A flexible micro-quantitative injection device for animal experiments

Abstract

This invention discloses a flexible micro-quantitative injection device for animal experiments, belonging to the field of biological experimental instrument technology. Its key technical features include: a micro-injector, an ultra-fine tubing, an infusion needle, and a glass electrode (glass capillary microneedle); the front end of the micro-injector is sealed to the ultra-fine tubing, the other end of which is connected to the infusion needle; the front end of the infusion needle is fixed to the glass electrode with hot melt adhesive, forming a through-flow liquid channel. The micro-injector is compatible with an infusion pump, enabling uniform and quantitative injection. This invention utilizes a flexible tubing to allow for multi-angle bending and needle insertion, solving the problems of fixed direction, inconvenient operation, and high risk of injection into dangerous areas associated with traditional syringes. It allows for precise injection into delicate and high-risk sites such as the vagus ganglion; the device has a simple structure, low cost, and is easy to assemble, is compatible with stereomicroscope operation, meets the needs of micro-injection of neuroviruses, and is highly practical.

Description

Technical Field

[0001] This invention relates to the field of biological experimental equipment technology, specifically to a flexible micro-quantitative injection device for animal experiments. Background Technology

[0002] Since the beginning of the 21st century, neuroscience and virology research have developed rapidly. Mice have been widely used as model animals for tracing neural viruses, analyzing brain region functions, and exploring peripheral-central neural pathway mechanisms. Experiments often require the injection of micro-volume (range 10μL), uniformly, and quantitatively into small, easily movable, and delicate or dangerous areas adjacent to blood vessels, such as the vagus ganglion and specific brain regions.

[0003] Current technologies primarily rely on Hamilton microsyringes or straight-needle glass microelectrodes, used in conjunction with injection pumps. However, these traditional devices have significant limitations: the syringe body, rigid fluid path, and distal needle are linked as a whole, with a fixed direction, restricting posture adjustment in confined operating spaces; the syringe body may also affect the ease of operation under a stereomicroscope; the syringe body is large and heavy, resulting in poor maneuverability under a stereomicroscope and a high risk of pulling and damaging surrounding tissues; for dangerous areas such as the vagus ganglion in the neck, traditional straight-needle manipulation is difficult and risky, often requiring precise manual fixation, resulting in poor stability; ordinary straight needles are difficult to adapt to extremely fine peripheral ganglia, and some simple devices cannot be matched with injection pumps, requiring manual injection, making it difficult to control the injection rate, which can easily lead to virus loss and reduced infection efficiency due to excessively rapid injection; commercial high-end multi-axis microinjection equipment is expensive and has low adoption rates, with most laboratories lacking the necessary equipment.

[0004] Therefore, there is an urgent need in the field for an improved device that is simple in structure, low in cost, easy to assemble, flexible, and compatible with micro-injection pumps. This device can achieve precise targeted injection into delicate / dangerous areas while ensuring quantitative, uniform, and low-damage injection, thus meeting the urgent needs of experiments such as neuroviral tracing. Summary of the Invention

[0005] The purpose of this invention is to solve the above-mentioned problems by providing a flexible micro-quantitative injection device for animal experiments. This addresses the technical issues in the prior art, such as traditional micro-injectors only being able to insert the needle vertically and being unable to inject at multiple angles, some devices being unable to adapt to micro-injection pumps, difficulty in controlling the injection rate, and poor experimental repeatability.

[0006] To achieve the above objectives, the technical solution of the present invention is as follows: A flexible micro-quantitative injection device for animal experiments includes a micro-injector, an ultra-fine tubing, an infusion needle, and a glass electrode; the front end of the micro-injector is sealed and connected to one end of the ultra-fine tubing to form a first connection part, the other end of the ultra-fine tubing is sealed and connected to the rear end of the infusion needle to form a second connection part, and the front end of the infusion needle is sealed and fixed to the rear end of the glass electrode by hot melt adhesive to form a third connection part; a liquid delivery channel is formed sequentially inside the micro-injector, ultra-fine tubing, infusion needle, and glass electrode.

[0007] Furthermore, the micro-syringe is a flat-head micro-syringe with a 10μL capacity, the body of which is made of borosilicate glass and fitted with a stainless steel plunger.

[0008] Furthermore, the micro-syringe is directly embedded inside one end of the ultra-fine tubing to achieve a gapless seal; the sealing structure consists of two layers, the inner layer being an interference fit layer formed by the ultra-fine tubing and the micro-syringe needle, and the outer layer being a sealing and fixing layer covering the outside of the fitting position.

[0009] Furthermore, the ultra-fine flexible tube is made of biocompatible medical-grade silicone material, with an outer diameter of 0.8-1.2mm and a length of 3-5cm, and has the ability to bend and twist arbitrarily.

[0010] Furthermore, a 2-3mm straight section is reserved at the other end of the ultra-fine tubing, which is connected to the rear end of the infusion needle with a connection depth of 2-3mm, forming a double-layer sealing structure.

[0011] Furthermore, the infusion needle is a metal needle disassembled from a disposable infusion needle, with an outer diameter of 0.4-0.5 mm, an inner diameter of 0.2-0.3 mm, and a length of 8-10 mm. The front end is a beveled needle tip, and the rear end is a flush tube opening. The glass electrode is a laboratory standard microelectrode with an outer diameter of 0.2-0.3 mm, an inner diameter of 0.1-0.15 mm, and a length of 10-15 mm. The tip has a micro-sharp structure.

[0012] Furthermore, before extracting viruses or reagents, the entire assembly of the microsyringe, ultra-fine tubing, infusion needle, and glass electrode needs to be filled with paraffin wax through the connecting tubing of the microsyringe, ultra-fine tubing, infusion needle, and glass electrode to ensure overall airtightness.

[0013] Furthermore, the beveled tip of the infusion needle is coaxially connected to the rear end of the glass electrode, and the connection is sealed with 60-80℃ low-temperature hot melt adhesive, with a wrapping length of 2-3mm and an adhesive layer thickness of 0.5-1mm.

[0014] Furthermore, the barrel and plunger of the microsyringe can be mounted on a microinjection pump, which drives the plunger to move relative to the barrel, enabling uniform quantitative injection at a rate of 0.1-1 μL / min in conjunction with the injection pump.

[0015] Furthermore, the device is adapted to stereomicroscope operation scenarios and can be used for micro-quantitative injection of neuroviruses into delicate or high-risk areas such as the vagus ganglion and specific brain regions in mice.

[0016] Compared with existing technologies, the beneficial effects of this solution are as follows: By sequentially sealing and connecting the micro-injector, ultra-fine tubing, infusion needle, and glass electrode in a series, a flexible injection pathway that can be bent at will is formed, fundamentally overcoming the shortcomings of traditional micro-injectors, which can only be inserted vertically and in a fixed direction. The ultra-fine tubing has good flexibility and bendability, which can flexibly adjust the angle and direction of needle insertion, helping to adjust the direction of the terminal injection needle, reducing the space occupied by the syringe body, bypassing neck muscles and dangerous blood vessels in the neck, and accurately reaching narrow and high-risk delicate tissue areas such as the vagus ganglion, significantly reducing the difficulty of operation and the risk of tissue damage; at the same time, the whole device is lightweight and compact, and can be easily manipulated under a stereomicroscope, avoiding the problem of traditional syringe bodies being bulky and easily pulled and displaced, greatly improving the positioning accuracy and operational stability of injections in delicate areas.

[0017] This device can be directly adapted to a microinjection pump to achieve uniform quantitative injection at a rate of 0.1-1 μL / min. It effectively solves the drawbacks of traditional simple devices that cannot control the injection speed and can only be manually pushed, avoiding the problem of virus spread and loss and reduced infection efficiency due to excessively rapid injection, and ensuring the stability and reproducibility of experimental results. Moreover, the whole device is assembled from commercially available standard parts, which is simple in structure, low in cost, easy to obtain and easy to assemble. It does not rely on expensive high-end microscopic orientation equipment, which greatly reduces the experimental threshold and facilitates its application in ordinary laboratories. It effectively meets the urgent need for precise micro-injection in fine and dangerous areas in neuroviral tracing and peripheral-central nervous system pathway research. Attached Figure Description

[0018] Figure 1 This is a schematic diagram of the overall structure of the flexible micro-quantitative injection device for animal experiments in an embodiment of the present invention;

[0019] Figure 2 This is an exploded view of the flexible micro-quantitative injection device for animal experiments in an embodiment of the present invention;

[0020] Figure 3 This is a physical diagram of the flexible micro-quantitative injection device for animal experiments in an embodiment of the present invention;

[0021] Figure 4 is a photograph of the assembled flexible micro-quantitative injection device for animal experiments according to the present invention.

[0022] The reference numerals in the accompanying drawings include: 1. Microsyringe; 2. Ultrafine tubing; 3. Infusion needle; 4. Glass electrode; 5. Connection 1; 6. Connection 2; 7. Connection 3. Detailed Implementation

[0023] To enable those skilled in the art to better understand the present invention, the technical solution of the present invention will be described in further detail below with reference to the embodiments and accompanying drawings. Obviously, the described embodiments are merely some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without creative effort should fall within the scope of protection of the present invention.

[0024] It should be noted that, unless otherwise specified, the embodiments and features described in the present invention can be combined with each other. The present invention will now be described in detail with reference to the embodiments.

[0025] Example: As attached Figure 1-4 As shown, this embodiment is a flexible micro-quantitative injection device for animal experiments. The device is assembled in series from four parts: a micro-syringe 1, an ultra-fine tubing 2, a disassembled infusion needle 3, and a glass electrode 4. The entire assembly employs a sealed, secure, and flexible connection method. The glass electrode is a glass capillary microneedle. The overall length is suitable for operation on delicate areas such as the mouse neck and ganglia. The entire procedure can be performed under a stereomicroscope and is used in conjunction with a micro-infusion pump. Before drawing viruses or reagents, the entire assembly of the micro-syringe 1, ultra-fine tubing 2, infusion needle 3, and glass electrode 4 requires filling the tubing with paraffin to ensure overall airtightness. The micro-syringe 1 is a commercially available Hamilton brand, 10μL capacity, flat-head type micro-syringe 1. The syringe barrel is made of borosilicate glass and equipped with a stainless steel plunger. The volume scale is precise, with a minimum division of 0.1μL. The front end of the syringe can be directly embedded into the inner tube to achieve a gapless seal. The inner layer is an interference fit layer between the ultra-fine tubing 2 and the needle tube, and the outer layer is a sealing and fixing layer covering the outer periphery of the socket. The barrel and plunger of the micro-syringe 1 can be installed on a micro-injection pump. The micro-injection pump is used to drive the plunger to move relative to the barrel. The rear end of the syringe can be directly inserted into the micro-injection pump plunger clamp. The injection pump pushes the syringe at a uniform speed, controlling the injection rate at 0.1-1μL / min, which meets the requirements of slow and stable injection of neuroviruses and avoids virus loss or tissue damage due to excessively rapid injection.

[0026] The flat-head connector at the front end of the micro-syringe 1 is directly inserted into and embedded in one end of an ultra-fine medical-grade flexible tubing, forming connection 15. The tubing is made of biocompatible medical-grade silicone or polytetrafluoroethylene (PTFE), which is transparent, soft, bend-resistant, and non-toxic. The tubing has an outer diameter of 0.8-1.2mm, an inner diameter of 0.4-0.6mm, and a length of 3-5cm, much thinner than the syringe body. It can be bent, twisted, and oriented arbitrarily, bypassing the neck muscles of mice and avoiding dangerous blood vessels in the neck, achieving oblique, lateral, and multi-angle needle insertion that traditional straight needles cannot reach. The inner wall of the tubing is smooth and burr-free, fitting tightly to the outer wall of the flat-head syringe tip, with an embedding depth of approximately 3-5mm. It relies on the material's elasticity for a tight seal, with no glue, no leakage, and is detachable, ensuring that the 10μL micro-liquid is delivered precisely without residue or air bubbles. The other end of the tubing has a straight section of approximately 2-3mm reserved for attaching the infusion needle tip.

[0027] The other end of the tubing is tightly fitted with a metal needle removed from a medical infusion needle, forming connection 26. This needle is the metal part of a conventional disposable infusion needle after removing the plastic base. It has an outer diameter of 0.4-0.5 mm, an inner diameter of 0.2-0.3 mm, and a length of 8-10 mm. The front end is a beveled needle tip, and the rear end is flush with the tube opening. The rear end of the needle is directly inserted into the end of the tubing to a depth of 2-3 mm. The outer wall of the tubing is tightly wrapped around the outer wall of the needle due to its elasticity, forming a double seal. The liquid only flows through the internal channel of the needle, without contacting the hot melt adhesive, without leakage, and without clogging the tube. The metal material of the needle has a certain rigidity, serving as a rigid transition section between the flexible tubing and the glass electrode 4, ensuring the puncture directionality of the terminal injection head and preventing the needle from deviating due to the tubing being too soft.

[0028] At the beveled tip of the infusion needle, the glass electrode 4 is completely wrapped, sealed, and fixed with hot melt adhesive to form a connection 37. The glass electrode 4 is a laboratory standard microelectrode with an outer diameter of 0.2-0.3 mm, an inner diameter of 0.1-0.15 mm, a length of 10-15 mm, a flat or slightly sharp tip, transparency, moderate hardness, and a smooth surface, suitable for observation under a stereomicroscope. During assembly, the rear end of the glass electrode 4 is aligned with the outlet of the infusion needle tip and coaxially connected to ensure complete unobstructed flow of the liquid channel without misalignment or blockage. Then, low-temperature hot melt adhesive (60-80 g / L) is used. The adhesive layer is evenly coated and wrapped around the connection between the needle tip and the rear end of the glass electrode 4. The wrapping length is about 2-3 mm and the thickness of the adhesive layer is 0.5-1 mm. After cooling and solidification, it forms a smooth, edgeless, and firmly sealed connection section to prevent the glass electrode 4 from falling off and liquid from leaking out. The tip of the glass electrode 4 is extremely fine and can accurately pierce the vagus nerve ganglion with a diameter of only tens of micrometers. With the help of a micro-injection pump, it can be pushed at a constant speed to achieve micro-volume, quantitative, uniform, and directional injection of neuroviruses within 10 μL. This solves the problems of traditional straight needles, which can only be inserted vertically, are difficult to operate in dangerous areas, and cannot control the speed and quantity.

[0029] Working Principle: First, a Hamilton flat-tip microsyringe with a 10 μL capacity is selected as the basic component. The flat-tip interface of the syringe is directly embedded into one end of an ultra-fine medical tubing to complete a sealed connection (connection 1). Then, the rear end of the metal needle from a disassembled medical infusion needle is tightly fitted onto the other end of the tubing to achieve a rigid transition connection (connection 2). Subsequently, the rear end of the glass electrode is coaxially aligned with the tip of the infusion needle, and the connection area is completely wrapped and sealed with hot melt adhesive (connection 3), completing the assembly of the entire device. After assembly, the rear end of the microsyringe is inserted into the microinfusion pump clamp. The device is calibrated under a stereomicroscope to ensure that the liquid channel is unobstructed and free of air bubbles, and that there is no leakage at any connection. The neuroviral fluid to be injected is drawn into the syringe, and the infusion pump rate is set to 0.1-1 μL / min to complete the pre-injection preparation.

[0030] Under a stereomicroscope, the delicate tissues of the mouse neck, such as the vagus ganglion, are exposed, avoiding dangerous structures such as adjacent blood vessels. Holding the lower end of the assembled microsyringe, the needle handle is used to precisely aim at the vagus ganglion, which is only tens of micrometers in diameter, by adjusting the angle and direction of the glass electrode tip using the flexible, extremely thin tubing. The needle is then slowly inserted into the target tissue. The microsyringe pump is activated, and the plunger is pushed at a constant speed, allowing the neuroviral fluid to be injected steadily into the target site at a set rate through a continuous channel formed by the syringe, tubing, infusion needle, and glass electrode. After injection, the pump is paused, and the glass electrode is slowly withdrawn. This process achieves precise, quantitative, and uniform injection into dangerous and delicate areas, avoiding the risks of traditional straight needle manipulation and ensuring experimental safety and accurate results.

[0031] The above specific embodiments are merely explanations of the present invention and are not intended to limit the present invention. After reading this specification, those skilled in the art can make modifications to these embodiments without contributing any inventive step, but as long as they are within the scope of the claims of the present invention, they are protected by patent law.

Claims

1. A flexible micro-quantitative injection device for animal experiments, characterized in that: It includes a micro-injector (1), an ultra-fine tubing (2), an infusion needle (3), and a glass electrode (4); the front end of the micro-injector (1) is sealed and connected to one end of the ultra-fine tubing (2) to form a first connection part, the other end of the ultra-fine tubing (2) is sealed and connected to the rear end of the infusion needle (3) to form a second connection part, and the front end of the infusion needle (3) is sealed and fixed to the rear end of the glass electrode (4) by hot melt adhesive to form a third connection part; the micro-injector (1), ultra-fine tubing (2), infusion needle (3), and glass electrode (4) form a sequentially penetrating liquid delivery channel inside.

2. The flexible micro-quantitative injection device for animal experiments as described in claim 1, characterized in that: The micro-injector (1) is a flat-head micro-injector (1) with a volume of 10μL. The body is made of borosilicate glass and is equipped with a stainless steel plunger.

3. The flexible micro-quantitative injection device for small animal experiments as described in claim 2, characterized in that: The micro-syringe (1) is directly embedded inside one end of the ultra-fine tubing (2) to achieve a gapless seal; the sealing structure is divided into two layers, the inner layer is an interference fit layer formed by the ultra-fine tubing (2) and the needle tube of the micro-syringe (1), and the outer layer is a sealing and fixing layer covering the outside of the socket position.

4. The flexible micro-quantitative injection device for animal experiments as described in claim 1, characterized in that: The ultra-fine flexible tube (2) is made of biocompatible medical-grade silicone material, with an outer diameter of 0.8-1.2 mm and a length of 3-5 cm, and has the ability to bend and twist arbitrarily.

5. The flexible micro-quantitative injection device for animal experiments as described in claim 4, characterized in that: The other end of the ultra-fine flexible tube (2) has a 2-3mm straight section reserved, which is connected to the rear end of the infusion needle (3) with a connection depth of 2-3mm to form a double-layer sealing structure.

6. The flexible micro-quantitative injection device for animal experiments as described in claim 1, characterized in that: The infusion needle (3) is a metal needle after disassembly of a disposable infusion needle, with an outer diameter of 0.4-0.5 mm, an inner diameter of 0.2-0.3 mm, and a length of 8-10 mm. The front end is a beveled needle tip, and the rear end is a flush tube opening. The glass electrode (4) is a laboratory standard microelectrode with an outer diameter of 0.2-0.3 mm, an inner diameter of 0.1-0.15 mm, and a length of 10-15 mm. The tip is a micro-sharp structure.

7. The flexible micro-volume quantitative injection device for animal experiments as described in claim 1, characterized in that: Before extracting viruses or reagents, the entire assembly of the microsyringe (1), ultra-fine tubing (2), infusion needle (3), and glass electrode (4) needs to be filled with paraffin wax to ensure overall airtightness.

8. The flexible micro-quantitative injection device for animal experiments as described in claim 7, characterized in that: The beveled tip of the infusion needle (3) is coaxially connected to the rear end of the glass electrode (4). The connection is sealed with 60-80℃ low temperature hot melt adhesive, with a wrapping length of 2-3mm and an adhesive layer thickness of 0.5-1mm.

9. The flexible micro-quantitative injection device for animal experiments as described in claim 1, characterized in that: The syringe barrel and plunger of the microsyringe can be mounted on a microsyringe pump. The microsyringe pump is used to drive the plunger to move relative to the barrel, and can work with the pump to achieve uniform quantitative injection at a rate of 0.1-1 μL / min.

10. The flexible micro-volume quantitative injection device for animal experiments as described in any one of claims 1 to 9, characterized in that: The device is adapted to stereomicroscope operation scenarios and is used for micro-quantitative injection of neuroviruses in delicate or high-risk areas such as the vagus ganglion of mice.

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