JP5964793B2 - Apatite thin film formation method - Google Patents

Description

  The present invention relates to an apatite thin film forming method for forming an apatite thin film made of hydroxyapatite.

Hydroxyapatite (HAp) is an inorganic compound crystal represented by the chemical formula Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ and is the main component constituting bones and teeth. This HAp can be artificially synthesized, is an inorganic material having biocompatibility, and is applied to medical engineering and biotechnology. In particular, it has been pointed out that by controlling the properties of HAp films formed on various substrates, it is possible to pioneer new application destinations characterized by defining the interaction with biological substances.

  Industrially manufactured HAp forms include slag, powder, paste, thin film, solid pellet, etc., which have been supplied to the market. For example, HAp powder is used as a packing material for columns used in chromatography. In addition, HAp solid pellets are used as culture substrates with high biocompatibility. “Scaffold” has been developed as a scaffold material for cell culture in the field of medical biology.

  Further, for example, in the treatment of bone, a treatment for accelerating bone regeneration by embedding a HAp porous material or paste in a defect portion is performed. When the deposited HAp thin film is used for the intermediate layer instead of these powders and pastes, it is expected that the strength of the joint with the bone is increased and a rapid recovery treatment becomes possible. Moreover, the HAp film | membrane is coated on the surface of the metal structure material embedded in the living body, and bioaffinity is provided mainly by the plasma spray method until now.

H. Nishikawa, R. Hatanaka, M. Kusunoki, T. Hayami, and S. Hontsu, "Preparation of Freestanding Hydroxyapatite Membranes with Excellent Biocompatibility and Flexibility", Applied Physics Express, vol.1, 088001, 2008. M. Kusunoki, Y. Kawakami, T. Matsuda, H. Nishikawa, T. Hayami, and S. Hontsu, "Fabrication of a Large Hydroxyapatite Sheet", Applied Physics Express, vol.3, 107003, 2010.

  For example, an HAp thin film obtained by processing HAp into a sheet shape may be applied to a bone defect to promote early regeneration of bone. Alternatively, application of the HAp thin film to a bone or tooth melted by periodontal disease can be expected to be applied to a treatment that promotes bone or tooth regeneration. There is a so-called nanosheet having a thickness of several nanometers, but this is not easy to handle by tweezers. For practical handling, it is important to have a sheet that is at least a few microns thick.

  Therefore, various attempts have been made to form HAp ultrathin sheets (see Non-Patent Document 1 and Non-Patent Document 2). For example, in Non-Patent Document 1, an HAp thin film is formed on a sodium chloride (NaCl) crystal substrate, and the NaCl crystal substrate is dissolved in water and removed to form a single HAp thin film. However, crystal substrates such as NaCl are commercially available but are very expensive. Furthermore, it can be said that the method of obtaining the HAp thin film by dissolving the NaCl crystal substrate in water after forming the HAp thin film is not suitable for the purpose of obtaining a large area HAp thin film.

  In Non-Patent Document 2, a single HAp thin film is formed by forming a HAp thin film on a resist film, and then dissolving and removing the resist with an organic solvent. However, when a resist is used, there is a possibility that carbon in the resist may diffuse into the HAp thin film, and that the influence of the organic solvent that dissolves the resist reaches the HAp thin film.

  From such a background, a method in which an inorganic thin film is formed on a substrate as a sacrificial layer, then a HAp film is formed on the inorganic thin film, and then the inorganic thin film is removed is considered most desirable. In removing the inorganic thin film, it is desirable to use water from various viewpoints. Therefore, it is important that the material used for the sacrificial layer is water-soluble.

  Speaking of water-soluble materials, compounds such as LiF, NaCl, and KCl classified as so-called salts have high solubility. Among these salts, LiF is used for optical window materials but is expensive. A further problem is that it is generally difficult to form a salt layer as described above on a substrate.

  As described above, conventionally, there has been a problem that it is not easy to form an apatite thin film made of hydroxyapatite in a stable state while suppressing an increase in cost.

  The present invention has been made to solve the above-described problems, and enables an apatite thin film made of hydroxyapatite to be easily formed in a stable state while suppressing an increase in cost. With the goal.

  An apatite thin film forming method according to the present invention includes a sacrificial layer forming step of forming a sacrificial layer made of lithium oxide on a substrate, an apatite thin film forming step of forming an apatite thin film made of hydroxyapatite on the sacrificial layer, A separation step of removing the sacrificial layer between the substrate and the apatite thin film by dissolving it in water and separating the apatite thin film from the substrate.

In addition, a crystallization step of crystallizing the apatite thin film and weakening the adhesion between the sacrificial layer and the substrate by heating under a temperature condition of 700 to 800 ° C. between the apatite thin film forming step and the separation step. Prepare .

The apatite thin film forming method according to the present invention includes a sacrificial layer forming step of forming a sacrificial layer made of lithium oxide on a substrate, and an apatite thin film forming step of forming an apatite thin film made of hydroxyapatite on the sacrificial layer. And a separation step in which the sacrificial layer between the substrate and the apatite thin film is removed by dissolving in water, and the apatite thin film is separated from the substrate. In the thin film formation step, an opening region where the lower sacrificial layer is exposed is formed. An apatite thin film is formed.

In addition, a crystallization process is provided between the apatite thin film forming process and the separation process, in which the apatite thin film is crystallized by heating at a temperature of 700 to 800 ° C. and weakens the adhesion between the sacrificial layer and the substrate. You may do it.

  As described above, according to the present invention, it is possible to obtain an excellent effect that an apatite thin film made of hydroxyapatite can be easily formed in a stable state while suppressing an increase in cost.

FIG. 1A is a configuration diagram showing a state in each intermediate step for explaining an apatite thin film forming method according to an embodiment of the present invention. FIG. 1B is a configuration diagram showing a state in each intermediate step for explaining the apatite thin film forming method in the embodiment of the present invention. FIG. 1C is a configuration diagram showing a state in each intermediate step for explaining the apatite thin film forming method in the embodiment of the present invention. FIG. 1D is a configuration diagram showing a state in each intermediate step for explaining the apatite thin film forming method in the embodiment of the present invention. FIG. 1E is a configuration diagram showing a state in each intermediate step for explaining the apatite thin film forming method in the embodiment of the present invention. FIG. 1F is a configuration diagram showing a state in each intermediate step for explaining the apatite thin film forming method in the embodiment of the present invention. FIG. 2 is a characteristic diagram showing the results of measuring the Raman scattering spectrum of the apatite thin film 103 formed on the sacrificial layer 102 in a state where no heat treatment is performed. FIG. 3 is a characteristic diagram showing X-ray diffraction patterns of the apatite thin film 103 and the sacrificial layer 102 obtained by X-ray diffraction measurement.

  Hereinafter, embodiments of the present invention will be described with reference to FIGS. 1A to 1F. FIG. 1A to FIG. 1F are configuration diagrams showing states in respective intermediate steps for explaining the apatite thin film forming method in the embodiment of the present invention. 1A, 1B, and 1D to 1F schematically show cross sections, and FIG. 1C shows a plane.

First, as shown in FIG. 1A, a sacrificial layer 102 made of lithium oxide (Li ₂ O) is formed on a substrate 101 (a sacrificial layer 102 forming step). The substrate 101 is, for example, a silicon wafer having a diameter of 4 inches with the surface orientation of the main surface being (100). Further, the sacrificial layer 102 is formed by depositing lithium oxide by RF magnetron sputtering. Formation of the sacrificial layer 102 The next substrate temperature condition is room temperature (about 25 ° C.). Under these conditions, as shown below, the sacrificial layer 102 is composed of amorphous lithium oxide.

The sacrificial layer 102 has a layer thickness of 300 nm. In the deposition of lithium oxide by RF magnetron sputtering, 3 sccm of oxygen gas was introduced to obtain a lithium oxide film having a thickness of 300 nm. It was confirmed by X-ray diffraction that the lithium oxide film was amorphous. Note that sccm is a unit of flow rate, and indicates that a fluid at 0 ° C. and 1013 hPa flows 1 cm ³ per minute.

Next, as shown in FIGS. 1B and 1C, an apatite thin film 103 made of hydroxyapatite is formed on the sacrificial layer 102 (apatite thin film 103 forming step). For example, by depositing hydroxyapatite on the sacrificial layer 102 by electron cyclotron resonance (ECR) sputtering using a target made of a sintered body of hydroxyapatite and a sputtering gas obtained by adding H ₂ O gas to xenon gas. Good. A gas of H ₂ O vapor is introduced at 2 × 10 ⁻² Pa. The substrate is not heated.

  In this example, a plurality of (4 × 4 = 16) apatite thin films 103 having a square shape in a plan view with a side of 14 mm were formed on a silicon wafer having a diameter of 4 inches. The pitch at which each apatite thin film 103 is arranged is 18 mm. Therefore, the interval between the adjacent apatite thin films 103 (the width of the opening region) is 4 mm. For example, by depositing hydroxyapatite using a well-known stencil mask, as described above, a plurality of apatite thin films 103 can be formed simultaneously with an opening region. The shape and size of the apatite thin film 103 may be a desired shape and size.

  Next, as shown in FIGS. 1D, 1E, and 1F, the sacrificial layer 102 between the substrate 101 and the apatite thin film 103 is removed by dissolving in water, and the apatite thin film 103 is separated from the substrate 101 (separation). Process). For example, the substrate 101 on which the apatite thin film 103 is formed as described above may be immersed in pure water. For example, pure water acts on the sacrificial layer 102 exposed in the gap (opening region) between adjacent apatite thin films 103, and the sacrificial layer 102 is dissolved (FIG. 1D). The dissolution reaches the substrate 101 (FIG. 1E) and proceeds in the planar direction of the substrate 101, with the result that the sacrificial layer 102 is removed (FIG. 1F). As a result, the apatite thin film 103 having a desired shape and size can be easily formed. The obtained apatite thin film 103 is not in a state of being fixed on the substrate, but is present alone.

  Next, the result of the characteristic investigation of the formed apatite thin film 103 will be described. First, as described above, a sample wafer is produced in which a plurality of apatite thin films 103 having a square shape of 14 mm on a side are formed on the sacrificial layer 102. A region where each apatite thin film 103 is formed is cut out from the prepared sample wafer to obtain an 18 mm square sample chip. In the sample chip, an apatite thin film 103 is formed on a chip substrate made of silicon via a sacrificial layer 102 made of lithium oxide.

The Raman scattering spectrum of the uppermost apatite thin film 103 was measured without heating the sample chip. The result of this measurement is shown in FIG. As shown in FIG. 2, the asymmetric stretching mode ν ₃ and the symmetric stretching mode ν _{1 of the} PO ₄ ^3- unit included in the apatite thin film 103 are clearly observed. These facts indicate that the apatite thin film 103 is composed of hydroxyapatite.

  Next, heat treatment is performed on the above-described sample chip. The heat treatment was performed in oxygen gas at atmospheric pressure. The conditions for the heat treatment are 550 ° C. for 10 hours, 600 ° C. for 3 hours, 700 ° C. for 3 hours, and 800 ° C. for 2 hours. The crystal state of the apatite thin film 103 and the sacrificial layer 102 was measured by X-ray diffraction for each of the heat-treated sample chips. The measurement results are shown in FIG. FIG. 3 shows X-ray diffraction patterns of the apatite thin film 103 and the sacrificial layer 102 obtained by X-ray diffraction measurement.

  As shown in FIG. 3, a peak attributed to a hydroxyapatite crystal is observed. Since lithium oxide is a light element oxide, the X-ray diffraction peak is very weak even if it is crystallized. For this reason, in FIG. 3, the peak attributed to lithium oxide is not observed.

  In the measurement results of the sample chip crystallized at 550 ° C. with sufficient time, preferential orientation in the hydroxyapatite (310) direction is observed. On the other hand, it was found that the film was composed of randomly oriented crystallites at a heating temperature of 600 ° C. or higher.

  Next, the crystallinity of the sacrificial layer 102 and the solubility of the sacrificial layer 102 will be described. As described with reference to FIG. 1B, when the apatite thin film 103 is formed on the sacrificial layer 102 and then immersed in water without performing heat treatment, the apatite is immersed in water for about 1 hour. The thin film 103 separated spontaneously. When heat treatment is not performed as described above, both lithium oxide and hydroxyapatite are in an amorphous state. The dissolution rate of amorphous hydroxyapatite in water is larger than the dissolution rate of crystalline hydroxyapatite. However, the dissolution rate of lithium oxide in water is much greater than these. As a result, as described above, the apatite thin film 103 can be separated from the substrate 101 in a short time.

  Next, the case where the apatite thin film 103 is formed on the sacrificial layer 102 and then heat-treated at 550 ° C. for 10 hours will be described. In this case, the apatite thin film 103 does not separate from the substrate 101 no matter how many days have passed after being immersed in water. By heating under the above-described conditions, the apatite thin film 103 is crystallized. The sacrificial layer 102 is also crystallized. In such a state, the apatite thin film 103 could not be peeled off from the substrate 101 as long as it was immersed in water for several days unless it was damaged by tweezers. Further, when crystallized by annealing at 600 ° C. for 3 hours, the apatite thin film 103 was not broken unless it was broken.

  Next, a case where the apatite thin film 103 is formed on the sacrificial layer 102 and then heat-treated at 700 ° C. or 800 ° C. for 2 hours will be described. When the hydroxyapatite film crystallized by annealing at 700 ° C. or 800 ° C. for 2 hours was immersed in water for one day, part of the hydroxyapatite film was spontaneously peeled off. It is considered that the lithium oxide film partially lifts from the Si substrate, and water penetrates there, so that the lithium oxide film easily peels off.

As described above, the present invention is characterized in that the sacrificial layer is particularly composed of lithium oxide. Not only lithium oxide but also an oxide of an alkali metal such as Na ₂ O or K ₂ O can be used as a water-soluble sacrificial layer. Among such alkali metal oxides, lithium oxide has the highest dissolution rate in water.

On the other hand, substance groups classified as so-called calcium phosphate include Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ (hydroxyapatite), Ca ₈ H ₂ (PO ₄ ) ₆ · 5H ₂ O (OCP), CaHPO ₄ · 2H. ₂ O (DCPD), Ca ₃ (PO ₄ ) ₂ (TCP), and the like. Among them, hydroxyapatite has the highest chemical stability, and other than this, it is positioned as a precursor of hydroxyapatite finally reached by equilibrium in an aqueous solution. Hydroxyapatite has the lowest solubility in water, but the solubility of an actual hydroxyapatite film may change dramatically due to a slight compositional shift or a decrease in crystallinity. For this reason, the time to immerse in water has never been short.

As described above, in consideration of shortening the time during which the apatite thin film made of hydroxyapatite is in contact with water as much as possible, the option of constituting the sacrificial layer from Na ₂ O or K ₂ O having a low dissolution rate is impossible. As an oxide suitable for film formation and having high solubility in water, lithium oxide can be cited as a promising candidate, but the fact that lithium oxide is actually a material suitable for the above-mentioned purpose has been determined by the inventors. It became clear for the first time by the earnest examination.

  When the apatite thin film made of hydroxyapatite is separated from the substrate, as described above, the apatite thin film is preferably patterned in a state having a gap (opening region) on the sacrificial layer. After the sacrificial layer exposed in the gap is dissolved in water and removed to reach the substrate, the sacrificial layer below the apatite thin film is also susceptible to water action (erosion). Practically, it is desirable to form an apatite thin film in a pattern shape having dimensions suitable for use in advance.

  In order to easily separate the apatite thin film from the substrate, the state of the sacrificial layer made of lithium oxide is important. When lithium oxide is sputtered at room temperature, amorphous lithium oxide is deposited. There are many voids in the sacrificial layer made of lithium oxide in this state, and water molecules easily penetrate into the sacrificial layer and dissolve in water very quickly.

  In contrast, when heat treatment is performed, atomic interdiffusion partially occurs at the interface between the apatite thin film and the sacrificial layer, and the apatite thin film and the sacrificial layer are easily integrated. At the same time, as the sacrificial layer (lithium oxide) is densified and crystallized, dissolution in water becomes extremely slow.

  However, when heated under higher temperature conditions, for example, when a silicon substrate is used, there is no adhesion layer between the sacrificial layer and the silicon substrate, so that the sacrificial layer floats from the silicon substrate and water easily enters. As a result, it is thought that it becomes easy to peel. Therefore, when the heat treatment is performed, the apatite film can be easily separated from the substrate under the conditions of 700 to 800 ° C. as described above.

  According to a conventional report, in order to obtain a thin film made of crystalline hydroxyapatite, it was necessary to obtain an amorphous hydroxyapatite thin film and then heat-treat it in a heat treatment furnace. On the other hand, by using lithium oxide for the sacrificial layer, it can withstand annealing at 800 ° C., and the apatite thin film can be crystallized before being separated from the substrate. In addition, the present invention is advantageous in that all processes can be performed in an environment where no organic material is used, and impurities can be prevented from entering the apatite thin film. As described above, according to the present invention, an apatite thin film made of hydroxyapatite can be easily formed in a stable state while suppressing an increase in cost.

  The present invention is not limited to the embodiment described above, and many modifications and combinations can be implemented by those having ordinary knowledge in the art within the technical idea of the present invention. It is obvious.

  101 ... substrate, 102 ... sacrificial layer, 103 ... apatite thin film.

Claims (2)

A sacrificial layer forming step of forming a sacrificial layer made of lithium oxide on the substrate;
An apatite thin film forming step of forming an apatite thin film made of hydroxyapatite on the sacrificial layer;
Removing the sacrificial layer between the substrate and the apatite thin film by dissolving in water, and separating the apatite thin film from the substrate , and
Crystallization that weakens the adhesion between the sacrificial layer and the substrate while crystallizing the apatite thin film by heating at a temperature of 700 to 800 ° C. between the apatite thin film forming step and the separation step. A process for forming an apatite thin film comprising the steps . A sacrificial layer forming step of forming a sacrificial layer made of lithium oxide on the substrate;
An apatite thin film forming step of forming an apatite thin film made of hydroxyapatite on the sacrificial layer;
A separation step of removing the sacrificial layer between the substrate and the apatite thin film by dissolving in water, and separating the apatite thin film from the substrate;
With
And in the thin film formation process, apatite film forming method with an opening area where the lower layer of the sacrificial layer is exposed, characterized that you form the apatite film.

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