CN215606546U

CN215606546U - Injection and in vivo detection device for chicken embryo model and VDAs efficacy research

Info

Publication number: CN215606546U
Application number: CN202120510992.8U
Authority: CN
Inventors: 李玥; 孔平; 陈磊; 张进勇; 杜雨晴; 栗艳飞; 黄钢
Original assignee: Shanghai University of Medicine and Health Sciences
Current assignee: Shanghai University of Medicine and Health Sciences
Priority date: 2021-03-11
Filing date: 2021-03-11
Publication date: 2022-01-25
Anticipated expiration: 2031-03-11

Abstract

The utility model relates to an injection and biopsy device for a chick embryo model and performing VDAs efficacy research, which comprises a containing piece for containing chick embryos, an injection mechanism for injecting chorioallantoic vessels and a biopsy mechanism for monitoring blood perfusion changes, wherein the containing piece is provided with a containing groove formed by downward depression, a light hole penetrating through the containing piece is arranged below the containing piece and communicated with the containing groove, the injection mechanism comprises a handle-free needle head, an extension tube and a microinjection pump, one end of the extension tube is used as a first connecting end, the other end of the extension tube is used as a second connecting end, the second connecting end is connected with an injector in the microinjection pump, and the first connecting end is connected with the handle-free needle head to form clearance fit. The utility model has the following advantages and effects: can realize trace, accurate and slow administration aiming at chick embryo chorioallantoic membrane, and can detect the effects of VDAs on vascular changes and blood perfusion in real time and in vivo.

Description

Injection and in vivo detection device for chicken embryo model and VDAs efficacy research

Technical Field

The utility model relates to the technical field of medical instruments, in particular to an injection and in-vivo detection device for chicken embryo models and for VDAs efficacy research.

Background

The vascular blocking agent, called VDAs for short, can reduce blood vessels and blood flow, can respectively play different degrees of roles on normal blood vessels and tumor blood vessels, and can preferentially act on the endothelium of the tumor blood vessels and destroy the original flat structure of the tumor blood vessels by utilizing the action difference between the normal blood vessels and the formed tumor blood vessels, so that the blood vessels are narrowed, the blood supply is blocked, and the large-area tumor is subjected to ischemic necrosis, thereby having the advantages of strong tumor inhibition effect, wide anti-tumor spectrum, short action time and the like, and having important value in tumor treatment.

At present, for various preclinical researches on various VDAs, adopted experimental animals are mammals such as mice, rats, rabbits, pigs and monkeys, but have certain defects and are not more and more suitable for the requirements of future animal welfare: these experimental animals are convenient for administration via blood vessels, but model animals are expensive; waiting for a relatively long time even if the self-molding and the molding can be carried out; tumor xenograft failure is also frequently encountered in these animal models; although some immunodeficient animals are available for transplantation, they are expensive, require a higher environment for breeding, and have a very long molding time. Moreover, the observation of the before and after VDAs administration effect of the experimental animal is generally carried out by adopting two modes, one mode adopts in-vitro detection which can cause irreversible damage to the experimental animal so as to consume a large amount of the experimental animal, and the other mode adopts in-vivo dynamic detection, such as dynamic enhanced magnetic resonance imaging technology,¹⁹F magnetic resonance imaging blood oxygenAssays and dynamic bioluminescence imaging techniques, but these are very costly, difficult to operate equipment, and technically demanding for the test personnel. Therefore, there is a need for improvement in experimental animals and methods for studying VDAs in view of the time to model, species differences, cost (of animals and tests), animal welfare, and the like.

The chicken embryo is used for replacing mammals to carry out preclinical research of new drugs, not only meets the requirements of animal welfare, but also can detect living body changes, and is low in cost, high in standardization degree, short in experimental period and easy to operate, thereby being a common model organism. The chick embryo chorioallantoic membrane has abundant blood vessels, is a natural immunodeficiency host, has high success rate of trans-tumor cell transplantation, and can be used as an ideal experimental model for researches on angiopharmacology, oncology and the like.

The traditional chick embryo chorioallantoic membrane model is mainly used for research on anti-tumor angiogenesis drugs and for research on the effects of VDAs on normal blood vessels and tumor blood vessels on the chorioallantoic membrane. There is also a report on the efficacy studies of combretastatin disodium phosphate (CA4P, one of VDAs) using chick embryos, but the research focus is not on the blocking effect of "formed tumor vessels" but on the inhibition effect of "tumor angiogenesis". Therefore, research on the effects and side effects of VDAs by using chorioallantoic vessels and tumor-bearing models thereof is a blank at present, and has development space.

However, in the course of implementing the embodiments of the present application, the inventors found that the efficacy studies of the chick embryo chorioallantoic membrane model for VDAs in the prior art have at least the following problems:

first, the mode of administration. The direct injection of cardiovascular drugs into blood vessels is the most convenient and accurate mode of administration. However, due to the relatively fine limitation of blood vessels of a chick embryo chorioallantoic membrane model, gelatin sponge, qualitative filter paper or methylcellulose is mostly used as a carrier in the current experimental operation, and after the drug liquid is adsorbed, the carrier is pasted outside the chorioallantoic membrane model blood vessels for exchange absorption, so that the administration dose is not accurate enough, if the injection is carried out through a needle, the needle is difficult to manually inject, the needle can be brought out by shaking hands slightly or the needle and the weight at the back of an injector can bias and puncture the blood vessels, and because the injectable capacity of the chick embryo is very limited, a small amount of drug cannot be slowly administered manually for a long time, but if the experimental injection time is shorter than the administration time in practical application, more obvious side effects can be brought to normal blood vessels, so that the side effects after clinical administration can not be simulated correctly.

Second, observation mode. When the chorioallantoic membrane model is used for anti-tumor angiogenesis drugs, in-situ shooting is generally carried out on live chick embryos by a dissecting microscope, but images can only be used for analyzing parameters such as blood vessel density, and the like, while the VDAs pay more attention to the observation of tumor blood vessel efficacy and normal blood vessel side effects to the change of blood flow perfusion information such as pipe diameter, flow velocity, micro blood vessels and the like, so that the requirement for researching the VDAs efficacy cannot be met by the in-situ shooting mode by the dissecting microscope.

SUMMERY OF THE UTILITY MODEL

Aiming at the defects in the prior art, the utility model aims to provide an injection and in-vivo detection device for a chick embryo model and used for VDAs efficacy research, which can realize trace, accurate and slow drug delivery aiming at chorioallantoic membrane vessels and can detect the efficacy of VDAs on vascular changes and blood flow perfusion in real time and in vivo.

In order to achieve the purpose, the utility model provides the following technical scheme:

an injection and biopsy device for chick embryo model and VDAs efficacy research is characterized in that: the injection mechanism comprises a containing piece for containing chick embryos, an injection mechanism for chorioallantoic membrane blood vessel injection and a living body detection mechanism for monitoring chorioallantoic membrane blood flow perfusion changes, wherein the containing piece is provided with a containing groove formed by downward sinking, a light hole penetrating through the containing piece is arranged below the containing piece, the light hole is communicated with the containing groove, the injection mechanism comprises a handle-free needle head, an extension tube and a microinjection pump, one end of the extension tube is used as a first connecting end, the other end of the extension tube is used as a second connecting end, the second connecting end is connected with an injector in the microinjection pump, the first connecting end is connected with the handle-free needle head to form clearance fit, the second connecting end is a cast-molded interface, and the interface is sleeved in the injector in the microinjection pump.

The utility model is further configured to: the living body detection mechanism comprises a laser speckle blood flow imaging instrument, an image processing workstation and a support, the laser speckle blood flow imaging instrument is fixed above the accommodating piece through the support and is vertically opposite to the accommodating groove, the laser speckle blood flow imaging instrument is used for collecting blood perfusion images of chorioallantoic membrane and transmitting image information to the image processing workstation, the image processing workstation is used for analyzing the blood flow images in real time, an opening is arranged on the side wall of the accommodating piece, and the opening is communicated with the accommodating groove.

The utility model is further configured to: the bottom of the containing groove is provided with a heating mechanism, the heating mechanism is used for ensuring that the chick embryos are in a normal physiological state, and the heating mechanism is attached to the bottom of the containing groove.

The utility model is further configured to: the shape of the accommodating groove is matched with that of the small end of the chick embryo, the accommodating groove and the chick embryo form a limit fit, and the accommodating piece is made of soft silica gel.

The utility model is further configured to: the outer diameter specification of the needle head without the handle is 0.3mm, the thickness of the extension tube is 0.5mm, and the extension tube is made of flexible materials.

The utility model is further configured to: the accommodation groove bottom with the light trap orientation the tip of accommodation groove is laminated mutually.

Compared with the prior art, the utility model has the beneficial effects that:

because the accommodating part, the injection mechanism and the living body detection mechanism are arranged, the chick embryos can be accommodated through the accommodating groove arranged in the accommodating part, the needle head of the chorioallantoic membrane blood vessel is prevented from slipping to affect injection during injection through the non-handle needle head and the flexible extension tube in the injection mechanism, manual injection is replaced by the micro-injection pump in the injection mechanism, thereby improving the injection precision and reducing the occurrence of misoperation, and the injection speed and the injection amount can be controlled by using the micro-injection pump before injection, thereby realizing the micro-injection and the slow injection of the chick embryos, so as to correctly simulate the side effect after clinical administration, monitor the blood perfusion condition in real time through the living body detection mechanism during injection, therefore, the technical problems that the injection precision is low when the injection is performed on the chick embryo, the side reaction after clinical administration cannot be correctly simulated due to the fact that slow injection cannot be performed, and the observation requirement for VDAs efficacy research cannot be met are effectively solved.

Drawings

FIG. 1 is a schematic view of the injection mechanism according to the present invention;

FIG. 2 is a schematic diagram of a positional relationship between a laser speckle blood flow imager and a containing member according to the present invention;

FIG. 3 is a schematic side view of the receiving member from a different perspective;

fig. 4 is a schematic sectional view of the receiving member of the present invention.

Detailed Description

The technical solutions of the present invention will be described clearly and completely with reference to the accompanying drawings, and it should be understood that the described embodiments are some, but not all embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

In the description of the present invention, it should be noted that the terms "center", "upper", "lower", "left", "right", "vertical", "horizontal", "inner", "outer", etc., indicate orientations or positional relationships based on the orientations or positional relationships shown in the drawings, and are only for convenience of description and simplicity of description, but do not indicate or imply that the device or element being referred to must have a particular orientation, be constructed and operated in a particular orientation, and thus, should not be construed as limiting the present invention. Furthermore, the terms "first," "second," and "third" are used for descriptive purposes only and are not to be construed as indicating or implying relative importance.

As shown in figures 1 to 4, the utility model discloses an injection and biopsy device for a chicken embryo model and performing VDAs efficacy research, comprising a containing part 1 for containing chicken embryos, an injection mechanism 2 for chorioallantoic membrane vascular injection and a biopsy mechanism for monitoring blood perfusion changes, wherein the containing part 1 is provided with a containing groove 3 formed by downward depression, a light hole 4 penetrating through the containing part 1 is arranged below the containing part 1, the light hole 4 is communicated with the containing groove 3, the injection mechanism 2 comprises a handleless needle 21, an extension tube 22 and a micro-injection pump 23, one end of the extension tube 22 is used as a first connecting end 221, the other end is used as a second connecting end 222, the second connecting end 222 is connected with an injector 231 in the micro-injection pump 23, the first connecting end 221 is connected with the handleless needle 21 to form clearance fit, so as to facilitate the connection of the extension tube 22 and the injector 231, the second connecting end 222 is a cast-molded interface, the interface is sleeved in an injector 231 in the micro-injection pump 23, when injecting blood vessels of chorioallantoic membrane of chicken embryo, the chicken embryo can stand in the accommodating groove 3, and when the chicken embryo is placed in the accommodating groove 3, the strong light source can enter the accommodating groove 3 through the light hole 4 communicated with the accommodating groove 3, so that the blood vessels in the chicken embryo can be clearly shown, the injection precision can be improved, errors during injection can be effectively prevented, the injection speed and the injection amount can be controlled by using the micro-injection pump 23 before injection, the slow constant-flow injection of the chicken embryo can be realized, the characteristic that the chicken embryo can bear small injection dosage is solved, the false positive result caused by VDAs (VDAs) caused by rapid administration on the blood vessels is avoided, the side reaction after clinical administration can be correctly simulated, and the blood flow change condition can be analyzed in real time through an analysis mechanism after injection, therefore, the research on the efficacy of VDAs is facilitated, when the chick embryo needs to be moved and is subjected to more comprehensive observation and analysis by using the living body detection mechanism, the weight of the handheld part of the needle is reduced by removing the handle of the needle 21 without the handle, so that the needle 21 without the handle is prevented from slipping out of the blood vessel in the movement process of the chick embryo, the observation and analysis are facilitated, the needle 21 without the handle and the micro injection pump 23 are connected through the extension tube 22, the movement range of the chick embryo is further enlarged on the premise that the needle 21 without the handle does not depart from the blood vessel, the observation and analysis are facilitated, the first connecting end 221 of the extension tube 22 is connected with the needle 21 without the handle to form clearance fit, the needle 21 without the handle and the extension tube 22 are convenient to mount or dismount, and the injection mode of the medicine can be switched.

The in-vivo detection mechanism comprises a laser speckle blood flow imager 5, an image processing workstation and a bracket 6, wherein the laser speckle blood flow imager 5 is fixed above the accommodating part 1 through the bracket 6 and is vertically opposite to the accommodating groove 3, the laser speckle blood flow imager 5 is used for collecting blood flow images and transmitting the image information to the image processing workstation, the image processing workstation is used for analyzing the blood flow images in real time, the side wall of the accommodating part 1 is provided with an opening 7, the opening 7 is communicated with the accommodating groove 3, the blood flow rate value and the blood vessel diameter can be analyzed more clearly and more rapidly through the laser speckle blood flow imager 5, the operation is simple and convenient, the cost is low, the side wall of the accommodating part 1 is provided with the opening 7 communicated with the accommodating groove 3, the injection on the side wall of the chick embryo can be realized, and the laser speckle blood flow imager 5 is arranged above the accommodating groove 3, and then can realize injecting the chicken embryo lateral wall simultaneously, chicken embryo top laser speckle blood flow imager 5 gathers the blood flow information of chicken embryo, and then through going on injection and analysis in step, has reduced the operating procedure, the operation of being convenient for.

The bottom of the accommodating tank 3 is provided with a heating mechanism (not shown in the figure), the heating mechanism (not shown in the figure) is used for ensuring that the chick embryo is in a normal physiological state, the heating mechanism (not shown in the figure) is attached to the bottom of the accommodating tank 3, and the chick embryo is heated by the heating mechanism (not shown in the figure) to be at a constant temperature of 37 ℃, so that the chick embryo can be ensured to be in a normal physiological state, the chick embryo is prevented from being reduced, slowed down and even stopped metabolism due to temperature loss, the change of blood flow is caused, and the information collected by the analysis mechanism is inaccurate.

The shape of the accommodating groove 3 is matched with the shape of the small end of the chick embryo to form the limit fit between the chick embryo and the accommodating part 1, and the accommodating part 1 is made of soft silica gel, so that the accommodating groove 3 can be more attached to the chick embryo, and the chick embryo is further prevented from being mistakenly moved in the injection process to reduce the injection precision.

The outer diameter specification of the handle-free needle 21 is 0.3mm, the thickness of the extension tube 22 is a thin-wall component of 0.5mm, the extension tube 22 is made of high-temperature-resistant flexible materials, the handle-free needle 21 of the specification is thin, the blood vessel can be conveniently punctured, the use is convenient, the texture of the extension tube 22 is soft, the stress can be reduced, therefore, under the condition that the extension tube 22 is not stretched straightly, the chick embryo can be freely moved, the handle-free needle 21 can still be kept in the blood vessel, and the handle-free needle 21 is prevented from falling off.

The bottom of the accommodating groove 3 is attached to the end part of the accommodating groove 3 facing the light hole 4, so that the highlight light source can be completely driven into the accommodating groove 3, the blood vessels on the chick embryo can be more clearly displayed, and the injection precision is improved.

The present embodiment is only for explaining the present invention, and it is not limited to the present invention, and those skilled in the art can make modifications of the present embodiment without inventive contribution as needed after reading the present specification, but all of them are protected by patent law within the scope of the claims of the present invention.

Claims

1. An injection and biopsy device for chick embryo model and VDAs efficacy research, characterized in that: the injection device comprises a containing part for containing chick embryos, an injection mechanism for injecting blood vessels of chick chorioallantoic membranes and a living body detection mechanism for monitoring blood flow perfusion changes of the chorioallantoic membranes, wherein the containing part is provided with a containing groove formed by downward sinking, a light hole penetrating through the containing part is arranged below the containing part and communicated with the containing groove, the injection mechanism comprises a handle-free needle head, an extension pipe and a microinjection pump, one end of the extension pipe is used as a first connecting end, the other end of the extension pipe is used as a second connecting end, the second connecting end is connected with an injector in the microinjection pump, the first connecting end is connected with the handle-free needle head to form clearance fit, the second connecting end is a cast-molded interface, and the interface is sleeved in the injector in the microinjection pump.

2. An injection and biopsy device for chick embryo model VDAs efficacy studies according to claim 1, wherein: the living body detection mechanism comprises a laser speckle blood flow imaging instrument, an image processing workstation and a support, the laser speckle blood flow imaging instrument is fixed above the accommodating piece through the support and is vertically opposite to the accommodating groove, the laser speckle blood flow imaging instrument is used for collecting blood perfusion images of chorioallantoic membrane and transmitting image information to the image processing workstation, the image processing workstation is used for analyzing the blood flow images in real time, an opening is arranged on the side wall of the accommodating piece, and the opening is communicated with the accommodating groove.

3. An injection and biopsy device for chick embryo model VDAs efficacy studies according to claim 1, wherein: the bottom of the containing groove is provided with a heating mechanism, the heating mechanism is used for ensuring that the chick embryos are in a normal physiological state, and the heating mechanism is attached to the bottom of the containing groove.

4. An injection and biopsy device for chick embryo model and VDAs efficacy studies according to claim 3, wherein: the accommodation groove bottom with the light trap orientation the tip of accommodation groove is laminated mutually.

5. An injection and biopsy device for chick embryo model VDAs efficacy studies according to claim 1, wherein: the shape of the accommodating groove is matched with that of the small end of the chick embryo, the accommodating groove and the chick embryo form a limit fit, and the accommodating piece is made of soft silica gel.

6. An injection and biopsy device for chick embryo model VDAs efficacy studies according to claim 1, wherein: the outer diameter specification of the needle head without the handle is 0.3mm, the thickness of the extension tube is 0.5mm, and the extension tube is made of flexible materials.