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CN113855303A - Brain dosing observation skull window and experimental animal fixing observation device - Google Patents

Brain dosing observation skull window and experimental animal fixing observation device Download PDF

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Publication number
CN113855303A
CN113855303A CN202111231677.2A CN202111231677A CN113855303A CN 113855303 A CN113855303 A CN 113855303A CN 202111231677 A CN202111231677 A CN 202111231677A CN 113855303 A CN113855303 A CN 113855303A
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China
Prior art keywords
observation
administration
hole
light
brain
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CN202111231677.2A
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Chinese (zh)
Inventor
欧阳雨林
董文秀
詹阳
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Shenzhen Institute of Advanced Technology of CAS
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Shenzhen Institute of Advanced Technology of CAS
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Priority to CN202111231677.2A priority Critical patent/CN113855303A/en
Publication of CN113855303A publication Critical patent/CN113855303A/en
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61DVETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
    • A61D3/00Appliances for supporting or fettering animals for operative purposes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/0059Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
    • A61B5/0082Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence adapted for particular medical purposes
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61DVETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
    • A61D3/00Appliances for supporting or fettering animals for operative purposes
    • A61D2003/003Appliances for supporting or fettering animals for operative purposes with head or neck restraining means

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  • Life Sciences & Earth Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Pathology (AREA)
  • Medical Informatics (AREA)
  • Molecular Biology (AREA)
  • Surgery (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Biomedical Technology (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Animal Husbandry (AREA)
  • Wood Science & Technology (AREA)
  • Zoology (AREA)
  • Endoscopes (AREA)

Abstract

The invention discloses a brain administration observation skull window and an experimental animal fixed observation device, the brain administration observation skull window comprises a body and a light-transmitting plate, a protruding part is arranged on the body, a light-transmitting hole and a first through hole are arranged on the end surface of the protruding part, a second through hole is arranged on the peripheral surface of the protruding part, the first through hole and the second through hole are used for being matched with an administration tube of an administration pump, and the light-transmitting plate is matched on the protruding part to seal the light-transmitting hole. The brain administration observation skull window can not only carry out accurate local administration without directly exposing tissues, but also can simultaneously carry out microscopic imaging, can also realize repeated administration and repeated observation at any time, and has simple operation and convenient use.

Description

Brain dosing observation skull window and experimental animal fixing observation device
Technical Field
The invention relates to the technical field of animal experiment devices, in particular to a brain administration observation skull window and an experimental animal fixed observation device.
Background
The brain is the most complex organ of the human body, and research methods for the brain are continuously updated and advanced. At present, a double/multi-photon microscope adopts near-infrared ultrafast laser as an excitation light source, and is particularly suitable for real-time imaging of living brain nerve cells, glial cells, cerebral blood flow, tissue oxidative metabolism and the like in the field of neuroscience due to small cytotoxicity and deeper penetration of a sample. To date, dual/multi-photon imaging has become an important indispensable experimental means in brain science research, and more experimental devices matched with dual/multi-photon microscope in vivo imaging are urgently needed.
In the process of double/multiphoton living brain imaging, a brain mounting head frame of an experimental object is fixed to ensure the stability of an observation plane image of an animal brain so as to obtain a long-time high-quality imaging image. In an imaging experiment for in-vivo acute stimulation administration, except for mounting a fixed head frame, an acute operation craniotomy window is usually adopted, and double/multi-photon imaging is carried out after a medicament or a stimulant is dripped on the surface of brain tissue; or after the fixed head frame is installed, the medicine is administered and the surface of the skull is covered with a glass head window for observation.
At present, the acute windowing method has the problems of easy activation of cell exposure, uncontrollable concentration of liquid medicine, corrosion to an objective lens and the like in the observation process; the method of installing a glass head window has problems that the administration of the drug cannot be repeated, and the observation cannot be performed at the same time, which leads to complicated operation.
Disclosure of Invention
The invention aims to provide a brain administration observation skull window which can not only carry out accurate local administration without directly exposing tissues but also simultaneously carry out microscopic imaging, can also realize repeated administration and repeated observation at any time, and has simple operation and convenient use.
The second purpose of the invention is to provide an experimental animal fixing observation device, which can fix the experimental animal during administration observation, and is convenient to operate and use.
In order to achieve the technical effects, the technical scheme of the invention is as follows:
the invention discloses a cranial window for brain administration observation, which comprises: the drug delivery pump comprises a body, wherein a bulge is arranged on the body, a light hole and a first through hole are formed in the end face of the bulge, a second through hole is formed in the peripheral face of the bulge, and the first through hole and the second through hole are used for being matched with a drug delivery pipe of the drug delivery pump; and the light-transmitting plate is matched on the protruding part to cover the light-transmitting hole.
In some embodiments, the end surface of the protruding portion is provided with a fitting groove disposed around the light-transmitting hole, and the light-transmitting plate is fitted in the fitting groove.
In some specific embodiments, the light-transmitting plate is in interference fit with the matching groove, or the light-transmitting plate is bonded in the matching groove.
In some embodiments, the body is further provided with a fixing hole, and a fixing piece for fixing the head of the experimental subject penetrates through the fixing hole.
In some specific embodiments, the fixing holes are multiple, and the fixing holes are uniformly spaced around the protruding portion.
In some embodiments, the light-transmissive plate comprises a glass plate or a transparent resin plate.
The invention also discloses a fixed observation device for experimental animals, which comprises the cerebral administration observation skull window, a fixing frame and an administration pump, wherein the administration pump is connected with the administration pipe, and the cerebral administration observation skull window is arranged on the fixing frame.
In some embodiments, the experimental animal fixation observation device further comprises an adjusting mechanism, wherein the adjusting mechanism is connected with the body and is used for adjusting the height of the body.
In some specific embodiments, the adjustment mechanism comprises: the adjusting block is provided with a threaded hole; the adjusting knob is provided with a stud matched with the threaded hole, and one end of the stud is matched on the body.
In some specific embodiments, the number of the adjusting mechanisms is two, and the two adjusting mechanisms are respectively connected to two ends of the body.
Additional aspects and advantages of the invention will be set forth in part in the description which follows and, in part, will be obvious from the description, or may be learned by practice of the invention.
Drawings
FIG. 1 is a schematic structural diagram of a cranial window for observing administration to a brain according to an embodiment of the present invention;
FIG. 2 is a schematic structural view of a window with a light-transmitting plate removed for a drug administration observation skull of a brain according to an embodiment of the present invention;
FIG. 3 is a schematic structural diagram of a fixed observation device for experimental animals according to an embodiment of the present invention;
fig. 4 is a schematic structural diagram of an adjusting mechanism of the experimental animal fixing observation device according to the embodiment of the present invention.
Reference numerals:
1. a body; 11. a projection; 111. a light-transmitting hole; 112. a first perforation; 113. a second perforation; 114. a mating groove; 12. a fixing hole;
2. a light-transmitting plate;
3. a fixed mount;
4. an adjustment mechanism; 41. an adjusting block; 42. adjusting a knob;
5. a drug delivery pump; 51. an administration tube.
Detailed Description
In order to make the technical problems solved, the technical solutions adopted and the technical effects achieved by the present invention clearer, the technical solutions of the present invention are further described below by way of specific embodiments with reference to the accompanying drawings.
In the description of the present invention, it is to be understood that the terms "central," "longitudinal," "lateral," "length," "width," "thickness," "upper," "lower," "front," "rear," "left," "right," "vertical," "horizontal," "top," "bottom," "inner," "outer," "clockwise," "counterclockwise," "axial," "radial," "circumferential," and the like are used in the orientations and positional relationships indicated in the drawings for convenience in describing the invention and to simplify the description, and are not intended to indicate or imply that the referenced device or element must have a particular orientation, be constructed and operated in a particular orientation, and are not to be considered limiting of the invention.
Furthermore, features defined as "first" and "second" may explicitly or implicitly include one or more of the features for distinguishing between descriptive features, non-sequential, non-trivial and non-trivial. In the description of the present invention, "a plurality" means two or more unless otherwise specified.
In the description of the present invention, it should be noted that, unless otherwise explicitly specified or limited, the terms "mounted," "connected," and "connected" are to be construed broadly, e.g., as meaning either a fixed connection, a removable connection, or an integral connection; can be mechanically or electrically connected; they may be connected directly or indirectly through intervening media, or they may be interconnected between two elements. The specific meanings of the above terms in the present invention can be understood in specific cases to those skilled in the art.
The specific structure of the administration observation cranial window for brain according to the embodiment of the present invention will be described with reference to fig. 1 to 2.
The invention discloses a brain administration observation skull window, as shown in fig. 1-2, the brain administration observation skull window of the embodiment comprises a body 1 and a light-transmitting plate 2, wherein a protruding part 11 is arranged on the body 1, a light-transmitting hole 111 and a first through hole 112 are arranged on the end surface of the protruding part 11, a second through hole 113 is arranged on the peripheral surface of the protruding part 11, the first through hole 112 and the second through hole 113 are used for being matched with an administration tube 51 of an administration pump 5, and the light-transmitting plate 2 is matched on the protruding part 11 to seal the light-transmitting hole 111.
It can be understood that, in the actual experiment process, install light-passing board 2 on body 1 after, go into experimental animals's head with 1 bulge 11 card of body to make light-passing board 2 stretch into the experiment opening of experimental subject head and seal the experiment opening, avoid the brain tissue and the outside air contact of animal. Then, the administration tube 51 of the administration pump 5 is passed through the second perforation 113 and the first perforation 112 in this order so that the end of the administration tube 51 can reach the experimental opening. After the experiment preparation work is completed, the microscope for observation is adjusted so that the lens barrel of the microscope can start the experiment corresponding to the light-transmitting hole 111. Can realize dosing many times through adjusting dosing pump 5 in the experimentation to need not to carry out the dismantlement of body 1 at the in-process of dosing, the phenomenon of having avoided experimental animal's experiment opening to expose in the air takes place.
Therefore, compared with the existing simple glass head window, the brain administration observation skull window of the embodiment can repeatedly administer medicine for a long time, can realize administration while imaging observation, can accurately control the administration dosage by matching with the administration pump 5, and solves the problems of complex operation and the like of the separation operation of the head frame and the head window. Compared with the mode of direct craniotomy administration, the method can solve the problems of easy activation of tissue cell exposure, uncontrollable liquid medicine concentration and corrosion to the objective lens in the experiment.
In some embodiments, the end surface of the protruding portion 11 is provided with a fitting groove 114 provided around the light-transmitting hole 111, and the light-transmitting plate 2 is fitted in the fitting groove 114. It can be understood that, the light-passing board 2 cooperation can promote the installation stability of light-passing board 2 in cooperation groove 114 on the one hand, avoids the phenomenon that light-passing board 2 drops to take place, thereby on the other hand can avoid the phenomenon emergence of the edge fish tail operating personnel or the experimental animals tissue of light-passing board 2 outstanding bulge 11.
In some specific embodiments, the light-transmitting plate 2 is interference-fitted with the fitting grooves 114, or the light-transmitting plate 2 is bonded in the fitting grooves 114. This can further improve the stability of connection between the light-transmitting plate 2 and the main body 1.
In some embodiments, the body 1 is further provided with a fixing hole 12, and a fixing member for fixing the head of the subject is inserted into the fixing hole 12. It can be understood that the body 1 is further provided with a fixing hole 12, and a fixing part for fixing the head of the experimental subject can be arranged in the fixing hole 12 in a penetrating manner, that is, the brain administration observation skull window of the embodiment can be directly used as a head frame for fixing the experimental subject, so that the fixation of the brain administration observation skull window is facilitated, the experimental device is simplified, and the experiment by the user is facilitated.
In some specific embodiments, the fixing holes 12 are plural, and the plural fixing holes 12 are uniformly spaced around the projection 11. From this, can adopt a plurality of mountings to carry out the fixed of subject head, promote the brain of this embodiment and dosed observation skull window and subject's the stability of being connected, ensure that the experiment can normally go on.
Of course, in other embodiments of the present invention, the number, arrangement and shape of the fixing holes 12 may be selected according to actual needs, and the number, arrangement and shape of the fixing holes 12 are not limited herein.
In some embodiments, the light-transmitting plate 2 comprises a glass plate or a transparent resin plate. It can be understood that the glass plate or the transparent resin plate is selected, so that the quality and the manufacturing cost of the cranial window for brain administration observation are reduced, the use is convenient, and in other embodiments of the invention, the light-transmitting plate 2 can also be made of other transparent materials.
Example (b):
the specific structure of a cerebral administration observation cranial window according to one specific embodiment of the present invention will be described with reference to fig. 1-2.
As shown in fig. 1-2, the brain administration observation skull window of this embodiment includes a body 1 and a light-transmitting plate 2, the body 1 is provided with a protruding portion 11, an end surface of the protruding portion 11 is provided with a light-transmitting hole 111, a first through hole 112, and a fitting groove 114 surrounding the light-transmitting hole 111, a second through hole 113 is provided on a peripheral surface of the protruding portion 11, and the light-transmitting plate 2 is bonded in the fitting groove 114 through light-curing glue. The first and second through holes 112 and 113 are used to fit the administration tube 51 of the administration pump 5, and the light-transmissive plate 2 is fitted over the projection 11 to cover the light-transmissive hole 111. The body 1 is further provided with four fixing holes 12 arranged around the protruding portion 11, and the fixing holes 12 are arranged in the fixing holes 12 in a penetrating mode and used for fixing the body 1 on the skull of the experimental object through cranial nails and dental cement.
The length of the body 1 is 40mm, the width is 6mm, the fixing hole 12, the first through hole 112 and the second through hole 113 are all round holes with the diameter equal to 0.5mm, the diameter of the outer ring of the protruding part 11 is 4.4mm, and the diameter of the light hole 111 is 2 mm; the depth of the projection 11 is 0.8 mm; the fitting groove 114 has a diameter of 3mm and a depth of 0.1 mm.
The advantages of the administration into the brain of this example to observe the cranial window are as follows:
firstly, the method comprises the following steps: can carry out double/multi-photon imaging while not exposing the local drug administration of the tissue, and ensures the precision accuracy of the experiment
Secondly, the method comprises the following steps: the administration dosage and concentration are accurately controlled while administration imaging is carried out, and the operation is convenient and the use is convenient;
thirdly, the method comprises the following steps: convenient for administration at any time and for a long time and repeated observation for a long time;
fourthly: the headstock and the administration observation skull window are integrated, so that the operation is simplified.
The specific structure of the administration observation cranial window of the brain according to the embodiment of the present invention will be described with reference to fig. 3 to 4.
The invention also discloses a fixed observation device for experimental animals, which comprises the brain administration observation skull window, the fixing frame 3 and the administration pump 5, wherein the administration pump 5 is connected with the administration pipe 51, and the brain administration observation skull window is arranged on the fixing frame 3.
It can be understood that, in the actual experiment process, place the laboratory object on mount 3, install light-passing board 2 after on body 1, install experimental animal's head with body 1 to make light-passing board 2 just to the experiment opening setting of laboratory object head, and seal the experiment opening, avoid the brain tissue and the outside air contact of animal. Then, the administration tube 51 of the administration pump 5 is passed through the second perforation 113 and the first perforation 112 in this order so that the end of the administration tube 51 can reach the experimental opening. Can realize dosing many times through adjusting dosing pump 5 in the experimentation to need not to carry out the dismantlement of body 1 at the in-process of dosing, the phenomenon of having avoided experimental animal's experiment opening to expose in the air takes place.
Therefore, due to the brain administration observation skull window, the experimental animal fixing observation device of the embodiment can realize administration while imaging observation, can accurately control administration dosage, and can solve the problems of easy activation of tissue cell exposure, uncontrollable liquid medicine concentration and corrosion to an objective lens in an experiment.
In some embodiments, the fixed observation device for experimental animals further comprises an adjusting mechanism 4, the adjusting mechanism 4 is connected with the body 1, and the adjusting mechanism 4 is used for adjusting the height of the body 1. From this, can adjust the height of body 1 through adjusting the structure in the experiment preparation stage to make body 1 can laminate with the experimental object betterly, and can guarantee that body 1 level sets up, avoided the crooked experimental error that leads to of body 1.
In some specific embodiments, the adjusting mechanism 4 includes an adjusting block 41 and an adjusting knob 42, the adjusting block 41 is provided with a threaded hole, the adjusting knob 42 has a stud matched with the threaded hole, and one end of the stud is matched on the body 1. Therefore, the adjustment of the body 1 can be realized only by rotating the adjusting knob 42 in the actual adjustment process, and the operation is very convenient.
Of course, in the embodiment of the present invention, the adjusting mechanism 4 may be of other types, for example, a plurality of mounting slots are provided on the fixing frame 3 at intervals, and the cerebral administration observation skull window may be fitted in a certain mounting slot according to actual needs.
In some specific embodiments, there are two adjusting mechanisms 4, and the two adjusting mechanisms 4 are respectively connected to two ends of the body 1. Therefore, the horizontal arrangement of the body 1 can be ensured in the process of adjusting the administration observation skull window of the brain, and the experimental error caused by the deflection of the body 1 is avoided.
In the description herein, references to the description of "some embodiments," "other embodiments," etc., mean that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the invention. In this specification, the schematic representations of the terms used above do not necessarily refer to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples.
The above description is only a preferred embodiment of the present invention, and for those skilled in the art, the present invention should not be limited by the description of the present invention, which should be interpreted as a limitation.

Claims (10)

1. A cranial window for brain drug administration observation, comprising:
the drug delivery pump comprises a body (1), wherein a protruding part (11) is arranged on the body (1), a light hole (111) and a first through hole (112) are formed in the end face of the protruding part (11), a second through hole (113) is formed in the peripheral surface of the protruding part (11), and the first through hole (112) and the second through hole (113) are used for being matched with a drug delivery pipe (51) of a drug delivery pump (5);
a light-transmitting plate (2), the light-transmitting plate (2) being fitted over the projection (11) to cover the light-transmitting hole (111).
2. The brain administration observation cranial window according to claim 1, wherein the end face of the protrusion (11) is provided with a fitting groove (114) arranged around the light-transmitting hole (111), and the light-transmitting plate (2) is fitted in the fitting groove (114).
3. The brain administration observation cranial window according to claim 2, wherein the light-transmitting plate (2) is interference fit with the fitting groove (114), or the light-transmitting plate (2) is bonded in the fitting groove (114).
4. The brain administration observation skull window according to claim 1, wherein the body (1) is further provided with a fixing hole (12), and a fixing piece for fixing the head of the experimental subject is arranged in the fixing hole (12) in a penetrating manner.
5. The brain drug delivery observation cranial window according to claim 4, wherein the fixation hole (12) is plural, and the plural fixation holes (12) are uniformly spaced around the protrusion (11).
6. The brain administration observation cranial window according to claim 5, wherein the light-transmitting plate (2) comprises a glass plate or a transparent resin plate.
7. A laboratory animal fixation observation device, characterized by comprising the cerebral administration observation skull window according to any one of claims 1 to 6, a fixing frame (3) and an administration pump (5), wherein the administration pump (5) is connected with the administration tube (51), and the cerebral administration observation skull window is mounted on the fixing frame (3).
8. Laboratory animal fixation observation device according to claim 7, characterized in that it further comprises an adjustment mechanism (4), said adjustment mechanism (4) being connected to said body (1), said adjustment mechanism (4) being adapted to adjust the height of said body (1).
9. Laboratory animal fixation observation device according to claim 8, characterized in that the adjusting mechanism (4) comprises:
the adjusting block (41), the adjusting block (41) is provided with a threaded hole;
an adjusting knob (42), wherein the adjusting knob (42) is provided with a stud matched with the threaded hole, and one end of the stud is matched on the body (1).
10. The fixed observation device of laboratory animal according to claim 8, characterized in that, the said adjustment mechanism (4) is two, two said adjustment mechanisms (4) are connected respectively at both ends of the said body (1).
CN202111231677.2A 2021-10-22 2021-10-22 Brain dosing observation skull window and experimental animal fixing observation device Pending CN113855303A (en)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105828602A (en) * 2013-12-19 2016-08-03 学校法人冲绳科学技术大学院大学学园 Chronic cranial window allowing drug application, cellular manipulations, and electrophysiology
CN207202966U (en) * 2017-01-22 2018-04-10 华中科技大学 A kind of small animal living body is imaged fixing device
US20180154073A1 (en) * 2016-12-07 2018-06-07 The Research Foundation For The State University Of New York Microfluidic intravital window
WO2020104580A1 (en) * 2018-11-22 2020-05-28 Institut Curie Intravital imaging device
CN216724856U (en) * 2021-10-22 2022-06-14 中国科学院深圳先进技术研究院 Brain dosing observation skull window and experimental animal fixing observation device

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN105828602A (en) * 2013-12-19 2016-08-03 学校法人冲绳科学技术大学院大学学园 Chronic cranial window allowing drug application, cellular manipulations, and electrophysiology
US20160296312A1 (en) * 2013-12-19 2016-10-13 Okinawa Institute Of Science And Technology School Corporation Chronic cranial window allowing drug application, cellular manipulations, and electrophysiology
US20180154073A1 (en) * 2016-12-07 2018-06-07 The Research Foundation For The State University Of New York Microfluidic intravital window
CN207202966U (en) * 2017-01-22 2018-04-10 华中科技大学 A kind of small animal living body is imaged fixing device
WO2020104580A1 (en) * 2018-11-22 2020-05-28 Institut Curie Intravital imaging device
CN216724856U (en) * 2021-10-22 2022-06-14 中国科学院深圳先进技术研究院 Brain dosing observation skull window and experimental animal fixing observation device

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