Design and use method of brain imaging movable base based on miniaturized microscopic system

Abstract

The invention discloses a design and use method of a brain imaging movable base based on a miniaturized microscopic system, the miniaturized microscopic system is placed on a substrate, the center of the substrate is provided with a hole with the same size as a gradient index lens (GRIN lens), and the lens can extend out of the hole; the bottom surface of the substrate is provided with four magnets which are opposite to the four magnets on the bottom surface of the miniaturized microscopic system in magnetism and are used for ensuring uniformity and levelness during installation. The two sides of the substrate are provided with two fixing screws which are used for fixing the microscopic system. The base plate is connected with the axial displacement platform, and the axial position of the axial displacement platform is adjusted through a spring and a screw which are connected with the transverse displacement platform below the axial displacement platform. The transverse displacement table is placed on the hollow sliding rail, and the transverse position of the transverse displacement table is adjusted through a screw penetrating through the positioning hole and a spring connected with the top plate. The center of the axial displacement table and the center of the transverse displacement table are each provided with a hole allowing the GRIN lens to pass through. The hollow slide rail is provided with four bases which are fixed on the head of a test animal through glue. According to the scheme, fast and convenient imaging at different positions of the head of the same animal is achieved, and influences on test results and injuries to the animal caused by multiple operations and installation processes are avoided.

Description

Technical Field

[0001] The present invention relates to a method for fixing a miniaturized microscopic imaging device, and more particularly to a design and use method of a movable base for brain imaging based on a miniaturized microscopic system. A miniaturized fluorescence microscopic imaging microscope has the advantages of being small in size and light in weight, and can image the brain neurons of experimental animals within the range in which they can move freely. However, how to stably fix the miniaturized microscopic imaging device on the head of an animal and adjust the position of the microscopic system within a certain range is a problem that needs to be solved. Background Art

[0002] Optical microscopes are key instruments for qualitative and quantitative analysis in precision manufacturing and life sciences. Compared with other imaging techniques, microscopes working in the visible light band have the characteristics of high resolution, high throughput, multi-spectrum, and non-invasiveness. By combining the excitation light with the localization expression technology of markers such as fluorescent proteins and fluorescent dyes in cells, the specificity of the emission spectrum can be used to distinguish different structural components and their interactions within organisms and even cells, and to dynamically record their functions when organisms and cells are active. Multifunctional in vivo imaging has always been one of the goals pursued by optical microscopes. For example, the observation of living cells in culture dishes is already very mature, but the imaging of living tissue cells in animals is still a big challenge. Among mammalian species, mice are excellent and tenacious genetic models for targeted manipulation of cell characteristics, but when using optical microscopes to observe their brains, their limbs and heads still need to be fixed, and the objective lens needs to be fixed above the head for observation. This restriction on their normal behavior and activities will greatly affect the universality of obtaining information. Later, scientists also tried to introduce VR technology to create a free activity scene for mice with fixed heads, but this technology has gradually been doubted by biologists. Therefore, head-mounted miniaturized microscopic imaging devices gradually came into the field of vision of researchers. The miniaturized microscopic imaging device has an objective lens structure, a stable working distance, imaging depth and spatial resolution, and because of its small size and light weight, the surgical trauma during the installation process is small, all of which are within the range that the experimental animals can bear, ensuring the physiological state of wakefulness and free will. With the passage of time, the miniaturized microscopic imaging system has made great progress in terms of volume, quality and performance. The improvement of manufacturing technology is the most critical progress in miniaturized integration. The GRIN lens replaces the traditional objective lens, the small-size optical components replace the conventional-size optical components, and all the optical components are integrated in the 3D-printed shell, and a miniaturized microscopic system that can be worn on the head comes into being. In life sciences, miniaturized microscopic systems have been proven to be able to achieve many uses, such as fluorescence imaging, two-photon imaging, optogenetics and three-dimensional imaging. Due to its advantages such as small size and high integration, miniaturized microscopic systems can complete measurement work under special circumstances. Therefore, miniaturized microscopic systems are of great significance in life sciences and industrial detection.

[0003] However, the miniaturized microscope system cannot be directly connected to the mouse head because of its complex structure and small size, which makes it difficult to fix. Even if it is barely fixed, the violent shaking will affect the imaging effect. This requires a device that can both stably connect to the mouse head and firmly fix the miniaturized microscope system. The traditional fixed platform can only be positioned at a single position, so that the microscope system can only observe a single position and cannot perform control observations on the surrounding tissue cells. Therefore, a movable miniaturized microscope system brain imaging base is very necessary. Summary of the invention

[0004] A brief overview of the present invention is provided below in order to provide a basic understanding of certain aspects of the present invention. It should be understood that this overview is not an exhaustive overview of the present invention. It is not intended to identify key or important parts of the present invention, nor is it intended to limit the scope of the present invention. Its purpose is merely to present certain concepts in a simplified form as a prelude to a more detailed description discussed later.

[0005] In view of this, in order to overcome the above-mentioned technical problems, the present invention provides a design and use method of a movable base for brain imaging based on a miniaturized microscope system. Through the dynamic design of a multi-layer displacement table, a device is realized that can firmly fix the miniaturized microscope system and can conveniently adjust the axial and lateral positions of the microscope system in real time, thereby avoiding secondary damage and waste of time costs caused by repeated installations.

[0006] Solution 1: The present invention provides a design method for a movable base for brain imaging based on a miniaturized microscopic system, comprising a lateral displacement module, an axial displacement module and a miniaturized microscopic system fixing module;

[0007] The transverse displacement module components are: a top plate, a hollow slide rail, a base, a transverse spring, a transverse displacement platform, a positioning hole and a transverse screw;

[0008] The axial displacement module components are: an axial spring, an axial screw and an axial displacement platform;

[0009] The fixing module components of the miniaturized microscopy system are: fixing screw 1, fixing screw 2, magnet and substrate;

[0010] Furthermore: the lateral translation stage, the axial translation stage and the center of the substrate all have a hole with a diameter of 2 mm, and the three holes are symmetrical in center, and a GRIN lens with a diameter of 2 mm passes through to form an image.

[0011] Furthermore: the substrate has a rectangular groove with a size of 10mm×6mm×5mm, a groove depth of 4mm and a wall thickness of 2mm.

[0012] Furthermore: the fixing screw 1 and the fixing screw 2 are both self-tapping screws with a diameter of 2 mm.

[0013] Furthermore: the magnets are all rare earth magnets with the same magnetic orientation, evenly distributed at the four corners of the substrate, and just coincide with the position of the magnets at the bottom of the designed miniaturized microscope system.

[0014] Furthermore: the dimensions of the lateral displacement stage and the axial displacement stage are 20 mm×18 mm×5 mm.

[0015] Furthermore: the transverse spring and the axial spring are both compression springs with a maximum preload of 8 mm.

[0016] Furthermore: the transverse screw and the axial screw are both self-tapping screws with a diameter of 5 mm.

[0017] Further: the size of the top plate is 18mm×8mm×2mm.

[0018] Furthermore: the size of the hollow slide rail is 40mm×18mm×2mm, and the wall thickness is 5mm.

[0019] Further: when the hollow slide rail is fixed to the head of the test animal, it is necessary to scratch some marks on its bottom with a sharp object to make the combination between it and the glue more firm and tight.

[0020] Furthermore: the top plate, hollow slide rail, base, lateral displacement table, positioning hole, axial displacement table and base are made of photosensitive resin using a 3D printer.

[0021] Solution 2: The present invention proposes a method for using a movable base for brain imaging based on a miniaturized microscope system. This method is implemented based on the design method of a movable base for brain imaging based on a miniaturized microscope system described in Solution 1. The method of use is divided into three parts, namely a fixing step, a microscope system installation step, and a position adjustment step.

[0022] Fixing steps:

[0023] After craniotomy, place the base in the appropriate position, and keep the hollow part of the hollow slide rail just above the craniotomy site. Use a sharp object to gently scrape the animal's skull and the bottom of the slide rail to make the connection with the glue tighter.

[0024] Microscope system installation steps:

[0025] The miniaturized microscope is gently placed on the substrate, and the rare earth magnet at the bottom of the microscope fits with the magnet with opposite magnetic properties at the bottom of the microscope, thereby ensuring the level of the microscope to avoid affecting the imaging effect. Then, the microscope is tightly fixed on the substrate by rotating the fixing screws 1 and 2.

[0026] Position adjustment steps

[0027] The lateral position of the microscope system is achieved by rotating the lateral screw fixed on the positioning hole, and the lateral spring provides dynamic support. The axial position of the microscope system is achieved by the axial screw. The top of the axial screw involved has a thread. The axial position of the translation stage is controlled by rotating the nut nested on its top, and the axial spring provides dynamic support.

[0028] Beneficial Effects

[0029] The present invention provides a solution based on the fixation and movement of a miniaturized microscopic system during a freely moving mouse head experiment. The present invention flexibly realizes the lateral and axial movement of the miniaturized microscopic system through the technology of a multilayer displacement stage, and the adjustment method is simple. At the same time, two screws at the base plate ensure that the microscopic system can be tightly fixed. In addition, four magnets are introduced on the base plate, which cooperate with four magnets with the same position and opposite magnetic properties on the microscopic system to ensure uniformity and levelness during installation of the microscopic system. BRIEF DESCRIPTION OF THE DRAWINGS

[0030] Figure 1 It is a schematic structural diagram of the movable base for brain imaging based on the miniaturized microscope system of the present invention.

[0031] In the figure: 1 top plate, 2 hollow slide rail, 3 base, 4 transverse spring, 5 transverse displacement stage, 6 positioning hole, 7 transverse screw, 8 axial spring, 9 axial screw, 10 axial displacement stage, 11 fixing screw 1, 12 fixing screw 2, 13 magnet, 14 base plate. DETAILED DESCRIPTION

[0032] Exemplary embodiments of the present invention will be described below in conjunction with the accompanying drawings. For the sake of clarity and conciseness, not all features of the actual implementation are described in the specification. However, it should be understood that many implementation-specific decisions must be made in the process of developing any such actual implementation in order to achieve the developer's specific goals, such as meeting those constraints related to the system and business, and these constraints may vary from implementation to implementation. In addition, it should be understood that although the development work may be very complex and time-consuming, it is only a routine task for those skilled in the art who benefit from the disclosure of the present invention.

[0033] It is also necessary to explain here that, in order to avoid obscuring the present invention due to unnecessary details, only the device structure and / or processing steps closely related to the scheme according to the present invention are shown in the accompanying drawings, while other details that are not closely related to the present invention are omitted.

[0034] Embodiment 1: As attached Figure 1As shown, the present invention provides a design method for a movable base for brain imaging based on a miniaturized microscopic system, which is used to solve the problem of fixation and two-dimensional movement of the miniaturized microscopic system on the head of a freely moving mouse.

[0035] A movable base for brain imaging based on a miniaturized microscopic system, comprising a lateral displacement module, an axial displacement module and a miniaturized microscopic system fixing module;

[0036] The transverse displacement module components are: a top plate 1, a hollow slide rail 2, a base 3, a transverse spring 4, a transverse displacement platform 5, a positioning hole 6 and a transverse screw 7;

[0037] The axial displacement module components are: an axial spring 8, an axial screw 9 and an axial displacement platform 10;

[0038] The fixing module components of the miniaturized microscope system are: fixing screws 111, fixing screws 212, magnets 13 and base plate 14;

[0039] More specifically: the lateral translation stage 5, the axial translation stage 10 and the substrate 14 all have a hole with a diameter of 2 mm in the center, and the three holes are symmetrical about the center, and a GRIN lens with a diameter of 2 mm passes through to form an image.

[0040] More specifically: the substrate 14 has a rectangular groove size of 10 mm×6 mm×5 mm, a groove depth of 4 mm, and a wall thickness of 2 mm.

[0041] More specifically, the fixing screws 111 and 212 are both self-tapping screws with a diameter of 2 mm.

[0042] More specifically: the magnets 13 are all rare earth magnets with the same magnetic orientation, evenly distributed at the four corners of the substrate, and just coincide with the position of the magnets at the bottom of the designed miniaturized microscope system.

[0043] More specifically, the dimensions of the lateral displacement stage 5 and the axial displacement stage 10 are 20 mm×18 mm×5 mm.

[0044] More specifically: the transverse spring 4 and the axial spring 8 are both compression springs with a maximum preload of 8 mm.

[0045] More specifically, the transverse screw 7 and the axial screw 9 are both self-tapping screws with a diameter of 5 mm.

[0046] More specifically: the size of the top plate 1 is 18mm×8mm×2mm.

[0047] More specifically: the size of the hollow slide rail 2 is 40mm×18mm×2mm, and the wall thickness is 5mm.

[0048] More specifically: when the hollow slide rail 2 is fixed to the head of the test animal, it is necessary to scratch some marks on the bottom thereof with a sharp object to make the combination between it and the glue more firm and tight.

[0049] More specifically: the top plate 1, the hollow slide rail 2, the base 3, the lateral displacement stage 5, the positioning hole 6, the axial displacement stage 10 and the base plate 14 are made of photosensitive resin using a 3D printer.

[0050] A method for using a movable base for brain imaging based on a miniaturized microscopic system, which is implemented based on the design method for a movable base for brain imaging based on a miniaturized microscopic system described in Example 1, and specifically comprises the following steps:

[0051] Fixing steps:

[0052] After the craniotomy, the base 3 is placed in a suitable position, and the hollow part of the hollow slide rail 2 is kept just above the craniotomy site. The animal skull and the bottom of the slide rail are gently scraped with a sharp instrument to make the connection with the glue more secure.

[0053] Microscope system installation steps:

[0054] The miniaturized microscope system is gently placed on the substrate 14, and the rare earth magnet 13 at the bottom thereof fits with the magnet with opposite magnetic properties at the bottom of the microscope system, thereby ensuring the level of the microscope system to avoid affecting the imaging effect. The microscope system is then tightly fixed on the substrate 14 by rotating the fixing screws 111 and 212.

[0055] Position adjustment steps

[0056] The lateral position of the microscope system is achieved by rotating the lateral screw 7 fixed on the positioning hole 6, and the lateral spring 4 provides dynamic support.

[0057] The axial position of the microscope system is achieved by an axial screw 9, the top of which is threaded. The axial position of the translation stage is controlled by rotating the nut nested on the top of the screw, and the axial spring 8 provides dynamic support.

[0058] Although the embodiments disclosed in the present invention are as above, the contents are only embodiments adopted for facilitating understanding of the technical solution of the present invention, and are not used to limit the present invention. Any technician in the technical field to which the present invention belongs can make any modifications and changes in the form and details of the implementation without departing from the core technical solution disclosed in the present invention, but the protection scope defined by the present invention shall still be subject to the scope defined in the attached claims.

Claims

1. A movable base for brain imaging based on a miniaturized microscopic system, characterized in that: It includes a lateral displacement module, an axial displacement module and a miniaturized microscopic system fixing module; The transverse displacement module components are: a top plate (1), a hollow slide rail (2), a base (3), a transverse spring (4), a transverse displacement platform (5), a positioning hole (6) and a transverse screw (7); The axial displacement module components are: an axial spring (8), an axial screw (9) and an axial displacement platform (10); The fixing module components of the miniaturized microscope system are: a fixing screw 1 (11), a fixing screw 2 (12), a magnet (13) and a base plate (14).

2. The movable base for brain imaging based on a miniaturized microscopic system according to claim 1, characterized in that: The lateral displacement stage (5), the axial displacement stage (10) and the base plate (14) all have a hole with a diameter of 2 mm at their centers, and the three holes are centrally symmetrical, through which a GRIN lens with a diameter of 2 mm passes, thereby forming an image.

3. The movable base for brain imaging based on a miniaturized microscopic system according to claim 1, characterized in that: The base plate (14) has a rectangular groove with a size of 10 mm×6 mm×5 mm, a groove depth of 4 mm and a wall thickness of 2 mm.

4. The movable base for brain imaging based on a miniaturized microscopic system according to claim 1, characterized in that: The fixing screw 1 (11) and the fixing screw 2 (12) are both self-tapping screws with a diameter of 2 mm.

5. The movable base for brain imaging based on a miniaturized microscopic system according to claim 1, characterized in that: The magnets (13) are all rare earth magnets with the same magnetic orientation and are evenly distributed at the four corners of the substrate, exactly coinciding with the position of the magnets at the bottom of the designed miniaturized microscope system.

6. The movable base for brain imaging based on a miniaturized microscopic system according to claim 1, characterized in that: The dimensions of the lateral displacement stage (5) and the axial displacement stage (10) are 20 mm×18 mm×5 mm.

7. The movable base for brain imaging based on a miniaturized microscopic system according to claim 1, characterized in that: The transverse spring (4) and the axial spring (8) are both compression springs with a maximum preload of 8 mm.

8. The movable base for brain imaging based on a miniaturized microscopic system according to claim 1, characterized in that: The transverse screw (7) and the axial screw (9) are both self-tapping screws with a diameter of 5 mm.

9. The movable base for brain imaging based on a miniaturized microscopic system according to claim 1, characterized in that: The size of the top plate (1) is 18 mm×8 mm×2 mm.

10. The movable base for brain imaging based on a miniaturized microscopic system according to claim 1, characterized in that: The hollow slide rail (2) has a size of 40 mm×18 mm×2 mm and a wall thickness of 5 mm.

11. The movable base for brain imaging based on a miniaturized microscopic system according to claim 1, characterized in that: When the hollow slide rail (2) is fixed to the head of the test animal, it is necessary to scratch some marks on its bottom with a sharp object to make the combination between it and the glue more firm and tight.

12. The movable base for brain imaging based on a miniaturized microscopic system according to claim 1, characterized in that: The top plate (1), hollow slide rail (2), base (3), lateral displacement platform (5), positioning hole (6), axial displacement platform (10) and base plate (14) are made of photosensitive resin using a 3D printer.

13. The method for using the movable base for brain imaging based on a miniaturized microscopic system according to claim 1 is divided into three parts, namely, a fixing step, a microscopic system installation step, and a position adjustment step, characterized in that: Fixing steps: After the craniotomy, the base (3) is placed in a suitable position, and the hollow part of the hollow slide rail (2) is kept just above the craniotomy site. The animal skull and the bottom of the slide rail are lightly scraped with a sharp object so that the connection between the two and the glue is more secure. Microscope system installation steps: The miniaturized microscope system is gently placed on the base plate (14), and the rare earth magnet (13) at the bottom thereof is fitted with the magnet with opposite magnetic properties at the bottom of the microscope system, thereby ensuring the level of the microscope system to avoid affecting the imaging effect. Subsequently, the microscope system is tightly fixed on the base plate (14) by rotating the fixing screw 1 (11) and the fixing screw 2 (12). Position adjustment steps The lateral position of the microscope system is achieved by rotating the lateral screw (7) fixed on the positioning hole (6), and the lateral spring (4) provides dynamic support. The axial position of the microscope system is achieved by the axial screw (9), and the top of the axial screw involved has a thread. The axial position of the translation stage is controlled by rotating the nut nested on the top of it, and the axial spring (8) provides dynamic support.

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