CN206964625U - A kind of binary channels animal nerve unit signal record and synchronous stimulating system - Google Patents
A kind of binary channels animal nerve unit signal record and synchronous stimulating system Download PDFInfo
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Abstract
The utility model belongs to biology, Neuscience, the fields such as medical science, more particularly to light genetics technology application field, more particularly to a kind of binary channels animal nerve unit signal record and synchronous stimulating system, the utility model is during free moving animals neuron activity is recorded, the excitement of light science of heredity and Inhibition test can be realized simultaneously, the utility model illustrates the contact between purpose neuron spontaneous emissions and purpose behavior from neuron spontaneous emissions record, neuronal excitation experiment is respectively adopted again and suppresses experiment and is verified from positive and negative two angles, the science and accuracy of experimental result are fully ensured that.The utility model can use same root optical fiber to realize record and stimulatory function, eliminate switching record and the process of stimulating apparatus in experimentation, saved experimental period, simplified experimental procedure, the cycle for making entirely to test greatly shortens.
Description
Technical field
The utility model belongs to the fields such as biology, Neuscience, medical science, more particularly to light genetics technology application neck
Domain, more particularly to a kind of binary channels animal nerve unit signal record and synchronous stimulating system.
Background technology
Human brain is made up of nearly hundred billion nerve cells, by Synaptic formation network between neuron, is got in touch with each other, is passed
Information is passed, some subsystems can be divided into again by forming system, each systems such as sensation, motion, such as the vision in feeling, smell, be listened
Feel, the sense of taste and body surface tactile etc., the implementation of its function depend on different type, the essence between nervous system different parts cell
The neural circuitry that standard is contacted and formed.Neural circuitry is to contact the bridge between molecular cell function and global behavior function, special
The research for determining functional neurosurgery loop is advantageous to understand the formation and modification of neural circuitry, information coding, processing and processing, Yi Jiqi
The relation between behavior, the operation principle of brain is understood so as to deeper level.
Neuromodulation is a kind of effective means for studying neural circuitry, and interfering effects of drug is a kind of conventional neuromodulation skill
Art, but the problem of drug effect time is slow, side effect is big be present;Electrode stimulating is a kind of conventional neuromodulation technology, but is pierced
Swash big region, shortage specificity and spatial selectivity, limit their applications in neural circuitry research.Light genetics technology
A kind of novel neuromodulation technology, can lossless, high-spatial and temporal resolution, both-way operation neuron, be especially suitable for research god
Contacting through circuit functionality, announcement animal behavior activity and neural circuitry and mechanism.
Light genetics technology is the product that genetics technology is combined with light stimulus technology.From genetics technology,
A variety of photaesthesia passages are developed, expression can be facilitated to culture cell or in living animal;It is dynamic to freely activity in real time for a long time
It is the important side for exploring brain function and finding relevant nerve diseases pathogenesis that each core group neuron activity of thing intracerebral, which is monitored,
One of method, tradition mainly applies electro physiology method, but its experimental procedure is numerous and diverse, experimental period is long, recording interval is limited, with
The development of calcium ion fluorescent dye and light science of heredity viral vector, optical fiber record and light genetics technology arise at the historic moment, so as to
Calcium ion fluorescence signal change caused by optical fiber record neuron activity can be used to monitor the activity of neuron, meanwhile, also
It can be suppressed by light genetic technique and excited target nerve is first, the change of object observing behavior.
But previous optical fiber tape deck and light science of heredity device are two equipment, record and light Genetics are carried out
Testing needs optical fiber inserting in distinct device, and can not realize and carry out light genetics experiments at any time during record, originally sets
It is standby record and light genetics experiments to be realized by same root optical fiber, while the behavior to animal is monitored, and experiment is walked
Suddenly reduce significantly, it is more true and reliable to record the experimental result for being made to obtain simultaneously with light genetics experiments.
Utility model content
Based on the above situation, it is necessary to provide a kind of binary channels animal nerve unit signal record and synchronous stimulating system.
A kind of binary channels animal nerve unit signal record and synchronous stimulating system, including optic module, light source module, photoelectricity
Modular converter, AD/DA modular converters, video acquisition module and host computer;
The optic module reaches the fluorescence signal of photosensitive protein brain area to acquisition tables, in addition to output blue light or gold-tinted are extremely
Corresponding brain area neuron;
The light source module is used for according to stimulus signal selectively output blue light or gold-tinted, in addition to the fluorescence of reception is believed
Number transmit to photoelectric conversion module;
The photoelectric conversion module is transmitted to AD/DA and turned the fluorescence signal of reception is converted into electric analoging signal
Change the mold block;
The AD/DA modular converters are used to electric analoging signal being converted to data signal, and are uploaded to host computer;It is described
AD/DA modular converters are additionally operable to control signal being converted to stimulus signal;
Behavior record is uploaded to host computer by the video acquisition module to record animal behavior;
The host computer reception behavior features record and data signal are simultaneously analyzed, and the host computer is also included as AD/DA turns
Change the mold block and send control signal.
As an improvement in addition to video marker module, the video marker module be connected with AD/DA modular converters,
The animal behavior record of collection to be marked according to electric analoging signal.
As a further improvement, after the light source module includes blue-ray LED, yellow light LED, is located at two groups of LED light sources respectively
The collimation lens and optical filter in face, the respectively dichronic mirror after two groups of LED light source optical filters;The collimation lens is arranged on
Between LED light source and optical filter, the blue light LED light source and yellow light LED light source are connected with AD/DA modular converters respectively, described
The output of AD/DA modular converters, switching and power output size, caused corresponding light beam reach the filter through the collimation lens
Dichronic mirror is sent to after mating plate, then is carried out by the dichronic mirror being reflected into optical link module.
Further, the photoelectric conversion module is specially photomultiplier, and the AD/DA modular converters are specially data
Capture card;The fluorescent signals of collection being amplified and be converted to analog electrical signal by the photomultiplier.
Further, the optic module includes the 4th collimation lens and optical fiber, anti-by the light source module dichronic mirror
The blue light or gold-tinted penetrated are sent to optical fiber, activation or the neuron for suppressing corresponding brain area through the 4th collimation lens.
As an improvement the video marker module is specially signal lamp, the signal lamp is connected with data collecting card,
The data collecting card analog electrical signal is strong and weak, control signal lamp bright dark time and flashing times, is caught by video acquisition module
Point of scintillation is grasped as mark, for animal behavior record and the calibration corresponding points of data signal.
Specifically, a width of 450-490nm of blue LED light source excitation band, the yellow LED light source excitation band are a width of
540-590nm。
Specifically, the blueness and yellow LED light source, the blue led light source can excite OGB-1, GCaMP and chR2,
The yellow LED light source can excite ArchT.
As an improvement distance is 5- between the blue-ray LED or the corresponding collimation lens left side plan of yellow light LED
10mm, right side convex surface summit to the distance of corresponding optical filter of the corresponding collimation lens is 0.5-2mm, the corresponding optical filter
Distance to the corresponding dichronic mirror is 10-20mm, and the blue-ray LED corresponds to dichronic mirror and the gold-tinted corresponds to dichronic mirror center
Point distance is 20-40mm, and the dichronic mirror is in 45 ° with the corresponding light source LED light axle clamp angle.
Filtered as a further improvement, being also disposed with the 3rd collimation lens and the 3rd before the photomultiplier
Piece;The distance between the 3rd collimation lens convex surface summit and the 3rd optical filter are 0.5-2mm, the 3rd optical filter and institute
The distance for stating photomultiplier lower end is 10-20mm;It is 5- that the 4th collimation lens planar ends, which separate out the distance between unthreaded hole,
10mm。
The utility model provides a kind of binary channels animal nerve unit signal record and synchronous stimulating system, the utility model
Purpose be during free moving animals neuron activity is recorded, can realize that light science of heredity is excited and suppresses simultaneously
Experiment, the utility model illustrate contacting between purpose neuron spontaneous emissions and purpose behavior from neuron spontaneous emissions record
Set out, neuronal excitation experiment is respectively adopted again and suppresses experiment and is verified from positive and negative two angles, fully ensured that experimental result
Science and accuracy.The utility model can use same root optical fiber to realize record and stimulatory function, eliminate experimentation
Middle switching record and the process of stimulating apparatus, have saved experimental period, have simplified experimental procedure, made the cycle entirely tested significantly
Shorten.
Brief description of the drawings
Fig. 1 is that a kind of binary channels animal nerve unit signal record of the utility model is illustrated with synchronous stimulating system overall structure
Figure.
Embodiment
In order that the purpose of this utility model, technical scheme and advantage become apparent from, it is right below in conjunction with drawings and Examples
The utility model is further elaborated.It should be appreciated that specific embodiment described herein is only explaining this reality
With new, it is not used to limit the utility model.
, it is necessary to which the intracerebral area-of-interest in experimental subjects expresses corresponding photosensitive protein before light genetic experiment is carried out
(there are two kinds of approach:1st, directly experiment 2 is carried out, by injecting virus in the transgenic animals intracerebral for expressing corresponding photosensitive protein,
Corresponding photosensitive protein is expressed in corresponding brain area interested by viral vector), optical fiber is to be implanted directly into intracerebral expression
The brain area of photosensitive protein.
If carrying out Calcium Signal record, GCaMP6 is expressed;Light science of heredity stimulation test is carried out, is expressed
CHR2;Suppress experiment to carry out light science of heredity, express NpHR;Can also be in the corresponding brain area injection of transgenic animals
Accordingly virus, so as to realize while record and the excited or experiment such as record and suppression simultaneously.Wherein, GCaMP6 and CHR2 is to indigo plant
The sensitive passage of coloured light, but the two power requirement difference to exciting light is very big, GCaMP6 only needs the power of very little
To excite, and CHR2 is then to need larger power to excite, and can carry out signal record using this feature and light is lost
Pass and learn excited experiment;NpHR is only sensitive to gold-tinted, is stimulated so as to receive gold-tinted, carries out light science of heredity Inhibition test (big work(
During the blue laser irradiation of rate, CHR2 passages are opened, it is allowed to are flowed in cation such as sodium ion is a large amount of, produced action potential, nerve
Member is in excitatory state;Small-power blue laser irradiate when, can record the calcium as caused by neuron fires from
The change of sub- concentration fluorescence signal;When yellow laser irradiates, NpHR passages are opened, and chlorion largely enters neuron, so as to
So that neuron is constantly in resting potential, so as to reach inhibition).
It is above-mentioned basis on, the utility model as shown in figure 1, a kind of binary channels animal nerve unit signal record with it is synchronous
Stimulating system, including optic module 1, light source module 2, photoelectric conversion module 3, AD/DA modular converters 4, video acquisition module 5 with
And host computer 6;
The optic module 1 reaches the fluorescence signal of photosensitive protein brain area, in addition to output blue light or gold-tinted to acquisition tables
To corresponding brain area neuron;The optic module 1 includes the 4th collimation lens 11 and optical fiber 12, by the light source module dichronic mirror
The blue light or gold-tinted of reflection are sent to optical fiber 12, activation or the neuron for suppressing corresponding brain area through the 4th collimation lens 11.It is described
Optical fiber limits without diameter and numerical aperture, can arbitrarily be replaced according to experiment demand.
The light source module 2 is used for according to stimulus signal selectively output blue light or gold-tinted, in addition to the fluorescence by reception
Signal is transmitted to photoelectric conversion module 3;The light source module includes blue-ray LED 21, yellow light LED 22, behind blue-ray LED 21
The first collimation lens 211 and the second optical filter 212, the second collimation lens 221 behind yellow light LED 22 and second filter
Piece 222, respectively the first dichronic mirror 213 and the second dichronic mirror 223 after two groups of LED light source optical filters;The collimation is saturating
Mirror is arranged between LED light source and optical filter, the blue light LED light source and yellow light LED light source respectively with AD/DA modular converters 4
Connection, the AD/DA modular converters 4 export, switch and power output size, and caused corresponding light beam is through the collimation lens
Dichronic mirror is sent to after reaching the optical filter, then is carried out by the dichronic mirror being reflected into optical link module.
The a width of 450-490nm of blue LED light source excitation band, a width of 540- of yellow LED light source excitation band
590nm.The blueness and yellow LED light source, the blue led light source can excite OGB-1, GCaMP and chR2 etc., the yellow
LED light source can excite ArchT etc..
Specifically, distance is 5- between the blue-ray LED 21 or the corresponding collimation lens left side plan of yellow light LED 22
10mm, as the utility model preferred embodiment, preferably distance is 8mm;The right side convex surface summit of the corresponding collimation lens is extremely
The distance of corresponding optical filter is 0.5-2mm, and as the utility model preferred embodiment, preferably distance is 1mm;The corresponding optical filtering
Piece to the distance of the corresponding dichronic mirror is 10-20mm, and as the utility model preferred embodiment, preferably distance is 15mm;Institute
State blue-ray LED correspond to dichronic mirror and the gold-tinted to correspond to dichronic mirror central point distance be 20-40mm, it is preferred as the utility model
Embodiment, preferably distance is 30mm;The dichronic mirror is in 45 ° with the corresponding light source LED light axle clamp angle.
The photoelectric conversion module 3 is transmitted to AD/DA and turned the fluorescence signal of reception is converted into electric analoging signal
Change the mold block 4;The photoelectric conversion module 3 is specially photomultiplier, and the AD/DA modular converters 4 are specially data collecting card;
The fluorescent signals of collection being amplified and be converted to analog electrical signal by the photomultiplier.The photomultiplier transit
The 3rd collimation lens 31 and the 3rd optical filter 32 are also disposed with before pipe;The convex surface summit of 3rd collimation lens 31 and the
The distance between three optical filters 32 are 0.5-2mm, and as the utility model preferred embodiment, preferably distance is 1mm;Described 3rd
The distance of optical filter 31 and the photomultiplier lower end is 10-20mm, as the utility model preferred embodiment, preferable distance
For 15mm;It is 5-10mm that the planar ends of 4th collimation lens 11, which separate out the distance between unthreaded hole, preferred as the utility model
Embodiment, preferably distance is 8mm.
The AD/DA modular converters 4 are used to electric analoging signal being converted to data signal, and are uploaded to host computer 6;It is described
AD/DA modular converters 4 are additionally operable to control signal being converted to stimulus signal;
Behavior record is uploaded to host computer 6 by the video acquisition module 5 to record animal behavior;
The reception behavior features of host computer 6 record and data signal are simultaneously integrated and analyzed, and obtain required data result, institute
Stating host computer 6 is also included as AD/DA modular converters 4 send control signal.
As an improvement in addition to video marker module 7, the video marker module 7 and AD/DA modular converters 4 connect
Connect, the animal behavior record of collection to be marked according to electric analoging signal;The video marker module is specially signal
Lamp, the signal lamp are connected with AD/DA modular converters 4 (i.e. data collecting card), and the data collecting card analog electrical signal is strong and weak,
Control signal lamp bright dark time and flashing times, capture point of scintillation by video acquisition module 5 (i.e. CCD camera) and are used as mark
Note, for animal behavior record and the calibration corresponding points of data signal.Signal lamp herein also can be infrared lamp, convenient at night
Without being arrived under lamp state by cameras capture, it is easy to night to be tested.
Because many light genetic experiments need to carry out in the lump with Behaviors survey in experiment, and then observation experiment object exists
When producing corresponding behavior, if brain area has corresponding signal to produce, and related behavior is recorded by camera, and this is related to
To signal record time shaft and behaviouristics record time shaft uniformity the problem of, although software is controlled, signal note
The screen of record and camera is recorded and started simultaneously at, but still has the other error of Millisecond, and some brain area neuron actions are electric
The generation of position is exactly that if time shaft is inaccurate, producing the sequencing of signal and corelation behaviour can not precisely sentence in millisecond rank
It is fixed, so, signal lamp is then set to solve the problem:I.e. signal lamp is the output end for being connected to capture card, experiment
After beginning, a very strong signal (phase can be occurred in the signal of record by software control signals lamp and audio video synchronization
For normal neuron signal), synchronous signal lantern festival is bright once, by cameras capture to (the bright time is adjustable, is generally located on
90ms can be arrived by cameras capture), after the completion of experiment, you can by signal lamp bright moment and a flash of record in analysis software
Between very strong signal alignment, so that it is guaranteed that the time shaft of the two definitely aligns.
Sum it up, a kind of binary channels animal nerve unit signal record of the utility model and synchronous stimulating system, described double
Passage includes stimulation channels and acquisition channel;
Wherein described acquisition channel is specially:The acquisition tables of optic module 1 reach the fluorescence signal of photosensitive protein brain area, warp
Light source module 2 is transferred to up to photoelectric conversion module 3, the photoelectric conversion module 3 fluorescence signal of collection being converted to electrical analogue
Signal simultaneously transmits to AD/DA modular converters 4, AD/DA modular converters 4 electric analoging signal is converted into data signal and exported supreme
Position machine 6, the host computer 6 receive electric signal and analyzed;
The stimulation channels are specially:Host computer 6 sends control signal, and being exported after the conversion of AD/DA modular converters 4 stimulates
Signal to light source module, the light source module exports corresponding blue light or gold-tinted, blue light or the gold-tinted warp according to stimulus signal
Optical link module is output to the brain area of intracerebral expression photosensitive protein, and excited stimulation or suppression are carried out to corresponding neuron areas.
Wherein, blueness and yellow led, can switch at any time according to demand.In continuous recording process, some strength can be given at any time, one
Fix time stimulates with intervals.
The utility model can choose at random suitable diameter and numerical aperture according to selected experimental animal and the difference of brain area
Optical fiber is tested, and can use same root optical fiber, controls the blue led light source to carry out neuron letter by selectivity
Number record with neuronal excitation test, be switched to yellow LED light source carry out neuron Inhibition test, in combination with cameras record
Animal behavior, signal i.e. available accurately spontaneous emissions synchronous with screen are suppressed with behavior, neuron using signal lamp and
A set of experimental result of behavior, neuronal excitation and behavior, it will largely improve Neuscience and neurogenic disease hair
The Efficiency of the interpretation of the cause, onset and process of an illness.
Described above is only preferred embodiment of the present utility model, it is noted that for the common skill of the art
Art personnel, on the premise of the utility model principle is not departed from, some improvements and modifications can also be made, these improvements and modifications
Also it should be regarded as the scope of protection of the utility model.
Claims (10)
1. a kind of binary channels animal nerve unit signal record and synchronous stimulating system, it is characterised in that including optic module, light source
Module, photoelectric conversion module, AD/DA modular converters, video acquisition module and host computer;
The optic module reaches the fluorescence signal of photosensitive protein brain area, in addition to output blue light or gold-tinted to acquisition tables to correspondingly
Brain area neuron;
The light source module is used for according to stimulus signal selectively output blue light or gold-tinted, in addition to the fluorescence signal of reception is passed
Transport to photoelectric conversion module;
The photoelectric conversion module is transmitted to AD/DA moduluss of conversion the fluorescence signal of reception is converted into electric analoging signal
Block;
The AD/DA modular converters are used to electric analoging signal being converted to data signal, and are uploaded to host computer;The AD/DA
Modular converter is additionally operable to control signal being converted to stimulus signal;
Behavior record is uploaded to host computer by the video acquisition module to record animal behavior;
The host computer reception behavior features record and data signal are simultaneously analyzed, and the host computer is also included to AD/DA moduluss of conversion
Block sends control signal.
2. binary channels animal nerve unit signal record as claimed in claim 1 and synchronous stimulating system, it is characterised in that also wrap
Include video marker module, the video marker module is connected with AD/DA modular converters, to according to electric analoging signal to collection
Animal behavior record is marked.
3. binary channels animal nerve unit signal record as claimed in claim 2 and synchronous stimulating system, it is characterised in that described
Light source module includes blue-ray LED, respectively yellow light LED, the respectively collimation lens behind two groups of LED light sources and optical filter, position
Dichronic mirror after two groups of LED light source optical filters;The collimation lens is arranged between LED light source and optical filter, the indigo plant
Light LED light source and yellow light LED light source are connected with AD/DA modular converters respectively, AD/DA modular converters output, switching and
Power output size, caused corresponding light beam are sent to dichronic mirror after the collimation lens reaches the optical filter, then by institute
Dichronic mirror is stated to carry out being reflected into optical link module.
4. binary channels animal nerve unit signal record as claimed in claim 3 and synchronous stimulating system, it is characterised in that described
Photoelectric conversion module is specially photomultiplier, and the AD/DA modular converters are specially data collecting card;The photomultiplier
The fluorescent signals of collection to be amplified and are converted to analog electrical signal.
5. binary channels animal nerve unit signal record as claimed in claim 4 and synchronous stimulating system, it is characterised in that described
Optic module includes the 4th collimation lens and optical fiber, by the blue light or gold-tinted of the light source module dichroic mirror through the 4th collimation
Lens are sent to optical fiber, activation or the neuron for suppressing corresponding brain area.
6. binary channels animal nerve unit signal record as claimed in claim 5 and synchronous stimulating system, it is characterised in that described
Video marker module is specially signal lamp, and the signal lamp is connected with data collecting card, the data collecting card analog electrical signal
Power, control signal lamp bright dark time and flashing times, capture point of scintillation by video acquisition module and are used as mark, for moving
The calibration corresponding points of thing behavior record and data signal.
7. binary channels animal nerve unit signal record as claimed in claim 6 and synchronous stimulating system, it is characterised in that blueness
The a width of 450-490nm of LED light source excitation band, a width of 540-590nm of yellow LED light source excitation band.
8. binary channels animal nerve unit signal record as claimed in claim 7 and synchronous stimulating system, it is characterised in that described
Blueness and yellow LED light source, the blue led light source can excite OGB-1, GCaMP and chR2, and the yellow LED light source can swash
Send out ArchT.
9. binary channels animal nerve unit signal record as claimed in claim 8 and synchronous stimulating system, it is characterised in that described
Distance is 5-10mm between blue-ray LED or the corresponding collimation lens left side plan of yellow light LED, the right side of the corresponding collimation lens
Side convex surface summit to the distance of corresponding optical filter is 0.5-2mm, and the distance of corresponding optical filter to the corresponding dichronic mirror is
10-20mm, the blue-ray LED corresponds to dichronic mirror and the gold-tinted to correspond to dichronic mirror central point distance be 20-40mm, the color separation
Mirror is in 45 ° with the corresponding light source LED light axle clamp angle.
10. binary channels animal nerve unit signal record as claimed in claim 9 and synchronous stimulating system, it is characterised in that institute
The 3rd collimation lens and the 3rd optical filter are also disposed with before stating photomultiplier;3rd collimation lens convex surface summit
The distance between 3rd optical filter is 0.5-2mm, and the distance of the 3rd optical filter and the photomultiplier lower end is 10-
20mm;It is 5-10mm that the 4th collimation lens planar ends, which separate out the distance between unthreaded hole,.
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CN107334471A (en) * | 2016-12-19 | 2017-11-10 | 中国科学院苏州生物医学工程技术研究所 | A kind of binary channels animal nerve unit signal record and synchronous stimulating system |
CN109288511A (en) * | 2018-09-21 | 2019-02-01 | 南京邮电大学 | A kind of sampling algorithm for obtaining neuron action potential from calcium ion fluorescence observation value and going out current moment |
CN109407327A (en) * | 2018-11-05 | 2019-03-01 | 中国科学院苏州生物医学工程技术研究所 | Multidigit point double-photon optical stimulating system and its stimulating method |
CN115316959A (en) * | 2022-10-13 | 2022-11-11 | 浙江大学医学中心(余杭) | Three-color multi-channel optical fiber brain information recording system |
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2016
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CN107334471A (en) * | 2016-12-19 | 2017-11-10 | 中国科学院苏州生物医学工程技术研究所 | A kind of binary channels animal nerve unit signal record and synchronous stimulating system |
CN109288511A (en) * | 2018-09-21 | 2019-02-01 | 南京邮电大学 | A kind of sampling algorithm for obtaining neuron action potential from calcium ion fluorescence observation value and going out current moment |
CN109288511B (en) * | 2018-09-21 | 2021-05-04 | 南京邮电大学 | Sampling algorithm for acquiring neuron action potential appearance time from calcium ion fluorescence observation value |
CN109407327A (en) * | 2018-11-05 | 2019-03-01 | 中国科学院苏州生物医学工程技术研究所 | Multidigit point double-photon optical stimulating system and its stimulating method |
CN115316959A (en) * | 2022-10-13 | 2022-11-11 | 浙江大学医学中心(余杭) | Three-color multi-channel optical fiber brain information recording system |
CN115316959B (en) * | 2022-10-13 | 2023-04-28 | 浙江大学医学中心(余杭) | Three-color multichannel optical fiber brain information recording system |
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