CN110638554A

CN110638554A - PDX model tumor body quantitative transplantation inoculation needle assembly

Info

Publication number: CN110638554A
Application number: CN201910775327.9A
Authority: CN
Inventors: 曹博; 卫勃; 刘国晓; 张旺; 张亚楠; 施亚娇
Original assignee: Chinese PLA General Hospital
Current assignee: Chinese PLA General Hospital
Priority date: 2019-08-21
Filing date: 2019-08-21
Publication date: 2020-01-03
Anticipated expiration: 2039-08-21
Also published as: CN110638554B

Abstract

The invention discloses a PDX model tumor body quantitative transplantation inoculation needle assembly which comprises a sampling needle head, a balance sleeve and a push-in plug, wherein the sampling needle head and the balance sleeve are in a cylindrical pipe shape, the head end of the balance sleeve is provided with a joint communicated with the inner cavity of the balance sleeve, the tail end of the sampling needle head is embedded with the joint, the push-in plug is pushed into the balance sleeve from the tail end of the balance sleeve and is in sliding sealing fit with the balance sleeve, and the head end of the sampling needle head is provided with a steel wire with the diameter coinciding with the cross section of the sampling needle head. The sampling needle head can be inserted into tumor tissues, and the tumor body is taken down in a horizontal rotation mode in a constant volume manner; after the sampling needle head and the balance sleeve are assembled, the tumor body can be directly injected into the target part of the animal model. The invention overcomes the complex steps that the tumor tissue needs to be taken off in advance and plugged into the needle tube in the existing product, has simple structure and convenient operation, and has durability, replaceability and great transformation potential.

Description

PDX model tumor body quantitative transplantation inoculation needle assembly

Technical Field

The invention belongs to a tumor body inoculation tool of a PDX animal model, and particularly relates to a PDX model tumor body quantitative transplantation inoculation needle assembly.

Background

The PDX (patient-derived tomorgenografs) model is a tumor model established by directly transplanting tumor tissues of a tumor patient into an immunodeficiency model. Compared with the traditional cancer cell line transplantation, the PDX model furthest reserves the genetic characteristics and tumor heterogeneity of patients, is widely applied to a plurality of fields of tumor research, and provides a solid experimental foundation for improving the research level of basic medicine. Meanwhile, the high conformity with human tumor endows the PDX model with good drug resistance predictability, and the PDX model is already clinically used for screening tumor drug resistance and drug combination effect, and has benefits for some patients.

Currently, the popular PDX tumor transplantation methods are mainly divided into two types: one approach is to cut fresh tumor tissue at a certain volume (usually 2x2x2mm), make an incision at the body surface of the immunodeficient animal model, inoculate the tumor tissue subcutaneously, and then suture the incision. The method has the advantages of complicated process, low efficiency, high requirement on the operation of the experimenter in the field of surgery, overlarge local wound and susceptibility to infection; the second is needle method. The method cuts off tumor tissues according to the inoculation requirement, plugs the prepared inoculation hollow needle, inserts the needle head into the subcutaneous part of the animal model, and enables the tumor tissues to enter the model body through a physical method. The needle method is essentially a further optimization of the cutting method, but the tumor tissue still needs to be cut and plugged into the needle tube manually in the operation, the volume of the tissue cannot be accurately quantified, the possibility of tumor body waste exists in the process of plugging the needle tube, the risk of blockage of the needle tube is high, and the operation efficiency is still not ideal. Therefore, the establishment of a PDX animal model needs to provide a convenient and efficient tumor inoculation apparatus.

Disclosure of Invention

Aiming at the problem that the tumor body needs to be manually cut and filled into a needle tube when tumor tissue is inoculated in the prior art, the invention aims to provide a PDX animal model inoculation tool which avoids manual cutting and filling of the tumor body into the needle tube.

In order to achieve the purpose, the invention adopts the following technical scheme to realize the purpose:

a PDX model tumor body quantitative transplantation inoculation needle assembly is characterized by comprising a sampling needle head, a balance sleeve and a push plug. The tail end of the sampling needle head is embedded with the head end of the balance sleeve in a protruding mode, the pushing plug is pushed into the balance sleeve from the tail end of the balance sleeve and is in sliding sealing fit with the balance sleeve, and the head end of the sampling needle head is provided with a thin steel wire which is coincident with the diameter of the cross section.

The invention has the characteristics and further improvements that:

the head end of the sampling needle is provided with a bevel cut.

Be provided with in the sample syringe needle and be used for spacing a plurality of magnetic baffle, magnetic baffle is located same sample syringe needle cross section, just arc magnetic baffle winds the axis of sample syringe needle is central symmetric distribution, magnetic baffle adsorbs through magnetic force towards one side of sample syringe needle head end has circular magnetic sheet, the diameter of circular magnetic sheet equals or slightly is less than the internal diameter of sample syringe needle.

A plurality of circular hollow holes are uniformly distributed in the circular magnetic sheet.

The tail end of the sampling needle head is a cylindrical hollow embedding groove body, the inner diameter of the embedding groove body is equal to or larger than the joint outer diameter of the head end of the balance sleeve, and the two are correspondingly embedded mutually.

And two rotating handles for screwing the embedded groove body are symmetrically arranged on the outer side of the embedded groove.

The head end of the push-in plug is a rubber piston, the outer diameter of the rubber piston is equal to or slightly smaller than the inner diameter of the balance sleeve, a piston rod is connected behind the rubber piston, and the tail end of the piston rod is connected with a piston handle 13 used for pushing and pulling.

The head end of rubber piston extends forward and is provided with cylindrical thimble, the thimble passes connect and embedding cell body get into in the sample syringe needle, just the thimble passes magnetic shield and meets with circular magnetic sheet and supports, the length of thimble equals the length of sample syringe needle, and the cross section diameter of thimble is less than clearance between a plurality of magnetic shield.

The head end face of the balance sleeve is provided with two arc-shaped hollow holes.

The tail end of the balance sleeve is provided with an arched sunken holding groove.

Compared with the prior art, the invention has the beneficial effects that:

the sampling needle head in the PDX model tumor body transplantation inoculation needle assembly can be inserted into tumor tissues, the tumor body is taken down in a horizontal rotation mode, the sampling needle head is pulled out and then inserted into the target part of a receptor, then the pushing plug is pushed, thrust can be generated on the tumor body in the sampling needle head, and then the tumor body is driven into the target part of the receptor. The PDX model tumor body transplantation inoculation needle assembly provided by the invention overcomes the complex steps that the tumor tissue needs to be taken off in advance and plugged into the needle tube in the existing product, and has the advantages of simple structure, convenience in operation, durability, replaceability and great transformation potential.

Drawings

FIG. 1 is a schematic overall structure diagram of an embodiment of the present invention;

FIG. 2 is an enlarged view of portion A of FIG. 1;

FIG. 3 is a cross-sectional view taken along plane E of FIG. 1;

FIG. 4 is a perspective view of the portion B in FIG. 1;

FIG. 5 is a cross-sectional view taken along plane C of section B of FIG. 1;

FIG. 6 is a cross-sectional view taken along plane D of section B of FIG. 1;

fig. 7 is a schematic overall structure diagram of another embodiment of the present invention.

In the figure: 10. a sampling needle; 11. a thin steel wire; 12. a magnetic baffle; 13. a magnetic sheet; 14. circular holes are drilled; 15. embedding into the groove body; 16. a rotation handle; 17. a bevel notch; 20. a balance sleeve; 21. a joint; 22. arc-shaped hollowed-out holes; 23. a grip recess; 30. pushing in the plug; 31. a rubber piston; 32. a piston rod; 33. a piston handle; 34. and (4) a thimble.

Detailed Description

Embodiments of the present invention will be described in detail below with reference to examples, but it will be understood by those skilled in the art that the following examples are only illustrative of the present invention and should not be construed as limiting the scope of the present invention.

Referring to fig. 1, 2 and 3, the PDX model tumor mass quantitative transplantation inoculation needle assembly of the present invention comprises a sampling needle 10, a balance sleeve 20 and a push-in plug 30, wherein the sampling needle 10 and the balance sleeve 20 are both in a cylindrical tube shape, the head end of the balance sleeve 20 is provided with a connector 21 communicated with the inner cavity of the balance sleeve 20, the tail end of the sampling needle 10 is engaged with the connector of the balance sleeve 20, the push-in plug 30 is pushed into the cavity of the balance sleeve 20 from the tail end of the balance sleeve 20, the push-in plug 30 is in sliding sealing fit with the inner cavity of the balance sleeve 20, so that the push-in plug 30 can move in parallel in the cavity of the balance sleeve 20, and the head end of the sampling needle 10 is provided with a steel wire 11 coinciding with the cross-sectional diameter thereof. The steel wire 11 is used to cut the root of the nodule at the time of sampling, and the push-in plug is used to generate a pushing force toward the sampling needle side at the time of inoculation, so as to push out the nodule in the sampling needle 10 and drive it into a target site of a recipient.

When utilizing the PDX model tumor body ration implantation inoculation needle subassembly that this embodiment provided to take a sample, insert tumor body tissue with sampling needle 10 in, the tumor body that receives the cutting gets into the inside predetermined length of sampling needle 10, through 180

rotatory sampling needle

10, 11 tumor body roots to in the sampling needle 10 of copper wire play the cutting action, make the tumor body root that gets into sampling needle 10 break away from completely, when guaranteeing that sampling needle 10 extracts, the tumor body can not deviate from in the needle, thereby obtain the tumor body sample of predetermined volume. Because the cross section diameters of the steel wire 11 and the sampling needle head 10 are coincident, when the sampling needle head 10 is rotated by 180 degrees, the steel wire 11 can cut the root of the tumor body in the sampling needle head 10 integrally without omission, and the tumor body in the sampling needle head 10 can be completely cut off when the sampling needle head 10 is rotated by 180 degrees; simultaneously, only set up 1 copper wire 11, can enough reduce the resistance when sample syringe needle 10 inserts tumor body tissue, can furthest reduce again to the vertical cutting of tumor body, can not be with the too fragmentary of tumor body cutting for when sample syringe needle 10 extracts, the tumor body in the sample syringe needle 10 is two complete half-cylinder tumor bodies, therefore the tumor body in the sample syringe needle 10 can not scatter easily.

Alternatively, said steel wire 11 is specially made of an ultra-thin steel wire, i.e. the diameter of the steel wire is less than 0.1 mm. On the basis of the mature existing manufacturing technology, the cutting effect of the extra-thin steel wire can be guaranteed to the maximum extent, and the influence of the self volume of the steel wire on the tumor volume is reduced.

Optionally, as shown in FIG. 2, the head end of sampling needle 10 has a beveled cut 17. Compared with a flat cut, the inclined cut 17 reduces the contact area of the sampling needle 10 and a tumor body, increases the pressure, facilitates the penetration of tissues and is less prone to blockage. In this embodiment, the steel wire 11 is disposed in the cross section of the sampling needle 10 where the lower edge of the bevel cut is located, so that when the sampling needle 10 is rotated to cut the nub, the nub completely entering the sampling needle 10 can be cut.

Optionally, the tail end of the sampling needle 10 is a cylindrical hollow insertion groove 15, the inner diameter of the insertion groove 15 is equal to or larger than the outer diameter of the joint 21, and the two are correspondingly embedded with each other.

Optionally, embedding cell body 15 outside symmetry is provided with two and is used for revolving soon embedding cell body 15's rotatory handle 16, the user utilizes the rotatory handle 16 of both sides of thumb and forefinger, middle finger respectively, and it is rotatory to drive sample syringe needle 10 to cut the tumor body, and is more convenient laborsaving.

Optionally, the push-in plug 30 includes a rubber piston 31, a piston rod 32 and a piston handle 33, which are connected in sequence, the rubber piston 31 is disposed in the balance sleeve 20, and the piston handle 33 is disposed outside the balance sleeve 20 and is used for pushing and pulling the rubber piston 31 through the transmission of the piston rod 32; the cross section of the piston handle 33 is larger than that of the piston rod 32 so as to be convenient for being held to push and pull; the outer diameter of the rubber piston 31 is equal to the inner diameter of the balance sleeve 20 so that the push-in plug 30 can be in sliding sealing engagement with the balance sleeve 20. Preferably, the piston rod 32 and the piston handle 33 are both cylindrical, the diameter of the cross section of the piston handle 33 is larger than that of the piston rod 32, and the piston rod 32 is a plastic piston rod, so that the manufacturing cost can be controlled as much as possible on the basis of ensuring the hardness of the piston rod. For example: the cross-sectional diameter of the piston shank 33 is 1cm and the cross-sectional diameter of the piston rod 32 is 0.5 cm.

More preferably, please refer to fig. 1, 4, 5 and 6 simultaneously, a plurality of magnetic baffles 12 for limiting are arranged in the sampling needle 10, the magnetic baffles 12 are located at the same cross section of the sampling needle 10, the plurality of magnetic baffles 12 are distributed in central symmetry around the central axis of the sampling needle 10, a circular magnetic sheet 13 is adsorbed on one side of the magnetic baffles 12 facing the head end of the sampling needle 10 through magnetic force, the circular magnetic sheet 13 is in sliding clearance fit with the inner wall of the sampling needle 10, and the diameter of the circular magnetic sheet 13 is equal to or smaller than the inner diameter of the sampling needle 10. The magnetic force of the magnetic baffle 12 relatively fixes the circular magnetic sheet 13. Taking the sampling needle 10 with the distance between the magnetic baffle 12 and the steel wire 11 being 3mm as an example, when the sampling needle 10 is inserted into tumor tissue, the blocking effect of the circular magnetic sheet 13 enables the tissue length entering the sampling needle 10 to be at most 3 mm-the thickness of the circular magnetic sheet 13, thereby playing the role of accurately quantifying the tumor volume. If tumor bodies with different volumes need to be cut, the sampling needle 10 with corresponding specifications is replaced, the balance sleeve 20 and the push plug 30 are reserved, and the replaceability is realized, so that the construction cost of the PDX model is reduced to the greatest extent. The circular magnetic sheet 13 should be as thin as possible, for example, the thickness of the circular magnetic sheet 13 is controlled to be less than 0.5mm, so as to reduce the frictional resistance between the circular magnetic sheet 13 and the inner surface of the sampling needle 10, and make the injection process of the tumor body smoother. The number of the magnetic baffles 12 can be 6, and the magnetic baffles are uniformly arranged on the inner wall of the sampling needle 10 at intervals.

Optionally, the tail end of the balancing sleeve 20 is provided with an arcuately recessed gripping recess 23. The operator pushes the piston rod 32 by holding the groove 23, which is more convenient.

Optionally, a plurality of circular hollow holes 14 are uniformly distributed on the circular magnetic sheet 13 to ensure that air on two sides of the circular magnetic sheet 13 is communicated, and air pressure on two sides of the circular magnetic sheet 13 is uniform, so that the circular magnetic sheet 13 can be fixed in front of the magnetic baffle 12 under magnetic adsorption, the push-pull process of the push-in plug 30 cannot be influenced, namely, after the sampling needle 10 is inserted into tumor tissue, a tumor body cannot be prevented from entering the sampling needle 10 and smoothly and completely reaching the circular magnetic sheet 13, and the push-in plug 30 cannot be prevented from pushing out the tumor body in the sampling needle 10; in addition, the air pressure on the two sides of the circular magnetic sheet 13 is uniform, so that the possibility of the circular magnetic sheet 13 overturning is very small.

Further, in an embodiment, a cylindrical thimble 34 extends forward from the head end of the push-in plug 30, the thimble 34 passes through the joint 21 and enters the sampling needle 10, the thimble 34 passes through the middle of the plurality of magnetic baffles 12 and abuts against the circular magnetic sheet 13, the length of the thimble 34 is equal to the length of the sampling needle 10, and the cross-sectional diameter of the thimble 34 is smaller than the gap between the plurality of magnetic baffles 12. Preferably, the magnetic baffle 12 is an arc, and the arc design can maximize the radial line of the cross section through which the thimble 34 passes under the effect of ensuring blocking, so as to prevent the damage to the whole mechanical structure due to the dislocation of the thimble 34 in use.

In this embodiment, after the sampling needle 10 is inserted into the target site of the subject, the push-in plug 30 is pushed, so that the thimble 34 crosses the joint 21 and further passes through the plane of the magnetic shield 12, and the magnetic disk 13 is pushed from the back side of the magnetic disk 1. The round magnetic sheet 13 pushes the tumor body on the head side to enter the receptor, thereby completing the inoculation process. When the thimble 34 pushes the circular magnetic sheet 13 to move and reach the steel wire 11, the circular magnetic sheet 13 will not fall off due to the blocking effect of the steel wire 11. Meanwhile, in the present embodiment, the thimble 34 and the circular magnetic sheet 13 are separately connected, so that the sampling needle 10 is replaceable.

Optionally, in this embodiment, a graduation mark is provided outside the balancing sleeve to identify the position where the thimble is pushed in.

Optionally, in this embodiment, the head end surface of the balance sleeve 20 is provided with a plurality of arc-shaped through holes 22, which ensure that the air pressure at the head side of the push-in plug 30 is always the same as the atmospheric pressure, so as to prevent the air from pushing the circular magnetic sheet 13 forward before the ejector pin 34 acts when the push-in plug 30 is pushed.

Further, in another embodiment, as shown in fig. 7, the connector 21 is in sealing fit with the balance tube sleeve 20, and the connector 21 is in sealing fit with the sampling needle 10, when sampling is performed, the push-in plug 30 is firstly pulled outwards to a first predetermined position of the balance tube 20 to form an air column between the sampling needle 10 and the push-in plug 30, then the sampling needle 10 is inserted into tumor tissue, the push-in plug 30 is pulled outwards to a second predetermined position of the balance tube to form an air pressure difference between the sampling needle 1 and the push-in plug 3, the tumor enters the inside of the sampling needle 10 to the circular position 13 under the action of the air pressure difference, then the sampling needle 10 is rotated, the steel wire 11 is used to cut the root of the tumor inside the sampling needle 10 to cut off the tumor with a predetermined length, the cut tumor is firmly adsorbed in the sampling needle 10 under the action of the pressure difference, and because of the existence of the air column and the circular magnetic sheet 13, the cut tumor body does not run into the balance sleeve 10, but stays in the sampling needle 10. Thus, the sampling needle 10 can be pulled out from the tumor tissue to complete the sampling. When inoculation is performed, the sampling needle 10 filled with tumor needs to be inserted into a target part of a recipient, then the pushing plug 30 is pushed towards the sampling needle 10 to compress the air column in the balance pipe sleeve 10, and the tumor in the sampling needle 10 is pushed out under the action of air pressure and is driven into the target part of the recipient.

In this embodiment, a graduation mark is provided outside the balancing sleeve to mark the first predetermined position and the second predetermined position.

The sampling needle head 1 can be inserted into tumor tissues, and a tumor body is taken down in a horizontal rotation mode in a constant volume mode; after the sampling needle head and the balance sleeve are assembled, the tumor body can be directly injected into the target part of the animal model. The invention overcomes the complex steps that the tumor tissue needs to be taken off in advance and plugged into the needle tube in the existing product, has the advantages of accurate constant volume, tumor body saving, slight damage to an animal model, convenient operation, simple structure, low cost, durability and replaceability and great transformation potential.

Although the present invention has been described in detail in this specification with reference to specific embodiments and illustrative embodiments, it will be apparent to those skilled in the art that modifications and improvements can be made thereto based on the present invention. Accordingly, such modifications and improvements are intended to be within the scope of the invention as claimed.

Claims

1. The PDX model tumor quantitative transplantation inoculation needle assembly is characterized by comprising a sampling needle head (10), a balance sleeve (20) and a push plug (30), wherein the sampling needle head (10) and the balance sleeve (20) are both in a cylindrical tube shape, a joint (21) communicated with an inner cavity of the balance sleeve (20) is arranged at the head end of the balance sleeve (20), the tail end of the sampling needle head (10) is embedded with the joint (21), the push plug (30) is pushed into the balance sleeve (20) from the tail end of the balance sleeve (20) and is in sliding sealing fit with the balance sleeve (20), and a steel wire (11) coincident with the cross section diameter of the sampling needle head (10) is arranged at the head end of the sampling needle head (10).

2. The PDX model tumor mass quantitative transplantation inoculation needle assembly of claim 1, wherein the head end of the sampling needle (10) has a beveled cut.

3. The PDX model tumor quantitative transplantation inoculation needle assembly of claim 1, wherein a plurality of magnetic baffles (12) for limiting are arranged in the sampling needle (10), the magnetic baffles (12) are positioned on the same cross section of the sampling needle (10), the magnetic baffles (12) are distributed around the central axis of the sampling needle (10) in a central symmetry manner, a circular magnetic sheet (13) is adsorbed on one side of the magnetic baffles (12) facing the head end of the sampling needle (10) through magnetic force, and the diameter of the circular magnetic sheet (13) is equal to or smaller than the inner diameter of the sampling needle (10).

4. The PDX model tumor quantitative transplantation inoculation needle assembly of claim 3, wherein a plurality of circular through holes (14) are uniformly distributed on the circular magnetic sheet.

5. The PDX model tumor quantitative transplantation inoculation needle assembly of claim 1, wherein the tail end of the sampling needle (10) is a cylindrical hollow insertion groove (15), the inner diameter of the insertion groove (15) is equal to or larger than the outer diameter of the joint (21), and the two are correspondingly embedded.

6. The PDX model tumor quantitative transplantation inoculation needle assembly according to claim 5, wherein two rotating handles (16) for screwing the embedding groove (15) are symmetrically arranged on the outer side of the embedding groove (15).

7. The PDX model tumor mass quantitative transplantation inoculation needle assembly of claim 3, wherein the head end of the push-in plug (30) is a rubber piston (31), and the outer diameter of the rubber piston (31) is equal to or less than the inner diameter of the balance sleeve (20); the rear part of the rubber piston (31) is connected with a piston rod (32), and the tail end of the piston rod (32) is connected with a piston handle (33) used for pushing and pulling.

8. The PDX model tumor mass quantitative transplantation inoculation needle assembly of claim 3, wherein the magnetic block (12) is arc-shaped, the head end of the push-in plug (30) extends forwards to form a cylindrical thimble (34), the thimble (34) passes through the joint (21) and enters the sampling needle (10), the thimble (34) passes through the magnetic baffle (12) and abuts against the circular magnetic sheet (13), the length of the thimble (34) is equal to that of the sampling needle (10), and the cross-sectional diameter of the thimble (34) is smaller than the gap between the magnetic baffles (12).

9. The PDX model tumor mass quantitative transplantation inoculation needle assembly of claim 8, wherein the head end face of the balance sleeve (20) is provided with two arc-shaped through holes (22).

10. The PDX model tumor mass quantitative transplantation inoculation needle assembly of claim 1, wherein the tail end of the balance sleeve (20) is provided with an arcuately recessed holding groove (23).