Device and method for absorbing sample for single crystal X-ray structure analysis

Abstract

A porous complex crystal that absorbs a sample can be reliably supplied to a single crystal X-ray structure analysis device. The absorption device that absorbs the sample comprises: a supply unit that supplies the sample to the porous complex crystal held by a sample holder (310); a temperature adjustment unit that controls the temperature of the porous complex crystal; a drive unit that drives the supply unit; and a control unit that controls the supply unit, the temperature adjustment unit, and the drive unit. The sample holder (310) is set in the absorption device in a state of being assembled to an applicator (311), the supply unit supplies the sample to the porous complex crystal held in the sample holder (310) inside the applicator (311), and the temperature adjustment unit controls the temperature of the porous complex crystal held in the sample holder (310) inside the applicator (311) to which the sample is supplied.

Description

Technical Field

[0001] The present invention relates to an adsorption device and a method for preparing analysis samples for use in single crystal X-ray structure analysis, and in particular, to an adsorption device and a method for adsorbing samples for X-ray structure analysis that are suitable for adsorbing a crystal sponge installed in a part of a sample holder used in a single crystal X-ray structure analysis device proposed in association with the present invention. Background Art

[0002] In the research and development of new equipment and materials, material synthesis, material evaluation, and the decision of the next research direction based on this are carried out on a daily basis. 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 realizes the function / physical properties of the target material, a material structure exploration method centered on the structural analysis of materials that can effectively perform structural analysis 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 accurate and high-precision three-dimensional structures of molecules, as is also known in the following patent document 1.

[0004] On the other hand, in the single crystal X-ray structural 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 sufficient for crystallization, etc., single crystal X-ray structural analysis can be widely applied.

[0005] In the field of single crystal X-ray structure analysis, when analyzing a single crystal sample using a single crystal X-ray structure analysis device to determine the crystal structure of the single crystal, it is difficult to prepare a single crystal sample of the analysis object. Furthermore, in order to determine the crystal structure of the single crystal from the data obtained by analyzing the single crystal sample of the analysis object using the single crystal X-ray structure analysis device, proficiency such as experience and intuition is required, and only a very limited number of people can operate.

[0006] On the other hand, in recent years, the technical development of single crystal X-ray structure analysis equipment has continued to advance. As long as a single crystal sample is obtained, even people who are not proficient in crystal structure analysis technology can use the single crystal X-ray structure analysis equipment to analyze the single crystal sample and can relatively easily determine the crystal structure of the single crystal sample.

[0007] In addition, as a polymer complex having two or more pore groups that can selectively take in and / or release specific compounds ranging from gaseous small molecules to macromolecules such as proteins and other biologically derived molecules, a polymer complex is described in Patent Document 1, which is characterized in that it has a three-dimensional lattice structure including a stacked structure formed by inserting the non-coordinating aromatic compound between aromatic compound ligands, the non-coordinating aromatic compound constituting the stacked structure forms the main skeleton of the polymer complex, and the three-dimensional lattice structure has two or more pore groups composed of mutually identical pores having inherent affinity for the guest component.

[0008] Prior Art Literature

[0009] Patent Literature

[0010] Patent Document 1: Japanese Patent Application Publication No. 2007-3394

[0011] Patent Document 2: JP Re-Publication Patent No. WO2016 / 017770

[0012] Non-patent literature

[0013] Non-patent literature 1: Makoto Fujita; X-ray analysis on the nanogram to microgramscale using porous complexes; Nature 495, 461-466; 28 March 2013

[0014] Non-patent document 2: Hoshino et al. (2016), The updated crystalline sponge method IUCrJ, 3, 139-151 Summary of the invention

[0015] Problems to be solved by the invention

[0016] In the prior art, as described in non-patent document 1, an extremely small and fragile crystal sponge having multiple tiny pores is formed, and a sample is absorbed inside the tiny pores of the crystal sponge. The sample is analyzed using a single crystal X-ray structure analysis device, thereby making it relatively easy to determine the crystal structure of the single crystal.

[0017] In order to analyze the crystal sponge using a single crystal X-ray structure analysis device, it is necessary to reliably mount the single crystal sample formed by absorption inside the fine pores of the crystal sponge on a part of the sample holder (the front end of the goniometer needle) used for analysis using the single crystal X-ray structure analysis device. However, in the above-mentioned prior art, there is no disclosure of a method or device for reliably mounting the sample formed by absorption in an extremely small and fragile crystal sponge on a measurement position in a single crystal X-ray structure analysis device.

[0018] The present invention solves the problems of the above-mentioned prior art and provides a sample absorption device and absorption method for single crystal X-ray structure analysis. The sample to be analyzed can be reliably absorbed in an extremely small and fragile crystal sponge installed on the sample holder by utilizing the sample holder proposed in conjunction with the present invention, thereby quickly and easily supplying it to the single crystal X-ray structure analysis device.

[0019] Means for solving problems

[0020] (1) In order to achieve the above-mentioned purpose, the absorption device of the present invention is an absorption device for absorbing a sample, and is characterized in that it comprises: a supply unit for supplying the sample to a porous complex crystal held by a sample holder; a temperature adjustment unit for controlling the temperature of the porous complex crystal; a driving unit for driving the supply unit; and a control unit for controlling the supply unit, the temperature adjustment unit and the driving unit.

[0021] (2) In addition, in the absorption device of the present invention, it is characterized in that the sample holder is set in the absorption device in a state of being assembled on the applicator, the supply unit supplies the sample to the porous complex crystals held in the sample holder inside the applicator, and the temperature adjustment unit controls the temperature of the porous complex crystals held in the sample holder inside the applicator to which the sample is supplied.

[0022] (3) In addition, in the absorption device of the present invention, it is characterized in that the supply unit is equipped with an injection tube for injecting the sample into the applicator equipped with the sample holder, and the absorption device is also equipped with a discharge unit for transporting a part of the sample out from the inside of the applicator equipped with the sample holder through a discharge tube, and the driving unit drives the injection tube and the discharge tube to carry out the injection tube and the discharge tube into and out of the inside of the applicator.

[0023] (4) In addition, in the absorption device of the present invention, the driving unit inserts the injection tube into the applicator through a first through hole formed in the sample holder, and inserts the discharge tube into the applicator through a second through hole formed in the sample holder.

[0024] (5) Furthermore, in the occlusion device of the present invention, when the injection tube and the discharge tube are inserted into the applicator, their insertion depths into the sample holder are different.

[0025] (6) Furthermore, in the storage device of the present invention, the first through hole and the second through hole are formed with tapered surfaces at the end portions on the inlet and outlet sides of the injection pipe or the discharge pipe.

[0026] (7) In addition, in the absorption device of the present invention, it is characterized in that the applicator has a first sealing portion for sealing between the sample holders, the driving portion has a holding portion for holding the injection tube and the discharge tube, and the holding portion has: a second sealing portion for sealing between the injection tube and the sample holder; and a third sealing portion for sealing between the discharge tube and the sample holder.

[0027] (8) In addition, in the absorption device of the present invention, it is characterized in that the holding portion is formed by a holding block, and the holding block is driven in a direction close to the sample holding rack by the driving portion, so that the injection tube and the discharge tube held by the holding block are inserted into the applicator, and the interior of the applicator is made airtight by operating the first sealing portion, the second sealing portion and the third sealing portion.

[0028] (9) Furthermore, in the storage device of the present invention, the first sealing portion, the second sealing portion, and the third sealing portion are O-rings.

[0029] (10) In addition, in the absorption device of the present invention, it is characterized in that the holding portion is pressed toward the sample holder by utilizing the driving portion, thereby pressing the O-rings forming the first to third sealing portions, thereby making the space between the applicator and the sample holder, and between the sample holder and the holding portion airtight.

[0030] (11) In addition, the absorption method of the present invention is a method for absorbing a sample, characterized in that the absorption method includes the following steps: a step of placing an applicator equipped with a sample holder holding a fine-porous complex crystal in an absorption device; a step of using a driving unit of the absorption device to lower a holding block holding an injection tube and a discharge tube, so that the injection tube and the discharge tube are respectively inserted into a first through hole and a second through hole formed in the sample holder, so that the injection tube and the discharge tube are exposed in an area surrounded by the sample holder and the applicator; a step of using the driving unit to The holding block is further lowered to press the sample holder against the applicator, and the holding block is pressed against the sample holder to make it airtight; the sample is supplied to the airtight area surrounded by the sample holder and the applicator through the injection tube; the sample is supplied to the applicator through the temperature adjustment unit according to the type of the sample so that the porous complex crystals absorb the sample; and the sample is discharged from the area surrounded by the sample holder and the applicator through the discharge tube.

[0031] (12) Furthermore, in the absorbing method of the present invention, in the airtight step, the sample holder is pressed against a sealing portion attached to one side of the applicator to thereby make the space between the sample holder and the applicator airtight.

[0032] (13) In addition, the absorption method of the present invention is characterized in that, in the airtight process, the sealing portion of the area surrounding the injection pipe and the area surrounding the discharge pipe mounted on one side of the holding block is brought into contact with the sample holder and pressed, thereby making the holding block and the sample holder airtight.

[0033] Effects of the Invention

[0034] According to the sample occlusion device for single crystal X-ray structural analysis of the present invention, the sample can be reliably occluded by the extremely small and fragile crystal sponge, that is, the fine-porous complex crystal held in the sample holder of the single crystal X-ray structural analysis device. BRIEF DESCRIPTION OF THE DRAWINGS

[0035] Figure 1 This is a block diagram schematically showing the overall system configuration of a single crystal X-ray structure analysis apparatus including a sample occlusion device for X-ray structure analysis according to an embodiment of the present invention.

[0036] Figure 2 It is a perspective view showing the system appearance structure of the above-mentioned single crystal X-ray structure analysis device.

[0037] Figure 3It is a perspective view showing the structure of a measuring section of the above-mentioned single crystal X-ray structure analysis apparatus.

[0038] Figure 4 (a) is a block diagram showing a detailed example of the electrical internal structure of the above-mentioned single crystal X-ray structure analysis device, and (b) is a diagram showing the data file structure for storing multiple measurement data in the electrical internal structure of the above-mentioned single crystal X-ray structure analysis device.

[0039] Figure 5 This is a front view showing an image of an XRDS pattern observed by the above-mentioned single crystal X-ray structure analysis device.

[0040] Figure 6 (a) is a front view of an execution screen of the measurement application software of the above-mentioned single crystal X-ray structure analysis device, and (b) is a front view of another execution screen of the measurement application software of the above-mentioned single crystal X-ray structure analysis device.

[0041] Figure 7 This is a front view of a screen showing a molecular model created using a structural analysis program of the single crystal X-ray structural analysis apparatus.

[0042] Figure 8 This is a block diagram showing the structure of a sample occlusion device for X-ray structure analysis according to an embodiment of the present invention.

[0043] Fig. 9 The diagram includes a graph showing an example of an output waveform of a sensor on the supply side in the above-mentioned storage device.

[0044] Fig.10 The diagram includes a graph showing an example of an output waveform of a sensor on the discharge side in the above-mentioned storage device.

[0045] Fig.11 This is a cross-sectional view of a sample holder used to occlude the sample for X-ray structure analysis in the crystal sponge in the occlusion device.

[0046] Fig.12 This is a cross-sectional view showing an example of the structure of a needle insertion portion into which an injection needle and a discharge needle are inserted into the sample holder in the above-mentioned occlusion device.

[0047] Fig.13 It is a cross-sectional view of an applicator storing a sample holder used in the above-mentioned occlusion device.

[0048] Fig.14 It is a cross-sectional view showing a state where the sample holder used in the above-mentioned occlusion device is accommodated in the applicator.

[0049] Fig.15This is a cross-sectional view showing a state in which an injection needle and a discharge needle are inserted through a needle insertion portion into a sample holder accommodated in an applicator in the above-mentioned occlusion device.

[0050] Fig.16 This is a perspective view of a sampling array that accommodates a plurality of applicators equipped with a sample holder having a crystal sponge attached to the front end portion in the above-mentioned absorbing device. DETAILED DESCRIPTION

[0051] Hereinafter, the absorbing device and absorbing method of the single crystal X-ray structure analysis sample for a single crystal X-ray structure analysis device of the present invention, which can absorb the analysis sample in a sponge-like material (crystal sponge or fine-porous complex crystal) and reliably supply it as a sample holder of the single crystal X-ray structure analysis device, will be described using 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.

[0052] Figure 1 The schematic structure of the whole single crystal X-ray structure analysis system 100 provided with the absorbing device for the sample for single crystal X-ray structure analysis according to the present embodiment is shown. The single crystal X-ray structure analysis system 100 according to the present embodiment is configured to include: a chromatograph device 200 for extracting a sample to be analyzed from a sample such as a gas or a liquid; an absorbing device 300 for single crystal X-ray structure analysis device (hereinafter also referred to as the absorbing device 300) for preparing a sample for single crystal X-ray structure analysis from the sample extracted by the chromatograph device 200; a sample tray 410 for storing and moving the sample for single crystal X-ray structure analysis prepared by the absorbing device 300; and a single crystal X-ray structure analysis device 500 for analyzing the sample stored in the sample tray 410 using X-rays.

[0053] Alternatively, the sample tray 410 may not be used, and the sample may be moved individually from the storage device 300 to the single crystal X-ray structure analysis device 500 .

[0054] In the attached Figure 2 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 500 comprises: a base 504, which accommodates a cooling device and an X-ray generating power supply unit; and an X-ray shield 506, which is placed on the base 504.

[0055] The X-ray shield 506 includes a housing 507 surrounding the single crystal X-ray diffraction device 509 and a door provided on the front surface of the housing 507. The door provided on the front surface of the housing 507 can be opened, and various operations can be performed on the single crystal X-ray diffraction device 509 inside in the opened state. In addition, the present embodiment shown in the figure is a single crystal X-ray structure analysis device 500 including a single crystal X-ray diffraction device 509 for performing structural analysis of a substance using a crystal sponge described later.

[0056] like Figure 3 As shown in FIG. 5 , the single crystal X-ray diffraction device 509 includes an X-ray tube 511 and a goniometer 512. Although not shown in the figure, the X-ray tube 511 includes a filament, a target (also called a "counter cathode") arranged opposite to the filament, and a housing for storing them in an airtight manner. Figure 2 The X-ray generating power supply unit of the base 504 is energized to generate heat and release thermal electrons.

[0057] 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 511 is configured to include optical elements such as a micro-focusing tube and a multi-layer film focusing reflector, and can irradiate a beam of higher brightness. In addition, it can be selected from ray sources such as Cu, Mo, and Ag. As illustrated above, the filament, the target arranged opposite to the filament, and the housing that stores them airtightly 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.

[0058] In addition, the goniometer 512 includes: a θ rotating table 516 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 517 that is arranged around the θ rotating table and can rotate around the sample axis ω. The goniometer 512 includes a goniometer head 514 that carries the sample S. In addition, in the case of this embodiment, the sample S is absorbed in the interior of a crystal sponge that is pre-installed in a part of a sample holder 513 described in detail later.

[0059] A driving device (not shown) for driving the above-mentioned θ rotating table 516 and 2θ rotating table 517 is stored inside the base 518 of the goniometer 512. The θ rotating table 516 is driven by these driving devices to rotate intermittently or continuously at a given angular velocity, so-called θ rotation. In addition, the 2θ rotating table 517 is driven by these driving devices to rotate intermittently or continuously, 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.

[0060] An X-ray detector 522 is mounted on a part of the periphery of the goniometer 512. The X-ray detector 522 is composed of, for example, a CCD type, a CMOS type two-dimensional pixel detector, a hybrid pixel detector, etc. In addition, 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 522 and a control unit that controls the X-ray detector 522.

[0061] The single crystal X-ray diffraction device 509 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 516 of the goniometer 512. During the θ rotation of the sample S, the X-rays generated from the X-ray focus in the X-ray tube 511 and directed toward the sample S are incident on the sample S at a given angle and diffracted / 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.

[0062] 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 522 and the X-ray intensity is measured. By the above, the angle of the X-ray detector 522 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.

[0063] Next, Figure 4 (a) shows a detailed example of the electrical internal structure of the control unit 550 in the single crystal X-ray structure analysis apparatus 500. It is needless to say that the present invention is not limited to the embodiments described below.

[0064] The single crystal X-ray structure analysis device 500 includes the above-mentioned internal structure, and further has: a measuring device 562 for measuring a suitable substance as a sample; an input device 563, which is composed of a keyboard, a mouse, etc.; an image display device 564 as a display unit; a printer 566 as a unit for printing and outputting analysis results; a CPU (Central Processing Unit) 557; a RAM (Random Access Memory) 558; a ROM (Read Only Memory) 559; a hard disk as an external storage medium, etc. These elements are electrically connected to each other through a bus bar 552.

[0065] The image display device 564 is composed of an image display device such as a CRT display or a liquid crystal display, and displays an image on a screen according to an image signal generated by the image control circuit 553. The image control circuit 553 generates an image signal based on the image data input to the image data. The image data input to the image control circuit 553 is formed by the operation of various computing units implemented by a computer including a CPU 557, a RAM 558, a ROM 559, and an analysis unit 551 having a hard disk.

[0066] The printer 566 can use an ink plotter, a dot printer, an inkjet printer, an electrostatic transfer printer, or any other printing device of any structure. In addition, the analysis unit 551 can be composed of a magneto-optical disk, a semiconductor memory, or any other storage medium of any structure other than a hard disk.

[0067] Inside the analysis unit 551 having a hard disk and performing single crystal structure analysis processing, there are stored analysis application software 5511 for managing the overall operation of the single crystal X-ray structure analysis apparatus 500, measurement application software 5512 for managing the operation of measurement processing using the measurement device 562, and display application software 5513 for managing the operation of display processing using the image display device 564. These application software are read from the hard disk of the analysis unit 551 and transferred to the RAM 558 as needed to realize given functions.

[0068] The single crystal X-ray structure analysis device 500 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 562. In the example of the figure, which will also be described later, there are shown an XRDS information database 571 storing XRDS image data obtained by the above-mentioned measurement device 562, a microscope image database 572 storing measured images obtained by a microscope, and other analysis databases 573 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 500, and for example, they can also be set outside and connected to each other via a network 580 or the like so that they can communicate with each other.

[0069] 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 4 As shown in (b), multiple measurement data are continuously stored in one data file. Figure 4 The storage area described as "condition" in (b) is an area for storing various information including device information and measurement conditions when obtaining measurement data.

[0070] 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.

[0071] XRDS (X-ray Diffraction and Scattering) pattern or image (refer to Figure 5 ) is obtained by receiving and accumulating the X-rays received in the two-dimensional space, i.e., the plane, of the X-ray detector 522 constituting the above-mentioned measuring device 562, according to each pixel (e.g., CCD, etc.) arranged in the plane of the detector, and measuring the intensity thereof. For example, by detecting and integrating the intensity of the received X-rays according to each pixel of the X-ray detector 522, a pattern or image in the two-dimensional space of r and θ can be obtained.

[0072] <Measurement application software>

[0073] 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 show 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.

[0074] As an example, Figure 6 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 structural analysis plug-in called "Auto Chem", structural analysis and structural refinement are performed in parallel with X-ray diffraction data collection. Then, by Figure 7 The one shown is called "Olex 2 "Structural analysis program, phase determination based on space group determination, construction and correction of molecular models, refinement of structures, final report, and preparation of CIF files.

[0075] The overall structure and functions of the single crystal X-ray structure analysis device 500 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.

[0076] <Crystal Sponge>

[0077] As mentioned 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 structural analysis can be widely used, including 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.

[0078] However, in the current situation, in order to perform crystallization absorption (post-crystallization) of the 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 an extremely small and fragile crystal sponge with an outer diameter of about 100 μm. The storage solvent (carrier) includes liquid, gas, and a supercritical fluid located in between. Furthermore, thereafter, the extremely 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 diffraction device, more specifically, a process needs to be performed while centering the tip of the sample shaft (so-called goniometer needle) of the goniometer 512.

[0079] These processes are very fine and rapid operations that require operators to be extremely dense regardless of whether they have professional knowledge of X-ray structural analysis, and 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 structural 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 structural analysis using crystal sponges.

[0080] The present invention is achieved based on the insights of the inventors as mentioned above. By using the crystal sponge sample holder (also referred to as the sample holder) described below, single crystal X-ray structure analysis of extremely small and fragile crystal sponge can be performed reliably and easily. In other words, a single crystal X-ray structure analysis device with good yield, high efficiency, excellent versatility and user-friendliness can be realized.

[0081] That is, in the next-generation single crystal X-ray structure analysis device involved in the present invention, an extremely small and fragile crystal sponge that absorbs an extremely small amount of sample S is prepared, and the sample S (crystal sponge) is further taken out from the absorption container. There is a large constraint that it must be accurately and quickly installed at a given position at the front end of the goniometer 12. However, in order to realize a user-friendly device with excellent versatility, it is necessary to be able to perform the operation quickly and easily without requiring a high degree of professional knowledge and precision (density) of the operation.

[0082] The present invention aims to solve this problem, that is, to provide a device, method and sample holder for single crystal X-ray structure analysis, which can be performed quickly, reliably and easily by anyone with good yield and high efficiency even when using extremely small and fragile crystal sponges that are difficult to handle. The device, method and sample holder for the instrument are described in detail below.

[0083] <Storage Device>

[0084] use Figures 8 to 16 To have Figure 1 The structure of the occlusion device 300 for occluding the analysis target sample in the crystal sponge among the structures of the single crystal X-ray structure analysis system 100 of the single crystal X-ray structure analysis apparatus 500 according to the first embodiment of the present invention shown in FIG.

[0085] Figure 8 1 is a block diagram showing the structure of the occlusion device 300 used in the single crystal X-ray structure analysis device 500 according to the embodiment of the present invention. The occlusion device 300 according to the embodiment of the present invention comprises: a supply side piping 301, a supply side first actuator 302, a supply side analysis unit 303, a supply side second actuator 304, a supply side piping 305, an injection needle (injection tube) 306, and a sample holder 310 (equivalent to Figure 3 The sample holder 513 includes an applicator 311, a temperature regulator (thermostat) 320, a discharge needle (discharge tube) 331, a discharge tube 332, a first actuator 333 on the discharge side, a discharge side analysis unit 334, a second actuator 335 on the discharge side, a discharge side piping 336, a control unit 340 and a reading unit 350.

[0086] The adsorption device 300 supplies a carrier or solvent (hereinafter referred to as a sample including them) of a sample (gas, liquid or supercritical fluid, etc.) of an analysis object supplied from a separation device (such as a gas chromatograph or a liquid chromatograph, etc.) 200 through a supply-side piping 301, and uses a supply-side first actuator 302 to adjust the flow rate, pressure, etc. of the sample.

[0087] Next, the support including the sample is sent to the supply-side analysis unit 303 , whereby components of the sample whose pressure, concentration, and temperature have been adjusted are analyzed. Fig. 9 An example of the analysis result is shown in FIG. Fig. 9 The graph of FIG. 2 shows that the signal intensity of a specific component of the sample sent from the separation device 200 has a peak 901 .

[0088] The sample analyzed by the supply-side analysis unit 303 is transported from the supply-side pipe 305 to the injection needle 306 inside the sample holder 310 mounted on the applicator 311, and is supplied from the injection needle 306 to the sample holder 310 inside the applicator 311. The injection needle 306 is driven by a driving unit (not shown) and inserted into the sample holder 310 mounted on the applicator 311.

[0089] In this state, the temperature regulator 320 is controlled by the control unit 340 to heat or cool the applicator 311 so that the applicator 311 including the sample holder 310 reaches a desired temperature.

[0090] After a given time has passed while the sample is injected from the injection needle 306 into the sample holder 310 mounted in the applicator 311 whose temperature is controlled by the temperature regulator 320, the first actuator 333 on the discharge side operates, and the front end portion of the sample supplied to the inside of the applicator 311 through the discharge tube 332 from the discharge needle 331 inserted into the inside of the sample holder 310 mounted on the applicator 311 is discharged. In other words, the excess sample refers to the sample discharged according to the length of the discharge needle 331. The discharge needle 331 is driven by a driving unit (not shown) and inserted into the inside of the sample holder 310.

[0091] In this way, the sample is transported from the supply side piping to the injection needle 306 on the supply side, and is supplied from the front end of the injection needle 306 on the supply side to the sample holder 310 inside the applicator 311. Only the sample or the solution mixed with the sample and the storage solvent (carrier) flows and is supplied in the injection needle 306 on the supply side. Thus, the introduced extremely small amount of sample S contacts the crystal sponge at the front end of the pin-shaped holding portion attached to the sample holder 310 in the storage space 301 of the applicator 300, and the sample is absorbed. In addition, the electrophoresis device herein includes various electrophoresis devices such as capillary electrophoresis and isoelectric point electrophoresis. When the absorption device 300 is used, after a given 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 discharge needle 331 on the discharge side. When the absorption device 300 is not used, the unnecessary storage solvent (carrier) or solution flows in the discharge needle 331 on the discharge side and is discharged. Therefore, there is a possibility that the sample does not flow through the discharge needle 331 on the discharge side.

[0092] When a gas or a supercritical fluid is used as a carrier, the carrier including the sample is discharged.

[0093] The sample discharged from the inside of the applicator 311 by the discharge-side first actuator 333 is analyzed for components by the discharge-side analysis unit 334 . Fig.10The sample discharged from the inside of the applicator 311 whose components are analyzed by the discharge side analysis unit 334 is sent to the mass spectrometer 600 from the discharge side piping 336 after the pressure, flow rate or concentration is adjusted in the discharge side second actuator 335 to analyze its mass components.

[0094] Here, if the data obtained by the discharge side analysis unit 334 is analyzed Fig.10 The chart obtained by the supply side analysis unit 303 Fig. 9 By comparing the chart of Fig. 9 The signal of the component with the peak intensity 901 corresponds to Fig.10 The level of the peak 1001 component in the graph is reduced. This indicates that Fig. 9 A portion of the component showing the peak in is consumed inside the applicator 311 .

[0095] By controlling the control unit 340 Fig. 9 The data shown and Fig.10 The data shown are compared, and when the difference or ratio between the peak values ​​reaches a preset value, it is determined that the sample to be analyzed is absorbed in the crystal sponge installed at the front end of the sample holder 310 installed inside the applicator 311, and a series of operations are completed.

[0096] Fig.11 : is a cross-sectional view of the sample holder 310 as viewed from the front. The sample holder 310 has a flat surface 3102 formed at one end of a root portion 3101 held by a processing operator. A main body portion 3103 having an outer diameter smaller than that of the root portion 3101 is formed at the front end of the flat surface 3102, a guide surface 310D processed into a tapered shape is formed at the front end of the main body portion 3103, and a thin pin 3104 is formed at the front end thereof.

[0097] A recess 3105 is formed on the upper surface 310A of the figure, which is the other end surface of the root portion 3101, as a positioning member for attaching the sample holder to the goniometer head 514 of the single crystal X-ray structure analysis apparatus 500. In addition, the sample holder 310 is formed with an injection needle hole 3106 and a discharge needle hole 3107 that penetrate from the root portion 3101 to the main body 3103.

[0098] In the injection needle hole 3106 and the discharge needle hole 3107, tapered portions 310B and 310C processed into a tapered shape are formed on the end surfaces on the recessed portion 3105 side thereof, respectively.

[0099] The tapered portions 310B and 310C serve as guide surfaces when inserting the injection needle 306 and the discharge needle 331. In addition, the periphery of the concave portion 3105 where the tapered surface 310B is formed and the periphery where the tapered surface 310C is formed serve as the sealing surface 1 when the injection needle 306 and the discharge needle 331 described later are inserted into the injection needle hole 3106 and the discharge needle hole 3107, respectively.

[0100] The recessed portion 3105 of the root portion 3101 which is the whole of the specimen holder 310 or a part thereof is magnetically coupled to the front end portion of the goniometer head 514 and is therefore formed of a magnetic body.

[0101] A crystal sponge 380 for absorbing a sample to be analyzed is attached (bonded) to the tip portion of the pin 3104. The crystal sponge 380 is formed of different components depending on the type of the sample to be analyzed.

[0102] Fig.12 The cross-sectional view shows a needle insertion section 390 for inserting the injection needle 306 and the discharge needle 331 into the sample holder 310. The needle insertion section 390 includes a holding block 360 for holding the injection needle 306 and the discharge needle 331, and a driving section 370 for driving the holding block 360 in the up-down direction (see arrows in the figure).

[0103] The injection needle 306 and the discharge needle 331 are held closely to the holding block 360 by welding or the like, for example.

[0104] In the holding block 360, on one side of the front end portion of the injection needle 306 and the discharge needle 331 (at Fig.12 A protrusion 361 is formed on the end surface of the protrusion 361. Further, grooves 3611 and 3621 for inserting an O-ring are formed on the end surface of the protrusion 361, and O-rings 3612 and 3622 are mounted on the respective grooves 3611 and 3621.

[0105] In addition, the outer diameter dimension of the protrusion 361 is formed to be slightly smaller than the inner diameter dimension of the recessed portion 3105 formed in the sample holder 310 .

[0106] Although details thereof are omitted, the driving unit 370 includes, for example, an electric motor, an air cylinder, or a hydraulic cylinder, and drives the holding block 360 in the up-down direction.

[0107] Fig.13: shows a cross section of the applicator 311. The applicator 311 is formed with an opening 3111, which is a portion where the root portion 3101 of the sample holder 310 is inserted, a cylindrical space 3112 where the main body 3103 of the sample holder 310 is inserted, and a front end space 3113 where the pin 3104 of the sample holder 310 is inserted. The front end space 3113 where the pin 3104 is inserted is formed in a so-called conical shape whose diameter decreases toward the front end. In addition, in the applicator 311, when the sample holder 310 is mounted, an O-ring groove 3115 is formed on a surface 3114 that contacts the flat surface 3102 of the root portion 3101 thereof.

[0108] Fig.14 The sample holder 310 is shown in a state where it is mounted on the applicator 311. With the crystal sponge 380 attached to the tip of the pin 3104 of the sample holder 310, the main body 3103 of the sample holder 310 is inserted into the cylindrical space 3112 of the applicator 311 using the guide surface processed into a tapered shape at the tip of the main body 3103 as a guide.

[0109] Furthermore, when the sample holder 310 is pressed against the applicator 311 , the main body 3103 of the sample holder 310 inserted into the cylindrical space 3112 of the applicator 311 serves as a guide, and the root portion 3101 of the sample holder 310 is inserted into the opening 3111 of the applicator 311 .

[0110] In this way, when the sample holder 310 is assembled on the applicator 311 and the root portion 3101 of the sample holder 310 is inserted into the opening 3111 of the applicator 311, the injection needle 306 and the discharge needle 331 are inserted into the injection needle hole 3106 and the discharge needle hole 3107, and the sample is supplied to the cylindrical space portion 3112 of the applicator 311 and its front end space portion 3113.

[0111] Fig.15 The state in which the injection needle 306 and the discharge needle 331 are inserted from the injection needle hole 3106 and the discharge needle hole 3107 into the cylindrical space portion 3112 of the applicator 311 is shown. In this state, the applicator 311 is held by a holding unit (not shown) to maintain the posture in which the injection needle 306 and the discharge needle 331 are inserted. The injection needle 306 and the discharge needle 331 are inserted into the injection needle hole 3106 or the discharge needle hole 3107 respectively by pressing the holding block 360 holding them downward by the driving unit 370.

[0112] In the order of inserting the injection needle 306 into the injection needle hole 3106 and inserting the discharge needle 331 into the discharge needle hole 3107, these needles are pushed down together by the driving unit 370 and the holding block 360. Thus, first, the tip of the injection needle 306 abuts against the tapered surface 310B processed into a tapered shape at the upper end of the injection needle hole 3106 and enters the injection needle hole 3106, and then, the tip of the discharge needle 331 abuts against the tapered surface 310C processed into a tapered shape at the upper end of the discharge needle hole 3107 and enters the discharge needle hole 3107.

[0113] By continuing the driving of the driving unit 370 in this state, the tip of the injection needle 306 descends inside the injection needle hole 3106 and reaches the cylindrical space 3112 of the applicator 311. Next, the tip of the discharge needle 331 descends inside the discharge needle hole 3107 and reaches the cylindrical space 3112 of the applicator 311.

[0114] After the front end portions of the injection needle 306 and the discharge needle 331 reach the cylindrical space 3112 of the applicator 311 , if the driving unit 370 continues to be driven in this state, the protrusion 361 of the holding block 360 reaches the recess 3105 formed in the sample holder 310 .

[0115] If the driving unit 370 continues to be driven in this state, the sample holder 310 is pressed to one side of the applicator 311 and is pressed by the O-ring 362 fitted in the O-ring groove 3115 , so that the space between the sample holder 310 and the applicator 311 is sealed.

[0116] Furthermore, O-ring 3612 fitted in O-ring groove 3611 formed in protrusion 361 of holding block 360 and O-ring 3622 fitted in O-ring groove 3621 are respectively pressed against recess 3105 of sample holder 310. Thus, holding block 360 and sample holder 310 are sealed.

[0117] With such a structure, the cylindrical space portion 3112 inside the applicator 311 to which the sample holder 310 is attached, that is, the space surrounded by the sample holder 310 and the applicator 311 can be maintained in an airtight state with respect to the outside.

[0118] In this state, Figure 8 The control unit 340 shown controls the supply-side first actuator 302, the supply-side analysis unit 303, the supply-side second actuator 304 and the temperature regulator 320, and supplies the sample sent from the chromatograph device 200 from the injection needle 306 to the cylindrical space part 3112 of the applicator 311 and its front end space part 3113.

[0119] Furthermore, the control unit 340 controls the first discharge-side actuator 333 , the discharge-side analysis unit 334 , and the second discharge-side actuator 335 to discharge the excess sample of the sample supplied from the discharge needle 331 to the inside of the cylindrical space 3112 of the applicator 311 .

[0120] Furthermore, the control unit 340 controls the temperature regulator 320 in a state where the sample is supplied to the cylindrical space portion 3112 of the applicator 311 and the front end space portion 3113 thereof, thereby promoting the absorption of the sample in the crystal sponge 380 .

[0121] In this way, the temperature of the applicator 311 is controlled and maintained for a given time by the temperature regulator 320, and after confirming that the sample is absorbed in the crystal sponge 380 based on the data from the supply-side analysis unit 303 and the discharge-side analysis unit 334, the control unit 340 controls the driving unit 370 to raise the holding block 360. Thus, the injection needle 306 and the discharge needle 331 are removed from the injection needle hole 3106 or the discharge needle hole 3107 formed in the sample holder, and the process of absorbing the sample in the crystal sponge is completed.

[0122] In addition, Fig.12 as well as Fig.15 In the structure shown, the injection needle 306 has a front end portion (at the Fig.12 as well as Fig.15 The discharge needle 331 has a shape in which the tip portion thereof protrudes from the holding block 360, that is, the length thereof is long, depending on the type of sample to be processed. However, in contrast, the discharge needle 331 may have a tip portion protruding from the holding block 360, that is, the length thereof is longer, compared to the injection needle 306.

[0123] In addition, the Fig.15 The status shown indicates the above Figure 8 The injection needle 306 and the discharge needle 331 are shown in the state where they are inserted into the sample holder 310 and the applicator 311. Figure 8 The display of the holding block 360 and the driving unit 370 is omitted.

[0124] In addition, Figure 8 In the illustrated structure, the mass spectrometer 600 is described as a structure different from the storage device 300 , but the mass spectrometer 600 and the storage device 300 may be integrated as a part of the storage device 300 .

[0125] Fig.16A perspective view of a sampling array (well plate) 410 showing a state in which a plurality of applicators 311 equipped with a sample holder 310 including a crystal sponge absorbing a sample at its front end portion are stored in a tray 400 by the absorbing device 300 involved in this embodiment. The sampling array 410 stores a plurality of applicators 311 equipped with the sample holder 310, but the colors of the applicators 311 are distinguished according to the type of the crystal sponge 380 absorbing the sample, so that the type of the sample absorbed in the crystal sponge 380 can be easily determined.

[0126] According to this embodiment, when the sample holder 310 is mounted in the applicator 311 , the sample can be more safely absorbed in the extremely fine and fragile crystal sponge 380 attached to the tip of the pin 3104 of the sample holder 310 .

[0127] In addition, according to the present embodiment, the control unit 340 controls the first actuator 302 on the supply side, the analysis unit 303 on the supply side, the second actuator 304 on the supply side, the first actuator 333 on the discharge side, the analysis unit 334 on the discharge side, the second actuator 335 on the discharge side, and the temperature regulator 320, so that the sample is adsorbed inside the crystal sponge 380. Therefore, compared with the existing situation where the sample is adsorbed by manual operation, it is easy to set the adsorption conditions of the sample to be analyzed.

[0128] Furthermore, according to this embodiment, by comparing the data analyzed by the supply-side analysis unit 303 and the data analyzed by the discharge-side analysis unit 334 in the control unit 340 , it is possible to easily confirm that a single crystal of the sample is formed inside the crystal sponge 380 .

[0129] 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 that are 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 each 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.

[0130] The present invention can be widely used in methods for exploring material structures, X-ray structure analysis devices used therefor, and the like.

[0131] Note that the present international application claims the benefit of priority based on Japanese Patent Application No. 2018-219811 filed on November 23, 2018, the entire contents of which are hereby incorporated by reference.

[0132] Explanation of symbols

[0133] 100...Single crystal X-ray structure analysis system,

[0134] 200...Chromatographic device,

[0135] 300...Absorption device for single crystal X-ray structure analysis device,

[0136] 302...supply side first actuator,

[0137] 303...Supply-side analysis department,

[0138] 304...supply side second actuator,

[0139] 306...Injection needle,

[0140] 310...Specimen holder,

[0141] 311...Applicator,

[0142] 320...Temperature regulator,

[0143] 333...discharge side first actuator,

[0144] 334...Discharge side analysis department,

[0145] 335...discharge side second actuator,

[0146] 340...Control Department,

[0147] 360...Hold block,

[0148] 370...Drive unit.

Claims

1. A storage device for storing a sample, characterized in that: have: a supply unit including an injection tube for injecting the sample into an applicator equipped with a sample holder and supplying the sample to the fine-porous complex crystal held by the sample holder; A temperature adjustment unit for controlling the temperature of the porous complex crystals; A driving unit, driving the supply unit; a control unit that controls the supply unit, the temperature adjustment unit, and the drive unit; and a discharge unit that discharges a portion of the sample from the inside of the applicator equipped with the sample holder through a discharge pipe, The sample holder is provided in the storage device in a state where it is mounted on the applicator. The driving unit drives the injection tube and the discharge tube to move the injection tube and the discharge tube into and out of the applicator. The control unit determines that the sample is absorbed in the fine porous complex crystals based on analysis results of components of the sample supplied to the injection tube and components of the sample discharged from the discharge tube.

2. The storage device according to claim 1, wherein: The supply unit supplies the sample to the porous complex crystal held by the sample holder in the applicator. The temperature adjustment unit controls the temperature of the porous complex crystals held by the sample holder in the applicator to which the sample is supplied.

3. The storage device according to claim 2, wherein: The driving unit inserts the injection tube into the applicator through a first through hole formed in the sample holder, and inserts the discharge tube into the applicator through a second through hole formed in the sample holder.

4. The storage device according to claim 3, wherein: When the injection tube and the discharge tube are inserted into the applicator, the insertion depths of the injection tube and the discharge tube into the sample holder are different.

5. The storage device according to claim 3 or 4, wherein: The first through hole and the second through hole have tapered surfaces at the end portions of the injection pipe or the discharge pipe on the inlet and outlet sides. The driving unit inserts the injection pipe from one side of the tapered surface of the first through hole, and inserts the discharge pipe from one side of the tapered surface of the second through hole.

6. The storage device according to any one of claims 2 to 4, wherein: The applicator includes a first sealing portion that seals between the sample holders. The driving unit includes a holding unit that holds the injection pipe and the discharge pipe. The holding portion includes: a second sealing portion that surrounds the injection tube and seals between the holding portion and the sample holder; and a third sealing portion that surrounds the discharge tube and seals between the holding portion and the sample holder.

7. The storage device according to claim 6, wherein: The holding portion is formed by a holding block, The holding block is driven in a direction approaching the sample holder by the driving unit, so that the injection tube and the discharge tube held by the holding block are inserted into the applicator, and the interior of the applicator is made airtight by operating the first sealing unit, the second sealing unit, and the third sealing unit.

8. The storage device according to claim 6, wherein: The first sealing portion, the second sealing portion, and the third sealing portion are O-rings.

9. The storage device according to claim 8, wherein: The holding portion is pressed toward the sample holder by the driving portion, thereby pressing the O-rings forming the first to third sealing portions, thereby making the space between the applicator and the sample holder and the space between the sample holder and the holding portion airtight.

10. A storage method for storing a sample, characterized in that: The storage method comprises the following steps: A step of placing an applicator equipped with a sample holder holding fine-porous complex crystals in an occlusion device; A step of lowering a holding block holding an injection tube and a discharge tube by using a driving unit of the absorbing device, inserting the injection tube and the discharge tube into a first through hole and a second through hole formed in the sample holder, respectively, so that the injection tube and the discharge tube are exposed in an area surrounded by the sample holder and the applicator; A step of further lowering the holding block by the driving unit to press the sample holder to the applicator, and pressing the holding block to the sample holder to perform airtightness; A step of supplying the sample through the injection tube to an area airtightly surrounded by the sample holder and the applicator; A step of controlling the temperature of the applicator for supplying the sample by a temperature adjusting unit according to the type of the sample, so that the porous complex crystals absorb the sample; a step of discharging the supplied sample from an area surrounded by the sample holder and the applicator via the discharge pipe; as well as A step of determining that the supplied sample is absorbed in the fine porous complex crystals based on analysis results of components of the sample supplied to the injection tube and components of the sample discharged from the discharge tube.

11. The storage method according to claim 10, wherein: In the airtight step, the sample holder is used to press a seal portion attached to one side of the applicator, thereby making the space between the sample holder and the applicator airtight.

12. The storage method according to claim 10 or 11, wherein: In the airtight step, the holding block and the sample holder are airtightly sealed by bringing a sealing portion surrounding the injection pipe and the discharge pipe mounted on one side of the holding block into contact with and pressing the sample holder.

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