Single crystal X-ray structure analysis device and method, and sample holder assembly therefor

Abstract

Provided are a single crystal X-ray structure analysis device, a method therefor, and a sample holder assembly capable of reliably and easily performing single crystal X-ray structure analysis using a crystal sponge. The device comprises: a sample holder for holding a sample; a goniometer for mounting the sample holder and rotating it back and forth; an X-ray irradiation unit for irradiating the sample held in the sample holder 250 mounted on the goniometer with X-rays from an X-ray source; and the sample holder (250) is provided by being equipped with a detachable applicator, the sample holder (250) comprising a porous complex crystal capable of absorbing the sample in a plurality of micropores formed therein, and the applicator comprising a space for absorbing the sample in the porous complex crystal of the sample holder (250).

Description

Technical Field

[0001] The present invention relates to a next-generation single crystal X-ray structure analysis device and method capable of analyzing the structure of a material through its microscopic collective structure such as the arrangement of atoms and molecules, and in particular to a single crystal X-ray structure analysis device and method comprising an apparatus for performing a process for preparing a single crystal sample to be analyzed, and a sample holder assembly therefor. Background Art

[0002] In the research and development of new equipment and materials, material synthesis and evaluation are routinely performed, and the next research direction is determined based on the synthesis and evaluation. In the structural analysis of materials using X-ray diffraction for material development in a short period of time, in order to efficiently explore the material structure that achieves the function / physical properties of the target material, a material structure exploration method centered on the structural analysis of materials that can perform structural analysis efficiently and X-ray structural analysis used therein are required.

[0003] However, to perform structural analysis based on the results obtained using this method, an expert in X-rays is required. Therefore, an X-ray structural analysis system that can perform structural analysis even if one is not an expert in X-rays is required. Among them, single crystal X-ray structural analysis has attracted attention as a method that can obtain the three-dimensional structure of a molecule accurately and with high precision, as is also known in the following patent document 1.

[0004] On the other hand, in the single crystal X-ray structure analysis, there is a great restriction that the sample must be crystallized to prepare a single crystal. However, as also known in the following non-patent documents 1, 2 and patent document 2, by developing a material called "crystal sponge" (for example, a porous complex crystal with countless pores of 0.5nm to 1nm in diameter open), including liquid compounds that cannot be guaranteed not to be crystallized, and samples that cannot be guaranteed to be in an amount sufficient for crystallization, single crystal X-ray structure analysis can be widely applied.

[0005] Prior Art Literature

[0006] Patent Literature

[0007] Patent Document 1: Japanese Patent Application Publication No. 2007-3394

[0008] Patent Document 2: JP Re-Publication Patent No. WO2016 / 017770

[0009] Non-patent literature

[0010] Non-patent literature 1: Makoto Fujita; X-ray analysis on the nanogram to microgramscale using porous complexes; Nature 495, 461-466; 28 March 2013

[0011] Non-patent document 2: Hoshino et al. (2016), The updated crystalline sponge method IUCrJ, 3, 139-151 Summary of the invention

[0012] Problems to be solved by the invention

[0013] However, in the single crystal X-ray structure analysis which is a conventional technique using the above-mentioned crystal sponge, the following steps need to be performed quickly and accurately: a step of absorbing a very small amount of sample of about several ng to several μg separated by various devices into the skeleton of a very small and fragile crystal sponge of about 100 μm in size; and a step of taking out the very small crystal sponge absorbing the sample and installing it in a tool and placing it at the X-ray irradiation position in the single crystal X-ray structure analysis device, which is accompanied by fine and meticulous operations. In addition, these fine and meticulous operations performed in a short time have a great influence on the measurement results of the sample after absorption in the crystal sponge, and become very important operations.

[0014] Therefore, the present invention is completed in view of the above-mentioned problems in the prior art, and its purpose is to be able to quickly, reliably and easily perform single crystal X-ray structure analysis using extremely small and fragile crystal sponge even without professional knowledge of X-ray structure analysis and without the existing fine and meticulous operations that require speed. In other words, to provide a single crystal X-ray structure analysis device and method that has good yield and high efficiency, excellent versatility and user-friendliness. Furthermore, its purpose is to provide an instrument therefor, namely a sample holder assembly consisting of an applicator and a new sample holder.

[0015] Means for solving problems

[0016] (1) To achieve the above object, the present invention provides a single crystal X-ray structure analysis apparatus for performing structure analysis of a substance, characterized in that the apparatus comprises: an X-ray source for generating X-rays; a sample holder for holding a sample; a goniometer to which the sample holder is mounted and rotated; an X-ray irradiation unit for irradiating the sample held in the sample holder mounted on the goniometer with X-rays from the X-ray source; an X-ray detection and measurement unit for detecting and measuring X-rays diffracted or scattered by the sample; and a structure analysis unit for performing structure analysis of the sample based on the diffracted or scattered X-rays detected by the X-ray detection and measurement unit, wherein the sample holder is provided by being attached to a detachable applicator, the sample holder including a porous complex crystal capable of absorbing the sample in a plurality of fine pores formed therein, the applicator having a space for absorbing the sample in the porous complex crystal in the sample holder, and the sample holder is attached to a position of the goniometer to be irradiated with X-rays from the X-ray irradiation unit in a state in which the sample holder is detached from the applicator.

[0017] (2) In addition, the sample holder assembly of the present invention is used in a single crystal X-ray structure analysis device, and the sample holder assembly is characterized in that it comprises: a sample holder installed on a goniometer of the single crystal X-ray structure analysis device; and an applicator for storing the sample holder, the sample holder comprising: a holding portion for holding porous complex crystals capable of absorbing a sample in a plurality of fine pores formed inside, and the applicator comprising: a space for absorbing the sample in the porous complex crystals of the sample holder.

[0018] (3) Furthermore, in the sample holder assembly of the present invention, the applicator is characterized in that a sample introduction structure for introducing the sample into the space for absorption is formed.

[0019] (4) Furthermore, in the sample holder assembly of the present invention, the sample introduction structure formed in the applicator is a through hole.

[0020] (5) In addition, the single crystal X-ray structure analysis method of the present invention uses a sample holder to perform structural analysis of a substance, and the single crystal X-ray structure analysis method is characterized in that it includes the following steps: for the porous complex crystal including a porous complex crystal capable of absorbing the sample in a plurality of fine pores formed therein and the sample holder is accommodated in an applicator having a space for absorbing the sample, the sample is absorbed by introducing the sample while the sample holder is accommodated in the applicator; the sample holder is removed from the applicator; the sample holder is mounted on a goniometer of the single crystal X-ray structure analysis device; an X-ray detection and measurement step of irradiating X-rays from an X-ray source of the single crystal X-ray structure analysis device to the sample mounted on the goniometer, detecting and measuring X-rays diffracted or scattered by the sample; and performing structural analysis of the sample based on the diffracted or scattered X-rays detected by the X-ray detection and measurement step.

[0021] Effects of the Invention

[0022] According to the present invention described above, a single crystal X-ray structure analysis device is provided. By utilizing a sample holder assembly composed of a newly proposed applicator and a sample holder, a series of operations including the absorption of a sample into an extremely small and fragile crystal sponge and the subsequent loading into the device can be performed quickly, reliably and easily without the existing meticulous and fine operations that also require speed. In other words, the yield is good and efficient, and the versatility is excellent and user-friendly. Further provided is a method thereof and an apparatus therefor, namely a sample holder assembly composed of an applicator and a sample holder. Therefore, single crystal X-ray structure analysis using crystal sponge can be easily utilized, and it can be widely popularized. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 This is a diagram showing the overall configuration of a single crystal X-ray structure analysis apparatus including a single crystal X-ray diffraction apparatus that is one embodiment of the present invention.

[0024] Figure 2 It is a diagram showing the structure of the above-mentioned single crystal X-ray diffraction apparatus.

[0025] Figure 3 (A) is a block diagram showing the internal electrical structure of the above-mentioned single crystal X-ray structure analysis device.

[0026] Figure 4 The diagram includes a photograph showing an XRDS pattern or image obtained by the above-mentioned single crystal X-ray structure analysis device.

[0027] Figure 5 (A) Figure 5(B) is a diagram including a photograph showing an example of a screen showing execution of X-ray diffraction data measurement / processing software in the above-mentioned single crystal X-ray structure analysis apparatus.

[0028] Figure 6 The figure includes a screen showing a molecular model created using a structure analysis program of the above-mentioned single crystal X-ray structure analysis apparatus.

[0029] Figure 7 (A) is a diagram including a photograph of an example of a structure centered on a goniometer of the single crystal X-ray diffraction apparatus.

[0030] Figure 8 It is a cross-sectional view showing an example of a sample holder assembly composed of an applicator and a sample holder attached to the goniometer.

[0031] Fig. 9 It is a cross-sectional view showing a sample holder assembly including an applicator and a sample holder according to another embodiment of the present invention.

[0032] Fig.10 This is a diagram showing an example of a state in which the sample holders are provided as a batch.

[0033] Fig.11 This is a flowchart showing an example of a single crystal X-ray structure analysis method using a sample holder.

[0034] Fig.12 This is a diagram showing an example of a pre-processing device used in the above-mentioned single crystal X-ray structure analysis method. DETAILED DESCRIPTION

[0035] Hereinafter, a single crystal X-ray structure analysis device using a crystal sponge according to an embodiment of the present invention will be described in detail with reference to the accompanying drawings. In addition, in the present application, the expression "A or B" means "at least one of A and B", and includes "A and B" as long as there is no special case such as A and B.

[0036] In the attached Figure 1 The figure shows the overall appearance structure of a single crystal X-ray structure analysis device including a single crystal X-ray diffraction device according to an embodiment of the present invention. As can be seen from the figure, the single crystal X-ray structure analysis device 1 comprises: a base 4 for storing a cooling device and an X-ray generating power supply unit; and an X-ray shield 6 mounted on the base 4.

[0037] The X-ray shield 6 includes a housing 7 surrounding the single crystal X-ray diffraction device 9 and a door 8 provided on the front surface of the housing 7. The door 8 provided on the front surface of the housing 7 can be opened, and various operations can be performed on the single crystal X-ray diffraction device 9 inside in the opened state. In addition, the present embodiment shown in the figure is a single crystal X-ray structure analysis device 1 including a single crystal X-ray diffraction device 9 for performing structural analysis of a substance using a crystal sponge described later.

[0038] like Figure 2 As shown in FIG. 1 , the single crystal X-ray diffraction device 9 includes an X-ray tube 11 and a goniometer 12. Although not shown in the figure, the X-ray tube 11 includes a filament, a target (also called a "counter cathode") arranged opposite to the filament, and a housing for storing these in an airtight manner. Figure 1 The X-ray generating power supply unit of the base 4 is energized to generate heat and release thermal electrons. In addition, a high voltage is applied between the filament and the target by the X-ray generating power supply unit, and the thermal electrons released from the filament are accelerated by the high voltage and collide with the target. The collision area forms an X-ray focus, and X-rays are generated and diverged from the X-ray focus. In more detail, although not shown here, the X-ray tube 11 is configured to include optical elements such as a micro-focusing tube and a multi-layer film focusing reflector, and can irradiate a light beam with a higher brightness. In addition, it can be selected from ray sources such as Cu, Mo, and Ag. As exemplified above, the filament, the target arranged opposite to the filament, and the housing that hermetically stores them function as an X-ray source, and the structure for X-ray irradiation including optical elements such as a micro-focusing tube and a multi-layer film focusing reflector functions as an X-ray irradiation unit.

[0039] In addition, the goniometer 12 includes: a θ rotating table 16 that supports the sample S to be analyzed and can rotate around the sample axis ω passing through the X-ray incident point of the sample S; and a 2θ rotating table 17 that is arranged around the θ rotating table 16 and can rotate around the sample axis ω. In the case of the present embodiment, the sample S is absorbed in the inside of a crystal sponge that is pre-installed in a part of a sample holder 250 described in detail later. Inside the base 18 of the goniometer 12, a driving device (not shown) for driving the above-mentioned θ rotating table 16 and 2θ rotating table 17 is stored. The θ rotating table 16 is driven by these driving devices to intermittently or continuously rotate at a predetermined angular velocity, so-called θ rotation. In addition, the 2θ rotating table 17 is driven by these driving devices to intermittently or continuously rotate, so-called 2θ rotation. The above-mentioned driving device can be composed of any structure, but for example, it can be composed of a power transmission structure composed of a worm and a worm wheel.

[0040] An X-ray detector 22 is mounted on a part of the outer periphery of the goniometer 12. The X-ray detector 22 is composed of, for example, a CCD type, a CMOS type two-dimensional pixel detector, a hybrid pixel detector, etc. The X-ray detection and measurement unit refers to a structure that detects and measures X-rays diffracted or scattered by a sample, and includes the X-ray detector 22 and a control unit that controls the X-ray detector 22.

[0041] The single crystal X-ray diffraction device 9 is configured as described above, so that the sample S is θ-rotated about the sample axis ω by the θ rotation of the θ rotation table 16 of the goniometer 12. During the θ rotation of the sample S, the X-rays generated from the X-ray focus in the X-ray tube 11 and directed toward the sample S are incident on the sample S at a predetermined angle and are diffracted and diverged. That is, the incident angle of the X-rays incident on the sample S changes according to the θ rotation of the sample S.

[0042] If the Bragg diffraction condition is satisfied between the incident angle of the X-ray incident on the sample S and the lattice plane, diffracted X-rays are generated from the sample S. The diffracted X-rays are received by the X-ray detector 22 and the X-ray intensity is measured. By the above, the angle of the X-ray detector 22 relative to the incident X-ray, that is, the intensity of the diffracted X-ray corresponding to the diffraction angle is measured, and the crystal structure related to the sample S is analyzed based on the measurement result.

[0043] then, Figure 3 (A) shows a detailed example of the electrical internal structure of the control unit 110 in the above-mentioned single crystal X-ray structure analysis apparatus. It is needless to say that the present invention is not limited to the embodiments described below.

[0044] The single crystal X-ray structure analysis device 1 includes the above-mentioned internal structure, and further has: a measuring device 102 for measuring a suitable substance as a sample; an input device 103, which is composed of a keyboard, a mouse, etc.; an image display device 104 as a display unit; a printer 106 as a unit for printing and outputting analysis results; a CPU (Central Processing Unit) 107; a RAM (Random Access Memory) 108; a ROM (Read Only Memory) 109; a hard disk 111 as an external storage medium, etc. These elements are electrically connected to each other through a bus bar 112.

[0045] The image display device 104 is composed of an image display device such as a CRT display and a liquid crystal display, and displays an image on a screen according to an image signal generated by an image control circuit 113. The image control circuit 113 generates an image signal based on the image data input thereto. The image data input to the image control circuit 113 is formed by the action of various computing units implemented by a computer including a CPU 107, a RAM 108, a ROM 109, and a hard disk 111. The printer 106 can use an ink plotter, a dot printer, an inkjet printer, an electrostatic transfer printer, or other printing devices of any structure. In addition, the hard disk 111 can also be composed of a magneto-optical disk, a semiconductor memory, or other storage media of any structure.

[0046] The hard disk 111 stores analysis application software 116 for controlling the overall operation of the single crystal X-ray structure analysis apparatus 1, measurement application software 117 for controlling the operation of measurement processing using the measurement device 102, and display application software 118 for controlling the operation of display processing using the image display device 104. These application software are read from the hard disk 111 and transferred to the RAM 108 as needed to realize predetermined functions.

[0047] The single crystal X-ray structure analysis device 1 further includes a database placed in a cloud region, for example, for storing various measurement results including the measurement data obtained by the above-mentioned measurement device 102. In the example in the figure, which will also be described later, there are shown an XRDS information database 120 storing XRDS image data obtained by the above-mentioned measurement device 102, a microscope image database 130 storing measured images obtained by a microscope, and other analysis databases 140 storing measurement results and physical property information obtained by analysis other than X-rays such as XRF and Raman rays. In addition, these databases do not necessarily need to be installed inside the single crystal X-ray structure analysis device 1, and for example, they can also be set outside and connected to each other via a network 150 or the like so that they can communicate with each other.

[0048] As a file management method for storing a plurality of measurement data in a data file, a method of storing each measurement data in a single file is also conceivable, but in this embodiment, Figure 3 As shown in (B), multiple measurement data are continuously stored in one data file. Figure 3 The storage area described as "conditions" in (B) is an area for storing various information including device information and measurement conditions when obtaining measurement data.

[0049] As such measurement conditions, it is possible to consider whether the following other conditions are used: (1) the name of the substance to be measured, (2) the type of measuring device, (3) the measurement temperature range, (4) the measurement start time, (5) the measurement end time, (6) the measurement angle range, (7) the moving speed of the scanning moving system, (8) the scanning conditions, (9) the type of X-rays incident on the sample, and (10) accessories such as the sample high temperature device.

[0050] XRDS (X-ray Diffraction and Scattering) pattern or image (refer to Figure 4 ) is obtained by receiving and accumulating X-rays received in a two-dimensional space, i.e., a plane, of the X-ray detector 22 constituting the above-mentioned measuring device 102, at each pixel arranged in a plane constituting the detector, and measuring the intensity thereof. For example, by detecting the intensity of X-rays received by integrating the light according to each pixel of the X-ray detector 22, a pattern or image in a two-dimensional space of r and θ can be obtained.

[0051] <Measurement application software>

[0052] The XRDS pattern or image in the observation space obtained by the diffraction and scattering of the X-rays irradiated by the object material reflects the information of the electron density distribution in the actual space of the object material. However, the XRDS pattern is a two-dimensional space of r and θ, and does not directly express the symmetry of the object material in the actual space as a three-dimensional space. Therefore, in general, it is difficult to determine the (spatial) arrangement of atoms and molecules constituting the material using only the existing XRDS image, and professional knowledge of X-ray structure analysis is required. Therefore, in this embodiment, the above-mentioned measurement application software is used to achieve automation. In this way, the single crystal X-ray structure analysis device 1 uses an X-ray detection measurement unit to control the action of the measurement processing using the measurement device 102, and accepts and manages various measurement results including the measurement data obtained by detecting the X-rays diffracted or scattered by the sample. In addition, the structure analysis unit performs structural analysis of the sample based on various measurement results including the measurement data obtained by detecting the X-rays diffracted or scattered by the sample.

[0053] As an example, Figure 5 As shown in (A) and (B) of FIG. 1 , the CrysAlis Pro " X-ray diffraction data measurement / processing software, performs preliminary measurement, measurement condition setting, actual measurement, data processing, etc. Furthermore, by installing an automatic structure analysis plug-in called "Auto Chem", structural analysis and structural refinement are performed in parallel with X-ray diffraction data collection. Then, by Figure 6The one shown is called "Olex 2 "Structural analysis program, phase determination based on space group determination, construction and modification of molecular models, structural refinement, final report, and preparation of CIF files.

[0054] The overall structure and functions of the single crystal X-ray structure analysis device 1 are described above. Hereinafter, the crystal sponge and the devices and instruments related thereto according to the present invention will be described in detail with particular reference to the accompanying drawings.

[0055] <Crystal Sponge>

[0056] As described above, by developing a material called "crystal sponge" that is an extremely tiny and fragile porous complex crystal with a size of about 10 μm to 100 μm and countless pores with a diameter of 0.5 nm to 1 nm opened inside, single crystal X-ray structure analysis can be widely applied to liquid compounds that do not crystallize, or extremely small amounts of samples of several ng to several μg that cannot be ensured to be sufficient for crystallization.

[0057] However, in the current situation, in order to perform crystallization absorption (post-crystallization) of a sample into the skeleton of the above-mentioned crystal sponge, the following process is required: as described above, a very small amount of sample of about several ng to several μg separated by various pre-treatment (separation) devices is immersed in a storage solvent (carrier) such as cyclohexane in a container and absorbed in the skeleton of a very small and fragile crystal sponge of about 100 μm in outer diameter. Furthermore, thereafter, the very small and fragile crystal sponge that absorbs the sample needs to be quickly taken out of the container (in a short time to the extent that the crystal sponge is not destroyed by drying) and accurately placed at the X-ray irradiation position in the single crystal X-ray diffraction device, more specifically, a process needs to be performed while centering the tip of the sample shaft (so-called goniometer head needle) of the goniometer 12. These processes are very delicate and quick operations that require operators to be extremely precise regardless of whether they have professional knowledge of X-ray structure analysis, and they have a great impact on the measurement results of the sample after being absorbed in the crystal sponge. In other words, these operations make the single crystal X-ray structure analysis using extremely small crystal sponges have a poor yield, which has become a factor that hinders the widespread use of single crystal X-ray structure analysis using crystal sponges.

[0058] The present invention is based on the above-mentioned findings of the inventors, and is to realize a single crystal X-ray structure analysis of extremely small and fragile crystal sponges quickly, reliably and easily by using a sample holder composed of an applicator as a handling (operation) tool and a sample holder for crystal sponges (also referred to as a sample holder) as described below, in other words, to realize a single crystal X-ray structure analysis apparatus with good yield, high efficiency, excellent versatility and user-friendly. That is, in the next generation single crystal X-ray structure analysis apparatus according to the present invention, an extremely small and fragile crystal sponge absorbing an extremely small amount of sample S is prepared, and the sample S (crystal sponge) is taken out from the absorbing container and quickly and accurately mounted at a predetermined position of the front end of the goniometer 12 in a short time to the extent that the crystal sponge is not destroyed by drying. However, in order to realize a user-friendly apparatus with excellent versatility, it is necessary to be able to perform this operation quickly and easily without requiring high expertise and meticulousness of operation.

[0059] In order to solve this problem, the present invention provides a device and method for performing single crystal X-ray structure analysis, which can enable anyone to perform single crystal X-ray structure analysis quickly, reliably, easily, with good yield, efficiently, user-friendly, and with excellent versatility while using extremely small and fragile crystal sponges that are difficult to handle. The present invention also provides an apparatus and method for performing single crystal X-ray structure analysis, which can be used for extremely small and fragile crystal sponges that are difficult to handle, and an apparatus and method for performing single crystal X-ray structure analysis, which is described in detail below.

[0060] Figure 7 (A) shows the front end of the goniometer 12 in an enlarged manner. In this figure, a device is shown in which a crystal sponge 200 for absorbing the sample to be analyzed proposed by the present invention is pre-installed at the front end thereof, that is, Figure 7 (B) shows an enlarged view of a so-called sample holder 250 mounted (assembled) on the goniometer head 121 at the front end of the goniometer 12. The sample holder 250 can be attached to and detached from the goniometer head 121 at the front end of the goniometer 12 by a mounting / positioning mechanism using magnetic force, etc., and can be easily and accurately mounted at a correct position by anyone.

[0061] <Specimen holder and applicator for crystal sponge>

[0062] Figure 8 2 shows a cross section of the sample holder 250. In the sample holder 250, the goniometer head 121 (see Figure 7The base part 251 of the holder of the disk or cone shape made of metal or the like is provided, and the pin (cylindrical)-shaped sample holding part (hereinafter, also referred to as holding part) 252 (corresponding to the so-called goniometer head pin) is erected at the central part of one surface (the lower surface in the figure), and the crystal sponge 200 for absorbing the sample to be analyzed is preliminarily fixed integrally with the sample holder 250 at a predetermined position at the front end of the pin-shaped holding part 252. In addition, a positioning mechanism such as a magnet (not shown) is provided on the other surface (the upper surface in the figure) of the disk-shaped base part 251. By means of this positioning mechanism, the sample holder 250 is detachably mounted on the front end of the goniometer 12.

[0063] In addition, Figure 8 , a so-called applicator 300 is shown as a processing (operation) tool used together with a sample holder 250 for causing a crystal sponge 200 pre-installed in the sample holder to absorb a sample. The applicator 300 is formed of a transparent or opaque member such as glass, resin, or metal, and has a storage space 301 formed therein for storing the sample holder 250. The sample holder 250 is further embedded in the upper portion thereof, and an opening 302 for taking out is formed. In the present invention, the sample holder assembly is composed of the applicator 300 and the sample holder 250.

[0064] Furthermore, a sealing portion (indicated by ○ in the figure) is provided at a part of the opening 302 of the applicator 300, for example, so that the state in which the sample holder 250 is stored in the storage space 301 inside the applicator 300 is maintained airtight from the outside. On the other hand, a pair of through pores 253, 253 for introducing the sample to be analyzed into the crystal sponge 200 located inside the applicator 300 (storage space 301) is formed in the base portion 251 of the sample holder 250. The pores 253, 253 are a preferred example of a sample introduction structure, and other structures can also be adopted. In addition, although not shown in the figure, these pores 253, 253 are also provided with sealing portions, thereby, as shown in the figure, even in the state in which the sample introduction tubes (hereinafter, also referred to as introduction tubes) 254, 254 for introducing the sample into the crystal sponge 200 are inserted into the pores 253, 253, the storage space 301 inside the applicator 300 is maintained in an airtight state.

[0065] According to the sample holder 250 of such a structure, or by further integrating (unitizing) with the applicator 300 as its processing (operation) tool, the crystal sponge 200 attached to the front end of the pin-shaped holding portion 252 (corresponding to the goniometer head needle) constituting a part of the sample holder 250 can be handled safely and easily without damaging it or without falling off the sample holder 250. That is, the crystal sponge 200 that has absorbed a very small amount of the sample can be prepared quickly on the goniometer head 121 in a short time, safely, simply, and easily without being damaged by drying, as in the past. In the present embodiment, the sample holder 250 that has finished absorbing the sample is removed from the applicator 300, and the goniometer head 121 (see FIG. 1 ) attached to the front end of the goniometer 12 is removed. Figure 7 (A)). Thus, the sample S absorbed in the crystal sponge 200 can be easily, accurately and quickly arranged at a predetermined position in the single crystal X-ray diffraction apparatus 9 without requiring high expertise or careful work.

[0066] In the above example, a pair of through pores 253, 253 for introducing the sample to be analyzed into the crystal sponge 200 located inside the applicator 300 (storage space 301) is formed in a part of the base portion 251 of the sample holder 250, but the present invention is not limited to this. These pores may also be formed as shown in the attached Fig. 9 As shown in the middle reference numerals 303 and 303 , it is formed as a part of the applicator 300 .

[0067] Furthermore, when introducing the sample to be analyzed into the crystal sponge 200, it is also possible to utilize an absorption device (permeation device) of which an example is also shown below. More specifically, a pair of sample introduction tubes 254, 254 from the device are inserted into the through pores 253, 253 (or 303, 303), and an extremely small amount of sample is introduced into the extremely small crystal sponge 200, thereby absorbing the sample into the required crystal sponge 200. In addition, the sample holder 250 is integrated (moduleized) with the applicator 300 as its processing (operation) tool, and further, as shown in FIG. Fig.10 As shown, only the number required for the analysis work can be accommodated in a box-shaped casing and provided as a so-called set.

[0068] <Single crystal X-ray structure analysis method using a crystal sponge sample holder and applicator>

[0069] Next, a single crystal X-ray structure analysis method performed by using the sample holder 250 pre-mounted with the crystal sponge 200 together with the applicator 300 as a processing tool thereof will be described below. In addition, as described above, the sample holder 250 and the applicator 300 may also be provided as a whole (assembly) or as a set.

[0070] Fig.11 The single crystal X-ray structure analysis method using the sample holder 250 and the applicator 300 as one embodiment of the present invention is summarized. In this method, as described above, a very small amount of sample is introduced into the sample holder 250 provided as a whole (assembly) with the applicator 300, and necessary absorption is performed. At this time, in the above-mentioned example, when the sample holder 250 is stored in the applicator 300, the sample holder 250 is connected to the sample holder 250 through a pair of through holes 253, 253 (see Figure 8 ), or a pair of fine holes 303, 303 formed in the applicator 300 (see Fig. 9 ) is inserted into a pair of sample introduction tubes 254, 254, thereby enabling the sample to be absorbed by the crystal sponge 200 installed at the front end of the sample holder 250.

[0071] More specifically, if Fig.12 As shown, for example, a very small amount of sample S extracted by LC (liquid chromatograph) 401, GC (gas chromatograph) 402, SFC (supercritical fluid chromatograph) 403, CE (electrophoresis) 404, etc. constituting a pretreatment device 400 is supplied to a pair of sample introduction tubes 254, 254 inserted into the fine holes 253, 253 of the sample holder 250 or the fine holes 303, 303 of the applicator 300 via an absorption device (permeation device) 500 equipped with various switching valves and a pressure regulating device to supply a fluid under necessary conditions (flow rate, pressure) (see Figure 8), the sample is selectively introduced into the storage space 301 inside the applicator 300. That is, the sample is transported from the supply side piping to the sample introduction tube 254 on the supply side, and is supplied from the front end portion of the sample introduction tube 254 on the supply side to the sample holder 250 inside the applicator 300. Only the sample, or a solution mixed with the sample and the storage solvent (carrier) flows and is supplied in the sample introduction tube 254 on the supply side. As a result, the introduced extremely small amount of sample S contacts the crystal sponge 200 at the front end of the pin-shaped holding portion 252 mounted on the sample holder 250 in the storage space 301 of the applicator 300 to absorb the sample. In addition, the electrophoresis device here includes various electrophoresis devices such as capillary electrophoresis and isoelectric point electrophoresis. In the case of using the absorption device 500, after a predetermined time has passed in the state where the sample is injected, the excess sample or the solution mixed with the sample and the storage solvent (carrier) is discharged from the sample introduction tube 254 on the discharge side. When the storage device 500 is not used, unnecessary storage solvent (carrier) or solution flows in the sample introduction tube 254 on the discharge side and is discharged. Therefore, there may be a case where the sample does not flow in the sample introduction tube 254 on the discharge side. In addition, when a gas or a supercritical fluid is used as a carrier, the carrier containing the sample is discharged.

[0072] Then, the sample holder 250 that has completed the absorption process is removed from the applicator 300, and is accurately mounted at a predetermined position in the single crystal X-ray diffraction device 9, that is, the goniometer head 121 at the front end of the goniometer 12, using a positioning mechanism such as the magnetic force described above. Therefore, the crystal sponge 200 mounted on a portion (front end) of the pin-shaped holding portion 252 of the sample holder 250 is arranged at the front end of the goniometer 12, that is, the position where the X-ray beam from the X-ray tube 11 is focused and irradiated after the absorption of the sample is completed. In other words, the sample S absorbed in the crystal sponge 200 is accurately arranged at a predetermined position in the single crystal X-ray diffraction device 9, and then the intensity of the diffracted X-ray from the sample S is measured by the X-ray detector 22, and its crystal structure and the like are analyzed.

[0073] Thus, by using the sample holder 250 provided as a component (integrated) together with the applicator 300 of the present invention, anyone can easily and safely absorb a very small amount of sample in the crystal sponge 200 of very small size pre-installed integrally with the sample holder 250, and then, by removing the applicator 300, the sample S can be quickly and safely mounted on the goniometer 12 at a correct position with high accuracy in a short time without the crystal sponge being damaged by drying. In addition, after that, while irradiating the sample S with X-rays of a required wavelength by the single crystal X-ray diffraction device 9, the diffraction and scattering measurement of the X-rays based on the target material is performed, and the structural analysis is performed by the measurement application software constituting the single crystal X-ray structure analysis device, and the molecular model is constructed, and the final report is prepared, etc., which is the same as the existing situation. That is, according to this embodiment, not only can the molecular structure / collective structure (real space) of a new structure discovered or designed in the field of pharmaceuticals, life sciences, and various material research be confirmed quickly, safely, and easily.

[0074] As described in detail above, according to the present invention, by utilizing a sample holder assembly consisting of a newly proposed applicator and a sample holder, single crystal X-ray structure analysis using extremely small and fragile crystal sponges can be performed quickly, reliably and easily without the meticulous and fine work required in the past, even without professional knowledge of X-ray structure analysis. In other words, single crystal X-ray structure analysis using crystal sponges can be performed with good yield and efficiently, and a single crystal X-ray structure analysis device with excellent versatility and user-friendliness can be realized, and a method therefor and a sample holder assembly consisting of an applicator and a sample holder are provided.

[0075] In addition, various embodiments of the present invention are described above, but the present invention is not limited to the above-mentioned embodiments, and includes various modified examples. For example, the above-mentioned embodiments are examples in which the entire system is described in detail in order to easily explain the present invention, and are not limited to all the structures described. In addition, a part of the structure of a certain embodiment can be replaced with the structure of another embodiment, and the structure of another embodiment can be added to the structure of a certain embodiment. In addition, for a part of the structure of each embodiment, other structures can be added / deleted / replaced.

[0076] The present invention can be widely used in methods for exploring material structures, X-ray structure analysis devices used therein, and the like.

[0077] Note that the present international application claims the benefit of priority based on Japanese Patent Application No. 2018-217815 filed on November 21, 2018, the entire contents of which are hereby incorporated by reference.

[0078] Explanation of symbols

[0079] 1...single crystal X-ray structure analysis device (whole), 9...single crystal X-ray diffraction device, 11...X-ray tube, 12...goniometer, 22...X-ray detector, 102...measuring device, 103...input device, 104...image display device, 107...CPU, 108...RAM, 109...ROM, 111...hard disk, 116...analysis application software, 117...measuring application software, 121...goniometer head, 250...sample holder, 200...crystal sponge, 251...base portion, 252...pin-shaped holding portion, 253...fine hole, 254...sample introduction tube, 300...applicator, 301...storage space, 302...opening portion, 303...fine hole.

Claims

1. A single crystal X-ray structure analysis device for performing structural analysis of a substance, characterized in that: have: an X-ray source for generating X-rays; a specimen holder to hold the specimen; A goniometer mounted on the sample holder and rotating back and forth; an X-ray irradiation unit for irradiating the sample held in the sample holder mounted on the goniometer with X-rays from the X-ray source; an X-ray detection and measurement unit for detecting and measuring X-rays diffracted or scattered by the sample; and a structural analysis unit for performing structural analysis of the sample based on the diffracted or scattered X-rays detected by the X-ray detection and measurement unit; The sample holder is provided by being equipped on a detachable applicator, The sample holder includes a porous complex crystal capable of absorbing the sample in a plurality of fine pores formed inside. The applicator includes a space for causing the sample to be absorbed by the porous complex crystals in the sample holder. A sample introduction structure is formed in either the sample holder or the applicator, wherein the sample introduction structure is two fine holes for absorbing the sample into the space. An introduction tube for supplying the sample into the space and an introduction tube for discharging the sample from the space are inserted into the two fine holes. The sample holder is attached to a position of the goniometer to be irradiated with X-rays from the X-ray irradiation unit in a state where the sample holder is detached from the applicator.

2. A sample holder assembly used in a single crystal X-ray structure analysis device, wherein the sample holder assembly is characterized by comprising: A sample holder mounted on a goniometer of the single crystal X-ray structure analysis apparatus; and an applicator for receiving the sample holder, The sample holder includes: a holding portion for holding a porous complex crystal capable of absorbing a sample in a plurality of fine pores formed inside; The applicator includes a space for allowing the sample to be absorbed by the porous complex crystals in the sample holder. Either the sample holder or the applicator is formed with a sample introduction structure, which is two fine holes for absorbing the sample into the space, and an introduction tube for supplying the sample into the space and an introduction tube for discharging the sample from the space are inserted into the two fine holes.

3. A single crystal X-ray structure analysis method, using a sample holder to perform structure analysis of a substance, wherein the single crystal X-ray structure analysis method is characterized in that it comprises the following steps: The sample holder provided with a space for absorbing the sample contains a fine-porous complex crystal capable of absorbing the sample in a plurality of fine pores formed therein, and the sample holder is provided so as to absorb the sample by introducing the sample while the sample holder is accommodated in the applicator; removing the sample holder from the applicator; Mounting the sample holder to a goniometer of a single crystal X-ray structure analysis device; An X-ray detection and measurement step of irradiating the sample mounted on the goniometer with X-rays from an X-ray source of the single crystal X-ray structure analysis device and detecting and measuring the X-rays diffracted or scattered by the sample; and Performing structural analysis of the sample based on the diffracted or scattered X-rays detected in the X-ray detection and measurement step, In the step of absorbing the sample, the sample is introduced into the space from a sample introduction structure, which is two fine holes formed in either the sample holder or the applicator, and a sample introduction tube is inserted into the two fine holes.

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