CN210963587U - Closed-loop regulating and controlling device for treating epilepsy based on optogenetics - Google Patents
Closed-loop regulating and controlling device for treating epilepsy based on optogenetics Download PDFInfo
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- CN210963587U CN210963587U CN201921180697.XU CN201921180697U CN210963587U CN 210963587 U CN210963587 U CN 210963587U CN 201921180697 U CN201921180697 U CN 201921180697U CN 210963587 U CN210963587 U CN 210963587U
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Abstract
The utility model discloses a closed-loop regulation and control device of treatment epilepsy based on optogenetics, including viral vector, wireless regulation and control device, current detection system, wired regulation and control system and L ED control system, plant L ED control system and current detection system at the epilepsy kitchen, wired regulation and control system is planted behind the ear subcutaneous pocket department, and is connected with L ED control system through output lead, is connected with current detection system through the input lead, and wireless regulation and control device is connected through wireless module with L ED control system.
Description
Technical Field
The utility model relates to the technical field of medical equipment, especially, relate to a closed loop formula regulation and control device of treatment epilepsy based on optogenetics.
Background
The first application of the principles of optogenetic technology was derived from studies conducted by Zemelman et al in 2002 to introduce chrge into target cells for the regulation of neural activity. In 2005, Boyden and Deissoth, et al, have collectively reported a technique for controlling nerve cell activity using a light-sensitive protein. The concept of optogenetics is proposed by Deisseroth et al in 2006, and refers to a cell biology research technology method combining genetics (recombinant DNA technology) and optical technology. The method expresses light-sensitive protein on selected cells, and then applies light with corresponding wavelength to irradiate and activate the light-sensitive protein, thereby realizing fine regulation and control of physiological functions of cells, tissues, organs and animals. Optogenetic techniques have now been applied to the study of many diseases, such as cardiovascular diseases, neurological diseases, etc. The first search in the field of epilepsy treatment is that Halorodopsin (NpHR) is introduced into main cells of hippocampus by Tnnesen and the like in 2009, and it is observed that the optogenetic technology can successfully inhibit epileptic seizure on a cultured rat brain slice epilepsy model. Therefore, the optogenetic technology is proposed to be possibly a new method for treating epilepsy in the future.
Epilepsy is a chronic brain disease caused by abnormal discharge of a group of neurons in a hypersynchronous manner, and is caused by an imbalance between excitatory and inhibitory properties of the central nervous system. At present, the main treatment method of epilepsy is drug treatment, but still some patients have unsatisfactory drug treatment effect, and epilepsy which is difficult to treat is developed. Traditional antiepileptic drugs show a deficient specificity in the epileptic neural circuit for a specific cell type. The hyperexcitability of many neurons during a seizure is dynamic and requires precise temporal control of neural activity for effective treatment. The optogenetic technology has temporal and spatial specificity, can be accurately positioned in a group or single neuron cells, and can provide a new choice for treating the epilepsy.
The patent publication CN106861050A "a wireless nerve control device based on optogenetics" realizes wireless energy supply and remote control of optogenetics stimulation system, has the characteristics of miniaturization, wireless control, less heat generation and small damage to target tissues, and treats arrhythmia, improves myocardial ischemia, heart failure, prevents sudden death and other diseases by rebalancing autonomic nerves; however, the device can only perform active and unidirectional stimulation on corresponding target cells, and when neurons are abnormally discharged, abnormal discharge cannot be detected to perform autonomous treatment on diseases, so that the neurons can be quickly inhibited or excited, and the symptom of disease attack can be improved or eliminated.
SUMMERY OF THE UTILITY MODEL
In order to solve the above problem, the utility model provides a closed-loop type regulation and control device of treatment epilepsy based on optogenetics, concrete technical scheme is:
a closed-loop regulation and control device for treating epilepsy based on optogenetics comprises a virus carrier and a wireless regulation and control device, wherein the virus carrier carries a promoter and photosensitive protein, and is characterized by further comprising a current detection system, a wired regulation and control system and a L ED control system, wherein the current detection system comprises an electrode tip for detecting local current of epileptic focus discharge and an input lead connected with the electrode tip and transmitting a current signal detected by the electrode tip, the wired regulation and control system comprises a processor connected with the input lead and used for receiving and processing the current signal and a first power supply module electrically connected with the processor and used for supplying power to the processor, the processor is connected with an output lead and used for controlling the L ED control system according to a processing result of the current signal, the L ED control system comprises a plurality of L ED arrays, a control module electrically connected with the L ED array and a second power supply system, the control module is electrically connected with the output lead and used for receiving the signal of the processor and controlling the L ED array to emit light, the L ED control system and the electrode tip are packaged in biocompatible insulating material and are implanted in an epileptic focus, and the subcutaneous ear after the regulation and control system is implanted in an.
Further, wireless regulation and control device includes the shell, sets up control panel on the shell and encapsulates the built-in APP of interconnect's bluetooth emission module, wifi module, integrated chip, procedure in the shell, control panel passes through integrated chip control bluetooth emission module transmission control signal, control signal is including control irradiant intermittent type time and duration.
Furthermore, a bluetooth receiving module for receiving the control signal transmitted by the bluetooth transmitting module is arranged in the control module, and controls L ED array to emit light.
Furthermore, the material of the electrode head is niobium-titanium alloy.
Furthermore, the input lead and the output lead are packaged in a silica gel protective sleeve, and the lead is made of carbon nano tubes or superconducting ceramics.
Further, the viral vector is an adenovirus or a lentivirus.
Furthermore, the photosensitive protein can be one of ChR2 or NpHR, if ChR2 is selected, the L ED array emits light with the wavelength of 350-550 nm, and if NpHR is selected, the L ED array emits light with the wavelength of 525-650 nm.
Has the advantages that:
the utility model detects the abnormal discharge of the neuron when the epileptic seizure is detected through the electrode tip, so as to realize the excitation of the autonomic inhibition neuron cell; meanwhile, the target cells can be stimulated through wireless control, and the attack of diseases can be prevented. The device combines wireless regulation and limited regulation, and realizes closed-loop treatment of epilepsy by optogenetic technology.
Drawings
Fig. 1 is a schematic diagram of the frame shape of the present invention.
Fig. 2 is a schematic connection diagram of the wired control of the present invention.
Fig. 3 is a schematic view of the wireless control device of the present invention.
In the figure, 1 electrode tip, 2 input leads, 3 processors, 4 output leads, 5 control modules, 6L ED arrays, 7 wireless regulation and control devices, 8 shells, 9 first power supply modules, 10 second power supply modules, 11 third power supply modules, 12 subcutaneous capsules, 13 silica gel protective sleeves, 14 insulating materials and 15 control signals.
Detailed Description
The invention will be further described with reference to the following drawings and specific embodiments:
as shown in fig. 1 and 2, a closed-loop control device for treating epilepsy based on optogenetics comprises a virus vector, a wireless control device 7, an L ED control system, a current detection system and a wired control system, wherein the virus vector is injected into brain astrocytes, the L ED control system and the current detection system are implanted at an epileptic focus, particularly a discharge position, the wired control system is implanted in a retroauricular subcutaneous sac 12 and connected with the L ED control system through an output lead 4 and the current detection system through an input lead 2, the wireless control device 7 is a handheld control device and connected with the L ED control system through a wireless module.
A current detection system comprises an electrode head 1 and an input lead 2 connected with the electrode head 1, wherein the electrode head 1 is used for detecting local current of epileptic focus discharge, and a detected current signal is input into a wired regulation and control system through the input lead 2, the wired regulation and control system comprises a processor 3 connected with the input lead 2 and an output lead 4 connected with the processor 3, the processor 3 receives the current signal input by the electrode head 1 and compares the current signal with a current threshold value built in the processor 3, when the current signal received by the processor 3 exceeds the threshold value, the processor 3 sends a command signal and transmits the command signal to a L ED control system through the output lead 4, the processor 3 adopts a built-in first power supply module 9 for supplying power, the L ED control system comprises a plurality of L ED arrays 6 and control modules 5 electrically connected with L ED arrays 6, the control modules 5 are electrically connected with the output lead 4 and used for receiving the command signal of the processor 3 and controlling L ED arrays 6 to send light, the control modules 5 are also internally provided with Bluetooth receiving modules, the built-in which are internally provided with a built-in ED 2 array 6, a power supply module 38710 which is used for receiving the insulation material, and is used for enabling the insulation material to be exposed to a corresponding tissue discharge detection point of an insulation material 38914, and enabling the insulation material to be conveniently exposed to be exposed to the corresponding to the insulation material, and be exposed to the insulation material.
In this embodiment, the electrode tip 1 is made of niobium-titanium alloy; the input lead 2 and the output lead 4 are wrapped by insulating layers and then are packaged in a silica gel protective sleeve 13, the lead is made of one of carbon nano tubes or superconducting ceramics, and the length of the lead is 8-10 cm.
As shown in FIG. 3, the wireless control device 7 includes a housing 8, a control panel arranged on the housing 8, a Bluetooth transmitting module, a wifi module, an integrated chip, and a built-in APP packaged in the housing 8, wherein the Bluetooth transmitting module and the wifi module are integrated on the integrated chip, and further integrated with an interval time module and a duration time module for controlling the illumination of the L ED array 6, control buttons for respectively triggering the interval time module and the duration time module are arranged on the control panel, after the corresponding control buttons are pressed, the integrated chip controls the Bluetooth transmitting module to send out corresponding control signals 15, which are received by a Bluetooth receiving module in the control module 5, so as to control the L ED array 6 to send out the illumination of the corresponding time, the integrated chip writes in the built-in APP, can record and store the interval time and duration time of L ED illumination sent each time, connects wifi, synchronizes with mobile devices such as mobile phones by uploading the APP, and draws a treatment curve, and the wireless control device 7 adopts a built-in third power supply module 11 or an external power supply to supply power supply.
Furthermore, the virus vector carries a promoter and a photosensitive protein, and can selectively carry a fluorescent protein, the promoter is used for specifically expressing the photosensitive protein in a specific target tissue to realize specific accurate control, and the fluorescent protein is used for confirming whether the photosensitive protein is successfully expressed in a target cell; the photosensitive protein is activated by being irradiated by specific light, thereby realizing the fine regulation and control of the physiological functions of cells, tissues, organs and animals.
The virus vector is one of adenovirus or lentivirus; adenovirus-associated vectors can express genes in a wide area, while lentiviral-associated vectors can express genes in target cells for a longer period of time and with stability. The adenovirus can select specific virus types and virus subtypes according to an acting object and a target tissue, can be used in animal experiments and short-term use, and is characterized by high transfection efficiency. The slow virus can be adopted in long-term experiment and clinical use, and is characterized by being capable of integrating into a host genome and stably expressing.
Furthermore, the photosensitive protein mainly comprises two major classes, one class is a sodium ion Channel which is represented by Channel-rhodopsin-2(ChR2) and can be activated by illumination, ChR2 is a 7-transmembrane non-selective cation Channel protein, cell membranes can be depolarized by illumination to cause cell excitation, and ChR2 is excitatory photosensitive protein; another class is a light-activated chloride pump represented by NpHR, which is an inhibitory light-sensitive protein, and which hyperpolarizes the cell membrane by light irradiation to inhibit cellular excitability. If the photosensitive protein is ChR2, the activation spectrum range is 350-550 nm, and the central wavelength is 470 nm; if the excitation photosensitive protein is selected from NpHR, the activation spectrum range is 525-650 nm, and the central wavelength is 578 nm.
The method is described by taking inhibitory photosensitive protein NpHR as an example, firstly, drilling a skull, injecting a lentiviral vector carrying an NpHR gene into cerebral astrocytes in an operative manner, implanting a current detection system and an L ED control system encapsulated in a biocompatible insulating material 14 into an epileptic focus, wherein an electrode tip 1 is implanted into a discharge position of the epileptic focus so that a discharge current value can be detected at the first time when the epileptic seizure occurs, L ED array 6 adopts a device which can emit light with a wavelength of 525-650 nm, and the direction of the light illumination faces the photosensitive protein NpHR, leading an input lead 2 and an output lead 4 out through a drilling hole to fix a bone hole, placing a wired regulation and control system into a subcutaneous sac 12 behind the ear so as not to affect the appearance and the quality of life, using a quick connector for the input lead 2 and the output lead 4, so that when the device is disassembled, the pH 1 detects local current, inputs a current signal into a processor 3 through the input lead 2, and when the current signal exceeds a set threshold value of the processor 3, the light sensitive protein NpHR processing module can emit a control signal to effectively control a target signal to transmit a signal to a target signal for controlling a target module which emits a signal to activate a target module for controlling the light emission control module 635 to receive a target signal to reduce the light emission and accordingly, thereby effectively controlling the signal to control the signal to reduce the signal to control signal to activate the target module to receive the target signal of the target signal to control module.
When a patient realizes that the epilepsy is about to occur, or the electrode head 1 cannot effectively detect a current signal and does not trigger the control module 5, or the epilepsy is prevented through the closed-loop control device, the wireless control device 7 can be used for pressing down a control button on the wireless control device 7 at a short distance to trigger the intermittent time module and the continuous time module, an integrated chip in the wireless control device controls the Bluetooth transmitting module to transmit a corresponding control signal 15, the control signal is received by the Bluetooth receiving module in the control module 5, and the L ED array 6 is controlled to emit light at a corresponding time, so that target cells are activated, and the epilepsy is prevented or inhibited.
However, it should be understood that the processor 3, the control module 5 and the integrated chip may be made of a single chip (integrated circuit chip), and program instructions are written in the single chip to process the current signal, control the power on/off, and control the bluetooth module to send out corresponding instructions, so as to implement corresponding functions.
Claims (7)
1. A closed-loop regulation and control device for treating epilepsy based on optogenetics comprises a virus vector and a wireless regulation and control device, wherein the virus vector carries a promoter and a photosensitive protein, and is characterized by further comprising:
the current detection system comprises an electrode tip for detecting partial current of epileptic focus discharge and an input lead which is connected with the electrode tip and transmits a current signal detected by the electrode tip;
the wired regulation and control system comprises a processor connected with the input lead and used for receiving and processing current signals, and a first power supply module electrically connected with the processor and used for supplying power to the processor, wherein the processor is connected with an output lead;
l ED control system including multiple L ED arrays, control modules electrically connected to L ED arrays, and second power supply modules, the control modules electrically connected to the output wires for receiving signals from the processor and controlling L ED arrays to emit light, the processor controlling the L ED control system according to the processing of the current signals;
the L ED control system and the electrode tip are packaged in a biocompatible insulating material and are implanted into an epileptic focus, and the wired regulation and control system is implanted into the subcutaneous bursa behind the ear.
2. The optogenetics-based closed-loop control device for epilepsy therapy according to claim 1, wherein the wireless control device comprises a housing, a control panel disposed on the housing, and a bluetooth transmitting module, a wifi module, an integrated chip, and a program-embedded APP packaged in the housing, wherein the control panel controls the bluetooth transmitting module to transmit a control signal through the integrated chip, and the control signal comprises an interval time and a duration time of control light.
3. The optogenetics-based closed-loop control device for epilepsy therapy of claim 2, wherein the control module is embedded with a bluetooth receiving module for receiving the control signal transmitted by the bluetooth transmitting module, and controls L ED array to emit light.
4. The closed-loop control device for the treatment of epilepsy based on optogenetics as claimed in claim 1, wherein the material of the electrode tip is niobium-titanium alloy.
5. The optogenetics-based closed-loop control device for epilepsy as claimed in claim 1, wherein the input lead and the output lead are encapsulated in a silicone sheath, and the leads are made of carbon nanotubes or superconducting ceramics.
6. The optogenetics-based closed-loop control device for epilepsy of claim 1, wherein the viral vector is an adenovirus or a lentivirus.
7. The closed-loop control device for treating epilepsy based on optogenetics as claimed in claim 1, wherein the photosensitive protein is selected from one of ChR2 or NpHR, the L ED array emits light with wavelength of 350-550 nm if ChR2 is selected, and the L ED array emits light with wavelength of 525-650 nm if NpHR is selected.
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| CN201921180697.XU CN210963587U (en) | 2019-07-25 | 2019-07-25 | Closed-loop regulating and controlling device for treating epilepsy based on optogenetics |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112640847A (en) * | 2020-12-30 | 2021-04-13 | 重庆医科大学附属第一医院 | Endogenous epileptic seizure animal model and construction method thereof |
| CN113967023A (en) * | 2021-10-27 | 2022-01-25 | 复旦大学 | Closed-loop optogenetic intervention system and intervention method |
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2019
- 2019-07-25 CN CN201921180697.XU patent/CN210963587U/en not_active Expired - Fee Related
Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN112640847A (en) * | 2020-12-30 | 2021-04-13 | 重庆医科大学附属第一医院 | Endogenous epileptic seizure animal model and construction method thereof |
| CN112640847B (en) * | 2020-12-30 | 2022-12-13 | 重庆医科大学附属第一医院 | Endogenous epileptic seizure animal model and construction method thereof |
| CN113967023A (en) * | 2021-10-27 | 2022-01-25 | 复旦大学 | Closed-loop optogenetic intervention system and intervention method |
| CN113967023B (en) * | 2021-10-27 | 2023-08-29 | 复旦大学 | Closed-loop optogenetic intervention system and intervention method |
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Granted publication date: 20200710 Termination date: 20210725 |