Fixation device suitable for blood sampling from conscious mice

Abstract

The present disclosure relates to a fixation device suitable for blood sampling from conscious mice, and the fixation device is configured to solve the problem that the existing devices for blood sampling from mice tend to induce stress responses in the mice, thereby affecting the blood sampling quality. The device of the present disclosure comprises at least a mouse restraint chamber, a mouse tail fixation module, a cutting and squeezing module, and a sample collection module. The mouse restraint chamber is configured to restrict the body motion of a mouse. The mouse tail fixation module is configured to adaptively clamp the tails of mice of different sizes and reserve space for squeezing the tail to sample blood. The cutting and squeezing module is configured for tail tip cutting and blood sampling via squeezing. The sample collection module is configured to collect tail tips and blood samples. The device can reduce the operating pressure of an operator and reduce the possibility of blood sample contamination as much as possible, and more importantly, can reduce the stress level of a mouse during blood sampling as much as possible.

Description

Fixation device suitable for blood collection from conscious mice Technical Field

[0001] This disclosure relates to experimental equipment, and more particularly to mouse blood collection equipment. Background Technology

[0002] Currently, manual blood collection is labor-intensive, yields low blood volumes, is prone to contamination, and carries the risk of bites and scratches from mice. Similarly, the stress experienced by mice during manual blood collection can significantly impact the assessment of their true stress levels in experiments. While various restraint devices exist for mouse blood collection, most focus on solving the problem of mouse restraint, reducing labor and the risk of bites, or increasing blood volume and reducing collection time through methods like water baths. They do not address the stress generated during the restraint process, which affects the levels of stress-related substances such as cortisol in the mouse blood sample and can also influence the secretion of other substances. Furthermore, most existing restraint devices place the mouse's torso in a confined space (centrifuge tube) or restrain its limbs, methods that can induce a strong stress response in the mouse. Summary of the Invention

[0003] Therefore, the purpose of this disclosure is to provide a fixation device suitable for blood collection from conscious mice. This device can minimize the operator's workload and the possibility of blood sample contamination, and more importantly, it can minimize the stress level of mice during blood collection. The specific technical solution is as follows.

[0004] A restraint device suitable for blood collection from awake mice, the device comprising a mouse restraint cavity (1), a tail fixation module, a cutting and squeezing module, and a sample collection module; the mouse restraint cavity is red and semi-transparent, with a temperature-controlled heating pad and a food / bite stick placement tray (3) at the bottom of the cavity, and a tail plate (17) of the cavity placing the mouse's torso in an independent space; the tail fixation module includes a tail root fixation component and a tail fixation component, the tail root fixation component being located on the tail plate (17) for fixing and clamping the mouse's tail root through the hole in the tail plate (17), and the tail fixation component fixing the exposed part of the mouse's tail, the tail fixation component including a placement groove (16) and an extension groove (14), the placement groove (16) containing a temperature-controlled heating pad (13), and the extension groove (14) for positioning according to different lengths of the mouse's tail. Fine-tuning; the cutting and squeezing module includes an electric cutting blade (25) and a rat tail squeezing assembly. The rat tail squeezing assembly includes a squeezing electric slide (26), a squeezing arm (27), a squeezing electric slider (28), a telescopic arm (29), and a squeezing groove (30). A replaceable alcohol swab is attached to the squeezing groove. The squeezing groove is adjusted to fit snugly against the rat tail by the telescopic arm (29). The telescopic arm (29) is located in the middle of the squeezing arm (27). The squeezing arm (27) spans across the telescopic arm (29). The lower ends of the two arms of the squeezing arm (27) are the squeezing electric sliders (28). After the electric cutting blade (25) cuts the tip of the rat tail, the squeezing electric slider (28) moves back and forth on the squeezing electric slide (26), so that the squeezing groove (30) fits snugly against the rat and moves back and forth to achieve squeezing blood collection. The sample collection module is used to collect the tail tip and blood samples.

[0005] In one embodiment of the above technical solution, the mouse restraint cavity is provided with degreased cotton or an odor groove.

[0006] In one embodiment of the above technical solution, a temperature sensor is also provided at the bottom of the mouse restraint cavity.

[0007] In one embodiment of the above technical solution, the mouse restraint cavity has a breathable plate (2).

[0008] In one embodiment of the above technical solution, the tail root fixing component includes a sliding groove (18), a tail root fixing slider (19), and a clamping groove (20). Adjusting the position of the tail root fixing slider (19) can make the clamping groove (20) fit snugly against the mouse tail root that passes through the hole on the tail plate (17).

[0009] In one embodiment of the above technical solution, the groove surface of the clamping groove (20) has anti-slip properties.

[0010] In one embodiment of the above technical solution, the tail fixing component further includes a slot (22) and a plate (21). The inner side of the plate (21) is made of silicone. The slot (22) and the plate (21) are matched and used to restrain the tail of the mouse in the placement slot (16) and improve the comfort of the mouse.

[0011] In one embodiment of the above technical solution, the fixing device has an anti-slip base (6).

[0012] In one embodiment of the above technical solution, the sample collection module includes a centrifuge tube rack (12), a rotating stage (10), a telescopic stage (9), an electric slider (8), and an electric chute (7); the centrifuge tube rack (12) has two holes: a blood sample collection hole (23) and a tail tip collection hole (24), and temperature control element semiconductor heating and cooling plates (11) are evenly distributed at the bottom of the two holes; the centrifuge tube rack (12) is located on the rotating stage (10), and the blood sample collection hole (23) can be changed by rotating the rotating stage (10). The position of the two holes (23) and the tail tip collection hole (24) is determined by the rotating platform (10) located on the telescopic platform (9). The height of the two holes (23) and the tail tip collection hole (24) is adjusted by the telescopic platform (9). The electric slider (8) is located below the telescopic platform (9). The position of the two holes (23) and the tail tip collection hole (24) can be adjusted horizontally by the electric slider (8) and the electric slide groove (7) so that the tail tip collection hole (24) or the blood sample collection hole (23) is located just below the tail tip.

[0013] In one embodiment of the above technical solution, the electric cutting blade (25) is anchored to the extension groove (14). The beneficial technical effects of this disclosed technical solution are:

[0014] 1. By placing the mouse's torso in an independent space with a semi-transparent red appearance, the risk of being bitten by the animal during the operation is eliminated; based on the fact that mice lack cone cells that perceive red and are insensitive to red, the red appearance reduces the impact on the mouse's daily rhythm to a certain extent, reduces its stress response, and the semi-transparent appearance makes it easier to observe the animal's condition during the operation.

[0015] 2. Mice are placed in an independent space where their torsos can move freely. Providing them with food / bite sticks reduces the anxiety and stress caused by the device fixation.

[0016] 3. Soft cotton can be placed inside the cavity to increase the comfort of the mice inside the cavity, or odor troughs can be placed and the bedding material of the original living cage of the mice can be placed to further reduce the mice's tension and anxiety. However, it needs to be replaced every time it is used to avoid the mice from being tense and anxious due to the cotton / bedding being stuck with the feces or urine of other mice or the odor of the cotton after being used for too long.

[0017] 4. By using the temperature control component and the replaceable alcohol swabs on the mouse squeezing device to fill the blood vessels in the mouse's tail, the amount of blood collected is increased and the blood collection time is reduced.

[0018] 5. The position of the extension groove can be finely adjusted to a suitable length according to the different tail lengths of mice (the tail tip extends about 0.5mm beyond the cutting piece), which facilitates blood collection operations for different individuals and multiple blood collections from the same mouse;

[0019] 6. The centrifuge tube rack is height-adjustable and rotatable, and has an internal temperature control element. It can be used in conjunction with the position of the extension tank for sampling, ensuring the quality of blood samples, and can maintain different temperatures for different experimental requirements.

[0020] 7. This device can perform a series of operations, including cutting the tip of a mouse tail, collecting the tip of the mouse tail, collecting blood by rotating a centrifuge tube rack, and squeezing the tail. It can also be easily automated by setting a program, thus reducing manpower and blood sample contamination. Attached Figure Description

[0021] To more clearly illustrate the technical solutions in the embodiments of this application, the accompanying drawings used in the description of the embodiments will be briefly introduced below. Obviously, the accompanying drawings described below are only some embodiments of this application. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0022] Figure 1. A front view of one embodiment of the device.

[0023] Figure 2. A schematic diagram of the tail root fixing component structure in one embodiment of the device.

[0024] Figure 3. A top view of the structure in one embodiment of the device.

[0025] Figure 4. Schematic diagram of the tail extrusion assembly structure in one embodiment of the device.

[0026] In the diagram: 1. Chamber, 2. Ventilation plate, 3. Placement tray, 4. Temperature sensor, 5. Display and operation screen, 6. Anti-slip base, 7. Electric slide, 8. Electric slider, 9. Telescopic table, 10. Rotary table, 11. Semiconductor heating / cooling element, 12. Centrifuge tube rack, 13. Temperature-controlled heating pad, 14. Extension slot, 15. Dust cover, 16. Placement slot, 17. Tail plate, 18. Slide, 19. Tail root fixing slider, 20. Clamping slot, 21. Card plate, 22. Card slot, 23. Blood sample collection hole, 24. Tail tip collection hole, 25. Electric cutting blade, 26. Extrusion electric slide, 27. Extrusion arm, 28. Extrusion electric slider, 29. Telescopic arm, 30. Extrusion slot. Detailed Implementation

[0027] Current research in mouse neuroscience typically requires long-term behavioral training or fixation adaptation training. It's crucial to assess the mice's stress levels during this training process, as experimental data obtained while the mice are under stress (physiological state, behavioral records, brain activity, etc.) cannot accurately reflect their true condition. The levels of stress-related substances such as cortisol in the blood are important assessment indicators. Multiple blood samples need to be collected during the training process to evaluate stress levels. However, the blood collection process introduces a new stress state, which can affect the final assessment of the true stress level.

[0028] Based on this, this technical solution proposes a restraint device suitable for blood collection from conscious mice, aiming to minimize operator stress and the possibility of blood sample contamination, and more importantly, to minimize stress levels in mice during blood collection. The device comprises at least a mouse restraint cavity, a tail fixation module, a cutting and squeezing module, and a sample collection module. The mouse restraint cavity restricts mouse movement and, through its color, design, food / bite stick placement tray, heating pad, and even the addition of cotton and ventilation panels, creates a comfortable environment to reduce mouse tension and anxiety. The tail fixation module adapts to hold the tails of mice of different sizes and provides space for tail squeezing and blood collection. The cutting and squeezing module is used for tail tip cutting and blood collection squeezing. The sample collection module collects the tail tip and blood sample.

[0029] The following description, in conjunction with the accompanying drawings, clearly and completely describes how the technical solution of this case is implemented. Obviously, the described embodiments are only a part of the embodiments of this case, and not all of them. Based on the embodiments in this case, all other embodiments obtained by those skilled in the art without inventive effort are within the scope of protection of this application.

[0030] Figure 1 is a schematic diagram of the front structure of this device. The overall rectangular structure consists of at least a mouse restraint cavity, a mouse tail fixation module, a cutting and squeezing module, and a sample collection module. The device has an anti-slip base (6) at the bottom to stabilize it.

[0031] The mouse restraint cavity (1) is red in appearance. Since mice lack cone cells that can perceive red and are insensitive to red, the red appearance reduces the impact on the mouse's daily rhythm and stress response. The semi-transparent appearance also facilitates observation of the animal's condition during operation. After the mouse enters the mouse restraint cavity (1), all parts of the mouse's body except the tail are inside the cavity (1), and the torso can move freely. A temperature-controlled heating pad is provided at the bottom of the cavity to maintain the mouse's body temperature. A temperature sensor (4) is also provided to monitor the cavity temperature in real time. More importantly, a food / bite stick placement tray (3) is provided to reduce the anxiety and stress caused by the device fixation. The bite stick is particularly suitable for mice that are testing fasting blood glucose.

[0032] The cavity (1) has a vent plate (2) on one side, with multiple vent holes to prevent the mouse from suffocating in a relatively enclosed space. In one embodiment, the front plate is the vent plate (2). The upper plate of the restraint cavity can be opened and closed to facilitate the insertion of the mouse. Defatted cotton can be placed inside the cavity to increase the mouse's comfort, or an odor trough can be placed to store the bedding from the mouse's original cage to further reduce the mouse's tension and anxiety. The bedding needs to be replaced each time it is used to avoid the mouse becoming tense and anxious due to the accumulation of feces or urine odor from other mice on the cotton / bedding that has been used for too long. The tail plate (17) of the cavity can be pulled out up and down. When lowered, the mouse's torso can be placed in an independent space. The tail plate (18) has a hole through which the mouse's tail can pass. That is, the tail plate (17) isolates the tail from the rest of the body, avoiding the risk of being bitten by the animal during the operation.

[0033] The mouse tail is clamped and fixed in the restraint cavity by a tail fixation module, which includes at least a tail root fixation component and a tail fixation component.

[0034] The tail root fixing assembly is located on the tail plate. Referring to Figure 2, the tail root fixing assembly consists of at least a groove (18), a tail root fixing slider (19), and a clamping groove (20). Specifically, the tail plate (17) has a recessed groove (18) on both sides of the hole through which the mouse's tail can pass. A matching tail root fixing slider (19) is located on the groove (18) and is anchored and slid along it. The clamping groove (20) is connected to the tail root fixing slider (19). After lowering the tail plate (17), the mouse's tail is passed through the hole in the tail plate (17), and the position of the tail root fixing slider (19) is adjusted so that the clamping grooves (20) on both sides are pressed tightly against the mouse's tail root for fixation. The groove surface of the clamping groove (20) is non-slip. One embodiment uses non-slip silicone material in the groove of the clamping groove (20) to prevent the mouse from escaping and to avoid injury to the mouse. The holes on the tailplate can be semi-circular notches, making it easy to directly hold the mouse's tail when lowering the tailplate.

[0035] For the mouse's tail, after the exposed portion is clamped and fixed using the tail root fixation component, a tail fixation component is used for further fixation. Referring to Figures 1 and 3, the tail fixation component consists of at least a tail placement slot (16), a slot (22), a plate (21), and an extension slot (14). First, the exposed tail of the mouse, after being clamped and fixed using the tail root fixation component, is placed in the tail placement slot (16). The position of the extension slot (14) is adjusted according to the length of the tail. Then, the slot (22) and plate (21) are matched and used to restrain the mouse's tail, so that the tail tip is exactly on the extension slot (14). There are multiple slots and plates; the selected slot position can be chosen according to the actual operation, so that the front and rear sections of the mouse's tail are fixed, leaving space in the middle section for blood collection by squeezing. The inner side of the plate is preferably made of silicone material to improve the mouse's comfort during restraint and to prevent injury to the animal. The placement groove (16) is a semi-recessed groove, and the inside of the groove is also made of non-slip silicone material. A temperature-controlled heating pad (13) is also laid under the placement groove (16) to maintain the temperature of the mouse tail tip, activate blood vessels, and facilitate blood collection. The extension groove (14) can be adjusted to fit mice of different sizes. Depending on the length of the mouse tail, the position of the extension groove (14) can be finely adjusted to a suitable length.

[0036] The cutting and squeezing module is configured to cut the tip of a mouse tail and collect blood samples. The module includes an electrically operated cutting blade (25) and a tail squeezing assembly. The electrically operated cutting blade (25) performs a top-down rotating cut, returning to its original position after cutting. The electrically operated cutting blade (25) is removable for cleaning. A blade sleeve can be installed on the blade to prevent accidental injury during operation; this sleeve can be removed before use. The electrically operated cutting blade (25) is positioned above and anchored to the extension groove (14), allowing adjustment of its position by adjusting the extension groove (14). During use, the position of the extension groove (14) is fine-tuned to a suitable length based on the mouse's tail length, ensuring the tail tip extends approximately 0.5 mm beyond the electrically operated cutting blade (25). This facilitates blood collection from different individuals and multiple blood collections from the same mouse. Blood collection is achieved through the tail squeezing assembly.

[0037] Referring to Figures 3 and 4, the mouse tail compression assembly consists of at least a compression electric slide (26), a compression arm (27), a compression electric slider (28), a telescopic arm (29), and a compression groove (30). The telescopic arm (29) is located in the middle of the compression arm (27), and the compression arm (27) spans across the telescopic arm (29). The lower ends of the two arms of the compression arm (27) are connected to the compression electric slider (28), and the compression arm (27) moves on the compression electric slide (26) via the compression electric slider (28). The compression electric slide (26) is located outside the slot (22). The compression arm (27) provides support, and the telescopic arm (29) can adjust the position of the compression groove (30) to make the compression groove (30) as close to the mouse tail as possible. Replaceable alcohol swabs are attached to the compression groove (30), which can further fill the blood vessels, reduce blood collection time, and also disinfect the mouse tail to prevent blood sample contamination. Then, blood is collected by squeezing the electric slider (28) to make reciprocating motion on the electric chute.

[0038] The sample collection module is used to collect mouse tail tip and blood samples. Referring to Figures 1 and 3, the sample collection module consists of at least a centrifuge tube rack (12), a rotating stage (10), a telescopic stage (9), an electric slider (8), and an electric chute (7). The centrifuge tube rack (12) has two holes: a blood sample collection hole (23) and a tail tip collection hole (24). Sampling is performed by adjusting the position of the centrifuge tube rack (12) in conjunction with the position of the extension chute (14). Temperature control elements (semiconductor heating elements 11) are installed at the bottom of both holes to regulate their temperature and maintain different temperatures for different experimental requirements, ensuring the quality of the blood samples. The position of the centrifuge tube rack can be adjusted via the telescopic stage, the electric slider, and the electric chute. The rotating stage can adjust the position of the mouse tail tip collection hole (24) and the blood sample collection hole (23) to prevent blood contamination and waste. Specifically, the centrifuge tube rack (12) is located on the rotating platform (10). By rotating the rotating platform (10), the positions of the two holes, the blood sample collection hole (23) and the tail tip collection hole (24), can be changed. The rotating platform (10) is located on the telescopic platform (9). The height of the two holes, the blood sample collection hole (23) and the tail tip collection hole (24), can be adjusted by the telescopic platform (9). Below the telescopic platform (9) is an electric slider (8). By cooperating with the electric slide rail (7), the positions of the two holes, the blood sample collection hole (23) and the tail tip collection hole (24), can be adjusted horizontally so that the tail tip collection hole (24) or the blood sample collection hole (23) is just below the tail tip for collecting the tail tip or collecting blood.

[0039] In this device, during blood collection, the mouse tail, cutting and squeezing module, and sample collection module are adjusted. The system can automatically perform continuous operations—cutting the mouse tail tip, collecting blood from the tail tip, rotating the centrifuge rack to collect blood, and squeezing the tail—thereby reducing manual labor and blood sample contamination. The program can be built into the device.

[0040] Specifically, after the mouse is restrained, fix the tail tip about 0.5 mm beyond the cutting blade (27), and adjust the cutting and squeezing module and the sample collection module to the corresponding positions. If the electric cutting blade (25) of the cutting and squeezing module has a blade sleeve, remove it before opening. Close the dust cover (15) to further prevent external contamination during the sampling process. The dust cover (15) can be made of semi-transparent material to facilitate observation of the blood collection status. Start the built-in program on the display operation screen (5). After the program is started, the electric cutting blade (25) will automatically cut the mouse tail, and the tail tip will fall into the tail tip collection hole (24). After receiving the fallen tail tip, the centrifuge tube rack will rotate so that the blood sample collection hole (23) is located below the tail tip where the original tail tip collection hole (24) was. The device then automatically adjusts the telescopic arm (29) of the mouse tail squeezing assembly to position the squeezing arm (27) at a suitable height, causing the squeezing electric slider (28) to reciprocate along the squeezing groove (30) to collect blood. The blood collection time can be flexibly set before the program starts and will automatically stop when the program is completed, thus completing the blood collection operation. Open the dust cover (15), first put on the blade cover to prevent accidental injury, and then remove the mouse.

[0041] In summary, the device proposed in this disclosure adapts to mice of different sizes for blood collection through multiple adjustable components, and utilizes partial automation to minimize the operator's workload and the possibility of blood sample contamination. More importantly, this device reduces the stress level of mice during blood collection by changing the appearance of the device and adding food / bite sticks.

[0042] It should be noted that the device disclosed herein is not only suitable for blood collection from the tail tip of mice, but also for blood collection and drug administration from the tail vein of mice, and the mouse tissue obtained through the tail tip collection orifice can also be used for experiments. Blood can be collected from the same mouse multiple times.

[0043] Although the embodiments of this disclosure have been described above in conjunction with the accompanying drawings, this disclosure is not limited to the specific embodiments and application fields described above. The specific embodiments described above are merely illustrative and instructive, and not restrictive. Those skilled in the art can make many other forms based on the guidance of this specification and without departing from the scope of protection of the claims of this disclosure, and all of these are within the scope of protection of this disclosure.

Claims

1. A fixation device suitable for blood collection from conscious mice, characterized in that: The device includes a mouse restraint cavity (1), a mouse tail fixation module, a cutting and squeezing module, and a sample collection module; The mouse restraint cavity is red and semi-transparent. The bottom of the cavity is equipped with a temperature-controlled heating pad and a food / bite stick placement tray (3). The tail plate (17) of the cavity places the mouse's torso in an independent space. The tail fixing module includes a tail root fixing component and a tail fixing component. The tail root fixing component is located on the tail plate (17) and is used to fix and clamp the tail root of the mouse through the hole of the tail plate (17). The tail fixing component is used to fix the exposed part of the mouse tail. The tail fixing component includes a placement groove (16) and an extension groove (14). The placement groove (16) contains a temperature-controlled heating pad (13). The extension groove (14) is used to make fine adjustments to the position according to the different lengths of the mouse tail. The cutting and squeezing module includes an electric cutting blade (25) and a rat tail squeezing assembly. The rat tail squeezing assembly includes a squeezing electric slide (26), a squeezing arm (27), a squeezing electric slider (28), a telescopic arm (29), and a squeezing groove (30). A replaceable alcohol swab is attached to the squeezing groove. The squeezing groove is adjusted to fit snugly against the rat tail by the telescopic arm (29). The telescopic arm (29) is located in the middle of the squeezing arm (27). The squeezing arm (27) spans across the telescopic arm (29). The lower ends of the two arms of the squeezing arm (27) are the squeezing electric slider (28). After the electric cutting blade (25) cuts the tip of the rat tail, the squeezing electric slider (28) moves back and forth on the squeezing electric slide (26), so that the squeezing groove (30) fits snugly against the rat and moves back and forth to achieve squeezing blood collection. The sample collection module is used to collect tail tip and blood samples.

2. The apparatus of claim 1, wherein: The mouse restraint cavity is equipped with defatted cotton or an odor chamber.

3. The apparatus of claim 1, wherein, A temperature sensor is also provided at the bottom of the mouse restraint cavity.

4. The apparatus of claim 1, wherein: The mouse restraint cavity has a breathable plate (2).

5. The apparatus according to claim 1, characterized in that: The tail root fixing assembly includes a slide groove (18), a tail root fixing slider (19), and a clamping groove (20). Adjusting the position of the tail root fixing slider (19) allows the clamping groove (20) to fit snugly against the mouse tail root that passes through the hole in the tail plate (17).

6. The apparatus of claim 5, wherein: The groove surface of the clamping groove (20) is non-slip.

7. The apparatus of claim 1, wherein: The tail fixing component also includes a slot (22) and a plate (21). The inner side (21) of the plate is made of silicone. The slot (22) and the plate (21) are matched and used to restrain the mouse tail in the placement slot (16) and improve the mouse's comfort.

8. The apparatus of claim 1, wherein: The fixing device has an anti-slip base (6).

9. The apparatus according to claim 1, characterized in that: The sample collection module includes a centrifuge tube rack (12), a rotating table (10), a telescopic table (9), an electric slider (8), and an electric chute (7). The centrifuge tube rack (12) has two holes: a blood sample collection hole (23) and a tail tip collection hole (24). Temperature control element semiconductor heating and cooling plates (11) are arranged at the bottom of both holes. The centrifuge tube rack (12) is located on the rotating table (10). By rotating the rotating table (10), the positions of the two holes, the blood sample collection hole (23) and the tail tip collection hole (24), can be changed. The rotating platform (10) is located on the telescopic platform (9), and the height of the two holes, the blood sample collection hole (23) and the tail tip collection hole (24), can be adjusted by the telescopic platform (9); The telescopic platform (9) is equipped with an electric slider (8). Through the cooperation of the electric slider (8) and the electric slide (7), the positions of the two holes, the blood sample collection hole (23) and the tail tip collection hole (24), can be adjusted horizontally so that the tail tip collection hole (24) or the blood sample collection hole (23) is located just below the tail tip.

10. The apparatus of claim 1, wherein: The electric cutting blade (25) is anchored to the extension groove (14).

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