WO2006028123A1

WO2006028123A1 - Process for producing polymer crystal and polymer crystal growing apparatus

Info

Publication number: WO2006028123A1
Application number: PCT/JP2005/016405
Authority: WO
Inventors: Hiroaki Adachi; Hiroshi Kitano
Original assignee: Sasaki, Takatomo; Mori, Yusuke; Takano, Kazufumi; Inoue, Tsuyoshi; Matsumura, Hiroyoshi; Murakami, Satoshi; Nikon Corporation
Priority date: 2004-09-08
Filing date: 2005-09-07
Publication date: 2006-03-16
Also published as: JP2006076820A

Abstract

A process for producing a large single crystal of polymer free of defectives. A single crystal of hen eggwhite lysozyme is grown in a culture medium (a). Part of this single crystal is exposed to solid ultraviolet short-pulse laser beams of 193 nm wavelength to thereby remove any ablation (b). Upon re-initiation of incubation, crystal re-growth from a worked surface as a starting point has been effected to thereby enable obtaining of a large crystal (c).

Description

Specification

Polymer crystal production method and polymer crystal growth apparatus

Technical field

[0001] The present invention relates to a method for producing a polymer crystal and a polymer crystal growing apparatus used therefor, and more specifically, by processing an unnecessary portion in a polymer crystal growing process, The present invention relates to a large-sized high-quality polymer crystal, a method for producing a polymer crystal in which a substance other than the polymer crystal is inserted into the crystal, and a polymer crystal growing apparatus used therefor.

Background art

[0002] In recent years, post-genome research called proteome has become popular. Of particular note is research that seeks to unravel the three-dimensional structure of proteins, which is called structural genomics. Protein structure and function analysis is an important research field in life science, and it is indispensable to elaborate on detailed three-dimensional structures in order to be directly linked to disease treatment and drug discovery. One of the main means is X-ray crystal structure analysis. In order to apply X-ray crystal structure analysis, it is necessary to crystallize the polymer substance to be analyzed.

[0003] In the growth of polymer crystals, crystals with shapes reflecting the molecular structure and growth conditions are grown in the same manner as the growth of inorganic crystals and organic low-molecular crystals. In addition, many polymer substances have established crystallization conditions and growth conditions for obtaining high-quality single crystals, and therefore, it is very difficult to control crystal precipitation and subsequent growth control. For this reason, there are many problems such as problems in crystal quality, and crystals deposited in close proximity to each other and polycrystallize.

[0004] For example, when X-ray crystal structure analysis is performed, a single crystal having a desired shape and high quality is required. For this reason, it is common to optimize the crystallization and growth conditions to obtain the crystal. However, as described above, it is very difficult to obtain these crystals for polymer substances. Therefore, from the obtained crystal, the size and shape necessary for X-ray crystal structure analysis, or a portion with good crystal quality can be taken out, or a single crystal can be obtained from a polycrystal. There are cases where processing such as cutting out is performed.

[0005] However, polymer crystals are often much softer and more brittle than crystals of, for example, inorganic substances and organic low-molecular substances. Therefore, if a large impact is applied during processing, cracks and cracks may occur in the periphery. Cause damage. In addition, it is known that it is sensitive to temperature changes and easily denatures by applying heat.

[0006] As described above, since polymer crystals are very difficult to handle, it is extremely difficult to directly apply the processing techniques that are widely used in inorganic crystals and other materials, and reliable crystal processing. There was no technology established.

[0007] A conventionally used processing technique for polymer crystals is a processing technique that requires mechanical contact with the crystal using a knife or a needle. This method is artificially observed under observation with a microscope or the like, and is mainly used for cutting polymer crystals.

Disclosure of the invention

Problems to be solved by the invention

[0008] However, in the case of processing with a scalpel or a needle that is mechanically fragile compared to a general crystal, the polymer crystal has a cutting surface that is sheared by the shearing force that is applied to the polymer crystal. There is a possibility of collapse. Therefore, the polymer crystal processing method currently used has many elements left to luck, and is a processing method with low success probability and low reproducibility, even for those who have craftsmanship. Furthermore, this method is capable of performing relatively simple processing such as crystal cutting, and it is very difficult to adapt when complicated and precise processing is required.

[0009] As a method for solving such a problem, the present inventors have performed an invention whose main point is to perform processing such as removing unnecessary portions of the polymer crystal by irradiation with ultraviolet short pulse laser light. The present invention has been filed as Japanese Patent Application Nos. 2003-32090, 2004-19516, and 2004-137991 (referred to as “prior invention”).

[0010] According to the invention of the prior application, it has been difficult to process a polymer single crystal without damaging the crystal structure in the prior art, without damaging the crystal structure. It became possible to remove unnecessary parts and observe the remaining parts by X-ray diffraction.

[0011] However, when the invention of the prior application is used, an unnecessary portion of the polymer crystal is processed. Therefore, for example, when there are many unnecessary portions of the polymer crystal, there is a problem that the size of the obtained normal polymer crystal becomes too small.

[0012] In addition, in order to evaluate the physical properties of a crystal, a probe or the like that requires physical contact with the crystal may be inserted into the crystal. However, as described above, a polymer crystal is brittle and soft. Techniques have made it difficult to insert such probes into the crystal.

[0013] The present invention has been made in view of such circumstances, and solves the problems of the prior application invention, a method for producing a high-quality and large polymer crystal, and a substance other than the polymer in the crystal. It is an object of the present invention to provide a method for producing a polymer crystal inserted in a polymer crystal and a polymer crystal growth apparatus used therefor.

Means for solving the problem

[0014] The first means for solving the above problem is that in the process of producing the polymer crystal, during the growth of the polymer crystal or once the growth of the polymer crystal is stopped, the polymer crystal Among these, an unnecessary portion is processed by irradiation with ultraviolet short pulse laser light, and thereafter grown, (claim 1).

Currently, laser light is widely used as a processing tool. However, the processing with carbon dioxide laser (wavelength 10.6 μm) and YAG laser (wavelength 1.06 μm), which are widely used, is thermal processing, and the temperature of the material to be processed increases when irradiated with laser light. . Furthermore, it is desirable that the laser light applied to the material to be processed is pulsed light that is not continuous light. This is because laser processing using continuous light generates far greater heat than processing using pulsed light. Therefore, for polymer crystals that must avoid thermal denaturation, these laser processing using infrared light or visible light laser, and laser processing using continuous light are not suitable.

[0016] Therefore, the inventors paid attention to the ultraviolet short pulse laser. In other words, ultraviolet short pulse laser light can be processed to directly cut the chemical bonds of polymer crystals with high photon energy due to its short wavelength. This processing can achieve high-precision and smooth processing that is far less affected by heat than processing using a normal carbon dioxide laser or YAG laser.

[0017] There are CN bonds and CC bonds in the main chain of the polymer. Nerghi is about 70 kcal / mol and the CC bond has a bond energy of about 84 kJ / mol.For example, an ultraviolet short pulse laser beam with a wavelength of 300 nm corresponds to a photon energy of about 95 kcal / mol. The bond can be broken.

[0018] Since the processing by irradiation with ultraviolet short pulse laser light basically cuts molecular bonds with photon energy and evaporates, no shear force acts on the cut surface during processing. This excellent property makes it possible to process a very fragile material called a polymer crystal without breaking it and to obtain a clean surface. In other words, processing using an ultraviolet short pulse laser is particularly effective when a high molecular crystal is brittle with a mechanical processing method that may damage the processed surface.

When this means is used, for example, when it is found that a part of the crystal is damaged or polycrystallized during the growth of the polymer single crystal, an unnecessary part of the crystal to be grown is obtained. By processing the portion, it is possible to suppress the growth of those unnecessary portions, so that it is possible to efficiently produce a large-sized polymer single crystal of high quality. The processing of the unnecessary portion is performed in the process of producing the polymer crystal. However, the method of processing the unnecessary portion during the growth of the polymer crystal, that is, the growth is continued, and the growth is stopped. There is a method of processing unnecessary portions and then restarting the growth, and a preferable method can be selected as appropriate.

[0020] The processed crystal can be grown by controlling the external environment such as temperature change, solvent evaporation, pressure change, concentration change, pH change, impurity change and the like.

[0021] A second means for solving the above problem is the first means, wherein the unnecessary portion is processed by removing an unnecessary portion using laser ablation with an ultraviolet short pulse laser beam. (Claim 2).

[0022] As the processing of the unnecessary portion of the polymer crystal by the ultraviolet short pulse laser beam, the unnecessary portion can be removed, modified, refined, etc. By removing the unnecessary portion using laser ablation, Processing surface force Crystal growth becomes easy. In this method, unnecessary parts are removed using an ultraviolet short pulse laser, so even if the processed surface is damaged, the degree of damage is small. Crystal grows. [0023] A third means for solving the above problem is the second means, wherein after removing the unnecessary part, a substance other than the polymer crystal is applied to at least a part of the removed part. It is characterized by being inserted (claim 3).

[0024] Since a polymer crystal is brittle and soft, when a substance is inserted into the crystal, breakage such as cleavage occurs due to stress generated when the substance comes into physical contact with the crystal. In this means, stress applied to the crystal at the time of insertion can be prevented by removing unnecessary portions by irradiation with an ultraviolet short pulse laser and inserting a substance into the removed region. In addition, if the crystal is grown after insertion, the crystal can continue to grow until it comes into contact with the inserted material, so inserts that require physical contact with the crystal are inserted into the polymer crystal with low damage. It becomes possible.

[0025] A fourth means for solving the above problem is any one of the first means to the third means, and the processing of the unnecessary portion is performed on the surface of the polymer crystal by ultraviolet short. It is performed by performing an operation for efficiently reaching the pulsed laser beam and then irradiating the surface of the polymer crystal with an ultraviolet short pulse laser beam (claims).

4).

[0026] Many growth solutions generally do not transmit ultraviolet light. Therefore, in this means, before the unnecessary portion is processed during the growth of the polymer crystal, an operation for efficiently reaching the ultraviolet short pulse laser beam on the surface of the polymer crystal is performed. In addition, irradiation with ultraviolet short pulse laser light is performed. Therefore, the growth solution must not transmit ultraviolet light.

Even if it is V, it can process unwanted parts.

[0027] As an operation for efficiently reaching the surface of the polymer crystal with the ultraviolet short pulse laser light, the growth solution is removed to expose the surface of the polymer crystal, or the growth solution is efficiently transmitted with ultraviolet rays. The polymer crystal is moved to expose the crystal surface, and ultraviolet short pulse laser light is propagated using a light guide such as an optical fiber, and its tip is placed near the polymer crystal surface. However, it is not limited to this.

[0028] The fifth means for solving the above-mentioned problems is any one of the first to fourth means, wherein the polymer crystal comprises rosin, protein, saccharide, lipid and Out of nucleic acids , Characterized in that it is at least one crystal (Claim 5).

[0029] Many of these polymer crystals having material strengths are particularly susceptible to destruction even when subjected to a fragile little shearing force. Therefore, the application of the first to fourth means is a particularly effective material.

[0030] A sixth means for solving the above problem is any one of the first to fifth means, wherein the wavelength of the ultraviolet short pulse laser beam is 400 nm or less. This is a feature (claim 6).

[0031] Since there are many CN bonds in the polymer crystal, in such a case, in order to cut the CN bond reliably, the wavelength of the irradiated ultraviolet short pulse laser light is 400 nm or less. Preferably there is. Further, considering that the C—C bond is surely broken, the wavelength is preferably 340 ηm or less. In terms of energy, it is not necessary to specifically limit the lower limit of the wavelength of the ultraviolet short pulse laser beam. In addition, currently available optical elements do not transmit light having a wavelength of less than 150 nm, so it is preferable to use ultraviolet short pulse laser light having a wavelength of 150 nm or more.

[0032] A seventh means for solving the above problem is any one of the first means to the sixth means, wherein an energy density per pulse of the ultraviolet short pulse laser beam is lmj / cm ² or more (Claim 7).

In the processing process using ultraviolet short pulse laser light, the cache characteristics are greatly influenced by the energy density (fluence) per pulse of ultraviolet short pulse laser light to be irradiated. Generally, the processing amount (force rate) per pulse of ultraviolet short pulse laser light does not show linearity with respect to fluence. If the fluence is too small, even if the chemical bond is broken, the subsequent transpiration becomes insufficient and the processing cannot be performed. In other words, a fluence above a certain threshold is required to cause machining. For fluences above the threshold, the processing rate increases as the fluence increases.

. Therefore, in order to obtain good cache characteristics, the fluence of the ultraviolet short pulse laser beam to be irradiated must be adjusted appropriately.

[0034] The preferred fluence depends on the absorption coefficient of the work material with respect to the irradiation light. The The larger the absorption coefficient, the more photons are absorbed per unit volume and the chemical bonds are efficiently broken, so the fluence value that is the threshold for processing becomes smaller. Since the absorption coefficient of the polymer varies greatly depending on the wavelength in the ultraviolet region, the preferred fluence varies depending on the wavelength of the irradiation light. In the wavelength range below 400 nm, a fluence of lmj / cm ² or more can be used. By applying ultraviolet short pulse laser irradiation to the appropriate fluence described above, the surface force of the crystal can be affected over a range of depth of 1 or more per pulse of ultraviolet short pulse laser light. It is.

[0035] An eighth means for solving the above problems includes a growth container in which a growth solution is introduced to grow a polymer crystal, a stage on which the growth container is placed and movable in a three-dimensional direction, A solution injection and suction device for injecting or aspirating the growth solution into the growth vessel, and irradiation with ultraviolet short pulse laser light for processing polymer crystals in the growth vessel A polymer crystal growth apparatus, comprising: an ultraviolet irradiation apparatus that performs the observation; an observation apparatus that observes the polymer crystal in the growth container; and a constant temperature and humidity apparatus that maintains a constant temperature and humidity of the growth container. (Claim 8).

[0036] In this means, a high molecular crystal can be grown by putting a growth solution in a growth container and maintaining the temperature at a predetermined temperature. Then, the growing polymer crystal is observed with an observation device, and if an unnecessary portion is generated, the growth solution is sucked with a solution injection and suction device as necessary to expose the polymer crystal to the growing solution force. The polymer crystal is processed by the ultraviolet short pulse laser light emitted from the ultraviolet irradiation device to process unnecessary portions, and then the growth solution is injected into the growth container by the solution injection and suction device, and the polymer crystal is injected. You can continue to train. When observing and processing a sample, the stage can be moved in a three-dimensional direction to observe the polymer crystal in the field of view, and ultraviolet short pulse laser light can be applied to any part of the polymer crystal. Can be irradiated. The invention's effect

[0037] According to the present invention, there is provided a method for producing a large, high-quality polymer crystal, a method for producing a polymer crystal in which a substance other than the polymer crystal is inserted into the crystal, and a polymer crystal growing apparatus. Can be provided.

Brief Description of Drawings FIG. 1 is a diagram showing an outline of a polymer crystal growth apparatus as an example of an embodiment of the present invention.

FIG. 2 is a diagram showing an outline of an ultraviolet short pulse laser processing apparatus used in an example of the present invention.

FIG. 3 is a photomicrograph showing chicken egg white lysozyme crystals before ultraviolet irradiation, immediately after ultraviolet irradiation, and after regrowth.

Explanation of symbols

[0039] 1 constant temperature & humidity chamber, 2 stages, 3 growth vessel, 4 injection and suction device, 5 growth solution, 6 polymer crystal, 7 observation device, 8 beam splitter, 9 ultraviolet short pulse laser generator, 10 condensing Lens, 11 Cover, 21 Ultraviolet short pulse laser system, 22 Condensing optics, 23 Stage, 24 Polymer crystal, 25 Sample container, 26 Illumination light source, 27 Reflector, 28 Objective lens, 29 Eyepiece, 30 Eyes

BEST MODE FOR CARRYING OUT THE INVENTION

[0040] Hereinafter, an example of a polymer crystal growth apparatus according to an embodiment of the present invention will be described with reference to the drawings. FIG. 1 is a diagram showing an outline of a polymer crystal growth apparatus as an example of an embodiment of the present invention.

[0041] In the constant temperature '[· wet humidity tank 1, an x-y-z stage 2 is provided, on which a growth vessel 3 can be placed. By driving the x—y—z stage 2, the growth vessel 3 can be moved in the X direction (left and right direction on the paper), y direction (front side, depth direction), and z direction (up and down direction on the paper surface). , Rotation around the z axis is possible.

[0042] In addition, an injection / suction device 4 is provided so that the growth solution 5 can be injected into the growth container 3 or the growth solution 5 can be sucked from the growth container 3. . The polymer single crystal 6 is grown in the growth vessel 3.

[0043] The growing polymer single crystal 6 is observed through the beam splitter 8 by the observation device 7. Then, when the occurrence of unnecessary parts is observed, the injection and suction device 4 sucks the medium growth solution 5 of the growth vessel 3 to expose the polymer crystal 6 from the surface of the growth solution 5, and generates an ultraviolet short pulse laser. The apparatus 9 irradiates the ultraviolet short pulse laser beam, and the light is condensed on the polymer crystal 6 by the condenser lens 10, and an unnecessary portion of the polymer crystal 6 is processed. Ultraviolet short pulse laser The one light is reflected by the beam splitter 8 and focused on the polymer crystal 6.

[0044] After the unnecessary portion of the polymer crystal 6 is processed in this way, the growth solution 5 is injected from the injection suction device 4 into the growth vessel 3, and the polymer crystal 6 is again immersed in the growth solution 5. Start training.

[0045] When removing unnecessary portions of the polymer crystal 6, while observing the processed portion with the observation device 7, the stage 2 is driven to perform processing such as removal of the target portion. Note that the portion irradiated with ultraviolet rays may not be visible. For example, the optical axis of the observation device 7 is aligned with the portion where the ultraviolet rays are collected so that a virtual image of the mark can be formed at that position. By observing the virtual image of the mark superimposed on the polymer crystal 6, the position irradiated with ultraviolet rays can be observed. In addition, for the z-direction position, the position where the ultraviolet rays are collected and the position where the observation device 7 is in focus are matched, and the stage 2 is driven so that the processed part is in focus during the ultraviolet irradiation. By doing so, the ultraviolet rays can be condensed at the target position.

The reason why the growth container 3 is placed in the constant temperature & humidity chamber 1 is to minimize the influence of changes in temperature and humidity on the growth conditions of the polymer crystal. For example, a change in temperature is not preferable because the supersaturation degree of the solution changes. Also, since the inside of the growth container is covered with the cover 11, it is saturated, and if the outside of the container is dry, the evaporation amount of the growth solution 5 increases when the force bar 11 is removed during the processing operation. Absent.

[0047] As described above, the stage 2 is driven when the polymer crystal 6 is observed or processed. In addition, the stage 2 is grown by temporarily or intermittently moving during the growth of the polymer crystal 6. Solution 5 can be agitated to suppress unnecessary nucleation and to improve the quality of crystals.

[0048] Ultraviolet light is irradiated into the constant temperature and humidity chamber 1 through the window 12, and the window 12 is made of a material such as quartz or fluorite that has a high transmittance with respect to the ultraviolet light. In FIG. 1, ultraviolet rays are incident (vertical) irradiation, but oblique irradiation may be used, and an optical fiber may be used as a propagation path.

The injection / suction device 4 has a function of injecting the growth solution 5 into the growth container 3 and suctioning it from the growth container 3 as described above. Debris (scattered matter generated by laser abrasion) generated during processing of crystal 6 is removed by suction, Operations such as taking out and removing crystals that are no longer needed, operations such as transferring the processed polymer single crystal 6 to another growth vessel, and operations such as adding or replacing a solution can also be performed. The injection / suction device 4 has a position control mechanism (not shown), and can be positioned so that the tip thereof enters the growth container 3 and further the growth solution 5 as necessary.

[0050] The cover 11 may be one that manually closes the upper portion of the growth vessel 3, but may also have an automatic opening and closing mechanism. Further, even when the tip of the injection / suction device 4 is inserted into the growth vessel 3, it is connected to the tip of the injection / suction arch I device 4 by means of, for example, a bellows mechanism so as to maintain hermeticity. Have you been?

In FIG. 1, the illuminating device of the observation device 7 is omitted, but a device as shown in FIG. 2 shown later can be used.

Example

[0052] In order to investigate the basic characteristics of crystal growth according to the present invention, a protein single crystal was irradiated with an ultraviolet short pulse laser beam using an apparatus as shown in Fig. 2, thereby A portion of the abrasion was removed. The laser-processed crystal was regrown and the X-ray diffraction pattern was measured on the grown crystal.

In this apparatus, the ultraviolet short pulse laser beam from the ultraviolet short pulse laser system 21 is condensed at a predetermined point via the condensing optical system 22. The stage 23 can move in the three-dimensional directions of the X, y, and z axes in the X-y-z Cartesian coordinate system with the optical axis direction of the optical microscope shown below as the z axis, and the z axis It can be rotated around. A sample container 25 containing polymer crystals 24 is placed on the stage 23. Visible light from the illumination light source 26 is reflected by the reflecting mirror 27, and the sample container 25 is Koehler illuminated. The polymer crystal 24 is visually observed by the eye 30 through the objective lens 28 and the eyepiece lens 29 of the optical microscope.

[0054] A cross-shaped mark is formed at the optical axis position of the optical microscope so that the optical axis position is visible. The focus position of the optical microscope (the in-focus position, that is, the object surface that is in focus when viewed) is fixed. The ultraviolet short pulse laser beam condensed by the condensing optical system 22 is collected at the optical axis position of the optical microscope and at the focal position of the optical microscope. Therefore, when the object is placed on the stage 23 and the image is observed with an optical microscope, it is in focus and at the center of the cross mark. The ultraviolet short pulse laser beam from the ultraviolet short pulse laser system 21 is condensed. The relative positional relationship of the ultraviolet short pulse laser system 21, the condensing optical system 22, and the optical microscope section is fixed, and only the stage 23 is movable relative to these fixed systems. The

[0055] Therefore, the processing is performed !, and the processing is performed while moving the stage 23 so that the location is the optical axis position of the optical microscope and the in-focus position. Shape processing can be performed.

[0056] As a model macromolecule, protein-amber chicken egg white lysozyme was selected, and a single crystal of this protein was grown in a sample container by vapor diffusion. The crystal growth solution was re-purified 6 times.-After preparing a 25 mg / ml solution of egg white egg lysozyme sample, 0.1 mg acetic acid sodium was adjusted to a concentration of 80 mg / ml in 0.1 M acetic acid buffer solution adjusted to pH 4.5 A solution of 5 1 was used, which was prepared by mixing the prepared solution at a ratio of 1: 1. As an external solution, 400 μl of a solution adjusted to 80 mg / ml sodium chloride was added to 0.1 M acetic acid buffer solution adjusted to pH 4.5.

[0057] When this sample container was allowed to stand at a constant temperature of 20 ° C for 20 hours, the size was about 0.1 mm X 0.

A 2mm x 0.03mm-bird hen egg white lysozyme single crystal was grown. Laser processing was performed on this growing crystal. A part of the growth solution in which the crystals were present was removed, and the crystal was sealed with quartz glass in a state where droplets of the growth solution were left in the vicinity of the crystals so that the crystals were not denatured by drying. Fig. 3 (a) shows a crystal photograph before irradiation with ultraviolet short pulse laser light.

As the ultraviolet short pulse laser system 21, a solid ultraviolet short pulse laser light source having a wavelength of 193 nm was used. The configuration of the light source is as follows. Directly modulate the vertical and horizontal single mode laser diodes to generate pulsed light with a wavelength of 1547 nm and a repetition rate of 1 kHz. This pulse light is amplified approximately 2 million times by a total of three stages of erbium-doped fiber amplifiers connected in series. Next, the output light with fiber amplifier power is converted to the 8th harmonic by a five-step wavelength conversion process using a nonlinear optical crystal, and light with a wavelength of 193 nm is generated.

[0059] The ultraviolet short pulse laser light emitted from the ultraviolet short pulse laser system 21 is passed through a shirt and then condensed by a synthetic quartz lens having a focal length of 100 mm, which is a condensing optical system 22. Thus, irradiation was performed in the Z-axis direction from the upper surface of the sample container 25 containing the egg white lysozyme crystal (polymer crystal) 24 placed on the stage 23. The irradiation position on the crystal was finely adjusted while observing with an optical microscope. The pulse energy of the irradiated light on the crystal was 0.25 μJ, the spot diameter was 25 μm, the fluence was 50 mJ / cm ² , the average intensity was 0.25 mW, and the pulse duration was Ins.

[0060] The spot position on the crystal was changed by reciprocating the stage 23 linearly in the XY plane at a moving speed of 0.5 mm / sec. Since the above-described reciprocating operation was continuously performed, the same location was irradiated with ultraviolet short pulse laser light a plurality of times. Irradiation was continued while observing the state of processing with a microscope, and a portion of the above-mentioned chicken hen egg white lysozyme crystal was removed by irradiation with a total of about 20,000 pulses. The total volume of crystals excised by this irradiation was about 3 X 10 ^_4 mm ³ . Figure 3 (b) shows a stereomicrograph of the eggplant lysozyme crystal immediately after processing by ultraviolet short pulse laser irradiation. It was confirmed that laser processing could be performed without causing mechanical damage such as cracks to the unirradiated site.

[0061] The growth solution removed immediately after the completion of laser processing was returned to resume the growth. When the sample container was allowed to stand at a constant temperature of 20 ° C, it was confirmed that the laser-processed crystal became a seed crystal and the crystal grew again. Figure 3 (c) shows a crystal photograph after 24 hours of laser processing. The size of the laser-processed eggplant lysozyme crystal was about 0.3 mm x 0.4 mm x 0.1 mm. Even if there was a deviation between the surface that was not laser-processed and the surface that was laser-processed, it was possible to grow crystals. Furthermore, when the growth was observed after standing at 20 ° C, the crystal growth was completed when it finally reached a size of about 0.35 mm × 0.45 mm × 0.12 mm.

[0062] X-ray diffraction patterns were measured at room temperature for egg white lysozyme crystals regrown after laser processing and egg white lysozyme crystals grown under the same conditions. Rigaku Denki ultraX18 (voltage 50kV, current 100mA) was used as the X-ray generator, and RAXI S IV ++ was used as the detector. The distance between the crystal and the detector was 150 mm, the detection angle was 2 °, and the measurement time was 30 minutes / 2 °.

[0063] 45 frames of data were collected for each crystal. The diffraction resolution of the laser-carrying crystal was 0.19 nm, which was the same as the diffraction resolution of the powerless crystal. Also, all Only the diffraction pattern from one single crystal was measured. From these results, it was found that the regrown egg white lysozyme crystals after processing the laser were single crystals. Furthermore, the crystal irradiance of the laser irradiated laser was 0.300, and it was confirmed that no significant crystal quality degradation was caused by the laser beam.

[0064] In this example, the portion where the abrasion is removed is a normal crystal part. From this example, when there is a defective part such as a damage, the defective part is removed by processing including the normal part. It can be seen that large crystals with few defective parts can be grown by regrowth.

Industrial applicability

[0065] The present invention can be preferably applied to the production of polymer crystals. For example, biopolymer crystals such as protein crystals and other organic polymer crystals can be produced, and the use thereof is not limited.

Claims

The scope of the claims

[1] In the process of producing the polymer crystal, during the growth of the polymer crystal, or once the growth of the polymer crystal is stopped, unnecessary portions of the polymer crystal are irradiated with ultraviolet short pulse laser light. A method for producing a polymer crystal, comprising a process of processing and subsequent growth.

[2] The method for producing a polymer crystal according to [1], wherein the processing of the unnecessary portion is removal of the unnecessary portion using laser ablation with an ultraviolet short pulse laser beam.

[3] The method for producing a polymer crystal according to [2], wherein after removing the unnecessary portion, a substance other than the polymer crystal is inserted into at least a part of the removed portion.

[4] The processing of the unnecessary portion performs an operation for efficiently reaching the surface of the polymer crystal with ultraviolet short pulse laser light, and then irradiating the surface of the polymer crystal with ultraviolet short pulse laser light. The method for producing a polymer crystal according to any one of claims 1 to 3, wherein the polymer crystal is carried out by performing the step.

[5] The polymer crystal according to any one of claims 1 to 4, wherein the polymer crystal is at least one crystal selected from coconut resin, protein, saccharide, lipid, and nucleic acid. A method for producing a high molecular crystal.

[6] The method for producing a polymer crystal according to any one of [1] to [5], wherein the wavelength of the ultraviolet short pulse laser beam is 400 or less.

[7] The polymer crystal according to any one of claims 1 to 6, wherein an energy density per pulse of the ultraviolet short pulse laser beam is lmj / cm ² or more. Production method.

[8] A growth vessel in which a growth solution is put to grow a polymer crystal, a stage on which the growth vessel is placed and movable in a three-dimensional direction, and the growth solution is injected into the growth vessel before or after A solution injection and suction device for sucking from the growth vessel, an ultraviolet irradiation device for irradiating an ultraviolet short pulse laser beam for processing the polymer crystal in the growth vessel, and a high in the growth vessel. A polymer crystal growth apparatus comprising: an observation apparatus for observing a molecular crystal; and a constant temperature and humidity apparatus for maintaining a constant temperature and humidity of the growth vessel.