DNA thin film manufacturing method

Abstract

To provide a method of producing a DNA thin film that is superior in controllability and can effectively thin the DNA thin film.SOLUTION: A method for producing a DNA thin film includes irradiating a target material containing DNA with a visible laser beam to form a DNA thin film on the surface of a substrate disposed facing the target material.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] This invention relates to a method for producing a DNA thin film. [Background technology]

[0002] Living organisms are known to possess many advantages in terms of energy and functionality, such as the ability to specifically detect target substances from a diverse range of materials with minimal energy consumption and to easily synthesize complex compounds. In recent years, the idea of ​​utilizing these superior functions of living organisms more broadly and proactively in industry has been gaining momentum, driven by advancements in biotechnology. This trend extends beyond food and chemicals to encompass industry, health and medicine, and even the environmental and energy sectors.

[0003] To utilize the functions of living organisms more stably and efficiently, while excluding the inherent uncertainties of the organisms themselves, it is necessary to integrate reaction elements responsible for biological functions with non-biological materials such as electronic and mechanical systems to create devices. This is what is known as living devices, and development is progressing in this area.

[0004] At the core of such living devices is a bio-functional element (hereinafter also referred to as the reaction unit) that detects or transforms target substances through biochemical reactions and interactions with those substances, thereby acquiring biochemical signals (such as changes in molecular three-dimensional structure and ion concentration gradients) and energy.

[0005] In fabricating biofunctional elements, which are the reaction parts of living devices, biomolecules such as deoxyribonucleic acid (DNA), ribonucleic acid (RNA), DNA and RNA fragments, nucleotides, and peptides are generally formed into thin films.

[0006] For example, Patent Document 1 describes an information recording element that includes at least one organic thin film between the anode and the cathode, and at least one of the organic thin films is composed of a DNA thin film. In Patent Document 1, the DNA thin film is prepared by coating and drying a solution in which DNA is dissolved.

[0007] Furthermore, Patent Document 2 proposes using a photoresponsive DNA thin film as a sensing element. In Patent Document 2, a photoresponsive DNA thin film is fabricated using an aqueous solution of DNA or an organic solution of hydrophobic DNA by methods such as spin coating, solvent evaporation, LB (Langmuir-Blodgett) method, and alternating adsorption method.

[0008] However, since Patent Documents 1 and 2 describe a wet film deposition method, it is extremely difficult to hybridize the film by layering it with other thin film materials or to microfabricate it into the shape of a device, and achieving further thinning is also not easy. Furthermore, the LB method has many challenges in terms of thin film formation speed and controllability. In addition, when introducing substances such as dyes, indicators, and drugs into biomolecules such as DNA, the wet method has limitations such as the electrostatic repulsion force caused by the presence of water molecules, which restricts the substances that can penetrate the biomolecules to molecules with a positive charge.

[0009] Furthermore, Non-Patent Documents 1 and 2 report on techniques for forming thin films of organic compounds using dry methods such as vacuum deposition, plasma polymerization, and molecular beam epitaxy. However, Non-Patent Documents 1 and 2 do not contain any studies on forming thin films of biomolecules such as DNA using these methods. [Prior art documents] [Patent Documents]

[0010] [Patent Document 1] Japanese Patent Publication No. 2007-73556 [Patent Document 2] Japanese Patent Publication No. 2003-344286 [Non-patent literature]

[0011] [Non-Patent Document 1] "Thin Film Formation Technology for Organic Functional Molecules," Michiko Shimura, Surface Technology, 1994, Vol. 45, No. 12, pp. 1189-1193. [Non-Patent Document 2] "Fabrication of Chiral Molecular Thin Films by Vapor Deposition Polymerization Using Selective Adsorption", Atsushi Kubono, Database of Scientific Research Grants, Research Achievement Report 23651090, 2013

Summary of the Invention

Problems to be Solved by the Invention

[0012] An object of the present invention is to provide a method for producing a DNA thin film that is excellent in controllability and can be well thinned.

Means for Solving the Problems

[0013] [1] A method for producing a DNA thin film, comprising irradiating a target material containing DNA with a visible laser to form a DNA thin film on the surface of a substrate disposed opposite to the target material. [2] The method for producing a DNA thin film according to [1] above, wherein the target material further contains glycerol. [3] The method for producing a DNA thin film according to [1] or [2] above, wherein the visible laser is a visible pulsed laser. [4] The method for producing a DNA thin film according to any one of [1] to [3] above, wherein in the infrared absorption spectrum measured by a Fourier transform infrared spectrometer for the DNA thin film, there are peaks derived from nucleobases and peaks derived from the phosphate backbone. [5] The method for producing a DNA thin film according to any one of [1] to [3] above, wherein in the gel electrophoresis analysis of the DNA thin film using a gel provided with a fluorescent substance that binds to DNA, a fluorescence spectrum corresponding to the DNA constituting the DNA thin film is obtained.

Effects of the Invention

[0014] According to the present invention, it is possible to provide a method for producing a DNA thin film that is excellent in controllability and can be well thinned.

Brief Description of the Drawings

[0015] [Figure 1]FIG. 1 is a schematic diagram showing an example of a DNA thin film manufacturing apparatus used in the method for manufacturing a DNA thin film according to an embodiment. [Figure 2] FIG. 2 is an image obtained by observing the DNA thin film obtained in Example 1 from above with an optical microscope. [Figure 3] FIG. 3 shows the ultraviolet-visible transmission spectrum results of the DNA thin film obtained in Example 1 and the DNA thin film obtained in Comparative Example 1. [Figure 4] FIG. 4 shows the infrared absorption spectrum results obtained by measuring the DNA thin film obtained in Example 1 and the DNA thin film obtained in Comparative Example 1 with a Fourier transform infrared spectrophotometer. [Figure 5] FIG. 5 shows the results of gel electrophoresis analysis of the DNA thin film obtained in Example 1 and the DNA thin film obtained in Comparative Example 1. [Figure 6] FIG. 6 is an image obtained by observing the DNA thin film obtained in Example 2 from above with an optical microscope. [Figure 7] FIG. 7 shows the results of measuring the DNA thin film obtained in Example 2 with a stylus surface profiler.

BEST MODE FOR CARRYING OUT THE INVENTION

[0016] Hereinafter, a detailed description will be given based on the embodiment.

[0017] The inventors of the present invention have found that in the conventional film formation method by the wet method, it is extremely difficult to form multilayers with other thin film materials for hybridization or to perform microfabrication on the shape of the device, and it is also not easy to achieve further thinning of the film. In addition, the inventors have also focused on the problem that when DNA is irradiated with a laser, the DNA is destroyed and the molecular structure of the DNA cannot be maintained. As a result of intensive research, the inventors have found that by irradiating a target material containing DNA with a visible laser, a DNA thin film that maintains the DNA structure can be successfully manufactured by a manufacturing method with excellent controllability, and based on such findings, the present invention has been completed.

[0018] Figure 1 is a schematic diagram showing an example of a DNA thin film manufacturing apparatus used in the DNA thin film manufacturing method of the embodiment. The DNA thin film manufacturing apparatus used in the DNA thin film manufacturing method of the embodiment is not particularly limited as long as it can perform the DNA thin film manufacturing method of the embodiment, but the DNA thin film manufacturing apparatus 1 shown in Figure 1 is preferred.

[0019] The method for manufacturing a DNA thin film in this embodiment involves irradiating a target material 4 containing DNA with a visible laser 5 to form a DNA thin film 2 on the surface of a substrate 3 placed opposite the target material 4.

[0020] In the DNA thin film manufacturing method of this embodiment, a visible laser 5 is irradiated onto a target material 4. When the visible laser 5 is irradiated onto the target material 4, the target material 4 is heated and the DNA contained in the target material 4 is vaporized. The vaporized DNA moves through the reaction vessel 6 and reaches the surface of the substrate 3. In this way, a DNA thin film 2 can be formed on the surface of the substrate 3.

[0021] Even when the DNA in target material 4 is vaporized by a visible laser, the DNA constituting DNA thin film 2 does not undergo significant thermal denaturation or degradation, indicating that DNA thin film 2 possesses DNA-based biological functions. The characteristics of DNA, such as its skeletal structure and function, are essentially maintained in DNA thin film 2.

[0022] Thus, in the DNA thin film manufacturing method of this embodiment, a visible laser 5 is irradiated onto the target material 4. As a result, a DNA thin film 2 that maintains the molecular structure of DNA can be obtained. Furthermore, because the DNA thin film manufacturing method of this embodiment utilizes irradiation with a visible laser 5, it offers excellent controllability and allows for good thinning of DNA. In addition, it becomes easy to hybridize the DNA thin film 2 by multilayering it with other thin film materials, and by adjusting the manufacturing conditions, it also becomes easy to microfabricate the DNA thin film 2 into the shape of a device or to make the DNA thin film 2 extremely thin.

[0023] The following describes in detail the method for manufacturing DNA thin films using DNA thin film manufacturing apparatus 1.

[0024] The DNA thin film manufacturing apparatus 1 shown in Figure 1 mainly comprises a substrate 3, a target material 4, a visible laser 5 irradiated from a laser source (not shown), a reaction vessel 6, a laser transmission window 7 provided in the reaction vessel 6, a film thickness gauge 8, and a stage 9. Inside the reaction vessel 6 are the substrate 3, the target material 4, the film thickness gauge 8, and the stage 9.

[0025] A target material 4 is placed on a stage 9 located below the reaction vessel 6. For example, the target material 4 is placed in the form of a film on a substrate such as silicon or quartz. The inside of the reaction vessel 6 is sealed.

[0026] The state of the DNA contained in the target material 4 is not particularly limited and is appropriately selected depending on the application and function of the DNA thin film to be manufactured. Preferably, it is DNA or DNA fragments. Furthermore, the DNA only needs to be capable of forming a double helix structure, and may also be a structure containing ribonucleic acid (RNA). For example, the target material 4 is solid at room temperature. As an example, the target material 4 can be obtained in a solid state at room temperature by dissolving DNA in pure water and drying it.

[0027] The DNA included in target material 4 can be either natural DNA or synthetic DNA, and is appropriately selected depending on the application and function of the DNA thin film to be manufactured. Preferred natural DNAs include bacterial viral lambda phage DNA, Escherichia coli chromosomal DNA, calf thymus DNA, and salmon sperm DNA. Preferred synthetic DNAs include those that can be synthesized by a synthesis apparatus using poly(dA), poly(dT), poly(dG), poly(dC), poly(dA-dT), poly(dG-dC), etc. Furthermore, the DNA may also include various synthetic RNAs with different base sequences and DNA / RNA hybrids having complementary base pairs.

[0028] The size of the DNA contained in target material 4 is generally limited depending on the type of manufacturing method, but it is not limited in the DNA thin film manufacturing method of this embodiment. The DNA size is, for example, between 1 bp and 150 Gbp.

[0029] Furthermore, it is preferable that the target material 4 also contains glycerol in addition to DNA. The inclusion of glycerol in the target material 4 can reduce the surface roughness (Rms) of the produced DNA thin film. Therefore, the surface roughness (Rms) of the DNA thin film can be easily controlled by adjusting the glycerol content in the target material 4.

[0030] Furthermore, if the manufactured DNA thin film has a DNA backbone and the controllability of the DNA thin film manufacturing method is not reduced, the target material 4 may also contain additives such as laser-absorbing materials in addition to DNA. Laser-absorbing materials can improve the heating efficiency with a visible laser.

[0031] Furthermore, when interlayer compounds are included in the DNA thin film 2, substances such as dyes, indicators, and drugs that penetrate the DNA constituting the DNA thin film may also be included in the target material 4. Unlike wet film deposition methods such as spin coating, there are no restrictions that limit such substances to positively charged molecules; negatively charged molecules can also be used.

[0032] In Figure 1, an example is shown where the substance to be introduced into the DNA is included in the target material 4. However, this substance may be provided separately in the reaction vessel 6 from the target material 4. In this case, the substance may be vaporized by high-frequency induction heating or irradiation with another laser, rather than by a visible laser 5, and mixed into the DNA thin film 2.

[0033] The visible laser 5 used to vaporize the target material 4 is preferably a continuous visible laser, a visible pulsed laser, a frequency-modulated visible laser, or an amplitude-modulated visible laser. Multiple lasers may be used in combination, or a single laser may be used. Among these, the visible laser 5 preferably includes a visible pulsed laser, and more preferably consists solely of a visible pulsed laser.

[0034] Furthermore, the visible laser 5 is preferably light with a wavelength of 500 nm to 600 nm. When the visible laser 5 is light with a wavelength within the above range, the manufacturing controllability of the DNA thin film is good, and the DNA structure in the manufactured DNA thin film is sufficiently maintained. Alternatively, the wavelength of the visible laser irradiated from a laser source (not shown) may be controlled using an optical filter to adjust the wavelength to within the above range.

[0035] Furthermore, if the visible laser 5 is a visible pulsed laser, the output of the visible pulsed laser is preferably 0.5W to 3.5W, from the viewpoint of improving the controllability of DNA thin film manufacturing and the maintenance of DNA structure. Also, from the same viewpoint, the repetition frequency of the visible pulsed laser is preferably 5Hz to 15Hz.

[0036] The substrate 3 on which the DNA thin film 2 is formed is positioned opposite the target material 4 in the reaction vessel 6. As shown in Figure 1, when the target material 4 is located below the reaction vessel 6, the substrate 3 is located above the reaction vessel.

[0037] The substrate 3 can be made of inorganic materials, organic materials, or hybrid materials, and is appropriately selected according to the application and function of the DNA thin film 2. Preferably, silicon (silicon wafer) or quartz is used. The substrate 3 may also be an electronic device or electronic element. The shape of the substrate 3 is not limited to a planar shape, but can be curved or mesh-shaped, as long as a good DNA thin film 2 can be formed on the surface of the substrate 3. Furthermore, the substrate 3 may be a liquid layer such as silicone oil, a gel-like layer, or a support having the properties of these on its surface.

[0038] During the production of the DNA thin film, the temperature of the substrate 3 is preferably between 15°C and 35°C, from the viewpoint of good production controllability and the formation rate of the DNA thin film 2. For example, the temperature of the substrate 3 can be controlled within a predetermined range by a heater (not shown) provided in the reaction vessel 6.

[0039] The pressure inside the reaction vessel 6 is preferably 1 × 10⁻⁶ -4 The pressure is preferably Pa or less. When the DNA thin film manufacturing method is carried out under a pressure within the above range, the DNA thin film 2 can be thinned well. For example, the pressure inside the reaction vessel 6 can be controlled within a predetermined range by a vacuum pump (not shown) provided in the DNA thin film manufacturing apparatus 1.

[0040] The reaction vessel 6 is provided with a laser-transmitting window 7 that allows a visible laser 5, emitted from a laser source (not shown) located outside the reaction vessel 6, to pass through. For example, as shown in Figure 1, the laser-transmitting window 7 is provided on a part of the side wall of the reaction vessel 6. The visible laser 5 emitted from the laser source enters the reaction vessel 6 from the outside through the laser-transmitting window 7 and irradiates the target material 4 on the stage 9. The laser-transmitting window 7 may be composed of an optical filter that controls the wavelength of the laser.

[0041] The visible laser 5 can be irradiated in a spot-like manner onto the surface of the target material 4. The spot-like irradiation position on the surface of the target material 4 can be changed as needed by rotating the stage 9 on which the target material 4 is mounted, or by changing the irradiation angle and position of the visible laser 5.

[0042] When the target material is heated as a whole, a large amount of DNA is vaporized, causing large pressure fluctuations in the reaction vessel 6, making it difficult to control the rate of DNA thin film deposition. On the other hand, as described above, by irradiating the surface of the target material 4 with a visible laser 5 in a spot manner, the DNA in the target material 4 can be vaporized locally. Therefore, since the pressure fluctuations in the reaction vessel 6 are small, the rate of DNA thin film deposition 2 can be easily controlled.

[0043] A film thickness gauge 8 is installed inside the reaction vessel 6. The film thickness gauge 8 can measure the thickness of the DNA thin film 2.

[0044] Furthermore, a mask 10 may be provided inside the reaction vessel 6. The mask 10 is provided near the substrate surface on the side where the DNA thin film 2 is formed. The mask 10 can be moved relative to the surface of the substrate 3 by a motor (not shown), and the exposure state of the substrate 3 surface can be controlled.

[0045] The DNA thin film 2 is not deposited on the surface portion of the substrate 3 covered by the mask 10, while the DNA thin film 2 is deposited on the surface portion of the substrate 3 not covered by the mask 10. By appropriately moving the mask 10 relative to the substrate surface, the thickness of the DNA thin film 2 deposited on the surface of the substrate 3 can be controlled. Such thickness control is suitable for the production of combinatorial film thickness gradient samples. A combinatorial film thickness gradient sample is a sample provided on a single substrate, comprising thin films with continuously varying film thicknesses.

[0046] Furthermore, by appropriately setting the movement and shape of the mask 10 and the irradiation conditions of the visible laser 5, it is possible to achieve nanometer-order precision (for example, 100 nm). 2 Fine DNA thin films (approximately 100 nm) can be formed. Furthermore, by increasing the size of the substrate 2, it is possible to create films on the order of meters (e.g., 100 nm). 2 It is possible to form large DNA thin films (of a certain size). Furthermore, it is possible to form fine DNA thin films on the nanometer scale over a meter scale.

[0047] Furthermore, while Figure 1 shows an example where one mask 10 is installed, two or more masks 10 may be installed.

[0048] After the thickness of the DNA thin film 2, as measured by the film thickness gauge 8, reaches a predetermined range, the irradiation of the visible laser 5 is stopped, and the production of the DNA thin film is terminated. Alternatively, after stopping the irradiation of the visible laser 5, nitrogen may be supplied to the reaction vessel 6 to nitrogen-treat the DNA thin film.

[0049] Furthermore, the DNA thin film 2 may be removed from the substrate 3 depending on the application and function. For example, the DNA thin film 2 can be removed from the substrate 3 by immersing the substrate 3, which is equipped with the DNA thin film 2, in a solution that dissolves the substrate 3. Subsequently, the DNA thin film 2 can be obtained by removing it from the solution.

[0050] Alternatively, the DNA thin film 2 provided on the surface of substrate 3 may be transferred to another substrate (transfer substrate). For example, a substrate 3 having a release agent on its surface may be used. After forming the DNA thin film 2 on the surface of the release agent, the DNA thin film 2 is transferred from the surface of the release agent to the surface of the transfer substrate. For example, a mesh-like substrate may be used for substrate 3.

[0051] Furthermore, the infrared absorption spectrum measured with a Fourier transform infrared spectrophotometer for the obtained DNA thin film 2 has peaks derived from nucleic acid bases and peaks derived from the phosphate skeleton. The DNA thin film 2 has biological functions. In addition, the DNA thin film 2 contains at least DNA fragments that have been cut in the direction of the DNA chain length, and it is preferable that it contains DNA (uncut DNA). The peaks derived from nucleic acid bases and peaks derived from the phosphate skeleton are derived from DNA. Specifically, the peaks derived from nucleic acid bases are peaks derived from the stretching vibrations of C=N, C=O, and C=C, and the peaks derived from the phosphate skeleton are PO2 - This peak originates from the stretching vibration.

[0052] If the infrared absorption spectrum of DNA thin film 2 shows peaks derived from nucleic acid bases and peaks derived from the phosphate backbone, then DNA thin film 2 possesses the basic structure of DNA and therefore has sufficient DNA-based biological functions. For this reason, it is suitable for use in reaction sections of living devices.

[0053] Furthermore, the surface roughness (Rms) (root mean square roughness) of the DNA thin film 2 is appropriately selected depending on the application and function, but is, for example, 500.0 nm or less. Preferably, the surface roughness (Rms) of the DNA thin film 2 is 10.0 nm or less, more preferably 9.0 nm or less, even more preferably 7.0 nm or less, and most preferably 5.0 nm or less. The lower limit of the surface roughness (Rms) of the DNA thin film 2 may be influenced by the surface condition of the substrate 3 used when manufacturing the DNA thin film, but is, for example, 0.1 nm or more. When the surface roughness (Rms) is within the above range, the flatness of the DNA thin film 2 is good, making it suitable for use in reaction parts of living devices and the like.

[0054] Furthermore, the thickness of the DNA thin film 2 is, for example, 1.0 × 10⁻⁶. -3 μm or more 1.0×10 3 The thickness is less than or equal to μm, preferably between 0.2 μm and 5.0 μm. When the thickness of the DNA thin film 2 is within the above range, it is suitably used in the reaction section of a living device. However, the thickness of the DNA thin film 2 is not particularly limited and can be appropriately selected depending on the application and function.

[0055] Furthermore, in gel electrophoresis analysis of the DNA thin film 2 using a gel containing a fluorescent substance that binds to DNA, a fluorescence spectrum corresponding to the DNA constituting the DNA thin film 2 is obtained. Thus, since a fluorescence spectrum corresponding to the DNA constituting the DNA thin film 2 is obtained in gel electrophoresis analysis, the DNA thin film 2 stably maintains the molecular structure of DNA, and is therefore suitable for use in the reaction section of living devices.

[0056] Furthermore, the DNA thin film 2 may further contain an interlayer compound having DNA and a substance that has entered the DNA. The substance that enters the DNA is preferably a colorant, a fluorescent substance, etc.

[0057] Furthermore, the area of ​​the DNA thin film 2 is not particularly limited and can be appropriately selected depending on the application and function. For example, the area of ​​the DNA thin film 2 is 100 nm. 2 (For example, 10nm x 10nm) or larger, up to 100m 2 (For example, 10m x 10m) or less. Thus, DNA thin films 2 can range from nanometer-order fine films to meter-order large films. Furthermore, nanometer-order fine DNA thin films 2 can be thinned to meter-order scales.

[0058] As described above, DNA thin film 2 has a DNA backbone. Furthermore, DNA thin film is excellent at thinning and possesses biological functions. For this reason, DNA thin film 2 is suitable for use in reaction parts of living devices. Suitable living devices include sensors that measure substances based on biochemical reactions, reactors that produce energy or substances through biochemical reactions, actuators that move substances using biochemical reactions, and processors that process information using biochemical reactions. Suitable sensors include ampere-measuring electrochemical biosensors, calorie-measuring sensors, acoustic sensors, potentiometer sensors, radiation detection sensors, optical sensors, and ISFET-based biosensors.

[0059] According to the embodiments described above, by irradiating a target material containing DNA with a visible laser, a DNA thin film that maintains the DNA structure can be successfully manufactured using a highly controllable manufacturing method.

[0060] Although embodiments have been described above, the present invention is not limited to the embodiments described above, and includes all aspects included in the concept and claims of the present invention, and can be modified in various ways within the scope of the present invention. [Examples]

[0061] Next, examples and comparative examples will be described, but the present invention is not limited to these examples.

[0062] (Example 1) Using the DNA thin film manufacturing apparatus shown in FIG. 1, a DNA thin film was produced on a substrate under the following conditions.

[0063] Substrate: Si substrate (100) (n-type) (length 42 mm × width 19 mm) System internal pressure: 4 × 10 -5 Pa Target material: Purified salmon sperm DNA (solid form) Substrate temperature: 23°C (room temperature) Distance between substrate and target material: 2 - 5 cm Wavelength of visible pulse laser: 532 nm Output of visible pulse laser: 1.0 - 3.0 W Repetition frequency of visible pulse laser: 10 Hz

[0064] (Comparative Example 1) A casting solution in which 20 g of purified salmon sperm DNA was dispersed in 1 ml of purified water was prepared. Subsequently, the casting solution was applied onto the same substrate as in Example 1 by the spin coating method, and then dried at 23°C (room temperature) at 1 atm (= 1013.25 hPa) for 96 hours to produce a DNA thin film. Note that Comparative Example 1 was conducted so that the DNA thin film covered the entire substrate surface and had the minimum film thickness.

[0065] Figure 2 shows an image of the DNA thin film obtained in Example 1, observed from above with an optical microscope. In Figure 2, the lower side shows the DNA thin film surface, and the upper side shows the substrate surface. Thus, it was found that the DNA was aggregated in the DNA thin film obtained in Example 1. Furthermore, the surface roughness (Rms) of the DNA thin film obtained in Example 1 was measured with a stylus-type surface profiler (stylus-type profiling system) and found to be 536.6 nm. Figure 3 shows the ultraviolet-visible transmission spectra of the DNA thin film obtained in Example 1 and the DNA thin film obtained in Comparative Example 1. From the ultraviolet-visible transmission spectra in Figure 3, a peak originating from nucleic acid bases was confirmed near a wavelength of 260 nm. Figure 4 shows the infrared absorption spectra of the DNA thin film obtained in Example 1 and the DNA thin film obtained in Comparative Example 1, measured with a Fourier transform infrared spectrophotometer. From the infrared absorption spectra in Figure 4, a peak originating from nucleic acid bases was found at 1704 cm⁻¹. -1 and 1667cm -1 The peak, and the 1230 cm peak originating from the phosphate skeleton. -1 and 1076cm -1 and 1015cm -1 and 967cm -1 The peak was confirmed. These results indicate that the DNA thin film obtained in Example 1 retained the DNA structure. Figure 5 shows the results of gel electrophoresis analysis of the DNA thin film obtained in Example 1 and the DNA thin film obtained in Comparative Example 1. From the results in Figure 5, the fluorescence distribution of the DNA thin film obtained in Example 1 behaved similarly to that of the raw material DNA.

[0066] (Example 2) A DNA thin film was prepared on a substrate in the same manner as in Example 1, except that glycerol was added to a solid target material. Then, the DNA thin film was treated with nitrogen by supplying nitrogen to the reaction vessel to produce the DNA thin film.

[0067] Figure 6 shows an image of the DNA thin film obtained in Example 2, observed from above with an optical microscope. In Figure 6, the right side shows the DNA thin film surface, and the left side shows the substrate surface. Figure 7 shows the results of measuring the DNA thin film obtained in Example 2 with a stylus-type surface profile analyzer. Compared to Example 1, the surface roughness (Rms) of the DNA thin film obtained in Example 2 was reduced, indicating that the DNA thin film was further planarized in Example 2. Thus, by using a target material containing glycerol, the surface roughness (Rms) of the DNA thin film could be easily controlled.

[0068] From the above examples, it was possible to accurately and successfully fabricate DNA thin films with a DNA backbone. Furthermore, the surface roughness of the DNA thin film could be easily controlled. For example, DNA thin films with low surface roughness have low reflectivity and are therefore suitable for application in optical devices, while DNA thin films with high surface roughness have a large surface area and are therefore suitable for application in sensors. [Explanation of Symbols]

[0069] 1 DNA thin film manufacturing equipment 2 DNA thin film 3 circuit boards 4. Target material 5. Visible laser 6. Reaction vessel 7. Laser-transmitting window 8. Film Thickness Gauge 9 stages 10 masks

Claims

1. A method for producing a DNA thin film, comprising irradiating a target material containing DNA and glycerol with a visible laser to form a DNA thin film on the surface of a substrate placed opposite the target material.

2. The method for producing a DNA thin film according to claim 1, wherein the visible laser is a visible pulsed laser.

3. A method for producing a DNA thin film according to claim 1 or 2, wherein the infrared absorption spectrum measured with a Fourier transform infrared spectrophotometer for the DNA thin film has peaks originating from nucleic acid bases and peaks originating from the phosphate skeleton.

4. A method for producing a DNA thin film according to claim 1 or 2, wherein a fluorescence spectrum corresponding to the DNA constituting the DNA thin film is obtained in gel electrophoresis analysis of the DNA thin film using a gel comprising a fluorescent substance that binds to DNA.

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