An efficient serial crystallography experimental device based on high viscosity nozzle technology

Abstract

The present invention discloses a high-efficiency serial crystallography experimental device based on high-viscosity nozzle technology. In this device, two turntables are coaxially rotatably connected to a base; the edges of the turntables are provided with multiple turntable external thread grooves; the turntable used to install the threaded sample chamber is called a sample turntable, and the turntable used to install the threaded piston chamber is called a piston turntable; the threaded sample chamber is used to store high-viscosity media containing crystals, and the threaded sample chamber is sealed by a sample chamber front end cap and a sample chamber rear end cap to form a sample module; the sample module is installed on the sample turntable via a turntable external thread groove on the sample turntable; the threaded piston chamber is installed on the piston turntable via a turntable external thread groove on the piston turntable; a bracket is connected to the base, and is used to support the threaded piston chamber and the threaded sample chamber for experimental alignment and to correct their positions. The present invention can achieve rapid pressure debugging, sample replacement, and storage of high-viscosity nozzle devices.

Description

Technical Field

[0001] The present invention relates to the field of protein crystal loading, and more particularly to an efficient serial crystallography experimental device and method using high viscosity technology. Background Art

[0002] With the development of serial crystallography, more and more mobile phase loading technologies have been developed. As a type of mobile phase technology, high-viscosity nozzle technology is not only suitable for loading samples of soluble proteins and membrane proteins, but also its viscous liquid flow rate can be controlled in a slower range, so the sample consumption is relatively low. Therefore, this technology has gradually become one of the most widely used mobile phase technologies in protein crystallography stations worldwide.

[0003] High-viscosity nozzle technology has been developed for the transport of high-viscosity media containing crystals. Generally speaking, a high-viscosity nozzle device is divided into several main modules: the liquid inlet section, piston section, sample section, air inlet section, intersection section, recovery section, and fixed section. Each module is connected via threaded interfaces to form a complete high-viscosity nozzle device. In high-viscosity nozzle experiments, the liquid inlet section provides hydraulic pressure, the piston section is used for pressure conversion, the sample section is used to store high-viscosity media, the air inlet section provides air pressure, and the remaining modules are mainly for device compatibility.

[0004] During the debugging and specific experiments of the high-viscosity nozzle device, it is necessary to test pressure piston segments of various specifications, and the samples stored in the sample segment also need to be replaced multiple times. These steps greatly reduce the efficiency of the experiment. At the same time, compared with the common nylon ring technology, the high-viscosity nozzle does not have a dedicated sample storage tank. These shortcomings have a great impact on users' use of the high-viscosity nozzle platform. Summary of the Invention

[0005] In order to solve the efficiency problem in the existing high-viscosity nozzle technology, the present invention provides a high-efficiency serial crystallography experimental device based on the high-viscosity nozzle technology.

[0006] According to the high-efficiency serial crystallography experimental device of the present invention, the device mainly includes a base, a turntable, a bracket, a threaded sample chamber, a sample chamber front end cap, and a sample chamber rear end cap.

[0007] First, assemble the base with two turntables. One turntable is assembled with the two modular liquid inlet sections and threaded piston chambers of the high-viscosity nozzle assembly, and the other turntable is assembled with a modular threaded sample chamber of the high-viscosity nozzle assembly. The threaded sample chamber can be sealed with a front cap and a rear cap. When conducting high-viscosity nozzle experiments, the two turntables can be used to respectively assemble multiple threaded piston chambers and threaded sample chambers. Rotating the turntables and securing the threaded piston chambers and sample chambers with brackets allows for sample storage, rapid replacement, and front-end pressure conversion.

[0008] Preferably, the base includes a card slot and a base support, and the upper end of the support has two left and right threaded columns, which are assembled with the turntable through the threads on the threaded columns.

[0009] Preferably, the turntable has a middle inner thread groove and a plurality of outer thread grooves, the inner thread groove is assembled with the base thread column, and the outer thread groove is assembled with the threaded piston chamber and the threaded sample chamber.

[0010] Preferably, the lower end of the bracket can be assembled with the slot of the base, and the upper end is semicircular for assembly with the threaded piston chamber and the threaded sample chamber. The bracket is moved along the slot and the turntable is rotated to correct and fix the position of the threaded piston chamber and the threaded sample chamber.

[0011] Preferably, the outer surface of the threaded sample chamber has a partial thread for assembling with the inner and outer thread grooves of the turntable.

[0012] Preferably, the front end cap of the sample chamber can be assembled with the threaded sample chamber input end through threads to achieve a sealing effect. At the same time, the front end cap of the sample chamber has external threads that can be assembled with the internal and external thread grooves of the turntable.

[0013] Preferably, the rear end cap of the sample chamber can be assembled with the output end of the threaded sample chamber through threads to achieve a sealing effect.

[0014] Preferably, the outer surface of the threaded piston chamber has a partial thread for assembling with the inner and outer thread grooves of the turntable.

[0015] The present invention also provides a system based on the efficient serial crystallography experimental device, characterized in that it includes a base 10, two turntables 20, a bracket 30, a threaded sample chamber 40, a sample chamber front end cap 50, a sample chamber rear end cap 60 and a high viscosity nozzle device; wherein,

[0016] The two turntables 20 are coaxially rotatably connected to the base 10;

[0017] The edge of the turntable 20 is provided with a plurality of turntable external thread grooves 22; the turntable 20 for mounting the threaded sample chamber 40 is referred to as a sample turntable, and the turntable 20 for mounting the piston chamber in the high viscosity nozzle device is referred to as a piston turntable; the piston chamber is a threaded piston chamber 70;

[0018] The threaded sample chamber 40 is used to store high-viscosity media containing crystals. The threaded sample chamber 40 is sealed by the sample chamber front cap 50 and the sample chamber rear cap 60 to form a sample module; the sample module is installed on the sample turntable through an external turntable thread groove 22 on the sample turntable; the threaded piston chamber 70 is installed on the piston turntable through an external turntable thread groove 22 on the piston turntable;

[0019] The bracket 30 is connected to the base 10 and is used to support the threaded piston chamber 70 and the threaded sample chamber 40 for experimental alignment and to correct their positions;

[0020] One end of the liquid inlet section 80 of the high viscosity nozzle device is connected to the threaded piston chamber 70, and the other end is used to be connected to the hydraulic equipment.

[0021] Preferably, a turntable internal thread groove 21 is provided at the center of the turntable 20; the base 10 includes a base support 14, a sample thread column 12 and a piston thread column 13; the sample thread column 12 and the piston thread column 13 are coaxially connected to both sides of the base support 14, and the turntable 20 connected to the sample thread column 12 through the turntable internal thread groove 21 is called a sample turntable, and the turntable 20 connected to the piston thread column 13 through the turntable internal thread groove 21 is called a piston turntable.

[0022] Preferably, the input end outer wall of the threaded sample chamber 40 is provided with a thread 42, the front end of the outer wall of the threaded sample chamber 40 is provided with a sample chamber outer thread 41, and the rear end of the inner wall of the threaded sample chamber 40 is provided with an output end thread 43; the front end cap 50 of the sample chamber is an annular structure, the inner wall of which is provided with a front end cap internal thread 51 and the outer wall is provided with a front end cap external thread 52;

[0023] A threaded column 61 is provided at the front end of the sample chamber rear end cap 60; the threaded sample chamber 40 and the sample chamber front end cap 50 are sealed together by the cooperation of the threaded column 61 and the output end thread 43 and the threaded column 61, respectively.

[0024] The sample chamber outer thread 41 and the front end cap outer thread 52 are combined together to serve as the sample module thread, and are used to be assembled with the turntable outer thread groove 22 on the sample turntable.

[0025] Preferably, the threaded piston chamber 70 is used to connect with the liquid inlet section 80, wherein the front end of the threaded piston chamber 70 is provided with a front end threaded column 72, the rear end outer wall is provided with a piston outer thread 71, and the inner wall of the liquid inlet section 80 is provided with a liquid inlet section internal thread 81; the connection between the liquid inlet section 80 and the threaded piston chamber 70 is realized by assembling the liquid inlet section internal thread 81 with the front end threaded column 72; the threaded piston chamber 70 is installed on the piston turntable by assembling the piston outer thread 71 with the turntable external thread groove 22 on the piston turntable.

[0026] Preferably, a slot 11 is provided on the base 10 for connecting and fixing the bracket 30 .

[0027] The present invention also provides a sample loading method based on the efficient serial crystallography experimental device, the steps of which include:

[0028] 1) Installing each selected sample module onto the sample turntable through an external threaded groove 22 on the sample turntable, wherein different sample modules are used to store different crystals or different types of high-viscosity media; Installing each selected threaded piston chamber 70 onto the piston turntable through an external threaded groove 22 on the piston turntable, wherein different threaded piston chambers 70 have different pressure conversion ratios;

[0029] 2) Rotate the sample turntable to select a sample module, and rotate the piston turntable to select a threaded piston chamber 70 of the required specifications; align the threaded sample chamber 40 with the threaded piston chamber 70 in the selected sample module, support and fix them with the bracket, and then perform a high viscosity nozzle test;

[0030] 3) When it is necessary to switch the sample module or the threaded piston chamber 70 for experiment, repeat step 2).

[0031] Compared with the prior art, the present invention has the following positive effects:

[0032] The present invention can achieve rapid pressure debugging, sample replacement and storage of a high-viscosity nozzle device, solve the pain points that affect efficiency, and enable efficient serial crystallography experiments. BRIEF DESCRIPTION OF THE DRAWINGS

[0033] Figure 1 Schematic diagram of an efficient experimental device for high viscosity nozzle technology according to a preferred embodiment of the present invention.

[0034] Figure 2 It is a structural schematic diagram of a base according to a preferred embodiment of the present invention.

[0035] Figure 3 2 is a schematic structural diagram of a turntable according to a preferred embodiment of the present invention.

[0036] Figure 4 1 is a schematic structural diagram of a bracket according to a preferred embodiment of the present invention.

[0037] Figure 5 2 is a schematic structural diagram of a threaded sample chamber according to a preferred embodiment of the present invention.

[0038] Figure 6 FIG. 4 is a rear view of a threaded sample chamber according to a preferred embodiment of the present invention.

[0039] Figure 7 1 is a schematic structural diagram of a front end cap of a sample chamber according to a preferred embodiment of the present invention.

[0040] Figure 8 1 is a schematic structural diagram of a rear end cap of a sample chamber according to a preferred embodiment of the present invention.

[0041] Figure 9 2 is a schematic structural diagram of a threaded piston chamber according to a preferred embodiment of the present invention.

[0042] Figure 10 It is a structural schematic diagram of the liquid inlet section according to a preferred embodiment of the present invention. DETAILED DESCRIPTION

[0043] The preferred embodiments of the present invention are given below in conjunction with the accompanying drawings and described in detail.

[0044] Example

[0045] like Figure 1 As shown, the high-efficiency experimental device for high-viscosity nozzle technology includes a base 10, a turntable 20, a bracket 30, a threaded sample chamber 40, a sample chamber front end cap 50, and a sample chamber rear end cap 60.

[0046] like Figure 2 As shown, the base 10 is provided with a slot 11, a base support 14, a sample threaded column 12 and a piston threaded column 13. The sample threaded column 12 and the piston threaded column 13 have no design difference according to their functions and can be transformed into each other.

[0047] like Figure 3 As shown, a turntable inner thread groove 21 is provided in the middle of the turntable 20, and a plurality of turntable outer thread grooves 22 are provided on the edge. Figure 4 shown.

[0048] During the experiment, the two turntables 20 can be respectively assembled with the sample threaded column 12 and the piston threaded column 13 through the inner thread groove 21 of the turntable. The two turntables 20 can be installed on the base 10. The turntable assembled with the sample threaded column 12 is used as the sample turntable, and the turntable assembled with the piston threaded column 13 is used as the piston turntable.

[0049] The structural design of the threaded sample chamber 40 is as follows Figure 5 、 Figure 6 As shown, the outer wall of the input end is provided with a thread 42, and the outer wall of the front end is provided with a sample chamber outer thread 41. The input end is the entrance for high viscosity samples to be placed into the threaded sample chamber.

[0050] The structural design of the sample chamber front end cap 50 is as follows Figure 7 As shown, it is an annular structure, the inner wall of which is provided with a front end cap internal thread 51, and the outer wall of which is provided with a front end cap external thread 52.

[0051] The structure design of the rear end cap 60 of the sample chamber is as follows Figure 8As shown, a threaded column 61 is provided at its front end.

[0052] The present invention also provides a system based on the efficient serial crystallography experimental device, characterized in that it includes a base 10, two turntables 20, a bracket 30, a threaded sample chamber 40, a sample chamber front end cap 50, a sample chamber rear end cap 60 and a high viscosity nozzle device; wherein,

[0053] The two turntables 20 are coaxially rotatably connected to the base 10;

[0054] The edge of the turntable 20 is provided with a plurality of turntable external thread grooves 22; the turntable 20 for mounting the threaded sample chamber 40 is referred to as a sample turntable, and the turntable 20 for mounting the piston chamber in the high viscosity nozzle device is referred to as a piston turntable; the piston chamber is a threaded piston chamber 70;

[0055] The threaded sample chamber 40 is used to store high-viscosity media containing crystals. The threaded sample chamber 40 is sealed by the sample chamber front cap 50 and the sample chamber rear cap 60 to form a sample module; the sample module is installed on the sample turntable through an external turntable thread groove 22 on the sample turntable; the threaded piston chamber 70 is installed on the piston turntable through an external turntable thread groove 22 on the piston turntable;

[0056] The bracket 30 is connected to the base 10 and is used to support the threaded piston chamber 70 and the threaded sample chamber 40 for experimental alignment and to correct their positions;

[0057] One end of the liquid inlet section 80 of the high viscosity nozzle device is connected to the threaded piston chamber 70, and the other end is used to be connected to the hydraulic equipment.

[0058] The structural design of the threaded piston chamber 70 is as follows Figure 9 As shown, the front end of the threaded piston chamber 70 is provided with a front thread column 72, and the rear end outer wall is provided with a piston chamber outer thread 71.

[0059] The structural design of the liquid inlet section 80 is as follows Figure 10 As shown, the inner wall is provided with an internal thread 81 of the liquid inlet section.

[0060] When the high-viscosity medium containing crystals is prepared, it is placed in the threaded sample chamber 40. The threaded sample chamber 40 is assembled with the front end cap internal thread 51 of the sample chamber front end cap 50 through the thread 42. The sample chamber rear end cap 60 can also be assembled with the output end thread 43 of the threaded sample chamber 40 through the threaded column 61. The assembled sample module is assembled with the front end cap external thread 52, the sample chamber external thread 41 and the turntable external thread groove 22 of the sample turntable. One sample turntable can be equipped with multiple sample modules to serve as a sample storage tank.

[0061] For the piston turntable, it is also assembled with the outer thread groove 22 of the turntable of the piston turntable and the outer thread 71 of the piston chamber 70. After the threaded piston chamber 70 is assembled to the piston turntable, the liquid inlet section 80 is assembled with the front end thread column 72 of the threaded piston chamber 70 through the inner thread 81 of the liquid inlet section. The liquid inlet section 80 is connected to the front end hydraulic equipment through the liquid inlet section input end 82. The internal structure of the liquid inlet section 80 and the threaded piston chamber 70 is consistent with the conventional liquid inlet section and piston chamber in this field. Its main function is to provide hydraulic and pressure conversion. The difference is that the threaded piston chamber 70 has the piston chamber outer thread 71. In this way, a piston turntable can be equipped with multiple threaded piston chambers 70 through the design of the piston chamber outer thread 71.

[0062] After the device is assembled, you can conduct a high-efficiency high-viscosity nozzle test. By turning the piston dial, you can quickly select the threaded piston chamber 70 of the appropriate specifications. Figure 1 As shown, after selecting the threaded piston chamber 70, rotate it to the position directly above the slot 11 of the base 10. At the same time, assemble the bracket 30 with the slot 11, thereby correcting the position of the threaded piston chamber 70 and supporting it. Similarly, the bracket 30 also corrects the position of the threaded sample chamber 40 and supports it. Subsequently, rotate the sample turntable to quickly align the stored threaded sample chamber 40 with the threaded piston chamber 70. After removing the front cap 50 of the sample chamber, the threaded sample chamber 40 and the threaded piston chamber 70 can be assembled for subsequent high-viscosity nozzle experiments.

[0063] The present invention is based on the sample loading method of the efficient serial crystallography experimental device, and the steps include:

[0064] 1) Installing each selected sample module onto the sample turntable through an external threaded groove 22 on the sample turntable, wherein different sample modules are used to store different crystals or different types of high-viscosity media; Installing each selected threaded piston chamber 70 onto the piston turntable through an external threaded groove 22 on the piston turntable, wherein different threaded piston chambers 70 have different pressure conversion ratios;

[0065] 2) Rotate the sample turntable to select a sample module, and rotate the piston turntable to select a threaded piston chamber 70 of the required specifications; align the threaded sample chamber 40 and the threaded piston chamber 70 in the selected sample module, support and fix them with the bracket, and then perform a high viscosity nozzle test;

[0066] 3) When it is necessary to switch the sample module or the threaded piston chamber 70 for experiment, repeat step 2).

[0067] The above description is merely a preferred embodiment of the present invention and is not intended to limit the scope of the present invention. Various modifications are possible. In other words, any simple, equivalent changes and modifications made in accordance with the claims and description of the present invention are within the scope of protection of the patent claims. Anything not fully described in this invention constitutes conventional technical content.

Claims

1. An efficient serial crystallography experimental device based on high viscosity nozzle technology, characterized in that: It comprises a base (10), two turntables (20), a bracket (30), a threaded sample chamber (40), a sample chamber front end cap (50), and a sample chamber rear end cap (60); wherein, The two rotating disks (20) are coaxially rotatably connected to the base (10); The edge of the turntable (20) is provided with a plurality of turntable inner thread grooves (22); the turntable (20) for mounting the threaded sample chamber (40) is referred to as a sample turntable, and the turntable (20) for mounting the threaded piston chamber (70) is referred to as a piston turntable; The threaded sample chamber (40) is used to store a high-viscosity medium containing crystals. The threaded sample chamber (40) is sealed by the sample chamber front end cap (50) and the sample chamber rear end cap (60) to form a sample module; the sample module is installed on the sample turntable through an internal thread groove (22) on the sample turntable; the threaded piston chamber (70) is installed on the piston turntable through an internal thread groove (22) on the piston turntable; The bracket (30) is connected to the base (10) and is used to support the threaded piston chamber (70) and the threaded sample chamber (40) for experimental alignment and to correct their positions.

2. The device according to claim 1, characterized in that A turntable inner thread groove (21) is provided at the center of the turntable (20); the base (10) includes a base support (14), a sample thread column (12) and a piston thread column (13); the sample thread column (12) and the piston thread column (13) are coaxially connected to both sides of the base support (14); the turntable (20) connected to the sample thread column (12) through the turntable inner thread groove (21) is called a sample turntable, and the turntable (20) connected to the piston thread column (13) through the turntable inner thread groove (21) is called a piston turntable.

3. The device according to claim 1, characterized in that The input end outer wall of the threaded sample chamber (40) is provided with a thread (42), the front end of the outer wall of the threaded sample chamber (40) is provided with a sample chamber outer thread (41), and the rear end of the inner wall of the threaded sample chamber (40) is provided with an output end thread (43); the front end cap (50) of the sample chamber is an annular structure, the inner wall of which is provided with a front end cap internal thread (51) and the outer wall is provided with a front end cap external thread (52); The threaded sample chamber (40) and the front end cap (50) are sealed together by the cooperation of the thread (42) and the internal thread (51) of the front end cap, and a threaded column (61) is provided at the front end of the rear end cap (60) of the sample chamber. The threaded sample chamber (40) and the rear end cap (60) are sealed together by the cooperation of the output end thread (43) and the threaded column (61) to form the sample module. The sample chamber outer thread (41) and the front end cap outer thread (52) are combined together to serve as the sample module thread, and are used to be assembled with the turntable inner thread groove (22) on the sample turntable.

4. The device according to claim 1, characterized in that The threaded piston chamber (70) is used to connect with the liquid inlet section (80), wherein the front end of the threaded piston chamber (70) is provided with a front end threaded column (72), the rear end outer wall is provided with a piston chamber outer thread (71), and the inner wall of the liquid inlet section (80) is provided with a liquid inlet section inner thread (81); the connection between the liquid inlet section (80) and the threaded piston chamber (70) is achieved by assembling the liquid inlet section inner thread (81) with the front end threaded column (72); the threaded piston chamber (70) is installed on the piston turntable by assembling the piston chamber outer thread (71) with the turntable inner thread groove (22) on the piston turntable.

5. The device according to claim 1, characterized in that The base (10) is provided with a slot (11) for connecting and fixing the bracket (30).

6. A system based on the efficient serial crystallography experimental device according to claim 1, characterized in that: It comprises a base (10), two turntables (20), a bracket (30), a threaded sample chamber (40), a sample chamber front end cap (50), a sample chamber rear end cap (60) and a high viscosity nozzle device; wherein, The two rotating disks (20) are coaxially rotatably connected to the base (10); The edge of the turntable (20) is provided with a plurality of turntable inner thread grooves (22); the turntable (20) for mounting the threaded sample chamber (40) is referred to as a sample turntable, and the turntable (20) for mounting the piston chamber in the high-viscosity nozzle device is referred to as a piston turntable; the piston chamber is a threaded piston chamber (70); The threaded sample chamber (40) is used to store a high-viscosity medium containing crystals. The threaded sample chamber (40) is sealed by the sample chamber front end cap (50) and the sample chamber rear end cap (60) to form a sample module; the sample module is installed on the sample turntable through an internal thread groove (22) on the sample turntable; the threaded piston chamber (70) is installed on the piston turntable through an internal thread groove (22) on the piston turntable; The support (30) is connected to the base (10) and is used to support the threaded piston chamber (70) and the threaded sample chamber (40) for experimental alignment and to correct their positions; One end of the liquid inlet section (80) of the high-viscosity nozzle device is connected to the threaded piston chamber (70), and the other end is used to be connected to the hydraulic equipment.

7. A sample loading method based on the efficient serial crystallography experimental device according to claim 1, comprising the steps of: 1) Each selected sample module is installed on the sample turntable through a turntable inner thread groove (22) on the sample turntable, wherein different sample modules are used to store different crystals or different types of high-viscosity media; and threaded piston chambers (70) of selected specifications are installed on the piston turntable through a turntable inner thread groove (22) on the piston turntable, wherein threaded piston chambers (70) of different specifications have different pressure conversion ratios; 2) rotating the sample turntable to select a sample module, and rotating the piston turntable to select a threaded piston chamber (70) of a desired specification; aligning the threaded sample chamber (40) and the threaded piston chamber (70) in the selected sample module, and then supporting and fixing them with the bracket to perform a high viscosity nozzle experiment; 3) When it is necessary to switch the sample module or the threaded piston chamber (70) to conduct the experiment, repeat step 2).

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