, the planar shape of the flow path 13 can be variously changed depending on the usage.

  In the present embodiment, the first base material 11 on which the flow path 13 shown in FIG. 1 is formed is immersed in a polysilane compound solution shown in the following chemical formula 3 to form a film on the surface 11a of the first base material 11. Is preferred. In this embodiment, the coating is formed not only on the surface 11 a but also on the entire peripheral surface of the first base material 11.

Here, a total of 2n Rs of R _{11 to} R _1n and R ₂₁ to _2n is either A or B shown below, and the molar ratio of A and B is between 40:60 and 60:40. It is.

A is a hydrocarbon having 2 to 5 carbon atoms in the main chain, and has one of the following structures:
_{CH 2 = C A · C B} · C C · C D · C E -
CH ₂ = C _A -X-C _B · C _C · C _{D-
CH 2 = C A · C B} -X-C C · C D -
CH ₂ = C _A · C _B · C _C -X-C _{D-
CH 2 = C A · C B} · C C · C D -X-
X is selected from any of —NH—, —S—, and —O—,
C _A -C _{E is, -CO -, - CH 2 -} , - C (CH 3) 2 -, - C (C 2 H 5) 2 -, - CH =, - CCH 3 =, - CC 2 H 5 =, -CCH ₃ (C ₂ H ₅ )-, and C _B to _CE may be blank.

B is a halogen or a hydrocarbon having 1 to 3 carbon atoms in the main chain,
X-C _A・ C _B・ C _C −
It has the structure of X is a halogen or alkoxy group, and C _{A to} C _C are selected from any one of —CO—, —CH ₂ —, —C (CH ₃ ) ₂ —, —CH═, —CCH ₃ =, and a blank. .

  In addition, the 2nd base material 12 shown by the process of FIG.1 (c) is also previously immersed in the solution of the polysilane compound shown in said Chemical Formula 3, and a 1st base material is covered over the perimeter surface of the 2nd base material 12. A film is formed in the same manner as in FIG.

  Furthermore, the said film may be formed in the surface of the silicone rubber sheet (sealing member) 14 shown by the process of FIG.1 (b). In this embodiment, although the said film may be formed in at least any one among the 1st base material 11, the 2nd base material 12, and the silicone rubber sheet 14, the 1st base material 11 provided with a joining interface at least. It is preferable that the coating film is formed on both the second substrate 12 and the second substrate 12.

  Subsequently, in the process of FIG. 1B, the light-transmissive silicone rubber sheet 14 is directly bonded and adhered to the surface (flow path forming surface) 11a of the first base material 11 on which the flow path 13 is formed. .

  The silicone rubber sheet 14 is thinner than the thickness of the first base material 11 and is soft.

  The silicone rubber sheet 14 is preferably formed by curing a two-component mixed addition reaction type silicone rubber material.

  Compared to the one-component type, the two-component type does not need to delay reactions such as cross-linking and curing, and the addition of a cross-linking agent, a curing agent, a reaction inhibitor, etc. can be reduced. In addition, in the addition reaction type, a vinyl group or hydrogen is added in advance to the main silicone resin, and they are crosslinked by heating and reaction in the presence of a platinum catalyst. On the other hand, in the condensation reaction type, the added crosslinking agent decomposes itself to cause the main resins constituting the rubber to react with each other, so that more crosslinking agents need to be added than in the addition type. For this reason, by using a two-component mixed addition reaction type silicone rubber, the silicone rubber sheet 14 can be made colorless and transparent and can be formed with low fluorescence. Further, since the two-component mixed addition reaction type silicone rubber material contains platinum as a catalyst, it can be proved by the composition analysis that the two-component mixed addition reaction type silicone rubber material is a two-component mixed addition reaction type silicone rubber material.

  As shown in FIG. 1B, the silicone rubber sheet 14 is bonded to the surface 11a of the first base material 11 while extruding air bubbles interposed between the silicone rubber sheet 14 and the first base material 11 with a roller 15, for example. The opening on the surface 11a side of the flow path 13 is closed.

  The silicone rubber sheet 14 has no adhesiveness (non-adhesiveness), but has a certain degree of tackiness, so that it is easy for air bubbles to be involved when pasting. As shown in FIG. 1 (b), the silicone rubber sheet 14 is directly adhered to the surface 11a of the first base material 11 by the roller 15, so that the silicone rubber sheet 14 and the first base material 11 are properly adhered while expelling air bubbles. It is possible to make it.

  The sheet thickness of the silicone rubber sheet 14 is preferably about 0.05 to 1 mm.

  In this embodiment, it is possible to use another sealing member (resin sheet) instead of the silicone rubber sheet 14, but it is necessary to have high transparency and low fluorescence, and further elastic deformation is possible (rubber). It is preferable to have elasticity, and a material that can be molded into a sheet shape is preferable.

  Next, in the step shown in FIG. 1C, a light transmissive liquid resin 16 is applied to the flat surface 14 a of the silicone rubber sheet 14. Here, “liquid” refers to a state having fluidity after application, and includes not only liquid but also paste. Even if the viscosity and thixotropy are high, those that flow and spread due to the level of pressure necessary to bond the plates together are included in the category of “liquid”.

  As with the silicone rubber sheet 14, the liquid resin 16 is preferably a two-component mixed addition reaction type silicone rubber material. That is, the uncured liquid mixture of the liquid A and the liquid B is dropped onto the surface 14 a of the silicone rubber sheet 14.

  Or you may apply | coat the liquid resin 16 to the flat surface 12a formed in the opposing surface with the 1st base material 11 of the 2nd base material 12, and the flat surface 12a of the 2nd base material 12, and the silicone rubber sheet 14 The liquid resin 16 may be applied to both of the surface 14a.

  In the step shown in FIG. 1D, the first base material 11 and the second base material 12 are bonded together, and pressure is applied between the first base material 11 and the second base material 12 while being heated. Join.

  The liquid resin 16 spreads in the gap between the silicone rubber sheet 14 and the second base material 12 by pressurization, fills the gap, and pushes out bubbles to the outside. Since the tackiness of the surface 14a of the silicone rubber sheet 14 is strong, it is possible to drive out entrained bubbles by applying the liquid resin 16 to the surface 14a. Further, the second base 12 and the silicone rubber sheet 14 can be slid, and as a result, the first base 11 and the second base 12 can be positioned with high accuracy.

  The liquid resin 16 is thermally cured and interposed as a resin cured layer 17 between the silicone rubber sheet 14 and the second substrate 12 (see FIG. 1D).

  However, as described above, when both the silicone rubber sheet 14 and the liquid resin 16 are two-component mixed addition reaction type silicone rubber materials, the cured resin layer 17 becomes rubbery, and the cured silicone rubber sheet 14 and the cured resin layer 17 are not illustrated. 2 are integrated (the portion indicated by the dotted line is the interface between the silicone rubber sheet 14 and the cured resin layer 17, but such an interface cannot be analyzed). However, a protrusion that protrudes outward from the outer peripheral portion 14b of the silicone rubber sheet 14 when the liquid resin 16 is pushed outward by pressurizing between the first base material 11 and the second base material 12. 17 a is easily formed on the cured resin layer 17, and the presence of the protruding portion 17 a shown in FIG. 2 can prove that the cured resin layer 17 is interposed between the silicone rubber sheet 14 and the second substrate 12. Alternatively, if the sheet thickness of the sheet composed of the silicone rubber sheet 14 and the resin cured layer 17 is thin, for example, at the outer peripheral portion away from the flow path 13, it can be seen that there is no resin cured layer 17 in that portion. It can be proved that the cured resin layer 17 is interposed in a portion including at least the detection region between the rubber sheet 14 and the second substrate 12. Further, when the compositions of the silicone rubber sheet 14 and the resin cured layer 17 are different, it can be verified by composition analysis.

  As described with reference to FIG. 1, in this embodiment, the silicone rubber sheet (sealing member) 14 is brought into close contact with the surface (flow path forming surface) 11 a of the first base material 11 on which the concave flow path 13 is formed. The opening on the surface 11 a side of the path 13 is closed, and then a liquid resin 16 is applied between the silicone rubber sheet 14 and the flat surface 12 a of the second base 12 to add a gap between the first base 11 and the second base 12. There is a characteristic part in the manufacturing process.

  In the present embodiment, the flow path 13 can be appropriately sealed with the silicone rubber sheet 14, and when the space between the first base material 11 and the second base material 12 is pressurized, the silicone rubber sheet 14 is securely sealed by elastic deformation. Can be realized. Therefore, for example, there is no problem of leakage of the sample liquid injected into the flow path 13. Further, there is no problem that the size of the flow path 13 is changed or collapsed as in the case of joining using an adhesive as in the prior art, and the flow path 13 can be formed with a highly accurate size. In addition, since the silicone rubber sheet 14 that seals the flow path 13 is suppressed by the second base material 12 that has higher rigidity than the silicone rubber sheet 14, the size of the flow path 13 is maintained even when pressure is applied to the flow path 13. Does not change, and the silicone rubber sheet 14 is not damaged by the pressure.

  In addition, in the present embodiment, the liquid resin 16 fills the gap between the silicone rubber sheet 14 and the second base material 12 and allows air bubbles to be expelled to the outside, so that the space between the second base material 12 and the silicone rubber sheet 14 is appropriately set. It can be in close contact. Since bubbles can be suppressed in this way, the presence of a medium having a different refractive index in the detection region (measurement region) can be suppressed, and high-precision optical measurement can be performed. Furthermore, by interposing the liquid resin 16 between the silicone rubber sheet 14 and the second base material 12, slipping is improved and the first base material 11 and the second base material 12 can be aligned with high accuracy.

  Furthermore, the bonding method of the present embodiment does not require a precise adhesive coating (printing) process as in the prior art, and the first base material 11 and the second base material 12 can be bonded in a simple bonding process as compared with the prior art. Production efficiency can be improved.

  Based on the above, based on the manufacturing method of the biochip plate (joining member) 10 of the present embodiment, the flow path 13 can be formed in a predetermined shape with high dimensional accuracy as well as reliable sealing with respect to the flow path (groove portion) 13. A highly transparent and low-fluorescence biochip plate 10 that can suppress the mixing of bubbles between the base material 11 and the second base material 12 can be manufactured with high productivity.

  In the present embodiment, “high transparency” and “light transmittance” refer to a state where the light transmittance is 85% or more (preferably 90% or more) at a wavelength of 450 to 600 nm (preferably 400 to 900 nm).

  In addition, after the silicone rubber sheet 14 is first brought into close contact with the flat surface 12a of the second base material 12, the liquid resin 16 is applied between the silicone rubber sheet 14 and the surface 11a of the first base material 11 to thereby form the first base material. When pressure is applied between 11 and the second substrate 12, the liquid resin 16 enters the flow path (groove) 13, and the flow path 13 cannot be formed with high accuracy. Therefore, in this embodiment, after the silicone rubber sheet 14 is first brought into close contact with the surface 11 a of the first base material 11, the liquid resin 16 is applied between the silicone rubber sheet 14 and the flat surface 12 a of the second base material 12. A pressure is applied between the first base material 11 and the second base material 12.

  In the present embodiment, the first base material 11 and the second base material 12 are preferably formed of any one of cycloolefin, glass, acrylic resin, and PDMS. The first base material 11 and the second base material 12 are preferably plastic materials in order to reduce the cost by mass production, and are particularly formed of a cycloolefin polymer (COP) or a cycloolefin copolymer (COC). Is preferred.

  For COP, the trade names ZEONEX and ZEONOR made by Nippon Zeon, and the trade name "ARTON" made by Nippon Synthetic Rubber, and for COC, the trade name "Optrez" by Nippon Kasei Kogyo, and the trade name "Topass" made by Polyplastics can be preferably used. These are all colorless and transparent and are low fluorescent materials. With ZEONEX, the fluorescence can be suppressed to several times that of alkali-free glass.

  Moreover, it is preferable that the 1st base material 11 and the 2nd base material 12 are formed with a plate with a thickness of 0.5 mm-5 mm.

  Further, as described above, in the present embodiment, it is preferable that both the silicone rubber sheet 14 and the liquid resin 16 are formed of a two-component mixed addition reaction type silicone rubber material. Thereby, transparency and high fluorescence can be realized more effectively. By the way, when both the silicone rubber sheet 14 and the liquid resin 16 are formed of a two-component mixed addition reaction type silicone rubber material, the silicone rubber sheet 14 and the liquid resin 16 are not adhesive. In addition, since it has tackiness, between the 1st base material 11 and the 2nd base material 12 can be stuck, but it is inferior to adhesive strength. For this reason, in order to obtain sufficient adhesive strength, in this embodiment, the 1st base material 11 in which the flow path 13 was formed in the surface 11a, and the opposing surface with the 1st base material 11 are the 2nd flat surfaces 12a. The base material 12 is immersed in the solution of the polysilane compound shown in Chemical Formula 3 above, and a film is formed on the surfaces of the first base material 11 and the second base material 12.

  And when it pressurizes between the 1st base material 11 and the 2nd base material 12 in the process of Drawing 1 (d), between silicone rubber sheet 14 and the 1st base material 11, resin hardened layer 17, and the 2nd The substrates 12 are firmly bonded by molecular bonding. Specifically, for example, the vinyl group of the coating reacts with the silicone rubber sheet 14, and the alkoxy group of the coating reacts with the base material to increase the adhesive strength.

  However, in this embodiment, without using molecular adhesion, for example, a commercially available adhesive is applied to the outer peripheral portion away from the detection region (measurement region), and the first base material 11 and the second base material 12 are bonded and fixed. Alternatively, the first base material 11 and the second base material 12 can be held in a state where pressure is applied from the outside (adhesion or the like is not performed).

  Moreover, in FIG. 1, although it was the manufacturing method of the biochip plate 10 which joined the 1st base material 11 and the 2nd base material 12, a base material can also be made into the laminated structure of 3 layers or more.

  Depending on the form of the flow path 13 and the like, an opening for allowing the liquid to pass may be provided at a position facing the flow path 13 of the silicone rubber sheet 14, but the opening of the silicone rubber sheet 14 is larger than the width of the flow path 13. By widening the width of the liquid resin, even if the liquid resin 16 protrudes somewhat to the opening portion, it is possible to minimize the influence on the liquid flow.

  First, two types of substrates (plates) were injection molded using a cycloolefin copolymer material (ZEONEX 480R) manufactured by ZEON. That is, a first base material in which grooves having a width of 100 μm and a depth of 100 μm were formed on the surface vertically and horizontally and a flat plate-like second base material were prepared. All the substrates had a size of 75 mm × 25 mm × 1 mm. These substrates were joined by the following three methods.

(Method of joining using adhesive)
In this method, a first base material and a second base material are joined using a commercially available adhesive. After a small amount of adhesive is dropped on the flat surface of the second base material and spread thinly and evenly with a scraper, the flow path forming surface side of the first base material is opposed to the adhesive application surface and pressed with a roller. The substrate was brought into close contact.

  In the case of using a double-sided adhesive tape, first, the double-sided adhesive tape is first applied to the flat surface of the second substrate, and then the flow path forming surface side of the first substrate is opposed to the double-sided adhesive tape and pressed with a roller. Both substrates were brought into close contact.

  Twelve types of samples (samples 1 to 12) were prepared using 7 items of liquid adhesive and 5 items of double-sided adhesive tape, respectively.

(Method of joining by thermocompression bonding)
A small amount of solvent was applied to the surface of the second base material and allowed to dry naturally, and then the pressure between the base materials was increased at 5 MPa and treated at 110 ° C. for 2 hours to prepare Sample 13.

(Joining method using sealing member (silicone rubber sheet) and liquid resin)
Three types of silicone rubber sheets were used. The first sheet is a heat-curing type millable rubber (thickness 0.5 mm), the second sheet is an electron beam cross-linking type silicone rubber sheet (thickness 0.4 mm), and the third sheet This sheet is a KE1935 silicone sheet made of Shin-Etsu Silicone. A liquid B and a liquid B of KE1935, which is a two-component mixed addition reaction type silicone rubber molding material made by Shin-Etsu Silicone, were mixed and put into a mold and thermally cured to produce a silicone rubber sheet. The sheet thickness was 0.5 mm.

  Subsequently, each substrate and each silicone rubber sheet were immersed in a 0.5 wt% ethanol solution of vinylmethoxysilane shown in the following chemical formula 3 for 3 minutes at room temperature.

  Subsequently, each silicone rubber sheet is placed on the flow path forming surface of the first substrate, and the silicone rubber sheet and the flow path forming surface are expelled from one end of the sheet so that bubbles do not enter using a roller. And stuck together.

  Subsequently, several drops of a mixed liquid of uncured KE1935 liquid A and liquid B are dropped on the surface of each silicone rubber sheet, and each second base material is placed on the surface of each silicone rubber sheet. With the material fixed with a jig, it was set in an oven and pressed at 120 ° C. for 5 minutes to prepare Samples 14-16.

The following experiment was performed on each sample.
(Destructive strength test)
When the four corners of each sample are fixed and the load is gradually increased from above at a constant speed to the center, the first base material and the second base material peel or the base material breaks. The load was measured. At this time, on the basis of the breaking strength of 3.5 kgf in the sample 13 joined by thermocompression bonding, the case where the breaking strength was exceeded was determined to be acceptable (OK), and the case where the breaking strength was below was determined to be unacceptable (NG).

(Measurement of fluorescence)
Each sample was set on a microscope and irradiated with 532 nm green monochromatic light serving as excitation light obliquely from above. On the other hand, the light from the objective lens of the microscope can be guided to the sensor by switching the optical path, and the sensor has a narrow band filter of 585 nm, and the intensity of this light is a relative value, but the fluorescence intensity and did.

  In addition, the fluorescence measurement was performed in a state where the first base material and the second base material were simply overlapped, and the fluorescence intensity (790) at this time was used as a reference value. Further, the fluorescence intensity of each sample was divided by the reference value, and if it was within 2 times, the fluorescence intensity was preferable.

(Liquid penetration test)
When water droplets colored with ink are dropped from the inlet of the flow path and the outlet of the flow path is sucked with a small vacuum pump, the liquid flows into the flow path, and the liquid leaks out or oozes out of the flow path. Otherwise, it was accepted.

(Visual test)
Changes in transparency such as white turbidity and coloring, unevenness, and air bubble contamination were checked.

  The experimental results of Samples 1 to 13 are shown in Table 1, and the experimental results of Samples 14 to 16 are shown in Table 2.

  Among samples 1 to 12, which were joined using the adhesives shown in Table 1, acrylic adhesives and silicone adhesives had sufficient joint strength, but the fluorescence value was very high, and the liquid permeability test. Some of the samples failed (NG). Some samples using double-sided tape were confirmed to have air bubbles by a visual test.

  Further, as shown in Table 1, in the sample using the cyanoacrylate adhesive, a part of the adhesion surface became cloudy, and both the bonding strength and the liquid permeability test failed (NG).

  Further, in sample 13 joined by thermocompression bonding, the fluorescence intensity was relatively low (about 3.7 times the reference value), but the liquid passing test failed (NG), and the flow path was crushed. confirmed.

  In the sample obtained by bonding using the silicone rubber sheet shown in Table 2, the fluorescence intensity of sample 14 became cloudy and became unmeasurable. Samples 15 and 16 all passed the bonding strength, the liquid permeability test, and the visual test (OK), but the fluorescence intensity of sample 15 was slightly higher.

  The sample 16 is securely sealed without air bubbles or crushing of the flow path. As shown in Table 2, the sample 16 passed all the tests of fluorescence intensity, bonding strength, liquid permeability test, and visual test. there were. When the body fluid was actually flowed through the sample 16 and optical measurement was performed, stable measurement could be performed.

10 Biochip Plate 11 First Base Material 12 Second Base Material 13 Channel 14 Silicone Rubber Sheet (Sealing Member)
15 Roller 16 Liquid resin 17 Resin cured layer 17a Protrusion

Claims (8)

In the manufacturing method of the joining member which is formed by joining the first base material and the second base material, and at least the detection region is light transmissive,
A step of closely attaching a light-transmitting sealing member to the groove forming surface of the first base material on which the concave groove portion is formed, and closing the opening on the groove forming surface side of the groove portion;
A step of applying pressure between the first base material and the second base material in a state where a light-transmitting liquid resin is applied between the second base material and the sealing member;
The manufacturing method of the joining member characterized by having.   The method for manufacturing a joining member according to claim 1, wherein the sealing member is formed by curing the liquid resin into a sheet shape.   The two-component mixed addition reaction type silicone rubber material is used for the sealing member and the liquid resin, and pressure is applied between the first base material and the second base material while heating. The manufacturing method of the joining member of.   4. The method for manufacturing a joining member according to claim 1, wherein the first base material and the second base material are formed of any one of cycloolefin, glass, acrylic resin, and PDMS. 5.   The manufacturing method of the joining member of any one of Claim 1 thru | or 4 which carries out molecular adhesion between the said 1st base material and the said 2nd base material. Before bringing the sealing member into close contact with the groove forming surface of the first base material,
6. The film is formed on the surface by immersing at least one of the first base material, the second base material, and the sealing member in a polysilane compound solution shown in Chemical Formula 1 below. The manufacturing method of the joining member of any one of these.

Here, a total of 2n R of R _{11 to} R _1n and R ₂₁ to _2n is either A or B shown below, and the molar ratio of A and B is between 40:60 and 60:40. It is.
A is a hydrocarbon having 2 to 5 carbon atoms in the main chain, and has one of the following structures:
_{CH 2 = C A · C B} · C C · C D · C E -
CH ₂ = C _A -X-C _B · C _C · C _{D-
CH 2 = C A · C B} -X-C C · C D -
CH ₂ = C _A · C _B · C _C -X-C _{D-
CH 2 = C A · C B} · C C · C D -X-
X is selected from any of —NH—, —S—, and —O—,
C _A -C _{E is, -CO -, - CH 2 -} , - C (CH 3) 2 -, - C (C 2 H 5) 2 -, - CH =, - CCH 3 =, - CC 2 H 5 =, -CCH ₃ (C ₂ H ₅ )-, and C _B to _CE may be blank.
B is a halogen or a hydrocarbon having 1 to 3 carbon atoms in the main chain,
X-C _A・ C _B・ C _C −
It has the structure of Where X is a halogen or alkoxy group, and C _{A to} C _C are selected from any one of —CO—, —CH ₂ —, —C (CH ₃ ) ₂ —, —CH═, —CCH ₃ =, and a blank. .   Provided in close contact with the groove-forming surface of the first base material, the second base material, and the first base material, each having a concave groove portion formed on the surface, and closing the opening on the groove-forming surface side of the groove portion. A joining member, comprising: a sealing member; and a cured resin layer interposed between the sealing member and the second base material, wherein at least the detection region is light-transmissive. The joining member according to claim 7, wherein the sealing member and the cured resin layer are formed of a two-component mixed addition reaction type silicone rubber material.

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