This application is based upon and claims the benefit of priority from Japanese Patent Application No. 2018-047146, filed Mar. 14, 2018, the entire contents of which are incorporated herein by reference.
Embodiments described herein relate generally to a method of manufacturing a microchannel which is applied to a biosensor used, for example, in chemical or biochemical analysis and in which a specimen liquid or the like can move.
Recently, various types of biosensors for inspecting cells, specimen liquids and the like in a microchannel have been developed. The microchannel includes an introduction hole for introducing a cell, a specimen liquid and the like and a discharge hole for discharging the cell, the specimen liquid and the like. When the microchannel is formed of a silicone resin such as poly-dimethyl-siloxane (PDMS) or the like, in the case in which the openings as a fine introduction hole and discharge hole are formed individually or collectively, there is a problem in that burrs occur in the openings.
In general, according to one embodiment, a method of manufacturing a microchannel includes: coating a silicone resin onto a mold corresponding to a microchannel and a first opening communicating with the microchannel and curing the silicone resin by light using a mask having a light shielding portion corresponding to the first opening, removing an uncured silicone resin, and releasing the cured silicone resin from the mold.
Hereinafter, the embodiments will be described with reference to the accompanying drawings. In the drawings, the same portions are denoted by the sane reference numerals. It should be noted that the drawings are schematic and thicknesses and dimensions are different from the actual ones. Further, the drawings include mutually different portions in terms of dimensional relationships and ratios.
The biosensor 10 includes a microchannel 11a formed of a silicone resin 11 such as PDMS or the like to be described below and a sensor 13 formed in the semiconductor substrate 12.
The silicone resin 11 has openings 11b and 11c for introducing cells or a fluid (hereinafter, also referred to as the specimen liquid) such as a specimen liquid or the like into the microchannel 11a and discharging the cells or fluid from the microchannel 11a.
The sensor 13 detects physical or chemical information of the specimen liquid. The sensor 13 can be changed depending on an object to be detected.
When the sensor 13 is an optical sensor, for example, it is possible to detect an intensity of fluorescence emitted from fluorescently stained cells contained in the specimen liquid flowing in the microchannel 11a using the photodiode as the sensor 13. Further, it is also possible to acquire an image of cells contained in the specimen liquid by using an image sensor as the sensor 13. In addition, it is possible to obtain pH and an ion concentration of liquids such as the specimen liquid or the like, for example, by using an ion sensitive field effect transistor (ISFET) as the sensor 13.
Further, in the following description, the microchannel 11a may be used as a general term including the openings 11b and 11c.
A method of manufacturing the biosensor 10 according to the first embodiment is described with reference to
As shown in
Further, heights of the second and third protrusions 2b and 2c may be the same as that of the first protrusion 2a. That is, the second and third protrusions 2b and 2c may be omitted.
As the substrate 1, for example, a silicon substrate, a glass substrate, a metal plate or the like used in manufacturing process of a semiconductor can be used.
The mold 2 can be formed as follows. First, for example, a liquid-state negative type thick photoresist can be coated on the substrate 1 by spin-coating. Next, the photoresist is exposed using a mask (not shown) corresponding to the shapes of the openings 11b and 11c of the microchannel 11a. Then, the mold 2 is formed by developing the photoresist.
Alternatively, a sneer, shaped negative thick photoresist is stacked on the substrate 1, and the photoresist is exposed using the mask (not shown). Then, the mold 2 can be formed by developing the photoresist.
The height (film thickness) of the microchannel 11a is different from the height (film thickness) of the openings 11b and 11c. For this reason, a lithography process may be performed several times depending on shapes of the microchannel 11a and the openings 11b and 11c. That is, the height of the first protrusion 2a or the second and third protrusions 2b and 2c of the mold 2 are adjusted to be equal to that of the microchannel 11a or the openings 11b and 11c by performing the lithography process several times.
Subsequently, as shown in
The silicone resin 3 is, for example, a photocurable PDMS. More specifically, for example, the silicone resin 3 is a UV-activated heat-curable PDMS. However, a material of the silicone resin 3 is not limited as long as it can be exposed and cured by light and an uncured silicone resin can be removed by development. Further, for example, a material that does not scatter light, emits fluorescence, and is not toxic to cells in the specimen liquid can be used. Therefore, the material of the silicone resin 3 is not limited.
Further, after coating the silicone resin 3, it may also be possible to remove bubbles contained in the silicone resin 3 under a reduced pressure or to allow the silicone resin 3 to be surely filled between the molds 2.
As another method, the silicone resin 3 may be surely filled between the molds 2 by coating the silicone resin 3 under the reduced pressure and allowing the coated silicone resin 3 to stand in the air.
Further, in the case in which the silicone resin 3 is spin-coated, the thickness of the silicone resin 3 is thicker in an edge region as compared to a region in the vicinity of a central portion of the substrate 1. For this reason, the silicone resin 3 may also be allowed to have a uniform thickness over the entire surface of the substrate 1 by allowing the silicone resin 3 to stand after being coated.
In addition, after curing the silicone resin 3, in order to improve releasability from the mold 2, surfaces of the substrate 1 and the mold 2 may be coated with a fluorine-based polymer by plasma treatment using trifluoromethane or the like, or the surfaces of the substrate 1 and the mold 2 may also be coated with a metal such as Au or the like by deposition treatment or the like.
Then, as illustrated in
In
Further, the light shielding portion 4a is formed to correspond to the openings 11b and 11c of the microchannel 11a. However, the light shielding portion 4a may be formed to correspond to a region where the cured silicone resin 11 is not required, for example, a dicing line or the like.
Next, as shown in
Next, as shown in
Finally, as shown in
Further, although the sensor 13 is disposed in the microchannel 11a, there is no need to dispose all the sensors 13 in the microchannel 11a, but some of the sensors 13 may be disposed in the microchannel 11a.
In addition, the cured silicone resin 11 and the semiconductor substrate 12 may be bonded to each other as follows. First, surfaces of the silicone resin 11 and the semiconductor substrate 12 are activated in oxygen plasma. Next, the silicone resin 11 is installed on a main surface of the semiconductor substrate 12, and a load and heat are applied thereto. Surface activation treatment conditions and load and heat application conditions are appropriately selected depending on the used silicone resin 3.
Further, although the surface activation treatment by the oxygen plasma is performed in the present embodiment, another bonding method except for a bonding method using surface activation treatment by the oxygen plasma may also be used as long as bonding strength enough to allowing the cured silicone resin 11 and the semiconductor substrate 12 to function as the microchannel is obtained.
Due to a structure shown in
According to the first embodiment, the silicone resin 3 is coated onto the mold 2 corresponding to the microchannel 11a and openings 11b and 11c provided on the substrate 1, the light is irradiated onto the silicone resin 3 using the mask 4 including the light shielding portion 4a corresponding to the openings 11b and 11c to cure the silicone resin 3, and the uncured silicone resin 3 and the mold 2 are sequentially removed, thereby forming the silicone resin 11 including the microchannel 11a and the openings 11b and 11c. For this reason, contrary to a case of forming the openings 11b and 11c using a drill or the like, smooth openings 11b and 11c can be formed without burrs at peripheral edges of the openings 11b and 11c.
Further, the microchannel 11a and the plurality of openings 11b and 11c communicating with the microchannel 11a can be formed at the same time. For this reason, a processing time can be shortened, and a process cost can be decreased.
That is, in the first embodiment, the cured silicone resin 11 is bonded to the semiconductor substrate 12 after being removed from the mold 2. On the contrary, in the second embodiment, before a cured silicone resin 11 is removed from the mold 2, a support substrate 8 is bonded to the silicone resin 11. Thereafter, the silicone resin 11 is released from the mold 2.
In the second embodiment, since
As shown in
It is preferable that a size of the openings 8a and 8b of the support substrate 8 is equal to or larger than that of the openings 11b and 11c of the silicone resin 11, but is not limited as long as the specimen liquid or the like can be introduced into and discharged from a microchannel 11a.
As a material of the support substrate 8, a material capable of being bonded to the cured silicone resin 11 is preferable. For example, glass, silicon, plastics or the like can be used.
The support substrate 8 and the cured silicone resin 11 can be bonded to each other by the same method as the bonding method of the cured silicone resin 11 and the semiconductor substrate 12 described above. That is, for example, after surfaces of the silicone resin 11 and the support substrate 8 are activated in oxygen plasma, the support substrate 8 is installed on the silicone resin 11, and a load and heat are applied thereto, such that the support substrate 8 can be bonded onto the silicone resin 11. Alternatively, it is also possible to bond the support substrate 8 and the silicone resin 11 to each other using an adhesive. A bonding method of the support substrate 8 and the cured silicone resin 11 can be appropriately selected.
Further, the openings 8a and 8b of the support substrate 8 can be formed by a machining process using a sandblast machine or drill. In addition, when the material of the support substrate 8 is glass or silicon, the openings 8a and 8b can also be formed by etching. Further, when the material of the support substrate 8 is plastic, the openings 8a and 8b can also be formed by injection molding.
Next, as shown in
Finally, as shown in
According to the second embodiment, the same advantage as that of the first embodiment can be obtained. However, in the second embodiment, before the cured silicone resin 11 is released from the mold 2, the support substrate 8 is bonded to the silicone resin 11. For this reason, even in the case in which a thickness of the silicone resin 11 is thin, the cured silicone resin 21 can be surely released from the mold 2 and the substrate 1 at once.
Further, since the support substrate 8 is bonded onto the cured silicone resin 11, the support substrate 8 can collectively hold the silicone resin 11 including a plurality of microchannels 11a and openings 11b and 11c. For this reason, a handling property of the silicone resin 11 is good, and the semiconductor substrate 12 including the sensor 13 can be easily aligned with the silicone resin 11.
Specifically, since the support substrate 8 is bonded to the cured silicone resin 11, at the time of bonding the semiconductor substrate 12 and the cured silicone resin 11 to each other, a uniform load can be applied to the silicone resin 11. Therefore, a bonding yield of the semiconductor substrate 12 and the silicone resin 11 can be improved.
In addition, the support substrate 8 can improve mechanical strength of the cured silicone resin 11. For this reason, the support substrate 8 can serve as a protective layer of the silicone resin 11.
In the first and second embodiments, the microchannel is formed using a single mold. On the other hand, in the third embodiment, a microchannel and a plurality of openings are formed using two molds.
More specifically, as shown in
As shown in
A size (diameter) of the light shielding layer 31 needs not necessarily to be larger than a size (diameter) of the third protrusions 2b-2 and 2c-2, but may be equal to or larger than that of the third protrusions 2b-2 and 2c-2.
As a material of the second substrate 1-2, a material capable of transmitting ultraviolet light irradiated in order to sure a silicone resin 3 to be described later is applied. More specifically, as the second substrate 1-2, a transparent material such as a glass plate is used.
The light shielding layer 31 may be disposed so as to partially or entirely cover a region in which the first and second molds 2-1 and 2-2 come in contact with each other as described later. Further, as shown in
As a material of the light shielding layer 31, a material capable of shielding UV light irradiated in order to cure the silicone resin 3 is preferable. For example, a metal material such as titanium, aluminum, platinum, gold or the like can be used. The light shielding layer 31 is formed in a desired pattern by etching after sputtering or depositing the metal on the second substrate 1-2 to form a thin film.
The third protrusions 2b-2 and 2c-2 as the second mold 2-2 are formed on the light shielding layer 31. A material and a method of manufacturing the second mold 2-2 are the same as those in the first embodiment.
A height H1 (film thickness) of the first mold 2-1 is slightly lower than a height H2 of the second mold 2-2. Therefore, releasability of the first mold 2-1 can be improved. A relationship between the height H1 of the first mold 2-1 and the height H2 of the second mold 2-2 is not limited thereto, but when the height H2 of the second mold 2-2 is lower than the height H1 of the first mold 2-1, releasability of the second mold 2-2 can be improved. Therefore, the height H1 of the first mold 2-1 and the height H2 of the second mold 2-2 may be set depending on, for example, a release sequence of the first and second molds 2-1 and 2-2.
In addition, the first mold 2-1 includes the second protrusions 2b-1 and 2c-1 corresponding to opening portions 11b and 11c but needs not necessarily to include the second protrusions 2b-1 and 2c-1. When the first mold 2-1 does not include the second protrusions 2b-1 and 2c-1, the height of the third protrusions 2b-2 and 2c-2 of the second mold 2-2 may be changed as needed.
Next, as shown in
Subsequently, as shown in
Then, as shown in
Then, as shown in
Here, when adhesion between the cured silicone resin 11 and the first mold 2-1 is higher than adhesion between the cured silicone resin 11 and the second mold 2-2, there is a possibility that the cured silicone resin 11 will not be removed even in the case of trying to remove the cured silicone resin 11 from the first mold 2-1. However, as described above, in the present embodiment, since the height of the first mold 2-1 is lower than the height of the second mold 2-2, the adhesion between the cured silicone resin 11 and the first mold 2-1 is lower than adhesion between the cured silicone resin 11 and the second mold 2-2. Therefore, the cured silicone resin 11 can be surely released from the first mold 2-1.
Next, as shown in
Next, as shown in
Then, as shown in
Further, the light shielding layer 31 is disposed between the second substrate 1-2 and the second mold 2-2, but is not limited thereto. The light shielding layer 31 can be formed on a surface and a side surface of the second mold 2-2, and if necessary, the light shielding layer 31 may also be formed on the first substrate 1-1 and a surface and a side surface of the first mold 2-1. In this way, it is possible to further suppress the silicone resin 3 remaining in regions close to the first and second molds 2-1 and 2-2 from being undesirably cured by scattering of the UV light irradiated onto the silicone resin 3.
According to the third embodiment, the liquid-state silicone resin 3 is applied onto the first substrate 1-1 including the first mold 2-1 corresponding to structures of the microchannel 11a and portions of the openings 11b and 11c and the second substrate 1-2 including the second mold 2-2 corresponding to structures of the remaining portions of the openings 11b and 11c, the first and second molds 2-1 and 2-2 are combined with each other, the silicone resin 3 is cured by the ultraviolet light, and then the first and second molds 2-1 and 2-2 are removed from the cured silicone resin 11. For this reason, the microchannel 11a and the openings 11b and 11c can be simultaneously formed.
Further, the silicone resin 3 remaining in a region in which the first and second molds 2-1 and 2-2 face each other is not exposed to the UV light but remains in an uncured state due to the light shielding layer 31, and the uncured silicone resin 3 is removed by a developer capable of dissolving the silicone resin 3. Therefore, similarly to the first embodiment, the openings 11b and 11c of which edges are smooth without burrs can be formed.
In addition, the height of the first mold 2-1 and the height of the second mold 2-2 are different from each other. For this reason, releasability between the first mold 2-1 and the second mold 2-2 can be appropriately set, and it is possible to form the first and second molds 2-1 and 2-2 in various shapes.
According to the fourth embodiment, since processes in
As shown in
That is, as shown in
Then, as shown in
Next, as shown in
Thereafter, as shown in
According to the fourth embodiment, the same advantage as that of the third embodiment can be obtained.
In addition, according to the fourth embodiment, the support substrate 8 is bonded to the cured silicone resin 11 in a state in which the first mold 2-1 is present in a region in which the microchannel 11a is formed. Therefore, as in the third embodiment, it is possible to apply a large load at the time of bonding as compared to the case in which the support substrate 8 is bonded to the silicone resin 11 cured in a hollow state in a region in which the microchannel 11a is formed. Therefore, occurrence of a bonding defect between the silicone resin 11 and the support substrate 8 can be suppressed.
Further, since the support, substrate 8 is bended to the cured silicone resin 11 in a state in which the first mold 2-1 is present in the region in which the microchannel 11a is formed, it is possible to prevent deformation of the microchannel 11a.
While certain embodiments have been described, these embodiments have been presented by way of example only, and are not intended to limit the scope of the inventions. Indeed, the novel embodiments described herein may be embodied in a variety of other forms; furthermore, various omissions, substitutions and changes in the form of the embodiments described herein may be made without departing from the spirit of the inventions. The accompanying claims and their equivalents are intended to cover such forms or modifications as would fall within the scope and spirit of the inventions.
Number | Date | Country | Kind |
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2018-047146 | Mar 2018 | JP | national |