JP3163230B2 - How to create a two-dimensional molecular pattern - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a method for forming a two-dimensional molecular pattern. More specifically, the present invention relates to a molecular regular structure (two-dimensional molecular pattern) in a monolayer by molecular recognition as a specific binding property of the molecule.
It is about how to create.

[0002]

BACKGROUND OF THE INVENTION In order to create small, high-performance devices, information must be collected in a smaller area. For that purpose, a technology for ultra-fine processing of a device is required. Therefore, various lithography techniques have been widely applied as such ultra-fine processing techniques.

For example, in photolithography, ultraviolet light is irradiated on a photoresist film through a photomask to cause a physicochemical reaction, and a portion irradiated with light (or a portion not irradiated with light) is removed (etching process). How to make a pattern. However,
Disadvantages of this method are that the resolution is limited by the photomask and that it is theoretically impossible to make a pattern finer than the wavelength of light, and the resolution is only on the order of submicrons. As an example using a wavelength shorter than light, a microfabrication technique using electron beam, X-ray, or ion beam lithography has been developed. Some of them have the advantage of not using a mask, but currently the maximum resolution is 10
In fact, the resolution is on the order of nm, and the resolution at the molecular level has not yet been reached.

As the latest technology, a processing method using a probe of a probe microscope has been proposed. A probe microscope is a method of observing the surface morphology of a sample at the molecular level by measuring the tunnel current between the probe and the sample, etc. A method of performing fine processing by removing at a level has been proposed. This method has been reported to remove any sulfur atoms from the molybdenum disulfide crystal surface.However, in many other cases, only sub-micron resolution has been obtained. Has not yet achieved a high resolution. The major cause is that the shape of the probe used is not sharp at the molecular level and a force is applied over a range larger than the molecular size, and this causes unnecessary deformation around the intended processing area. (Especially, when an organic sample is used, the effect of deformation is large). Also, this method is not suitable for producing the same pattern over a wide range.

[0005] As described above, in the case of performing fine processing by physically applying an external action, the processing accuracy depends on the structural accuracy of the device to which the operation is applied, and the operation is an object. The problem is that it extends to the periphery of the part. If the molecular arrangement can be controlled by utilizing the self-organizing property of the molecule itself without giving light or force from the outside,
The above problems can be avoided. The term "self-organizing property" as used herein refers to the ability of the compound itself to form a regular aggregate even at a dilute concentration without any external modification, and exhibits a complex function in a living body. It is the driving force for the construction of aggregates such as biological membranes.

As a method of forming an artificial aggregate utilizing the self-organization of molecules, the Langmuir-Blowjet (LB) method is well known. This involves dissolving an amphipathic substance such as lipid in an organic solvent, developing it on an aqueous solution, and transferring the resulting monomolecular film onto a solid substrate, thereby laminating a thin film of any thickness. This is a method of laminating while controlling the order. This method is an extremely effective method for controlling the structure in the thickness direction of the aggregate, such as sequentially laminating different lipids from the first layer, the second layer, and the third layer. However, there is a limitation that this is not a method for controlling the molecular arrangement in a single layer (in a single molecular plane). Atomic force microscopy and the like have reported that lipid molecules are arranged in LB membranes and monolayers, but this reflects a thermodynamically stable structure. Is uniquely determined by the type. Thus, this is not an arbitrarily controlled molecular sequence. Further, attempts have been made to process an LB film transferred on a substrate or a monomolecular film formed by an adsorption method with a fine probe of a photolithography or a probe microscope. Since an action is applied from the outside, there remains a problem in resolution and the like as in the above-described method.

As described above, in the various lithography methods and the method using the probe of the probe microscope, since the structural accuracy of the equipment used for processing is not at the molecular level, it is necessary to achieve the molecular level structural control in a two-dimensional plane. I haven't. Therefore, in order to obtain a pattern whose sequence is controlled at the molecular level, it is necessary to control the self-organizing property of the molecule and control the sequence structure that the molecule spontaneously constitutes without applying external force. To this end, a method can be considered in which a new chemical component is added, and recognition between molecules changes the spontaneous assembly mode of the molecules based on the interaction.This technology is mainly formed in solution. It has been applied to fine aggregates and crystals, but has not yet been applied to two-dimensional systems.

Accordingly, the present invention solves the above-mentioned drawbacks of the prior art, and more simply and accurately controls the assembled state of molecules to a required state through specific molecule recognition. It is intended to provide a new method by which two-dimensional molecular patterns can be created.

[0009]

In order to solve the above-mentioned problems, the present invention provides a functional group capable of interacting with a lipid molecule.
Each of the water-soluble compounds is placed on an aqueous solution of a plurality of water-soluble compounds.
Multiple lipid molecules interacting with different functional groups of the compound
By unfolding, lipid molecules in a two-dimensional plane on the water surface
A method for creating a two-dimensional molecular pattern (claim 1), characterized in that a pattern is formed by controlling the aggregation state .

[0010] In addition, the present invention is, for the above-described method, the fat
Molecules are bonded to an organic chain having orientation and hydrophobicity by ionic bonding.
The bond ability of either hydrogen bond or coordination bond
An aqueous group (claim 2), wherein the lipid molecule is
Chemical formula (1);

Embedded image (However, in the compound (b), n is 14 or 1
8, m is 1 or 4, and in the compound (f), n is 1
4 or 16, m represents 2, 6, or 10)
Shown compounds (a), (b), (c), (d),
(E) or (f) (claim 3); and
Functional groups that can interact with lipid molecules
Compound, polyfunctional phosphate compound, water-soluble carboxylic acid compound
Products, polyfunctional carboxylic acid compounds, nucleotides, and
Selected from the group consisting of metal-containing ion molecules (claim
Item 4) is provided as an embodiment.

[0011] In addition, the present invention is, Oite to the above-described method,
Water-soluble with multiple functional groups that can interact with lipid molecules
The compound is adenosine triphosphate (ADP)
Phosphate (ADP), adenosine monophosphate (AMP), flavin
Mononucleotide (FMN) and flavin adenine
Be selected from the group consisting of nucleotides (FAD)
Claim 5 is also provided as an embodiment. In addition, the present invention
Is a monomolecular film formed by any of the above methods.
Transferring and fixing on a solid substrate (Claim 6)
Diluting the monomolecular film with non-binding lipid (claim
7) is also provided as a method for creating a two-dimensional molecular pattern.

[0012]

In the present invention, an array pattern (two-dimensional molecular pattern) of molecules whose structure is controlled at the molecular level is formed in a two-dimensional plane called a monomolecular film. This sequence pattern is formed by spontaneous assembly (self-assembly) of lipid molecules, and the self-assembly structure is a water- soluble compound in water.
(Substrate molecule) . Therefore, in the method of the present invention, it is not necessary to use an external device such as a photomask or a probe of a probe microscope, and the resolution is not necessarily limited by the structural accuracy of those devices. This method using only the interaction between molecules such as self-organization and molecular recognition essentially provides a resolution at the molecular level.

In addition, a plurality of functional groups capable of interacting with lipid
There are endless water-soluble compounds , and various molecular patterns can be constructed by appropriately selecting a combination with a lipid . In addition, lipids and such water-soluble compounds
The binding form of the substance is not limited to 1: 1 but can be a combination such as 2: 1 or 3: 1. Therefore, by changing the lipid composition of the mixed monolayer, one lipid and the above-mentioned water-soluble
Various molecular patterns can be created only by changing the composition from the combination of compounds (substrate molecules) . Alternatively, the molecular pattern can also be changed by adding unrecognizable lipid molecules to these systems.

The lipid molecule generally comprises a hydrophilic head having a functional group and a water-insoluble hydrophobic part. Although it is the functional group of the hydrophilic head that directly interacts with the substrate molecule in water, the packing of the hydrophobic part also greatly affects the self-organization of the molecule. Synthetic methods of lipid molecules combining various hydrophilic heads and hydrophobic parts have been established, and by chemically synthesizing new lipid molecules, it is possible to create new molecular patterns corresponding to them.

The method of the present invention is based on the property that molecules form an ordered structure spontaneously, so that under one condition, one molecular pattern can be obtained in an infinite number of large areas. On the other hand, even if it is possible to perform fine processing at the molecular level by a method such as using a probe of a probe microscope as in the past, the method of making patterns one by one by an external operation is as described above. It takes enormous effort to form a large number of patterns.

More specifically, the synthetic lipid capable of forming a monomolecular film used in the present invention includes hydrophobic chains having excellent orientation and sufficient water insolubility, for example, monoalkyl and dialkyl. Molecules that have long chains or alkyl long chains containing rigid segments such as azobenzene, and have ionic, hydrogen, coordination bond and moderate hydrophilicity such as guanidinium, diaminotriazine, orotic acid, etc. .

Specifically, compounds having structures represented by the following formulas (a) to (f) are mentioned as examples.

[0018]

Embedded image

However, in the formula (b), preferably n
Is 14, 18, and m is 1, 4, and in (f), preferably n is 14, 16, and m is 2, 6, 10. In addition, those having a functional group having an ionic bond, a hydrogen bond, and a coordination bond function on the hydrophilic head and having a hydrophobic structure similar to those of the above (a) to (f) are generally used. It can be used in the method of the invention. Further, many non-recognizable lipids such as methyl stearate and stearyl alcohol can be used as the lipid molecules for diluting these lipid monolayers.

Examples of the water-soluble substrate that interacts with these lipids include a water-soluble phosphate compound, a water-soluble carboxylic acid compound, and a water-soluble carboxylic acid compound capable of binding complementarily to (a) to (c).
Adenine, adenosine, which complementarily binds to (d),
Molecules having sites such as flavin, thymine, thymidine, and cadmium ion capable of complementary binding to (e), such as adenosine triphosphate (ATP) and adenosine; Diphosphate (AD
P), adenosine-phosphate (AMP), flavin mononucleotide (FMN), flavin adenine dinucleotide (FAD) and the like. In addition, a plurality of (a) to
(C) Polyfunctional phosphoric acid compounds and carboxylic acid compounds capable of binding simultaneously with the molecules are also used. Generally, any compound that forms a complementary bond with the hydrophilic head of the corresponding lipid molecule can be applied to the method of the present invention.

The method for creating a two-dimensional molecular pattern is basically based on the LB method, for example, “New Experimental Chemistry Course 18 Interfaces and Colloids, Chapter 6, Thin Film” (October 2, 1977)
On March 0, published by Maruzen Co., Ltd., written by Kiyonari Fukuda and Yoshio Ishino), it is possible to follow a common law as described in detail. In the present invention, a stock solution is first prepared in which lipid molecules are dissolved in an organic solvent such as benzene or chloroform. In this case, if the solubility of the lipid is not high, a small amount of a polar solvent such as ethanol or dimethyl sulfoxide is added as necessary. When preparing a mixed monomolecular film, these stock solutions are mixed at an appropriate ratio to prepare a solution having an arbitrary composition.

Next, about 1 L of a solution prepared by dissolving a water-soluble substrate in ultrapure water at an appropriate concentration (0.001 to 10 mM) is prepared, and the solution is filled in the LB trough. LB trough temperature is 2
The temperature was controlled at 0.0 ± 0.2 ° C. After spreading an appropriate amount of the lipid solution on the aqueous solution and leaving it for an appropriate time, the monomolecular film is slowly compressed to a predetermined surface pressure. Then, after the relaxation behavior of the monolayer reaches equilibrium and the monolayer becomes stable, the solid substrate previously immersed in the aqueous phase is slowly pulled up, and the patterned monolayer is fixed on the substrate. Become As the solid substrate, a cleavage surface of a mica plate (about 10 × 15 mm) which is smooth at a molecular level is used. In addition, a smooth surface such as a silicon wafer or graphite can be used as the substrate.

Next, the present invention as described above will be described in more detail with reference to examples.

[0024]

EXAMPLES Examples 1 to 7 Mixed monomolecular films of various lipids (a), (d) and (e) described above were prepared on a substrate solution such as FAD, ADP, and FMN, and then formed on a solid substrate. Then, elemental analysis was performed by X-ray photoelectron spectroscopy to confirm the binding of the substrate molecule to the monomolecular film as shown in Table 1 below. FIG. 1 illustrates the binding mode between the lipid molecule and the substrate molecule.

[0025]

[Table 1]

From Table 1, it can be seen that the amount of substrate binding varies depending on the type of monolayer, the type and concentration of the substrate. For example, an ADP that binds to three lipids a, d, and e, such as FAD, binds well to a lipid monolayer even at a low concentration (Example 2) and can bind only to two lipids.
FMN has a slightly lower binding amount at low concentration (Example 4
And 6). Alternatively, even when FAD is used, no binding is observed at a low concentration when a monomolecular film of a single component is used (Example 3). This indicates that the binding of the substrate molecule occurs effectively only when multiple types of binding points are formed at the same time. Conversely, for example, when FAD is used as a template substrate, a complex in which all three lipids are simultaneously bound to FAD is formed preferentially over a complex in which lipids are partially bound. I understand.

That is, this result indicates that when a substrate molecule such as FAD that can bind to a plurality of lipids is used, the binding of the lipid molecule occurs selectively using the substrate molecule as a template to form a molecular pattern. Means that. On the other hand, even with a substrate such as FMN having a small number of binding points, an extremely high binding rate can be obtained when used at a high concentration (Example 5). This indicates that a substrate solution having a relatively high concentration may be used as an aqueous phase in order to form a molecular pattern using a substrate having a small number of bonding points as a template.

These results indicate that the mode of complex formation between the lipid and the substrate is controlled by the combination of the lipid and the substrate and the concentration conditions, and a molecular pattern corresponding to the mode is obtained. Further, as Example 7, d / e / f
(1/1/1; f = n = 16, m = 6) mixed monomolecular film was formed on an aqueous phase containing 0.1 mM FAD and 1 mM CdCl _2, and the X-ray of the film was transferred to a solid substrate. Photoelectron spectroscopy was performed. As a result, the same F
The amount of Cd almost equivalent to the amount of AD binding was detected in the membrane. This indicates that (f) and FAD are bound via Cd ²⁺ , and that a molecular pattern is also formed by coordination bond. Examples 8 to 19 The surface pressure-area curve behavior of a mixed monolayer with lipid molecule a was studied on a 0.01 mM FAD aqueous solution. Examples 8 to 1
Table 2 shows the lipid composition of No. 7. FIG. 2 shows surface pressure-area curves of Examples 8, 10, 12, 13, 16, and 17 among these. FIG. 3 shows the deviation of the area occupied by these monomolecular films from the ideal state. In this graph, at a high surface pressure, when the mixing ratio of a and d is 2: 1, the deviation from the ideal state is maximum, and it is shown that two molecules a and one d molecule interact with one FAD molecule. Have been.

[0029]

[Table 2]

Further, as Embodiments 18 and 19, Embodiment 1
1: 1 and 1: 2 (a ₂ de: methyl stearate) of methyl stearate having no molecular recognition in a monolayer of
To prepare a diluted monomolecular film. Elemental analysis by X-ray photoelectron spectroscopy revealed FA corresponding to the degree of dilution.
The D-binding amount and lipid composition were confirmed. These two examples show that various molecular patterns can be obtained not only by combining lipids with molecular recognition but also by adding lipids without molecular recognition. Examples 20 to 22 As Example 20, the monomolecular film of Example 17 was placed on a mica plate, and an atomic force microscope image was examined (FIG. 4). As Example 21, an atomic force microscope image of the monomolecular film of Example 13 placed on a mica plate was examined (FIG. 5). As Example 22, an atomic force microscope image of a monomolecular film having the same composition as that of Example 12 transferred from pure water containing no FAD onto a mica plate was examined (FIG. 6).

By comparing FIG. 4 with FIG. 5, it can be seen that the molecular arrangement in the monolayer differs depending on the lipid composition. That is, the lipid is hexagonal in the monomolecular film of d alone, but the monomolecular film in which a and d are mixed at a ratio of 1: 1: has a different ordered structure from these. In addition, the intermolecular distance between the two is also different. This is because FAD is weakly bound to a monolayer of d alone, whereas a and d are 1: 1.
This indicates that FAD binding occurs effectively to the monomolecular film mixed in the above, and as a result, a different molecular pattern is formed.

The fact that this molecular pattern is controlled by FAD binding becomes clear by comparing FIG. 5 and FIG. That is, in FIG. 6 where FAD is not bound, the molecular image is not clear and the ordered structure is not clear, whereas in FIG. 5 where FAD is bound, a more clear and clear molecular pattern is formed in the molecular image. You can see that it is. These examples show that the specific arrangement of lipid molecules with the substrate molecules in the aqueous phase and the mixed composition of lipids control the molecular arrangement pattern in a two-dimensional plane (two-dimensional molecular pattern). is there. Examples 23 to 25 As Example 23, the same monomolecular film as in Example 22 was used for 5 ×.
The molecular image was observed in a narrow area of 5 nm ² (FIG. 7).
Further, as Examples 24 and 25, a profile (cross-sectional view) in the height direction was scanned along a constant straight line with the molecular image of the example (FIGS. 8 and 9).

As can be seen from FIG. 7, a regular molecular arrangement, that is, a so-called molecular pattern is obtained at a resolution of 5 × 5 nm ^{2 at} the molecular level. In the cross-sectional view of FIG. 8, four peaks are observed, which indicate the regular arrangement of the four alkyl chains of the d2 molecule. FIG. 9 is a cross-sectional view along a vertical straight line in FIG. 8, but high peaks and low peaks are alternately seen. The high peak corresponds to the d molecule having a long molecular length, and the low portion corresponds to the a molecule having a short molecular length. It can be seen from these height profiles (cross-sectional views) that a regular molecular pattern is obtained.

[0034]

As described in detail above, in the present invention, the specific interaction between a water-soluble substrate and a lipid monolayer is utilized to obtain a molecular arrangement pattern of lipids in the monolayer. Can be controlled. Therefore, by applying the method of the present invention to various combinations of lipids and substrates, it is possible to form a molecular pattern designed in advance. Furthermore, by combining this method with the LB method which is excellent in controlling the structure in the thickness direction, it is possible to obtain an ultrathin film whose structure is three-dimensionally controlled at the molecular level. The two-dimensional and three-dimensional molecular patterns created in this way are useful as a unit of a molecular element, and the method of the present invention is a basic technology in the development of various devices capable of writing information at an extremely high density. Becomes

[Brief description of the drawings]

FIG. 1 is a conceptual diagram showing an example of the form of interaction between a lipid and a substrate used in the present invention.

FIG. 2 is a diagram showing a surface pressure-area curve of the monomolecular films of Examples 8, 10, 12, 13, 16, and 17.

FIG. 3 is a diagram showing a deviation from an ideal state of an area occupied by the monomolecular films of Examples 8 to 17.

FIG. 4 is a photograph instead of a drawing showing an atomic force microscope image of the monomolecular film of Example 20.

FIG. 5 is a photograph instead of a drawing showing an atomic force microscope image of the monomolecular film of Example 21.

FIG. 6 is a photograph instead of a drawing showing an atomic force microscope image of the monomolecular film of Example 22.

FIG. 7 is a photograph instead of a drawing showing an atomic force microscope image of the monomolecular film of Example 23.

FIG. 8 is a photograph replacing a drawing showing an atomic force microscope image (cross-sectional view) of the monomolecular film of Example 24.

FIG. 9 is a photograph replacing a drawing showing an atomic force microscope image (cross-sectional view) of the monomolecular film of Example 25.

──────────────────────────────────────────────────の Continued on the front page (51) Int.Cl. ⁷ Identification code FI G11B 7/24 G11B 7/24 H01L 21/027 H05K 3/10 H05K 3/10 H01L 21/30 564Z (72) Inventor Yuji Oishi Ark Heights Ohori 604, 1-1-13 Imagawa, Chuo-ku, Fukuoka City, Fukuoka Prefecture (56) Reference JP-A-2-3035 (JP, A) JP-A-3-246300 (JP, A) JP-A-63-54399 JP-A-63-54400 (JP, A) JP-A-2-238029 (JP, A) JP-A-5-275831 (JP, A) JP-A-5-310679 (JP, A) Kaihei 5-310960 (JP, A) (58) Fields investigated (Int. Cl. ⁷ , DB name) G03F 7/004 C07C 279/00 C07K 17/00 C08J 5/18 G03F 7/16 G11B 7/24 H01L 21/027 H05K 3/10

Claims (7)

(57) [Claims] (1) a plurality of functional groups capable of interacting with a lipid molecule;
Each of the water-soluble compounds is placed on an aqueous solution of a water-soluble compound having a species.
Multiple lipid molecules that interact with different functional groups
By doing, the aggregation of lipid molecules in a two-dimensional plane on the water surface
A method for forming a two-dimensional molecular pattern, characterized in that a state is controlled to form a pattern. 2. The method according to claim 1, wherein the lipid molecule has orientation and hydrophobicity.
Ionic, hydrogen, or coordination bonds
It is characterized by consisting of a group having binding ability and hydrophilicity
The method for creating a two-dimensional molecular pattern according to claim 1. 3. The method according to claim 1, wherein the lipid molecule is represented by the following chemical formula (1) : (However, in the compound (b), n is 14 or 1
8, m in 1 or 4, of compound (f), n is 1
4 or 16, m represents 2, 6, or 10)
Shown compounds (a), (b), (c), (d),
The method is selected from (e) and (f).
How to create a two-dimensional molecular pattern of either 1 or 2
Law. 4. The method according to claim 1, wherein the functional group capable of interacting with the lipid molecule is water.
Soluble phosphoric acid compound, polyfunctional phosphoric acid compound, water-soluble
Bonic acid compounds, polyfunctional carboxylic acid compounds, nucleotides
Selected from the group consisting of
The creation of the two-dimensional molecular pattern according to claim 1.
Method. 5. A plurality of functional groups capable of interacting with a lipid molecule.
Is a water-soluble compound having adenosine triphosphate (AD
P), adenosine diphosphate (ADP), adenosine monophosphate
(AMP), flavin mononucleotide (FMN), and
From the group consisting of rabin adenine dinucleotide (FAD)
The two-dimensional molecular pattern according to any one of claims 1 to 4, which is selected.
How to create a turn. 6. The method according to claim 1, wherein
Transfer the formed two-dimensional molecular pattern onto a solid substrate
And a method for producing an immobilized two-dimensional molecular pattern. 7. The method according to any one of claims 1 to 5,
Dilute the formed two-dimensional molecular pattern with non-binding lipids
A method for creating a two-dimensional molecular pattern.