CN117158982A - Dual-mode detection and regulation micro-nano electrode array for sleep-refreshment area, detection system and preparation method - Google Patents
Dual-mode detection and regulation micro-nano electrode array for sleep-refreshment area, detection system and preparation method Download PDFInfo
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Abstract
The invention discloses a sleep-wake area dual-mode detection and regulation micro-nano electrode array, a detection system and a preparation method. The implanted micro-nano electrode array consists of a silicon substrate layer, a metal conducting layer and a silicon nitride silicon oxide insulating layer, has low invasiveness and better biocompatibility, and simultaneously aims at the difficulties of small sleep-wake nucleus structure, deep position and the like in the brain, thereby realizing high-precision positioning and implantation of multiple brain areas. The electrode array can realize synchronous detection and electric stimulation regulation and control of nerve electrophysiology and electrochemical signals in sleep-wake brain regions. The experiment is carried out in a behavior box, and a long-term closed-loop experimental system is built by combining an infrared physiological telemetry system, a nerve dual-mode signal acquisition system and an electric stimulator, is used for measuring nerve electrophysiology and electrochemical signals of an experimental animal in a sleep-wake cycle, synchronously records a behavior track, and jointly analyzes physiological parameters such as activity, body temperature and heart rate, so that the method is beneficial to exploring a nerve mechanism of sleep-wake in brain.
Description
Technical Field
The invention relates to the field of micro-processing of biosensors, in particular to a sleep-wake-up area dual-mode detection and regulation micro-nano electrode array, a detection system and a preparation method.
Background
Sleep is an indispensable periodic physiological phenomenon for human beings and is critical for the physical health and even the life condition of human beings. More and more cerebral nuclei have been found to play a role in regulating sleep-wake processes in recent years, such as PAG brain regions (Periaqueductual Gray, peri-midbrain aqueduct grey), LDT brain regions (Laterodorsal Tegmental Nucleus, dorsal lateral covered nuclei), PAG brain regions (Periaqueductal Gray, midbrain aqueduct grey), and the like. Complex electrophysiological and chemical transmitter activities exist between the brain regions, forming multiple interdigitated neuromodulation loops within the brain. However, the existing world has a plurality of people suffering from sleep disorder and serious harm, but the lack of accurate detection and regulation technology for deep brain sleep nuclear clusters has limited means for analyzing sleep-wake loops and treating sleep disorder.
The transmission mode of the brain nerve information mainly comprises an electric signal on a single neuron and a chemical signal between neurons, but the change characteristics of the two signals are difficult to record in vivo. Studies have shown that the nucleus associated with sleep-arousal is mostly located deep in the brain, with varying shapes and smaller volumes. The conventional macro electrode such as a screw electrode and the like can record scalp brain electricity and intracranial endothelial layer brain electricity, and the signal precision, the anti-interference performance and the like are still to be improved.
The silicon-based implanted micro-nano electrode array prepared based on the micro-electromechanical system process has certain rigidity, and can be deep into the brain while keeping small damage. The nerve electrode array can detect electrophysiological activity of a single neuron at the sub-millisecond level, and can record local field potential signals generated by superposition of group neuron activities; the nano material can be modified on the site to detect the oxidation peak potential of neurotransmitter so as to determine the concentration thereof; in addition, the control on the nerve signals in the brain can be realized by applying electric pulse stimulation to the position points.
In summary, the implanted nerve micro-nano electrode array has the advantages of high resolution, high flux, high precision, high signal to noise ratio, low invasiveness and the like, micron-level electrode sites can completely cover the range of a target brain region through reasonable arrangement, a plurality of probe structures can be accurately implanted into a plurality of sleep-wake association nuclei in the deep part of the brain, nerve electrophysiology and electrochemical signals can be synchronously detected and regulated, the change rule of nerve information among the nuclei is explored, and the implanted nerve micro-nano electrode array has important research significance for exploring the sleep-wake mechanism and treating sleep disorder diseases.
Disclosure of Invention
In order to solve the technical problems, the invention provides a sleep-wake-up area dual-mode detection and regulation micro-nano electrode array, a detection system and a preparation method, which are an implanted nerve micro-nano electrode array with integrated functions and simultaneously have the functions of nerve electrophysiology and electrochemical signal detection and electric stimulation regulation. The implanted micro-nano electrode array consists of a silicon substrate layer, a metal conducting layer and a silicon nitride silicon oxide insulating layer, and can realize synchronous detection and electric stimulation regulation and control of nerve electrophysiology and electrochemical signals in a sleep-wake-up area. On the premise of considering the normal living state of the experimental animal, an infrared physiological telemetry system, a nerve dual-mode signal acquisition system and an electric stimulator are combined to build a long-term closed-loop experimental system which is used for measuring nerve electrophysiology and electrochemical signals of the experimental animal such as mice, rats and the like in the sleep-wake cycle, synchronously recording animal behavior tracks, and jointly analyzing physiological parameters such as activity, body temperature and heart rate and the like, thereby being beneficial to exploring the nerve mechanism of sleep-wake in brain.
In order to achieve the above purpose, the invention adopts the following technical scheme:
a sleep-wake zone dual mode detection and regulation micro-nano electrode array comprising:
the electrode basal layer is positioned at the bottommost layer of the micro-nano electrode array and plays a role in supporting and protecting;
the electrode conducting layer is positioned on the electrode basal layer and is composed of an upper layer and a lower layer, and plays a role in conducting electric signals;
a silicon needle positioned at the front end of the electrode, long and sharp and used for being implanted into the brain region;
the electrophysiology and electrochemical detection sites are round sites, the electrostimulation sites and the counter electrodes are rectangular electrodes, the bonding pads are square sites, and the connecting leads are used for connecting the bonding pads with the detection sites, the electrostimulation sites and the counter electrodes;
the electrode insulating layer is positioned on the electrode conducting layer and separates the connecting lead from the outside, so that the transmitted signals are prevented from being interfered;
in some embodiments of the present disclosure, the material of the electrode base layer is single crystal silicon or SOI, which is treated by insulation, and is composed of silicon and silicon oxide or silicon nitride;
in some embodiments of the present disclosure, the upper layer of the electrode conductive layer is made of platinum or gold, the thickness is 250-300nm, and the lower layer is made of titanium, tungsten, molybdenum or chromium, and the thickness is 30nm.
In some embodiments of the present disclosure, the number of silicon needles is 4-8, and the length of a single silicon needle is 8.5-10 mm.
In some embodiments of the present disclosure, the electrophysiology and electrochemical detection sites are 5-10 μm in diameter, the electrostimulation sites are (150-200). Times.40 μm, the counter electrode size is 300X 20 μm, the bond pad size is 200X 200 μm, the wire width is 4-6 μm, and the wire spacing is 8-12 μm.
In some embodiments of the present disclosure, the modification materials of the electrochemical detection sites are PtNPs and PEDOT: PSS.
In some embodiments of the present disclosure, the material of the electrode insulating layer is 400nm silicon oxide and 500nm silicon nitride.
As a second aspect of the present invention, there is also provided a method for preparing the sleep-wake zone dual-mode detection and control micro-nano electrode array as described above, comprising:
cleaning and insulating the SOI sheet to form an electrode basal layer, and forming a silicon oxide insulating film on the electrode basal layer in a deposition and thermal oxidation mode;
forming a mask of the electrode conductive layer after the first photoetching development;
sputtering metal on the mask to serve as an electrode conducting layer and stripping redundant metal;
depositing an electrode insulating layer on the electrode conducting layer by adopting a thin film deposition technology;
developing by the second photoetching to form a mask of the electrode insulating layer;
exposing electrode sites of the conductive layer by adopting a thin film dielectric etching method;
developing by third photoetching to form a mask of the electrode substrate layer;
etching the electrode shape by adopting a dry etching method, and etching an insulating layer generated by back oxidation by adopting a hydrofluoric acid wet etching or dry etching method;
immersing in strong alkali, heating in water bath, and wet etching to release micro-nano electrode array;
electroplating the electrode sites by using an electrochemical workstation, and modifying different kinds of nano materials according to requirements.
As a third aspect of the present invention, there is also provided a detection system set up for laboratory mice as described above, comprising:
the behavior box is used as a place for the experimental animal to move and rest, and sufficient food and water are ensured in the experimental process;
the infrared camera is used for recording the activity condition of the experimental animal;
the electromagnetic shielding box is used for shielding noise caused by external electromagnetic interference;
an implantable capsule implanted in the abdomen of the experimental animal for recording physiological parameters including body temperature, heart rate and activity;
the infrared physiological telemetry system is used for receiving physiological parameter signals acquired by the implantable capsule and performing primary treatment;
the electric stimulator is used for generating electric stimulation pulses to stimulate brain areas of experimental animals;
the nerve dual-mode signal acquisition system is used for recording electrophysiological signals and electrochemical signals of nerves acquired in the brain of the experimental animal;
the lead and the bracket are used for connecting the front-end amplifying circuit of the electrode with the nerve dual-mode signal acquisition system and the electric stimulator at the rear end.
As can be seen from the above technical solution, compared with the prior art, the present invention has at least one or some of the following advantages:
1. the shape design of the implanted micro-nano electrode array and the arrangement of the sites thereof are matched with sleep-wake nuclei in the brain, so that the nerve signals of a target brain region can be detected and regulated to the maximum extent without affecting the surrounding brain region;
2. the implanted micro-nano electrode array integrates the functions of nerve electrophysiology and electrochemical signal dual-mode detection and electric pulse stimulation regulation and control in the sleep-wake brain region, and can realize in-situ synchronous detection and regulation and control on a target brain region;
3. the implanted micro-nano electrode array can detect and regulate the neural information of a plurality of nuclear clusters with different positions and different shapes in the brain at the same time;
4. the experimental system built around the implanted micro-nano electrode array can be applied to the experimental animal long-term sleep-wake neural signal detection and regulation experiment, and based on electrophysiological and electrochemical signals and physiological parameters such as body temperature, heart rate and activity, the experimental animal behavior activity is synchronously monitored, and the sleep-wake neural activity law is analyzed by multi-factor combination.
Drawings
For a better understanding of the objects, features and advantages of the present invention, reference should be made to the following detailed description of the invention, taken in conjunction with the accompanying drawings, in which:
FIG. 1 is a schematic diagram of the design structure of a micro-nano electrode array for dual-mode detection and control in sleep-wake area according to the present invention;
FIG. 2 is a partial enlarged view of a dual mode detection and control micro-nano electrode array for sleep-wake zone according to the present invention;
FIG. 3 is a schematic diagram of a dual-mode detection and control micro-nano electrode array for detecting and controlling the brain regions in the brain;
FIG. 4 is a process flow diagram of a method for preparing a micro-nano electrode array for dual mode detection and control in sleep-wake area according to the present invention; wherein, figure (a) is thermal oxidation, figure (b) is spin-on negative photoresist, figure (c) is photolithography, figure (d) is sputtered metal film, figure (e) is lift-off, figure (f) is PECVD, figure (g) is spin-on positive photoresist, figure (h) is photolithography and etching an insulating layer window at an electrode site, figure (i) is spin-on positive photoresist, figure (j) is photolithography and deep etching, figure (k) is spin-on photoresist, figure (l) is coated with black photoresist, and figure (m) is a wet etching release electrode array;
fig. 5 is a schematic diagram of a detection and control system for long-term monitoring of sleep cycle neural signals and physiological parameter changes in experimental animals according to the present invention.
Reference numerals illustrate:
1 is an electrode insulating layer, 2 is an electrode conducting layer, 3 is an electrode basal layer, 4 is a bonding pad, 5 is a connecting lead, 6 is a counter electrode, 7 is a stimulating electrode, 8 is an electrophysiological and electrochemical detection site, 9 is a PAG brain region, 10 is an LDT brain region, 11 is an infrared camera, 12 is an infrared physiological telemetry system, 13 is a behavior box, 14 is an implantable capsule, 15 is a nerve micro-nano electrode array, 16 is food and water, 17 is an electromagnetic shielding box, 18 is a lead and a bracket, 19 is an electric stimulator, and 20 is a nerve dual-mode signal acquisition system.
Detailed Description
The invention discloses a micro-nano electrode array integrating neurophysiologic electrochemical dual-mode detection and electric stimulation regulation and control and a detection regulation system thereof, which can realize in-situ monitoring and regulation and control of nerve electric signals in sleep-wake cycle states of experimental animals, and simultaneously combine physiological parameter joint analysis of movement tracks, body temperature, activity, heart rate and the like to be beneficial to further exploring sleep-wake mechanisms of brains.
The present invention will be further described in detail below with reference to specific embodiments and with reference to the accompanying drawings, in order to make the objects, technical solutions and advantages of the present invention more apparent.
Certain embodiments of the present disclosure will now be described more fully hereinafter with reference to the accompanying drawings, in which some, but not all embodiments are shown. Indeed, various embodiments of the disclosure may be embodied in many different forms and should not be construed as limited to the embodiments set forth herein; rather, these embodiments are provided so that this disclosure will satisfy applicable legal requirements.
As shown in fig. 1 and fig. 2, the dual-mode detection and regulation micro-nano electrode array for sleep-wake brain area provided by the embodiment of the invention comprises an electrode basal layer 3, which is positioned at the bottommost layer of the micro-nano electrode array and plays a role in supporting and protecting; the electrode conducting layer 2 is positioned in the middle layer of the micro-nano electrode array and plays a role in conducting electric signals; the electrode insulating layer 1 is positioned at the topmost layer of the micro-nano electrode array and separates the connecting lead 5 from the outside, so that the transmitted signals are prevented from being interfered.
The electrode conductive layer 2 is composed of a bonding pad 4, a connecting lead 5, an electrophysiological detection site, an electrochemical detection site and an electrical stimulation site, wherein the tip electrode site is connected with the bonding pad 4 in a one-to-one correspondence manner through the connecting lead 5, the size of the bonding pad 4 is 200 multiplied by 200 mu m, the width of the connecting lead 5 is 4-6 mu m, the distance between the connecting leads 5 is 8-12 mu m or more, the number of silicon needles is 4, and the implantation of a plurality of sleep-wake association nuclear clusters in a brain area is ensured; the length of the single silicon needle is 8.5-10 mm, so that the single silicon needle can be implanted into deep brain sleep-wake associated nucleus. The silicon needle is positioned at the front end of the electrode, is long and sharp and is used for being implanted into the brain region.
The electrophysiological and electrochemical detection sites 8 are circular sites with the diameter of 5-10 mu m, and the site arrangement can completely cover the range of a sleep-wake-up area; the counter electrode 6 is a rectangular site with a size of 300×20 μm.
The electric stimulation sites of the micro-nano electrode array are matched with the shape of the deep sleep-wake associated nucleus, the size of the electric stimulation sites is (150-500) multiplied by 40 mu m, each silicon needle is provided with one electric stimulation site, the electric stimulation sites between the two silicon needles form a parallel plate capacitor, the parallel plate capacitor is connected with the electric stimulator 19 at the rear end through the connecting lead 5 and the bonding pad 4, and the electric stimulator 19 releases electric pulses to realize electric stimulation regulation and control of the sleep-wake nucleus.
As shown in fig. 2, in the sleep-wake-up area dual-mode detection and regulation micro-nano electrode array provided by the embodiment of the invention, an electrophysiological and electrochemical detection site 8 at the tip end part of the electrode, an electrical stimulation site of a stimulation electrode 7 and a counter electrode 6 are connected with sites of different bonding pads 4 at the front end of the electrode through connecting leads 5, wherein weak nerve signals detected by the electrophysiological and electrochemical detection site 8 are transmitted to a nerve dual-mode signal acquisition system 20 through the connecting leads 5 and the bonding pads 4, and electrical pulses generated by an electrical stimulator 19 are transmitted to the electrical stimulation site through the bonding pads 4 and the connecting leads 5 to be released, and the counter electrode 6 is used for forming a three-electrode system, so that the detection of electrochemical signals is facilitated.
As shown in FIG. 3, when the dual-mode detection and control micro-nano electrode array for sleep-wake brain region is used for detecting and controlling multiple brain regions in brain, the PAG brain region 9 and the LDT brain region 10 are two important brain regions for regulating sleep-wake state in brain at the position of 0.90mm beside a middle seam, and are positioned at different positions in brain and are different in shape, and the two brain regions can be implanted with silicon needles with different lengths for detecting and controlling nerve signals. The present disclosure also provides a method for preparing the micro-nano electrode array for dual-mode detection and regulation of sleep-wake brain area as described above, based on the mems manufacturing process as shown in fig. 4, which specifically comprises the following steps:
step (1) taking a 4 inch SOI sheet as an electrode substrate layer, and growing a layer of silicon oxide with the thickness of 500nm on the surface of the SOI sheet by adopting a thermal oxidation process to ensure that the electrode substrate layer is completely isolated from an electrode conductive layer, as shown in (a) of fig. 4;
step (2) spin-coating negative photoresist AZ5214 on the surface of the electrode substrate layer on which the silicon oxide is deposited, wherein the spin-coating process is set to have a rotation speed of 500r/min for 10s and a rotation speed of 2000r/min for 60s, as shown in (b) of fig. 4.
And (3) photoetching by using the prepared mask plate of the electrode conductive layer, absorbing vacuum and exposing for 1s, reversely baking for 3min on a hot plate at 125 ℃, cooling, and developing for about 12s in a 0.6% NaOH solution without adding the mask plate for flood exposure for 12s, wherein the step is shown in (c) of fig. 4.
Step (4) sequentially sputtering a metallic titanium seed layer with the thickness of 30nm and a metallic platinum conductive layer with the thickness of 250nm on the developed silicon wafer, as shown in (d) of fig. 4.
And (5) soaking the sputtered silicon wafer in an acetone solution, gradually dissolving the residual photoresist, peeling off the sputtered metal film on the photoresist, and stripping off the redundant metal, wherein the positions of the bonding pads, the connecting leads and the electrode positions are left on the surface of the silicon wafer, as shown in (e) of fig. 4.
Step (6) is to sequentially arrange 400nm silicon oxide and 500nm silicon nitride on the peeled silicon wafer as an electrode insulating layer using PECVD (plasma enhanced chemical vapor deposition), as shown in (f) of FIG. 4.
Step (7) spin-coating positive photoresist AZ1500 on the surface of the silicon wafer after the PECVD insulating layer, wherein the spin-coating process is set to have a rotating speed of 500r/min for 10s and a rotating speed of 1000r/min for 60s, as shown in (g) of FIG. 4.
Step (8), photoetching by using a mask plate of the prepared electrode insulating layer, wherein the exposure time is 4s; developing in 0.6% naoh solution for about 40s to form a mask exposing the electrode sites and pads; the electrode insulating layer is etched using reactive ion etching to expose the sites and pads of the electrode conductive layer, as shown in fig. 4 (h).
Step (9) spin-coating positive photoresist AZ4620, the spin-coating process is set to have a rotation speed of 500r/min for 10s, a rotation speed of 4500r/min for 60s, and a rotation speed of 500r/min for 5s, as shown in (i) of FIG. 4.
Step (10) using the prepared mask plate of the electrode substrate layer for photoetching, exposing for 9s, and developing for about 2min 40s in 0.6% NaOH solution; the silicon oxide formed by thermal oxidation and the silicon on the upper surface of the SOI are etched on the surface by dry etching to form the electrode shape, as shown in (j) of FIG. 4.
Step (11) spin-coating two to three layers of negative photoresist BN303 on the surface of the silicon wafer to keep the etched surface of the silicon wafer flat, as shown in (k) of FIG. 4.
Heating the black glue solid on a hot plate to melt the black glue solid, covering the front surface of the silicon wafer on the black glue downwards, and sealing the edge part by using the black glue; the hot plate temperature was gradually lowered to room temperature and the wafer was removed as shown in fig. 4 (l).
And (13) placing the silicon wafer sealed with the black glue in a 50% KOH solution with the temperature of 75 ℃ for water bath heating, corroding the bottom silicon of the original SOI on the back, stopping heating until the electrode array is completely displayed, taking out, placing in a negative glue developer for soaking for one day, removing the residual black glue on the electrode, and corroding the release electrode by a wet method, as shown in (m) of fig. 4.
In one embodiment of the present disclosure, an experimental system is provided that uses the above-described sleep-wake zone dual-mode detection and regulation micro-nano electrode array, as shown in fig. 5, where the pads of the electrodes are designed to have a rectangular structure with a size of 200×200 μm. The electrode silicon needle has a length of 9mm, the electrophysiological detection site and the electrochemical detection site have circular structures with diameters of 5 mu m, the counter electrode has a length of 300 mu m, and the electro-stimulation site has a length of 150 mu m, so that the electrode silicon needle can be used for detecting action potential and neurotransmitter concentration of sleep nuclear nerve cells.
The detection regulation system comprises an infrared camera 11, an infrared physiological telemetry system 12, a behavior box 13, an implantable capsule 14, a nerve micro-nano electrode array 15, an electromagnetic shielding box 17, a lead wire and bracket 18, an electric stimulator 19 and a nerve dual-mode signal acquisition system 20. The behavior box 13 is a place for the experimental animals to move and rest, and sufficient food and water 16 are ensured in the experimental process; the infrared camera 11 is used for recording the activity condition of the experimental animal; the electromagnetic shielding box 17 is used for shielding noise caused by external electromagnetic interference; the implanted capsule 14 is implanted into the abdomen of the experimental animal and is used for recording physiological parameters such as body temperature, heart rate, activity and the like; the electric stimulator 19 generates electric pulses to stimulate brain areas of experimental animals; the nerve dual-mode signal acquisition system 20 is used for recording nerve electrophysiological and electrochemical signals acquired in the brain of the experimental animal; the lead and bracket 18 is used for connecting an amplifying circuit at the front end of the electrode and a nerve dual-mode signal acquisition system and an electric stimulator at the rear end.
The nerve micro-nano electrode array 15 is implanted into the brain of the experimental animal and fixed by dental cement; the implantable capsule 14 is implanted in the abdomen of the experimental animal and the wound is sutured. Placing the animals in a behavior box 13 after recovery, and ensuring sufficient food and water 16; the rear end of the nerve micro-nano electrode array 15 is connected with the outside through a wire and a wire of a bracket 18; the whole behavior box 13 is placed on the platform of the infrared physiological telemetry system 12; the behavior box 13 and the infrared physiological telemetry system 12 are arranged in an electromagnetic shielding box 17 to shield external electromagnetic noise; outside the electromagnetic shielding box 17, an infrared camera 11 is arranged to record the behavior track of the experimental animal, a wire and a bracket 18 are arranged at the same time, one end of the wire is connected with a nerve micro-nano electrode array 15 of the head of the experimental animal in the behavior box 13, and the other end is connected with an electric stimulator 19 and a nerve dual-mode signal acquisition system 20.
In combination with this embodiment, the system for detecting and controlling sleep-wake nerve information in brain based on the micro-nano electrode array specifically operates as follows:
the developed nerve micro-nano electrode array 15 is implanted in the brain of the experimental animal through animal surgery, is fixed by dental cement, and can be used for experiments after being put into a feeding box for one to two days. The experimental animal is placed in a behavior box 13 for long-term monitoring of sleep-wake cycle physiological parameters, the activity state and track of the experimental animal are recorded through an infrared camera 11, physiological parameters such as body temperature, activity amount and heart rate of the experimental animal are synchronously recorded by an implanted capsule 14 and transmitted to an infrared physiological telemetry system 12 below for preliminary recording treatment, the physiological parameters are combined with the electrophysiological signals and electrochemical signals recorded by using a nerve micro-nano electrode array 15 for analysis, and meanwhile, the electrical pulse generated by an electrical stimulator 19 can be used for regulating and controlling the nerve signals and other parameters in the brain, so that the study of normal conditions and the nerve mechanism of sleep-wake under the regulation of the electrical stimulation is facilitated.
The foregoing description of the embodiments has been provided for the purpose of illustrating the general principles of the invention, and is not meant to limit the invention thereto, but to limit the invention thereto, and any modifications, equivalents, improvements and equivalents thereof may be made without departing from the spirit and principles of the invention.
Claims (10)
1. The utility model provides a sleep-wake brain district bimodulus detects and regulates and control micro-nano electrode array which characterized in that includes: the electrode basal layer is positioned at the bottommost layer of the micro-nano electrode array and plays a role in supporting and protecting; the electrode conducting layer is positioned in the middle layer of the micro-nano electrode array and plays a role in conducting electric signals; the electrode insulating layer is positioned at the topmost layer of the micro-nano electrode array and separates the connecting lead from the outside, so that the transmitted signals are prevented from being interfered.
2. The dual-mode detection and control micro-nano electrode array for sleep-wake brain regions according to claim 1, wherein the electrode substrate layer is made of single crystal silicon or SOI (silicon on insulator) which is processed by insulation, and is composed of silicon and silicon oxide or silicon nitride.
3. The dual-mode detection and control micro-nano electrode array for sleep-wake brain area according to claim 1, wherein the electrode conducting layer is composed of double-layer metal with good biocompatibility, and the upper layer material is platinum or gold with the thickness of 250-300nm and is used for conducting electricity; the lower layer is made of titanium, tungsten, molybdenum and chromium, and has a thickness of 30nm, and is used as a seed layer to enable the adhesion between the electrode conductive layer and the electrode basal layer to be more compact.
4. The dual-mode detection and control micro-nano electrode array for sleep-wake area according to claim 1 or 3, wherein the tip part of the electrode is provided with 4-8 silicon needles, so that a plurality of sleep-wake related nuclei can be implanted into the brain; the length of the single silicon needle is 8.5-10 mm, so that the single silicon needle can be implanted into deep brain sleep-wake associated nucleus.
5. The dual-mode detection and control micro-nano electrode array for sleep-wake brain area according to claim 1 or 3, wherein the electrode conducting layer consists of a bonding pad, a connecting lead, an electrophysiological detection site, an electrochemical detection site and an electrical stimulation site, the tip electrode and the bonding pad are connected in one-to-one correspondence through the connecting lead, wherein the bonding pad is 200×200 μm in size, the lead width is 4-6 μm, and the lead spacing is 8-12 μm; the electrophysiological and electrochemical detection sites are circular sites with the diameter of 5-10 mu m, and the site arrangement can completely cover the range of a sleep-wake brain region; the counter electrode is a rectangular site with a size of 300×20 μm.
6. The dual-mode detection and control micro-nano electrode array for the sleep-wake brain area according to claim 5, wherein the electric stimulation sites are matched with the deep sleep-wake related nucleus of the brain in shape, the size is (150-200) multiplied by 40 μm, one electric stimulation site is designed on each silicon needle, the electric stimulation sites between the two silicon needles form a parallel plate capacitor, and the electric stimulation control on the sleep-wake nucleus is realized by releasing electric pulses through a connected electric stimulator.
7. The dual-mode detection and control micro-nano electrode array for sleep-wake brain regions according to claim 1, wherein the electrode insulating layer is made of an insulating material, and the insulating material is silicon oxide, silicon nitride or silicon oxynitride.
8. The dual-mode detection and control micro-nano electrode array for sleep-wake brain regions according to claim 4, wherein the electrophysiological detection site, the electrochemical site and the electro-stimulation site are modified by electrochemical deposition to improve detection and control performance; the electrochemical site is further modified with nanomaterials, wherein the nanomaterials comprise oxidase and PEDOT, are used for detecting oxidation peak potential of neurotransmitters related to sleep-wake, including dopamine, serotonin and norepinephrine, and are compared with in-vitro calibration results to further obtain the concentration of the neurotransmitters in the brain.
9. The method for preparing the dual-mode detection and control micro-nano electrode array for sleep-wake brain regions according to any one of claims 1-8, comprising the steps of:
cleaning and insulating the SOI sheet to form an electrode basal layer, and forming a silicon oxide insulating film on the electrode basal layer in a deposition and thermal oxidation mode;
forming a mask of the electrode conductive layer after the first photoetching development;
sputtering metal on the mask to serve as an electrode conducting layer and stripping redundant metal;
depositing an electrode insulating layer on the electrode conducting layer by adopting a thin film deposition technology;
developing by the second photoetching to form a mask of the electrode insulating layer;
exposing electrode sites of the conductive layer by adopting a plasma etching method;
developing by third photoetching to form a mask of the electrode substrate layer;
etching the electrode shape by adopting a dry etching method, and etching an insulating layer generated by back oxidation by adopting a hydrofluoric acid wet etching or dry etching method;
immersing in strong alkali, heating in water bath, and wet etching to release micro-nano electrode array;
electroplating the electrode sites by using an electrochemical workstation, and modifying different kinds of nano materials according to requirements.
10. A detection system employing the dual mode detection and modulation micro-nano electrode array of the sleep-wake zone of one of claims 1-8, comprising:
the behavior box is used as a place for the experimental animal to move and rest, and sufficient food and water are ensured in the experimental process;
the infrared camera is used for recording the activity condition of the experimental animal;
the electromagnetic shielding box is used for shielding noise caused by external electromagnetic interference;
an implantable capsule implanted in the abdomen of the experimental animal for recording physiological parameters including body temperature, heart rate and activity;
the infrared physiological telemetry system is used for receiving physiological parameter signals acquired by the implantable capsule and performing primary treatment;
the electric stimulator is used for generating electric stimulation pulses to stimulate brain areas of experimental animals;
the nerve dual-mode signal acquisition system is used for recording electrophysiological signals and electrochemical signals of nerves acquired in the brain of the experimental animal;
the lead and the bracket are used for connecting the front-end amplifying circuit of the electrode with the nerve dual-mode signal acquisition system and the electric stimulator at the rear end.
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| CN112842366A (en) * | 2020-12-30 | 2021-05-28 | 中国科学院空天信息创新研究院 | Multi-mode nerve stimulation regulation and synchronous detection system |
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| Publication number | Priority date | Publication date | Assignee | Title |
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| CN112842366A (en) * | 2020-12-30 | 2021-05-28 | 中国科学院空天信息创新研究院 | Multi-mode nerve stimulation regulation and synchronous detection system |
| CN112842366B (en) * | 2020-12-30 | 2024-02-06 | 中国科学院空天信息创新研究院 | Multimode nerve stimulation regulation and control and synchronous detection system |
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