JP2021154413A - Membrane device and method for manufacturing the same - Google Patents

Abstract

To provide a membrane device that is low in manufacture cost, and a method for manufacturing the same.SOLUTION: A membrane device has a silicone substrate 1 that has first and second surfaces and has an inclined opening 1a narrower from the first surface toward the second surface, a membrane layer 2 provided so as to block the second surface side of the inclined opening 1a of the silicone substrate 1, and a resin block 5 provided on a side opposite to the silicon substrate 1 of the membrane layer 2 so as to surround the inclined opening 1a.SELECTED DRAWING: Figure 1

Description

The present invention relates to a membrane device and a method for manufacturing the same.

Multifunctional silicon devices have been developed by microelectromechanical systems (MEMS) and the like, and in recent years, the demand for application of multifunctional silicon devices to living organisms has been increasing. For example, Raman spectroscopy, tunneling current, and nanopore technologies are being developed with a view to application to next-generation sequencers. In addition, an electron beam permeable membrane for observation with an electron microscope for biological samples is also being developed. A thin film membrane is used for such a next-generation sequencer and an electron beam transmitting membrane for electron microscope observation for biological samples.

In the next-generation sequencer, pores (nanopores) having the same size as DNA are provided in the thin film membrane. In this case, the thinner the thin film membrane, the better. This is because the distance between the four bases arranged in the DNA strand is about 0.34 nm, and it is necessary to make the thickness of the thin film membrane as thin as possible in order to reduce the number of bases entering the nanopore to one. Further, even in the case of acquiring structural features of biomolecules other than DNA, it is necessary to make the thickness of the thin film membrane as thin as possible in order to increase the spatial resolution.

On the other hand, the thicker the thin film membrane, the more scattered the electron beam that passes through the thin film membrane as the electron beam transmitting film for observing the biological sample with an electron microscope, making it impossible to observe the biological sample. Therefore, the thinner the thin film membrane, the better. For example, the thickness of the thin film membrane is 10 nm or less.

Further, the width of the effective region of the thin film membrane should be as small as possible. By reducing the membrane effective region of the thin film membrane, unavoidable defects in the membrane effective region that occur during film formation of the thin film membrane, such as weak spots and pinholes, can be reduced, and the manufacturing yield can be improved.

3A and 3B are cross-sectional views for explaining a conventional method for manufacturing a membrane device, in which FIG. 3A shows a film-forming state before etching and FIG. 3B shows a film-forming state after etching (see: Patent Document 1).

As shown in FIG. 3A, a silicon nitride (SiN) layer 102 having a thickness of 3 nm is formed on the surface of a single crystal silicon (Si) substrate 101 having a thickness of 725 μm by a chemical vapor deposition (CVD) method or the like. do. The SiN layer 102 acts as a membrane layer. Next, a polycrystalline silicon (Si) layer 103 having a thickness of 150 nm is formed on the SiN layer 102 by a CVD method, and a silicon nitride (SiN) layer 104 having a thickness of 100 nm is further formed on the polycrystalline Si layer 103 by a CVD method. To form a film. On the other hand, a silicon nitride (SiN) layer 105 having a thickness of 200 nm is formed on the back surface of the single crystal Si substrate 101 by a CVD method.

Next, as shown in FIG. 3B, the SiN layer 104 is patterned by a photolithography / etching method to form openings to form a mask layer. The SiN layer 105 is also used in the photolithography / etching method to pattern and form openings to form a mask layer. Next, an organic holding layer is applied to the openings of the SiN layer 104 and the SiN layer 104 to protect the SiN layer 104 and the polycrystalline Si layer 103, the SiN layer 105 is used as an etching mask, and the back surface of the single crystal Si substrate 101 is alkaline. Anisotropic wet etching with a solution is performed to form an inclined opening 101a. After anisotropic wet etching, the organic retaining layer is removed by acetone and oxygen ashing. On the other hand, using the SiN layer 104 as a mask, the polycrystalline Si layer 103 is isotropically wet-etched with an alkaline solution to open it. As a result, a membrane effective region 102a having a size of 1 μm × 1 μm or less and a thickness of 3 nm is formed in the center of the SiN layer 102.

In FIG. 3B, in order to construct a next-generation sequencer, a nanopore (not shown) having a size similar to that of DNA is opened in the membrane effective region 102a of the SiN layer 102, and the membrane effective region 102a is formed. The upper and lower chambers are filled with an aqueous solution, and two electrodes (not shown) are provided so as to be in contact with both chambers. When the DNA to be measured is placed in one of the chambers, a potential difference is applied to both electrodes, and the DNA is electrophoresed to pass through the nanopore, the structure of the DNA is measured by measuring the time change of the ion current flowing between the two electrodes. Features and base sequence can be determined.

As described above, in FIG. 3, the upper and lower sides of the SiN layer 102 as the membrane layer are sandwiched between two layers of Si, that is, the single crystal Si substrate 101 and the polycrystalline Si layer 103, and the single crystal Si substrate 101 is anisotropically wet-etched. The polycrystalline Si layer 103 is opened by an isotropic wet etching method to form a chamber. In this case, the size of the membrane effective region 102a is determined by isotropic wet etching rather than anisotropic wet etching.

WO2016 / 12911A1

However, in the conventional method for manufacturing the membrane device shown in FIG. 3 described above, the polycrystalline Si layer 103 and the SiN layer 104 are formed on the SiN layer 102 forming the membrane effective region 102a, and the layer under the SiN layer 102 is formed. An organic retaining layer is applied when forming openings in the single crystal Si substrate 101 by the anisotropic wet etching method, and the organic retaining layer is removed after the anisotropic wet etching. Therefore, a step of applying and removing an extra organic retaining layer is required, and the manufacturing cost is high. Moreover, the size of the membrane effective region 102a is large because it is determined not by anisotropic wet etching of the single crystal Si substrate 101 but by isotropic wet etching of the polycrystalline Si layer 103. Therefore, the yield is lowered and the manufacturing cost is also high. As described above, according to the above-mentioned conventional method for manufacturing a membrane device, there is a problem that the manufacturing cost is high.

In order to solve the above-mentioned problems, the membrane device according to the present invention includes a silicon substrate having first and second surfaces and having an inclined opening narrowing from the first surface to the second surface. , A membrane layer provided so as to close the second surface side of the inclined opening of the silicon substrate, and a resin block provided on the opposite side of the membrane layer from the silicon substrate and provided so as to surround the inclined opening. Is.

Further, the method for manufacturing a membrane device according to the present invention includes a membrane layer forming step of forming a membrane layer on the entire surface or a part of a second surface of a silicon substrate having first and second surfaces, and a first silicon substrate. After the mask layer forming step of forming the mask layer on the first surface, the resin block joining step of joining the cap-shaped resin block on the second surface side of the silicon substrate, and the resin block joining step, the first first of the silicon substrate. An anisotropic wet etching step of performing anisotropic wet etching on a silicon substrate from the surface side using a mask layer to form an inclined opening that narrows from the first surface to the second surface and leads to the membrane layer. Is provided.

According to the present invention, it is not necessary to provide a silicon layer and a mask layer (organic retaining layer) thereof on the opposite side of the membrane layer from the silicon substrate. Moreover, the effective membrane region is small because it is determined by anisotropic wet etching rather than isotropic wet etching. Therefore, the manufacturing cost can be reduced.

It is sectional drawing for demonstrating 1st Embodiment of the manufacturing method of the membrane device which concerns on this invention. It is sectional drawing for demonstrating the 2nd Embodiment of the manufacturing method of the membrane device which concerns on this invention. It is sectional drawing for demonstrating the manufacturing method of the conventional membrane device, (A) shows the film formation state before etching, (B) shows the film formation state after etching.

FIG. 1 is a cross-sectional view for explaining a first embodiment of the method for manufacturing a membrane device according to the present invention. The membrane device of FIG. 1 is for a next-generation sequencer.

First, referring to the membrane layer forming step of FIG. 1A, a single crystal silicon (Si) substrate 1 having a thickness of 700 μm is prepared. The surface of the single crystal Si substrate 1 is in the <100> or <110> direction, and the etching rate is higher than in the <111> direction. The monocrystalline Si silicon nitride having a thickness of 10nm on the back surface of the substrate 1 (SiN) was deposited by a CVD method or NH ₃ 1000 ° C. or more heat nitridation in an atmosphere, to form the membrane layer 2 having a thickness of 10nm.

Next, referring to the mask forming step of FIG. 1 (B), SiN having a thickness of 100 nm is formed on the surface of the single crystal Si substrate 1 by the CVD method, and the SiN is patterned by the photolithography / etching method to be described later. A SiN layer 3 having an opening 3a as an etching mask for the crystalline Si substrate 1 is formed.

Next, referring to the cap-shaped resin block forming step of FIG. 1 (C), a mold 4 having a convex portion having a height of 300 μm is prepared. The mold 4 is composed of, for example, a single crystal Si substrate 41 and a negative photoresist SU-8 layer 42 having a high aspect ratio and a thickness of 300 μm formed on the single crystal Si substrate 41, but is not limited thereto. The mold 4 is used to form a cap-shaped resin block 5 made of chemical-resistant (in this case, alkali-resistant) polydimethylsiloxane (PDMS). The cap-shaped resin block 5 may be made of another alkali-resistant resin.

With reference to the cap-shaped resin block mold release step (D) of FIG. 1, the cap-shaped resin block 5 is released from the mold 4.

Next, referring to the joining step of FIG. 1 (E), the cap-shaped resin block 5 of FIG. 1 (D) is turned upside down, and the membrane layer on the back surface of the single crystal Si substrate 1 of FIG. 1 (B) ( The SiN layer) 2 is bonded by ultraviolet irradiation or plasma treatment. At this time, since the cap-shaped resin block 5 does not contact the membrane effective region 2a of the membrane layer 2, the membrane effective region 2a of the membrane layer 2 is not damaged. The membrane effective region 2a is a region in which nanopores, which will be described later, are formed.

Next, referring to the anisotropic wet etching step of FIG. 1 (F), the SiN layer 3 is used as an etching mask, and a part of the single crystal Si substrate 1 is an aqueous potassium hydroxide (KOH) solution and tetramethylammonium hydroxide. Etching is performed at a low temperature of 90 ° C. with an alkaline solution such as (TMAH) aqueous solution. As a result, an inclined opening 1a narrowing from the front surface to the back surface is formed in the single crystal Si substrate 1, and a chamber in which the front surface side is open is formed. In this case, at the time of etching, the membrane effective region 2a in the central portion of the membrane layer 2 becomes small, and the etching is accurately controlled so as to be just etching. Therefore, the alkaline solution on the front side of the membrane effective region 2a. There is almost no damage due to. Therefore, the unavoidable defects of the membrane effective region 2a can be reduced. Further, the back side of the membrane effective region 2a is covered with the cap-shaped resin block 5, and the back side of the membrane effective region 2a is not damaged by the alkaline solution.

Finally, referring to the frame-shaped resin block forming step of FIG. 1 (G), the lower portion of the cap-shaped resin block 5 is removed to form the frame-shaped resin block 5'. As a result, an open chamber 5a is formed in the frame-shaped resin block 5'.

In FIG. 1 (G), nanopores (not shown) having the same size as DNA are opened in the membrane effective region 2a of the membrane layer 2, and the upper and lower chambers 1a and 5a of the membrane layer 2 are filled with an aqueous solution. Two electrodes (not shown) are provided so as to be in contact with both chambers 1a and 5a. When the DNA to be measured is placed in one of the chambers 1a and 5a, a potential difference is applied to both electrodes, and the DNA is electrophoresed to pass through the nanopore, the time change of the ion current flowing between the two electrodes is measured. The structural characteristics and base sequence of DNA can be determined.

In the method for manufacturing the membrane device of FIG. 1, since the polycrystalline Si layer and its mask layer are not formed on the back surface of the membrane layer 2, the manufacturing cost can be reduced. Further, during the anisotropic wet etching of the single crystal Si substrate 1 on the surface of the membrane layer 2, there is almost no damage to the membrane effective region 2a of the membrane layer 2. Further, since the membrane effective region 2a is determined by anisotropic wet etching, it can be made small, and therefore the manufacturing yield can be improved.

FIG. 2 is a cross-sectional view for explaining a second embodiment of the method for manufacturing a membrane device according to the present invention. The membrane device of FIG. 2 is for an electron beam transmitting membrane for electron microscope observation for a biological sample.

First, referring to the membrane layer forming step of FIG. 2A, a single crystal silicon (Si) substrate 1 having a thickness of 700 μm is prepared as in the case of FIG. 1A. The surface of the single crystal Si substrate 1 is in the <100> or <110> direction, and the etching rate is higher than in the <111> direction. SiN having a thickness of 10 nm is formed on the back surface of the single crystal Si substrate 1 by a CVD method or _{a thermal nitriding method at 1000 ° C. or higher in an NH 3} atmosphere to form a membrane layer 2 having a thickness of 10 nm.

Next, referring to the mask forming step of FIG. 2 (B), SiN having a thickness of 100 nm is formed on the surface of the single crystal Si substrate 1 by the CVD method as in the case of FIG. 1 (B). A SiN layer 3 having an opening 3a as an etching mask for the single crystal Si substrate 1 described later is formed by patterning by a photolithography / etching method.

Next, referring to the cap-shaped resin block forming step of FIG. 2 (C), a mold 4 having a convex portion having a height of 300 μm is prepared as in the case of FIG. 1 (C). The mold 4 is composed of, for example, a single crystal Si substrate 41 and a negative photoresist SU-8 layer 42 having a high aspect ratio and a thickness of 300 μm formed on the single crystal Si substrate 41, but is not limited thereto. The mold 4 is used to form a cap-shaped resin block 5 made of polydimethylsiloxane (PDMS) having chemical resistance (in this case, alkali resistance). The cap-shaped resin block 5 may be made of another alkali-resistant resin.

With reference to the cap-shaped resin block mold release step of FIG. 2 (D), the cap-shaped resin block 5 is released from the mold 4 as in the case of FIG. 1 (D).

Next, referring to the charge-up electrode forming step of FIG. 2 (E), the cap-shaped resin block 5 is turned upside down and Ti having a thickness of 100 nm is formed by a sputtering method to form the charge-up electrode 6. The charge-up electrode 6 is not limited to Ti, as long as it is made of a highly conductive material, can be formed and patterned, and has biocompatibility. The charge-up electrode 6 is for absorbing an electron beam that has not hit the biological sample, and is set to a constant potential, for example, grounded. The cap-shaped resin block 5 is provided with a plate having an opening facing the recess of the cap-shaped resin block 5 in advance so that Ti is formed only in the recess of the cap-shaped resin block 5.

Next, referring to the joining step of FIG. 2 (E), the cap-shaped resin block 5 of FIG. 2 (E) is the single crystal of FIG. 2 (B) as in the case of FIG. 1 (E). It is bonded to the membrane layer (SiN layer) 2 on the back surface of the Si substrate 1 by ultraviolet irradiation or plasma treatment. At this time, since the cap-shaped resin block 5 does not contact the membrane effective region 2a of the membrane layer 2, the membrane effective region 2a of the membrane layer 2 is not damaged. The membrane effective region 2a is a lower region of the inclined opening 1a described later.

Next, referring to the anisotropic wet etching step of FIG. 2 (G), as in the case of FIG. 1 (F), the SiN layer 3 is used as an etching mask, and a part of the single crystal Si substrate 1 is water. Etching is performed at a low temperature of 90 ° C. with an alkaline solution such as an aqueous solution of potassium oxide (KOH) or an aqueous solution of tetramethylammonium hydroxide (TMAH). As a result, an inclined opening 1a narrowing from the front surface to the back surface is formed in the single crystal Si substrate 1, and a chamber in which the front surface side is open is formed. In this case, at the time of etching, the membrane effective region 2a in the central portion of the membrane layer 2 becomes small, and the etching is accurately controlled so as to be just etching. Therefore, the alkaline solution on the front side of the membrane effective region 2a. There is almost no damage due to. Therefore, the unavoidable defects of the membrane effective region 2a can be reduced. On the other hand, in the case of electron microscope application, the wider the membrane effective region 2a is, the wider the observation range may be. Therefore, the size of the effective membrane area 2a is determined from the relationship between the yield and the observation range. Further, the back side of the membrane effective region 2a is covered with the cap-shaped resin block 5, and the back side of the membrane effective region 2a is not damaged by the alkaline solution.

As shown on the left side of FIG. 2 (G), when the inclined opening 1a is singular, the membrane effective region 2a of the membrane layer 2 is formed by the inclined opening 1a (chamber) and one chamber 5a of the cap-shaped resin block 5. It is sandwiched.

On the other hand, as shown on the right side of FIG. 2 (G), when there are a plurality of inclined openings 1a, the plurality of membrane effective regions 2a of the membrane layer 2 are the plurality of inclined openings 1a (chambers) and the cap-shaped resin block 5. It is sandwiched by one chamber 5a'. That is, one chamber 5a'is commonly provided in the plurality of inclined openings 1a to form a microchannel, whereby a biological sample observed by an electron microscope is taken together with an aqueous solution from the inlet hole 5-1 into the chamber 5a'. Is designed to enter and be discharged from the outlet hole 5-2.

Also in the method for manufacturing the membrane device of FIG. 2, since the polycrystalline Si layer and its mask layer are not formed on the back surface of the membrane layer 2, the manufacturing cost can be reduced. Further, during the anisotropic wet etching of the single crystal Si substrate 1 on the surface of the membrane layer 2, there is almost no damage to the membrane effective region 2a of the membrane layer 2. Further, since the membrane effective region 2a is determined by anisotropic wet etching, it can be made small, and therefore the manufacturing yield can be improved.

Further, in the membrane device of FIG. 2, the electron beam enters the membrane layer 2 from the inclined opening 1a of the silicon substrate 1, and the reflected electrons from the biological sample in the chamber 5a (5a') of the cap-shaped resin block 5 are inclined. Not blocked by the side wall of opening 1a. Therefore, it is suitable for an electron microscope for biological samples.

In the above-described embodiment, the membrane layer 2 is formed on the entire back surface of the single crystal Si substrate 1, but only a part of the back surface of the single crystal Si substrate 1 may be provided. That is, it is sufficient that only the membrane effective region 2a of the membrane layer 2 and its vicinity can be secured. In this case, after forming the membrane layer 2 of FIGS. 1A and 2A, a part of the membrane layer 2 is left by a photolithography / etching method. Further, in this case, in the bonding steps of FIGS. 1 (E) and 2 (F), the bonding between the cap-shaped resin block 5 and the single crystal Si substrate 1 is not performed by ultraviolet irradiation or plasma treatment, but at a low temperature. For example, it is carried out by contact at about 80 ° C.

Further, although the SiN layer 3 having a thickness of about 100 nm is used as the mask layer of the isotropic wet etching method in the above-described embodiment, the SiN layer having a thickness of 10 nm is used in order to reduce the thickness of the SiN layer 3. A Cr layer having a thickness of 150 nm may be provided on the Cr layer, and a mask layer may be formed by the Cr layer and the SiN layer. In this case, SiN and Cr are sequentially deposited by a sputtering method, Cr is patterned by a photolithography etching method, and then SiN is etched by a reactive ion etching method using ^{SF 4 gas with Cr as a mask.} To form an opening.

It should be noted that the present invention can be applied to any modification within the obvious scope of the above-described embodiment.

1: Single crystal Si substrate 1a: Inclined opening 2: Membrane (SiN) layer 2a: Membrane effective region 3: SiN layer 4: Mold 5: Cap-shaped resin block 5': Frame-shaped resin block 5a, 5a': Chamber 6: Charge-up electrode 101: Single crystal Si substrate 102: SiN layer 102a: Membrane effective region 103: Polycrystalline Si layer 104, 105: SiN layer

Claims (15)

A silicon substrate having first and second surfaces and having an inclined opening that narrows from the first surface toward the second surface.
A membrane layer provided so as to close the second surface side of the inclined opening of the silicon substrate, and
A membrane device including a resin block on the opposite side of the membrane layer from the silicon substrate and provided so as to surround the inclined opening. The membrane device according to claim 1, wherein the membrane layer is provided on the entire surface or a part of the second surface of the silicon substrate. The membrane device according to claim 1, wherein the resin block has a frame shape. The membrane device according to claim 1, wherein the resin block has a cap shape. The membrane device according to claim 4, further comprising a charge-up electrode provided in a recess of the cap-shaped resin block. The membrane device according to claim 1, wherein the resin block is made of an alkali-resistant resin. The membrane device according to claim 6, wherein the alkali-resistant resin is polydimethylsiloxane. A membrane layer forming step of forming a membrane layer on the entire surface or a part of the second surface of a silicon substrate having the first and second surfaces, and
A mask layer forming step of forming a mask layer on the first surface of the silicon substrate, and
A resin block joining step of joining a cap-shaped resin block to the second surface side of the silicon substrate,
After the resin block joining step, anisotropic wet etching is performed on the silicon substrate from the first surface side of the silicon substrate using the mask layer to from the first surface to the second surface. A method for manufacturing a membrane device including an anisotropic wet etching step of forming an inclined opening leading to the membrane layer. The method for manufacturing a membrane device according to claim 8, further comprising a charge-up electrode forming step of forming a charge-up electrode in the recess of the cap-shaped resin block. The method for manufacturing a membrane device according to claim 8, further comprising a resin block cutting step of removing the cap portion of the cap-shaped resin block to form a frame-shaped resin block. The method for manufacturing a membrane device according to claim 8, wherein the membrane layer is provided on the entire surface or a part of the second surface of the silicon substrate. The method for manufacturing a membrane device according to claim 8, wherein the cap-shaped resin block is made of an alkali-resistant resin. The method for producing a membrane device according to claim 12, wherein the alkali-resistant resin is polydimethylsiloxane. A silicon substrate having a first and second surfaces and having a plurality of inclined openings narrowing from the first surface toward the second surface.
A membrane layer provided so as to close the second surface side of the plurality of inclined openings of the silicon substrate, and
It is provided with a cap-shaped resin block provided on the opposite side of the membrane layer from the silicon substrate and surrounding the plurality of inclined openings, and a charge-up electrode provided in a recess of the cap-shaped resin block.
The membrane layer is a membrane device sandwiched between the plurality of inclined openings and the recesses. A membrane layer forming step of forming a membrane layer on the entire surface or a part of the second surface of a silicon substrate having the first and second surfaces, and
A mask layer forming step of forming a mask layer on the first surface of the silicon substrate, and
A charge-up electrode forming step of forming a charge-up electrode in the recess of the cap-shaped resin block,
A resin block joining step of joining the cap-shaped resin block in which the charge-up electrode is formed on the second surface side of the silicon substrate.
After the resin block joining step, anisotropic wet etching is performed on the silicon substrate from the first surface side of the silicon substrate using the mask layer to from the first surface to the second surface. It is provided with an anisotropic wet etching step of forming a plurality of inclined openings leading to the membrane layer.
A method for manufacturing a membrane device in which the membrane layer is sandwiched between the plurality of inclined openings and the recesses.

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