CN210472126U - In vivo drug screening system - Google Patents

In vivo drug screening system Download PDF

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Publication number
CN210472126U
CN210472126U CN201920180201.2U CN201920180201U CN210472126U CN 210472126 U CN210472126 U CN 210472126U CN 201920180201 U CN201920180201 U CN 201920180201U CN 210472126 U CN210472126 U CN 210472126U
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box body
inner container
drug screening
screening system
lower box
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CN201920180201.2U
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周哲
尹焕才
付威威
潘力
陈名利
刘敏
朱海龙
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Suzhou Institute of Biomedical Engineering and Technology of CAS
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Suzhou Institute of Biomedical Engineering and Technology of CAS
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Abstract

The utility model discloses an internal medicine live body screening system, include: the device comprises a lower box body, an upper box body arranged on the upper part of the lower box body, an electron multiplication CCD arranged in the upper box body, light-shading gloves arranged on the lower box body, an inner container arranged in the lower box body, and a biological placing constant temperature table, an exciting light source, a PMT weak light detection counting device, a lens and a camera arranged in the inner container. The in-vivo drug screening system provided by the utility model can meet the requirements of rapid measurement and accurate counting of local weak light in the animal body, and can also observe and detect the whole animal body; when local precise measurement is carried out, the direct living body measurement can be realized without anesthesia on animals, the luminous value is stable, the result is accurate, and the measured data value can be directly used for objective evaluation of medicines without other processing; the system can effectively overcome the defects of the existing method, improve the efficiency of drug screening and reduce the cost of drug research and development.

Description

In vivo drug screening system
Technical Field
The utility model relates to a medicine development field, in particular to internal medicine live body screening system.
Background
With the practical use of antibacterial agents such as antibiotics, the mortality rate caused by microbial infection is effectively controlled, but the problem of drug resistance associated therewith is becoming more serious. Infections caused by drug-resistant pathogens have become the most troublesome problem facing clinicians. The more cruel reality is that the research and development speed of corresponding new drugs is slow. In the case of tuberculosis, only 2 new anti-TB drugs have been approved worldwide in the last 60 years and are restricted for potential risks. Therefore, the development of new antibacterial drugs is a necessary trend, otherwise, the health of the whole human being is greatly threatened by the danger of no drug availability after several years.
At present, the more commonly used drug screening process comprises a plurality of links such as animal infection, drug administration, animal sacrifice, organ grinding, viable bacteria counting and the like, and has the disadvantages of complex operation, long drug development period and high cost. In use, due to the lack of reasonable process monitoring means, whether the animal is infected successfully or not and the drug treatment effect after drug administration and the like cannot be monitored, and the method can only be judged according to the counting result of the dead bacteria of the animal. Moreover, the concentration of the cells before counting is unknown, so that it is very difficult to obtain the correct number of cells, the accuracy of the counting result is poor, and the result cannot be obtained sometimes. When the concentration of the drug in the animal tissue is higher, the concentration of the drug on the flat plate after the plate is paved can be influenced, the growth of thalli on the flat plate is interfered, and the deviation of the counting result is extremely large. The relative efficacy evaluation results can only be obtained by continuous repetition and using a statistical method. Repeated experiments also resulted in a cost increase. The key scientific problem that the in vivo drug screening technology based on the thallus counting method has low system accuracy is not solved. At present, some antibacterial drug screening systems based on luminous bacteria exist, the imaging systems of the devices can detect the luminous signals of the animal bodies, but the acquired images are pseudo-color and cannot give specific objective luminous values, the later data analysis can be finished only by means of third-party software, and a consistency tool is lacked among multiple groups of data. And because the time required by exposure imaging is long, animals need to be anesthetized during imaging detection, and the luminous intensity of the animals before and after anesthesia has great influence. The operator found that the luminescence value of the animals could be reduced by as much as 30% with the increase of the anesthesia time, and that the inconsistency of the detection time after anesthesia could result in a larger deviation between the measured data. The current instrument can not stably measure the luminous value of the whole living animal and can not meet the requirement of accurately measuring the local luminous value of the animal, and the measurement output data has great deviation from the actual value, so that the deviation is great when the action of newly developed drugs is actually judged.
The main defects of the prior art are as follows: the conventional commonly used anatomical calculation and statistics method has the disadvantages of complex operation, long medicament development period, high cost and large counting result deviation. The existing in-vivo drug screening instrument cannot stably determine the luminous value of the whole living animal and cannot meet the requirement of accurately determining the local luminous value of the animal, and the deviation of the data output by measurement compared with the actual result is also very large, so that the deviation is larger when the action of newly developed drugs is actually judged.
SUMMERY OF THE UTILITY MODEL
The utility model aims to solve the technical problem that to the not enough among the above-mentioned prior art, provide a simple structure, multiple functional internal medicine live body screening system. The device can meet the requirements of rapid measurement and accurate counting of local weak light in the animal body, and can also carry out overall observation and detection on the weak light in the animal body. When local precise measurement is carried out, the animal can be directly measured in vivo without anesthesia, the luminous value is stable, the result is accurate, and the measured data value can be directly used for objective evaluation of the medicine without other processing.
In order to solve the technical problem, the utility model discloses a technical scheme is: an in vivo drug screening system comprising: the device comprises a lower box body, an upper box body arranged on the upper part of the lower box body, an electron multiplication CCD arranged in the upper box body, light-shading gloves arranged on the lower box body, an inner container arranged in the lower box body, and a biological placing constant temperature table, an exciting light source, a PMT weak light detection counting device, a lens and a camera arranged in the inner container.
Preferably, the upper end of the lens is connected with the electron multiplication CCD, and the lower end of the lens penetrates through the upper box body, the lower box body and the preformed holes in the inner container and extends into the inner container.
Preferably, go up the internal mutual isolation setting of box and lower box, still be provided with radiator fan, switching power supply, control mainboard, data line adapter and power adapter in going up the box.
Preferably, the inner container is fixedly embedded in the inner wall of the lower box body; the biological placing constant temperature table is arranged in the middle of the bottom of the inner container and corresponds to the position right below the lens; the PMT weak light detection counting device is arranged on the inner wall of the left side of the inner container; the excitation light source is arranged on the inner wall of the upper right side of the inner container, and the center of a light spot of the excitation light source irradiates on the biological placing constant temperature table.
Preferably, a camera base is arranged on the upper portion of the inner wall of the inner container, and the camera is arranged on the camera base.
Preferably, the lower box body is provided with a left box door and a right box door, and the left box door and the right box door are both provided with door locks.
Preferably, a photoelectric switch is further disposed on the lower box body to detect opening and closing of the box door.
Preferably, the inner wall edges of the left box door and the right box door are both provided with light-resistant sealing strips.
Preferably, the light-resistant glove is arranged in the right box door and extends into the inner container.
Preferably, a large round chamfer is arranged inside the inner container.
The utility model has the advantages that: the in-vivo drug screening system provided by the utility model can meet the requirements of rapid measurement and accurate counting of local weak light in the animal body, and can also observe and detect the whole animal body; when local precise measurement is carried out, the direct living body measurement can be realized without anesthesia on animals, the luminous value is stable, the result is accurate, and the measured data value can be directly used for objective evaluation of medicines without other processing; the system can effectively overcome the defects of the existing method, improve the efficiency of drug screening and reduce the cost of drug research and development. The system can be used for screening antibacterial drugs, and also has other applications, such as rapid detection of in vivo effects of antiviral (such as influenza virus) drugs, vaccines and antibodies; efficient research of virulence related genes of mycobacterium tuberculosis (Mtb); and the effect in the antitumor drug can be rapidly detected.
Drawings
FIG. 1 is a schematic diagram of the internal structure of the in vivo drug screening system of the present invention;
FIG. 2 is a schematic diagram of the external structure of the in vivo drug screening system of the present invention;
FIG. 3 is a schematic diagram of the in vivo drug screening system according to the present invention;
fig. 4 is a schematic block diagram of the in vivo drug screening system of the present invention.
Description of reference numerals:
1. an inner container; 2. a lower box body; 3. PMT weak light detection counting device; 4. an upper box body; 5. a switching power supply; 6. a control main board; 7. a photoelectric switch; 8. electron multiplying CCD; 9. a data line adapter; 10. a heat radiation fan; 11. a power supply adapter; 12. a lens; 13. a camera; 14. a camera head base; 15. an excitation light source; 16. a door lock; 17. a light-resistant glove; 18. placing a constant temperature platform for the organism; 19. a right box door; 20. a left box door; 21. an observation window; 22. a workstation.
Detailed Description
The present invention is further described in detail below with reference to examples so that those skilled in the art can implement the invention with reference to the description.
It will be understood that terms such as "having," "including," and "comprising," as used herein, do not preclude the presence or addition of one or more other elements or groups thereof.
As shown in fig. 1 to 3, an in vivo drug screening system of the present embodiment includes: the biological light source device comprises a lower box body 2, an upper box body 4 arranged on the upper part of the lower box body 2, an electron multiplying CCD8(EMCCD) arranged in the upper box body 4, a light-shading glove 17 arranged on the lower box body 2, an inner container 1 arranged in the lower box body 2, and a biological placing constant temperature table 18, an exciting light source 15, a PMT weak light detection counting device 3, a lens 12 and a camera 13 which are arranged in the inner container 1. The upper end of the lens 12 is connected with the electron multiplication CCD8, and the lower end passes through the upper box 4, the lower box 2 and the preformed holes on the inner container 1 and extends into the inner container 1. Fig. 3 is a schematic diagram of a schematic structure of a system according to an embodiment of the present invention.
In one embodiment, a workstation 22 is also included, and the workstation 22 may be a computer used for system control and data processing.
The whole structure adopts a vertical separation type design, namely the interiors of the upper box body 4 and the lower box body 2 are mutually isolated; go up and be used for placing electrical components and parts in the box 4, be used for biological detection in the box 2 down, realize the electrical separation, avoid the biological detection environment to the influence of electrical stability, avoided electrical components to measuring result's influence simultaneously, go up box 4 through the fix with screw under on the box 2. Lower box 2 adopts inside and outside disconnect-type design, and inner bag 1 is fixed to be inlayed on 2 inner walls of lower box, and biological detection and control etc. are accomplished in inner bag 1, and the cable of the various components and parts of fixed in inner bag 1 all is connected to on the control mainboard 6 in last box 4 through the intermediate layer between inner bag 1 and the lower box 2 to guarantee the inside clean and tidy of inner bag 1, the inside big fillet design of adoption of inner bag 1 is convenient for clean simultaneously.
Referring to fig. 2, the internal structure of the in vivo drug screening system of the present invention is schematically illustrated.
Wherein, still be provided with radiator fan 10, switching power supply 5, control mainboard 6, data line adapter 9 and power adapter 11 in the upper box body 4. Data line adapter 9, radiator fan 10, power adapter 11 are installed fixedly on the inner wall in last box 4, conveniently carry out the interactive connection of data, power etc. with external workstation 22.
Wherein, the biological placing constant temperature table 18 is arranged in the middle of the bottom of the inner container 1 and corresponds to the right lower part of the lens 12; the PMT weak light detection counting device 3 is arranged on the inner wall of the left side of the liner 1, so that a worker can conveniently operate the liner by the right hand of the light-shading glove 17; the excitation light source is arranged on the inner wall of the right upper side of the inner container 1, and the center of the light spot of the excitation light source irradiates on the biological placing constant temperature table 18.
Wherein, the inner wall upper portion of inner bag 1 is provided with camera base 14, and camera 13 sets up on camera base 14. The camera 13 is used for shooting and monitoring the condition in the liner 1.
Wherein, the lower box body 2 is provided with a left box door 20 and a right box door 19, and the left box door 20 and the right box door 19 are both provided with a door lock 16 for locking the box doors. The lower box body 2 is also provided with a photoelectric switch 7 to detect the opening and closing of the box door.
The inner wall edges of the left box door 20 and the right box door 19 are both provided with light-proof sealing strips. The light-resistant sealing strip is embedded into the square-shaped structure at the edge of the inner container 1, so that the effect of completely sealing and protecting the inner container 1 of the lower box body 2 from light is achieved.
Wherein, the light-resistant glove 17 is arranged in the right box door 19 and extends into the inner container 1. The right hand of the worker can grab the operation experimental object conveniently. The left box door 20 is provided with an observation window 21, which is convenient for the operation of the working personnel.
Referring to fig. 4, which is a schematic block diagram of the operation in an embodiment of the present invention, an experimental subject (mouse) can perform both the whole imaging measurement and the local luminescence measurement, and the workstation 22 (in this embodiment, a computer) performs data acquisition, processing and analysis, obtains a detection result, and outputs the detection result in a curve or report form; the computer can also display the monitoring picture of the camera 13 at the same time,
the utility model discloses both can carry out the whole measurement of subject, can carry out local accurate measurement again. In an embodiment, the utility model discloses a workflow:
when large-batch screening is carried out in the early stage of drug development, the system design of the utility model is utilized to carry out preliminary screening, firstly, luminous strains are injected into the bodies of the small animals, the small animals are fixed and placed on the biological placing constant temperature table 18 after a certain time, the box door is closed, no external stray light enters the inner container 1, and then preliminary rough photon counting is carried out through EMCCD (electron multiplying CCD 8); injecting the developed drugs into the small animals, taking out the small animals for stocking for a certain time, roughly counting photons through EMCCD (electron multiplying CCD8), comparing the strain quantity change of two times, and screening out the drugs with certain drug effect from a large amount of developed drugs;
accurate measurements are required to further determine whether a pharmaceutically effective drug meets expected requirements; through the utility model discloses can carry out the accurate medicine screening of small batch again, at this moment at first in injecting the little animal of luminous bacterial, the little animal is fixed after the certain time and is placed on biological placing constant temperature platform 18, close the chamber door, it gets into to guarantee that no external stray light in inner bag 1, then carry out photon counting and observe the position that the bacterial infects the little animal through EMCCD (electron multiplication CCD8), then open infrared surveillance camera 13, under the direction of camera 13, operating personnel stretches into hand in box inner bag 1 through light-resistant gloves 17, grasp the little animal, it is attached on PMT weak light detection counting assembly 3 to infect the position, close infrared camera 13, open PMT weak light detection counting assembly 3, its quick accurate detection calculates the thallus number at this position, this testing process is about 3 seconds, and is swift accurate; then injecting the developed medicine into the small animal, taking out the small animal and stocking for a certain time, counting by a PMT weak light detection counting device 33, comparing the number change of the strains for two times, and explaining the efficacy of the developed medicine through accurate data. The whole screening process is quick and accurate, the efficiency and the accuracy of drug screening can be improved, and the drug research and development cost is reduced.
While the embodiments of the invention have been disclosed above, it is not limited to the applications listed in the description and the embodiments, which are fully applicable in all kinds of fields where the invention is suitable, and further modifications may readily be made by those skilled in the art, and the invention is therefore not limited to the specific details without departing from the general concept defined by the claims and the scope of equivalents.

Claims (10)

1. An in vivo drug screening system, comprising: the device comprises a lower box body, an upper box body arranged on the upper part of the lower box body, an electron multiplication CCD arranged in the upper box body, light-shading gloves arranged on the lower box body, an inner container arranged in the lower box body, and a biological placing constant temperature table, an exciting light source, a PMT weak light detection counting device, a lens and a camera arranged in the inner container.
2. The in vivo drug screening system of claim 1, wherein the upper end of the lens is connected to the electron multiplying CCD, and the lower end of the lens passes through the upper box, the lower box and the preformed holes on the inner container and extends into the inner container.
3. The in vivo drug screening system of claim 1, wherein the upper and lower cases are isolated from each other, and the upper case further comprises a heat dissipation fan, a switching power supply, a control motherboard, a data line adapter and a power adapter.
4. The in vivo drug screening system of claim 1, wherein the inner container is fixedly embedded in the inner wall of the lower box body; the biological placing constant temperature table is arranged in the middle of the bottom of the inner container and corresponds to the position right below the lens; the PMT weak light detection counting device is arranged on the inner wall of the left side of the inner container; the exciting light source is arranged on the inner wall of the upper right side of the inner container, and the center of a light spot of the exciting light source irradiates on the biological placing constant temperature table.
5. The in vivo drug screening system of claim 4, wherein a camera base is disposed on an upper portion of an inner wall of the inner container, and the camera is disposed on the camera base.
6. The in vivo drug screening system of claim 1, wherein the lower box body is provided with a left box door and a right box door, and the left box door and the right box door are both provided with a door lock.
7. The in vivo drug screening system of claim 6, wherein the lower box is further provided with a photoelectric switch for detecting the opening and closing of the box door.
8. The in vivo drug screening system of claim 7, wherein the inner wall edges of the left and right box doors are provided with light-proof sealing strips.
9. The in vivo drug screening system of claim 8, wherein the light-resistant glove is disposed in the right box door and extends into the inner container.
10. The in vivo drug screening system of claim 1, wherein a large round chamfer is arranged inside the inner container.
CN201920180201.2U 2019-02-01 2019-02-01 In vivo drug screening system Active CN210472126U (en)

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109998480A (en) * 2019-02-01 2019-07-12 中国科学院苏州生物医学工程技术研究所 Internal drug Vivo Studies on Screening system

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN109998480A (en) * 2019-02-01 2019-07-12 中国科学院苏州生物医学工程技术研究所 Internal drug Vivo Studies on Screening system

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