CN105769373B - A kind of compatible optical imaging and the automation cortex cooling inactivating system of electrophysiological recording - Google Patents
A kind of compatible optical imaging and the automation cortex cooling inactivating system of electrophysiological recording Download PDFInfo
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- CN105769373B CN105769373B CN201610195714.1A CN201610195714A CN105769373B CN 105769373 B CN105769373 B CN 105769373B CN 201610195714 A CN201610195714 A CN 201610195714A CN 105769373 B CN105769373 B CN 105769373B
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61D—VETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
- A61D1/00—Surgical instruments for veterinary use
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61D—VETERINARY INSTRUMENTS, IMPLEMENTS, TOOLS, OR METHODS
- A61D7/00—Devices or methods for introducing solid, liquid, or gaseous remedies or other materials into or onto the bodies of animals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B2503/00—Evaluating a particular growth phase or type of persons or animals
- A61B2503/40—Animals
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B2503/00—Evaluating a particular growth phase or type of persons or animals
- A61B2503/42—Evaluating a particular growth phase or type of persons or animals for laboratory research
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Abstract
A kind of compatible optical imaging and the automation cortex cooling inactivating system of electrophysiological recording, this system is broadly divided into automatic temperature controlling circuit and titanium alloy implanted device two parts, for automatic temperature controlling circuit to controlling and regulating system temperature, titanium alloy implanted device is the agent structure of this system；Pass through a set of electronics and mechanical system, on the one hand automatic constant-temperature control is carried out to cortex temperature using microcontroller, and record the temperature of cortex in real time with computer communication, experimenter is made not need to constantly carry out temperature-compensating adjusting manually during the experiment, misoperation is avoided and causes the too low damage cortex that freezes of temperature；On the other hand pass through three adjustable inactivations of dimension --- the integrated titanium alloy implanted device of imaging, miniature cooling tube is allow accurately to be located in target cortex position, and record observation and stimulation can be synchronized using technologies such as microelectrode, cortex optical imagery, two photon imaging and light heredity while inactivation.
Description
Technical field
The present invention relates to a kind of imaging of compatible optical and the automation cortex cooling inactivating system of electrophysiological recording, the skills
Art is mainly used in animal nerve Physiology Experiment research.
Background technology
The work studied using information transmission of the method for cooling inactivation between the function and cortex of a certain cortex is begun
In early in the twentieth century (survey article that the development of cortex falling temperature technique is introduced referring to Brooks).The research of early stage passes through in cortex
The wire chamber that an one side has wrapped up thin rubber membrane is placed on surface, flows there through 4 DEG C of ice water, and playing reduces cortex temperature
Effect.The cortex range of this method inactivation is larger, but specific deactivated area is difficult to control, and is not used in inactivation brain ditch
Cortical region.
In the 1970s, with the development of semiconductor technology, occur carrying out cortex drop using semiconductor refrigerating original paper
The experimental method of temperature is used to conduct heat, silver strip opposite side and semiconductor chilling plate by placing a fritter silver strip on cortex
Fitting, cools down to cortex；The representative studies work carried out using this method is referred to.Due to the easy root of the shape of silver strip
It cuts and processes according to brain area shape, it is possible to by deactivated area control within the scope of specific.But semiconductor chilling plate draws
The new problem entered causes limitation to its scope of application：The hot face of semiconductor chilling plate can release more heat transfer, it usually needs into
Row water-cooling causes single unit system thickness larger, be unsuitable for for a long time be implanted on cortex under animal waking state into
Row chronic experiment；In addition the electric current flowed through when cooling piece works is larger, can be carried out at the same time extracellular electro physiology to brain area aside
It records (signal only has V grades of μ) and generates larger interference.
Salsbury and Horel is reported for the first time in nineteen eighty-three carries out cortex cooling using the miniature cooling tube of implanted
Experimental method, Lomber et al. has carried out systematic test in 1999 to the cooling Inactivation Effect of this method, has write phase
Technical article is closed specific embodiment and effect is introduced.The program by the implantable miniature cooling tube at target cortex,
Under the driving of water pump, the cold alcohol for flowing through dry ice alcohol bath is made to be flowed through from miniature cooling tube, reaching reduces cortex temperature
Purpose, principle are shown in Fig. 1.
The advantages of this method is that cooling tube can bend to the cortical region institute that plan carries out deactivation experiment as required
Corresponding shape, and can for a long time be implanted on cortex or brain ditch in without causing cortical lesions.Additionally due to it is connected to
Only water pipe and the very faint thermocouple probe line of electric current at cortex, do not interfere with electrophysiological recording.However this method
It needs that manually water pump is carried out according to the reading of thermometer constantly to adjust the temperature that could maintain cortex, it is careless slightly to be easy to cause
The too low icing of temperature and damage cortex, operation is complex, therefore is not widely applied very much.In addition this method passes through
Miniature cooling tube and connector are fixed on skull by dental cement, it is impossible to rose in recent years cortex optical imagery, bis- (more)
Photon imaging technology is mutually compatible with, and can not realize and deactivation experiment is carried out under imaging.
Invention content
The present invention passes through a set of electronics and mechanical system, a side on the basis of Salsbury and Lomber et al. method
Face carries out automatic constant-temperature control using microcontroller to cortex temperature, and records the temperature of cortex in real time with computer communication, makes reality
The personnel of testing do not need to constantly carry out temperature-compensating adjusting manually during the experiment, avoid misoperation and cause the too low knot of temperature
Ice damages cortex；On the other hand passing through three adjustable inactivations of dimension --- the integrated titanium alloy implanted device of imaging makes miniature
Cooling tube can accurately be located in target cortex position, and can while inactivation using microelectrode, cortex optics into
The technologies such as picture, two photon imaging and light heredity synchronize record observation and stimulation.
To achieve the above object, the technical solution adopted by the present invention is oneself of a kind of imaging of compatible optical and electrophysiological recording
Dynamicization cortex cooling inactivating system, this system are broadly divided into automatic temperature controlling circuit and titanium alloy implanted device two parts,
For automatic temperature controlling circuit to controlling and regulating system temperature, titanium alloy implanted device is the agent structure of this system；Automatic warm
Degree control circuit is made of (Fig. 2) host computer, control single chip computer and temperature measurement circuit based on operational amplifier.Temperature measurement circuit
Using the thermoelectric voltage of the T-shaped thermocouple probe of operational amplifier reading, control monolithic is sent to by spi bus after AD conversion
Machine.Temperature measurement circuit is independently-powered using lithium battery, with the spi bus of microcontroller communication using high-speed photoelectric coupler carry out every
From, and isolation circuit part is integrally electromagnetically shielded, to ensure that it is raw to electricity that temp measuring system will not introduce outer source noise
Reason record generates interference.Control single chip computer by spi bus read brain temperature data after, according to the target temperature of setting with
The mode of PWM (Pulse-width modulation, pulse width modulation) controls the rotating speed of refrigeration pump, finally controls cold alcohol
The flow velocity of cooling tube is flowed through, makes brain temperature stabilization near set temperature.The real time temperature of brain tissue is by control single chip computer
UART serial ports is turned by USB and is sent to host computer, and is recorded by host computer.The target temperature of refrigeration, refrigeration
The order such as beginning and stopping of work turns UART serial ports by USB by host computer and is sent to microcontroller.On host computer
Thermograph and system control completed by independently developed software.
Titanium alloy implanted device is by pellosil 9, chassis 1, sliding block 4, cover board 2, head cover 3, side cover 5, wiring tower 6 and wiring tower
Lid 7 forms.Wherein, pellosil 9 is inserted by the shirt rim of stretching under endocranium, by intracranial pressure and endocranium inner wall gluing, sealing
And be fixed at skull windowing, brain tissue is protected, and provide transparent imaging window.Chassis 1 is by three titanium alloy nails
10 are fixed on skull, are used to support and fix cooling tube 8 and other parts.Cooling tube 8 is passed through from the hole of sliding block 4,
Relative position can adjust, and after final position determines, be fixed on sliding block 4 by M2 jackscrews.Sliding block 4 can be in the fluting on chassis 1
It slides up and down or left-right rotation angle, for adjusting position of the cooling tube 8 on cortex, is slotted after location determination by chassis 1
The M1.4 jackscrews on side are fixed.Cover board 2 is fixed on by the flat head screw of eight symmetrical M1.4 on chassis 1, is remembered for transferring
Record or imaging system, the size and specification of 2 threaded upper ends of cover board according to record and imaging system be adapted to.Wiring tower
6 are fixed on by three titanium alloy nails on skull, and for connecting thermocouple probe line 11, wiring tower 6 is internally provided with to install
The mounting hole of the wire connection terminal 12 (OMEGA SMTC-CO-S and SMTC-CU-S) of thermocouple, needs thermocouple before use with connecing
Line terminals 12 are inserted into trepanning, and be sealed from the bottom of wiring tower 6 with orthopaedics cement after connecting.Head cover 3 is installed by screw thread
On cover board 2, centre is equipped with venthole, and passes through and screw in the sealing of M2 screws.Side cover 5 is fixed on chassis by two M1.4 screws
On 1.Wiring tower lid 7 is by being threadably mounted on wiring tower 6.Head cover 2, side cover 5 and wiring tower lid 7 are used to protect cooling tube 8, silicon
Glued membrane 9, cortex and wire connection terminal 12 is contaminated, corrosion and external force damage, need with Iodophor in experimentation to the system
It is opened after carrying out disinfection in outside.
Pellosil 9 is suppressed by transparent silica gel.
Wiring tower 6 is process by polyetheretherketonematerials materials, other parts by titanium alloy (Ti-6Al-4V ELI) process and
Into.
Description of the drawings
Fig. 1 is cortex cooling device schematic diagram.
Fig. 2 is the circuit diagram of automatic temperature-adjusting control system.
Fig. 3 is the structure chart of titanium alloy implanted device.
Fig. 4 .1 are the schematic diagram of operation installation titanium alloy implanted device.
Fig. 4 .2 are the schematic diagram of operation installation titanium alloy implanted device A-A sections.
Fig. 5 is the implementation result figure of cortex cooling.
In figure：1st, chassis, 2, cover board, 3, head cover, 4, sliding block, 5, side cover, 6, wiring tower, 7, wiring tower lid, 8, cooling tube,
9th, pellosil, 10, titanium alloy nail, 11, thermocouple probe line, 12, wire connection terminal.
Specific embodiment
Fig. 1 is cortex cooling device schematic diagram.The cool principle that the present invention uses and Salsbury and Lomber et al. phase
Together, but on the basis of them increase automatic temperature-adjusting control system, and have changed the fixed form of cooling tube, using with light
Study picture, the titanium alloy implanted device of electrophysiological recording compatibility fixes cooling tube.
The method according to Salsbury and Lomber et al. is needed before experiment, by stainless steel lumbar puncture needle (or thin stainless steel tube)
It bends to cooling tube 8 and T-shaped thermocouple probe (being manufactured using OMEGA TT-T-30-SLE) is welded on cooling tube root (position
The relationship of putting is shown in Fig. 3), after polytetrafluoroethylene (PTFE) pyrocondensation protection of pipe, pipe end will be cooled down and be inserted into the hole of sliding block, and will flow into and flow
Entrance separates certain angle, and anti-limited slip block comes off.Load onto the wire connection terminal 12 of same metal material in 11 end of thermocouple probe line
(constantan and copper both threads use OMEGA SMTC-CO-S and SMTC-CU-S respectively), after being packed into the hole of wiring tower from bottom
(Fig. 3) is shut hole with bone cement.
Before carrying out cortex cooling deactivation experiment, need to perform the operation to animal, be implanted into cooling tube and titanium alloy implanted device,
It is as follows：After animal stablizes and anaesthetizes and be fixed on operating table, operation of opening cranium is carried out at target cortex position, in
On skull centered on target location, the round bone window (cortex that bone window diameter can inactivate according to schedule of diameter about 20mm is opened
Regional extent size is adjusted, correspondingly, the diameter of implanted device should also adjust therewith).Then endocranium is cut off, exposure
Brain area to be inactivated maps out position of the cooling tube 8 on cortex, and cooling tube passes through No. 12 injection needles in place on pellosil 9
Head punctures a round duck eye.8 head of cooling tube from pellosil 9 is passed through, adjusts position and the angle of cooling tube 8, and will
The shirt rim of pellosil 9 is inserted into the gap of endocranium and cortex.Chassis 1 is placed on skull, at the same by sliding block 4 it is careful from
It is inserted into the slot on chassis 1, adjusts position and the angle of chassis 1, sliding block 4, cooling tube 8 and pellosil 9, be positioned exactly at cooling tube
At target cortex to be inactivated.Chassis 1 is fixed on skull with titanium alloy nail 10 (2.7mm diameters), to sliding block 4 and cooling
The position of pipe 8 carries out tightening the jackscrew on chassis 1 and sliding block 4 after finally finely tuning, and cooling tube 8 is fixed, and with screw by cover board 2
It is fixed on chassis 1.Wiring tower 6 is fixed on the skull on side by chassis 1 with titanium alloy nail 10 (2.7mm diameters) after fixing
On, it is sealed, and to cold in the gap where bone cement is inserted the gap on chassis 1 and skull and sliding block 4 above and below fluting
But pipe 8 is protected to the thermocouple probe line 11 between wiring tower 6.Head cover 3 and bleed screw are finally screwed on, loads onto side cover 5
With wiring tower lid 7, skin suture (makes skin be looped around around titanium alloy implanted device, it is impossible to influence to open head cover, side during experiment
Lid and wiring tower lid), complete operation.The position relationship of all parts and skull, cortex is with reference to figure 4.1-4.2 after installation.
The implementation result of cortex cooling is see Fig. 5, it is seen that a certain god before cooling near (the 1st minute) cooling tube in cortex
Action potential (spike) granting frequency through member is very high, and almost no longer generation acts electricity to (the 3rd minute) cell after cooling inactivation
Position, and the discharge activities of (the 6th minute) cell are restored after temperature recovery.
Claims (4)
1. a kind of compatible optical imaging and the automation cortex cooling inactivating system of electrophysiological recording, it is characterised in that：This is
System is broadly divided into automatic temperature controlling circuit and titanium alloy implanted device two parts, and automatic temperature controlling circuit is controlling to adjust
System temperature, titanium alloy implanted device are the agent structure of this system；Automatic temperature controlling circuit is single by host computer, control
Piece machine and the temperature measurement circuit composition based on operational amplifier；Temperature measurement circuit reads T-shaped thermocouple probe using operational amplifier
Thermoelectric voltage is sent to control single chip computer after AD conversion by spi bus；Temperature measurement circuit is independently-powered using lithium battery, with list
The spi bus of piece machine communication is isolated using high-speed photoelectric coupler, and isolation circuit part integrally needs to carry out electromagnetism
Shielding generates interference to ensure that temp measuring system will not introduce outer source noise to electrophysiological recording；Control single chip computer passes through spi bus
After reading brain temperature data, the rotating speed of refrigeration pump is controlled in a manner of PWM according to the target temperature of setting, is finally controlled cold
Alcohol flows through the flow velocity of cooling tube, makes brain temperature stabilization near set temperature；The real time temperature of brain tissue is single by control
Piece machine turns UART serial ports by USB and is sent to host computer, and recorded by host computer；The target temperature of refrigeration,
It the beginning of refrigeration work and ceases and desist order and UART serial ports is turned by USB by host computer is sent to microcontroller；Host computer
On thermograph and system control completed by independently developed software；
Titanium alloy implanted device is by pellosil (9), chassis (1), sliding block (4), cover board (2), head cover (3), side cover (5), wiring tower
(6) it is formed with wiring tower lid (7)；Wherein, pellosil (9) is inserted by the shirt rim of stretching under endocranium, by intracranial pressure and firmly
Meninx inner wall gluing, sealing is simultaneously fixed at skull windowing, protects brain tissue, and provide transparent imaging window；Chassis
(1) it is fixed on skull by three titanium alloy nails (10), is used to support and fixes cooling tube (8) and other parts；It is cold
But pipe (8) is passed through from the hole of sliding block (4), and relative position can adjust, and after final position determines, sliding block is fixed on by M2 jackscrews
(4) on；Sliding block (4) can be slided up and down in the fluting of chassis (1) or left-right rotation angle, for adjusting cooling tube (8) in skin
Position on layer is fixed by the M1.4 jackscrews on chassis (1) fluting side after location determination；Cover board (2) is symmetrical by eight
The flat head screw of M1.4 is fixed on chassis (1), for transfer record or imaging system, the size of cover board (2) threaded upper ends and
Specification according to record and imaging system be adapted to；Wiring tower (6) is fixed on by three titanium alloy nails on skull, is used
In connection thermocouple probe line (11), wiring tower (6) be internally provided with for install thermocouple wire connection terminal (12) mounting hole,
It needs to be inserted into trepanning after thermocouple is connect with wire connection terminal (12) before use, and with orthopaedics cement from the bottom of wiring tower (6)
It is sealed；For head cover (3) by being threadably mounted on cover board (2), centre is equipped with venthole, and passes through and screw in the sealing of M2 screws；
Side cover (5) is fixed on by two M1.4 screws on chassis (1)；Wiring tower lid (7) is by being threadably mounted on wiring tower (6)；
Head cover (3), side cover (5) and wiring tower lid (7) are for protecting cooling tube (8), pellosil (9), cortex and wire connection terminal (12) no
Contaminated, corrosion and external force are damaged, and are needed in experimentation with Iodophor to being opened after carrying out disinfection on the outside of the system.
2. a kind of compatible optical imaging according to claim 1 and the automation cortex cooling inactivation system of electrophysiological recording
System, it is characterised in that：Pellosil (9) is suppressed by transparent silica gel.
3. a kind of compatible optical imaging according to claim 1 and the automation cortex cooling inactivation system of electrophysiological recording
System, it is characterised in that：Wiring tower (6) is process by polyetheretherketonematerials materials.
4. a kind of preparation method before experiment of the implementation carried out using system described in claim 1, it is characterised in that：It is real
Before testing, stainless steel lumbar puncture needle or thin stainless steel tube are bent into cooling tube (8) and T-shaped thermocouple probe is welded on cooling tube root
Portion after polytetrafluoroethylene (PTFE) pyrocondensation protection of pipe, will cool down pipe end and be inserted into the hole of sliding block, and will flow into and separate one with inflow entrance
Determine angle, anti-limited slip block comes off；The wire connection terminal (12) of same metal material is loaded onto in thermocouple probe line (11) end, from bottom
Hole is shut with bone cement after being packed into the hole of wiring tower.
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| Application Number | Priority Date | Filing Date | Title |
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| CN201610195714.1A CN105769373B (en) | 2016-03-30 | 2016-03-30 | A kind of compatible optical imaging and the automation cortex cooling inactivating system of electrophysiological recording |
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| CN201610195714.1A CN105769373B (en) | 2016-03-30 | 2016-03-30 | A kind of compatible optical imaging and the automation cortex cooling inactivating system of electrophysiological recording |
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| CN105769373A CN105769373A (en) | 2016-07-20 |
| CN105769373B true CN105769373B (en) | 2018-06-19 |
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| CN113712575B (en) * | 2021-07-16 | 2023-01-10 | 清华大学 | Whole brain multi-modal neural activity detection photoelectric brain-computer interface system |
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| US9089316B2 (en) * | 2009-11-02 | 2015-07-28 | Endocare, Inc. | Cryogenic medical system |
| US9849025B2 (en) * | 2012-09-07 | 2017-12-26 | Yale University | Brain cooling system |
| CN103800116A (en) * | 2012-11-07 | 2014-05-21 | 赵银香 | Medical human body cooling device controlled by single-chip microcomputer |
| CN103006344B (en) * | 2012-12-05 | 2014-12-03 | 山东大学 | Semiconductor refrigerating frostbite model instrument |
| CN104490372A (en) * | 2014-12-30 | 2015-04-08 | 续嘉 | Cooling device |
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