JP5580271B2 - Method for producing hydroxyapatite thin film - Google Patents

Description

  The present invention relates to a method for producing a hydroxyapatite thin film, which forms a hydroxyapatite thin film on various substrates.

Hydroxyapatite [Ca ₁₀ (PO ₄ ) ₆ (OH) ₂ ] is a biocompatible inorganic material. For example, bone is a self-organized arrangement of apatite nanocrystals with c-axis orientation on collagen fibers. Hydroxyapatite has a hexagonal crystal structure and a melting point of 1650 ° C. The c-plane of the single crystal is hydrophobic, but the a-plane is characterized by being hydrophilic. Examples of materials composed of elements such as Ca, P, O, and H similar to hydroxyapatite include biological apatite and calcium phosphate [β-Ca ₃ (PO ₄ ) ₂ ]. Depending on the body tissue site, these materials are mixed, and by utilizing the preferential orientation, the elastic constants, deformation behavior, environmental resistance, biocompatibility, etc. are subtly changed. Realized.

  Hydroxyapatite is being searched for developmental applications in medical engineering and bioscience. It is no exaggeration to say that how to combine with other materials is the key to becoming a major bioscience material in the future. In this sense, precise control of the morphology and physical properties of hydroxyapatite is required.

C. M. Cotell et al., "Pulsed Laser Deposition of Hydroxylapatite Thin Films on Ti-6Al-4V", J. Appl. Biomater. Vol.3, pp.87-93, 1992. R. K. Singh et al., "Excimer laser deposition of hydroxyapatite", Biometerials, vol.15, no.7, pp.522-528, 1994. K. Yamashita et al., "Preparation of Apatite Thin Films through rf-Sputtering from Calcium Phosphate Glasses", J. Am. Ceram. Soc., Vol.77, no.9, pp.2401-2407, 1994 K.van Dijk et al., "Influence of annealing temperature on RF magnetron aputtered calcium phosphate coatings", Biometerials, vol.17, pp.405-410, 1996.

  For example, although the artificial tooth root is mainly made of pure titanium, a strong bonding force with bone cannot be obtained. Therefore, a method of forming an apatite film on the surface has been studied. For the formation of such a film, a hydroxyapatite paste is used. However, a film formed by using a hydroxyapatite paste has a problem that adhesion and crystallinity with different materials are not good. Furthermore, it has been pointed out that a film formed using a paste is easily decomposed and melted at a high temperature. Therefore, various hydroxyapatite film forming methods have been tried.

In particular, if a thinner film (thin film) of hydroxyapatite can be formed, there is an advantage that processing using a semiconductor process can be performed. However, since the crystal unit is large, it has not yet been achieved to obtain a thin film with a good crystalline state. In the approach using a crystal engineering technique, research using a pulsed laser deposition (PLD) method has preceded (see Non-Patent Documents 1 and 2). PLD film formation is advantageous in that the PO ₄ bond is not broken during ablation and is easily evaporated, and the target composition is maintained and a thin film is formed. However, the area where the film can be formed is too small and is not suitable for manufacturing. On the other hand, there are not so many examples of research reports in the sputtering method capable of increasing the area (see Non-Patent Documents 3 and 4).

  Furthermore, even if a hydroxyapatite film is formed on various substrates by the above-described thin film formation technology, the crystal of the formed thin film is not used unless an epitaxial substrate lattice-matched with hydroxyapatite such as a sapphire substrate is used. Usually random orientation. From such a background, for example, a technique for forming a hydroxyapatite film having excellent crystallinity with a uniform orientation on a substrate usually used in a semiconductor process such as silicon by using a sputtering method has been desired. Precise control of crystal orientation leads to control of the interaction between hydroxyapatite and biological materials and living organisms, making it possible to maximize the functions of hydroxyapatite and directly develop new biosensors. is there.

  The present invention has been made to solve the above-described problems, and an object of the present invention is to allow a hydroxyapatite thin film to be formed on various substrates in a state where crystallinity is controlled.

The method for producing a hydroxyapatite thin film according to the present invention forms a thin film on a substrate under non-heating conditions by a sputtering method using a target made of a sintered hydroxyapatite and a sputtering gas containing H ₂ O gas. It includes at least a first step and a second step in which the thin film is heated and crystallized in an atmosphere containing oxygen. The sputtering method may be an electron cyclotron resonance sputtering method.

  In the method for producing a hydroxyapatite thin film, in the second step, heating may be performed in the range of 700 ° C. to 900 ° C. In the second step, heating may be performed for 3 hours or more in the range of 550 ° C to 600 ° C.

  As described above, according to the present invention, it is possible to obtain an excellent effect that a hydroxyapatite thin film can be formed on various substrates in a state where crystallinity is controlled.

FIG. 1 is an explanatory diagram for explaining a method for producing a hydroxyapatite thin film according to an embodiment of the present invention. FIG. 2 is a configuration diagram showing the configuration of the ECR sputtering apparatus. FIG. 3 is a characteristic diagram showing an X-ray diffraction pattern of each sample manufactured under a plurality of temperature conditions by the manufacturing method according to the embodiment of the present invention. FIG. 4 is a characteristic diagram showing an infrared transmission spectrum of the hydroxyapatite thin film of each sample whose X-ray diffraction pattern is shown in FIG. FIG. 5 shows that each hydroxyapatite thin film formed with H ₂ O partial pressures of 9.4 × 10 ⁻⁴ Pa and 5.3 × 10 ⁻³ Pa was heated at 700 ° C. for 1 hour in an oxygen atmosphere. It is a characteristic view which shows the X-ray-diffraction pattern of each obtained sample. FIG. 6 shows an X-ray diffraction of a sample obtained by heating a hydroxyapatite amorphous thin film formed at a H ₂ O partial pressure of 3.3 × 10 ⁻³ Pa in an oxygen atmosphere at 550 ° C. for 10 hours. It is a characteristic view which shows a pattern. FIG. 7 shows X-rays of samples obtained by heating a hydroxyapatite amorphous thin film in an oxygen atmosphere at 600 ° C. for 1 hour (1 h), 2 hours (2 h), and 3 hours (3 h). It is a characteristic view which shows a diffraction pattern. FIG. 8 is a characteristic diagram showing an infrared transmission spectrum of each sample crystallized at 550 ° C. for 10 hours and at 600 ° C. for 3 hours. FIG. 9 shows an as-depo amorphous thin film formed at a H ₂ O partial pressure of 3.3 × 10 ⁻³ Pa, a sample obtained by heating the amorphous thin film at 600 ° C. for 1 hour in an oxygen atmosphere, It is a characteristic view which shows the difference spectrum which deducted the infrared transmission spectrum of the silicon substrate from the infrared transmission spectrum measured about the sample heated at 550 degreeC for 10 hours. FIG. 10 is obtained by heating a hydroxyapatite amorphous thin film formed at a H ₂ O partial pressure of 3.3 × 10 ⁻³ Pa at 900 ° C. in a vacuum, in the air, and in an oxygen gas atmosphere for 1 hour. It is a characteristic view which shows the result of having compared the X-ray-diffraction pattern of each sample. FIG. 11 shows that the infrared transmission spectrum of a silicon substrate was subtracted from the infrared transmission spectrum of a film obtained by heating a hydroxyapatite amorphous thin film in vacuum at 800 ° C. and 900 ° C. for 1 hour. It is a characteristic view which shows a difference spectrum.

Hereinafter, embodiments of the present invention will be described with reference to the drawings. FIG. 1 is an explanatory diagram for explaining a method for producing a hydroxyapatite thin film according to an embodiment of the present invention. In this manufacturing method, in the first step S101, the thin film 102 is formed on the substrate 101 by a sputtering method using a target made of a sintered hydroxyapatite and a sputtering gas containing H ₂ O gas. The substrate 101 may be a silicon substrate, for example. Next, in the second step S102, the thin film 102 is heated and crystallized in an atmosphere containing oxygen. For example, heating may be performed in an oxygen gas atmosphere or in the air.

Here, in the first step, an electron cyclotron resonance (ECR) sputtering method may be used. By using the ECR sputtering method, it is possible to form a film under a gas pressure as low as 10 ⁻² Pa, and it has been demonstrated for many materials that a high-quality thin film can be obtained. The ECR plasma is a remote plasma, and when combined with a cylindrical target, the plasma damage to the thin film due to anion incidence is small.

  In addition, although the film formation rate of the ECR sputtering method is not so high, since the film formation time is required, the time during which the plasma is irradiated during the film formation is long. As a result, the plasma promotes atomic diffusion between the hydroxyapatite thin film and the substrate, and the greatest feature is that excellent adhesion can be obtained without interposing an adhesive layer between the substrate and the hydroxyapatite thin film. doing. This is an advantage not found in other sputtering methods or PLD methods. Furthermore, an apparatus that realizes the ECR sputtering method can form a large-area film up to an 8-inch substrate, which is impossible with the PLD method, and is suitable for production purposes.

Next, the use of a sputtering gas containing H ₂ O gas will be described. Hydroxyapatite contains an OH group as a constituent element. However, when a hydroxyapatite target is sputtered, OH having a small mass is scattered in a wide range, and all of these do not reach the substrate. For this reason, it is necessary to supplement the OH groups incorporated into the thin film. When a mixed gas of H ₂ and O ₂ gas is used, it is necessary to decompose H ₂ and O ₂ , and the flow rate ratio between them must be controlled. On the other hand, H ₂ O molecules are excellent as a reaction gas because they generate OH groups immediately by being decomposed into OH and H.

Conventionally, a hydroxyapatite thin film sputtered in an argon gas atmosphere has been crystallized by annealing in a gas containing H ₂ O vapor. In contrast, in the present embodiment, a sufficient amount of OH groups and H ₂ O molecules are first included in the film at the stage of film formation by sputtering. This realizes an environment similar to growing hydroxyapatite crystals at low speed in a solution in a hydroxyapatite thin film formed by sputtering. In addition, according to the present embodiment, it is possible to control the crystallization speed by changing the temperature at the time of crystallization, and to select whether the preferred orientation is the c-axis orientation or the random orientation. It is.

  Next, formation of a hydroxyapatite thin film (sample) using the ECR sputtering method will be described together with the configuration of the ECR sputtering apparatus.

  As shown in FIG. 2, the ECR sputtering apparatus includes a film formation chamber 201 and a plasma generation chamber 203 that communicates with the film formation chamber 201. For example, 2.45 GHz microwaves can be supplied to the plasma generation chamber 203 by a microwave supply source 204. Further, around the plasma generation chamber 203, for example, a magnetic coil 205 that generates a magnetic field of 0.0875 T (Tesla) in the plasma generation chamber 203 is provided.

  In the film forming chamber 201, a ring-shaped target 202 surrounding the vicinity of the outlet of the plasma generation chamber 203 is disposed. The target 202 is made of, for example, a sintered body obtained by sintering hydroxyapatite powder, and a predetermined target bias (high frequency power) can be applied. Further, the substrate 101 placed in the film formation chamber 201 can be heated by a heater 206.

After the substrate 101 is placed at a predetermined distance from the target 202 in the film forming chamber 201 of the ECR sputtering apparatus configured as described above, the film is formed by a well-known exhaust mechanism (not shown). The inside of the chamber 201 is evacuated to a predetermined pressure. For example, the inside of the film forming chamber 201 is depressurized to a high vacuum state pressure of 10 ⁻⁴ to 10 ⁻⁵ Pa. As the substrate 101, a Si (001) wafer from which a natural oxide film is removed with hydrofluoric acid is used.

Next, an inert gas such as argon is introduced into a processing chamber of the ECR sputtering apparatus, for example, the plasma generation chamber 203 to obtain a predetermined degree of vacuum (pressure). In this state, a 2.45 GHz microwave is generated by the magnetic coil 205. ECR plasma is formed in the plasma generation chamber 203 by supplying an electron cyclotron resonance condition by supplying a magnetic field of about 500 W and about 0.0875 T. In this state, H ₂ O gas is introduced into the film forming chamber 201 through a variable leak valve (not shown). The internal pressure was set to a level of 10 ⁻⁴ Pa to 10 ⁻³ Pa by introducing H ₂ O gas.

The ECR plasma generated as described above is emitted from the plasma generation chamber 203 to the film formation chamber 201 connected to the plasma generation chamber 203 by the divergent magnetic field of the magnetic coil of the ECR sputtering apparatus. In this state, for example, high frequency power (target bias) of 13.56 MHz · 500 W is supplied (applied) to the target 202 disposed at the outlet of the plasma generation chamber 203. As a result, the particles generated by the generated ECR plasma collide with the target 202 to cause a sputtering phenomenon, and the particles constituting the target 202 jump out. Further, OH and H are generated from H ₂ O introduced into the film formation chamber 201.

By generating ECR plasma in the sputter state as described above, particles sputtered from the target 202 are deposited on the substrate 101, and a thin film 102 (hydroxyapatite thin film) is formed on the substrate 101. Is done. Further, OH and H are taken into the film deposited on the substrate 101. Note that the substrate 101 was not heated during the film formation, but the substrate temperature rose to about 70 ° C. by the plasma irradiation. A hydroxyapatite thin film having a film thickness of 0.8-1 μm was formed, although it varied somewhat depending on the H ₂ O gas pressure during film formation.

Heating for crystallization is performed in an oxygen atmosphere and in the air. Further, a plurality of samples are manufactured by changing the H ₂ O gas partial pressure during film formation and the heating temperature for crystallization. For comparison, a comparative sample heated in vacuum was also produced. Note that heating may be performed by the heater 206 inside the deposition chamber 201. For example, if oxygen is introduced into the deposition chamber 201 without generating plasma, heating in an oxygen atmosphere can be performed. The formed thin film had a smooth surface and was not cracked or peeled off under any film forming / annealing conditions.

FIG. 3 is a characteristic diagram showing an X-ray diffraction pattern of each sample produced by the manufacturing method in the present embodiment described above. Here, a hydroxyapatite amorphous thin film formed by sputtering with a partial pressure of H ₂ O of 3.3 × 10 ⁻³ Pa is subjected to temperature conditions of 600 ° C., 700 ° C., and 800 ° C. in an oxygen atmosphere. 3 shows an X-ray diffraction pattern of a hydroxyapatite thin film in a sample formed by heating (annealing) at 900 ° C. for 1 hour. The strong peak at 2θ = 33 ° corresponds to Si (002) reflection.

  Since hydroxyapatite is a substance composed of light elements, the obtained diffraction intensity is very weak. Similar to the literature, no specific strong peak is observed, and diffraction peaks from randomly oriented hydroxyapatite crystallites such as (002), (211), (202), (310), (222), (213) are not observed. It can be seen. Particularly, the strength of (211) is the strongest characteristic of normal hydroxyapatite crystals. The (300) peak overlaps the Si (200) reflection.

FIG. 4 shows an infrared transmission spectrum of the hydroxyapatite thin film of each sample showing the X-ray diffraction pattern in FIG. For comparison, spectra of a film (as-depo) and a silicon substrate (Si substrate) which are not heated after the sputter deposition are also shown. By referring to the spectrum of the silicon substrate, a peak different from this spectrum can be identified as being derived from hydroxyapatite. From the hydroxyapatite thin film, the PO ₄ ^3- unit PO bond asymmetric stretching mode is ν ₃ = 1020 cm ⁻¹ , the symmetric stretching mode is ν ₁ = 950 cm ⁻¹ , and the bending vibration mode is ν ₄ = 575. It is seen at −610 cm ⁻¹ .

Absorption over 950-1100 cm ⁻¹ of the unheated film is broad, reflecting the lack of crystallization.

When heated at 600 ° C. or 700 ° C., absorption due to OH bending vibration is observed at ν ₂ = 1600 cm ⁻¹ . On the other hand, when heated at a high temperature of 800 ° C. and 900 ° C., the absorption due to the bending vibration of OH of ν ₂ = 1600 cm ⁻¹ is weak. From the X-ray diffraction pattern shown in FIG. 3, there is no significant difference in crystallinity depending on the heating temperature. Therefore, in the case of 800 ° C. and 900 ° C., no OH is lost even though the crystal lattice is formed. It is highly probable that it has occurred. Further, when heated at 900 ° C., it can be seen that the transmittance decreases as it goes from 2500 cm ⁻¹ to the low wavenumber side. This suggests that the thin film is totally reduced. Moreover, the absorption by PO ₄ ³⁻ is also crushed, suggesting that more PO ₂ and PO are contained than PO ₄ .

When the H ₂ O partial pressure in forming the hydroxyapatite thin film is changed, the amount of OH or H taken into the film changes, which affects the crystal orientation after heating. FIG. 5 shows that each hydroxyapatite amorphous thin film formed with H ₂ O partial pressures of 9.4 × 10 ⁻⁴ Pa and 5.3 × 10 ⁻³ Pa is formed in an oxygen atmosphere at 700 ° C. for 1 hour. It is an X-ray diffraction pattern of a sample (hydroxyapatite thin film) obtained by heating. Under the condition where the H ₂ O partial pressure is low, the (211) peak is strong, but under the condition where the H ₂ O partial pressure is high, the (002) peak is as high as the (211) peak.

FIG. 6 shows a sample (hydroxyapatite thin film) obtained by heating a hydroxyapatite amorphous thin film formed with an H ₂ O partial pressure of 3.3 × 10 ⁻³ Pa in an oxygen atmosphere at 550 ° C. for 10 hours. ) X-ray diffraction pattern. Since the hydroxyapatite thin film was not crystallized by heating at 500 ° C., it was found that the lower limit of the crystallization temperature was 550 ° C. The intensity of the (002) peak in FIG. 6 is 30 to 50 times stronger than the results in FIGS. 3 and 5, and it can be seen that the intensity is strongly oriented in the (002) direction. Such (002) preferential orientation was confirmed even when heated at 600 ° C. for a long time.

  FIG. 7 shows a sample (hydroxyapatite thin film) obtained by heating a hydroxyapatite amorphous thin film in an oxygen atmosphere at 600 ° C. for 1 hour (1 h), 2 hours (2 h), and 3 hours (3 h). ) X-ray diffraction pattern. Up to 2 hours, the diffraction pattern has a random orientation similar to the result of FIG. 3, but the (002) peak suddenly becomes stronger by heating for 3 hours. This means that a certain amount of time is required until a (002) -oriented crystal nucleus is formed, but once a (002) plane is formed, crystal growth on this plane is fast.

However, at a heating temperature of 700 ° C. or higher, such a c-axis preferential orientation does not occur even when heated for a long time. This is probably because OH and H ₂ O contained in the film are desorbed at an initial stage of heating at a high temperature of 700 ° C. Alternatively, at 700 ° C., the crystallization proceeds rapidly, resulting in random orientation, but at a low temperature of 550 ° C., the rate of crystallization is low, so the hydroxyapatite preferentially oriented in the c-axis direction over time. It can be interpreted that a crystal film is grown.

  FIG. 8 shows infrared transmission spectra of a sample (hydroxyapatite thin film) crystallized at 550 ° C. for 10 hours and at 600 ° C. for 3 hours. As shown in FIG. 8, OH absorption is also clearly observed. From this result, the difference from the infrared transmission spectrum of the sample heated at 600 ° C. and 700 ° C. shown in FIG. 4 is not known. However, it is certain that the crystal thin film strongly oriented in the (002) direction contains a sufficient amount of OH.

As-depo amorphous thin film formed at H ₂ O partial pressure 3.3 × 10 ⁻³ Pa, sample heated at 600 ° C. for 1 hour, and sample heated at 550 ° C. for 10 hours The difference spectrum shown in FIG. 9 was obtained by subtracting the infrared transmission spectrum of the silicon substrate from the infrared transmission spectrum measured for. This shows the light absorption characteristics of the hydroxyapatite sample itself excluding the effect of absorption of the silicon substrate. In the case of the as-depo film, the absorption peak at ν ₃ = 1020 cm ⁻¹ by PO ₄ ³⁻ is broader and the absorption at ν ₁ = 950 cm ⁻¹ is broader than other spectra. Furthermore, the absorption peak at ν ₄ = 575-610 cm ⁻¹ is not split into two, and the fine structure is not clear. This is due to the fact that the hydroxyapatite thin film is amorphous, and the chemical bond lengths and bond angles are not uniform.

On the other hand, in the sample heated at 600 ° C. for 1 hour and the sample heated at 550 ° C. for 10 hours, all the absorption peaks are sharp and OH absorption is visible at 1600 cm ⁻¹ . The absorption at 510 cm ⁻¹ is a variable vibration of the O═PO unit, which is also clearly observed.

From the above results, in order to obtain a (002) -oriented hydroxyapatite crystal film, for example, in the temperature range of 550 ° C. or more and 600 ° C. or less after film formation under a sufficient H ₂ O gas pressure, for example, 10 It has become clear that heating may take time, such as heating for a period of time.

So far, the results of heating in an oxygen gas atmosphere have been described. A hydroxyapatite amorphous thin film formed at an H ₂ O partial pressure of 3.3 × 10 ⁻³ Pa was vacuumed at 900 ° C. FIG. 10 shows a result of comparison of X-ray diffraction patterns of samples (hydroxyapatite thin films) obtained by heating in the atmosphere and in an oxygen gas atmosphere for 1 hour. The intensity of the (002) and (211) peaks is approximately the same in the atmosphere and in the oxygen gas atmosphere, indicating that the same result is obtained if oxygen gas is included in the atmosphere during heating.

On the other hand, when heated in vacuum, both the (002) and (211) peaks of hydroxyapatite become strong, indicating that crystallization is progressing. However, a peak that appears to be from Ca ₃ (PO ₄ ) ₂ also appears at the position of 2θ = 13 °. This is considered to be produced by the removal of OH from hydroxyapatite. Therefore, when heated at 900 ° C. in a vacuum, crystals containing Ca ₃ (PO ₄ ) _{2 in} addition to hydroxyapatite can be obtained.

The difference between the infrared transmission spectrum of a hydroxyapatite amorphous thin film heated at 800 ° C. and 900 ° C. in vacuum for 1 hour (hydroxyapatite thin film) and the spectrum of the silicon substrate is taken. The absorption spectrum of the film obtained by this is shown in FIG. Compared to 550 ° C. or 600 ° C. heating the sample in FIG. 9, the 1400cm ^-1 P-O ^- absorption attributed to stretching vibration of the P-OH per 1450 cm ^-1, to 2870cm ^-1 P-OH The characteristic feature is that a new absorption peak of stretching vibration is generated. This suggests that part of the PO ₄ ^3- unit is broken and is in the form of POH. In particular, in the case of heating at 900 ° C., the absorption of P—OH at 470 cm ⁻¹ is greatly increased. From these experimental facts, it can be seen that when heated at a high temperature in a vacuum, crystallization is fast, but decomposition also proceeds easily.

As described above, according to the present invention, the crystallinity is controlled on the substrate by controlling the H ₂ O gas partial pressure during sputtering film formation and the heating temperature in an atmosphere containing oxygen. Thus, a hydroxyapatite thin film can be formed. As a result, according to the present invention, it is possible to form a hydroxyapatite thin film on many materials to impart biocompatibility, which can lead to wide use of the hydroxyapatite thin film in the fusion field of medicine and engineering. Be expected. Although other film-forming methods have pointed out problems such as film peeling and generation of cracks, according to the present invention, a hydroxyapatite thin film with good adhesion can be formed. Furthermore, the crystal orientation of the hydroxyapatite thin film can be selected as c-axis or random orientation, and can be applied to a biosensor utilizing the surface characteristics.

  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 ... thin film.

Claims (4)

A first step of forming a thin film on a substrate under non-heating conditions by a sputtering method using a target made of a sintered body of hydroxyapatite and a sputtering gas containing H ₂ O gas;
And a second step of crystallizing the thin film by heating it in an atmosphere containing oxygen. A method for producing a hydroxyapatite thin film, comprising: In the manufacturing method of the hydroxyapatite thin film of Claim 1,
The method for producing a hydroxyapatite thin film, wherein the sputtering method is an electron cyclotron resonance sputtering method. In the manufacturing method of the hydroxyapatite thin film of Claim 1 or 2,
In the second step, heating is performed in a range of 700 ° C. to 900 ° C., and the method for producing a hydroxyapatite thin film. In the manufacturing method of the hydroxyapatite thin film of Claim 1 or 2,
In the second step, the method for producing a hydroxyapatite thin film is characterized in that heating is performed in a range of 550 ° C. to 600 ° C. for 3 hours or more.

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