CN106861050A - A kind of wireless neuromodulation device based on light science of heredity - Google Patents
A kind of wireless neuromodulation device based on light science of heredity Download PDFInfo
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Abstract
The present invention relates to medical device technology, specifically related to a kind of wireless neuromodulation device based on light science of heredity, including viral vectors, viral vectors carries promoter, photaesthesia albumen and fluorescin, promoter is used in the specific expressed photaesthesia albumen of specific objective tissue, realize that specificity is precisely controlled, photaesthesia albumen is the key for playing a role;Also include LED light module and wireless regulation and control device;LED light module includes LED array and energy acceptance system;Wireless regulation and control device includes energy emission system and controller;Energy emission system transmits energy to energy acceptance system;LED array and energy acceptance system are packaged in biocompatibility insulating materials, at the destination organization where being arranged on viral vectors.The arrangement achieves the wireless energy supply and remote control of light science of heredity stimulating system.With miniaturization, wireless regulation and control, heat production is few, and small feature is damaged to target tissue, and the applicable field of light science of heredity institute can be used the device.
Description
Technical field
The invention belongs to technical field of medical instruments, more particularly to a kind of wireless neuromodulation dress based on light science of heredity
Put.
Background technology
Light science of heredity(optogenetics)Be for developing rapidly in recent years incorporate optics, software control,
The biotechnology of the multi-crossed disciplines such as gene manipulation techniques, electro physiology.Its cardinal principle is to use genetic manipulation skill first
Be transferred to light sensation gene in specific cells by art carries out the expression of photaesthesia albumen, and photaesthesia albumen is pierced in the illumination of respective wavelength
Swash it is lower can be respectively to cation or anion by producing selectivity, so as to cause the film potential inside and outside cell membrane to become
Change, purpose that is excited to cell selective ground or suppressing is reached, so as to the physiology work(to cell, tissue, organ and organism
Control accurate can be realized.Light genetics technology is developed rapidly in fields such as Neuscience, and the technology is selected within 2010
《Nature Methods》The year method of magazine 2010, and be considered as the technology for being most hopeful to obtain the prize of Nobel's biology
One of.
Although autonomic nerves system is not arranged by consciousness, played a significant role in terms of body life and health is maintained, than
Breathing, heart rate, the change of blood pressure are by autonomic nerve control such as under different conditions.Autonomic nerve it is sympathetic, fan walk composition it is mutual
Antagonism, balance therebetween is to maintaining body health particularly significant.By a large amount of bases and clinical research, it is found that heart is autonomous
The loss of equilibrium of nervous system especially it is orthosympathetic be overexcited participate in and mediated arrhythmia cordis, heart failure, cardiac muscle stalk
Extremely, various diseases such as hypertension develop.Therefore regulating and controlling autonomic nerve by various means makes its releveling particularly significant,
And the method to cardiac autonomic nervous releveling is generally the damage methods such as ablation, excision at present, side effect is easily produced, use light
Genetics technology regulation and control autonomic nerve not only not injured nerve, and can accomplish accurate, controllable.But current light science of heredity thorn
Sharp system is generally wired setting, it is necessary to an optical fiber is connected in vitro, it is difficult in clinical expansion, even if zoopery there is also to it
The deficiencies such as the limitation of activity.
The content of the invention
It is an object of the invention to provide a kind of light science of heredity stimulating system of wireless energy supply, can utilize and connect wifi and lead to
Cross APP to interact, so as to realize wireless regulation and control.
To achieve the above object, the technical solution adopted by the present invention is:A kind of wireless neuromodulation based on light science of heredity
Device, including viral vectors, the viral vectors carry promoter, photaesthesia albumen and fluorescin implantation destination organization, institute
Promoter is stated in the specific expressed photaesthesia albumen of specific objective tissue, realizing that specificity is precisely controlled, the fluorescence egg
Given full expression to for confirmation in vain;Characterized in that, also including LED light module and wireless regulation and control device;The LED light module
Including LED array and energy acceptance system;The wireless regulation and control device includes energy emission system and controller;The energy hair
Penetrate system and transmit energy to the energy acceptance system;The LED array and energy acceptance system are packaged in biocompatibility
In insulating materials, at the destination organization where being arranged on the viral vectors.
In the above-mentioned wireless neuromodulation device based on light science of heredity, the LED array includes several LED;It is described
Energy acceptance system includes being arranged on multiple antennas around several LED, the multiple antenna be sequentially connected rectifier and
Amplifier;The amplifier connects several LED.
In the above-mentioned wireless neuromodulation device based on light science of heredity, the energy emission system includes being sequentially connected
Electric power system, inverter, control module and RF transmitter units;The controller includes the control panel, the wifi that are connected with each other
Receiver module, integrated chip, the built-in APP of program;The energy emission system is connected with controller and is encapsulated in same shell
In.
In the above-mentioned wireless neuromodulation device based on light science of heredity, the control module is used to adjust stimulates ginseng
Number, sends matrix ripple;The stimulation parameter includes stimulation voltage, stimulating current, stimulates pulsewidth, intermittent time, duration.
In the above-mentioned wireless neuromodulation device based on light science of heredity, the wireless regulation and control device uses internal battery
Or external power supply.
In the above-mentioned wireless neuromodulation device based on light science of heredity, the viral vectors includes slow virus and gland phase
Close virus;The adeno-associated virus includes AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, according to mesh
Mark tissue selects virus subtype.
In the above-mentioned wireless neuromodulation device based on light science of heredity, the photaesthesia albumen is photosensitive from excitability
Sense albumen, inhibition photaesthesia albumen, bidirectional modulation photaesthesia albumen.
In the above-mentioned wireless neuromodulation device based on light science of heredity, if the excitability photaesthesia albumen from
ChR2, the then light of LED array transmitting 470nm or so wavelength;If from VChR1, the LED array launches 545nm
The light of left and right wavelength;If from C1V1, the light of the LED array transmitting 540nm or so wavelength;The inhibition light
If sensitive Protein launches the light of 565nm or so wavelength from ArchT, the LED array;If from eNpHR3.0, institute
State the light of LED array transmitting 590nm or so wavelength;If from eBR, the light of the LED array transmitting 540nm or so wavelength
Line;If the bidirectional modulation photaesthesia albumen is from ChR2-step function opsins, the LED array transmitting
470nm wavelength light activation nearby, nearby wavelength light suppresses transmitting 590nm;If from VCHR-step function
Opsins, then the LED array transmitting 560nm wavelength light activation nearby, nearby wavelength light suppresses transmitting 390nm.
In the above-mentioned wireless neuromodulation device based on light science of heredity, the photaesthesia albumen can both be carried by virus
Body is specific expressed in targeted tissue, also can make mesh by transgenic animal model, Cre-loxP systems in zoopery
Mark tissue expression photaesthesia albumen.
Photaesthesia albumen is the key that the wireless neuromodulation device based on light science of heredity plays a role, by special wavelength light
Channel opener after line activation, causes ion flow inside and outside cell membrane, changes cell membrane potential, causes depolarising, hyperpolarization, so that
Play excited, inhibitory action.
The beneficial effects of the invention are as follows:Realize the wireless energy supply and remote control of light science of heredity stimulating system.With small
Type, wireless regulation and control, heat production is few, and the characteristics of small to target tissue damage, the applicable field of light science of heredity institute can be used the dress
Put.
Brief description of the drawings
Fig. 1 is the overall structure diagram of one embodiment of the invention;
Fig. 2 is the LED array and energy acceptance system schematic of one embodiment of the invention;
Fig. 3 is the wireless regulation and control device and energy emission system schematic diagram of one embodiment of the invention;
Fig. 4 is the energy emission system and energy acceptance system connection diagram of one embodiment of the invention;
Fig. 5 is the workflow schematic diagram of one embodiment of the invention;
Wherein, 101- wireless regulation and controls device, 102- radio frequency signals, 103-LED light emitting modules, the starlike nerve in 104- left sides
Section, 105-LED arrays, 106-LED transmitting specific wavelength light, 201- energy emission systems, 202- energy acceptances system and LED
Array, 401- viral vectors injection schematic diagram, 402- viral vectors, 403- light stimulation mechanism of action figures.
Specific embodiment
Embodiments of the present invention are described in detail below in conjunction with the accompanying drawings.
The present embodiment is adopted the following technical scheme that:A kind of wireless neuromodulation device based on light science of heredity, including virus
Carrier, the viral vectors carries promoter, photaesthesia albumen and fluorescin implantation destination organization, and the promoter is used for
The specific expressed photaesthesia albumen of specific objective tissue, realizes that specificity is precisely controlled, and the fluorescin is used to confirm fully
Expression;Characterized in that, also including LED light module and wireless regulation and control device;The LED light module include LED array and
Energy acceptance system;The wireless regulation and control device includes energy emission system and controller;The energy emission system is to described
Energy acceptance system transmits energy;The LED array and energy acceptance system are packaged in biocompatibility insulating materials, if
Put at the destination organization where the viral vectors is pressed close to.
Further, the LED array includes several LED;The energy acceptance system includes being arranged on described several LED weeks
The multiple antennas for enclosing, the multiple antenna is sequentially connected rectifier and amplifier;The amplifier connects several LED.
Further, the energy emission system includes the electric power system, inverter, control module and the RF transmittings that are sequentially connected
Unit;The controller includes the control panel, wifi receiver modules, the integrated chip that are connected with each other, the built-in APP of program;It is described
Energy emission system is connected and is encapsulated in same shell with controller.
Further, the control module is used to adjust stimulation parameter, sends matrix ripple;The stimulation parameter includes stimulating electricity
Pressure, stimulating current, stimulation pulsewidth, intermittent time, duration.
Further, the wireless regulation and control device uses internal battery or external power supply.
Further, the viral vectors includes slow virus and adeno-associated virus;The adeno-associated virus include AAV1,
AAV2, AAV3, AAV4, AAV5, AAV6, AAV7, AAV8, AAV9, virus subtype is selected according to destination organization.
Further, the photaesthesia albumen selects excitability photaesthesia albumen, inhibition photaesthesia albumen, bidirectional modulation light
Sensitive Protein.
Further, if the excitability photaesthesia albumen is from ChR2, described LED array transmitting 470nm or so wavelength
Light;If from VChR1, the light of the LED array transmitting 545nm or so wavelength;If from C1V1, the LED
The light of array emitter 540nm or so wavelength;If the inhibition photaesthesia albumen is from ArchT, the LED array transmitting
The light of 565nm or so wavelength;If from eNpHR3.0, the light of the LED array transmitting 590nm or so wavelength;If choosing
With eBR, then the light of described LED array transmitting 540nm or so wavelength;If the bidirectional modulation photaesthesia albumen is from ChR2-
Step function opsins, then the LED array transmitting 470nm wavelength light activation nearby, wavelength near transmitting 590nm
Light suppresses;If from VCHR-step function opsins, nearby wavelength light swashs the LED array transmitting 560nm
Living, nearby wavelength light suppresses transmitting 390nm.
Further, the photaesthesia albumen both can be specific expressed in targeted tissue by viral vectors, also can be
Destination organization is set to express photaesthesia albumen by transgenic animal model, Cre-loxP systems in zoopery.
During specific implementation, as shown in figure 1, a kind of wireless neuromodulation device based on light science of heredity, comprising viral vectors,
LED light module and wireless regulation and control device.Viral vectors makes the specific expressed photaesthesia albumen in target area, LED light module
Including LED array and energy acceptance system, LED array is used to launch the illumination of suitable photaesthesia albumen wavelength, energy acceptance system
Unite for receiving energy;Wireless regulation and control device includes energy emission system and controller;Energy emission system include electric power system,
Inverter, control module and RF transmitter units;Controller includes the control panel, wifi receiver modules, the integrated core that are connected with each other
Piece, the built-in APP of program, energy emission system and controller merge on a device, and are encapsulated in same shell.Every time
The record storage integrated chip for stimulating is provided, wifi can be connected, upload APP, by the mobile terminal synchronization such as mobile phone, draw treatment bent
Line.
As shown in Fig. 2 LED light module, for sending specific wavelength illumination, photaesthesia albumen in stimulation target tissue,
Change film potential inside and outside target tissue cells, so that excited or suppress destination organization, LED light module contains several LED arrays
Be packaged within biocompatibility insulating materials with energy acceptance system, LED array presses close to destination organization, can complete illumination arrive
Each destination organization.LED institutes launch wavelength depends on photaesthesia albumen, and ArchT can be shone using 565nm or so wavelength light, ChR2
Can be shone using 470nm or so wavelength light.Energy acceptance system includes the antenna around LED, rectifier and amplifier;Antenna can be received
Radiofrequency signal is sent to wireless regulation and control device, so as to be converted into electric signal, and direct current is converted into by rectifier, then by putting
Big device hair is big, and generation is enough to supply the luminous energy of LED.Energy acceptance system is packaged in biocompatibility together with LED array
In insulating materials.
As shown in figure 3, wireless regulation and control device includes energy emission system and controller.Energy emission system is by power supply system
System, inverter, control module and RF transmitter units composition;Controller is made up of control panel, wifi receiver modules and APP.Nothing
Line regulation device is powered by internal battery or extraneous power supply, and energy emitting element is converted into exchange after producing electric current by inverter
Electricity, alternating current sends radiofrequency signal by RF transmitter units, passes out energy, and energizing quantity reception system is received.Its control mould
Block, can adjust stimulation parameter, including stimulation voltage, stimulating current, stimulation pulsewidth, intermittent time, duration, send matrix
Ripple.Wireless regulation and control device also carry wifi receiver modules, integrated chip, the built-in APP of program, can will every time provide stimulate and note
Address book stored is got off, and is connected wifi and is synchronized by uploading the mobile devices such as APP and mobile phone, is drawn and is treated curve.
Wireless neuromodulation device can be not only used for autonomic nervous system, be treated by releveling autonomic nerve
The diseases such as arrhythmia cordis, improvement myocardial ischemia, heart failure, prevention sudden death, it can also be used to be implanted into other positions such as neck, realize
Other are acted on treatment depression etc., can be not only used for clinic, also can be used for zoopery.
Viral vectors is mainly slow virus, adeno-associated virus, adeno-associated virus include AAV1, AAV2, AAV3, AAV4,
AAV5, AAV6, AAV7, AAV8, AAV9, specific Virus Type and virus subtype are selected according to effective object and destination organization, are moved
Thing experiment, short-period used can use adeno-associated virus, and feature is transfection efficiency high.Long-term experiment, Clinical practice can be using slow diseases
Poison, its feature is that can be integrated into host genome, stabilization expression.Adeno-associated virus AAV9 hypotypes are mainly to heart, maincenter
The tissue affinities such as nervous system, muscle are high, and AAV8 hypotypes are mainly high to liver, eye, nervous system affinity, and causing can basis
Different target organs select specific virus hypotype, and AAV9 hypotypes can be used for heart.Excitability photaesthesia albumen is used as needed,
Inhibition photaesthesia egg, bidirectional modulation photaesthesia albumen can be used for suppressing stellate ganglion active treatment arrhythmia cordis
ArchT, eNpHR also carry specificity promoter as inhibition photaesthesia albumen, viral vectors, only express purpose in target organ
Gene, reaches specificity and is precisely controlled.In zoopery, also reusable transgenic animal model, Cre-loxP system expressions
Photaesthesia albumen, only uses the LED light lighting system and wireless controlled energy, control system in the present invention.
LED array is used to send specific wavelength illumination, and photaesthesia albumen in stimulation target tissue changes target tissue cells
Inside and outside film potential so that excited or suppress target tissue, LED array contain several LED be packaged in biocompatibility insulating materials it
It is interior, press close to destination organization, can complete illumination to whole destination organization.LED institutes launch wavelength depends on photaesthesia albumen, ChR2
Shone using 470nm or so wavelength lights, VChR1, using 545nm or so wavelength light;C1V1 is using 540nm wavelength or so light;
ArchT is using 565nm or so wavelength light;ENpHR3.0 is using 590nm or so wavelength light;EBR, using 540nm or so ripples
Light long.
The wireless neuromodulation device of the present embodiment, in addition to it can be used to regulate and control cardiac autonomic nervous, it may also be used in control
Pivot nerve, the neck vagus nerve treatment purposes such as depression, due to its miniaturization, wireless regulation and control, heat production is few, target tissue is damaged
Small the characteristics of, the applicable field of light science of heredity institute can be used the system.
Hereinafter the wireless neuromodulation device of the present embodiment is applied to reduce room by suppressing Left Stellate Ganglions
Property arrhythmia cordis, improve myocardial ischemia prognosis.As shown in figure 1, the AAV9 viruses of ArchT will be carried by modus operandi first
Left Stellate Ganglions 104 are injected to, and are nearby implanted into LED light module 103, ArchT stabilizations are expressed at about 4 weeks, now
The controlling switch of wireless regulation and control device 101 is opened, stimulation parameter is adjusted in control panel, wireless regulation and control device 101 sends nothing
Line radiofrequency signal 102, the LED light module 103 being implanted is received, and the energy acceptance system inside LED light module 103 is received
, there is electric current in signal, and supply LED array 105 sends the irradiation Left Stellate Ganglions 104 of 565nm wavelength light 106, left side star
ArchT is activated in shape neuromere 104, causes ion distribution inside and outside nerve cell to change, and film potential is presented hyperpolarization and changes, suppression
The neural electrical activity of system, so that sympathetic excitability is reduced, the generation of VA etc. after reduction myocardial infarction.
The irradiation of LED array 104 Left Stellate Ganglions schematic diagram as shown in Figure 2.Energy inside LED light module 103
Antenna receives radiofrequency signal in reception system 202, is converted into electric energy, and is converted into direct current by rectifier, and amplified device is put
Greatly, supply LED lights.
Energy emission system 201 includes electric power system, inverter, control module in wireless regulation and control device 101 as shown in Figure 3
With RF transmitter units, and built-in integrated chip and wifi module, the built-in APP of program.Energy is supplied by internal battery or external power supply
Should, and alternating current is converted into by adverse current device, electric current flows through RF transmitter units, launches radio frequency signal for LED energy supplies.
As shown in figure 4, energy emission system 201 launches wireless energy received by energy acceptance system 202, for supplying
LED lights.
As shown in Figure 5, viral vectors injection schematic diagram 401, light stimulation mechanism of action Figure 40 3.Carry specific sequence
The viral vectors 402 of row, promoter act as it is specific expressed in specific objective tissue, opsin be photaesthesia protein exhibits from
Subchannel is acted on, and is the core of the system, can as needed from types such as inhibition or sensitiveness, and fluorescin can be used to examine
Survey and confirm whether target protein expresses.ArchT can be carried as photaesthesia albumen using AAV9 in the present embodiment, and connect fluorescence egg
In vain, after in virus 104 Left Stellate Ganglions of injection, expressed by 4 weeks or so viral steadies, now give 565nm illumination
Left side shape neuromere(LSG)So that film potential changes inside and outside nerve cell, nerve cell hyperpolarization, with suppression LSG
The generation of arrhythmia cordis after neural activity reduction myocardial infarction.
It should be appreciated that the part that this specification is not elaborated belongs to prior art.
Although the specific embodiment of the invention above in association with Description of Drawings, those of ordinary skill in the art should
Understand, these are merely illustrative of, and various deformation or modification can be made to these implementation methods, without departing from original of the invention
Reason and essence.The scope of the present invention is only limited by the claims that follow.
Claims (9)
1. a kind of wireless neuromodulation device based on light science of heredity, including viral vectors, the viral vectors carrying promoter,
Photaesthesia albumen and fluorescin implantation destination organization, the promoter are used in the specific expressed photaesthesia of specific objective tissue
Albumen, realizes that specificity is precisely controlled, and the fluorescin gives full expression to for confirmation;Characterized in that, also luminous including LED
Module and wireless regulation and control device;The LED light module includes LED array and energy acceptance system;The wireless regulation and control device
Including energy emission system and controller;The energy emission system transmits energy to the energy acceptance system;It is described LED gusts
Row and energy acceptance system are packaged in biocompatibility insulating materials, the target where being arranged on the viral vectors
At tissue.
2. the wireless neuromodulation device of light science of heredity is based on as claimed in claim 1, it is characterised in that the LED array
Including several LED;The energy acceptance system includes the multiple antennas being arranged on around several LED, the multiple antenna
It is sequentially connected rectifier and amplifier;The amplifier connects several LED.
3. the wireless neuromodulation device of light science of heredity is based on as claimed in claim 1, it is characterised in that the energy transmitting
System includes the electric power system, inverter, control module and the RF transmitter units that are sequentially connected;The controller includes being connected with each other
Control panel, wifi receiver modules, integrated chip, the built-in APP of program;The energy emission system is connected and seals with controller
In same shell.
4. the wireless neuromodulation device of light science of heredity is based on as claimed in claim 3, it is characterised in that the control module
For adjusting stimulation parameter, matrix ripple is sent;When the stimulation parameter includes stimulation voltage, stimulating current, stimulates pulsewidth, interval
Between, the duration.
5. the wireless neuromodulation device of light science of heredity is based on as claimed in claim 1, it is characterised in that the wireless regulation and control
Device uses internal battery or external power supply.
6. the wireless neuromodulation device of light science of heredity is based on as claimed in claim 1, it is characterised in that the viral vectors
Including slow virus and adeno-associated virus;The adeno-associated virus include AAV1, AAV2, AAV3, AAV4, AAV5, AAV6, AAV7,
AAV8, AAV9, virus subtype is selected according to destination organization.
7. the wireless neuromodulation device of light science of heredity is based on as claimed in claim 1, it is characterised in that the photaesthesia egg
It is white to select excitability photaesthesia albumen, inhibition photaesthesia albumen, bidirectional modulation photaesthesia albumen.
8. the wireless neuromodulation device of light science of heredity is based on as claimed in claim 7, it is characterised in that the excitability light
If sensitive Protein launches the light of 470nm or so wavelength from ChR2, the LED array;If from VChR1, the LED
The light of array emitter 545nm or so wavelength;If from C1V1, the light of the LED array transmitting 540nm or so wavelength;
If the inhibition photaesthesia albumen launches the light of 565nm or so wavelength from ArchT, the LED array;If from
ENpHR3.0, the then light of LED array transmitting 590nm or so wavelength;If from eBR, the LED array transmitting
The light of 540nm or so wavelength;If the bidirectional modulation photaesthesia albumen is from ChR2-step function opsins,
The LED array transmitting 470nm wavelength light activation nearby, nearby wavelength light suppresses transmitting 590nm;If from VCHR-
Step function opsins, then the LED array transmitting 560nm wavelength light activation nearby, wavelength near transmitting 390nm
Light suppresses.
9. the wireless neuromodulation device of light science of heredity is based on as claimed in claim 1, it is characterised in that the photaesthesia egg
Bai Jike by viral vectors it is specific expressed in targeted tissue, can also pass through in zoopery transgenic animal model,
Cre-loxP systems make destination organization express photaesthesia albumen.
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