Small animal low-stress caudal vein injection fixing device

Abstract

The invention belongs to the technical field of animal experiment instruments, and particularly relates to a small animal low-stress tail intravenous injection fixing device which comprises a main body fixing system, an intelligent partition type air bag pressure reduction system and a tail near-infrared visual operation system. The main body fixing system comprises a transparent cylindrical shell of which one end is open and the other end is closed, and an adjustable end cover fixed at the open end of the transparent cylindrical shell, and the center of the adjustable end cover is provided with a through hole for leading out a mouse tail; by integrating the intelligent partitioned airbag pressure reduction system and the tail near-infrared visual operation system, remarkable comprehensive benefits are brought. The core of the method is that the high tension state of the animal back muscle caused by traditional rigid fixation is fundamentally eliminated, so that the non-specific physiological uptake of 18F-FDG in the muscle is greatly reduced, the background noise of a PET image is remarkably reduced, the signal-to-noise ratio is improved, and the method is particularly beneficial to accurate qualitative and quantitative analysis of tiny focuses in a spine and a retroperitoneal region, and has a wide application prospect. And the data reliability is greatly improved.

Description

Technical Field

[0001] This invention belongs to the field of animal experimental equipment technology, specifically relating to a low-stress tail vein injection fixation device for small animals. Background Technology

[0002] In preclinical molecular imaging studies based on small animal models, positron emission tomography (PET) has become an indispensable tool due to its high sensitivity and quantitative analysis capabilities. Among these studies, fluorodeoxyglucose (FDEG) is used to detect FDEG. 18 FDG (F-FDG) is the most commonly used imaging agent, and its distribution in vivo directly reflects the glucose metabolism activity of tissue cells. However, the biological interpretation of FDG-PET images is highly dependent on specific physiological and pathological backgrounds. Any factor that causes abnormal hyperactivity in the metabolism of non-target tissues or organs will introduce indistinguishable noise into the images, directly affecting the accuracy of the data.

[0003] Currently, the fixation devices commonly used for tail vein injection in mice mostly employ a rigid polymer cylinder supplemented with mechanically adjustable baffles. The core design principle is to achieve mechanical immobilization of the animal through forced physical constraint. However, this rigid restraint inevitably triggers a severe stress response after the animal is placed in the restraint system, manifested as activation of the autonomic nervous system and defensive skeletal muscle tension, particularly in the core muscle groups such as the erector spinae muscles along the spine, generating sustained resting tension. From a molecular imaging perspective, the energy metabolism of skeletal muscle contraction is highly dependent on glucose, and under stress, the non-specific uptake of FDG by muscle cells is significantly enhanced. This results in linear radioactive concentrations along the spine in PET images, constituting severe background noise. This not only seriously interferes with the detection and accurate quantitative analysis of potential microlesions in adjacent areas (such as the spinal cord, vertebrae, retroperitoneal lymph nodes, and kidneys), but may also lead to confusion between pathological uptake and physiological stress-induced uptake, fundamentally challenging the reliability and reproducibility of experimental data.

[0004] The fundamental flaw in existing technologies lies in their design philosophy, which unilaterally pursues the robustness of physical fixation while completely ignoring the uncontrollable interference that the fixation process itself, as a strong stressor, causes to the observed core biological signal—namely, basal glucose metabolism level. Therefore, developing a low-stress device that can achieve reliable and humane fixation while maximally maintaining the physiological and psychological homeostasis of animals has become a critical technical problem that urgently needs to be solved in this field. Summary of the Invention

[0005] To address the technical problems of the aforementioned fixation devices used for tail vein injection in mice, this invention provides a low-stress tail vein injection fixation device for small animals.

[0006] To solve the above-mentioned technical problems, the technical solution adopted by the present invention is as follows: A low-stress tail vein injection fixation device for small animals includes a main fixation system, an intelligent zoned airbag decompression system, and a tail near-infrared visualization operating system. The main body fixing system includes a transparent cylindrical shell with one end open and the other end closed, and an adjustable end cap fixed to the open end of the transparent cylindrical shell. The adjustable end cap has a through hole in the center for the rat's tail to be led out. The intelligent partitioned airbag decompression system includes independent flexible airbags that are circumferentially and partitionedly fixed to the inner wall of a transparent cylindrical shell, inflation and deflation pipelines, a micro air pump, multiple electronically controlled proportional valves, pressure sensors, micro-motion sensors, and a central controller. Each independent flexible airbag is connected to the micro air pump through the inflation and deflation pipelines. Each inflation and deflation pipeline is equipped with an electronically controlled proportional valve. The pressure sensor is integrated into the independent flexible airbag. The micro-motion sensor is integrated into the corresponding position of the independent flexible airbag fixed to the platform or abdomen. The central controller is electrically connected to the pressure sensor, the micro-motion sensor, and the electronically controlled proportional valve. The tail near-infrared visualization operating system includes a tail fixing groove located below the through hole inside the adjustable end cap, near-infrared LED beads installed at the bottom of the tail fixing groove, and a magnification observation mechanism consisting of a high-definition optical magnifying glass and a sliding rail mechanism, wherein the sliding rail mechanism allows the magnifying glass to slide along a direction parallel to the long axis of the tail.

[0007] The transparent cylindrical shell has a cuboid structure, and multiple ventilation holes are provided on the side wall of the transparent cylindrical shell.

[0008] The adjustable end cap is fixed to the transparent cylindrical shell by means of threaded connection or snap-fit ​​connection.

[0009] The number of independent flexible airbags is at least four, and each independent flexible airbag is physically isolated from each other.

[0010] The independent flexible air sacs are divided into dorsal air sacs, abdominal air sacs, and left and right lateral air sacs according to the animal's physiological structure.

[0011] The independent flexible airbag is fixedly connected to the inner wall of the shell by adhesive or pre-embedded mechanical buckles.

[0012] The near-infrared LED light bead emits wavelengths of 805nm-850nm, and the tail fixing groove is a U-shaped groove adapted to the physiological curvature of the rat's tail. The near-infrared LED light bead is installed in an embedded structure at the bottom of the tail fixing groove.

[0013] The slide rail mechanism adopts a linear ball bearing slide rail, and the number of near-infrared LED beads is 6-20, which are evenly distributed at the bottom of the tail fixing groove.

[0014] The central controller has a built-in closed-loop control algorithm that can dynamically adjust the opening of the electronically controlled proportional valve based on feedback signals from the pressure sensor and the micro-motion sensor.

[0015] The transparent cylindrical shell is made of polycarbonate.

[0016] Compared with the prior art, the beneficial effects of this invention are: This invention brings significant comprehensive benefits by integrating an intelligent zoned airbag decompression system with a tail-mounted near-infrared visualization operating system. Its core lies in fundamentally eliminating the high-tension state of the animal's back muscles caused by traditional rigid fixation, thereby greatly reducing... 18 The non-specific physiological uptake of F-FDG in muscle significantly reduces background noise in PET images and improves the signal-to-noise ratio, which is particularly beneficial for the precise qualitative and quantitative analysis of small lesions in the spine and retroperitoneal region, greatly improving data reliability. Simultaneously, the system applies differentiated pressure to the animal's back, abdomen, and sides and intelligently and dynamically adjusts this pressure to minimize interference with respiration and circulation, ensuring the animal's physiological homeostasis. Furthermore, the use of specific near-infrared illumination, invisible to animal vision, efficiently highlights blood vessels under conditions without psychological stress, and its gentle thermal effect assists in vasodilation, significantly improving the success rate and efficiency of tail vein injection. This invention achieves a comprehensive improvement from physiological to psychological perspectives, and from image quality to operational efficiency. Attached Figure Description

[0017] To more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly introduced below. Obviously, the drawings in the following description are merely exemplary, and those skilled in the art can derive other embodiments based on the provided drawings without creative effort.

[0018] The structures, proportions, sizes, etc. illustrated in this specification are only for the purpose of assisting those skilled in the art in understanding and reading the content disclosed herein, and are not intended to limit the conditions under which the present invention can be implemented. Therefore, they have no substantial technical significance. Any modifications to the structure, changes in the proportions, or adjustments to the size, without affecting the effects and objectives that the present invention can produce, should still fall within the scope of the technical content disclosed in the present invention.

[0019] Figure 1 This is a schematic diagram of the structure of the present invention; Figure 2 This is a structural schematic diagram of the present invention from another angle; Figure 3 This is a schematic diagram of the structure of the near-infrared visual operating system at the tail of the present invention; Figure 4This is a schematic diagram of the interior of the transparent cylindrical shell of the present invention; Figure 5 This is a circuit connection block diagram of the present invention.

[0020] The components are as follows: 1 is a transparent cylindrical shell, 2 is an adjustable end cap, 3 is a through hole for the rat's tail to extend out, 4 is an independent flexible airbag, 5 is an inflation / deflation pipeline, 6 is a miniature air pump, 7 is an electronically controlled proportional valve, 8 is a pressure sensor, 9 is a micro-motion sensor, 10 is a central controller, 12 is a tail fixing groove, 13 is a near-infrared LED bead, 14 is a high-definition optical magnifying glass, 15 is a sliding rail mechanism, and 16 is a vent. Detailed Implementation

[0021] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. Obviously, the described embodiments are only some embodiments of this application, and not all embodiments. These descriptions are only for further illustrating the features and advantages of the present invention, and not for limiting the claims of the present invention. Based on the embodiments in this application, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of this application.

[0022] The specific embodiments of the present invention will be described in further detail below with reference to the accompanying drawings and examples. The following examples are for illustrative purposes only and are not intended to limit the scope of the invention.

[0023] In the description of this application, it should be noted that, unless otherwise expressly specified and limited, the terms "installation," "connection," and "linking" 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 between two components. Those skilled in the art can understand the specific meaning of the above terms in this application based on the specific circumstances.

[0024] I. Overall Structure of the Device The low-stress tail vein injection fixation device for small animals described in this invention consists of three main functional modules: a main fixation system, an intelligent zoned airbag decompression system, and a tail near-infrared visualization operating system. Through optimized spatial layout and functional synergy, each module achieves the dual goals of low-stress fixation and precise injection. The device employs a modular design for easy assembly, disassembly, and maintenance. All parts that come into contact with the animal comply with ethical requirements for laboratory animals and are non-irritating and non-toxic.

[0025] II. Detailed Structure and Component Parameters of Each System (a) Main fixing system Transparent cylindrical shell 1: Made of polycarbonate (PC) material through one-piece injection molding. This material combines high transparency (light transmittance ≥90%), impact resistance, and biocompatibility, facilitating real-time observation of the animal's condition inside the shell. The shell is a cuboid structure with one end open and the other closed, with dimensions suitable for standard laboratory mice (body length 18-25cm), preferably 22cm long × 6cm wide × 6cm high. Multiple ventilation holes 16 are evenly distributed on the sidewalls of the shell, with a diameter of 2-3mm and a spacing of 3cm, ensuring air circulation inside the shell and preventing additional stress to the animal due to hypoxia.

[0026] Adjustable end cap 2: Made of the same polycarbonate material as the shell, it is fixed to the open end of the transparent cylindrical shell 1 by a threaded connection (a snap-fit ​​connection can also be used as needed). The edge of the end cap has anti-slip texture for easy manual adjustment. A through hole 3 with a diameter of 1.5-2cm is opened in the center of the adjustable end cap 2. A flexible silicone ring is attached to the inner wall of the through hole to ensure that the rat tail can be led out smoothly and to prevent the tail from being damaged by friction from the hard edge.

[0027] (II) Intelligent zoned airbag decompression system Independent flexible air sac 4: Made of medical-grade silicone rubber, it has good flexibility and airtightness, with a Shore hardness of 30-40HA, avoiding hard pressure on the animal. There are 4 air sacs, which are completely isolated from each other in physical structure. They are circumferentially fixed to the inner wall of the transparent cylindrical shell 1 by medical-grade adhesive (or pre-embedded mechanical buckles), corresponding to the back, abdomen and left and right sides of the animal: the back air sac covers the area corresponding to the spine (15cm long × 3cm wide), the abdominal air sac covers the chest and abdomen area (12cm long × 3cm wide), and the left and right side air sacs are symmetrically distributed (each 15cm long × 2cm wide).

[0028] Inflation / Deflator Assembly: The inflation / deflator line 5 uses a polytetrafluoroethylene (PTFE) flexible hose with an inner diameter of 2mm and an outer diameter of 4mm, which has the characteristics of high pressure resistance and no odor; the miniature air pump 6 is a silent diaphragm pump with a rated working pressure of 0-10kPa, a flow rate of 50ml / min, and a working noise of ≤40dB to avoid noise stress; each inflation / deflator line 5 is connected in series with an electronically controlled proportional valve 7, model VQZ1000, with a response time of ≤50ms, which can accurately adjust the inflation flow rate and pressure.

[0029] Sensing and Control Module: Pressure sensor 8 is integrated inside each independent flexible air bladder 4, model MPX5010DP, with a measurement range of 0-10kPa and an accuracy of ±0.05kPa, and collects the actual pressure value of each air bladder in real time; Micro-motion sensor 9 is a piezoelectric sensor integrated into the bottom of the shell corresponding to the abdominal air bladder, model PZT-5H, which can detect the frequency (measurement range 10-100 times / minute) and amplitude of animal respiratory fluctuations; Central controller 10 uses an STM32F103 series microprocessor with built-in closed-loop control algorithm, and is electrically connected to pressure sensor 8, micro-motion sensor 9 and electronic proportional valve 7 via CAN bus, with a data sampling frequency of 10Hz, and can dynamically adjust the opening of electronic proportional valve 7.

[0030] (III) Tail-mounted near-infrared visualization operating system Tail fixing groove 12: Made of medical-grade silicone in one piece, it is a U-shaped groove that matches the physiological curvature of the mouse tail. The groove is 1cm wide, 0.8cm deep and 8cm long. The inner wall of the groove is set with anti-slip texture to prevent the mouse tail from sliding during injection.

[0031] Near-infrared LED beads 13: 6-20 high-power LED beads are selected and evenly distributed at the bottom of the tail fixing slot 12. The near-infrared LED beads 13 emit a wavelength of 805nm-850nm, which is outside the range of light perception of mice and can create a significant difference in light absorption between hemoglobin and surrounding tissues; each bead has a power of 50mW, an operating voltage of 3.3V, and is powered by a constant current drive module, producing soft and non-irritating light.

[0032] Magnification observation mechanism: The high-definition optical magnifying glass 14 has a magnification of 3-5 times, and the lens is made of optical glass with a light transmittance of ≥95%. The high-definition optical magnifying glass 14 is connected to the sliding rail mechanism 15 and can slide smoothly along the direction parallel to the long axis of the tail, which makes it easy to adjust the observation angle and distance.

[0033] III. Operating Process of the Device Animal placement and initial fixation: Based on the body length of the experimental mouse, screw on the adjustable end cap 2 to adjust its position on the transparent cylindrical shell 1 so that the internal space of the shell is adapted to the animal's body size; place the mouse head towards the closed end of the shell and slowly put it into the shell, so that the mouse tail is led out through the through hole 3 in the center of the adjustable end cap 2 and placed in the U-shaped groove of the tail fixing groove 12. Then fine-tune the adjustable end cap 2 to achieve the initial fixation of the animal.

[0034] Intelligent airbag decompression and immobilization: The micro air pump 6 is activated, and the central controller 10 initializes inflation according to the preset pressure gradient: the abdominal airbag is inflated to 0.5-1.5 kPa (preferably 1.0 kPa) to provide gentle support without restricting breathing; the back airbag and the left and right side airbags are inflated to 2.0-4.0 kPa (preferably 3.0 kPa for the back and 2.5 kPa for the sides) to achieve stable restraint of the body. During the immobilization process, the pressure sensor 8 provides real-time feedback on the pressure of each airbag, and the micro-motion sensor 9 monitors the breathing signal: if the animal's struggle is detected, causing pressure fluctuations in a certain area to exceed ±0.3 kPa, the central controller 10 adjusts the corresponding electronically controlled proportional valve 7 through a closed-loop algorithm, restoring the set pressure within 50 ms; if the respiratory rate is lower than 15 breaths / minute or the amplitude decreases by 30%, the abdominal airbag pressure is automatically reduced by 0.2-0.3 kPa to relieve respiratory pressure.

[0035] Near-infrared assisted injection: Near-infrared LED beads 13 are activated, and near-infrared light in the 830nm band penetrates the rat's tail skin, making the subcutaneous veins appear as high-contrast shadows. Simultaneously, the slight thermal effect of the near-infrared light (a local temperature increase of 0.5-1℃) promotes mild vasodilation and improves vascular filling. The operator slides the high-definition optical magnifying glass 14 to the appropriate position, clearly identifying the vein's course under magnified vision, and quickly completing the tail vein puncture and injection.

[0036] Operation complete: After injection, the central controller 10 controls the electronic proportional valve 7 to release air synchronously. After all airbag pressures drop to 0 kPa, loosen the adjustable end cap 2, remove the animal from the transparent cylindrical shell 1, and turn off the power to the equipment.

[0037] The device of this embodiment was used to perform tail vein injection and 18F-FDG PET / CT imaging experiments on C57BL / 6 mice. The results showed that the incidence of stress response in mice was reduced to below 15%, the non-specific uptake of FDG in the back muscles was reduced by 70%, the signal-to-noise ratio of PET images was improved by 65%, and the success rate of tail vein injection was increased from 75% with conventional devices to over 95%. The reliability and reproducibility of the experimental data were significantly improved.

[0038] The above description only illustrates the preferred embodiments of the present invention. However, the present invention is not limited to the above embodiments. Within the scope of knowledge possessed by those skilled in the art, various changes can be made without departing from the spirit of the present invention, and all such changes should be included within the protection scope of the present invention.

Claims

1. A tail vein injection fixation device for low-stress small animals, characterized in that: Includes a main body fixation system, an intelligent zoned airbag decompression system, and a tail-mounted near-infrared visualization operating system; The main body fixing system includes a transparent cylindrical shell (1) with one end open and the other end closed, and an adjustable end cap (2) fixed to the open end of the transparent cylindrical shell (1). The adjustable end cap (2) has a through hole (3) in the center for the rat's tail to be led out. The intelligent partitioned airbag decompression system includes independent flexible airbags (4) that are circumferentially and partitionedly fixed to the inner wall of a transparent cylindrical shell (1), inflation and deflation pipelines (5), a micro air pump (6), multiple electronically controlled proportional valves (7), pressure sensors (8), micro-motion sensors (9), and a central controller (10). Each independent flexible airbag (4) is connected to the micro air pump (6) through the inflation and deflation pipelines (5). Each inflation and deflation pipeline (5) is equipped with an electronically controlled proportional valve (7). The pressure sensor (8) is integrated into the independent flexible airbag (4). The micro-motion sensor (9) is integrated into the corresponding position of the independent flexible airbag (4) fixed on the platform or abdomen. The central controller (10) is electrically connected to the pressure sensor (8), the micro-motion sensor (9), and the electronically controlled proportional valve (7) respectively. The tail near-infrared visualization operating system includes a tail fixing groove (12) located below the through hole (3) inside the adjustable end cap (2), a near-infrared LED bead (13) installed at the bottom of the tail fixing groove (12), and a magnification observation mechanism composed of a high-definition optical magnifying glass (14) and a slide rail mechanism (15), wherein the slide rail mechanism (15) allows the magnifying glass (14) to slide along a direction parallel to the long axis of the tail.

2. The tail vein injection fixation device for small animals under low stress according to claim 1, characterized in that: The transparent cylindrical shell (1) has a cuboid structure, and multiple ventilation holes (16) are provided on the side wall of the transparent cylindrical shell (1).

3. The tail vein injection fixation device for small animals under low stress according to claim 1, characterized in that: The adjustable end cap (2) is fixed to the transparent cylindrical shell (1) by means of threaded connection or snap-fit ​​connection.

4. The tail vein injection fixation device for small animals under low stress according to claim 1, characterized in that: The number of independent flexible airbags (4) is at least four, and each independent flexible airbag (4) is physically isolated from each other.

5. The tail vein injection fixation device for small animals under low stress according to claim 1, characterized in that: The independent flexible air sac (4) is divided into dorsal air sac, abdominal air sac and left and right side air sacs according to the animal's physiological structure.

6. The tail vein injection fixation device for small animals under low stress according to claim 1, characterized in that: The independent flexible airbag (4) is fixedly connected to the inner wall of the shell (1) by adhesive or pre-embedded mechanical buckles.

7. The tail vein injection fixation device for small animals under low stress according to claim 1, characterized in that: The near-infrared LED bead (13) emits wavelengths of 805nm-850nm. The tail fixing groove (12) is a U-shaped groove adapted to the physiological curvature of the rat tail. The near-infrared LED bead (13) is installed at the bottom of the tail fixing groove (12) in an embedded structure.

8. The tail vein injection fixation device for small animals under low stress according to claim 1, characterized in that: The slide rail mechanism (15) adopts a linear ball slide rail, and the number of near-infrared LED beads (13) is 6-20, which are evenly distributed at the bottom of the tail fixing groove (12).

9. A low-stress tail vein injection fixation device for small animals according to claim 1, characterized in that: The central controller (10) has a built-in closed-loop control algorithm, which can dynamically adjust the opening of the electronically controlled proportional valve (7) according to the feedback signals of the pressure sensor (8) and the micro-motion sensor (9).

10. A low-stress tail vein injection fixation device for small animals according to claim 1, characterized in that: The transparent cylindrical shell (1) is made of polycarbonate.

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