WO2021184462A1 - 脑立体定向注射装置 - Google Patents

脑立体定向注射装置 Download PDF

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Publication number
WO2021184462A1
WO2021184462A1 PCT/CN2020/084440 CN2020084440W WO2021184462A1 WO 2021184462 A1 WO2021184462 A1 WO 2021184462A1 CN 2020084440 W CN2020084440 W CN 2020084440W WO 2021184462 A1 WO2021184462 A1 WO 2021184462A1
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WIPO (PCT)
Prior art keywords
leveling
scale
assembly
ear
injection device
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PCT/CN2020/084440
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English (en)
French (fr)
Inventor
黄强
欧阳雨林
詹阳
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中国科学院深圳先进技术研究院
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Publication of WO2021184462A1 publication Critical patent/WO2021184462A1/zh

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61D—VETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
    • A61D7/00—Devices or methods for introducing solid, liquid, or gaseous remedies or other materials into or onto the bodies of animals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61D—VETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
    • A61D3/00—Appliances for supporting or fettering animals for operative purposes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/008—Racks for supporting syringes or needles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61M—DEVICES FOR INTRODUCING MEDIA INTO, OR ONTO, THE BODY; DEVICES FOR TRANSDUCING BODY MEDIA OR FOR TAKING MEDIA FROM THE BODY; DEVICES FOR PRODUCING OR ENDING SLEEP OR STUPOR
    • A61M5/00—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests
    • A61M5/46—Devices for bringing media into the body in a subcutaneous, intra-vascular or intramuscular way; Accessories therefor, e.g. filling or cleaning devices, arm-rests having means for controlling depth of insertion
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61D—VETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
    • A61D3/00—Appliances for supporting or fettering animals for operative purposes
    • A61D2003/003—Appliances for supporting or fettering animals for operative purposes with head or neck restraining means

Definitions

  • This application relates to the technical field of biological experimental supplies, for example, to a brain stereotactic injection device.
  • intracerebral injection is an important method of animal experiments, which plays a vital role in the establishment of disease models, intracerebral drug treatment, and the exploration of the projection relationship between the central nucleus.
  • Injection of samples, such as viruses, cells, protein molecules, drugs, labeled dye probes, etc. into the brain can directly act on the target brain areas of living animals, including neurons, glial cells, blood vessels, and the microenvironment in the brain.
  • This kind of precise brain location drug delivery does not involve the drug metabolism of organs and tissues and the blood-brain barrier. That is to say, the precise brain location drug delivery can more accurately reflect the direct effects of drugs than the results obtained by other routes of administration.
  • the commercialized stereotactic injection device in the laboratory in the related technology requires a combination of a laboratory table, a stereotaxic device, a micro-injection pump, and a skull drill.
  • To locate the origin determine the injection point according to the coordinates, use a skull drill to open a cranial window, and use a micro-injection pump and a syringe to slowly inject the sample.
  • the disadvantage of this method is that the instrument needs a fixed experimental table and stable facilities as support, the equipment cost is high, the operation method is cumbersome and the experiment time is long. It takes 40-60 minutes from the fixed mouse to the completion of the injection.
  • the experimental mice caused damage or even death, which could not meet the requirements of accurate and rapid drug delivery to the brain under the limited experimental space and equipment.
  • the location of each nucleus in the brain is intricately distributed, and direct intracranial administration using an injection needle cannot accurately inject the sample into the target brain area. Therefore, a set of convenient and practical three-dimensional intracerebral injection tools is required.
  • This application proposes a brain stereotactic injection device, which has a simple structure and is convenient to use.
  • a stereotactic brain injection device comprising: a housing, the housing defines an accommodating cavity, the accommodating cavity is configured to place an animal to be tested, and the housing is provided with a device extending in the up and down direction The upper and lower scales; positioning assembly, the positioning assembly is slidably arranged on the housing, the positioning assembly is provided with a first scale and a second scale, the extension direction of the first scale and the second The extension direction of the scale is vertical, the positioning component is provided with a matching hole; a fixing component, the fixing component is arranged in the containing cavity, and the fixing component is configured to fix the animal to be tested in the containing cavity An injection component, the injection component can pass through the matching hole and extend into the accommodating cavity, the injection component is provided with a pointer configured to point to the upper and lower graduations, the injection component is configured to The animal to be tested is injected with experimental reagents; a leveling component can pass through the matching hole and extend into the containing cavity, and the leveling component is configured to detect the
  • Fig. 1 is a schematic diagram of a partial structure of a brain stereotactic injection device according to an embodiment of the present application.
  • FIG. 2 is a schematic structural diagram of the leveling component of the stereotactic brain injection device according to the embodiment of the present application fitted in the matching hole.
  • FIG. 3 is a schematic diagram of the structure of the injection component of the stereotactic brain injection device fitted in the matching hole according to the embodiment of the present application.
  • FIG. 4 is a schematic diagram of the structure of the head fixing module of the brain stereotactic injection device according to the embodiment of the present application.
  • FIG. 5 is a schematic diagram of the structure of the ear bar module of the brain stereotactic injection device according to the embodiment of the present application.
  • Fig. 6 is a schematic structural diagram of an injection assembly of a brain stereotactic injection device according to an embodiment of the present application.
  • Fig. 7 is a schematic structural diagram of the leveling assembly of the brain stereotactic injection device according to the embodiment of the present application.
  • Fig. 8 is a schematic diagram of the skull of an animal to be tested in an embodiment of the present application.
  • Fixing components 31, head fixing module; 311, column; 312, support member; 313, rotating shaft; 32, ear rod module; 321, ear fixing member; 322, adjusting part; 3221, adjusting sleeve; 3222. Adjusting block; 3223. Adjusting stud; 323. Locking piece;
  • Injection assembly 41. Injection syringe; 42, connecting rod; 421, pointer; 422, connecting hole; 43, locking piece;
  • Leveling components 51. Leveling main body; 511. Leveling rod; 512. Leveling block; 5121, Leveling groove; 52. Level; 53, Bifurcation part; 531. Cooperating part; 532, Bifurcation part ;
  • first and second may explicitly or implicitly include one or more of these features, which are used to distinguish and describe the features, without ordering, and without priority.
  • plural means two or more.
  • connection should be understood in a broad sense, unless otherwise clearly specified and limited.
  • it can be a fixed connection or a detachable connection.
  • Connected or integrally connected it can be a mechanical connection or an electrical connection; it can be directly connected or indirectly connected through an intermediate medium, and it can be the internal communication between two components.
  • connection should be understood in a broad sense, unless otherwise clearly specified and limited.
  • it can be a fixed connection or a detachable connection.
  • Connected or integrally connected it can be a mechanical connection or an electrical connection; it can be directly connected or indirectly connected through an intermediate medium, and it can be the internal communication between two components.
  • the specific meanings of the above terms in this application can be understood under specific circumstances.
  • the structure of the brain stereotactic injection device according to the embodiment of the present application will be described below with reference to FIGS. 1 to 8.
  • the stereotactic brain injection device of this embodiment includes a housing 1, a positioning assembly 2, a fixing assembly 3, an injection assembly 4, and a leveling assembly 5.
  • the housing 1 defines a receiving cavity 11 for accommodating The cavity 11 is used to place the animal 100 to be tested.
  • the housing 1 is provided with upper and lower scales 12 extending in the vertical direction.
  • the positioning assembly 2 is slidably arranged on the housing 1, and the positioning assembly 2 is provided with a first scale 211 And the second scale 221, the extension direction of the first scale 211 is perpendicular to the extension direction of the second scale 221, the positioning assembly 2 is provided with a matching hole 201, the fixing assembly 3 is arranged in the containing cavity 11, and the fixing assembly 3 is used to The animal 100 to be tested is fixed in the accommodating cavity 11, the injection assembly 4 can pass through the fitting hole 201 and extend into the accommodating cavity 11.
  • the injection assembly 4 is provided with a pointer 421 for pointing to the upper and lower scales 12, and the injection assembly 4 is used to
  • the animal 100 is injected with experimental reagents, the leveling component 5 can pass through the matching hole 201 and extend into the containing cavity 11, and the leveling component 5 is used to adjust the head of the animal 100 to be tested.
  • the animal 100 to be tested is placed in the containing cavity 11, the animal to be tested 100 is fixed in the containing cavity 11 by the fixing assembly 3, and the leveling assembly 5 is used after the experimental animal is initially fixed.
  • the level of the skull of the animal 100 to be tested is detected, and the skull of the animal 100 to be tested is leveled by continuously adjusting the fixing assembly 3.
  • the marker pen passes the marker pen through the matching hole 201, use the marker pen to mark a certain biological marker point of the skull of the animal to be tested 100 as the coordinate origin, and record the coordinates of the first scale 211 and the second scale 221 at this time, Then move the positioning component 2 to find the position of the target brain area by calculating the offset distance between the matching hole 201 and the coordinate origin of the XY axis, and use a marker to make the injection point on the skull. Then the injection is performed. During the injection process, the needle of the injection assembly 4 is inserted into the point to be injected.
  • the brain stereotactic injection device of this embodiment ensures that the skull level of the animal to be tested 100 can be ensured during the injection process through the interaction of the positioning assembly 2, the leveling assembly 5, and the fixing assembly 3, and that the injection can be stabilized. And it's done accurately.
  • the injection assembly 4 is provided with a pointer 421 pointing to the upper and lower scales 12, precise control of the injection depth of the injection assembly 4 is realized, thereby ensuring the injection accuracy.
  • the brain stereotactic injection device of this embodiment has a very simple structure and convenient operation, which improves experiment efficiency and reduces experiment costs.
  • the brain stereotactic injection device of this embodiment is provided with a fixing assembly 3 and a leveling assembly 5 for fixing and adjusting the posture of the animal to be tested 100, and has a positioning assembly 2 for positioning the injection assembly 4 and an upper and lower scale for positioning the injection depth 12 and pointer 421 simplifies the operation process of stereotactic injection, realizes standardized and precise stereotactic injection operation, saves experiment space, and improves experiment efficiency.
  • the whole brain stereotactic injection device has a very simple structure and a small volume, which better solves the problems of high instrument cost and cumbersome operation in the stereotactic injection experiment in related technologies.
  • the positioning assembly 2 includes a first scale 21, a second scale 22, and a slider 23.
  • the first scale 21 is provided with a first scale 211
  • the second scale 22 is connected to the first scale.
  • the scale 21 is connected
  • the second scale 22 is provided with a second scale 221
  • the mating hole 201 is provided at the connecting end of the first scale 21 and the second scale 22, there are two sliding blocks 23, and the two sliding blocks 23 are respectively sleeved
  • the housing 1 is provided with two sliding grooves 13 respectively matched with the two sliding blocks 23. It is understandable that in the actual practical process, the sliding slider 23 makes the two sliders 23 located at different positions of the housing 1.
  • the first and second scales 21 and 22 can be slid to adjust the matching hole 201 in space.
  • first scale 21 and the second scale 22 adopt the structure of the sliding block 23 to cooperate with the sliding groove 13 to achieve relative sliding with the housing 1.
  • the stable movement of the first scale 21 and the second scale 22 is ensured. It avoids the shaking of the first scale 21 and the second scale 22.
  • the housing 1 may be provided with protrusions
  • the slider 23 is provided with grooves that cooperate with the protrusions.
  • the fixing assembly 3 includes a head fixing module 31, the head fixing module 31 includes a column 311, a support 312, and a rotating shaft 313, and the column 311 is connected to the housing 1.
  • the support 312 is used to support the lower jaw of the animal 100 to be tested, the first end of the rotating shaft 313 is connected with the support 312, and the second end of the rotating shaft 313 is connected with the upright 311 by threads. It can be understood that, in actual use, the rotating support 312 can adjust the head position of the animal 100 to be tested, so that the leveling assembly 5 can easily achieve the leveling of the skull of the animal 100 to be tested.
  • the first end of the rotating shaft 313 is connected with the upright 311 by threads to ensure that the support 312 will not rotate after being rotated in place, thereby causing the skull of the animal 100 to be tested to shake.
  • the shape of the support 312 can be any shape capable of supporting the animal 100 to be tested, such as U-shaped, L-shaped, etc., according to actual needs.
  • the fixing assembly 3 further includes an ear bar module 32.
  • the two ear bar modules 32 are respectively inserted through the housing 1.
  • two ear rod modules 32 are used to press against the bone socket of the lower edge of the outer ear canal of the animal 100 to be tested. It is understandable that the two ear bar modules 32 cooperate with the head fixing module 31 to achieve triangulation positioning, which can fix the animal 100 to be tested in the containing cavity 11 relatively fixedly, thereby ensuring the precise execution of the injection experiment.
  • each ear bar module 32 includes an ear fixing member 321, an adjusting member 322, and a locking member 323.
  • the ear fixing member 321 is penetrated on the side wall of the housing 1, and the ear
  • the fixing member 321 is provided with ear fixing scales, the adjusting member 322 cooperates with the ear fixing member 321 to adjust the height position of the ear fixing member 321, the locking member 323 is fitted on the adjusting member 322, and the locking member 323 can abut against the adjusting member 322 To lock the ear fixing part 321 on top.
  • the brain stereotactic injection device of this embodiment can adapt to various body types of animals to be tested 100, which improves the applicability of the brain stereotactic injection device. Scope.
  • the additional locking member 323 can ensure the stability of the ear fixing member 321 against the bone socket of the outer lower edge of the ear canal of the animal 100 to be tested, and avoid the positioning of the animal 100 to be tested due to the shaking of the locking ear fixing member 321. Inaccuracy occurs.
  • the ear fixing scale can ensure that the animal 100 to be tested is fixed in the center of the containing cavity 11, thereby facilitating subsequent operations.
  • the adjustment component 322 includes an adjustment sleeve 3221, an adjustment block 3222, and an adjustment stud 3223.
  • the adjustment sleeve 3221 is fitted on the housing 1, and the upper end of the adjustment sleeve 3221 is provided with an adjustment groove.
  • the lower end is provided with an adjusting threaded hole, the adjusting groove is communicated with the adjusting threaded hole, the adjusting block 3222 is slidably arranged in the adjusting groove along the up and down direction, the adjusting block 3222 is sleeved on the ear fixing part 321, and the adjusting stud 3223 is fitted in Inside the adjusting screw hole, and the upper end of the adjusting stud 3223 abuts on the adjusting block 3222.
  • the height of the adjustment block 3222 can be realized only by rotating the adjustment stud 3223, so that the height of the ear fixing member 321 can be adjusted. This adjustment method is very simple, which is convenient for users to adjust and simplifies the experimental operation.
  • the locking member 323 needs to be screwed into the adjusting block 3222 and pressed against the ear fixing rod to lock the ear fixing rod.
  • the locking structure can not only ensure the stability of the ear fixing rod, but also The adjustment and fixing operation of the ear fixing rod is simplified.
  • the ear rod module 32 can be formed as a telescopic rod installed on the housing 1, or a detachable fixed rod of different lengths, etc., can also be used to fix the test rod.
  • the function of animal 100 can be formed as a telescopic rod installed on the housing 1, or a detachable fixed rod of different lengths, etc., can also be used to fix the test rod.
  • the function of animal 100 can be formed as a telescopic rod installed on the housing 1, or a detachable fixed rod of different lengths, etc.
  • the injection assembly 4 includes an injection syringe 41, a connecting rod 42 and a lock 43.
  • the first end of the connecting rod 42 is provided with a connecting hole 422, and the injection syringe 41 is fitted in the connection In the hole 422, the second end of the connecting rod 42 is provided with a pointer 421.
  • the connecting rod 42 is a telescopic rod.
  • the locking piece 43 is fitted on the connecting rod 42.
  • the locking piece 43 is used to lock the injection syringe 41 on the connecting rod. 42 on. It is understandable that the locking member 43 can ensure the stability of the injection syringe 41 and avoid the injection deviation caused by the skew of the injection syringe 41 during the injection process.
  • the connecting rod 42 is a telescopic rod, which can ensure that the pointer 421 abuts on the upper and lower scales 12 during the injection process, which facilitates the observation of the injection depth by the user, thereby ensuring the injection accuracy.
  • the leveling assembly 5 includes a leveling main body 51, a level 52, and a bifurcation member 53.
  • the leveling main body 51 is provided with a leveling groove 5121, and the level 52 is fitted in the leveling groove 5121.
  • the leveling body 51 is inserted through the matching hole 201 on the positioning assembly 2 to adjust the position of the positioning assembly 2 so that the bifurcation member 53 directly acts on the skull of the animal 100 to be tested.
  • point A is the Bregma point (anterior fontanelle point)
  • point B is the Lambda point (posterior fontanelle point)
  • the opening and closing angle of the bifurcation portion 532 remains unchanged, twist it by 90 degrees, and the intersection line between the bifurcation portion 532 and the skull is perpendicular to the line segment AB.
  • adjust the height of the ear fixation piece 321 until the level 52 shows the level it can be considered that the head of the mouse is already level Zero plane. Therefore, the use of the leveling assembly 5 with two bifurcation members 53 can easily achieve the leveling of the skull of the animal to be tested 100, and the four-point two-line leveling method can improve the leveling accuracy during the leveling process. , So as to help improve the accuracy of injection.
  • level 52 in the embodiment of the present application can be obtained by outsourcing.
  • each furcation member 53 includes a matching portion 531 and a furcation portion 532.
  • the matching portion 531 and the leveling body 51 are connected by a pin, and the furcation portion 532 is connected to the matching portion 531.
  • the end of the forked portion 532 away from the mating portion 531 has a tapered tip shape.
  • the shape of the bifurcated portion 532 can be any one or a combination of cones, pyramids, or irregular cones according to actual needs.
  • the leveling body 51 includes a leveling rod 511 and a leveling block 512.
  • the leveling rod 511 can fit in the fitting hole 201, and the bifurcation member 53 is fitted to the leveling rod 511.
  • a leveling block 512 is fitted to the upper end of the leveling rod 511 at the lower end, and a leveling groove 5121 is provided on the leveling block 512. It can be understood that, in order to pass through the matching hole 201, the diameter of the leveling rod 511 will be limited by the matching hole 201, and the size of the level 52 is relatively large. If the level 52 is directly installed on the leveling rod 511, the level will be caused. 52 instability occurs. In this embodiment, the upper end of the leveling rod 511 has a relatively large leveling block 512 to ensure the stability of the level 52 and thus the leveling accuracy.
  • the stereotactic brain injection device of this embodiment includes a housing 1, a positioning assembly 2, a fixing assembly 3, an injection assembly 4, and a leveling assembly 5.
  • the housing 1 defines a containing cavity 11, which is used for When the animal 100 to be tested is placed, the housing 1 is provided with upper and lower scales 12 extending in the vertical direction, and the upper and lower scales 12 are accurate to millimeters.
  • the shell is a rectangular box with a length of 6cm, a width of 3cm, and a height of 4cm.
  • the main material is polypropylene, which is transparent and resistant to acids, alkalis and organic reagents.
  • the positioning assembly 2 includes a first scale 21, a second scale 22 and a slider 23.
  • a first scale 211 is provided on the first scale 21, and the first scale 211 is accurate to a millimeter.
  • the second scale 22 is connected to the first scale 21, and a second scale 221 is provided on the second scale 22, and the second scale 221 is accurate to a millimeter.
  • the connecting ends of the first scale 21 and the second scale 22 are provided with a mating hole 201, there are two sliding blocks 23, and the two sliding blocks 23 are respectively sleeved on the first scale 21 and the second scale 22, and the housing 1 is provided with There are two sliding grooves 13 respectively matched with two sliding blocks 23.
  • the fixing assembly 3 is used to fix the animal 100 to be tested in the containing cavity 11, and the fixing assembly 3 includes a head fixing module 31 and an ear rod module 32.
  • the head fixing module 31 includes a column 311, a support 312, and a rotating shaft 313.
  • the column 311 is connected to the bottom wall of the housing 1.
  • the support 312 is used to support the lower jaw of the animal 100 to be tested.
  • the first end of the rotating shaft 313 is connected to the support
  • the piece 312 is connected, and the second end is connected with the upright 311 by threads.
  • the two ear bar modules 32 are respectively penetrated on two opposite side walls of the housing 1, and the two ear bar modules 32 are used to bear against the ears of the animal 100 to be tested. Bone fossa on the lower edge of the lateral side of the canal.
  • Each ear bar module 32 includes an ear fixing part 321, an adjusting part 322, and a locking part 323.
  • the ear fixing part 321 penetrates through the side wall of the housing 1, and the ear fixing part 321 is provided with an ear fixing scale. The scale is accurate to millimeters.
  • the adjusting member 322 cooperates with the ear fixing member 321 to adjust the height position of the ear fixing member 321, the locking member 323 is fitted on the adjusting member 322, and the locking member 323 can abut on the adjusting member 322 to lock the ear fixing member 321.
  • the adjusting component 322 includes an adjusting sleeve 3221, an adjusting block 3222, and an adjusting stud 3223.
  • the adjusting sleeve 3221 is fitted on the housing 1.
  • the upper end of the adjusting sleeve 3221 is provided with an adjusting groove, and the lower end is provided with an adjusting threaded hole.
  • the threaded holes are connected, the adjusting block 3222 is slidably arranged in the adjusting groove in the up and down direction, the adjusting block 3222 is sleeved on the ear fixing part 321, the adjusting stud 3223 is fitted in the adjusting threaded hole, and the upper end of the adjusting stud 3223 Rest on the adjustment block 3222.
  • the injection assembly 4 includes an injection syringe 41, a connecting rod 42 and a lock 43.
  • the first end of the connecting rod 42 is provided with a connecting hole 422.
  • the injection syringe 41 is fitted in the connecting hole 422, and the connecting rod
  • the second end of 42 is provided with a pointer 421, the connecting rod 42 is a telescopic rod, the locking member 43 is fitted on the connecting rod 42, and the locking member 43 is used to lock the injection syringe 41 on the connecting rod 42.
  • the leveling body 51 includes a leveling rod 511 and a leveling block 512.
  • the leveling rod 511 can be fitted in the fitting hole 201, and the bifurcating piece 53 is fitted to the lower end of the leveling rod 511, and the leveling block 512 is fitted to the leveling rod.
  • the upper end of 511, and the leveling groove 5121 is provided on the leveling block 512.
  • the first step During the experiment, the mice were first weighed and anesthetized, and the weight of the mice was weighed with an electronic balance, and an intraperitoneal injection of 80mg/kg, 0.5%-1% sodium pentobarbital solution;
  • Step 2 Place the anesthetized mouse on the bottom wall of the housing 1, use the ear fixation piece 321 to hold the lower edge of the mouse’s ear canal, and adjust the length of the ear fixation pieces 321 on both sides (by ear fixation). Scale judgment) so that the head of the mouse is at the center of the bottom wall of the housing 1;
  • the third step adjust the head fixing module 31 to fix the head of the mouse, adjust the heights of the ear fixing parts 321 and the support parts 312 on both sides so that the mouse head is in a horizontal zero plane position;
  • Step 4 Use erythromycin ointment to moisten the mouse's eyeballs to prevent the cornea from drying out.
  • Use curved scissors to cut off the coat on the top of the mouse's head.
  • Use a scalpel or ophthalmology Cut the skin along the midline to expose the sagittal suture and herringbone suture.
  • Use a sterile absorbent cotton ball to wipe away the skull fascia tissue and blood to make the Bregma point (anterior fontanelle point) and Lambda point (posterior fontanelle point) of the mouse skull. )clear and distinct;
  • Step 5 Pass the leveling body 51 through the matching hole 201 on the positioning assembly 2 and adjust the position of the positioning assembly 2 so that the bifurcating member 53 directly acts on the mouse skull.
  • point A is Point Bregma
  • point B is Lambda point
  • Step 6 Take out the leveling component 5, replace it with a marker pen, slide the positioning component 2, align the pen tip to point A, write down the real-time coordinates on the first scale 211 and the second scale 221 at this time, and select this
  • the point is the origin of the coordinates. Refer to the brain atlas coordinates. Move the positioning component 2. By calculating the offset distance between the matching hole 201 and the XY axis coordinates of point A, you can find the location of the target brain area, and use a marker to mark the point on the skull ;
  • Step 7 Use a mini skull drill to drill a hole vertically at the marked point.
  • there is a sense of loss you can choose whether to use the skull drill according to the experimental situation. For example, using a needle to directly penetrate the skull when ventricular drug is used can also achieve the experimental purpose) ;
  • Step 8 Use the injection syringe 41 to suck the sample, and disinfect the needle with 75% alcohol. Insert the injection syringe 41 through the fitting hole 201, then align the needle with the skull window, and lower the needle tip to be tangent to the surface of the skull, clamp the connecting rod 42 on the injection syringe 41, and adjust the length of the connecting rod 42 to make the pointer 421 Attach the upper and lower scale 12 on the wall closely, and record the corresponding Z-axis coordinates at this time;
  • Step 9 Slowly sink the needle to the target area according to the coordinates provided by the brain atlas.
  • the connecting rod 42 descends with the descending of the injection syringe 41, and the needle penetration depth is controlled by the distance moved by the pointer 421 on the upper and lower scales 12 ;
  • Step 10 Use a disposable syringe to drip saline at the opening of the skull to prevent the tissue from drying out. Slowly inject the injection sample into the target point. After the injection, stop the needle for 10-15 minutes to allow the sample to fully diffuse, and then slowly lift it up after the injection. Injection syringe 41 to prevent the sample liquid from leaking out due to excessive speed;
  • Step 11 Suture the scalp with angle needles and sterile sutures and use lidocaine and lincomycin gel for pain relief and anti-inflammatory.
  • the mice are placed on a heating blanket to keep their body temperature until they are awake and then returned to the cage.
  • the intracerebral stereotactic injection device of this embodiment can realize standardized and precise intracranial injection in mice. Compared with the related technology, the intracerebral stereoscopic injection operation can only be carried out with the help of an experimental platform and a stereotaxic instrument.
  • the intracerebral stereotactic injection device in this example has lower requirements for the experimental environment, reduces the time for leveling the mouse skull and positioning the target nucleus, reduces the operating difficulty of the device, and improves the efficiency of the experiment. Especially for the intracranial injection of large nuclei such as hippocampus, cortex, ventricle, etc., the experimental effect is remarkable.
  • the main body material of the stereotactic injection device in the brain of this embodiment is polypropylene, which has low production cost, is easy to process, can be mass-produced, and can meet the experimental needs of more experimenters.
  • stereotactic injection in mice is taken as an example to express the implementation of this example.
  • the device can be used for stereotactic injection in the brain other than mice.
  • This device can be used for stereotactic injection in the brain of relatively small animals.
  • the brain stereotactic injection device of this embodiment is provided with a fixing assembly and a leveling assembly for fixing and adjusting the posture of the animal to be tested, and has a positioning assembly for positioning the injection assembly and an upper and lower scale and pointer for positioning the injection depth, which simplifies The operation process of stereotactic injection realizes standardized and precise stereotactic injection operation, saves experiment space and improves experiment efficiency.
  • the whole brain stereotactic injection device has a very simple structure and a small volume, which better solves the problems of high instrument cost and cumbersome operation in the stereotactic injection experiment in related technologies.

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Abstract

一种脑立体定向注射装置，包括壳体（1）、定位组件（2）、固定组件（3）、注射组件（4）和调平组件（5），壳体（1）限定出容纳腔（11），壳体（1）上设有沿上下方向延伸设置的上下刻度（12），定位组件（2）可滑动地设在壳体（1）上，定位组件（2）上设有第一刻度（211）和第二刻度（221），定位组件（2）上设有配合孔（201），固定组件（3）设在容纳腔（11）内，注射组件（4）能够穿过配合孔（201）且伸入容纳腔（11），注射组件（4）上设有被配置为指向上下刻度（12）的指针（421），注射组件（4）被配置为向待实验动物注射实验试剂，调平组件（5）能够穿过配合孔（201）且伸入容纳腔（11）。

Description

脑立体定向注射装置
本公开要求在2020年03月17日提交中国专利局、申请号为202010187121.7的中国专利申请的优先权，以上申请的全部内容通过引用结合在本公开中。
技术领域
本申请涉及生物实验用品技术领域，例如涉及一种脑立体定向注射装置。
背景技术
在脑科学基础研究领域中，脑内注射是动物实验的重要方法，其对于疾病模型的建立、脑内给药治疗及探究中枢核团之间的投射关系等起着至关重要的作用。将注射样品，如病毒、细胞、蛋白分子、药物、标记染料探针等注入脑内可以直接作用于活体动物的目标脑区，包括神经元、胶质细胞、血管以及脑区内微环境等，这种精准脑区定位给药不涉及器官组织的药物代谢以及血脑屏障，也就是说，精准脑区定位给药比其他给药途径得出的结果更能准确的反应药物的直接作用。
相关技术中的实验室商品化立体定向注射装置，需要实验台、脑立体定位仪、微量注射泵和颅骨钻组合使用，其操作方法为将动物头部固定于立体定位仪后，以颅骨前囟为定位原点，根据坐标确定注射点，使用颅骨钻钻开一个颅窗，利用微量注射泵和注射器缓慢注入样品。但此方法缺点为，仪器需要固定的实验台和稳定设施作为支撑，设备成本高、操作方法繁琐且实验时间长，从固定小鼠到注射完毕，所需时间40-60分钟，新手操作容易对实验小鼠造成损伤甚至导致死亡，无法满足在实验空间和设备有限的情况下进行脑区精确快速给药。而大脑中各个核团的位置分布错综复杂，使用注射针直接颅内给药又无法精准的将样品注射入目的脑区，因此需要一套便捷实用的脑内立体定位注射工具。
发明内容
本申请提出一种脑立体定向注射装置，该脑立体定向注射装置的结构简单，使用方便。
本申请的技术方案如下：
本申请公开了一种脑立体定向注射装置，包括：壳体，所述壳体限定出容 纳腔，所述容纳腔被配置为放置待实验动物，所述壳体上设有沿上下方向延伸设置的上下刻度；定位组件，所述定位组件可滑动地设在壳体上，所述定位组件上设有第一刻度和第二刻度，所述第一刻度的延伸方向与所述第二刻度的延伸方向垂直，所述定位组件上设有配合孔；固定组件，所述固定组件设在所述容纳腔内，所述固定组件被配置为将所述待实验动物固定在所述容纳腔内；注射组件，所述注射组件能够穿过所述配合孔且伸入所述容纳腔，所述注射组件上设有被配置为指向所述上下刻度的指针，所述注射组件被配置为向所述待实验动物注射实验试剂；调平组件，调平组件能够穿过所述配合孔且伸入所述容纳腔，所述调平组件被配置为检测所述待实验动物的颅骨的水平程度。
附图说明
图1是本申请实施例的脑立体定向注射装置的局部结构示意图。
图2是本申请实施例的脑立体定向注射装置的调平组件配合在配合孔内的结构示意图。
图3是本申请实施例的脑立体定向注射装置的注射组件配合在配合孔内的结构示意图。
图4是本申请实施例的脑立体定向注射装置的头部固定模组的结构示意图。
图5是本申请实施例的脑立体定向注射装置的耳杆模组的结构示意图。
图6是本申请实施例的脑立体定向注射装置的注射组件的结构示意图。
图7是本申请实施例的脑立体定向注射装置的调平组件的结构示意图。
图8是本申请实施例的待实验动物的颅骨示意图。
附图标记：
1、壳体；11、容纳腔；12、上下刻度；13、滑槽；
2、定位组件；21、第一标尺；211、第一刻度；22、第二标尺；221、第二刻度；23、滑块；201、配合孔；
3、固定组件；31、头部固定模组；311、立柱；312、支撑件；313、转轴；32、耳杆模组；321、耳固定件；322、调节部件；3221、调节套筒；3222、调节块；3223、调节螺柱；323、锁紧件；
4、注射组件；41、注射针筒；42、连接杆；421、指针；422、连接孔；43、锁合件；
5、调平组件；51、调平主体；511、调平杆；512、调平块；5121、调平槽； 52、水平仪；53、分叉件；531、配合部；532、分叉部；
100、待实验动物。
具体实施方式
下面结合附图并通过具体实施方式来进一步说明本申请的技术方案。
在本申请的描述中，需要理解的是，术语“中心”、“纵向”、“横向”、“长度”、“宽度”、“厚度”、“上”、“下”、“前”、“后”、“左”、“右”、“竖直”、“水平”、“顶”、“底”、“内”、“外”、“顺时针”、“逆时针”、“轴向”、“径向”、“周向”等指示的方位或位置关系为基于附图所示的方位或位置关系，仅是为了便于描述本申请和简化描述，而不是指示或暗示所指的装置或元件必须具有特定的方位、以特定的方位构造和操作，因此不能理解为对本申请的限制。
此外，限定有“第一”、“第二”的特征可以明示或者隐含地包括一个或者更多个该特征，用于区别描述特征，无顺序之分，无轻重之分。在本申请的描述中，除非另有说明，“多个”的含义是两个或两个以上。
在本申请的描述中，需要说明的是，除非另有明确的规定和限定，术语“安装”、“相连”、“连接”应做广义理解，例如，可以是固定连接，也可以是可拆卸连接，或一体地连接；可以是机械连接，也可以是电连接；可以是直接相连，也可以通过中间媒介间接相连，可以是两个元件内部的连通。对于本领域的普通技术人员而言，可以具体情况理解上述术语在本申请中的具体含义。
下面参考图1-图8描述本申请实施例的脑立体定向注射装置的结构。
如图1-图3所示，本实施例的脑立体定向注射装置包括壳体1、定位组件2、固定组件3、注射组件4和调平组件5，壳体1限定出容纳腔11，容纳腔11用于放置待实验动物100，壳体1上设有沿上下方向延伸设置的上下刻度12，定位组件2可滑动地设在壳体1上，定位组件2上设有第一刻度211和第二刻度221，第一刻度211的延伸方向与第二刻度221的延伸方向垂直，定位组件2上设有配合孔201，固定组件3设在容纳腔11内，固定组件3用于将待实验动物100固定在容纳腔11内，注射组件4能够穿过配合孔201且伸入容纳腔11，注射组件4上设有用于指向上下刻度12的指针421，注射组件4用于向待实验动物100注射实验试剂，调平组件5能够穿过配合孔201且伸入容纳腔11，调平组件5用于调整待实验动物100的头部。
可以理解的是，在实际使用过程中，将待实验动物100放置在容纳腔11内， 采用固定组件3将待实验动物100固定在容纳腔11内，在初步固定实验动物之后采用调平组件5检测待实验动物100的颅骨水平程度，通过不断调节固定组件3使得待实验动物100的颅骨水平。然后将记号笔穿过配合孔201，采用笔记号笔标记待实验动物100的颅骨的某个生物学标志点作为坐标原点，并且记录下此时第一刻度211和第二刻度221的坐标，然后移动定位组件2，通过计算配合孔201与坐标原点的XY轴坐标的偏移距离，即可找到目标脑区的位置，使用记号笔在颅骨上做待注射点。然后进行注射，在注射过程中注射组件4的针头插入待注射点，由于注射组件4上设有用于指向上下刻度12的指针421，即可根据指针421的位置来判断针头注入的伸入。由此，本实施例的脑立体定向注射装置通过定位组件2、调平组件5和固定组件3的相互作用，确保了在注射过程中能够确保待实验动物100的颅骨水平，确保了注射能够稳定且精准进行。与此同时，由于注射组件4上设有指向上下刻度12的指针421，实现了注射组件4注射深度的精准控制，从而确保了注射精度。此外，本实施例的脑立体定向注射装置的结构十分简单，操作十分方便，提升了实验效率，降低了实验成本。
本实施例的脑立体定向注射装置，由于设有固定以及调整待实验动物100姿态的固定组件3和调平组件5，且具有用于定位注射组件4的定位组件2和定位注射深度的上下刻度12和指针421，简化了立体定向注射的操作过程，实现了标准化、精确化的立体定向注射操作，节省了实验空间，提升了实验效率。此外，整个脑立体定向注射装置的结构非常简单，体积较小，较好地解决了相关技术中立体定向注射实验中仪器成本高、操作繁琐等问题。
在一些实施例中，如图1所示，定位组件2包括第一标尺21、第二标尺22和滑块23，第一标尺21上设有第一刻度211，第二标尺22与第一标尺21相连，且第二标尺22上设有第二刻度221，配合孔201设在第一标尺21和第二标尺22的连接端，滑块23为两个，两个滑块23分别套设在第一标尺21和第二标尺22上，壳体1上设有分别与两个滑块23配合的两个滑槽13。可以理解的是，在实际实用过程中，滑动滑块23使得两个滑块23位于壳体1的不同位置，在滑动第一标尺21和第二标尺22上，即可调整配合孔201在空间平面内X轴和Y轴两个方向的位置，由于调平组件5和注射组件4均可以配合在配合孔201内，调整配合孔201的在空间平面内X轴和Y轴两个方向的位置，就是调整调平组件5和注射组件4的位置。由此，方便了根据待实验动物100的体型以及 实验注射要求调整注射组件4和调平组件5，从而方便了注射实验的进行，提升了实验效率。
此外，第一标尺21和第二标尺22采用滑块23配合滑槽13的结构实现与壳体1的相对滑动，一方面保证了第一标尺21和第二标尺22的稳定运动，较好地避免了第一标尺21和第二标尺22发生晃动，另一方面限制了第一标尺21和第二标尺22的滑动方向，确保了采用第一刻度211和第二刻度221定位注射组件4和调平组件5时的准确性。这里需要说明的是，当然，在某些实施例中，壳体1上可以设有凸起，而滑块23上设有与凸起配合的凹槽。
在一些实施例中，如图1、图4所示，固定组件3包括头部固定模组31，头部固定模组31包括立柱311、支撑件312和转轴313，立柱311连接在壳体1的底壁上，支撑件312用于支撑待实验动物100的下颌，转轴313的第一端与支撑件312相连，转轴313的第二端与立柱311通过螺纹相连。可以理解的是，在实际使用过程中，转动支撑件312可以调整待实验动物100的头部位置，从而配合调平组件5即可方便地实现待实验动物100的颅骨调平。而转轴313的第一端与立柱311通过螺纹相连则是确保了支撑件312转动到位后不会发生转动，从而造成待实验动物100颅骨晃动的现象发生。这里需要补充说明的是，在本实施例中，支撑件312的形状可以根据实际需要选择U型、L型等任何能够支撑待实验动物100的形状。
在一些实施例中，如图1-图3所示，固定组件3还包括耳杆模组32，耳杆模组32为两个，两个耳杆模组32分别穿设在壳体1的相对设置的两个侧壁上，两个耳杆模组32用于抵在待实验动物100的耳道外侧下缘骨窝。可以理解的是，两个耳杆模组32配合头部固定模组31实现了三角定位，能够较为固定地将待实验动物100固定在容纳腔11内，从而保证了注射实验的精准进行。
在一些实施例中，如图5所示，每个耳杆模组32包括耳固定件321、调节部件322和锁紧件323，耳固定件321穿设在壳体1的侧壁上，耳固定件321上设有耳固定刻度，调节部件322与耳固定件321配合以调整耳固定件321的高度位置，锁紧件323配合在调节部件322上，锁紧件323能够抵在调节部件322上以锁紧耳固定件321。可以理解的是，由于调节部件322能够调整耳固定件321的高度位置，这样使得本实施例的脑立体定向注射装置能够适应各种体型的待实验动物100，提升了脑立体定向注射装置的适用范围。与此同时，增设的锁紧件323能够确保耳固定件321抵在待实验动物100的耳道外侧下缘骨窝后的 稳定性，避免锁紧耳固定件321晃动导致的待实验动物100定位不准确的现象发生。此外，耳固定刻度可以确保待实验动物100被固定在容纳腔11的正中心，从而方便后续操作。
在一些实施例中，如图5所示，调节部件322包括调节套筒3221、调节块3222和调节螺柱3223，调节套筒3221配合在壳体1上，调节套筒3221上端设有调节槽，下端设有调节螺纹孔，调节槽与调节螺纹孔相连通，调节块3222沿上下方向可滑动地设在调节槽内，调节块3222套设在耳固定件321上，调节螺柱3223配合在调节螺纹孔内，且调节螺柱3223的上端抵在调节块3222上。可以理解的是，在实际使用过程中，只需要转动调节螺柱3223即可实现调节块3222的高度，从而实现调节耳固定件321的高度。这样调节方式非常简单，方便了用户调节，简化了实验操作。而在调整结束后只需要将锁紧件323旋入调节块3222并且抵在耳固定杆上即可实现耳固定杆的锁紧，这样锁紧的结构既能保证耳固定杆的稳定性，又简化了耳固定杆的调整和固定操作。
当然，在本申请的其他实施例中，耳杆模组32可以形成为安装在壳体1上的伸缩杆、或者采用可拆卸的长短不一的固定杆等结构，同样可以起到固定待实验动物100的功能。
在一些实施例中，如图6所示，注射组件4包括注射针筒41、连接杆42和锁合件43，连接杆42的第一端设有连接孔422，注射针筒41配合在连接孔422内，连接杆42的第二端设有指针421，连接杆42为伸缩杆，锁合件43配合在连接杆42上，锁合件43用于将注射针筒41锁紧在连接杆42上。可以理解的是，锁合件43能够保证注射针筒41的稳定性，避免了注射过程中注射针筒41歪斜导致的注射偏差。而连接杆42为伸缩杆能够确保在注射过程中指针421抵在上下刻度12上，方便了用户对注射深度的观察，从而保证注射精度。
在一些实施例中，如图7所示，调平组件5包括调平主体51、水平仪52和分叉件53，调平主体51上设有调平槽5121，水平仪52配合在调平槽5121内，分叉件53为两个，两个分叉件53均可转动地设在调平主体51的下方，两个分叉件53能够抵在待实验动物100的颅骨上。可以理解的是，在实际使用的过程中，将调平主体51穿过定位组件2上的配合孔201，调节定位组件2的位置，使分叉件53直接作用在待实验动物100的颅骨，待实验动物100的颅骨示意图8所示，A点为Bregma点(前囟点)，B点为Lambda点(后囟点)，A点与B点之间有一条骨缝。首先用镊子调节两个分叉件53的开合角度，使两个分叉件 53的针尖对准A、B两点相应的位置。根据水平仪52显示情况，调节头部固定模组31的支撑件312，当两个分叉部532均与颅骨接触且水平仪52显示水平，说明颅骨已达到纵向水平状态。然后，保持分叉部532开合角度不变，扭转90度，分叉部532与颅骨的交底连线与线段AB垂直。当两个分叉部532再次与颅骨接触(接触点为图8中CD两点，AB＝CD)，调节耳固定件321的高度，直至水平仪52显示水平，可以认为小鼠头部已处于水平零平面。由此，采用具有两个分叉件53的调平组件5能够较为方便地实现待实验动物100的颅骨调平，并且在调平过程中采用四点两线的调平方式能够提升调平精度，从而有利于提升注射精度。
这里需要额外说明的是，在本申请的实施例中水平仪52可以外购获得。
在一些实施例中，如图7所示，每个分叉件53均包括配合部531和分叉部532，配合部531与调平主体51通过销轴相连，分叉部532与配合部531相连，分叉部532的远离配合部531的一端呈锥尖形状。可以理解的是，分叉部532与待实验动物100的颅骨的接触面积越小，调平精度越高，分叉部532的远离配合部531的一端呈锥尖形状能够使得分叉件53与待实验动物100的颅骨是点接触，从而保证了调平精度。在本实施例中，分叉部532的形状可以根据实际需要选择圆锥、棱锥或者不规则的锥体中的任何一种或者多种组合。
在一些实施例中，如图7所示，调平主体51包括调平杆511和调平块512，调平杆511能够配合在配合孔201内，且分叉件53配合在调平杆511的下端，调平块512配合在调平杆511上端，且调平槽5121设在调平块512上。可以理解的是，为了穿过配合孔201，调平杆511的直径会受到配合孔201的限制，而水平仪52的尺寸相对较大，如果直接将水平仪52安装在调平杆511上会造成水平仪52不稳定的现象发生，在本实施例中，调平杆511的上端具有体积相对较大的调平块512能够确保水平仪52的稳定性，从而确保调平精度。
实施例：
下面参考图1-图7描述本申请一个实施例的脑立体定向注射装置。
如图1所示，本实施例的脑立体定向注射装置包括壳体1、定位组件2、固定组件3、注射组件4和调平组件5，壳体1限定出容纳腔11，容纳腔11用于放置待实验动物100，壳体1上设有沿上下方向延伸设置的上下刻度12，上下刻度12精确到毫米。
壳体为长6cm，宽3cm，高4cm的长方体盒，使用透明度较高且耐酸碱和有机试剂程度较高的聚丙烯作为主要材质制成。
如图1所示，定位组件2包括第一标尺21、第二标尺22和滑块23。第一标尺21上设有第一刻度211，第一刻度211精确到毫米。第二标尺22与第一标尺21相连，且第二标尺22上设有第二刻度221，第二刻度221精确到毫米。第一标尺21和第二标尺22的连接端设有配合孔201，滑块23为两个，两个滑块23分别套设在第一标尺21和第二标尺22上，壳体1上设有分别与两个滑块23配合的两个滑槽13。
如图1、图4及图5所示，固定组件3用于将待实验动物100固定在容纳腔11内，固定组件3包括头部固定模组31和耳杆模组32。头部固定模组31包括立柱311、支撑件312和转轴313，立柱311连接在壳体1的底壁上，支撑件312用于支撑待实验动物100的下颌，转轴313的第一端与支撑件312相连，第二端与立柱311通过螺纹相连。耳杆模组32为两个，两个耳杆模组32分别穿设在壳体1的相对设置的两个侧壁上，两个耳杆模组32用于抵在待实验动物100的耳道外侧下缘骨窝。每个耳杆模组32包括耳固定件321、调节部件322和锁紧件323，耳固定件321穿设在壳体1的侧壁上，耳固定件321上设有耳固定刻度，耳固定刻度精确到毫米。调节部件322与耳固定件321配合以调整耳固定件321的高度位置，锁紧件323配合在调节部件322上，锁紧件323能够抵在调节部件322上以锁紧耳固定件321。调节部件322包括调节套筒3221、调节块3222和调节螺柱3223，调节套筒3221配合在壳体1上，调节套筒3221上端设有调节槽，下端设有调节螺纹孔，调节槽与调节螺纹孔相连通，调节块3222沿上下方向可滑动地设在调节槽内，调节块3222套设在耳固定件321上，调节螺柱3223配合在调节螺纹孔内，且调节螺柱3223的上端抵在调节块3222上。
如图6所示，注射组件4包括注射针筒41、连接杆42和锁合件43，连接杆42的第一端设有连接孔422，注射针筒41配合在连接孔422内，连接杆42的第二端设有指针421，连接杆42为伸缩杆，锁合件43配合在连接杆42上，锁合件43用于将注射针筒41锁紧在连接杆42上。
如图7所示，调平组件5包括调平主体51、水平仪52和分叉件53，调平主体51上设有调平槽5121，水平仪52配合在调平槽5121内，分叉件53为两个，两个分叉件53均可转动地设在调平主体51的下方，两个分叉件53能够抵在待实验动物100的颅骨上。每个分叉件53均包括配合部531和分叉部532， 配合部531与调平组件5通过销轴相连，分叉部532与配合部531相连，分叉部532的远离配合部531的一端呈锥尖形状。调平主体51包括调平杆511和调平块512，调平杆511能够配合在配合孔201内，且分叉件53配合在调平杆511的下端，调平块512配合在调平杆511上端，且调平槽5121设在调平块512上。
本实施例的脑立体定向注射装置的使用方法如下：
第一步：实验时，首先对小鼠进行称重麻醉，使用电子天平称量小鼠体重，腹腔注射80mg/kg、0.5％-1％的戊巴比妥钠溶液；
第二步：将麻醉后的小鼠放置在壳体1的底壁上，使用耳固定件321顶住小鼠耳道外侧下缘骨窝，通过调节两边耳固定件321的长度(通过耳固定刻度判断)，使小鼠头部处于壳体1的底壁的中心位置；
第三步：调节头部固定模组31实现小鼠头部固定，调节两侧耳固定件321和支撑件312的高度使得小鼠头部处于水平零平面位置；
第四步：用红霉素眼膏湿润小鼠眼球，防止角膜干燥，用弯剪将小鼠头顶被毛剪除，依次使用碘伏和75％酒精棉球对头皮进行消毒，用手术刀或眼科剪沿正中线剪开头皮，暴露矢状缝和人字缝，用无菌脱脂棉球擦拭除去颅骨筋膜组织和血液，使小鼠颅骨的Bregma点(前囟点)和Lambda点(后囟点)清晰可见；
第五步：将调平主体51穿过定位组件2上的配合孔201，调节定位组件2的位置，使分叉件53直接作用在小鼠颅骨，小鼠颅骨示意图8所示，A点为Bregma点，B点为Lambda点，A点与B点之间有一条骨缝。首先用镊子调节两个分叉部532的开合角度，使两个分叉部532的针尖对准A、B两点相应的位置，根据水平仪52显示情况，调节头部固定模组31的支撑件312，当两个分叉部532均与颅骨接触且水平仪52显示水平，说明颅骨已达到纵向水平状态。然后，保持分叉部532开合角度不变，扭转90度，分叉部532与颅骨的交底连线与线段AB垂直，当两个分叉部532再次与颅骨接触(接触点为图8中CD两点，AB＝CD)，调节耳固定件321的高度，直至水平仪52显示水平，可以认为小鼠头部已处于水平零平面；
第六步：将调平组件5取出，换为记号笔，滑动定位组件2，将笔尖对准A点，记下此时与第一刻度211和第二刻度221上的实时坐标，选择该点为坐标原点，参考脑图谱坐标，移动定位组件2，通过计算配合孔201与A点的XY轴坐标的偏移距离，即可找到目标脑区的位置，使用记号笔在颅骨上做标记点；
第七步：使用迷你颅骨钻在标记点垂直钻孔，当钻通时有落空感(可根据实验情况选择是否使用颅骨钻，例如脑室给药时使用针头直接刺入颅骨也可达到实验目的)；
第八步：使用注射针筒41吸取样品，并用75％酒精对针头进行消毒。将注射针筒41穿过配合孔201，随后将针头对准颅窗，针尖下降到与颅骨表面相切，在注射针筒41夹上连接杆42，并调整连接杆42的长度，使指针421紧贴墙壁上的上下刻度12，记录此时对应的Z轴坐标；
第九步：根据脑图谱提供的坐标，缓慢将针头下沉到靶区，连接杆42随着注射针筒41的下降而下降，通过指针421在上下刻度12上移动的距离，控制入针深度；
第十步：用一次性注射器在颅骨开口处滴上生理盐水封闭，防止组织干燥，缓慢的将注射样品注入靶点，注射结束后停针10min-15min，使样品充分扩散，完毕后缓慢上提注射针筒41，以防止速度过快导致样品液渗出；
第十一步：用角针和无菌缝合线缝合头皮并使用利多卡因林可霉素凝胶镇痛和消炎，将小鼠放在加热毯上保持体温直到清醒后放回饲养笼内。
本实施例的脑内立体定向注射装置可以实现标准化、精确化的小鼠颅内注射，相比于相关技术中必须借助实验台、脑立体定位仪才可进行的脑内立体注射操作，本实施例的脑内立体定向注射装置对实验环境要求较低，降低了小鼠颅骨调平、目标核团定位时间，降低了装置的操作难度系数，提升了实验效率。特别针对海马、皮层、脑室等较大核团的颅内注射，实验效果显著。本实施例的脑内立体定向注射装置主体材料为聚丙烯，生产成本低，易加工，可批量生产，能够满足更多实验人员的实验需求。
此外，需要说明的是，本实施例阐述中以小鼠的立体定向注射为例，表达了本实施例的实施方式，在实际使用过程中，该装置可用于小鼠以外的脑内立体定向注射，但凡体型相对较小动物的脑内立体定向注射均可使用该装置。
在本说明书的描述中，参考术语“有些实施例”、“其他实施例”等的描述意指结合该实施例或示例描述的具体特征、结构、材料或者特点包含于本申请的至少一个实施例或示例中。在本说明书中，对上述术语的示意性表述不一定指的是相同的实施例或示例。而且，描述的具体特征、结构、材料或者特点可以在任何的一个或多个实施例或示例中以合适的方式结合。
本实施例的脑立体定向注射装置，由于设有固定以及调整待实验动物姿态 的固定组件和调平组件，且具有用于定位注射组件的定位组件和定位注射深度的上下刻度和指针，简化了立体定向注射的操作过程，实现了标准化、精确化的立体定向注射操作，节省了实验空间，提升了实验效率。此外，整个脑立体定向注射装置的结构非常简单，体积较小，较好地解决了相关技术中立体定向注射实验中仪器成本高、操作繁琐等问题。

Claims (10)

  1. 一种脑立体定向注射装置，包括：
    壳体(1)，所述壳体(1)限定出容纳腔(11)，所述容纳腔(11)被配置为放置待实验动物(100)，所述壳体(1)上设有沿上下方向延伸设置的上下刻度(12)；
    定位组件(2)，所述定位组件(2)可滑动地设在壳体(1)上，所述定位组件(2)上设有第一刻度(211)和第二刻度(221)，所述第一刻度(211)的延伸方向与所述第二刻度(221)的延伸方向垂直，所述定位组件(2)上设有配合孔(201)；
    固定组件(3)，所述固定组件(3)设在所述容纳腔(11)内，所述固定组件(3)被配置为将所述待实验动物(100)固定在所述容纳腔(11)内；
    注射组件(4)，所述注射组件(4)能够穿过所述配合孔(201)且伸入所述容纳腔(11)，所述注射组件(4)上设有被配置为指向所述上下刻度(12)的指针(421)，所述注射组件(4)被配置为向所述待实验动物(100)注射实验试剂；
    调平组件(5)，调平组件(5)能够穿过所述配合孔(201)且伸入所述容纳腔(11)，所述调平组件(5)被配置为检测所述待实验动物(100)的颅骨的水平程度。
  2. 根据权利要求1所述的脑立体定向注射装置，其中，所述定位组件(2)包括：
    第一标尺(21)，所述第一标尺(21)上设有所述第一刻度(211)；
    第二标尺(22)，所述第二标尺(22)与所述第一标尺(21)相连，且所述第二标尺(22)上设有所述第二刻度(221)，所述配合孔(201)设在所述第一标尺(21)和所述第二标尺(22)的连接端；
    滑块(23)，所述滑块(23)设有两个，两个所述滑块(23)分别套设在所述第一标尺(21)和所述第二标尺(22)上，所述壳体(1)上设有分别与两个所述滑块(23)配合的两个滑槽(13)。
  3. 根据权利要求1所述的脑立体定向注射装置，其中，所述固定组件(3)包括头部固定模组(31)，所述头部固定模组(31)包括：
    立柱(311)，所述立柱(311)连接在所述壳体(1)的底壁上；
    支撑件(312)，所述支撑件(312)被配置为支撑所述待实验动物(100)的下颌；
    转轴(313)，所述转轴(313)的第一端与所述支撑件(312)相连，所述转轴(313)的第二端与所述立柱(311)通过螺纹相连。
  4. 根据权利要求1所述的脑立体定向注射装置，其中，所述固定组件(3)还包括耳杆模组(32)，所述耳杆模组(32)设有两个，两个所述耳杆模组(32)分别穿设在所述壳体(1)的相对设置的两个侧壁上，两个所述耳杆模组(32)被配置为抵在所述待实验动物(100)的耳道外侧下缘骨窝上。
  5. 根据权利要求4所述的脑立体定向注射装置，其中，每个所述耳杆模组(32)包括：
    耳固定件(321)，所述耳固定件(321)穿设在所述壳体(1)的侧壁上，所述耳固定件(321)上设有耳固定刻度；
    调节部件(322)，所述调节部件(322)与所述耳固定件(321)配合以调整所述耳固定件(321)的高度位置；
    锁紧件(323)，所述锁紧件(323)设在所述调节部件(322)上，所述锁紧件(323)被配置为抵在所述调节部件(322)上以锁紧所述耳固定件(321)。
  6. 根据权利要求5所述的脑立体定向注射装置，其中，所述调节部件(322)包括：
    调节套筒(3221)，所述调节套筒(3221)设在所述壳体(1)上，所述调节套筒(3221)上端设有调节槽，下端设有调节螺纹孔，所述调节槽与所述调节螺纹孔相连通；
    调节块(3222)，所述调节块(3222)沿上下方向可滑动地设在所述调节槽内，所述调节块(3222)套设在所述耳固定件(321)上；
    调节螺柱(3223)，所述调节螺柱(3223)配合在所述调节螺纹孔内，且所述调节螺柱(3223)的上端被配置为抵在所述调节块(3222)上。
  7. 根据权利要求1所述的脑立体定向注射装置，其中，所述注射组件(4)包括：
    注射针筒(41)；
    连接杆(42)，所述连接杆(42)的第一端设有连接孔(422)，所述注射针筒(41)设在所述连接孔(422)内，所述连接杆(42)的第二端设有所述指针(421)，所述连接杆(42)为伸缩杆；
    锁合件(43)，所述锁合件(43)设在所述连接杆(42)上，所述锁合件(43)被配置为将所述注射针筒(41)锁紧在所述连接杆(42)上。
  8. 根据权利要求1所述的脑立体定向注射装置，其中，所述调平组件(5)包括：
    调平主体(51)，所述调平主体(51)上设有调平槽(5121)；
    水平仪(52)，所述水平仪(52)设在所述调平槽(5121)内；
    分叉件(53)，所述分叉件(53)设有两个，两个所述分叉件(53)均可转动地设在所述调平主体(51)的下方，两个所述分叉件(53)被配置为抵在所述待实验动物(100)的颅骨上。
  9. 根据权利要求8所述的脑立体定向注射装置，其中，每个所述分叉件(53)均包括：
    配合部(531)，所述配合部(531)与所述调平主体(51)通过销轴相连；
    分叉部(532)，所述分叉部(532)与所述配合部(531)相连，所述分叉部(532)的远离所述配合部(531)的一端呈锥尖形状。
  10. 根据权利要求8所述的脑立体定向注射装置，其中，所述调平主体(51)包括：
    调平杆(511)，所述调平杆(511)能够穿过所述配合孔(201)，且所述分叉件(53)设在所述调平杆(511)的下端；
    调平块(512)，所述调平块(512)设在所述调平杆(511)上端，且所述调平槽(5121)设在所述调平块(512)上。
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