JP5725554B2 - Wiring board for gene analysis - Google Patents

Description

  The present invention relates to a wiring board for gene analysis used for analyzing genes.

  In recent years, techniques for analyzing genes have made rapid progress. Among such techniques for analyzing genes, gene analysis methods using nanopores are attracting attention. This gene analysis method using nanopores is a method for detecting a change in current when a gene passes through a nanopore that is a pore having a size slightly larger than that of a gene molecule to read a base sequence.

JP 2001-242135 A

  The problem to be solved by the present invention is to provide a wiring board for gene analysis suitable for use in a gene analysis method using nanopores.

The wiring board for gene analysis of the present invention is a wiring board for gene analysis used in a gene analysis method using nanopores, and is arranged in a matrix on the first insulating layer and the upper surface of the first insulating layer. A plurality of detection electrodes made of copper and laminated on the first insulating layer, a detection recess having the detection electrode as a bottom surface is formed , and a film having nanopores is formed in the recess A second insulating layer deposited so as to cover, the entire surface of the detection electrode exposed in the detection recess, and a region from the detection electrode to a height in the middle of the side wall of the detection recess And a plated metal layer covering the surface.

  According to the wiring board for gene analysis of the present invention, the plating metal layer covering the entire surface of the detection electrode exposed in the detection recess and the region from the detection electrode to the middle height of the side wall of the detection recess. Because it is equipped, it can prevent elution of unnecessary copper ions from the detection electrode into the detection recess, thereby making it suitable for gene analysis using nanopores. A wiring board can be provided.

FIG. 1 is a schematic cross-sectional view showing an example of an embodiment of a wiring board for gene analysis of the present invention. 2 is a top view of the wiring board for gene analysis shown in FIG. FIG. 3 is an enlarged schematic cross-sectional view of the main part of the wiring board for gene analysis shown in FIG.

  Next, an example of an embodiment of the wiring board for gene analysis of the present invention will be described with reference to FIGS. As shown in FIG. 1, the wiring board for gene analysis of this example is formed by laminating an insulating layer 2 and an insulating layer 3 on the upper and lower surfaces of a core substrate 1.

  The core substrate 1 is made of, for example, an electrically insulating material obtained by impregnating a glass cloth obtained by weaving glass fiber bundles vertically and horizontally with a thermosetting resin such as a bismaleimide triazine resin or an epoxy resin. The core substrate 1 has a thickness of about 100 to 1000 μm, and a through hole 4 having a diameter of about 100 to 300 μm is formed from the upper surface to the lower surface of the core substrate 1.

  Core conductor layers 5 are attached to the upper and lower surfaces of the core substrate 1 and the inner walls of the through holes 4. The core conductor layer 5 is made of a highly conductive metal material such as a copper foil having a thickness of about 5 to 25 μm or a copper plating layer. Furthermore, the inside of the through hole 4 to which the core conductor layer 5 is attached is filled with a hole filling resin 6 made of a thermosetting resin such as an epoxy resin.

  Such a core substrate 1 is formed as follows. First, a double-sided copper-clad plate is prepared in which a copper foil having a thickness of about 5 to 35 μm is deposited on both upper and lower surfaces of an insulating plate obtained by impregnating a glass cloth with a thermosetting resin. Next, the through-hole 4 is drilled in the double-sided copper-clad plate by drilling or laser processing. Next, after desmearing the inside of the through hole 4, an electroless copper plating layer and an electrolytic copper plating layer are sequentially deposited in the through hole 4 and the upper and lower copper foil surfaces. The thickness of the electroless copper plating layer is about 0.1 to 1 μm, and the thickness of the electrolytic copper plating layer is about 5 to 25 μm. Next, a hole-filling resin 6 is filled in the through hole 4 provided with the electrolytic copper plating layer. The filling of the hole filling resin 6 is performed by filling the through hole 4 with a paste-like thermosetting resin by a screen printing method and then thermosetting it. The filled hole filling resin 6 is flattened by polishing the upper and lower ends thereof together with the upper and lower copper plating layers. Next, an electroless copper plating layer and an electrolytic copper plating layer are sequentially deposited on the upper and lower end surfaces and the upper and lower copper plating layers of the planarized hole filling resin 6. The thickness of the electroless copper plating layer is about 0.1 to 1 μm, and the thickness of the electrolytic copper plating layer is about 5 to 25 μm. Finally, the core substrate 1 is obtained by patterning the copper foil and the copper plating layer thereon by a known subtractive method to form the core conductor layer 5.

  The insulating layer 2 is made of an insulating material containing a thermosetting resin such as an epoxy resin. The insulating layer 2 has a thickness of about 30 to 50 μm, and via holes 7 having a diameter of about 50 to 100 μm are formed from the upper surface to the lower surface of the insulating layer 2. Such an insulating layer 2 is formed as follows, for example. First, a thermosetting resin film is laminated on the upper and lower surfaces of the core substrate 1. A vacuum press is used for lamination. The resin film contains an uncured thermosetting resin component and an inorganic insulating filler. Finally, after thermally curing the resin film, the insulating layer 2 is formed by drilling the via hole 7 by laser processing from the surface. In addition, after drilling the via hole 7, a desmear process or a soft etching process is performed as needed.

  A conductor layer 8 is deposited on the surface of the insulating layer 2 and in the via hole 7. The conductor layer 8 is made of a copper plating layer having a thickness of about 5 to 25 μm. A part of the conductor layer 8 forms a detection electrode 9 for detecting a current corresponding to the base sequence of the gene on the surface of the insulating layer 2 on the upper surface side. The detection electrodes 9 have a circular shape with a diameter of about 50 to 100 μm, and are arranged in a matrix at a pitch of about 100 to 200 μm, as shown in FIG. A part of the conductor layer 8 forms an external connection terminal 10 connected to an external analyzer on the surfaces of the upper and lower insulating layers 2. These detection electrodes 9 and external connection terminals 10 are electrically connected to each other through the conductor layer 8 and the core conductor layer 5.

  Such a conductor layer 8 is formed as follows. First, an electroless copper plating layer is deposited on the surface of the insulating layer 2 and the via hole 7. The thickness of the electroless copper plating layer is about 0.1 to 1 μm. Next, a plating resist layer having an opening corresponding to the pattern of the conductor layer 8 is deposited on the electroless copper plating layer. The plating resist layer is formed by adhering a photosensitive thermosetting resin film on the electroless copper plating layer and using a well-known photolithography technique to expose and develop in a predetermined pattern. Next, an electrolytic copper plating layer is deposited on the electroless copper plating layer exposed in the opening of the plating resist layer. The thickness of the electrolytic copper plating layer is about 5 to 25 μm. Finally, after the plating resist layer is peeled and removed, the electroless copper plating layer exposed from the electrolytic copper plating layer is removed by etching to form the conductor layer 8.

  The insulating layer 3 is made of the same electrical insulating material as the insulating layer 2 or a different insulating material. The thickness of the insulating layer 3 is about 20 to 30 μm, and is about 5 to 25 μm thinner than the insulating layer 2. In the insulating layer 3, a detection recess 11 having a detection electrode 9 as a bottom surface is formed by laser processing. The opening diameter of the detection recess 11 is about 30 to 50 μm. Further, the insulating layer 3 is formed with a window portion 12 through which the external connection terminal 10 is exposed. The window portion 12 is formed in a size sufficient to expose the external connection terminal 10.

  Such an insulating layer 3 is formed as follows. First, a photosensitive thermosetting resin layer is laminated on the surface of the insulating layer 2 to which the conductor layer 8 is applied. The lamination includes a method of applying a resin paste and drying it, and a method of attaching a resin film using a vacuum press. Next, the laminated photosensitive resin layer is exposed to light and developed so as to have the detection concave portion 11 and the window portion 12 by adopting a photolithography technique, and finally the resin layer is thermally cured to be insulated. Layer 3 is formed. Alternatively, after the thermosetting resin film is attached to the surface of the insulating layer 2 and thermally cured, the insulating layer 3 is formed by forming the detection recess 11 and the window 12 by laser processing from the surface. It is formed.

  According to the wiring board for gene analysis of this example, as shown in the enlarged schematic sectional view of the main part in FIG. 3, the film M having the nanopore P is deposited so as to cover the detection recess 11 and the gene G The base sequence of gene G is detected by detecting the current generated according to its base sequence when passing through the nanopore P and analyzing the current with an external analyzer connected to the external connection terminal 10 Can do. The connection between the external connection terminal 10 and the external analysis device is performed by providing a socket corresponding to the external connection terminal 10 in the external analysis device and inserting the end portion on which the external connection terminal 10 is formed into the socket. It is.

  In the wiring board for gene analysis of this example, the plating covering the entire surface of the detection electrode 9 exposed in the detection recess 11 and the region from the detection electrode 9 to the middle height of the side wall of the detection recess 11. A metal layer 13 is deposited. The plated metal layer 13 is composed of a composite plating layer in which, for example, a nickel plating layer having a thickness of 2 to 10 μm and a gold plating layer having a thickness of 0.02 to 0.1 μm are sequentially deposited, and is formed by an electroless plating method. Has been. Specifically, after a large amount of the electroless plating catalyst is attached only to the surface of the detection electrode 9 in the detection recess 11 and the lower end portion of the side wall of the detection recess 11, the catalyst is not applied only to the portion where the catalyst is much attached. A method of depositing the plated metal layer 13 by an electrolytic plating method is employed. In addition, after the catalyst is attached to the surface of the insulating layer 3 and the detection recess 11 using a highly active catalyst solution, the step of removing the catalyst on the surface of the insulating layer 3 by washing is performed. Since the contact with the cleaning liquid is weak at the lower end, a large amount of catalyst can be attached only to the surface of the detection electrode 9 in the detection recess 11 and the lower end of the side wall of the detection recess 11. By having such a plated metal layer 13, copper ions are effectively prevented from eluting from the detection electrode 9 into the detection recess 11. When copper ions elute in the detection recess 11, it becomes difficult to accurately detect the current generated according to the base sequence when the gene G passes through the nanopore P.

  In the present invention, the plated metal layer 13 covers the entire surface of the detection electrode 9 exposed in the detection recess 11 and the region from the detection electrode 9 to the middle height of the side wall of the detection recess 11. The boundary between the detection electrode 9 and the insulating layer 3 at the outer peripheral edge of the bottom surface of the detection recess 11 can be covered with the plated metal layer 13 with a wide width. Therefore, it is possible to very effectively prevent elution of copper ions from the detection electrode 9 through the boundary between the detection electrode 9 and the insulating layer 3 on the outer peripheral edge of the bottom surface of the detection recess 11.

  When the plated metal layer 13 is formed of a nickel plated layer and a gold plated layer thereon, if the thickness of the nickel plated layer is less than 2 μm, it becomes difficult to satisfactorily deposit the gold plated layer thereon. If it exceeds 10 μm, it takes a long time to form such a thick nickel plating layer, so that the production efficiency of the substrate becomes poor. If the thickness of the gold plating layer is less than 0.02 μm, the nickel plating layer underneath cannot be satisfactorily covered and the nickel plating layer is likely to be oxidized, and 0.1 μm is reduced. If it exceeds, the gold plating layer becomes thicker than necessary, and the manufacturing cost of the substrate becomes high. Therefore, when the plating metal layer 13 is formed of a nickel plating layer and a gold plating layer thereon, the thickness of the nickel plating layer is preferably in the range of 2 to 10 μm, and the thickness of the gold plating layer is 0.02 to 0 It is preferably in the range of 1 μm.

  When the height that the plated metal layer 13 covers from the detection electrode 9 to the middle of the side wall of the detection recess 11 is less than 2 μm, the detection electrode 9 and the insulating layer 3 on the outer peripheral edge of the bottom surface of the detection recess 11 The boundary portion cannot be covered with the plating metal layer 13 with a sufficiently wide width, and the elution of copper ions from the boundary between the detection electrode 9 and the insulating layer 3 at the outer peripheral edge of the bottom surface of the detection recess 11 is effectively prevented. It becomes difficult to do. Therefore, the height that the plated metal layer 13 covers from the detection electrode 9 to the middle of the side wall of the detection recess 11 is preferably 2 μm or more.

  Furthermore, according to the wiring board for gene analysis of the present invention, the plated metal layer 13 is formed on the entire surface of the detection electrode 9 exposed in the detection recess 11 and on the middle of the detection recess 9 side wall from the detection electrode 9. Since the region up to this point is covered, the detection electrode 9 and the insulating layer 3 are in direct contact with each other without the plating metal layer 13 interposed therebetween. Therefore, the copper of the detection electrode 9 having excellent adhesion to the thermosetting resin of the insulating layer 3 is firmly adhered.

  When the detection recess 11 is formed in the insulating layer 3 by laser processing, the dimensional accuracy in the fine detection recess 11 having an opening diameter of 30 to 50 μm is high, and thereby the gene passing through the nanopore P. The current generated according to the base sequence of G can be accurately detected. Therefore, the detection recess 11 is preferably formed by laser processing.

  Further, when the insulating layer 2 and the insulating layer 3 are formed of the same insulating material, the warpage of the substrate can be reduced and the lamination of the insulating layer 2 and the insulating layer 3 can be made strong. Therefore, the insulating layer 2 and the insulating layer 3 are preferably formed of the same insulating material.

  Moreover, if the thickness of the insulating layer 3 is made thinner than the thickness of the insulating layer 2, a fine detection recess having excellent dimensional accuracy can be easily formed in the insulating layer 3 by laser processing. Therefore, it is preferable to make the thickness of the insulating layer 3 thinner than the thickness of the insulating layer 2.

  Furthermore, when the dummy electrode 14 that occupies at least the projected portion of the external connection terminal 10 is disposed between the insulating layer 2 and the insulating layer 3, the flatness of the external connection terminal 10 is kept good. Thus, the connection with the outside can be made more reliable. Therefore, it is preferable to dispose a dummy electrode 14 that occupies at least a portion where the external connection terminal 10 is projected between the insulating layer 2 and the insulating layer 3.

  Thus, according to the present invention, it is possible to provide a gene analysis wiring board suitable for use in a gene analysis method using nanopores. The present invention is not limited to an example of the above-described embodiment, and various modifications can be made without departing from the gist of the present invention. For example, in the above-described example, the plated metal layer 13 is formed. Although the nickel plating layer and the gold plating layer are sequentially deposited, the plating metal layer 13 may be a nickel plating layer, a palladium plating layer, and a gold plating layer that are sequentially deposited.

  The wiring board for gene analysis of the present invention can also be used for analysis of substances other than genes.

2 First Insulating Layer 3 Second Insulating Layer 9 Detection Electrode 11 Detection Recess 13 Plating Metal Layer

Claims (3)

A wiring board for gene analysis used in a gene analysis method using nanopores , comprising a first insulating layer and a plurality of detection electrodes made of copper disposed in a matrix on the upper surface of the first insulating layer And a detection recess having the detection electrode as a bottom surface is formed , and a film having nanopores is deposited to cover the recess . And a plated metal layer that covers the entire surface of the detection electrode exposed in the detection recess and a region from the detection electrode to the middle height of the side wall of the detection recess. A wiring board for gene analysis, characterized by comprising:   2. The gene analysis according to claim 1, wherein the plating metal layer comprises a nickel plating layer having a thickness of 2 to 10 [mu] m and a gold plating layer having a thickness of 0.02 to 0.1 [mu] m. Wiring board. The wiring board for gene analysis according to claim 1 or 2, wherein a height that the plated metal layer covers from the detection electrode to the middle of the side wall of the concave portion for detection is 2 µm or more.

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