CN113317903A

CN113317903A - Mouse operation and optical imaging experimental device

Info

Publication number: CN113317903A
Application number: CN202010130502.1A
Authority: CN
Inventors: 程庆元; 李俐漫; 钱琨
Original assignee: Individual
Current assignee: Individual
Priority date: 2020-02-28
Filing date: 2020-02-28
Publication date: 2021-08-31

Abstract

The invention relates to a mouse operation and optical imaging experimental device, which comprises: the operation table is used for placing the mouse; the fixing piece is used for accommodating four limbs and the tail of the mouse and flexibly fixing the mouse together with the operating platform; the nose cover is used for gas anesthesia of the mouse; the eyeshade is used for protecting the eyes of the mouse and can be used independently; a scalp spreader for fully exposing the mouse brain operative field; further comprising: and the tail vein injection auxiliary device is connected with the operating platform and is used for assisting the puncture and the injection of the tail vein of the mouse. The experimental device for mouse surgery and optical imaging provided by the invention can uniformly and smoothly complete experimental operations including mouse fixation, anesthesia, tail vein puncture administration and the like in surgery and imaging on the device, and can provide good eye protection and body temperature maintenance for the mouse, thereby facilitating the operation of the experiment, improving the success rate of the experiment, expanding the research range, saving the experimental cost and fully enhancing the animal welfare.

Description

Mouse operation and optical imaging experimental device

Technical Field

The invention relates to the field of animal experiment devices for biomedical scientific research experiments, in particular to a mouse operation and optical imaging experiment device.

Background

Mouse head surgery operations, such as brain drug injection or in situ glioma model construction, are very important and common biomedical animal experimental techniques. One of the experimental instruments commonly used in the above-mentioned surgical operations is a brain stereotaxic instrument. The instrument is characterized in that an anesthetized mouse is firmly fixed on an operation table, the scalp is cut to expose the skull, and a micro-injector is used for accurately administering drugs or tumor cells and the like to a specific region of the brain of the mouse under the assistance of a strong lamp, a cranial drill, a three-dimensional coordinate instrument and the like.

The molecular imaging technology such as optical living body imaging technology, surgery under fluorescence guidance and the like has the advantages of accurate positioning, accurate excision and the like, has good development prospect and large clinical application potential, and therefore becomes a research hotspot in recent years. In vivo animal imaging experiments are the most important means of assessment before further clinical use, and mice are the most common animal model for the latter. The optical in vivo imaging experiment of the mouse is generally carried out in a small animal in vivo imager, and comprises the following steps: after a mouse is anesthetized, optical contrast agents such as fluorescent materials and the like are injected into the abdominal cavity or veins and placed on an imaging platform, laser is used for exciting the fluorescent contrast agents to emit fluorescence, and real-time high-quality imaging of in-vivo parts such as blood vessels, tumors and the like of the mouse is achieved through fluorescent imaging equipment.

The two experiments not only have communication parts in specific operation, such as strict fixation of a mouse, use of a strong light source and the like, but also are often used in a combined manner, such as firstly constructing a tumor animal model through brain surgery, then imaging the tumor through optical imaging and then performing imaging-guided surgical excision, so that the two experiments are relatively closely related. Due to the complicated experiment, multiple operations including anesthesia induction maintenance of the mouse, fixation of the head and limbs, surgery, injection administration and the like are required, and the mouse needs to be moved for several times due to different instruments or operations during the operation, thereby causing inconvenience to the experiment. Although the prior art develops a fixed table (CN110353720A) or a multifunctional small animal operating table (CN106308967B), various experimental operations can be completed on the device, but the requirements of experimental conditions such as a head operation, optical living body imaging and the like cannot be met. For example, the existing small animal operating table has too large volume and cannot be placed into a stereotaxic apparatus or a living body imaging apparatus; for another example, the material and color of the material can interfere with fluorescence imaging, and thus is not suitable for optical in vivo imaging.

Moreover, these experiments are long in cycle, difficult to operate, expensive, and often require repeated, long-term observation and intervention of the mice. Therefore, it is important to take care and provide the mice with necessary protective measures during the operation process, so as to avoid the mice from being damaged or even dying to cause experimental failure.

In the optical living body imaging process of the mouse, the limbs and the tail of the mouse need to be fixed, and imaging is carried out in the same posture in multiple experiments so as to obtain a high-quality and attractive imaging effect picture. However, the existing optical living body imaging instrument is lack of a fixing device, and can only be fixed by adopting modes of adhesive tapes, pins and the like, so that the fixing effect is poor, the operation is inconvenient, the repeated use is difficult, and the mouse is easily injured.

Safe and stable mouse anesthesia technology is one of the important prerequisites for the success of the experiment. In mouse anesthesia, the most common problems are two: firstly, how to stably maintain anesthesia and secondly, how to avoid death caused by hypothermia in the mouse anesthesia process. In addition to optimizing anesthetic, the solution of the gas anesthesia method is to perform induction anesthesia on the mouse in a closed space and then maintain the mouse in anesthesia with a catheter or a simple mask with a lower concentration of anesthetic gas (CN 201720510414.8); the liquid anesthesia mode adopts the mode of multiple administration and proper needle repair; in response to the second problem, the prior art adopts a thermostatic device for animal anesthesia assistance, which is used for maintaining the body temperature of anesthetized mice, such as CN 209203614U. However, the above-mentioned anesthesia devices or methods all lack flexibility, and can not be adapted with instruments such as brain stereotaxic apparatus, living body imager, for example, the above-mentioned operation often needs to fix the mouse in the prone position, but often needs to mend the needle in the abdominal cavity anesthesia in-process, and it can bring a lot of inconvenience to remove fixed, snatch the mouse and fix again and can bring for experimental operation, greatly reduced experimental efficiency.

The mouse brain surgery equipment and the living body imager need to use a strong light source (such as light used on a positioning instrument and laser used in the imager), and the continuous irradiation of the equipment can easily cause burn and even blindness of the eyes of the mouse, so that great pain is brought to the mouse, and the subsequent experiment is seriously influenced. However, there is currently a lack of corresponding measures to protect the eyes of mice in the above experiments.

During mouse brain surgery or brain imaging, the head of the mouse needs to be rigidly fixed and the scalp on both sides of the incision needs to be pulled to expose the surgical field as much as possible. The brain stereotaxic apparatus is provided with a special mouse head fixer which can firmly fix the head of a mouse, but is lack of a scalp strutting device and brings inconvenience to the operation to a certain degree.

In addition, in the experiment process, a large amount of excrement generated by stimulation is received by the mouse, so that the experiment operation space (such as an operation table) is polluted, inconvenience is brought to the experiment, and discomfort is brought to the mouse. But methods for timely cleaning the excrement of the mice are lacked at present.

Mouse optical in vivo imaging and fluorescence guided surgical procedures require administration of a corresponding imaging contrast agent to the subject. For mice, tail vein puncture bolus injection is the most commonly used mode of contrast agent administration. Furthermore, to further enable dynamic real-time vessel and blood flow imaging observation, it is often necessary to perform imaging immediately at the same time as the administration injection. However, the tail vein of the mouse is very tiny and difficult to observe, and the blood vessel is further contracted after anesthesia, so that the puncture difficulty is high, and once the puncture fails, repeated puncture of the rat tail is difficult. Therefore, the prior art develops a special injection device (CN107334560A) for the tail vein of the mouse, which improves the success rate of puncture, but the device is heavy and brings inconvenience to the whole experimental operation process, and the device can not be adapted to a living body imager, so that real-time imaging is difficult to realize.

Therefore, there is a need for a mouse surgery and optical imaging experimental apparatus that can solve the above problems.

Disclosure of Invention

In order to solve the problems, the invention provides a mouse operation and optical imaging experimental device, which can uniformly and smoothly complete experimental operations such as mouse brain operation, optical living body imaging and the like on the device, comprises body fixation, safe and stable anesthesia and fast and efficient puncture drug delivery in the operations and imaging, and can provide good eye protection and body temperature maintenance for a mouse, thereby facilitating the operation of the experiments, improving the success rate of the experiments, expanding the research range, saving the experimental cost and fully enhancing the animal welfare.

In order to achieve the above object, the present invention provides an experimental apparatus for mouse surgery and optical imaging, comprising: the operation table is used for placing a mouse and comprises an operation window, wherein the operation window can be opened and closed, and the position of the operation window corresponds to the position of the abdominal cavity of the mouse placed on the operation table; the bottom surfaces of the fixing pieces can be connected with the operating table, and are provided with grooves formed by upward sinking for accommodating the limbs and the tail of the mouse; and the tail vein injection auxiliary device is connected with the operating platform and is used for assisting the puncture and the injection of the tail vein of the mouse.

In this technical scheme, the mounting can cooperate with the operation panel according to the experiment needs to nimble fixed mouse's position, the posture of adjustment mouse, this mode is fixed and adjustment easy operation, and does not have stimulation, not damaged to the mouse.

In the technical scheme, the position of the operation window corresponds to the position of the abdominal cavity of the mouse fixed on the operation table, when the operation window is in an open state, the abdominal cavity of the mouse is exposed to the operation window, the operation table can be directly turned over for intraperitoneal injection without taking the mouse off the operation table and then injecting the mouse after being grasped, and convenience is brought to experimental operation. Simultaneously, through opening the operation window, can conveniently in time clear up the operation window and lean on the excrement of placing mouse abdominal cavity one side production, alleviate the influence of mouse excrement to experimental operation and mouse comfort level.

In this technical scheme, the setting of tail vein injection auxiliary device can show the success rate that promotes this experimental operation of mouse tail vein puncture and bolus.

In a preferred technical scheme of the invention, the experimental device for mouse surgery and optical imaging further comprises a constant temperature device, wherein the constant temperature device is arranged on the operating platform and can keep the temperature of the operating platform within a preset range.

In the technical scheme, the constant temperature device can maintain the body temperature of the mouse in the experimental process, so that the mouse is prevented from being coma or even dying due to low body temperature in an anesthesia state, and the smooth experiment is guaranteed.

In a preferred embodiment of the present invention, the experimental device for mouse surgery and optical imaging further comprises: the nose cup, the nose cup with the operation panel is connected for supply mouse gas anesthesia to use, the nose cup is hourglass hopper-shaped, and the mouth nose looks adaptation of size and mouse.

In this technical scheme, the nose cup is the mouth nose looks adaptation of leaking hopper-shaped and size and mouse, can form the relative seal of the mouth nose of nose cup and mouse, not only can improve anesthesia effect, can also prevent that anesthetic gas from revealing the waste and the healthy harm of experimenter of the anesthetic reagent that cause. In addition, the nose mask is connected to the console to assist in fixing the posture of the mouse.

In a preferred embodiment of the present invention, the experimental device for mouse surgery and optical imaging further comprises: an eye shield for protecting the eyes of a mouse during an experiment, the eye shield comprising: the eyeshade body is used for shielding eyes of a mouse; and the headband is connected with the eyeshade body on one hand for the mouse to wear and connected with the operating console on the other hand.

In this technical scheme, the laser irradiation that the eye-shade set up and can avoid in the operation strong lamp light or imager to use to mouse eyes's damage, in addition, eye-shade simple structure wears the convenience, can keep steadily firm and let the mouse keep comfortable in wearing for a long time to the eye-shade can play the effect of supplementary fixed mouse posture with being connected of operation panel.

In a preferred embodiment of the present invention, the experimental device for mouse surgery and optical imaging further comprises: the scalp spreader is arranged on two sides of the head of the mouse and used for spreading the scalp of the mouse, and the scalp spreader comprises: the scalp spreading hook is of an arc-shaped structure and is provided with a plurality of blunt hooks arranged along an arc-shaped surface in a tooth shape; and the supporting rod extends along the height direction, one end of the supporting rod is connected with the operating platform, and the other end of the supporting rod is connected with the scalp opening hook.

In the technical scheme, the pair of scalp opening hooks are arc-shaped and are oppositely arranged, and the scalp opening hooks are provided with the plurality of blunt hooks which are arranged along the arc-shaped surface in a tooth shape, so that when the scalp opening hooks draw the scalp by using the plurality of blunt hooks, the scalp can be opened to be approximately round under the condition that the head incision of a mouse is as small as possible, and the experiment operation is convenient; the scalp of the mouse can be hooked by only one of the blunt hooks, and one corner of the scalp of the mouse is pulled, so that the stretching size and shape of the scalp of the mouse can be flexibly adjusted, and the optimization of an operation exposure area is realized.

In a preferred embodiment of the present invention, the tail vein injection assisting apparatus further includes: the supporting piece is fixed on one side close to the tail of the mouse along the length direction of the operating platform opposite to the operating platform; and the telescopic piece is connected with the support piece in a sliding manner along the length direction of the operating platform, wherein a containing groove for containing the tail of the mouse is formed in the telescopic piece.

In a preferred embodiment of the present invention, the tail vein injection assisting apparatus further includes: and the indicating lamp is arranged in the telescopic piece accommodating groove and is used for displaying the tail vein of the tail of the mouse.

In this technical scheme, accomodate the afterbody of mouse in the storage tank, can realize the position of mouse afterbody and prescribe a limit to, help going on of mouse tail vein puncture and bolus. And, under the irradiation of pilot lamp, can be comparatively clear show the tail vein of mouse, further provide convenience for the tail vein puncture of mouse and push. In addition, the relative positions of the mouse tails with different lengths and the indicating lamps in the telescopic piece accommodating grooves can be changed by adjusting the telescopic amount of the telescopic pieces, so that the indicating lamps always irradiate the parts most easily punctured by the mouse tails.

In a preferred embodiment of the present invention, the tail vein injection assisting apparatus further includes: and the telescopic piece fixing piece is used for fixing the relative position of the telescopic piece and the supporting piece.

In this technical scheme, the setting of extensible member mounting can be after the position adjustment of extensible member for the extensible member has improved the stability of mouse tail vein puncture and bolus for support piece fixed setting.

In a preferred embodiment of the present invention, the tail vein injection assisting apparatus further includes: the heating pad is arranged on the inner wall of the expansion piece accommodating groove and used for expanding veins at the tail of the mouse.

In this technical scheme, the setting of heating pad can make the tail of a mouse become warm to make the abundant expansion of the afterbody blood vessel of original shrink, make more clear that it shows, and can hold the syringe needle that the diameter is bigger, thereby further improve the success rate of puncture and injection experiment operation.

Compared with the prior art, the tail vein injection auxiliary device provided by the invention can be directly connected to the operating platform, so that the tail vein puncture and injection can be performed on a mouse in a state of anesthesia and after the mouse is fixed on the operating platform, and even the tail vein puncture and injection can be performed on the mouse in a living body imager under the condition of starting camera shooting, so that real-time imaging of the mouse after the mouse is injected with the optical contrast agent is realized, the research requirements of more optical living body imaging and the operation under optical guidance are met, and the research range is expanded.

Drawings

Fig. 1 is a schematic top view of an operation table of the experimental apparatus for mouse surgery and optical imaging according to the present embodiment;

FIG. 2 is a side view of the console of FIG. 1;

FIG. 3 is a schematic structural view of the nose mask;

FIG. 4 is a schematic view of the construction of the eye mask;

FIG. 5 is a schematic view of the eye shield of FIG. 4 in a configuration when used alone;

fig. 6 is a schematic structural view of a scalp distractor;

FIG. 7 is a schematic view showing an application structure of the scalp distractor, the eye mask and the nose mask;

FIG. 8 is a schematic view of the fastener;

FIG. 9 is a schematic view of an application structure of the fixing member;

FIG. 10 is a schematic top view of the tail vein injection aid;

fig. 11 is a front view schematically illustrating the structure of the tail vein injection assisting device;

FIG. 12 is a schematic diagram of an application structure of a tail vein injection auxiliary device;

FIG. 13 is a flowchart of the operation of the temperature control device.

Description of the reference numerals

1-operation table, 11-thermostatic device, 12-switch, 13-operation window, 14-mouse, 15-operation table scale mark; 2-nose mask, 21-narrow mouth, 22-wide mouth, 23-base; 3-eyeshade, 31-eyeshade body, 32-headband, 33-eyeshade magnetic connecting component; 4-scalp spreader, 41-support bar, 42-scalp spreading hook, 43-blunt hook; 5-anesthesia machine connecting pipe; 6-scalp incision; 7-surgical field of view region; 8-fasteners, 81-limb fasteners, 82-tail fasteners, 83-grooves, 84-fastener magnetic connections; 9-tail intravenous injection auxiliary device, 91-telescopic piece, 92-supporting piece, 93-containing groove, 94-indicator light, 95-indicator light switch, 96-telescopic piece fixing piece, 97-heating pad and 98-hemostasis pressure button.

Detailed Description

The present invention will be described in further detail with reference to the accompanying drawings. The structure and the like of the mouse operation and imaging device are schematically and simply shown in the attached drawings. These drawings are simplified schematic diagrams only to illustrate the basic structure of the present invention. It should be emphasized that the following embodiments are illustrative, not restrictive, and should not be taken as limiting the invention.

In the description of the present invention, it is to be understood that the terms "upper", "lower", "front", "rear", "left", "right", "top", "bottom", "inner", "outer", and the like, indicate orientations or positional relationships based on the orientations or positional relationships shown in the drawings, are merely for convenience in describing the present invention and simplifying the description, and do not indicate or imply that the device or element being referred to must have a particular orientation, be constructed and operated in a particular orientation, and thus, should not be construed as limiting the present invention.

Experiments such as mouse brain surgery, optical living body imaging and the like are very important medical research animal experiments, and have a plurality of communication points in the aspects of experiment operation and application, but a proper experimental device is not available at present. Therefore, the embodiment provides a mouse operation and optical imaging experimental device, which can realize uniform and smooth completion of experimental operations such as mouse brain operations and optical living body imaging on the device, including body fixation, safe and stable anesthesia in operations and imaging, fast and efficient puncture drug delivery, and can provide good eye protection and body temperature maintenance for mice, thereby facilitating the operations of the experiments, improving the success rate of the experiments, expanding the research range, saving the experimental cost, and fully enhancing the animal welfare.

The experimental device for mouse surgery and optical imaging provided by the embodiment mainly comprises: the operating platform 1 is used for placing a mouse and providing a proper operating platform for the experiment; a plurality of fixing pieces 8 for fixing the four limbs and the tail of the mouse 14; the nose mask 2 is used for anaesthetizing the mouse by gas; the eyeshade 3 is used for protecting the eyes of the mouse from being damaged by strong light in an experiment; a scalp spreader 4 for spreading the scalp of the mouse; and the tail vein injection auxiliary device 9 is connected with the operating platform 1 and is used for assisting the puncture and the injection of the tail veins of the mice. The following are detailed below:

the brain surgery and the optical living body imaging experiment both need special instruments, such as a brain stereotaxic apparatus and a small animal living body imaging apparatus. The brain stereotaxic apparatus has a positioning table for placing a mouse, and the space size and shape thereof are limited or even specific. Although the internal space of the small-animal living body imager is relatively large, the device to be placed therein must be black, and the surface is preferably rough, or optical interference may be caused. In order to meet the specific requirements of the above instruments and devices, the present embodiment provides an operation table 1 for placing a mouse and providing a suitable operation platform for experiments such as mouse brain surgery, optical living body imaging, and the like. As shown in fig. 1 and 2, the console 1 is preferably adapted to the body shape of the mouse 14, specifically, the length of the console 1 may slightly exceed the body length (excluding the tail length) of the mouse 14, the width may slightly exceed the body width of the mouse 14 after the four limbs are spread in a cross, the weight range of the mouse 14 is 15g-40g, and the thickness is as low as possible. Meanwhile, the operation table 1 is matched with a brain stereotaxic apparatus (not shown) and a living body imager (not shown) in volume, so that the operation table can be placed on a positioning table of a brain stereotaxic apparatus and a camera table of a small animal living body imager. The operation table 1 is black, made of metal or other materials with good heat conduction and magnetism, and is slightly rough, so that optical interference during imaging can be eliminated.

The experiment described above requires that the mouse 14 be maintained under anesthesia during the procedure. The body temperature of the mouse 14 under anesthesia is lowered, and if the body temperature is lowered too low, the death of the mouse 14 is easily caused, and the experiment fails. For this purpose, a thermostat 11 is further provided inside the console 1 for maintaining the body temperature of the mouse 14. The thermostat device 11 can be opened and closed under the control of a switch 12 connected thereto, and the switch 12 may be provided on the console 1 or may be provided separately from the console 1 by being wired to the thermostat device 11. The thermostat 11 includes a heating element (not shown), a temperature sensing element (not shown), and a control element (not shown). The temperature sensing element senses the temperature of the console 1 and is capable of comparing it with a preset temperature, wherein the threshold range of the preset temperature is preferably 37 ℃ to 40 ℃. When the temperature sensing element senses that the temperature of the operating table 1 exceeds the preset temperature, a control signal is sent to the control element to control the control element to turn off the heating element. On the contrary, when the temperature sensing element senses that the temperature of the console 1 is lower than the preset temperature, a control signal is sent to the control element to turn on the heating element to heat the console 1, so as to form a negative feedback loop of the temperature, and specifically, the working flow chart of the feedback loop is shown in fig. 13. According to this preferred embodiment, the console 1 can be kept at a constant temperature after the thermostat is opened. Therefore, the body temperature of the mouse 14 can be maintained in the experimental process, coma and even death caused by hypothermia of the mouse 14 in an anesthesia state are avoided, and smooth experiment is guaranteed.

Further, as a preferred option, the edge of one side of the console 1 along the length direction and the width direction is provided with console scale marks 15, specifically, the characters and scales of the console scale marks 15 are all white for easy recognition, and the minimum scale is millimeter. According to this preferred embodiment, the body length of the mouse 14 can be measured easily without causing optical interference. Furthermore, the organ or tumor dissected by the mouse 14 can be placed on the console (not shown) and photographed by bright field or fluorescence in the same visual field as the console scale 15, so that an image conforming to the scientific standards can be photographed while obtaining the best effect.

In the above experiments, due to the limitations of experimental conditions, it is often necessary to inject liquid anesthetic into the mouse 14 to induce and maintain anesthesia. Of these, intraperitoneal injection of mouse 14 is the most common mode of administration because of its simplicity and rapidity. Because the above experiment is long and the mouse 14 is injured by the excessive amount of anesthetic, it is necessary to perform a supplementary intraperitoneal injection of anesthetic to maintain the anesthetic state of the mouse 14. However, in the above experiment, the mouse 14 is often fixed in the prone position, and if anesthesia needs to be supplemented, the fixing is released, the mouse 14 is grabbed and then fixed again, which brings inconvenience to the experiment operation and greatly reduces the experiment efficiency. Therefore, in particular, the operation table 1 is provided with an openable and closable operation window 13, the position of the operation window 13 corresponds to the position of the abdominal cavity of the mouse 14 placed on the operation table 1, and when the operation window 13 is in the opened state, if the mouse 14 is fixed in the prone position, the entire abdominal cavity and perineum of the mouse 14 can be exposed to the operation window 13. After the mouse 14 is placed and fixed, in a long-time experiment process, if supplementary anesthesia of intraperitoneal injection is needed to be performed on the mouse 14, the operation table 1 can be turned over, then the operation window 13 is opened, the abdominal cavity of the mouse 14 is exposed, and the intraperitoneal injection can be directly performed without taking down the mouse 14 from the operation table 1 and then injecting after gripping, so that repeated grabbing and fixing operation steps are avoided, and convenience is brought to experiment operation.

In addition, because the mouse 14 is stimulated during the experiment, a large amount of excrement generated by the mouse 14 is accumulated on the operating platform 1, which not only pollutes the experiment operating space (such as the operating platform 1) and causes inconvenience to the experiment, but also causes discomfort to the mouse 14. Through opening operation window 13, can conveniently in time clear up (if wipe with cotton stick, gauze etc. then dip in the alcohol disinfection) and lean on the excrement (no matter which position mouse 14 takes) that places mouse 14 one side and produce on operation window 13 to alleviate the influence of mouse 14 excrement to experimental operation and mouse 14 comfort level.

In the process of experiments such as optical live body imaging of a mouse, the limbs and the tail of the mouse need to be fixed under the condition of not damaging the mouse, and imaging is preferably carried out in the same posture in multiple experiments so as to obtain a high-quality and attractive imaging effect picture. For this purpose, as shown in fig. 8 and 9, the mouse surgery and optical imaging experimental apparatus further includes fasteners 8, preferably, five fasteners 8 are provided, including four limb fasteners 81 and one tail fastener 82, wherein the limb fasteners 81 and the tail fastener 82 have substantially the same shape, but have different sizes to adapt to different parts of the mouse 14. Specifically, the fixing members 8 are trapezoidal in shape, and the bottom portions thereof are provided with grooves 83 formed by upward depressions for placing the limbs and the tails of the mice 14, and the sizes of the grooves 83 of the limb fixing members 81 and the tail fixing members 82 are respectively adapted to the limbs and the tails of the mice 14. Further, the fixing member 8 may be made of a magnetic material, or alternatively, it may have a magnetic coupling member 84 having a magnetic material adhered to a bottom surface thereof to be stably attached to the operation table 1, thereby achieving fixing with the operation table 1. The fixture 8 and the console 1 have strong magnetic attraction, and can bear the weight of the mouse 14 and the weight of the fixture 8 when the console 1 is turned upside down.

In the present embodiment, the fixing member 8 can be engaged with the operation table 1 according to the experiment requirement, so as to flexibly fix the position of the mouse 14 and adjust the posture of the mouse 14, and the fixing and adjusting operation is simple, and no stimulation or damage is caused to the mouse 14. Specifically, as shown in fig. 9, the mouse is placed on the operation table 1 in the prone position after intravenous anesthesia, and then placed into the living body imager using the fixing member 8 to perform imaging. Since the four-limb fixing member 81 and the tail fixing member 82 are magnetically attached to the console 1, after one imaging is finished, the mouse can be taken out and put back into a mouse cage (not shown), and the fixing member 8 is left in the console 1, so that the same posture of the mouse 14 is maintained in multiple imaging, and the experimental result can be clearly and beautifully displayed.

The experimental device for mouse surgery and optical imaging provided by the invention further comprises a nose mask 2 for mouse gas anesthesia, and specifically, the nose mask 2 is a nose mask for gas anesthesia and can be matched with an instrument provided with a small animal gas anesthesia machine (not shown) for use. As shown in FIGS. 3 and 7, the mask 2 has a funnel-like configuration including a narrow opening 21, a wide opening 22, and a base 23. The narrow mouth 21 can be connected with a pipeline (not shown) of a gas anaesthesia machine for small animals, and the wide mouth 22 can be plugged into the front part of the mouth and nose of the mouse 14. The base 23 has a magnet (not shown) attached or embedded to the bottom thereof, and the magnet can stably attach the nose mask 2 to the console 1, and prevent the nose mask from falling off from the console 1, and also prevent the nose mask from being displaced by the swinging of the duct of the gas anesthesia apparatus, thereby assisting the fixing.

Further, compare in current mouse anesthesia face guard structure heavy, thereby the volume is great not be suitable for experimental operation such as mouse head brain operation and optical imaging, the anterior anatomical structure laminating degree of the anterior part of the hourglass hopper-shaped structure of nose cup 2 that this embodiment provided and the mouth nose of mouse 14 is better, can form relatively sealed to not only can improve anesthesia effect, can also prevent that anesthetic gas from revealing the waste and the healthy harm of experimenter of reagent. Meanwhile, the nose mask 2 has a small structure, and only covers the front end part of the mouth and nose of the mouse 14 (for example, the front end of the olfactory bulb of the mouse is covered to the tip of the nose), without affecting the operation range of the brain operation.

Because of animal experiments such as mouse experiments, continuous research is often required, in other words, the experimental animals need to be observed continuously after the experiments and even repeated experimental treatments, and the experimental treatments often inevitably cause damage to the experimental animals and also include non-experimental objective damage. Therefore, how to reduce non-experimental objective damage in the experimental process as much as possible gives the experimental animal maximum protection, and has great significance to the success rate of the experiment and the welfare of the animal.

For the mouse experiment related to the head surgery and the optical imaging, a main non-experimental objective injury of the mouse 14 in the experimental process and having a large influence on the subsequent experiment is the injury of the strong lamp light used on the locator or the laser irradiation used by the imager to the eyes of the mouse 14 in the experiment, and is very easy to cause blindness.

In order to avoid the above adverse effects, the present embodiment provides the eyecup 3. The eyecup 3 includes an eyecup body 31 and a headband 32 connected to the body. As shown in fig. 4 and 7, the eyecup body 31 is made of a hard light-shielding material, has a black color, a slightly rough surface, and an overall oval shape, and is adapted to the eyeball of the mouse, so that the eyeball can be covered by the eyecup body 31 but not pressed when the eyecup 3 is worn by the mouse 14. Also, the eyecup body 31 is connected to the headband 32, thereby forming a ring-shaped structure that can be worn by the mouse 14. The headband 32 is made of a resilient material and is black in color, so that the eye mask can be stabilized by the elastic force of the mouse 14 after wearing the eye mask, and is not easy to fall off and shift. Further, the magnetic coupling member 33 is attached to or fitted to the bottom side of the headband 32, and when the mouse 14 is fixed to the console 1 in the prone posture, the eyecup 3 can be stably attached to the console 1 by the magnetic coupling member 33, and the function of assisting the fixation can be achieved.

It should be noted that the eyeshade 3 can be used with the experimental device for mouse surgery and optical imaging provided in this embodiment, or can be used alone. The following two cases are described separately: when the eyeshade is used in combination with the experimental device for mouse surgery and optical imaging provided in this embodiment, the eyeshade 3 can be inserted from the nose end of the mouse after the mouse 14 is anesthetized and before the nose mask 2 is worn, the eyeshade body 31 is aligned with the eyeball of the mouse 14, and then the headband 32 is fixed on the console 1 via the magnetic connecting member 33 on the headband 32. When the eyeshade 3 is used alone, as shown in fig. 5, the headband 32 can be caught inside the incisors of the mouse 14, and the magnetic connecting member 33 on the headband 32 can effectively reduce the loss caused by the friction between the incisors and the headband 32 of the mouse 14.

In this embodiment, the eyeshade 3 is simple in structure and convenient to wear, and can be stably and comfortably worn for a long time and the mouse 14 is kept comfortable, and it should be noted that the eyeshade 3 is not limited to the damage to the eyes of the mouse received by the strong light in the experiments such as brain surgery, brain micro-positioning injection and optical imaging, and can be applied to any experimental operation requiring the shielding protection of the eyes of the mouse 14, for example, effectively avoiding the stimulation of the depilatory cream to the eyes when the head of the mouse 14 is depilated. Thereby well protecting the eyesight and eye health of the mouse 14.

In stereotaxic apparatus use, brain surgery experiment and to the optics live imaging experiment of head, need open the scalp of mouse 14 to expose the skull and operate, at this moment, can use scalp spreader 4 in order fully to expose the operation field of vision, convenient experiment operation, and prior art lacks the scalp spreader 4 who is applicable to above-mentioned instrument. Therefore, in the present embodiment, the mouse surgery and optical imaging experimental apparatus includes the scalp distractor 4, the scalp distractor 4 is respectively provided on both sides of the head of the mouse 14, and as shown in fig. 6 and 7, the scalp distractor 4 includes the support rod 41 and the scalp distracting hook 42. The support rod 41 is in a shape of a slender cylinder, is made of a material with certain toughness, and can be vertically fixed on the operation table 1 by means of magnet adsorption or other means (such as sucker adsorption) so as to fully ensure the stability thereof. In the present embodiment, the support rod 41 is magnetically connected to the console 1. The other end of the support rod 41 is elastically deformed and bent when being stressed, and is restored to its original shape when not being stressed. The scalp spreading hooks 42 are arranged at one end of the support rod 41 far away from the operating platform 1, the scalp spreading hooks 42 of the pair of scalp spreaders 4 are oppositely arranged, one side of the scalp spreading hooks 42 which are oppositely arranged is of an arc structure which is inwardly arched, the angle of the arc is 120-150 degrees, the corners of the scalp spreading hooks 42 are smooth blunt surfaces, and the scalp of the mouse 14 can be effectively spread while the scalp is prevented from being damaged.

Further, a plurality of blunt hooks 43 are disposed along a side of the scalp opening hook 42 opposite to the scalp opening hook 42, specifically, the plurality of blunt hooks 43 are disposed on an inner arc surface of the scalp opening hook 42 at regular intervals in a tooth shape, a tip of the blunt hook 43 is in a hook shape for hooking the scalp of the mouse 14, and preferably, a surface of the tip of the blunt hook 43 is smooth and bluntly disposed to prevent damage to the scalp or other parts of the head of the mouse 14.

Further, the supporting rod 41 and the scalp distraction hook 42 have multiple specifications, specifically, the diameters of the arc surfaces of the scalp distraction hooks 42 with different specifications are different, the heights of the supporting rods 41 with different specifications are also different, and the supporting rods 41 with different specifications are preferably connected in a nesting mode and the like, so that the supporting rods are freely combined and matched to adapt to mice with different body shapes and brain surgery operations with different incision sizes. In the present embodiment, since the pair of scalp opening hooks 42 are provided in an arc shape on the opposite sides and have a plurality of blunt hooks arranged in a tooth shape along the arc-shaped surface, when the scalp opening hooks 42 hook the scalp of the mouse 14 using the plurality of blunt hooks 43, the scalp can be opened to be approximately circular in a state where the head incision of the mouse 14 is as small as possible, so as to facilitate the experiment operation. Furthermore, although the plurality of blunt hooks 43 are provided, in some embodiments, only one of the blunt hooks 43 may be used to hook the scalp of the mouse 14 and pull a corner of the scalp of the mouse 14, thereby flexibly adjusting the size and shape of the scalp distraction of the mouse 14 and optimizing the surgical exposure area. In addition, in the experiment operation, the scalp distractor 4 with the corresponding specification can be selected according to the body type difference of different mice and the head operation visual field required by the experiment, for example, the scalp distractor 4 with the longer support rod 41 is selected for the mouse with the larger body type, and the scalp distractor 4 with the smaller body type is selected for the mouse with the smaller body type. In addition, the scalp distractor 4 with a large specification can be applied to mouse operations other than the mouse head and brain operations or other experimental operations requiring distraction. For example, when the mouse 14 is dissected, the dissecting operation can be facilitated by distracting the abdomen (not shown) of the mouse 14 on both sides using the distractor 4.

The combined use of the console 1, the fixing member 8, the nose mask 2, the eye cup 3, and the scalp distractor 4 in the present embodiment will be described below with reference to fig. 1 and 7: when the brain of the mouse 14 is operated, the mouse 14 is placed on the console 1 in the prone position, and the four limbs of the mouse 14 are fixed by the fixing members 8, as shown in fig. 1 and 7, in the case of the gas anesthesia method, the nose and mouth portion of the mouse 14 is worn by the nose mask 2 connected to the gas anesthesia machine to maintain anesthesia, specifically, the gas anesthesia machine is connected to the nose mask 2 via the anesthesia machine connection pipe 5, and the anesthesia gas is supplied from the narrow mouth 21 of the nose mask 2, the eye mask 3 is worn on both eyes to prevent strong light irradiation, and the scalp incision 6 is pulled by the scalp distractor 4 to sufficiently expose the operation visual field region 7.

Mouse optical in vivo imaging and fluorescence guided surgical operation require injecting corresponding imaging contrast agent into the experimental object. Because of the great potential of clinical application of in vivo imaging, real-time imaging research after administration becomes increasingly one of the needs of common in vivo imaging research because the real-time imaging research after administration can better observe blood vessel and tumor imaging, contrast agent metabolism and the like and better accords with the real clinical simulation situation. Mouse tail vein injection administration is a necessary key technology for a series of imaging and operation operations in the experiment, but mouse tail veins are very tiny and difficult to observe, and blood vessels shrink further after anesthesia, so that puncture difficulty is high, and repeated puncture of mouse tails is difficult to add once puncture fails. Moreover, the tail vein must be injected immediately after successful puncture, and moving the mouse 14 can easily cause the needle to be pulled out, which results in failure of the experiment. Therefore, real-time imaging after injection is also difficult to achieve.

Therefore, the experimental device for mouse surgery and optical imaging provided by the embodiment comprises a tail vein injection auxiliary device 9 for assisting the injection of the tail vein of the mouse. As shown in fig. 10 to 12, the tail vein injection assisting device 9 preferably includes an extension member 91, a support member 92, a receiving groove 93, an indicator light 94, a power cord (not shown), an indicator light switch 95, an extension member fixing member 96, a heating pad 97, a heating pad switch (not shown) and a hemostatic pressure button 98, which are respectively described in detail below: the retractable member 91 is a rectangular parallelepiped structure, and a containing groove 93 is formed on a side of the retractable member close to the console 1, the containing groove 93 has a width corresponding to the tail of the mouse, and can contain and fix the tail of the mouse 14. The telescopic member is disposed as close to the bottom surface of the console 1 as possible, and the console is made as thin as possible, so that the body height of the mouse 14 is the same as that of the mouse tail when the mouse tail is straightened and fixed in the accommodation groove 93. The indicator light 94 is disposed in the extensible member accommodating groove 93 and can be turned on and off under the control of the indicator light switch 95, preferably, the indicator light 93 has a yellow color, has a strong penetrating power, can clearly display the tail vein of the mouse 14, and provides a strong visual support for puncture. The heating mat 97 is disposed on the inner wall of the bellows storage groove 93 and can be opened and closed under the control of the heating mat switch, and preferably, the area of the heating mat 97 is equivalent to the area of the bellows storage groove 93, so as to maximize the contact area with the tail of the mouse. The setting of heating pad 97 can make the tail of a mouse become warm to make the abundant expansion of the afterbody blood vessel of original shrink, make more clear of its demonstration, and can hold the injection syringe needle that the diameter is coarser, thereby further improve the success rate of puncture and injection experiment operation. In addition, a hemostatic pressure button 98 is disposed on a side of the telescopic member 92 away from the console 1. Preferably, the hemostatic pressure button 98 has one end fixed to the opposite side of the expansion member receiving groove 93 and is connected to the other end of the pressure button through an elastic connection member. The pressure button can be attracted to the position of the indicator light 94 by means of magnetic force and the like after being turned over. The arrangement of the hemostatic pressure button 98 can lead the mouse to timely press the injection needle hole through turning the hemostatic pressure button 98 after the tail vein puncture injection, so as to stop bleeding at the tail of the mouse as soon as possible and reduce the loss of the injection medicament caused by bleeding at the tail of the mouse. Further, the support member 92 is fixed to a side close to the tail of the mouse 14 placed on the console 1 in the length direction of the console 1, and more specifically, the support member 92 is provided to a side distant from the mouse 14 placed on the console 1 in the height direction of the console 1. The support member 92 is an inverted arch structure, and is fixed to the bottom end of the console 1 by a screw or other means, and can be installed or removed as required. The support 92 and the bottom surface of the console 1 form a hollow channel. The cross sectional area of the hollow channel is equal to that of the telescopic piece 91, so that the telescopic piece 91 can be inserted and stably placed, and further, the telescopic piece 91 is connected with the support piece 92 in a sliding manner and can slide along the length direction of the operating table 1 relative to the hollow channel without swinging up and down or falling off. The experimenter can change the relative positions of the rat tails with different lengths and the indicator lights 94 in the extensible member accommodating grooves 93 by adjusting the extension amount of the extensible members 91, so that the indicator lights 94 always irradiate the parts most easily punctured by the rat tails. In addition, one side of the supporting member 92 along the width direction of the console 1 is provided with an expansion member fixing member 96, the expansion member fixing member 96 can be movably connected with the supporting member 92 by screws or other methods, and can pass through the side wall of the supporting member 92 to move along the width direction of the console 1, when the expansion member fixing member 96 moves into the hollow channel, the expansion member fixing member 96 and the inner side wall of the supporting member 92 far away from the expansion member fixing member 96 can fix the expansion member 91 relative to the supporting member 92 together, so as to maintain the position fixing stability of the tail portion of the mouse 14.

One embodiment of the tail vein injection assisting device provided by the present invention is described below with reference to fig. 12. After the tail vein injection assisting device 9 is assembled to the operation table 1, the mouse 14 is anesthetized and fixed on the operation table 1, the tail of the mouse 14 is straightened and placed in the containing groove 93, then the heating mat 97 is turned on, after a little moment, the obvious expansion of the tail vein blood vessel is observed, the indicator lamp 94 is turned on, then the position of the telescopic piece 91 is adjusted, the position of the tail illuminated by the indicator lamp 94 is the position suitable for tail vein injection (usually located at the tail end backward 1/3), then the support fixing piece 96 is screwed, the position of the telescopic piece 91 is fixed, and then the operation table 1 can be placed on a living body imaging instrument to puncture and inject the tail vein of the mouse 14. After the injection is finished, the hemostatic pressure button 98 is turned over immediately to stop the bleeding of the rat tail. At the same time, the subsequent experimental operation can be started.

Compared with the prior art, the tail vein injection auxiliary device 9 provided by the embodiment can be directly connected to the console 1, so that the mouse 14 can be subjected to tail vein puncture and bolus injection under the state of being anesthetized and fixed on the console 1, and even placed in a living body imager, and then the tail vein puncture and bolus injection are performed under the condition of starting to shoot, so that real-time imaging after the mouse is injected with the optical contrast agent is realized, more research requirements of the optical imaging and the optical guidance operation are met, and the research range is expanded.

In the present embodiment, when the present invention is used in an optical living body imaging experiment, the color of each member is preferably set to black, and the surface is preferably set to a rough surface, so as to eliminate optical interference during imaging. In addition, among the components of the experimental device for mouse surgery and optical imaging provided in the present embodiment, the nose mask 2, the eye mask 3, the scalp distractor 4, the fixing member 8 and the tail vein injection auxiliary device 9 may be connected to the console 1, and may be flexibly mounted, combined and dismounted according to different actual requirements, or may be used alone. The nose mask 2, the eye mask 3 and the fixing piece 8 are preferentially installed and fixed on the operating platform 1 in a magnetic connection mode, and the adopted magnetic material has strong adsorption force, so that the bearing and fixing requirements of each operation in the mouse 14 anesthesia, administration, imaging and operation processes can be met. The tail vein injection auxiliary device 9 is preferably fixed on the operation table 1 in a threaded screw mode to ensure the stability of the tail vein puncture injection.

It will be appreciated by those of ordinary skill in the art that in the embodiments described above, numerous technical details are set forth in order to provide a better understanding of the present application. However, the technical solutions claimed in the claims of the present application can be basically implemented without these technical details and various changes and modifications based on the above-described embodiments. Accordingly, in actual practice, various changes in form and detail may be made to the above-described embodiments without departing from the spirit and scope of the invention.

Claims

1. A mouse operation and optical imaging experimental device is characterized by comprising:

the operation table is used for placing a mouse and comprises an operation window, wherein the operation window can be opened and closed, and the position of the operation window corresponds to the position of the abdominal cavity of the mouse placed on the operation table;

the bottom surfaces of the fixing pieces can be connected with the operating table, and are provided with grooves formed by upward sinking for accommodating the limbs and the tail of the mouse; and

and the tail vein injection auxiliary device is connected with the operating platform and is used for assisting the puncture and the injection of the tail vein of the mouse.

2. The experimental device for mouse surgery and optical imaging as set forth in claim 1, further comprising:

and the constant temperature device is arranged on the operating platform and can keep the temperature of the operating platform within a preset range.

3. The experimental device for mouse surgery and optical imaging as set forth in claim 1, further comprising:

the nose cup, the nose cup with the operation panel is connected for supply the mouse anesthesia, the nose cup is hourglass hopper-shaped, and the size is with the oral cavity nose looks adaptation of mouse.

4. The experimental device for mouse surgery and optical imaging as set forth in claim 1, further comprising:

an eye shield for protecting the eyes of a mouse during an experiment, the eye shield comprising:

the eyeshade body is used for shielding eyes of a mouse; and

the headband is connected with the eyeshade body on one hand for the mouse to wear, and is connected with the operating console on the other hand.

5. The experimental device for mouse surgery and optical imaging as set forth in claim 1, further comprising:

the scalp spreader is arranged on two sides of the head of the mouse and used for spreading the scalp of the mouse, and the scalp spreader comprises:

the scalp spreading hook is arc-shaped and is provided with a plurality of blunt hooks arranged along an arc-shaped surface in a tooth shape; and

the supporting rod extends in the height direction, one end of the supporting rod is connected with the operating table, and the other end of the supporting rod is connected with the scalp opening hook.

6. The mouse surgical and optical imaging experimental apparatus according to any one of claims 1 to 5, wherein the tail vein injection auxiliary device further comprises:

the supporting piece is fixed on one side close to the tail of the mouse arranged on the operating platform in the length direction of the operating platform; and

the extensible member is arranged in the support member and is in sliding connection with the operation table along the length direction, wherein an extensible member accommodating groove used for accommodating the tail of the mouse is formed in the extensible member.

7. The experimental device for mouse surgery and optical imaging as set forth in claim 6, wherein the tail vein injection auxiliary device further comprises:

and the indicator light is arranged in the telescopic piece accommodating groove and is used for displaying veins at the tail of the mouse.

8. The experimental device for mouse surgery and optical imaging as set forth in claim 6, wherein the tail vein injection auxiliary device further comprises:

the telescopic piece fixing part is arranged in the supporting part and used for fixing the relative position of the telescopic piece and the supporting part.

9. The experimental device for mouse surgery and optical imaging as set forth in claim 6, wherein the tail vein injection auxiliary device further comprises:

the heating pad is arranged on the inner wall of the expansion piece accommodating groove and used for expanding veins at the tail of the mouse.