Animal brain positioning injection device

Abstract

The invention relates to an animal brain positioning injection device which comprises a machine base, a mechanical arm, an injection mechanism and a brain fixing mechanism. The mechanical arm comprises a first operating arm, a second operating arm and a third operating arm which can form an XYZ three-axis coordinate system, and the second operating arm is rotatably pivoted and fixed with the first operating arm through a first rotating shaft; the injection mechanism is fixedly mounted on the second operating arm; the brain fixing mechanism comprises a fixing frame base and a brain fixing frame, the fixing frame base is rotatably and fixedly connected with the machine base in a pivoted mode through a second rotating shaft, the axis of the first rotating shaft and the axis of the second rotating shaft can intersect at an intersection point, the axis of an injection needle of the micro-injector penetrates through the intersection point, and the brain fixing frame is fixed to the brain fixing frame. According to the animal brain positioning injection device, multi-angle needle insertion can be achieved, the needle head can be aligned to the position close to the origin of coordinates of the fonfonis of the mouse brain, and therefore the time for positioning the origin coordinates can be shortened, and the positioning efficiency is improved.

Description

TECHNICAL FIELD

[0001] The present application relates to the biomedical technology field, and in particular to an animal brain positioning injection device. BACKGROUND

[0002] Building a rat brain tumor model or other brain disease model requires positioning injection of tumor cells or drugs into the specified brain region of the rat. The current positioning injection of tumor cells or drugs requires the help of a brain stereotaxic apparatus. The injection process is roughly as follows: animal anesthesia, fixing the rat brain to the stereotaxic apparatus fixing frame, dissecting the scalp to expose the upper surface of the skull, positioning the marker drill hole, positioning the slow needle insertion (5-10 min), slow injection (5-30 min), retention and waiting (5-20 min), slow needle withdrawal (5-10 min), and suture of the scalp. The above injection process is time-consuming and laborious. Using the current conventional operation method, each skilled operator needs at least half an hour to complete one model. Since the number of models required for each experiment varies from dozens to hundreds, multiple operators are required to operate simultaneously or over several days, which affects the experimental results due to the poor uniformity of the models caused by the deviation in the operation process.

[0003] In addition, most of the current positioning injection apparatuses are manual, and the modeling process requires slow needle insertion and slow needle withdrawal, which is difficult to ensure uniform rate and occupies the operator's time. Although there are electric positioning apparatuses on the market, they are not only expensive, require a computer, and are bulky, but also are not brain tumor construction dedicated devices, and cannot improve the modeling efficiency. Therefore, there is an urgent need to design a small, simple, and low-cost automatic rat brain tumor inoculation device to improve the modeling efficiency and uniformity. SUMMARY

[0004] The purpose of the present application is to provide an animal brain positioning injection device that can improve the modeling efficiency.

[0005] To achieve the above purpose, the technical solution adopted by the present application is as follows:

[0006] An animal brain positioning injection device, comprising:

[0007] a machine base;

[0008] a mechanical arm, the mechanical arm comprising a first operation arm, a second operation arm and a third operation arm which can be constructed into an XYZ three-axis coordinate system, the first operation arm being fixedly connected with the machine base, the second operation arm being pivotally fixed with the first operation arm through a first rotating shaft, the axis of the first rotating shaft extending along the Y-axis direction, and the second operation arm being movable along the X-axis direction, the third operation arm being movably connected with the second operation arm;

[0009] An injection mechanism, comprising a syringe holder and a micro-injector, wherein the syringe holder is fixedly mounted on the second operating arm and the micro-injector is fixedly mounted on the syringe holder;

[0010] A brain fixation mechanism includes a fixation base and a brain fixation frame, the brain fixation frame being fixedly connected to the fixation base; the fixation base is rotatably pivotally fixed to the base via a second rotating shaft, the axis of the second rotating shaft extending along the Z-axis, the axes of the first rotating shaft and the second rotating shaft intersecting at an intersection point, and the axis of the injection needle of the micro-injector passing through this intersection point.

[0011] In one embodiment, the axis of the first rotating shaft and the axis of the second rotating shaft intersect at the anterior fontanelle of the mouse brain, which is fixed to the brain fixation frame.

[0012] In one embodiment, the first, second, and third manipulators all have both manual and automatic modes.

[0013] In one embodiment, the first, second, and third manipulators each include a lead screw, a stepper motor, a guide rail, a slider, and a knob. The slider is slidably connected to the guide rail. The axial ends of the lead screw are respectively driven by the stepper motor and the knob, and the lead screw is driven by the slider.

[0014] In one embodiment, the syringe holder includes a tube fixing plate and a syringe displacement mechanism. The tube fixing plate is fixed to the end of the second operating arm and has a tube fixing groove that matches the tube of the micro-syringe. The syringe displacement mechanism acts on the push rod of the micro-syringe fixed on the tube fixing plate.

[0015] In one embodiment, the tube fixing plate further includes an insulated flow channel surrounding the outside of the tube fixing groove, the insulated flow channel having an inlet and an outlet.

[0016] In one embodiment, the tube body fixing plate is further provided with an injection needle fixing groove that matches the injection needle of the micro-injector, and the injection fixing groove is connected to the tube body fixing groove.

[0017] In one embodiment, the bottom of the tube body fixing plate has a fixing groove, and lateral openings penetrating the tube body fixing plate are provided on both sides of the fixing groove. The bottom of the tube body fixing plate is also provided with a locking member that penetrates the fixing groove radially.

[0018] In one embodiment, the brain fixation frame is magnetically connected and fixed to the fixation frame base.

[0019] In one embodiment, the mounting base is provided with two vertical baffles, and magnets are installed on the opposing surfaces of the mounting base and the brain fixation frame, with the magnets on the mounting base being closer to the baffles than the magnets on the brain fixation frame.

[0020] In one embodiment, the brain fixation frame includes a fixation frame base, an X-axis slider, a Z-axis slider, a maxillary fixation member, and a head fixation rod. The X-axis slider is slidably mounted on the fixation frame base along the X-axis direction, and the Z-axis slider is slidably mounted on the X-axis slider along the Z-axis direction. The maxillary fixation member is hinged to the Z-axis slider, and the Z-axis slider is provided with a head receiving groove for accommodating the animal's brain. The maxillary fixation member has a fixing surface that matches the maxilla of the animal's brain. The head fixation rod is fixed to both sides of the fixation frame base in the Y-axis direction and is correspondingly provided to the head of the animal fixed to the brain fixation frame.

[0021] In one embodiment, the maxillary fixation member is provided with an anesthetic gas inlet at the position corresponding to the head receiving groove, and the head receiving groove is provided with an anesthetic gas outlet.

[0022] In one embodiment, a temperature-controlled pad is provided on the base of the fixation frame, and the temperature-controlled pad is provided corresponding to the body part of the animal fixed to the brain fixation frame.

[0023] The present invention, employing the above-mentioned technical solution, has the following beneficial effects: the robotic arm of the improved animal brain positioning injection device allows the micro-injector to move in the XYZ three-axis direction, while the second operating arm on the Z-axis can rotate around the first rotating shaft, and in conjunction with the rotation of the fixed base around the second rotating shaft, it can achieve movement in five-axis direction. Furthermore, the axes of the first and second rotating shafts intersect at the same intersection point, which is located on the extension line of the injection needle axis of the micro-injector. This allows the animal brain positioning injection device to achieve multi-angle needle insertion, and ensures that when adjusting the angle, the needle tip can still be aligned with the coordinate origin near the anterior fontanelle of the mouse brain. This reduces the time required to locate the origin coordinates and improves the positioning efficiency. Attached Figure Description

[0024] Figure 1 A schematic diagram of an animal brain localization injection device is shown.

[0025] Figure 2 A schematic diagram of an animal brain localization injection device is shown from another perspective.

[0026] Figure 3 A schematic diagram of the base is shown.

[0027] Figure 4 A schematic diagram of the robotic arm and the injection mechanism on the robotic arm is shown.

[0028] Figure 5 A schematic diagram of the sliders and guide rails for the Z and Y axes is shown.

[0029] Figure 6 A schematic diagram of a tube body fixing plate is shown.

[0030] Figure 7 A schematic diagram of another tube body fixing plate is shown.

[0031] Figure 8 A schematic diagram of a tube body fixing plate is shown from another perspective.

[0032] Figure 9 A schematic diagram of the fixed frame base is shown.

[0033] Figure 10 A schematic diagram of a brain fixation device is shown.

[0034] Figure 11 A schematic diagram of the slider in the Z-axis direction is shown.

[0035] Figure 12 A schematic diagram of the jawbone fixation device is shown. Detailed Implementation

[0036] The preferred embodiments of the present invention will be described in detail below with reference to the accompanying drawings to provide a clearer understanding of the purpose, features, and advantages of the present invention. It should be understood that the embodiments shown in the drawings are not intended to limit the scope of the present invention, but are merely illustrative of the essential spirit of the technical solution of the present invention.

[0037] In the following description, certain specific details are set forth for the purpose of illustrating various disclosed embodiments in order to provide a thorough understanding of the various disclosed embodiments. However, those skilled in the art will recognize that embodiments may be practiced without one or more of these specific details. In other instances, well-known apparatuses, structures, and techniques associated with this application may not have been shown or described in detail to avoid unnecessarily obscuring the description of the embodiments.

[0038] Unless the context requires otherwise, throughout the specification and claims, the word “comprising” and its variations, such as “including” and “having”, shall be understood to have an open, inclusive meaning, that is, to be interpreted as “including, but not limited to”.

[0039] Throughout this specification, references to "an embodiment" or "an embodiment" indicate that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one embodiment. Therefore, the appearance of "in an embodiment" or "an embodiment" in various places throughout the specification does not necessarily refer to the same embodiment. Furthermore, a particular feature, structure, or characteristic may be combined in any manner in one or more embodiments.

[0040] The singular forms “a” and “the” used in this specification and the appended claims include plural references unless otherwise expressly stated herein. It should be noted that the term “or” is generally used to mean “and / or” unless otherwise expressly stated herein.

[0041] In the following description, in order to clearly demonstrate the structure and working method of the present invention, a number of directional terms will be used. However, terms such as "front", "back", "left", "right", "outside", "inside", "outward", "inward", "up", and "down" should be understood as convenient terms and not as limiting terms.

[0042] Furthermore, terms such as "horizontal," "vertical," and "sag" do not imply that components must be absolutely horizontal or suspended, but rather that they can be slightly tilted. For example, "horizontal" simply means that its direction is more horizontal relative to "vertical," and does not mean that the structure must be completely horizontal, but can be slightly tilted.

[0043] In the description of this application, it should also be noted that, unless otherwise expressly specified and limited, the terms "set up," "install," "connect," and "link" should be interpreted broadly. For example, they can refer to a fixed connection, a detachable connection, or an integral connection; they can refer to a mechanical connection or an electrical connection; they can refer to a direct connection or an indirect connection through an intermediate medium; and they can refer to the internal connection of two components. Those skilled in the art can understand the specific meaning of the above terms in this application based on the specific circumstances.

[0044] like Figure 1 and Figure 2 As shown, this embodiment provides an animal brain localization injection device, including a base 1, a robotic arm 2, an injection mechanism 3, and a brain fixation mechanism 4.

[0045] See Figure 3The base 1 is a hollow shell with a roughly rectangular parallelepiped structure. Components such as the circuit board used to control the robotic arm 2 can be installed inside the base 1. The top surface of the base 1 has a flat surface 11, and a first groove 12 is provided above the flat surface 11. A screen 13 is fixedly installed in the first groove 12. The screen 13 is preferably a touch screen that can be operated by touch, allowing the operator to directly operate the animal brain positioning and injection device through the screen, such as controlling the movement of the robotic arm 2, the injection time of the injection mechanism 3, and the injection dosage.

[0046] See Figure 4 The robotic arm 2 includes a first manipulator 21, a second manipulator 22, and a third manipulator 23, which can be configured into an XYZ three-axis coordinate system. The first manipulator 21, second manipulator 22, and third manipulator 23 all have automatic and manual modes. The first manipulator 21 is arranged along the X-axis and includes a first lead screw 211, a first stepper motor (not shown), a first guide rail 212, a first slider 213, and a first knob 214. The first lead screw 211 is arranged along the X-axis, and its axial ends are respectively driven by the first stepper motor and the first knob 214, allowing both the first stepper motor and the first knob 214 to drive the first lead screw 211 to rotate. The output shaft of the first stepper motor can be directly connected to the first lead screw 211, or it can be driven by a transmission mechanism such as a gear pair. The transmission accuracy of the first lead screw 211 can also be improved by the gear ratio. Similarly, the first knob 214 can be driven by a gear pair. Figure 4 The lead screw 211 shown is directly formed at the end of the first lead screw 211, or it can be driven and connected to the first lead screw 211 through a transmission mechanism such as a gear pair.

[0047] The first guide rail 212 and the first slider 213 are configured to allow the first slider 213 to slide on the first guide rail. In this embodiment, the first guide rail 212 consists of three smooth first rods arranged parallel to the first lead screw 211. The first slider 213 has a first channel 2131 through which the first lead screw 211 passes. The external thread on the first lead screw 211 (not shown) engages with a lead screw nut (not visible in the view) fixedly installed in the first channel 2131. When the first lead screw 211 rotates clockwise or counterclockwise, it drives the first slider 213 to move along the X-axis. The first slider 213 has three first through holes 2132 on the outside of the first channel 2131. Each first through hole is used for one first rod to pass through. The multiple first rods together define the direction of movement of the first slider 213, thereby ensuring the accuracy of the first slider 213's movement along the X-axis. The two ends of the multiple first rods and the first lead screw 211 are supported on the side walls of opposite sides of the groove 12, so that most of the first operating arm 21 is sunk into the first groove 12, thereby reducing the overall height of the robotic arm 2.

[0048] The second operating arm 22 is arranged along the Z-axis and includes a Z-base 220, a second lead screw 221, a second stepper motor (not shown), a second guide rail 222, a second slider 223, and a second knob 224. The Z-base 220 is arranged along the Z-axis, and its bottom end is pivotally connected to the first slider 213 via a first rotating shaft 225. The axis of the first rotating shaft 225 is arranged along the Y-axis, allowing the Z-base 220 to rotate around it. The first rotating shaft 225 can also be driven by the stepper motor to achieve automatic rotation. The second lead screw 221 is arranged along the Z-axis, and its two axial ends are respectively driven by the second stepper motor and the second knob 224, allowing both the second stepper motor and the second knob 224 to drive the second lead screw 221 to rotate. The output shaft of the second stepper motor can be directly connected to the second lead screw 221, or it can be driven by a transmission mechanism such as a gear pair. Furthermore, the transmission ratio of the gear pair can be used to improve the transmission accuracy of the second lead screw 221. Similarly, the second knob 224 can be... Figure 4 The lead screw 221 shown is directly formed at the end of the second lead screw 221, or it can be driven and connected to the second lead screw 221 through a transmission mechanism such as a gear pair.

[0049] The second guide rail 222 is configured to cooperate with the second slider 223 so that the second slider 223 can slide on the second guide rail. See also... Figure 5In this embodiment, the second guide rail 222 consists of two smooth second rods arranged parallel to the second lead screw 221. The second slider 223 has a second channel 2231 through which the second lead screw 221 passes. The external thread on the second lead screw 221 (not shown) engages with a lead screw nut (not visible in the view) fixedly installed in the second channel 2231. When the second lead screw 221 rotates clockwise or counterclockwise, it drives the second slider 223 to move along the Z-axis. The second slider 223 has two second through holes 2232 on the outside of the second channel 2231. Each second through hole is used for one second rod to pass through. The multiple second rods together define the movement direction of the second slider 223, thereby ensuring the accuracy of the movement of the second slider 223 along the Z-axis. A second groove 2201 is provided on the Z-axis base 220. The two ends of multiple second rods and the second lead screw 221 are supported on the upper and lower side walls of the second groove 2201, so that most of the second slider 223 is sunk into the second groove 2201, thereby reducing the overall thickness of the second operating arm 22.

[0050] The third operating arm 23 is arranged along the Y-axis and includes a Y-axis base 230, a third lead screw 231, a third stepper motor (not shown in the figure), a third guide rail 232, a third slider 233, and a third knob 234. See also... Figure 5 In this embodiment, the third slider 233 and the second slider 223 are integrally formed as a single unit. The Y-axis base 230 is arranged along the Y-axis direction and is slidably connected to the third slider 233, allowing the Y-axis base 230 to move along the Z-axis direction with the second slider 223 and also along the Y-axis direction via the third slider 233. The third lead screw 231 is arranged along the Y-axis direction, with its axial ends respectively connected to the third stepper motor and the third knob 234, allowing both the third stepper motor and the third knob 234 to drive the third lead screw 231 to rotate. The output shaft of the third stepper motor can be directly connected to the third lead screw 231, or it can be driven by a transmission mechanism such as a gear pair. Furthermore, the transmission ratio of the gear pair can be used to improve the transmission accuracy of the third lead screw 231. Similarly, the third knob 234 can be... Figure 5 The screw shown is formed directly at the end of the third lead screw 231, or it can be driven and connected to the third lead screw 231 through a transmission mechanism such as a gear pair.

[0051] The third guide rail 232 and the third slider 233 are configured to allow the third slider 233 to slide on the third guide rail 232. In this embodiment, the third guide rail 232 consists of two smooth third rods arranged parallel to the third lead screw 231. The third slider 233 has a third channel 2331 through which the third lead screw 231 passes. The external thread on the third lead screw 231 (not shown) engages with the lead screw nut 2333 fixedly installed in the third channel 2331. When the third lead screw 231 rotates clockwise or counterclockwise, it drives the third slider 233 to move along the Y-axis. The third slider 233 has two third through holes 2332 on the outside of the third channel 2331. Each third through hole 2332 is used for one third rod to pass through. The multiple third rods together define the direction of movement of the third slider 233, thereby ensuring the accuracy of the movement of the third slider 233 along the Y-axis. A third groove is provided on the Y-axis base 230. The two ends of multiple third rods and the third lead screw 231 are supported on the front and rear side walls of the third groove, so that most of the third slider 233 is sunk into the third groove, thereby reducing the overall thickness of the third operating arm 23.

[0052] See Figure 4 The injection mechanism 3 includes a syringe holder 31 and a micro-syringe (not shown in the figure). The syringe holder includes a fourth lead screw 311, a fourth stepper motor (not shown in the figure), a fourth guide rail 312, a fourth slider 313, a fourth knob 314, and a tube body fixing plate 315. The fourth lead screw 311 is arranged along the Z-axis direction. Its lower end is driven and connected to the fourth stepper motor fixedly installed in the Y-axis base 230, and its upper end is driven and connected to the fourth knob 314, so that both the fourth stepper motor and the fourth knob 314 can drive the fourth lead screw 311 to rotate. The output shaft of the fourth stepper motor can be directly connected to the fourth lead screw 311, or it can be driven and connected to the fourth lead screw 311 through a transmission mechanism such as a gear pair. At the same time, the transmission ratio of the gear pair can be used to improve the transmission accuracy of the fourth lead screw 311. Similarly, the fourth knob 314 can be driven and connected to the fourth lead screw 311 through a transmission mechanism such as a gear pair. Figure 4 The fourth lead screw 311 is directly formed at the end shown, or it can be driven and connected to the fourth lead screw 311 through a transmission mechanism such as a gear pair.

[0053] The fourth guide rail 312 and the fourth slider 313 are configured to allow the fourth slider 313 to slide on the fourth guide rail 312. In this embodiment, the fourth guide rail 312 consists of two smooth fourth rods arranged parallel to the fourth lead screw 311. The fourth slider 313 has a fourth channel 3111 through which the fourth lead screw 311 passes. The external thread on the fourth lead screw 311 (not shown) engages with a lead screw nut fixedly installed inside the fourth channel 3111. When the fourth lead screw 311 rotates clockwise or counterclockwise, it drives the fourth slider 313 to move along the Z-axis. The fourth slider 313 has two fourth through holes 3112 on the outside of the fourth channel 3111. Each fourth through hole 3112 is used for one fourth rod to pass through. The multiple fourth rods together define the direction of movement of the fourth slider 313, thereby ensuring the accuracy of the fourth slider 313's movement along the Z-axis. The fourth slider 313 is provided with a fixing groove 3131 that matches the push rod head of the micro-syringe. The movement of the fourth slider 313 in the Z-axis direction will drive the push rod of the micro-syringe to move in the Z-axis direction, thereby realizing the liquid aspiration and injection operation of the micro-syringe.

[0054] See Figure 4 and Figure 6 The tube body fixing plate 315 is fixedly installed at the front end of the Y-axis base 230. The tube body fixing plate 315 has a tube body fixing groove 3151 that matches the tube body of the micro-syringe. The tube body of the micro-syringe can be fixed into the tube body fixing groove 3151, thus enabling three-dimensional movement with the Y-axis base 230. The tube body fixing groove 3151 on the tube body fixing plate 315 can be designed according to different sizes of syringes, allowing each tube body fixing plate 315 to fit a specific size syringe. Correspondingly, to facilitate the disassembly and installation of the tube body fixing plate 315, the tube body fixing plate 315 and the Y-axis base 230 are fixedly connected by bolts.

[0055] refer to Figure 6 In one embodiment, the tube body fixing plate 315 is further provided with an injection needle fixing groove 3152 that matches the injection needle of the syringe. Because existing syringe pumps cannot be fixed when directly installed and used, the slender needle lacks sufficient flexibility and will wobble, resulting in inaccurate positioning. However, the injection needle fixing groove 3152 provided on the tube body fixing plate 315 in this embodiment, which matches the injection needle, can limit needle wobble, thereby improving the positioning accuracy of the injection needle.

[0056] See Figure 7In another embodiment, to maintain the viability of biological samples or cells in the syringe, the syringe fixing plate 315 is also provided with a heat-insulating flow channel 316 surrounding the outside of the syringe fixing groove 3151, as the injection time is long when constructing mouse and rat brain tumor models or other brain disease models. The heat-insulating flow channel 316 is an annular groove located outside the syringe fixing groove 3151. The heat-insulating flow channel 316 also has an inlet 3161 and an outlet 3162. The inlet 3161 and the outlet 3162 are located on opposite sides of the upper part of the heat-insulating flow channel 316, and a partition is also provided in the annular groove. The partition is arranged vertically to divide the upper part of the annular groove into two chambers. The bottoms of the chambers are connected, allowing the heat-insulating liquid to flow from the inlet 3161 into the heat-insulating flow channel 316. After circulating in the heat-insulating flow channel 316, it flows out from the outlet 3162, which has a heat-insulating effect on the injection liquid in the syringe located in the syringe fixing groove 3151, so as to maintain the viability of biological samples or cells in the syringe. The insulating liquid is typically water at 4 degrees Celsius or 37 degrees Celsius. An external water-cooling device is connected via pipes to the inlet 3161 and outlet 3162 of the insulating flow channel 316. Water flows around the syringe through the tube fixing plate 315, and the temperature of the sample inside the syringe is controlled by the water temperature. The water-cooling device can consist of a semiconductor cooling chip, heat sink, heating rod, cooling fan, water pump, water pipes, and connectors. A PID control system allows the temperature to be set directly on the controller, achieving automatic temperature adjustment.

[0057] See Figure 8 In another embodiment, the bottom of the tube body fixing plate 315 is designed with a fixing groove 3153. Lateral openings 3154 penetrating the tube body fixing plate 315 are provided on opposite sides of the fixing groove 3153. A locking member (not visible in the view of the figure) is also provided at the bottom of the tube body fixing plate 315, penetrating the fixing groove 3153 radially. This locking member can fix the object located in the fixing groove 3153 onto the tube body fixing plate 315. The fixing groove 3153 can be used to fix external needles of the syringe, such as glass needles or implantable needles. Taking an implantable needle as an example, an implantable needle is a type of indwelling tube inserted into a specific location within the skull and fixed to the surface of the skull for multiple sampling or administration. In use, the implantable needle is inserted into the fixing groove 3153 and locked in place with the locking member. Loosening the locking head releases the needle, making installation convenient.

[0058] See Figure 3 , Figure 9 and Figure 10The brain fixation mechanism 4 includes a fixation base 41 and a brain fixation frame 42. The fixation base 41 is rotatably pivotally fixed to the base 1 via a second rotating shaft 43. The axis of the second rotating shaft extends along the Z-axis and is located in the middle of the plane 11 on the top surface of the base 1. The axes of the first rotating shaft 225 and the second rotating shaft 43 intersect at the same point, which is located on the extension line of the injection needle axis of the micro-injector. Taking a commonly used experimental mouse as an example, this intersection point is located at the origin of the coordinate system at the anterior fontanelle of the mouse brain. After the operation of each manipulator arm of the robotic arm 2, it can automatically reset and automatically rotate to a preset angle and maintain the angle. See also Figure 1 and Figure 2 The first, second, and third manipulators of the robotic arm 2 allow the micro-injector to move along the XYZ axes. Simultaneously, the second manipulator on the Z-axis can rotate around the first pivot 225, and in conjunction with the base 41, rotates around the second pivot 43. This embodiment of the animal brain positioning injection device allows for movement along five axes. The axes of the first pivot 225 and the second pivot 43 intersect at the same point, which is located on the extension line of the micro-injector's needle axis. This allows the animal brain positioning injection device to perform multi-angle needle insertion, ensuring that when adjusting the angle, the needle is still aligned with the coordinate origin near the anterior fontanelle of the mouse brain. This reduces the time required to locate the origin coordinates and improves positioning efficiency.

[0059] See Figure 9 and Figure 10 The fixation base 41 and the brain fixation frame 42 are magnetically secured together, allowing for easy removal for manual fixation, dissection, drilling, and other operations. One animal brain positioning injection device can be equipped with two or more brain fixation frames 42, enabling simultaneous injection of the injection into another mouse, saving time. To ensure the reliability of the magnetic fixation, two vertical baffles 411 are provided on the fixation base 41. Magnets are installed on both the fixation base 41 and the brain fixation frame 42, but their positions are not perfectly aligned. The magnet on the fixation base 41 is offset approximately 2mm from each of the two baffles 411, ensuring that the brain fixation frame 42 is tightly attached to the two baffles 411, increasing the angular stability of the brain fixation frame 42.

[0060] See Figure 10The brain fixation frame 42 includes a fixation frame base 421, an X-axis slider 422, a Z-axis slider 423, a maxillary fixation member 424, and two head fixation rods 425. The fixation frame base 421 has a generally rectangular shape and a protruding protrusion 4211 at one end along the X-axis. An X-axis adjusting screw 4212 extending along the X-axis is provided on the protrusion 4211. One end of the X-axis adjusting screw 4212 is fixedly connected to the X-axis slider 422, and the other end is provided with an X-axis adjusting knob 4213. The X-axis slider 422 is slidably connected to the fixed frame base 421 via two smooth fifth rods 4214 extending along the X direction. The protrusion 4211 is provided with a fifth channel 4215 through which the X-axis adjusting screw 4212 passes. The external thread (not shown in the figure) on the X-axis adjusting screw 4212 cooperates with the internal thread of the fifth channel 4215 or a screw nut fixedly installed in the fifth channel 4215 to allow the X-axis adjusting screw 4212 to achieve linear movement in the X-axis direction, thereby adjusting the displacement of the X-axis slider 422 in the X-axis direction.

[0061] A gantry 4221 is provided on the X-axis slider 422, and a Z-axis adjusting screw 4222 extending along the Z-axis direction is provided on the gantry 4221. One end of the Z-axis adjusting screw 4222 is fixedly connected to the Z-axis slider 423, and the other end is provided with a Z-axis adjusting knob 4223. The Z-axis slider 423 is slidably connected to the X-axis slider 422 via two smooth sixth rods 4224 extending along the Z-axis. A sixth channel 4225 is provided on the gantry 4221 for the Z-axis adjusting screw 4222 to pass through. The external thread (not shown in the figure) on the Z-axis adjusting screw 4222 cooperates with the internal thread of the sixth channel 4225 or a screw nut fixedly installed in the sixth channel 4225 to allow the Z-axis adjusting screw 4222 to achieve linear movement in the Z-axis direction, thereby adjusting the displacement of the Z-axis slider 423 in the Z-axis direction. The Z-axis slider 423 is provided with a head receiving groove 4231 for accommodating the mouse's head. The Z-axis slider 423 is also provided with a hinge protrusion 4232 that is hinged to the maxillary fixation member 424. One end of the maxillary fixation member 424 is hinged to the hinge protrusion 4232 of the Z-axis slider 423 via a pivot, and the other end extends above the head receiving groove 4231 and has a maxillary fixation surface 4241 that matches the maxilla of the mouse's head.

[0062] The mounting base 421 has a lug 4216 on each side of the mouse's head. Two head fixing rods 425 pass through the two lugs 4216 along the Y-axis. The two ends of the two head fixing rods 425 are pyramidal tips, used to fix the sides of the mouse's head, thereby fixing the mouse's skull and leveling it. Each lug 4216 is also provided with a fixing rod locking member 426 for fixing the corresponding head fixing rod 425. In this embodiment, the fixing rod locking member 426 is a hand-tightening screw. The hand-tightening screw is threaded to the lug 4216, and its head passes through the through hole of the head fixing rod 425 through the lug 4216, abutting against the head fixing rod 425 to limit the displacement of the head fixing rod 425.

[0063] The brain fixation frame 42 uses the jawbone fixation member 424 to cooperate with the head receiving groove 4231 to position and fix the mouse head on the Z-axis slider 423. At the same time, through the movement of the X-axis slider 422 in the X-axis direction and the movement of the Z-axis slider 423 in the Z-axis direction, the brain fixation frame 42 can be adapted to different head sizes of mice and rats, making it more versatile.

[0064] In one embodiment, see Figure 10 The base 41 of the fixation frame is also equipped with a temperature-regulating pad module 427. The temperature-regulating pad module 427 is positioned corresponding to the body part of the mouse that is fixed on the brain fixation frame 42. The temperature-regulating pad module 427 can elevate the mouse's body and control heating to maintain body temperature. Since mice and rats are generally anesthetized by drug injection, deaths due to body position and hypothermia occur during surgery. After adding the temperature-regulating pad module 427 to the base 41 of the fixation frame to maintain the mouse's body position and body temperature, almost no deaths occurred during the experiment.

[0065] In another embodiment, see Figure 11 and Figure 12 The maxillary fixation component 424 has an anesthetic gas inlet 4242 positioned at the corresponding head receiving slot 4231, aligned with the mouse's nose. An anesthetic gas outlet 4233 is provided on the head receiving slot 4231 for collecting waste gas. The anesthetic gas inlet 4242 is connected to a gas anesthesia machine, and the anesthetic gas outlet 4233 is connected to a negative pressure unit to recover waste gas, thus achieving gas anesthesia for the mouse. Gas anesthesia has the advantages of rapid anesthesia and rapid recovery, reducing anesthesia time and postoperative care, improving modeling efficiency, and allowing for intermittent ventilation during injection to maintain the anesthetic effect. After connecting to the gas anesthesia machine, tests showed that administering isoflurane anesthetic gas for 10 seconds every two minutes maintained a stable anesthetized state in the mouse.

[0066] The operation process of the animal brain localization injection device provided in this embodiment is as follows:

[0067] S1. Power on the device and set the parameters on the control panel, such as the injector volume model, injection volume, injection speed, injection site coordinates XYZ, angle EF (angle EF is the deflection angle of the second operating arm in the Z-axis direction and the rotation angle of the fixed frame base), needle insertion speed, needle retraction speed, and settling time. After setting the parameters, you can save them to EEPROM.

[0068] S2. Install the microsyringe on the syringe holder 31 and secure the needle.

[0069] S3. Fix the head of the anesthetized mouse to the brain fixation frame, cut open the scalp to expose the needle insertion point and the surrounding skull;

[0070] S4. Install the brain fixation frame on the fixation frame base, manually adjust the X, Y, and Z axes so that the tip of the microsyringe is aligned with and touches the intersection of the sutures at the anterior fontanelle of the skull. Set the origin on the control screen (the system sets this point as the origin of the three-axis rectangular coordinate system).

[0071] S5. Press the coordinate test button on the control panel. The robotic arm will automatically move to the xy coordinate of the needle insertion point. Remember this coordinate position. Press the lift button. The Z-axis will rise to a certain height. Use a skull drill to make a hole at the needle insertion point. The hole diameter should be slightly larger than the needle diameter.

[0072] S6. After mixing the tumor cell sample, insert the syringe needle and take a sample. The micro-syringe will automatically extract the preset volume of cell sample.

[0073] S7. Press the Run button, and the system will automatically complete the needle insertion, injection, resting, and needle withdrawal process (this process takes about 20 minutes or more), while the progress of each process will be displayed on the screen.

[0074] S8. After the injection, suture the mouse's scalp and remove it. If multiple mice need to be injected, during step S7, a second brain fixation device can be used to process another mouse in step S3. After the injection of the previous mouse is completed, directly replace the first brain fixation device with the second brain fixation device and execute steps S4 to S8 simultaneously until all samples have been injected.

[0075] The animal brain localization injection device provided in this embodiment can be operated by one person at the same time for 3-5 devices, creating 6-12 models per hour. Compared with the existing localization devices, where one person can operate a maximum of two devices at the same time, the modeling efficiency is about 3-5 models per hour. Moreover, manual operation results in poor model uniformity, which is not conducive to large-scale preclinical animal experiments. Therefore, the animal brain localization injection device provided in this embodiment can greatly improve the modeling efficiency and ensure good uniformity among samples.

[0076] The preferred embodiments of the present invention have been described in detail above. However, it should be understood that after reading the above teachings, those skilled in the art can make various alterations or modifications to the present invention. These equivalent forms also fall within the scope defined by the appended claims.

Claims

1. An animal brain localization injection device, characterized in that, The utility model relates to a mouse brain microinjection device, comprising: a base; a mechanical arm, which comprises a first operation arm, a second operation arm and a third operation arm that can be constructed into an XYZ three-axis coordinate system, the first operation arm is fixedly connected with the base, the second operation arm is pivotally fixedly connected with the first operation arm through a first rotating shaft, the axis of the first rotating shaft extends along the Y-axis direction, and the second operation arm can move along the X-axis direction, the third operation arm is movably connected with the second operation arm; an injection mechanism, which comprises an injector fixing frame and a microinjector, the injector fixing frame is fixedly installed on the second operation arm, and the microinjector is fixedly installed on the injector fixing frame; a brain fixing mechanism, which comprises a fixing frame base and a brain fixing frame, the brain fixing frame is fixedly connected with the fixing frame base, the fixing frame base is pivotally fixedly connected with the base through a second rotating shaft, the axis of the second rotating shaft extends along the Z-axis direction, the axes of the first rotating shaft and the second rotating shaft can intersect at a point, and the axis of the injection needle of the microinjector passes through the point.

2. The animal brain positioning and injection device of claim 1, wherein, The axes of the first rotating shaft and the second rotating shaft intersect at the bregma position of a mouse brain fixed on the brain fixing frame.

3. The animal brain positioning and injection device of claim 1, wherein, The first operation arm, the second operation arm and the third operation arm both have a manual mode and an automatic mode.

4. The animal brain positioning and injection device of claim 3, wherein, The first operation arm, the second operation arm and the third operation arm all comprise a lead screw, a stepping motor, a guide rail, a sliding block and a knob, the sliding block is slidably connected with the guide rail, the axial ends of the lead screw are respectively drivingly connected with the stepping motor and the knob, and the lead screw is drivingly connected with the sliding block.

5. The animal brain positioning and injection device of claim 1, wherein, The injector fixing frame comprises a tube body fixing plate and an injector displacement mechanism, the tube body fixing plate is fixed on the end of the second operation arm, the tube body fixing plate is provided with a tube body fixing groove matched with the tube body of the microinjector, and the injector displacement mechanism acts on the push rod of the microinjector fixed on the tube body fixing plate.

6. The animal brain positioning and injection device of claim 5, wherein, The tube body fixing plate further comprises a heat preservation flow channel surrounding the outside of the tube body fixing groove, and the heat preservation flow channel further has an inlet and an outlet.

7. The animal brain positioning and injection device of claim 1, wherein, The brain fixing frame and the fixing frame base are fixedly connected through magnetic attraction.

8. The animal brain positioning and injection device of claim 7, wherein, The fixing frame base is provided with two vertical stop edges, magnets are installed on the opposite surfaces of the fixing frame base and the brain fixing frame, and the magnet on the fixing frame base is closer to the stop edges than the magnet on the brain fixing frame.

9. The animal brain positioning and injection device of claim 1, wherein, The brain fixing frame comprises a fixing frame base, an X-axis direction sliding block, a Z-axis direction sliding block, a maxilla fixing piece and a head fixing rod, the X-axis direction sliding block is slidably installed on the fixing frame base along the X-axis direction, the Z-axis direction sliding block is slidably installed on the X-axis direction sliding block along the Z-axis direction, the maxilla fixing piece is hingedly connected to the Z-axis direction sliding block, the Z-axis direction sliding block is provided with a head accommodating groove for accommodating the brain of an animal, the maxilla fixing piece is provided with a fixing surface matched with the maxilla of the brain of the animal, and the head fixing rod is fixed to the two sides of the fixing frame base along the Y-axis direction and is arranged corresponding to the head of the animal fixed to the brain fixing frame.

10. The animal brain positioning and injection device of claim 9, wherein, The maxilla fixing piece is provided with an anesthetic gas inlet at a position corresponding to the head accommodating groove, and the head accommodating groove is provided with an anesthetic gas outlet.

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