Trace virus intestinal wall injection device and injection method

Abstract

The invention belongs to the technical field of virus injection, and relates to a trace virus intestinal wall injection device and an injection method. Comprising an input assembly and a supplementing assembly, the supplementing assembly comprises a sample injection needle cylinder, a piston is arranged in the sample injection needle cylinder, a needle tube is arranged at the lower end of the sample injection needle cylinder, the input assembly comprises an injection hose detachably connected to the lower end of the needle tube and an injection needle connected with the lower end of the injection hose, and the piston moves through a quantitative driving device. By means of the technical scheme, an experimenter can conveniently hold the injection device and position the injection device to the intestinal tract position where virus liquid needs to be injected, the defects in the current micro virus injection technology are overcome, the supplementing device is matched with a craniocerebral injection experiment device commonly used in a laboratory, and the practicability of the technology can be improved.

Description

Technical Field

[0001] The invention belongs to the technical field of virus injection, and relates to a device and method for injecting a trace amount of virus into the intestinal wall. Background Art

[0002] Exploring various neurological diseases from the perspective of the gut-brain axis has become a hot topic in current basic research. Many studies require the injection of various viruses into the intestine to achieve regulation or tracing of the intestine. Due to the characteristics of the movable and hollow structure of the intestine, it is difficult to achieve high-precision microinjection of viruses into the intestine using existing virus injection methods.

[0003] Since the insulin needle has the characteristics of small needle tip, easy operation and small unit injection volume, the existing technology uses the insulin needle to directly inject the virus into the intestinal wall to achieve intestinal wall delivery of the virus. However, this injection method has the following disadvantages: (1) The local injection dose is completely manually controlled, and the dosage is not easy to master. Once the drug is injected too much, mucosal necrosis is likely to occur; (2) At the same time, when injecting the drug, the syringe needle is not convenient to fix on the intestinal wall, and the injection depth is unstable and cannot be controlled. Specifically, during the actual injection, the hand holding the insulin injection syringe is relatively far from the needle tip, which increases the torque. The mouse intestine is thin, and it is difficult to grasp the fixed position of the needle in the intestinal wall; (3) The minimum injection unit of the insulin needle is 10ul, and the injection of many viruses only requires 1-3ul, or even nanoliters. The use of insulin needles cannot achieve the purpose of intestinal micro-injection of viruses.

[0004] In addition, some studies have used a brain stereotaxic injection system and a virus microinjector for microinjection of viruses. This method is suitable for fixed brain injections and can achieve nanoliter-level virus injection volumes. It can also be connected to a micropump system for precise injections. However, this method still has disadvantages when applied to the intestine: (1) The intestine is a movable peripheral organ with cavities that cannot be fixed. In this injection method, the needle cannot move with the intestine, resulting in virus leakage; (2) Since the needle of the virus microinjector is made of glass, the needle is extremely thin and fragile, making it difficult to puncture the intestine.

[0005] Currently, there is no microinjection device specifically for intestinal virus injection on the market. However, with the deepening of research on the gut-brain axis, the demand for different doses of virus injection into the intestine is increasing day by day, and a microviral intestinal wall injection device is urgently needed. Summary of the invention

[0006] The purpose of the present invention is to overcome the shortcomings of the prior art and to provide a device and method for injecting trace amounts of virus into the intestinal wall.

[0007] In order to achieve the above object, the present invention adopts the following technical solutions:

[0008] A device for micro-virus intestinal wall injection comprises an input component and a supplementary component, wherein the supplementary component comprises an injection syringe, wherein a piston is arranged inside the injection syringe, and a needle tube is arranged at the lower end of the injection syringe, wherein the input component comprises an injection hose detachably connected to the lower end of the needle tube and an injection needle connected to the lower end of the injection hose, and the piston is moved by a quantitative drive device.

[0009] Furthermore, the quantitative driving device includes a micro-injection pump, and the micro-injection pump drives the piston to achieve quantitative extraction and injection of the virus.

[0010] Furthermore, the quantitative drive device includes a piston rod, the piston is provided with a groove, the piston rod rotates in the groove, the upper end of the piston rod is provided with a rotating part, the piston rod is provided with a thread, a slider is threaded on the piston rod, the bottom surface of the slider is connected to a plurality of push rods, and the lower end of the push rod is connected to the piston.

[0011] Furthermore, a wireless control unit is provided on the rotating part, and the wireless control unit includes a driver and a control module. The driver action is controlled by the control module, thereby controlling the rotation of the piston rod.

[0012] Furthermore, a connecting pipe opening is provided between the injection hose and the syringe.

[0013] Furthermore, the diameter of the injection needle is 1 mm to 4 mm.

[0014] Furthermore, a scale is arranged on the tube wall of the injection hose.

[0015] Furthermore, the injection hose is made of polyurethane.

[0016] Furthermore, the outer diameter of the injection hose is 1 to 1.04 mm, the inner diameter of the injection hose is 0.59 to 0.63 mm, and the length of the injection hose is 8 to 12 cm.

[0017] In addition, the present application also discloses an injection method using a micro-virus intestinal wall injection device, comprising the following steps:

[0018] Step 1: Fill the input assembly and the injection syringe with paraffin oil that is incompatible with the virus solution, and connect the input assembly and the syringe;

[0019] Step 2: Immerse the injection needle completely into the virus liquid surface, and drive the piston upward through the quantitative drive device until the virus is sucked into the injection hose;

[0020] Step 3: Cut open the abdomen of the experimental animal to expose the intestine, clamp the intestinal wall with tweezers and insert the injection needle into the intestinal wall, drive the piston downward through the quantitative drive device, and adjust the virus amount and injection speed according to the experimental requirements. After the injection is completed, leave the needle in for 10 seconds and remove it;

[0021] Step 4: Suture the abdomen and wait for the mouse to wake up.

[0022] Compared with the prior art, the present invention has the following beneficial effects:

[0023] 1. In the present invention, the injection hose of the input component is connected to a movable needle and a fixable supplementary device, which is convenient for the experimenter to better hold the injection device and position it to the intestinal position where the virus liquid needs to be injected, which makes up for the shortcomings of the current micro-virus injection technology. In addition, the supplementary device is compatible with the commonly used cranial injection experimental device (micro-injection pump) in the laboratory, which can improve the practicality of the present invention. Finally, the convenience of storage of each component is improved by a detachable connection, which has a high practical value.

[0024] 2. The present invention is different from the traditional virus injection that uses a fixed, non-tough glass device. The device provides a controllable hose part for virus injection into a retractable and movable organ, which can achieve arbitrary movement; the quantitative drive device can achieve quantitative and trace virus injection into the intestine, making the injection more precise, and can solve the needs of trace virus injection into the intestinal wall, which is more accurate, efficient and convenient. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] The accompanying drawings are incorporated in and constitute a part of this specification and, together with the description, serve to explain the principles of the present invention.

[0026] In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, for ordinary technicians in this field, other drawings can be obtained based on these drawings without paying any creative labor.

[0027] Figure 1 This is a schematic diagram of a micro-amount virus intestinal wall injection device according to Example 2 of the present invention;

[0028] Figure 2 Schematic cross-sectional view of the device for micro-virus intestinal wall injection according to Example 2 of the present invention.

[0029] Among them: 1 is a supplementary component; 1.1 is a sample injection syringe; 1.2 is a piston; 2 is an input component; 2.1 is an injection hose; 2.2 is an injection needle; 3 is a quantitative drive device; 3.1 is a piston rod; 3.2 is a slider; 3.3 is a push rod; 3.4 is a rotating part; 4 is an infinite control unit. DETAILED DESCRIPTION

[0030] Here, exemplary embodiments will be described in detail, and the embodiments described in the following exemplary embodiments do not represent all embodiments consistent with the present invention. Instead, they are only examples of devices consistent with some aspects of the present invention as detailed in the appended claims.

[0031] Example 1

[0032] like Figure 1 As shown, a micro-virus intestinal wall injection device includes an input component 2 and a supplement component 1, the supplement component 1 includes an injection syringe 1.1, a piston 1.2 is arranged in the injection syringe 1.1, and a needle tube 1.3 is arranged at the lower end of the injection syringe 1.1, the input component 2 includes an injection hose 2.1 detachably connected to the lower end of the needle tube 1.3 and an injection needle 2.2 connected to the lower end of the injection hose 2.1, and the piston 1.2 is moved by a quantitative driving device 3. The quantitative driving device 3 drives the piston 1.2 to move, thereby realizing the quantitative extraction and injection of the virus liquid.

[0033] The invention discloses a device for micro-injection of intestinal wall virus, comprising an input component 2 and a supplement component 1; the input component 2 comprises an injection hose 2.1 for virus liquid, an injection needle 2.2 and a connecting pipe mouth located at both ends of the injection hose 2.1. The supplement component comprises an injection syringe 1.1 and a piston 1.2. The input component 2 of the invention can be used to transport the virus liquid required in the process of injecting micro-virus, and the injection needle 2.2 can transport the required virus into the human intestine. The input component 2 and the supplement component 1 are detachable to achieve portable storage and disassembly. At the same time, the design of the injection needle 2.2 connecting the injection hose 2.1 makes it more convenient for experimenters to better perform intestinal wall puncture, greatly improving safety and virus delivery efficiency. The injection hose 2.1 is 10 cm long and is sealed and connected to the injection needle 2.2. The connected needle tube 1.3 is a stainless steel flat-end needle, which is fixed on the bottom wall of the injection syringe 1.1.

[0034] Furthermore, the quantitative drive device 3 includes a microinjection pump, which drives the piston 1.2 to achieve quantitative extraction and injection of the virus. During the injection process, the supplementary component 1 is fixed on the syringe holder and connected to the microinjection pump. The microinjection pump can accurately control the injection volume and rate, and the injection accuracy reaches the nanoliter level. The injection needle 2.2 of the input component 2 is inserted into the virus liquid, and the required virus liquid content is extracted using the withdrawal system of the microinjection pump. After the injection needle 2.2 of the input component 2 pierces the intestine of the experimental animal, the microinjection pump injection system is used to inject a trace amount of virus liquid into the intestinal wall. After the injection is completed, the needle is retained for 10 seconds and then withdrawn to prevent leakage.

[0035] Furthermore, a connecting pipe opening is provided between the injection hose 2.1 and the injection syringe 1.1, and the connecting pipe opening and the injection hose 2.1 are detachably connected.

[0036] Furthermore, the diameter of the injection needle 2.2 is 1 mm to 4 mm. Preferably, the injection needle is a 1 mm needle, which is easy to hold and pierce into the intestinal wall and is not easy to pierce, resulting in a small wound.

[0037] Furthermore, a scale is provided on the wall of the injection hose 2.1, through which the liquid level and injection volume can be clearly determined, and the virus injection volume can be accurately determined.

[0038] Furthermore, the injection hose 2.1 is made of polyurethane, an inert catheter material with good anti-kink properties, chemical inertness, biocompatibility and air permeability, and will not react with drug solvents and chemicals.

[0039] Furthermore, the outer diameter of the injection hose 2.1 is 1 to 1.04 mm, the inner diameter of the injection hose 2.1 is 0.59 to 0.63 mm, and the length of the injection hose 2.1 is 8 to 12 cm.

[0040] In addition, the present application also provides an injection method using a micro-virus intestinal wall injection device, comprising the following steps:

[0041] Step 1: Fill the input assembly 2 and the injection syringe 1.1 with paraffin oil that is incompatible with the virus solution, and connect the input assembly 2 and the needle tube 1.3;

[0042] Step 2: completely immerse the injection needle 2.2 into the virus liquid surface, and drive the piston 1.2 upward through the quantitative drive device 3 until the virus is sucked into the injection hose 2.1;

[0043] Step 3: Cut open the abdomen of the experimental animal to expose the intestine, clamp the intestinal wall with tweezers and insert the injection needle 2.2 into the intestinal wall, drive the piston 1.2 downward through the quantitative drive device 3, and adjust the virus amount and injection speed according to the experimental requirements. After the injection is completed, leave the needle in for 10 seconds and remove it;

[0044] Step 4: Suture the abdomen and wait for the experimental animal to wake up.

[0045] Specifically, in step 1: the input component 2 and the injection syringe 1.1 need to be filled with paraffin oil that is incompatible with the virus liquid in advance to remove the gas in the two components to prevent errors caused by gas compression during trace virus injection, and the input component 2 and the injection syringe 1.1 are connected through the connecting pipe to ensure that no gas is generated. If necessary, the connection can be sealed with hot melt adhesive to form an integrated device that can be used continuously when injecting the same virus.

[0046] In step 2: inject the required virus into the injection hose 2.1 through the microinjection pump or rotating part 3.4. Make sure that the injection needle 2.2 is completely inserted into the virus liquid surface to prevent gas inhalation. After the virus is injected, if the liquid surface between the virus liquid and the paraffin oil can be seen through the injection hose 2.1, it proves that the inhalation is successful.

[0047] In step three: after anesthetizing the mouse, place it with its back facing down to expose the abdomen. After disinfecting the skin, cut it in the middle to expose the mouse intestine. Find the cecum from the left and distinguish between the large and small intestines. Then inject the virus into the required intestine. Use tweezers to clamp the intestinal wall with your left hand, hold the injection needle 2.2 with your right hand, and pierce it parallel to the intestinal wall to be injected. Stop inserting the needle when you feel the puncture. Drive the piston 1.2 downward through the quantitative drive device 3. The amount of virus and the injection speed can be adjusted according to the experimental requirements. After the injection is completed, leave the needle in for 10 seconds and pull it out.

[0048] In step 4: Generally, the virus is injected into multiple parts of the intestine, and the above steps can be repeated. After all the viruses are injected, the abdomen is closed and continuous sutures are performed, and the mouse is allowed to wake up.

[0049] Example 2

[0050] like Figure 2 As shown, the difference between this embodiment and embodiment 1 is that: the quantitative driving device 3 includes a piston rod 3.1, a groove is provided on the piston 1.2, the piston rod 3.1 rotates in the groove, the upper end of the piston 1.2 rod is provided with a rotating part 3.4, the piston rod 3.1 is provided with a thread, a slider 3.2 is screwed on the piston rod 3.1, the bottom surface of the slider 3.2 is connected with a plurality of push rods 3.3, and the lower end of the push rod 3.3 is connected to the piston 1.2. The rotating part 3.4 is rotated, and the rotating part 3.4 drives the piston rod 3.1 to rotate (at this time, the piston rod 3.1 only rotates in the groove, and the piston 1.2 does not rotate), and the slider 3.2 is driven to rise or fall by the rotation of the piston rod 3.1. When the slider 3.2 rises, it drives the push rod 3.3 to rise, and pulls the piston 1.2 to rise. At this time, the virus liquid can be extracted, and when the slider 3.2 falls, it pushes the piston 1.2 to fall, and the virus liquid can be injected.

[0051] Furthermore, a wireless control unit is provided on the rotating part 3.4. The wireless control unit includes a driver and a control module. The control module controls the driver action, thereby controlling the rotation of the piston 1.2 rod. Through wireless control, the control module receives instructions and controls the driver action to rotate the piston 1.2. In addition, it can also be controlled by a PLC program.

[0052] Furthermore, the thread on the piston rod 3.1 is a precision thread. Combined with the size diameter of the injection syringe 1.1 and the size diameter of the piston 1.2, 0.05ul of venom can be extracted or injected with each rotation.

[0053] The above description is only a specific embodiment of the present invention, so that those skilled in the art can understand or implement the present invention. Various modifications to these embodiments will be apparent to those skilled in the art, and the general principles defined herein can be implemented in other embodiments without departing from the spirit or scope of the present invention.

[0054] It should be understood that the present invention is not limited to what has been described above and that various modifications and changes may be made without departing from its scope. The scope of the present invention is limited only by the appended claims.

Claims

1. A micro-virus intestinal wall injection device, characterized in that: The invention comprises an input component (2) and a supplement component (1), wherein the supplement component (1) comprises an injection syringe (1.1), wherein a piston (1.2) is arranged inside the injection syringe (1.1), and a needle tube (1.3) is arranged at the lower end of the injection syringe (1.1); the input component (2) comprises an injection hose (2.1) detachably connected to the lower end of the needle tube (1.3) and an injection needle (2.2) connected to the lower end of the injection hose (2.1); and the piston (1.2) is moved by a quantitative drive device (3).

2. A micro-virus intestinal wall injection device according to claim 1, characterized in that: The quantitative driving device (3) comprises a microinjection pump, and the microinjection pump drives the piston (1.2) to achieve quantitative extraction and injection of the virus.

3. A micro-virus intestinal wall injection device according to claim 1, characterized in that: The quantitative drive device (3) comprises a piston rod (3.1), the piston (1.2) is provided with a groove, the piston rod (3.1) rotates in the groove, the upper end of the piston (1.2) rod is provided with a rotating part (3.4), the piston rod (3.1) is provided with a thread, a slider (3.2) is threadedly connected to the piston rod (3.1), the bottom surface of the slider (3.2) is connected to a plurality of push rods (3.3), and the lower ends of the push rods (3.3) are connected to the piston (1.2).

4. A micro-virus intestinal wall injection device according to claim 3, characterized in that: The rotating part (3.4) is provided with a wireless control unit (4), and the wireless control unit (4) comprises a driver and a control module. The driver action is controlled by the control module, thereby controlling the rotation of the piston rod (3.1).

5. A micro-virus intestinal wall injection device according to claim 1, characterized in that: A connecting pipe opening is provided between the injection hose (2.1) and the needle tube (1.3).

6. A micro-virus intestinal wall injection device according to claim 1, characterized in that: The diameter of the injection needle (2.2) is 1 mm to 4 mm.

7. A micro-virus intestinal wall injection device according to claim 1, characterized in that: The tube wall of the injection hose (2.1) is provided with scales.

8. A micro-virus intestinal wall injection device according to claim 1, characterized in that: The injection hose (2.1) is made of polyurethane.

9. A micro-virus intestinal wall injection device according to claim 1, characterized in that: The outer diameter of the injection hose (2.1) is 1 to 1.04 mm, the inner diameter of the injection hose (2.1) is 0.59 to 0.63 mm, and the length of the injection hose (2.1) is 8 to 12 cm.

10. The injection method using the micro-virus intestinal wall injection device according to claims 1 to 9, characterized in that: The following steps are involved: Step 1: Fill the input component (2) and the injection syringe (1.1) with paraffin oil that is incompatible with the virus liquid, and connect the input component (2) and the needle tube (1.3); Step 2: completely immerse the injection needle (2.2) into the virus liquid surface, and drive the piston (1.2) upward through the quantitative drive device (3) until the virus is sucked into the injection hose (2.1); Step 3: Cut open the abdomen of the experimental animal to expose the intestine, clamp the intestinal wall with tweezers and insert the injection needle (2.2) into the intestinal wall, drive the piston (1.2) downward through the quantitative drive device (3), and adjust the virus amount and injection speed according to the experimental requirements. After the injection is completed, leave the needle in for 10 seconds and remove it; Step 4: Suture the abdomen and wait for the experimental animal to wake up.

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