JP5251983B2 - Microchip manufacturing method - Google Patents

Description

The present invention relates to a method for manufacturing a microchip .

  2. Description of the Related Art Conventionally, in a technical field that performs chemical reaction, separation, analysis, and the like of a liquid sample such as nucleic acid, protein, and blood in a minute space, a microchip having a minute channel or circuit formed therein has been put into practical use.

  Such a microchip has two substrates formed of a resin or the like, and after performing microfabrication such as a through hole or a channel for liquid sample injection on one substrate, It is manufactured by sandwiching a substrate between hot plates and performing heat bonding (see, for example, Patent Document 1).

JP-A-2005-77218

  However, in the technique described in Patent Document 1, the through hole provided in one substrate is sealed by the hot plate contacting the substrate and the other substrate, so that heating by the hot plate and subsequent cooling are performed. At this time, the space between the other substrate and the hot plate and the air in the through hole expand and contract, which causes the other substrate to be deformed, which may impair dimensional accuracy.

This invention is made | formed in view of the said situation, and makes it a subject to provide the manufacturing method of the microchip which can prevent the fall of a dimensional accuracy.

According to the first aspect of the present invention, in the method of manufacturing a microchip, in which two substrates that are stacked and have a flow path formed inside are sandwiched between two hot plates facing each other and heat bonded.
As the two substrates, a flow channel substrate in which a through hole communicating with the flow channel is formed in the thickness direction, and a cover that covers one opening of the through hole with a bonding surface that is heat-bonded to the flow channel substrate Using the substrate,
And with the two hot plates, when brought into contact with the flow path substrate or the cover substrate, abutting surfaces has an opening to the contact surface between the flow path substrate or the cover substrate Each having a communication hole that communicates with the outside air,
With the two hot plates being sandwiched in the thickness direction by the two hot plates so that the positions of the through holes and the openings of the communication holes correspond to each other, A bonding step of heat-bonding the two substrates ;
Prior to the joining step, when heated by the two hot plates, the pressure in the communication hole and the pressure in the through hole of one of the hot plates in contact with the cover substrate are substantially the same. A condition setting step for setting the bonding conditions in the bonding step;
It is characterized by providing.

In this microchip manufacturing method,
Wherein out of two hot plates, as one of the hot plate to contact with the cover substrate, the pore diameter X of the opening of the communication hole be used that satisfies the following formula (1) preferred.
X <Y [mm] (1)
(However, Y: Hole diameter [mm] of the through hole of the flow path substrate)

Moreover, in this microchip manufacturing method,
Of the two hot plates, it is preferable to use one of the two hot plates that abuts the cover substrate so that the hole diameter X of the opening of the communication hole satisfies the following expression (2).
X <Y-0.4 [mm] (2)

Moreover, in this microchip manufacturing method,
Of the two hot plates, it is preferable to use one of the two hot plates that abuts the cover substrate so that the hole diameter X of the opening of the communication hole satisfies the following expression (3).
X> Y-0.5 [mm] (3)

  According to the first aspect of the present invention, as at least one of the two heat plates, the communication hole having an opening on the contact surface with the substrate and communicating the contact surface with the outside air The two substrates are heated and bonded in a state where the positions of the through hole of the flow path substrate and the opening of the communication hole correspond to each other, so that heating by two hot plates and subsequent cooling It is possible to suppress the expansion / contraction of one or both of the air in the gap and the through hole between the cover substrate and the hot plate. Therefore, deformation of the cover substrate can be suppressed, and deterioration of dimensional accuracy can be prevented.

  Further, as the two heat plates, the hole diameter X of the communication hole of one of the heat plates in contact with the cover substrate is more preferably X <Y with respect to the hole diameter Y of the through hole of the flow path substrate. Since X <Y−0.4 is used, it is possible to prevent the occurrence of a region where the contact surface of the heat plate does not contact the required joint surface of the microchip, and in the peripheral portion of the through hole. Generation | occurrence | production of an unjoined part can be prevented.

  Thereby, the fall of dimensional accuracy can be prevented, without reducing the joint strength of two board | substrates.

  In addition, since one of the heat plates in contact with the cover substrate is such that the hole diameter X of the opening of the communication hole is X> Y−0.5, the heating with the two heat plates and the subsequent cooling are performed. In addition, even if a slight deformation trace having a hole diameter X following the opening shape of the opening of the communication hole remains on the cover substrate, the diameter of the deformation trace is not significantly different from the hole diameter Y of the through hole of the flow path substrate. It is possible to prevent the deformation trace from being noticeable by being distorted into the opening shape of the through hole.

It is a top view of the microchip concerning the present invention. 4 is a cross-sectional view of the microchip according to the present invention, and is a cross-sectional view taken along the line IV-IV in FIG. It is a top view of the resin-made board | substrates in which the groove | channel for flow paths was formed. It is a conceptual diagram which shows schematic structure of the manufacturing apparatus of the microchip which concerns on this invention. It is a conceptual diagram which shows schematic structure of the modification of the manufacturing apparatus of the microchip which concerns on this invention. It is sectional drawing of the modification of a resin-made board | substrate.

  Hereinafter, preferred embodiments of the present invention will be described with reference to the drawings.

  1 is a top view of a microchip 1 according to the present invention, FIG. 2 is a sectional view taken along the line IV-IV in FIG. 1, and FIG. 3 is a top view of a resin substrate 10 constituting the microchip 1.

  As shown in these drawings, the microchip 1 includes two rectangular plate-like resin substrates 10 and 20 bonded to each other.

  Among these, as shown in FIGS. 2 and 3, the resin substrate 10 has linear flow channel grooves 12 and 13 formed on one surface (the upper surface in FIG. 2). Further, as shown in FIG. 3, through holes 14 penetrating in the thickness direction of the resin substrate 10 are respectively formed at both ends of the flow path grooves 12 and 13. In the present embodiment, the other surface of the resin substrate 10 (the surface where the channel grooves 12 and 13 are not formed) is smooth. Further, the channel groove 12 and the channel groove 13 in the present embodiment are formed orthogonal to each other, but may be formed without being orthogonal to each other. The resin substrate 10 is a flow path substrate in the present invention.

  On the other hand, as shown in FIG. 2, the resin substrate 20 is a member having a smooth surface, and is bonded to the formation surface of the flow path grooves 12 and 13 in the resin substrate 10. By this bonding, the resin substrate 20 functions as a cover (cover) for the flow path grooves 12 and 13 and the through hole 14, and the fine flow path 15 is formed between the flow path grooves 12 of the resin substrate 10 and the flow path. A fine channel 16 is formed between the groove 13 and the through hole 14 to form an opening 17. The resin substrate 20 is a cover substrate in the present invention.

  Here, the shape of the microchannels 15 and 16 (channel grooves 12 and 13) takes into consideration the fact that the amount of analysis sample and reagent used can be reduced, the fabrication accuracy of molds, transferability and mold release properties. The width and the depth are preferably in the range of 10 μm to 200 μm, but are not particularly limited, and may be determined according to the use of the microchip. And may be the same or different. In the present embodiment, the cross-sectional shape of the microchannels 15 and 16 is a rectangular shape, but this shape is an example, and other shapes such as a circular shape may be used.

  Since the through hole 14 of the resin substrate 10 is connected to the flow path grooves 12 and 13 as described above, the opening 17 formed by the through hole 14 is connected to the fine flow paths 15 and 16. . The opening 17 is a hole for introducing, storing, and discharging a gel, a sample, and a buffer solution, and is connected to a tube or nozzle provided in an analyzer (not shown). Thus, a gel, a sample, a buffer solution, or the like is introduced into or discharged from the fine channels 15 and 16. Note that the shape of the opening 17 (through hole 14) is not limited to a circular shape, and may be various other shapes such as a rectangular shape. Further, the inner diameter of the opening 17 (through hole 14) may be adjusted to the analysis method or the analysis apparatus, and is preferably about 2 mm, for example.

  The shape of the resin substrates 10 and 20 may be any shape as long as it is easy to handle and analyze. For example, a shape such as a square, a rectangle, or a circle is preferable. Moreover, the size of the resin substrates 10 and 20 is preferably about 10 mm square to 200 mm square, and more preferably 10 mm square to 100 mm square. In addition, the plate thickness of the resin substrate 10 on which the channel grooves 12 and 13 are formed is preferably about 0.2 mm to 5 mm, more preferably 0.5 mm to 2 mm in consideration of moldability. The thickness of the resin substrate 20 functioning as a lid (cover) is preferably about 0.2 mm to 5 mm, more preferably 0.5 mm to 2 mm in consideration of moldability. However, when the channel groove is not formed in the resin substrate 20 as in the present embodiment, a film (sheet member) may be used as the resin substrate 20 instead of a plate member. . In this case, the thickness of the film is preferably 30 μm to 300 μm, and more preferably 50 μm to 150 μm. In the present embodiment, the resin substrate 20 is thinner than the resin substrate 10.

  Resin is used for the material of the resin substrates 10 and 20. As this resin, those having good moldability (transferability, releasability), high transparency, and low autofluorescence with respect to ultraviolet rays and visible light are preferable. For example, thermoplastic resins are used.

  Examples of the thermoplastic resin include polycarbonate, polymethyl methacrylate, polystyrene, polyacrylonitrile, polyvinyl chloride, polyethylene terephthalate, polyamide, polyvinyl acetate, polyvinylidene chloride, polypropylene, polyisoprene, polyethylene, polydimethylsiloxane, and cyclic polyolefin. Etc. are preferably used. It is particularly preferable to use polymethyl methacrylate and cyclic polyolefin. The resin substrate 10 and the resin substrate 20 may be made of the same material or different materials.

  In addition to the thermoplastic resin, a thermosetting resin, an ultraviolet curable resin, or the like may be used for the resin substrate 20 in which the channel groove is not formed. As the thermosetting resin, polydimethylsiloxane is preferably used.

  The resin substrate 10 on which the channel grooves 12 and 13 are formed is preferably formed by an injection molding method or a press molding method, and the resin substrate 20 on which the channel groove is not formed is an extrusion molding method. It may be produced by a method other than an injection molding method such as a T-die molding method, an inflation molding method, or a calendar molding method, or by an injection molding method.

  Then, the manufacturing apparatus of said microchip 1 is demonstrated.

  FIG. 4 is a conceptual diagram showing a schematic configuration of a microchip manufacturing apparatus (hereinafter referred to as a manufacturing apparatus) 5. In this figure, the microchip 1 is shown in a simplified manner.

  As shown in this figure, the manufacturing apparatus 5 includes two hot plates 51 and 52 that are disposed vertically opposite to each other.

  The hot plates 51 and 52 are flat plate members that sandwich and heat-bond the resin substrates 10 and 20, and are moved in the contact / separation direction (vertical direction in the drawing) by the moving means 53. The moving means 53 may move the hot plates 51 and 52, respectively, or only one of them. As such a moving means 53, a conventionally known apparatus can be used. Further, in the following description, the resin substrate 10 is disposed on the lower side and the resin substrate 20 is disposed on the upper side between the hot plates 51 and 52 so that the resin substrates 10 and 20 are sandwiched between them. This will be explained.

  Communication holes 510 and 520 are formed in the hot plates 51 and 52, respectively. As shown in the figure, these communication holes 510 and 520 have contact surfaces 51a and 52a (when the hot plates 51 and 52 are brought into contact with the resin substrates 20 and 10, respectively. Opening portions 510a and 520a are provided on the lower surface of the heat plate 51 and the upper surface of the heat plate 52, and the contact surfaces 51a and 52a are communicated with the outside air. Further, the opening 510a and the opening 520a open at positions facing each other in the contact surfaces 51a and 52a, and the positions of the through holes 14 when the resin substrates 10 and 20 are heat-bonded. Are provided at positions corresponding to the through-holes 14 respectively. In the present embodiment, the contact surfaces 51a and 52a of the hot plates 51 and 52 are smooth at portions other than the communication holes 510 and 520. In addition, at least one of the communication holes 510 and 520 may be formed.

  The upper limit of the hole diameter X of the opening 510a of the communication hole 510 opened on the contact surface 51a of the hot plate 51 is preferably X <Y with respect to the hole diameter Y of the through hole 14 of the resin substrate 10. [Mm], and more preferably X <Y−0.4 [mm]. The lower limit of the pore diameter X is preferably X> Y−0.5 [mm].

  Here, the communication hole 510 is described as having a circular shape, but the shape of the hole is not particularly limited thereto. That is, even if it is not circular shape, the shape obtained by offsetting a through-hole other than rectangular shape and polygonal shape may be sufficient. Further, the hole diameter X in these cases refers to the length of the longest diagonal line.

  Then, the manufacturing method of the microchip 1 is demonstrated.

  First, a release agent (not shown) that prevents the resin substrates 20 and 10 from sticking is applied to the contact surfaces 51a and 52a of the two hot plates 51 and 52 (application process). A conventionally known release agent can be used as such a release agent.

  Next, the resin substrates 20 and 10 are stacked one above the other with the formation surfaces of the flow path grooves 12 and 13 on the resin substrate 10 facing inward (upper side), and disposed between the hot plates 51 and 52. To do.

  Next, the hot plates 51 and 52 are brought close to the moving means 53 so that the resin substrates 20 and 10 are sandwiched in the thickness direction by the hot plates 51 and 52 while pressing the resin substrates 20 and 10 in this state. Heat joining (joining process).

  At this time, the positions of the through holes 14 of the resin substrate 10 and the openings 510a and 520a of the communication holes 510 and 520 of the heat plates 51 and 52 opened in the contact surfaces 51a and 52a correspond to each other, that is, In the state where the through hole 14 and the openings 510a and 520a overlap each other when viewed from the top, the resin substrates 20 and 10 are heat bonded by the hot plates 51 and 52. However, in the present embodiment, the through hole 14 and the openings 510a and 520a are substantially concentric in a top view.

  In this way, the resin substrates 20 and 10 are heated in a state where the positions of the through hole 14 of the resin substrate 10 and the opening 510a of the communication hole 510 of the heat plate 51 opened on the contact surface 51a correspond to each other. By joining, in the heating by the hot plates 51 and 52 and the subsequent cooling, the expansion / contraction of the air in the slight gap between the resin substrate 20 and the hot plate 51 above the through hole 14 can be suppressed.

  Further, the positions of the through hole 14 of the resin substrate 10 and the opening portion 520a of the communication hole 520 of the heat plate 52 opened in the contact surface 52a correspond to each other, that is, the through hole 14 and the communication hole 520 By heat-bonding the resin substrates 20 and 10 in a connected state, in the heating by the hot plates 51 and 52 and the subsequent cooling, the expansion / expansion of the air in the through-hole 14 is performed without sealing the through-hole 14. Shrinkage can be suppressed.

  Here, the resin substrate 10 and the resin substrate 20 are joined by heat welding such as thermocompression bonding or heat lamination. By applying thermocompression bonding or heat laminating to the resin substrates 10 and 20, the resin on the bonding surface of the resin substrates 10 and 20 is melted, and the resin substrate 10 and the resin substrate 20 are bonded to each other. Chip 1 is formed. In addition, as heating temperature, the temperature of 70 to 200 degreeC can be used, for example.

  Next, the hot plates 51 and 52 are separated from the moving means 53 (separation step).

  Then, the microchip 1 is manufactured by peeling the resin substrate 20 or the resin substrate 10 attached to the hot plate 51 or the hot plate 52 (peeling step).

  According to the microchip manufacturing method described above, in the heating by the hot plates 51 and 52 and the subsequent cooling, a slight gap between the resin substrate 20 and the hot plate 51 above the through hole 14 and one of the through holes 14 or Since the expansion / contraction of both airs can be suppressed, the deformation of the resin substrate 20 can be suppressed and the reduction of the dimensional accuracy can be prevented.

  The upper limit of the hole diameter X of the opening 510a of the communication hole 510 opened on the contact surface 51a of the hot plate 51 is preferably X <Y with respect to the hole diameter Y of the through hole 14 of the resin substrate 10. [Mm], and more preferably X <Y−0.4 [mm], thereby preventing the occurrence of a region where the contact surface of the hot plate 51 does not contact the required joint surface of the microchip 1. It is possible to prevent the occurrence of an unjoined portion around the through hole 14.

  Thereby, the fall of dimensional accuracy can be prevented, without reducing the joint strength of the resin-made board | substrates 10 and 20. FIG.

Further, the lower limit of the hole diameter X of the opening 510a of the communication hole 510 opened on the contact surface 51a of the hot plate 51 is preferably X> Y with respect to the hole diameter Y of the through hole 14 of the resin substrate 10. Since the thickness is −0.5 [mm], a slight deformation trace of the hole diameter X following the opening shape of the opening 510a of the communication hole 510 is formed during the heating by the hot plates 51 and 52 and the subsequent cooling. 20, since the diameter of the deformation trace is not significantly different from the hole diameter Y of the through hole 14 of the resin substrate 10, the deformation trace is lost to the opening shape of the through hole 14 to prevent it from being noticeable. can do.
[Modification]
Then, the modification of the manufacturing method of the microchip which concerns on this invention is demonstrated. In addition, the same code | symbol is attached | subjected to the component similar to said embodiment, and the description is abbreviate | omitted.

  As shown in FIG. 5, in addition to the configuration of the manufacturing apparatus 5 in the above embodiment, the microchip manufacturing apparatus 5A in the present modification includes pressure sensors 61 and 62, pressure adjusting means 71 and 72, and control means 54. And.

  The pressure sensors 61 and 62 are disposed on the hot plates 51 and 52 so that each pressure in the communication holes 510 and 520 can be measured. Moreover, it connects so that a measured value may be output to the control means 54. FIG.

  The pressure adjusting means 71 and 72 are pumps connected to the open air openings of the communication holes 510 and 520 by pipes, and can pressurize and depressurize the communication holes 510 and 520. Further, it is connected to the control means 54 and its drive is controlled.

  The control means 54 is connected to the pressure sensors 61 and 62 and the pressure adjustment means 71 and 72, and the pressure adjustment means according to the measured values from the pressure sensors 61 and 62 so that the communication holes 510 and 520 have a predetermined pressure. 71 and 72 are controlled.

  Then, the manufacturing method of the microchip 1 by 5 A of manufacturing apparatuses is demonstrated.

  First, as in the above-described embodiment, a release agent is applied to the contact surfaces 51a and 52a of the hot plates 51 and 52 (application process).

  Next, the joining conditions in the joining process are set (condition setting process). In this process, in the joining process, which is a subsequent process, the pressure adjusting means 71 and 72 of the pressure plate 71 and 72 are set so that the pressure in the communication hole 510 of the hot plate 51 and the pressure in the through hole 14 of the resin substrate 10 are substantially the same. Determine the driving state. More specifically, the resin substrates 20 and 10 are sandwiched and heated by the hot plates 51 and 52 in the same manner as in the subsequent bonding step, and in this state, the control unit 54 controls the driving of the pressure adjusting units 71 and 72. Thus, the measured values of the pressure sensor 61 and the pressure sensor 62 are made substantially the same. At this time, the drive state of the pressure adjusting means 71 and 72 where the measured values of the pressure sensor 61 and the pressure sensor 62 are substantially the same is stored in the control means 54.

  Next, the hot plates 51 and 52 are separated (separation process), and the microchip 1 used for setting the conditions in the condition setting process is separated (peeling process).

  Then, a release agent is applied again to the contact surfaces 51a and 52a of the hot plates 51 and 52 (application process).

  Next, similarly to the above-described embodiment, the new resin substrates 20 and 10 are sandwiched between the hot plates 51 and 52 and heat-bonded (bonding step). However, at the time of this heat bonding, the driving state of the pressure adjusting means 71 and 72 stored in the condition setting step is reproduced by the control means 54. Thereby, the heat bonding of the resin substrates 10 and 20 can be performed in a state where the pressure in the communication hole 510 of the hot plate 51 and the pressure in the through hole 14 of the resin substrate 10 are substantially the same.

  Next, the hot plates 51 and 52 are separated from the moving means 53 (separation step).

  Then, the resin substrate 20 or the resin substrate 10 is peeled from the hot plate 51 or the hot plate 52 (peeling step).

  According to the microchip manufacturing method by the manufacturing apparatus 5A as described above, by providing the condition setting step before the bonding step, the pressure in the communication hole 510 of the hot plate 51 and the penetration of the resin substrate 10 in the bonding step. Since the resin substrates 10 and 20 can be heat-bonded in a state where the pressure in the hole 14 is substantially the same, the same effect as in the above embodiment can be obtained more reliably.

  Further, even when the microchip 1 is repeatedly manufactured, that is, when the joining process is repeated, the condition setting process does not need to be repeated, and the driving state of the pressure adjusting means 71 and 72 determined in the initial condition setting process is changed to each joining process. By reproducing the above, the above effect can be obtained repeatedly.

  It should be noted that the present invention should not be construed as being limited to the above-described embodiments and modifications, and of course can be modified or improved as appropriate.

  For example, in the embodiment and the modification described above, the microchip 1 has been described as including the resin substrate 10 in which the non-formation surfaces of the flow path grooves 12 and 13 are smooth, but the resin substrate as illustrated in FIG. 40 may be provided instead of the resin substrate 10. Here, the resin substrate 40 is formed with flow channel grooves 12 and 13 on one surface, and a cylindrical protrusion 41 is provided around each through hole 14 on the other surface. Yes. These protrusions 41 surround the through-holes 14 and protrude in the thickness direction of the resin substrate 40 and are fitted into tubes and nozzles of an analyzer (not shown) to introduce and discharge samples and the like. To do. Such a protrusion 41 may have a cylindrical shape, or may have another shape such as a polygonal shape. However, the concavo-convex member provided on the non-formation surface of the flow path grooves 12 and 13 in the resin substrate 40 is not limited to the protrusion 41, and for example, for controlling the flow of the sample flowing in the fine flow path. It may be a switch or a lens for collecting light from the analyzer.

  In the above modification, the condition setting step is described as being performed before the bonding step. However, in the bonding step, the pressure in the communication hole 510 of the hot plate 51 and the pressure in the through hole 14 of the resin substrate 10 are described. And the driving of the pressure adjusting means 71 and 72 may be controlled so as to be substantially the same.

1 Microchip 5, 5A Manufacturing equipment (Microchip manufacturing equipment)
10 Resin substrate (channel substrate)
14 Through hole 20 Resin substrate (cover substrate)
51, 52 Heat plate 51a, 52a Contact surface 510, 520 Communicating hole 510a, 520a Communicating hole opening X Hole diameter (Communicating hole diameter)
Y hole diameter (hole diameter of through hole)

Claims (4)

In a method of manufacturing a microchip, in which two substrates that are stacked and have a flow path formed inside are sandwiched between two hot plates facing each other and heat bonded,
As the two substrates, a flow channel substrate in which a through hole communicating with the flow channel is formed in the thickness direction, and a cover that covers one opening of the through hole with a bonding surface that is heat-bonded to the flow channel substrate Using the substrate,
And with the two hot plates, when brought into contact with the flow path substrate or the cover substrate, abutting surfaces has an opening to the contact surface between the flow path substrate or the cover substrate Each having a communication hole that communicates with the outside air,
With the two hot plates being sandwiched in the thickness direction by the two hot plates so that the positions of the through holes and the openings of the communication holes correspond to each other, A bonding step of heat-bonding the two substrates ;
Prior to the joining step, when heated by the two hot plates, the pressure in the communication hole and the pressure in the through hole of one of the hot plates in contact with the cover substrate are substantially the same. A condition setting step for setting the bonding conditions in the bonding step;
A method for producing a microchip, comprising: In the manufacturing method of the microchip of Claim 1,
Of the two hot plates, microchips, characterized in that as one of the hot plate into contact with the cover substrate, used as the pore diameter X of the opening of the communication hole satisfies the following formula (1) Manufacturing method.
X <Y [mm] (1)
(However, Y: Hole diameter [mm] of the through hole of the flow path substrate) In the manufacturing method of the microchip of Claim 2,
Of the two heat plates, a microchip using one of the two heat plates that contacts the cover substrate and having a diameter X of the opening of the communication hole satisfying the following expression (2): Manufacturing method.
X <Y-0.4 [mm] (2) In the manufacturing method of the microchip of Claim 2 or 3,
Of the two heat plates, a microchip using one of the two heat plates that contacts the cover substrate and having a diameter X of the opening of the communication hole satisfying the following expression (3): Manufacturing method.
X> Y-0.5 [mm] (3)